text
stringlengths 0
128k
|
|---|
/*
* To change this license header, choose License Headers in Project Properties.
* To change this template file, choose Tools | Templates
* and open the template in the editor.
*/
package task;
/**
*
* @author graphics
*/
public class Teacher {
private String name;
private int age;
private String mobile;
private String department;
private String address;
public String getName() {
return name;
}
public void setName(String name) {
if (name.length()>3) {
this.name = name;
}
else{
System.out.println(" error ");
}
}
public int getAge() {
return age;
}
public void setAge(int age) {
this.age = age;
}
public String getMobile() {
return mobile;
}
public void setMobile(String mobile) {
this.mobile = mobile;
}
public String getDepartment() {
return department;
}
public void setDepartment(String department) {
this.department = department;
}
public String getAddress() {
return address;
}
public void setAddress(String address) {
this.address = address;
}
}
|
NIAT implementation from Equivalence Class Signatures
x2 should be negated instead of inverted!
Let's get the NIZK in here, and then I will push the whole thing together.
|
SCARLET TANAGER.
LIKE the vireos, the scarlet tanager is associated with green tree tops; but if you ask just where you will see him, it is hard to answer. In Northampton, I remember finding him in three quite dissimilar spots. The bird of Paradise has become a familiar sight in our museums, but the good people of Northampton follow Dante and see “ Paradise” itself before they die. ‘“ Purgatory” is there, too, for warning, and the river runs between the two abodes! They lie just outside the town, and if you could get some kindly spirit to guide you, they would surely seem well named. “ Purgatory” hes barren and desolate, strewn with sand and stones on which the sun beats down as if with intent to torture imprisoned souls. Opposite stands ‘“ Paradise,” a wood of wondrous beauty, —a true elysium for the immortal spirits of birds and flowers! In its heart is a grove of musical pines, whose brown, pineneedle carpet is garlanded with clumps of ferns. Close to the river’s edge, reaching their branches low over it as it narrows to a stream, the maples and birches offer cool green shade when the sun is parching the banks of “ Purgatory”; and in autumn, when the bare sand and stones grow cold,
|
const debug = require('debug')('media-server:playlist-service')
const MongoClient = require('mongodb').MongoClient
const getPlaylist = () => new Promise((resolve, reject) => {
MongoClient.connect(process.env.MONGO_URL, (err, client) => {
debug('connected to client')
if (err) {
debug(err)
reject(err)
}
else {
const db = client.db('simple_media')
db.collection('tracks').find({}).toArray((err, tracks) => {
debug('got tracks', tracks)
if (err) {
reject(err)
}
else {
resolve(tracks)
}
client.close()
})
}
})
})
module.exports = {
getPlaylist
}
|
Hi.
Hello, how can I help you today?
Help me in booking a flight from DFW to DTW?
On which dates would you like me to book a flight ticket for you?
My travelling dates are May 06 to 08.
On what name, do I need to reserve your ticket?
I am Gary Campbell.
Let me know your connection limit?
I prefer travelling in connection flight.
Do you have any other requirements?
No.
Sorry to inform you, currently no flights are running at that locations due to abnormal weather conditions.
That's ok, thank you.
Thank you for choosing us.
|
Recent trends and variations in general practitioners’ involvement in accident care in Switzerland: an analysis of claims data
Abstract/summary Background As in other countries, there is concern and some fragmentary evidence that GPs’ central role in the Swiss healthcare system as the primary provider of care might be changing or even be in decline. Our study gives a systematic account of GPs’ involvement in accident care from 2008 to 2016 and identifies changes in GPs’ involvement in this typical field of primary care: how frequently GPs were involved along the care pathway, to what extent they figured as initial care provider, and what their role in the care pathway was. Methods Using a claims dataset from the largest Swiss accident insurer with two million accident cases, we constructed individual care pathways, i.e., when and from which providers patients received care. We calculated probabilities for the involvement of various care provider groups, for initial care provision, and for the role of GPs in patients’ care pathways, adjusted for injury and patient characteristics using multinomial regression. Results In 2014, GPs were involved in 70% of all accident cases requiring outpatient care but no inpatient stay, and provided initial care in 56%. While involvement stayed at about the same level for accidents occurring from 2008 to 2014, the share of accidents where GPs provided initial care decreased by 4 percentage points. The share of cases where GPs acted as sole care provider decreased by 7 percentage points down to 44%. At the same time, accident cases involving care from an ED at any point in time increased from 38 to 46% and the share receiving initial care from an ED from 30 to 35 percentage points – apparently substituting for the declining involvement of GPs in initial care. GPs’ involvement in accident care is higher in rural compared to urban regions, among elderly compared to younger patients, and among Swiss compared to non-Swiss citizens. Conclusions GPs play a key role in accident care with considerable variation depending on region and patient profile. From 2008 to 2014, there is a remarkable decline in GPs’ provision of initial care after an accident. This is a strong indication that the GPs’ role in the Swiss healthcare system is changing.
Background
As in many other European countries, general practitioners (GPs) have an essential function in the Swiss health care system as the main provider of ambulatory care [1,2]. General practitioners include physicians in private practice certified as general practitioners, specialists in general internal medicine, and physicians without a specialty qualification. With 83 GPs per 100,000 inhabitants, Switzerland has a high GP density when compared with other countries [3]. Besides seeing patients by appointment and during daytime, they usually provide out-of-hours emergency care, often by participating in local emergency networks operated by GPs themselves.
Patients traditionally first turn to their personal GP when in need of care, even in the case of an emergency. If necessary, GPs then refer patients to a hospital emergency department (ED) or to some other specialized (secondary) care provider. However, there is no general formal gatekeeping system that regulates access to hospitals or specialized care for patients in Switzerland. Still, GPs usually function as gatekeepers in practice and health insurance schemes employing GPs as the central point of contact are increasingly popular as they come with reduced premiums.
Accident insurance in Switzerland is organized separately from health insurance, which only covers nonaccident related health care. Both accident insurance nd health insurance are compulsory. However, while individuals choose and pay their health insurance provider on their own, accident insurance is paid for by employers and employees jointly. It covers both occupational and non-occupational accidents. Non-working persons or marginally employed persons need to obtain non-occupational accident coverage from their health insurance provider.
All health care services provided by medical doctors (GPs and specialists) as well as hospital outpatient services covered by the mandatory health insurance are reimbursed on the basis of a nationally uniform tariff system. For hospital inpatient care and rehabilitation care, similar tarif systems are in place. Since 2012, hospital inpatient care has been paid on a case-based lump sum basis (Swiss-DRG), leading to some significant changes such as a decrease in average hospital stay [3]. Reimbursement for accident care follows in general the same regulating principles and tariffs. However, accident care is fully reimbursed to patients without any deductibles and there are no restrictions as to where patients seek care (as compared to health insurance where gatekeeping schemes are available).
While GPs' importance is particularly acknowledged in the long-term provision and coordination of care for chronically ill and multimorbid patients, GPs also treat a substantial share of patients who have suffered an accident. Approximately 15% of all GP consultations are related to accidents [4]. However, there is no data on the actual share of accident care that GPs provide relative to other providers, in particular hospital EDs. In addition, not much is known about the precise role GPs play, i.e. how often they act as initial care provider, are the sole care provider, refer patients to other providers, or act as a follow-up care provider only. Accident patients are a very heterogeneous group, as their injuries can vary greatly in nature, cause, location and severity. Approximately one-third of all accidents are related to patients' occupational activities and two-thirds are leisure accidents [5]. Both occupational and non-occupational accidents mostly lead to minor to moderate injuries such as superficial wounds and bruises or sprains and strains, injuries which could be treated by a GP and which, in general, do not require care in an outpatient ED.
The role of GPs in Switzerland has been changing in recent years in various regards. First, patients increasingly have been seeking care directly in EDs, also for minor issues for which a GP could provide suitable care [6][7][8]. Potential explanations for this development are patients' ignorance of emergency services operated by GPs, the absence of a personal GP, the geographical proximity to a hospital, or the subjectively-felt urgency of treatment [9].
Second, there is a relatively low and continuously decreasing number of GPs that are based in rural areas [10], a problem that will be accentuated in the near future due to a lack of young GPs that could replace an aging GP population [11]. Third, treatments that GPs do and do not provide seem to have changed. According to a survey of GPs, they provided less trauma-related care in 2012 compared to 1993 and the share of GPs that never perform surgical interventions increased from zero to 9%however, with large regional variations. Compared to their urban counterparts, GPs in rural areas were more likely to perform a broader spectrum of treatments [12]. Also, GPs are no longer required to cover traumatology during continuous medical education. In sum, these developments may have led to a shift in the role of GPs in general care and particularly in accident care. However, the precise characteristics and the extent of this shift are not well understood. This is a gap that our study addresses.
The aim of our study is to identify the degree of involvement and the actual role of GPs in accident care, the corresponding changes in recent years, and regional variations and differences depending on patients' characteristics. Our analysis is an important first step in gaining a clear understanding of the scope of the changes and provides guidance in exploring potential driving factors. Also, it might help to partly explain increases in average treatment costs. Various studies have shown that GPs provide emergency services at lower costs than EDs, partly due to the less intensive use of diagnostic measures [13,14]. Patient satisfaction with GPs' emergency care is, nonetheless, at a very high level and no different to EDs [15]. Additionally, the study might help to identify topics in traumatology that should be taught to young GPs.
Data
We analyzed claims data from 2008 to 2016 for accidents registered from 2008 to 2014 with the Swiss National Accident Insurance Fund (SUVA), Switzerland's largest accident insurance provider covering about half of the active working population. From all accidents over this seven-year period, we excluded cases of victims living abroad or receiving any medical treatment abroad, because this study is about accident care in Switzerland. Also, accident victims under the age of 18 and above retirement age (65) were excluded, in order to improve the homogeneity of the study subjects. For the same reason, we excluded accidents with dental lesions as main injury, which have quite different care pathways than other accidents. Furthermore, cases were excluded for which the accident happened more than 3 months prior to registration, since these cases are not typical for primary care. Cases without any treatment costs were excluded as well as cases for which none of the medical provider groups under consideration was involved (i.e. only pharmaceutical services). We excluded accidents with an inpatient stay at any point during the care pathway from our main analyses because of only partially reported data on patients' beginning of inpatient stays prior to 2014. However, we do report analysis results including inpatient cases, where possible, in the Supporting Information S 5.
Our data contains the year of the accident, information about the point in time of the accident (day-of-week and time-of-day), the injury type and anatomical location as reported by the insured person or their employers in the accident report form, the patient's gender, citizenship (Swiss or foreign), age, and place of residence using an urban-intermediate-rural typology according to FOS classification [16]. We have information on the reimbursed daily allowances, which permits us to indirectly infer the injury severity. An incapacity duration exceeding three working days entitles the employer to a compensation through daily allowances and hence is reflected in the data.
From the billing data of all healthcare services provided that are related to one particular accident, we extracted the direct medical costs incurred in the 2 years following the accident, as well as the date of the first patient contact of specific health care provider groups such as general practitioners, medical specialists, or hospitals. Hospital care is differentiated according to outpatient and inpatient service. Inpatient service is defined as care that involved an overnight stay of the patient.
Provider groups are defined as follows: GPs include physicians in private practice certified as general practitioners, specialists in general internal medicine, and physicians without a specialty qualification. The GP category also includes, to a very small degree, emergency walk-in centers, i.e. clinics with extended availability but no beds, which are operated mostly by GPs (locally called "Permanence"). Medical specialists include orthopedic surgeons, ophthalmologists, non-orthopedic surgeons, and other specialists. We did not consider radiologists, pharmacists, physiotherapists, dentists or rescue services in the construction of care pathways because they generally have a supportive function beside one or more main care provider. ED outpatient includes hospital emergency departments providing outpatient care, i.e. care without an overnight stay of the patient.
We have information about the date of the first patient contact of a particular provider group, but not about the number and timing of subsequent contacts with the same provider or other providers of the same provider group. However, the date of the first patient contact allows us to identify who figured as initial care provider and to reconstruct individual care pathways: the first provider group providing care, the second provider group, the third provider group, etc. With this information, we can distinguish care pathways, for instance, cases where GPs acted as sole care provider from others where GPs provided initial care and then referred a patient to the hospital.
If more than one group of providers had their first patient contact on the same day, we assumed the following plausible ordering of the care sequence for trauma patients to unequivocally define an initial care provider: 1) GPs prior to 2) medical specialists prior to 3) ED outpatient service prior to 4) ED inpatient service.
Statistical analysis
Statistical analysis was carried out with Stata 15.1 SE and figures were produced using the user-written command coefplot [17]. We calculated probabilities for involvement in the care pathway and for the provision of initial care for the different care providers, as well as for the various roles GPs play in the whole care pathway. To consider potential effects of a changing patient population or injury types, we also calculated model-based adjusted probabilities for the outcomes "provider involvement" and "initial care provider" using multinomial logistic regression models controlling simultaneously for patients' gender, citizenship, age, place of residence, the anatomical location of the injury, and the point in time of the accident. Multinomial logistic regression allows for modelling multiple, unordered nominal outcomes and is a straightforward extension of the logistic regression for binomial outcomes [18]. We report adjusted predicted probabilities which were computed using Stata's margins command [19]. We do not report confidence intervals or p-values in the text nor in the figures because, due to our very large sample size, confidence intervals are typically very small. All the reported differences are statistically significant at the 1 % level (two-sided).
Results
The base data set for our study contains more than 3 million cases registered from 2008 to 2014. The data set used for our main analysis comprises N = 2,007,513 accidents that required outpatient medical care but no hospital inpatient stay. The number of included and excluded cases are reported in the supplementing information S 1.
Injuries suffered by patients with an outpatient stay only are mostly of low to moderate severity, as can be indirectly inferred by the typically short incapacity duration and the average low case costs (see descriptives in Table 1). Most of the accidents (58%) resulted in no work absence or in an incapacity duration of three working days or less. 32% of the cases resulted in 4 to 10 working days absence, 8% in 2 weeks to 3 months, and only 2% in more than 3 months. The median of reimbursed direct medical costs per accident was 352 CHF (mean: 806 CHF; 75th percentile: 804 CHF). Hence, the provided medical care consisted in half of the cases of just one or two visits to a healthcare provider performing minor treatments.
80% of the patients in our sample are male, only 20% femalewhich reflects the fact that the insurance provider from which our data stem has a particularly strong client base in the secondary sector (e.g., manufacturing, construction, infrastructure), where females are employed underproportionally. The mean age is 37 years, about 3 years less than that of the total Swiss workforce; the share of non-Swiss, with 27%, is at the level of the total workforce. In 4.1% of all cases, more than one group of providers had their first patient contact on the same day, of which 71% were a combination of GP with ED outpatient care, 16% of GP with medical specialist, and 13% of medical specialist and ED outpatient. For these, we assumed a treatment sequence as outlined in the methods section to define an unequivocal initial care provider.
Of those patients receiving care from medical specialists, 35% were treated by orthopedic surgeons, 33% by ophthalmologists, 20% by non-orthopedic surgeons, and 17% by other specialists.
GPs' involvement in accident care and initial care provision from 2008 to 2014
In 2014, GPs were involved in 70.2% of all injury cases requiring outpatient medical care but no inpatient stay and provided initial care in 56.4% (Fig. 1). While GPs' involvement remained almost constant between 2008 and 2014 (drop of − 0.9 percentage points), there was a more pronounced decline by − 4.3 percentage points of GPs providing initial care. For emergency departments (ED), we observe that both involvement (from 38.1 to 45.6%, 7.5 percentage points) and provision of initial care (from 30.4 to 35.4%, 5.0 percentage points) increased substantially. Medical specialists were involved in 16.4% of all cases in 2014 and provided initial care in 8.2% of cases. Over time, involvement increased slightly (+ 0.9 percentage points) while initial care provision declined somewhat (− 0.8%).
Variations in GPs' probability of providing initial care by patients' place of residence, gender, citizenship, age, and point in time of the accident Whether GPs provide initial care varies substantially between patients residing in urban vs. rural regions (Fig. 2). While in 2014, 54.4% of patients residing in urban regions were provided initial care by GPs, it was 58.1% of patients residing in intermediate, and 60.3% of patients residing in rural regions. EDs show a complementary pattern: the probability that EDs provided initial care was highest in urban regions with 37.0% and lowest in rural regions with 31.9%. Even when adjusting for differences in the patient population, these geographical differences remain.
Males (55.1%) had a somewhat lower probability of seeking initial care from GPs compared to females (61.3%), although the difference diminishes considerably when adjusting for other patient characteristics and injury type (adjusted: 56.1% males vs. 58.0% females). Non-Swiss citizens (49.6%) have a considerably lower probability of seeking initial care from GPs than Swiss citizens (59.0%). The difference decreases somewhat after adjustment but remains large (adjusted: 51.0% Non-Swiss vs. 58.7% Swiss). Finally, younger patients aged 20 to 35 had a lower probability of GPs figuring as initial care provider (about 54%) than elderly patients aged 55+ (above 61%) (Fig. 3). Again, these differences get slightly smaller after covariate adjustment, but remain substantial.
Regarding ED outpatient use, we observe a complementary pattern. Groups with lower probability of receiving initial care from GPs show higher probabilities for ED use.
Concerning medical specialists, there are only minor differences in initial care provision: after adjustment, there is no substantial difference between males and Further analyses show that there is considerable variation in the provision of initial care depending on the time-of-day and day-of-week the accident occurred. As Fig. 4 shows, accidents occurring during daytime/evening show a considerably higher probability (between 51 and 60%) of GPs providing initial care compared to those happening at night (49% at 11 pm, 40% at 1 am, 43% at 4 am). The Who provides initial care after an accident (GPs, medical specialists or a hospital ED) determines strongly the role of GPs during the subsequent care pathway. In the following, we categorize care pathways by GPs' role in the whole care pathway: -GP sole care provider: GPs were the only care provider -GPs → specialists/ED outpatient: initial care by GPs, subsequent care by medical specialists or emergency department (outpatient) -GP follow-up only: GPs provided only follow-up care after a medical specialist or an ED provided initial care -GP not involved: GPs were not involved at all In 2014, GPs were the sole care provider in 44.4% of the cases, i.e. no other provider group than GPs was involved (Fig. 5). This is a substantial drop by 7.0 percentage points compared to 2008 when this share was 51.4%. Correspondingly, the share of cases where GPs provided follow-up-only care increased by 3.4 percentage points Extending the above analyses of the involvement of the various providers, the initial care provider, and the role of GPs to subgroups of injuries shows that the observed pattern applies to a wide range of injuries (see Supplementing Information S 3). While the percentage of GPs providing initial and sole care is in general higher for less severe types of injuries such as bites or cuts compared to more severe ones such as fractures, the trend of an increasing substitution of EDs for GPs is observable for all injuries considered. The decline in GPs providing initial and/or sole care and the complementary increase in Eds' involvement is, however, more pronounced for less severe injuries compared to more severe ones (see Supplementing Information S 3).
Main results
Overall, our results reveal a very important role for GPs in accident care. In 2014, GPs were involved in 70% of all injury cases requiring medical care but no inpatient stay and figured as initial care provider in 56% of them. While involvement stayed at about the same level from 2008 to 2014, cases in which GPs figured as initial care providers have decreased by 4 percentage points during that period. At the same time, accident cases involving care from an emergency department (ED) increased from 38 to 46% and the share receiving initial care from an ED from 30 to 35%apparently substituting for the declining involvement of GPs in initial care. Because of the decline in providing initial care, GPs acted less as sole care providers (decrease from 51 to 44%) and increasingly as follow-up carers only (increase from 10 to 14%). Also, patients who received initial care from GPs increasingly visit EDs or a medical specialist for follow-up care, which indicates that GPs have become more inclined to refer patients to other providers.
While GPs' general involvement in accident care remained stable over time, they acted less and less as initial care provider. Apparently, EDs stepped in as a replacement resulting in the observed complementary increase in both involvement and initial care provision by EDs. Neither an increase in the non-Swiss population nor an increase in people living in urban areas can explain these changes over time because adjusting for these factors barely affects the trend identified (see Supporting Information S2 for a comparison of raw and adjusted estimates). The share of non-Swiss in the analysis sample only slightly increased from 26 to 28% between 2008 and 2014; the urban-rural ratio stayed constant.
We also found considerable variation in GPs' role by region and patient characteristics: GPs are less involved in accident care in more urban compared to more rural regions. Males, younger patients, and non-Swiss citizens have a lower probability of receiving initial care from GPs andas a resultalso show a lower probability of having GPs as their sole care provider.
Comparison with related literature
Our results are consistent with other studies on the topic that report that patients in Switzerland are increasingly treated in hospital EDs [6,7]. Our study provides systematic evidence of this development from 2008 to 2014 and clearly shows that this is at the cost of GPs, who have been providing less accident care, especially as initial care provider. Hence, Switzerland seems to increasingly suffer from "ED crowding" [20] as most countries in the industrialized world do [21]. Similar developments in the changing role of GPs have been reported for other countries with a comparable health care system relying on a strong GP-led primary care network such as The Netherlands [9] or Germany [22].
Regarding regional variations and differences between patient groups, our results are in line with existing findings from both Switzerland and abroad showing that, for instance, in urban regions, patients rather seek help directly at EDs because EDs are more accessible and convenient [22,23]. Younger people, as well as nonnationals, mighton averagebe less attached to their GPs or might not even have a personal GP, which leads to them seeking help at an ED rather than at GPs' practices when they need care urgently after an accident [24].
Implications
Our results provide detailed evidence of a profound and rapid ongoing change regarding GPs' role in accident care. Potential causes include: changing patient behavior; GPs' changing skills, preparedness and willingness to treat accident patients; structural factors such as GPs' opening-hours and availability; and the introduction of new or the more frequent application of special diagnostic tools that are not at easily at GPs' disposal. In our view, rather than just changing patients' preferences alone, also structural reasons, such as a change in the way healthcare services are operated and provided to patients, are important drivers of the observed development. The rapid pace of the development suggests this, as does the finding that changes in the patient population over time, such as an increase in urban residents or non-Swiss citizens, are not a driving force behind it.
The fact that the time-of-day and day-of-week of an accident substantially influence whether GPs act as initial care provider indicates that the choice of the initial care provider is shaped by the actual or perceived availability of GPs. One strategy to improve both the actual as well as the perceived out-of-hour availability of GPs is the cooperation of GP-networks with hospitals to create hospital-integrated primary care emergency centers. GPled, hospital-integrated primary care centers have the potential to improve service quality for patients [25], to increase the job satisfaction of GPs with respect to their out-of-hours duty periods [26,27], and to reduce costs in hospital EDs [13]. The introduction of primary care physician cooperatives located within hospital EDs led to a sizeable reduction in ED use in the Netherlands [28]. Extending GPs' opening hours to up to 12 h per day reduced the inappropriate ED use in Italy's Emilia-Romagna Region by between 10 and 15% [29].
The substantial substitution of services provided by GPs with EDs might impact the quality of care, patient satisfaction and health care costs. A preliminary costincrease-decomposition (Blinder-Oaxaca, not reported) shows that about a third of the average costs-per-case increase for outpatient cases from 768 CHF (2008) to 853 CHF (2014) is associated with the changing role of GPs.
There are also implications for the education of future GPs. Despite their decreasing involvement in accident care overall, GPs are still confronted with a wide range of injuries and need the corresponding traumatological skills (sutures, treatment of fractures). Our data can contribute to the design of educational tracks that are "evidence-based", tailored to the most frequently treated injury patterns by GPs [30].
Strengths and limitations
Our administrative data has some clear advantages over, for instance, self-reported data from population surveys: the data generating process was quite constant over the analysis period and the variables of interest are based on claims and, hence, very valid. Compared to hospital data on ambulatory and inpatient care, our data has the major advantage that it allows for reconstructing care pathways related to one particular accident. Lastly, we have information on all types of providers and can clearly show how, for instance, the decline in GPs' involvement is related to an increase in care provided by EDs.
Our study has several limitations. First, because of only partially reported data on patients' beginning of hospital inpatient stays prior to 2014, we restricted the analysis to accidents with no inpatient stay at any point during the care pathway. Accidents with no inpatient stay account for 91.5% of all accidents and its share remained quite stable during the analysis period (91.1% in 2008, 92.0% in 2014, see Figure 8 in the Supporting Information). Also, GPs, the focus of the analyses, provide initial care mostly to outpatients. Results on all patients including inpatient cases, where possible, are reported in the Supporting Information S 5. Our main conclusions regarding the changing GPs' role are supported in these analyses. Second, we have no information about the reasons why patients are treated by a particular provider. We do not know whether it was the patients' choice to seek care directly at an ED, whether they were told to do so by their GPs when trying to arrange an appointment, or whether their GPs simply weren't available. Third, patients' care pathways could only partially be reconstructed because we only know the date of the initial treatment of a provider group (GPs, medical specialists, EDs). Fourth, our information regarding the patient's injury is based on self-administered accident report forms and might not always be completely accurate. Consequently, there might be some unobserved injury heterogeneity we cannot control for in our analysis. However, it can reasonably be assumed that, over the analysis period, overall injury patterns did not change substantially. Hence, changes in service provision are likely not due to an (unobservable) change in the composition of the injuries. Fifth, regarding differences in patients' behavior, we, unfortunately, have no information on relevant patient characteristics such as education, professional background, family situation, or the existence or not of a personal GP. Finally, our results on the SUVA insured are not straightforwardly generalizable to the general population because our data includes only the working population, and no patients younger than 18 and older than 65 years. In addition, patients from the service sector are underrepresented, which leads to an underrepresentation of female employees in our analysis sample. As we have shown, females in our sample have a considerably lower rate of ED use (2014, outpatients only: 33% females vs. 36% males, see Fig. 2). For both males and females, however, there is an identical decline of 5 percentage points between 2008 and 2014, as additional analyses show. Hence, while there is a difference in levels, the observed trend over time is the same for both genders.
Conclusion
GPs play a key role in accident care with considerable variation depending on region and patient profile. From 2008 to 2014, there is a remarkable decline in GPs' provision of initial care after an accident at the cost of emergency departments. This is a strong indication that the GPs' role in the Swiss healthcare system is changing, which may have implications for their continuing education and training as well as for healthcare costs.
|
drivers: regulator: add LDO/DCDC support for Smartbond.
This add regulator driver for Smartbond DA1469X SOC. Driver can control VDD, V14, V18, V18P, V30 rails, full voltage range supported by SOC is covered.
For VDD, V14, V18, V18P DCDC can be configured.
Special VDD_CLAMP (always on) and VDD_SLEPP are added to allow configuration of VDD in sleep modes.
Whole configuration can be done in device tree and alter changed by Zephyr regulator API.
@gmarull separate PR as requested
|
Proposal talk:Platform Centric
From Strategic Planning
Jump to navigation Jump to search
User sorting
This proposal would restrict information access depending on which software is used. Also, operating system says something about the people that use it so such grouping at the end will produce rather different articles on socially sensitive topics. If this would be accepted, people would need at least two computers at time just for getting neutral point of view from Wikipedia. I think that the current cross platform approach is more reasonable. Audriusa 17:57, 27 August 2009 (UTC)
Impact?
Some proposals will have massive impact on end-users, including non-editors. Some will have minimal impact. What will be the impact of this proposal on our end-users? -- Philippe 00:14, 3 September 2009 (UTC)
|
mini-router
-----------
## Install
```bash
npm install mini-router
bower install mini-router
```
## Files
* `dist/click-interceptor.js` - ClickInterceptor (standalone library, exported as global var)
* `dist/mini-router.core.js` - Router without ClickInterceptor (standalone library)
* `dist/mini-router.js` - Router + ClickInterceptor (standalone library)
* `router.js` - CommonJS module (use with webpack or browserify)
* `ClickInterceptor.js` - CommonJS module
## Usage
```javascript
var router = new Router({
html5: true // default true if browser supports it
base: '' // optional base url (gets stripped away when routing)
routes: { '/some/route': callback } // optional routes
clickInterceptor: ClickInterceptor // override or set the ClickInterceptor
})
// Define and handle route. You can use :named parameters.
router.add('/route/:param1',function(params){
// handle your route
console.log(params.param1);
});
// Note: If you define multiple routes with the same name, only the latest callback is called!
// Manually set location and fire route handler
router.set(url)
// Normalize URL;
// - remove domain name.
router.normalize('http://yourwebsite.com/some/path/') // /some/path
// - remove ending slash
router.normalize('/some/path/') // /some/path
// - add prepending slash
router.normalize('some/path') // /some/path
// You can also only use the click interceptor.
// It translates link-clicks to hash-changes or html5 popState()
ClickInterceptor({
html5: true,
base: '',
normalize: function(url){
return url;
},
set: function(url) { } // callback function to set URL of the router in HTML5 mode
});
```
## Why?
It seems that you only listen to **history** events. There is no event fired when the user navigates to a new location.
So we have to intercept click events. However, no [micro router library](http://microjs.com/#router) has this functionality.
So I wrote this one!
## Changelog
* 0.5.0: Bugfix
* 0.4.0: Fixed ClickInterceptor bug with HTML5 (there is no `onpushstate` listener, so explicitly call `router.set(url)`)
* 0.3.0: Fixed some versioning issues with NPM and Bower
* 0.2.0: Split Router into Router + ClickInterceptor. Some minor improvements.
* 0.1.0: Initial release
## Contribute
Feel free to contribute to this project in any way. The easiest way to support this project is by giving it a star.
## Contact
- @markmarijnissen
- http://www.madebymark.nl
-<EMAIL_ADDRESS>
© 2014 - Mark Marijnissen
|
[Federal Register Volume 72, Number 187 (Thursday, September 27, 2007)]
[Pages 54916-54917]
[FR Doc No: E7-19130]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Request for Nominations for Voting Members on Public Advisory
Committee, Veterinary Medicine Advisory Committee
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
The Food and Drug Administration (FDA) is requesting nominations
for voting members to serve on the Veterinary Medicine Advisory
Committee (VMAC), Center for Veterinary Medicine (CVM).
FDA has a special interest in ensuring that women, minority groups,
and individuals with disabilities are adequately represented on
advisory committees and, therefore, encourages nominations of qualified
candidates from these groups.
DATES: Nominations received on or before October 30, 2007, will be
given first consideration for membership on the Veterinary Medicine
Advisory Committee. Nominations received after October 30, 2007, will
be considered for nomination to the committee should nominees still be
needed.
ADDRESSES: All Nomination for membership should be sent electronically
to [email protected], or by mail to Advisory Committee Oversight &
Management Staff, 5600 Fisher Lane, HF-4, rm. 15A-12, Rockville, MD
20857.
FOR FURTHER INFORMATION CONTACT: Regarding all nomination questions for
membership, the primary contact is Aleta Sindelar, Center for
Veterinary Medicine (HFV-6), Food and Drug Administration, 7519
Standish Pl., Rockville, MD 20855, 240-276-9004, FAX: 240-276-9020, e-
mail: [email protected]. Information about becoming a member
on a FDA advisory committee can also be obtained by visiting FDA's Web
site by using the following link http://www.fda.gov/oc/advisory/default.htm.
SUPPLEMENTARY INFORMATION: FDA is requesting nomination for voting
members on the Veterinary Medicine Advisory Committee.
I. Function of the Veterinary Medicine Advisory Committee
The Committee reviews and evaluates available data concerning the
safety and effectiveness of marketed and investigational new animal
drugs, feeds, and devices for use in the treatment and prevention of
animal diseases and increased animal production, and makes appropriate
recommendations to the Commissioner of Food and Drugs regarding
scientific issues and regulatory policies.
II. Criteria for Voting Member
FDA is requesting nominations of voting members with appropriate
expertise in the following veterinary specialties: companion animal
medicine, food animal medicine (avian, bovine, porcine and minor
species), microbial food safety and risk assessment, biometrics,
toxicology, pathology, pharmacology, animal science, epidemiology.
III. Nomination Procedures
Any interested person may nominate one or more qualified persons
for membership on one the advisory committee. Self-nominations are also
accepted. Nominations shall include the name of the committee, a
complete curriculum vitae of each nominee, and their current business
address and telephone number and e-mail address if available. Each
nomination shall state that the nominee is aware of the nomination, is
willing to serve as a member, and appears to have no conflict of
interest that would preclude membership. FDA will ask the potential
candidates to provide detailed information concerning such matters as
financial holdings, employment, and research grants and/or contracts to
permit evaluation of possible sources of conflict of interest.
This notice is issued under the Federal Advisory Committee Act (5
U.S.C. app.2) and 21 CFR part 14 relating to advisory committees.
Dated: September 13, 2007.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E7-19130 Filed 9-26-07; 8:45 am]
BILLING CODE 4160-01-S
|
/*
* Project: is-yarn
* Version: 0.0.1
* Author: Akash Nimare
* Twitter: @meakaakka
* License: MIT
* GitHub: https://github.com/akashnimare/is-yarn
*/
'use strict'
const cmd = require('child_process').exec
// function to check if yarn is installed globally
function isyarn () {
cmd('npm ls | npm list --depth 1 --global yarnpkg', (error) => {
if (error === null) {
console.log('true')
} else {
console.log('false')
}
})
}
// exports
module.exports = {
isyarn
}
|
"use strict";
var __importDefault = (this && this.__importDefault) || function (mod) {
return (mod && mod.__esModule) ? mod : { "default": mod };
};
Object.defineProperty(exports, "__esModule", { value: true });
var Service_1 = __importDefault(require("../../network/Service"));
var sinon_1 = __importDefault(require("sinon"));
require("isomorphic-fetch");
var fetchResponses_1 = require("../TestUtils/fetchResponses");
var requestOptions = {
csrfToken: 'abc',
baseUrl: 'http://localhost'
};
describe('test Service', function () {
var service;
beforeEach(function () {
service = new Service_1.default(requestOptions, "/");
sinon_1.default.stub(window, "fetch").returns(fetchResponses_1.jsonOk({ 'status': 'ok' }));
});
afterEach(function () {
//@ts-ignore
window.fetch.restore();
});
describe('test save() with FormData', function () {
var formData;
beforeEach(function () {
formData = new FormData();
formData.append('name', 'John');
});
test('fetch-url', function () {
return service.save(formData).then(function () {
//@ts-ignore
expect(fetch.getCall(0).args[0]).toBe('http://localhost/');
});
});
test('request headers', function () {
return service.save(formData).then(function () {
//@ts-ignore
var fetchCall = fetch.getCall(0);
expect(fetchCall.args[1]).toMatchObject({
headers: {
'Accept': 'application/json',
'X-CSRF-TOKEN': requestOptions.csrfToken
}
});
expect(fetchCall.args[1]).not.toMatchObject({
headers: { 'Content-Type': 'application/json' }
});
});
});
test('request body', function () {
return service.save(formData).then(function (res) {
//@ts-ignore
expect(fetch.getCall(0).args[1]).toMatchObject({
body: formData
});
});
});
});
describe('test save() with Model', function () {
var blog;
beforeEach(function () { return blog = { content: 'abc' }; });
test('request url', function () {
return service.save(blog).then(function () {
//@ts-ignore
expect(fetch.getCall(0).args[0]).toBe('http://localhost/');
});
});
test('request headers', function () {
return service.save(blog).then(function () {
//@ts-ignore
expect(fetch.getCall(0).args[1]).toMatchObject({ headers: {
'Accept': 'application/json',
'X-CSRF-TOKEN': requestOptions.csrfToken,
'Content-Type': 'application/json'
} });
});
});
test('request body', function () {
return service.save(blog).then(function () {
//@ts-ignore
expect(fetch.getCall(0).args[1]).toMatchObject({
body: JSON.stringify(blog)
});
});
});
});
});
//# sourceMappingURL=Service.spec.js.map
|
<?php
namespace App\Models;
use Illuminate\Database\Eloquent\Factories\HasFactory;
use Illuminate\Database\Eloquent\Model;
class Estimates extends Model
{
use HasFactory;
protected $fillable=['cust_name','agentid','machine_name','machine_number','estimated_price','age_id','complaints'];
}
|
package com.zlyx.easysocket.utils;
import java.util.ArrayList;
import java.util.List;
import java.util.Set;
import java.util.concurrent.ConcurrentHashMap;
import java.util.concurrent.ConcurrentMap;
import java.util.concurrent.ExecutorService;
import java.util.concurrent.Executors;
import org.springframework.context.ApplicationListener;
import org.springframework.context.event.ContextRefreshedEvent;
import com.zlyx.easysocket.annotations.EasyBean;
/**
* @Auth 赵光
* @Desc 线程池自动化管理工具
* @2018年12月12日 下午2:19:03
*/
@EasyBean(todo = "线程池自动化管理工具")
public class ThreadManager{
private static ConcurrentMap<String,Thread> threads = new ConcurrentHashMap<String,Thread>();
private static ExecutorService threadPool = Executors.newCachedThreadPool();
/**
* 分配一个线程执行任务
* @param thread
* @return
*/
public static String execute(Thread thread) {
return execute(thread, thread.getName());
}
/**
* 分配一个线程执行任务
* @param name
* @param command
* @return
*/
public static String execute(Thread thread, String name) {
if(isActive()) {
threads.put(name, thread);
threadPool.execute(thread);
}
return name;
}
/**
* 根据名称获取线程
* @param name
* @return
*/
public static Thread getThread(String name) {
return threads.get(name);
}
/**
* 判断某个线程是否存活
* @param name
* @return
*/
public static boolean isAlive(String name) {
clearDead();
return threads.containsKey(name);
}
/**
* 判断线程池是否可用
* @return
*/
private static boolean isActive() {
return threadPool != null && !threadPool.isShutdown();
}
/**
* 获取当前存活的所有线程的名称
* @return
*/
public static Set<String> getNames(){
clearDead();
return threads.keySet();
}
/**
* 获取所有存活中的线程列表
* @return
*/
public static List<Thread> getThreads(){
return new ArrayList<Thread>(threads.values());
}
/**
* 清除已经死亡的线程
*/
public static void clearDead() {
Set<String> names = threads.keySet();
for(String name : names) {
if(!isAlive(name)) {
threads.remove(name);
}
}
}
@EasyBean(todo = "系统更新时重新启动线程池")
public static class ThreadRefresher implements ApplicationListener<ContextRefreshedEvent> {
@Override
public void onApplicationEvent(ContextRefreshedEvent event) {
if(isActive()) {
threadPool.shutdown();
}
threadPool = Executors.newCachedThreadPool();
}
}
}
|
24 A MANUAL FOB NORTHERN WOODSMEN
corner to leave there his initials, or some mark peculiar to him which will identify it as his work, together with the year in which the survey was made. The same thing may be done by a succeeding surveyor.
Practice in all these matters, however, varies a good deal in different parts of the country. The methods presciibed for use in the United States land surveys will be found on later pages of this volume.
Lines. A property line in the forests of Germany is kept cleared out several yards wide and blocks of cut stone are deeply set along it near enough together so that one may be seen from another. In addition, the range of a transit line is inscribed upon them. This renders the property limit prominent and durable, and, further, defines it to within a quarter of an inch.
Such ideal marking is seldom to be looked for in this country, but the ends to be aimed at, which in the fore going case were attained, should be in the mind of every man who has to do with forest boundaries. A property owner's interests are first, to have his bounds prominent so that he and other parties may know where they are and so that there will be no excuse for trespass ; second, to have them durably marked for obvious reasons ; and third, to have them so closely defined that all possible causes of dispute may be avoided.
Stone walls, ditches, and fences are the common bounds of property in settled and half-settled countries, and each of these methods of delimitation has its grade of efficiency, considered from the above points of view. In large forest areas blazed trees are the means almost universally em ployed for the purpose. That system has been reasonably satisfactory in the past. It would have been more so had care and system always been employed in the marking and more attention paid to renewal.
The directions for marking lines in timbered lands, as contained in the " Manual of Instructions for the Survey of tin- Public Lands of the United States," are as follows:
mes cm which are to IK- established the le-ral corner boun daries \M!| !< marked after this method, vi/. : Those trees which may be intersected by the line will have two chops or notches cut
|
sect in Ontario, ranging northward about as far as Muskoka and the Bruce Peninsula. It frequents fields, vacant lots and road sides, which resound at night with the incessant monotonous song. During the summer and autumn * * * I have occasionally heard it stridulating in bright sunshine in the afternoon. It is the most easily approached of all our locustarians while thus engaged and is in fact difficult to find in "any other way, hence the females are but seldom seen. Although it usually perches upon tall weeds, I have occasionally traced its song to a tree or vine, the insect being sometimes stationed at a considerable height."
Allard (1911) says that in September near Oxford, Mass., cnsiger is a very common species in all upland localities where it "prefers the fresh herbage of cultivated fields and is especially to be looked for in fields of corn. One oftentimes finds a noisy singer perched six or seven feet from the ground on a corn stalk or tassel. One also sometimes meets with it in large colonies among the luxuriant weeds and grasses of the lowlands. Its call notes are intermittent and follow each other rather briskly tslp-tsip-tsip-tsip. They are rather soft and lisping, recalling to mind the staccato lisps of an OrclicUnniin."
Size large, form robust. Pale green, rarely brown; fore and middle legs, hind tibiae and tarsi and under surface greenish-yellow; sides of fastigium and lateral carinag of pronotum yellowish; antennae pale reddish yellow. Fastigium with under surface immaculate, 06 about as long as oc ciput, distinctly narrowed from middle to apex, its upper surface convex, tip narrowly rounded (Fig. 169, f.) Pronotum with lateral carinse dis tinctly divergent, more strongly so in male, hind margins broadly rounded, surface finely punctate; lateral lobes almost as deep as long their lower margin oblique, obtusely angulate; humeral sinus shallow, broadly rounded. Tegmina broader than in allied species, surpassing hind fe mora about 13 mm. Stridulating field of male large, its main vein heavy. Fore and middle femora either unarmed beneath or with a few small spines. Hind femora long, slender, armed beneath with three to 12 rather short spines on each carina. Length of body, $ , 30, $, 31 37; of fastigium, $, 2.73.6, $, 3.13.7; of pronotum, $, 89.9, 9, 7.38.3; of tegmina, $, 4048, $, 4354; of hind femora, $, 2328, $, 2428; of ovipositor, 25 31 mm. (Fig. 175.)
66 This is true of all the specimens at hand and R. & H. (.1915, 387) say that the ver tex is always immaculate, but Scudder, in his original description, loc. cit., says of the type: "tubercle of the vertex tipped with black, not extending or but very faintly and narrowly, down the sides."
|
Securing data stored on a file
Suppose I have an application, which when opened asks you to open a file and then "unlock" that file using a password that's configurable by the user.
The file should be encrypted with something like AES-256, right? The key would be the password, but should the users password be hashed using something like SHA-256? Should I salt the hash as well? If I do salt the hash, do I just store the salt at the start of the file?
Is this the correct way to go about things?
A typical (and relatively weak) password usually is not a suitable key for encryption, you need to learn about key derivation functions (https://en.wikipedia.org/wiki/Key_derivation_function). Those functions often perform key stretching or strengthening, and can slow down bruteforce attacks.
Just asking to understand your question better - is your application a file-store, that has access controls (user-specific) for different files? Can each user see only the files that are accessible for him/her?
Additionally, please check this answer, it may have some useful information for you.
@MSSripati When the user uses the app for the first time, they can save the data with their own (customizable) key. So every user has their own files representing the data
You can use AES for basic symmetric file encryption. The key can be derived from a password using PBKDF2 or some other key derivation function. See https://crypto.stackexchange.com/questions/3298/is-there-a-standard-for-openssl-interoperable-aes-encryption for how openssl does it, and for the structure of the encrypted file.
There can be many different solutions possible. I'd suggest to consider following.
First consider standard tools. Can your users use VeraCrypt?
If not, how about using some broadly used archiving formats like ZIP, RAR, 7z? They all support encryption.
Use any of encryption algorithms that are broadly known like AES-256, ChaCha20, Threefish-256.
Think of proper mode. For instance, if files are relatively big and if you need random access to different file fragments, you may prefer AES GCM to AES CBC.
Applying passwords for encryption as is can make brute-forcing easier, because depending an attacker can test a considerable number of passwords in a short time. Instead, derive the encryption key using algorithms like Argon2, bcrypt, scrypt. Configure it in such way that derivation of a single key takes 1s. Such delay can be acceptable for user and this will reduce brute-forcing speed to 1 password per second.
To derive encryption key you will need the same parameters as used for encryption: salt, the number of iterations, memory factor (Argon2), parallelism (Argon2). That's why you need to store them. How you store them (at the beginning, at the end) is up to you.
|
# SISGA
[](https://travis-ci.org/csimons/sisga)
An extensible genetic algorithm engine and benchmarking suite.
## BUILDING
Assuming the JDK (version 1.8+ should work), Apache Maven, and Gnuplot have
been properly installed, the project can be built by issuing the following
command from the project's root directory: mvn install.
## RUNNING (SINGLE RUNS)
Algorithm configuration and parameters are specified in configuration files
located in the config/ directory. An example has been provided in the
"ga.properties" file. To run a configuration, execute the JAR, specifying the
configuration name (the file name without the ".properties" suffix) as the
argument. Optionally, you may also specify the "-v" flag, which will print
summary information during execution; if specified, this flag must come BEFORE
the configuration name:
$ java -jar target/sisga.jar -v config/ga
This will create a GnuPlot data file with a name "A-T.dat", where A is the name
of the run configuration and T is a timestamp, in the format specified in the
run's configuration file (here, "config/ga.properties"). For example, for the
default "ga" configuration, the file might be named "ga-201112131733.dat".
To plot the results as a PNG image file, run the following:
$ bash scripts/plot.sh
The above will create PNG image files in the current directory for any GnuPlot
data files it finds in the current directory ("testing-1234.png" would be
generated from "testing-1234.dat").
## AGGREGATE ANALYSIS
Scripts can be used to handle multiple runs of data. These scripts must be run
from the project root directory, and can be executed only after the project has
been built.
1. Several runs can be executed at once by using the scripts/n-runs.sh program.
Run the program without arguments to view the usage message.
2. Aggregate metrics can be viewed by using the aggregate analyzer program.
The user interface for this is the scripts/analyze.sh program. Run the
program without arguments to view the usage message.
So, a common manner of gathering aggregate data might be as follows:
$ git clone http://github.com/csimons/sisga # download the project
$ cd sisga # go to project root directory
$ ant # build the project
$ cd config # navigate to configurations
$ cp ga.properties my-ga.properties # create a configuration
$ vim my-ga.properties # set parameters, function
$ cd .. # go to project root directory
$ bash scripts/n-runs.sh 50 config/my-ga # execute 50 runs
$ bash scripts/analyze.sh my-ga-*.dat # view aggregate metrics
The script "scripts/do-collect.sh" will run a collection for all existing
configurations in the "config" directory, for the number of executions
specified in the command-line argument. This may be useful if one wishes to
compare performance among configurations.
## EXTENDING
To extend the engine, to do things like implementing other GAs (GENITOR, etc.),
fitness functions, decoders, and so forth, simply create a new class extending
the appropriate interface, which will be one of the following:
com.oracli.sisga.alg.ga.GA
com.oracli.sisga.alg.mutation.chromosome.ChromosomeMutation
com.oracli.sisga.alg.mutation.population.PopulationMutation
com.oracli.sisga.alg.recombination.Recombination
com.oracli.sisga.alg.selection.parent.ParentSelection
com.oracli.sisga.alg.selection.survivor.SurvivorSelection
com.oracli.sisga.decode.Decoder
com.oracli.sisga.fitness.Function
The class com.oracli.sisga.alg.ga.AbstractGA has been provided to make the
development of new GA implementations more finger-friendly. It implements the
GA interface and can be extended rather than implementing GA directly. See
how this is used in the CHC and CanonicalGA classes for examples.
Once you have created your new component implementations (and they are in the
appropriate directory and implement the appropriate interface), simply rebuild
the project in order to be able to use the components in new configurations.
|
Valentina Vlasenko (Subbocheva)
Biography
Awards
* Order of Bogdan Khmelnitsky (Ukraine), 3rd class № 40880
* Defender of the Motherland Medal
* Order of the Patriotic War, 2nd class № 34128 (1943)
* Order of the Patriotic War, 2nd class № 3504341
* Order of the Red Star № 265792 (1943)
* Medal for Battle Merit № 2335160 (1945)
* Medal "For the Defence of Stalingrad"
* Medal "For the Victory over Germany in the Great Patriotic War 1941–1945"
* Medal "For the Capture of Berlin"
* Medal "For the Liberation of Warsaw"
* Twelve Jubilee Medals
|
listview with different view layouts
I have a listview with different rows with different layout.
layout1.xml
<LinearLayout
android:height="wrap_content"
android:width="fill_parent">
<TextView
android:height="wrap_content"
android:width="wrap_content"
android:text="One"
android="@+id/one"/>
</LinearLayout>
layout2.xml
<LinearLayout
android:height="wrap_content"
android:width="fill_parent">
<TextView
android:height="wrap_content"
android:width="wrap_content"
android:text="One"
android="@+id/one" />
<TextView
android:height="wrap_content"
android:width="wrap_content"
android:text="Two"
android="@+id/one" />
</LinearLayout>
Since the adapter recycles all of its views, how will it know if
layout1 is recycled. If layout1 is recycled, convertView is not null,
and I try to find textview2. Should this throw null pointer?
Assume convertView is always recycled and no need to inflate view. So,
layout1 is recycled, but the below code is expecting layout2 for the
position.
in the getView(),
@Override
public View getView(int position, View convertView,
ViewGroup parent) {
//A method to tell if layout1 or layout2 should be inflated based on the position
boolean inflateOne = inflateLayoutOne(position);
if(convertView == null){
if(inflateOne)
convertView = inflater.inflate(R.layout.layout1, null);
else
convertView = inflater.inflate(R.layout.layout2, null);
}
if(inflateOne){
TextView tv1 = (TextView)convertView.findViewById(R.id.one);
tv1.setText("Hello one");
}
else{
TextView tv1 = (TextView)convertView.findViewById(R.id.one);
tv1.setText("Hello one");
TextView tv2 = (TextView)convertView.findViewById(R.id.two);
tv1.setText("Hello Two");.
return convertView;
}
My question is to understand, how does the listview know which type it is, while getting the recycled view
http://stackoverflow.com/questions/11945563/how-listviews-recycling-mechanism-works. see this
you are doing it wrong. If you want to have different kind of rows, you have to override getViewTypeCount and getViewItemType. Both return an int value. getView will receive a number of null convertView equals to the value you return in getViewTypeCount. You should use getViewItemType to distinguish between the different view
Your adapter must override getItemViewType(int position). From the docs:
Returns: An integer representing the type of View. Two views should
share the same type if one can be converted to the other in
getView(int, View, ViewGroup). Note: Integers must be in the range 0
to getViewTypeCount() - 1. IGNORE_ITEM_VIEW_TYPE can also be
returned.
http://developer.android.com/reference/android/widget/Adapter.html#getItemViewType(int)
To tell which layout the convertView is returning, you should be able to just compare the ids.
if (convertView.getId() == R.layout.layout1){
//set data for layout 1
}else if(convertView.getId() == R.layout.layout1){
//set data for layout 1
}
Exactly, but this is not done on any of the reference articles, or here, http://stackoverflow.com/a/15706073/563306
|
Storage rack with wood cross bars and end bracket for the same
ABSTRACT
A novel end bracket for the ends of each of several wood cross bars that support the shelf decking in a storage rack, and a storage rack incorporating the same. The end bracket has a rigid main rectangular plate with a thin, flat, rigid supporting tongue extending rigidly outward from one side of the plate for a substantial distance beyond the cross bar end. A rigid flange extends downward from each end of the main rectangular plate for embracing the cross bar end. A rigid finger extends inward at the bottom of each of the flanges, at a slight obtuse angle to the flange, for confining the cross bar end. At least one rigid hook member extends inward at the bottom of each flange, with a rigid tapered tip oriented at an acute angle to the shank of the hook member, for fixedly securing the end bracket to the cross bar by driving the hook into the cross bar.
This invention relates to a storage rack in which the shelves are formed of particle board or plywood decking and are supported by wood cross bars, and to a novel bracket for supporting the ends of such cross bars.
BACKGROUND OF THE INVENTION
Storage racks have been used for many decades in which several wood cross bars (which are themselves supported on steel step ledge beams running lengthwise of the shelves) support shelving formed of particle board or plywood decking. Some users prefer to employ formed steel cross bars in place of wood cross bars to support the shelf decking, but such structures cost substantially more. For the relatively short spans involved, wood cross bars for supporting the decking are much more economical.
Although they have been in use a very long time, conventional storage racks utilizing wood cross bars have several disadvantages. One such storage rack has the advantage that both longitudinal edge portions of the rectangular shelving are fully supported on the steel step ledge beams on each side of the rack, so that a minimum number of cross bars is required to provide support across the lateral mid-portion of the shelf decking. However, in this type of storage rack the typical decking of 3/4" thickness uses up storage space because it extends above the step ledge beams on which it is supported. In addition, the raw decking edge is exposed, which from time to time may cause the user of the storage rack to get wood slivers in his hand or in the products being stored. Finally, the decking must be fastened down by fasteners such as nails driven into the wood cross bars.
In a variation of this conventional storage rack, the ends of the wood cross bars are notched to drop them down farther on the step ledge beams so that the decking thickness does not use up any storage space, there are no exposed sliver-carrying edges on the decking and, since the decking is contained by the rear wall of each step, no nails or other fasteners are required. In addition, the top of the step ledge beam on each side of the shelf is flush with the decking and this maintains the effective usable area of the shelf. However, since the shelf decking is ordinarily not flexible enough to bend down the required 1" or so to bring it into contact with the step of the steel step ledge beam, this variation provides no support for the longitudinal edge portions of the decking, which makes it necessary to employ more cross bars and therefore increases the cost. In addition, the notches in the two ends of each cross bar add to the cost of fabrication and reduce the strength of the structure.
If the last two disadvantages of this variation of the conventional deck were avoided by omitting the notches in the cross bars and making the steps in the steel step ledge beams deeper, this would require the beams themselves to be of deeper dimensions, and would thereby very substantially increase the materials cost for the storage rack.
The storage rack and end bracket of the present invention achieve all the advantages referred to that are achieved with the conventional storage racks with decking shelves supported as just described, and present none of the disadvantages involved in those conventional racks.
SUMMARY OF THE INVENTION
The storage rack of this invention includes a novel end bracket for the ends of each of several wood cross bars that support the shelf decking in the rack. Each of the cross bars has a predetermined maximum and minimum length, two major surfaces of a predetermined width,and predetermined maximum and minimum thicknesses.
The end bracket of this invention comprises:
1. A rigid main rectangular plate that has a predetermined width sufficiently large that the plate provides a secure overlying contact with the end of the cross bar even when the cross bar is of its predetermined minimum length;
2. A thin, flat, rigid supporting tongue extending rigidly outward from one side of the rectangular plate for a predetermined distance sufficiently large that the tongue extends a substantial distance beyond the cross bar end even when the cross bar is of its predetermined maximum length;
3. A rigid flange extending rigidly downward from each end of the main rectangular plate for embracing the cross bar end in a position in which the tongue extends outward from the cross bar a substantial distance;
4. A rigid finger extending rigidly inward at the bottom of each of the flanges for confining the cross bar end; and
5. At least one rigid hook member extending inward at the bottom of each of the flanges for fixedly securing the end bracket to the cross bar by driving the hook into the cross bar.
The finger that extends inward at the bottom of each of the described flanges has its base at a distance from the main rectangular plate that is substantially equal to the predetermined minimum thickness of the cross bar. The free end of the finger is at a distance from the main rectangular plate that is substantially equal to the predetermined maximum thickness of the cross bar.
Each of the one or more hook members that extends inward at the bottom of each of the flanges has a rigid shank connected at its base to the flange, and the shank carries at its free end a rigid, tapered tip that is rigidly oriented at an acute angle to the shank. The base of this shank is at a distance from the main rectangular plate that is substantially equal to the predetermined minimum thickness of the cross bar. The free end of the tapered tip is normally at a distance from the main rectangular plate that is substantially equal to the predetermined maximum thickness of the cross bar.
As pointed out above, the present invention achieves all the advantages and avoids all the disadvantages of the prior art storage racks that employ wood cross bars. In addition, the rack and end bracket of this invention provide several additional advantages.
First, as a result of the construction described above, the end bracket can be securely attached to a cross bar of any thickness between its predetermined maximum and minimum thicknesses. The bracket can, in other words, accommodate variations in the thickness of the cross bar, yet provide a positive securing force at both the bottom and the t qp surfaces of the cross bar.
Second, the end bracket can be secured to a wood cross bar at any of several positions to accommodate a bar of any length between the predetermined maximum and minimum lengths. Put another way, the end bracket of this invention has a lengthwise adjustability to accommodate cross bars of slightly different lengths.
Finally, the hook members of the end bracket provide a very secure connection of the bracket to the cross bar end, for when the end bracket is installed in place not only are the hooks driven into the wood cross bar but, because of the acute angle between the hook tip and its shank, the hooks slant back within the wood that comprises the end portion of the cross bar, thus providing additional security of attachment of the bracket to the bar.
An improved storage rack results when the end bracket of this invention is incorporated in a rack to provide support for the ends of the wood cross bars (which in turn support the shelf decking) on the ledges of the steel step ledge beams along the sides of each shelf.
BRIEF DESCRIPTION OF THE DRAWING
This invention will now be described with reference to the accompanying drawing, in which:
FIG. 1 is a fragmentary, isometric three-quarters view of shelf decking of a storage rack supported in a conventional manner;
FIG. 2 an enlarged end elevation of the shelf support system of FIG. 1 seen from the right-hand side of the latter Figure;
FIG. 3 a view similar to FIG. 1 of another form of a conventional support for deck shelving in a storage rack;
FIG. 4 is an enlarged end elevation of the shelf support system of FIG. 3 seen from the right-hand side of the latter Figure;
FIG. 5 is a view similar to FIGS. 1 and 3 of shelf decking supported according to the present invention;
FIG. 6 is an enlarged end elevation of the shelf support system of FIG. 5 seen from the right-hand side of the latter Figure;
FIG. 7 is a further enlarged, fragmentary, side elevation of the end bracket of this invention attached to the end of a cross bar having the predetermined minimum length;
FIG. 8 is a view similar to FIG. 7 of the end bracket of this invention mounted on the end of a wood cross bar having the predetermined maximum length;
FIG. 9 is a three-quarters isometric view of the end bracket of this invention from the bottom of the bracket; and
FIG. 10 is an end elevation of the embodiment of the end bracket of this invention shown in FIG. 7, taken from the right-hand side of the latter Figure.
DETAILED DESCRIPTION OF ONE EMBODIMENT OF THE INVENTION
FIGS. 5-10 show one embodiment of the storage rack and end bracket of this invention. This embodiment is to be contrasted with the prior art storage racks shown in FIGS. 1-4.
PRIOR ART STORAGE RACKS First Prior Art Storage Rack
FIG. 1 is a fragementary, isometric three-quarters view of rectangular shelf decking 20 of storage rack 22 supported in a conventional manner. Both longitudinal edges 24 of the rectangular shelving are fully supported on each side of the rack on the top walls of steel step ledge beams 26, which are in turn supported on suitable vertical frame posts (not shown).
The rectangular shelf decking shown in FIG. 1 is approximately 4' wide and 8' long. In this prior art storage rack, three or four wood cross bars 28 (typically formed of conventional 2"×4" lumber) are supported at each end by step 30 of beam 26. In conjunction with the support of edge portions 24 of deck shelving 20 by beams 26 already mentioned, this minimum number of wood cross bars provides sufficient support for shelf decking 20 when product to be stored is placed on the shelf.
Despite the advantage of the indicated positive support of edge portions 24 of shelf decking 20, it is seen that this prior art shelving system has several disadvantages. Decking 20 is typically formed of 3/4" thick particle board or plywood, and this thickness uses up a small but important part of the available storage space because it extends above beams 26 on which the decking is supported. In addition, raw edge 32 of decking 20 is in an exposed position where, from time to time, it may cause the user of the storage rack to get wood slivers in his hand or in the product being stored. Finally, decking 20 must be fastened down by fasteners such as nails 34 that are driven into the wood decking and wood cross bars 28 beneath the decking.
If no such fasteners were employed, it is seen that decking 20 would be free to slide on step ledge beams 26. FIG. 2 shows how nails 34 and cross bars 28 secure decking 20 in this prior art storage rack against sidewise displacement.
Second Prior Art Storage Rack
FIGS. 3 and 4 show a second prior art storage rack 38 in which the ends of wood cross bars 40 are notched at 42 to drop them down farther on step ledge beams 44.
In this embodiment, the extra space provided when cross bars 40 are dropped down a distance accommodates the thickness of shelf decking 46 so that that thickness does not use up any storage space. In addition, there are no exposed sliver-carrying edges on decking 46 because raw edges 48 of the decking nest within steps 50 of beams 44. Since decking 46 is contained by rear wall 52 of each step 50, no nails or other fasteners are required to prevent sidewise movement of decking 46 in this form of storage rack. In addition, top wall 54 of each step ledge beam 44 on each side of shelf 46 is flush with the decking, which maintains the effective useful area of the shelf.
One of the disadvantages of this form of storage rack is that wood cross bars 40 provide support for decking 46 only at the two shorter edge portions 56 of the shelf, along which the outer cross bars 40 are positioned. As will be seen from FIGS. 3 and 4, longer edges 48 of decking 46 are supported only at intervals by cross bars 40.
In addition, notches 42 in the two ends of each cross bar 40 add to the cost of fabrication of the storage rack. Moreover, since thickness 60 of the portion of cross bar 40 lying above notch 42 is less than thickness 62 of the remainder of cross bar 40, the strength of the support supplied by the cross bars to decking 46 is reduced.
It might be suggested that to avoid the latter two disadvantages notches 42 in cross bars 40 could be eliminated by increasing the depth of steel step ledge beams 44. However, this would obviously require that these beams be deeper and would very greatly increase the materials cost for the rack.
STORAGE RACK AND END BRACKET OF THIS INVENTION
The storage rack of this invention, in which the shelves are formed of particle board or plywood decking and are supported by wood cross bars, and the novel bracket for supporting the ends of these cross bars, will now be described with reference to FIGS. 5-10 of the drawing.
Support Of Shelving
FIG. 5 shows a portion of storage rack 70 in which shelf decking 72 is supported by three wood cross bars 74 and their end brackets 76, which are securely attached to each end of cross bars 74.
Thin, flat, rigid, supporting tongue 78 of end bracket 76 is the only material that is interposed between cross bar 74 and the overlying portions of decking 72, and between edge portions 80 of decking 72 and step 82 of beam 84.
Since tongue 78 is typically formed of steel that is only a little more than about 1/16"thick, and decking 72 has a slight degree of flexibility, the structure described means that when a heavy load is placed on shelf 72, the decking will bow down along wood cross bars 74 and along steps 82 of steel beams 84, to be supported positively by members 74 and 84 in a very large part of the areas of shelf decking 72 that overlie those members.
Advantages Of This Invention
The described structure avoids the following prior art disadvantages that have been referred to above:
1. Shelf decking 72, typically formed of μ" thick particle board or plywood decking, does not extend above step ledge beam 84 to intrude into the storage space.
2. The raw decking edges along edge portions 80 of shelf decking 72 are not exposed, so that the user of the storage rack does not run the risk of getting wood slivers in his hand or in the products being stored.
3. No fasteners need to be provided for shelf decking 72, because rear walls 86 of steps 82 of steel step ledge beams 84 enclose and contain the decking.
4. The top surface of each step ledge beam 84 is flush with decking 72, which maintains the effective usable area of the shelf.
As will be seen from the following discussion of FIGS. 7-10, the end bracket of this invention has additional advantages that provide an improved construction for any storage rack in which the end bracket is incorporated.
Main Rectangular Plate
In FIG. 7, end bracket 76 is securely attached to the end of wood cross bar 74, which in this showing has the predetermined minimum length of cross bars employed with the end bracket of this invention.
Cross bar 74 has two major surfaces 94 of a predetermined width d₁ (FIG. 5). Bracket 76 includes main rectangular plate 96 for overlying secure contact with one of the cross bar major surfaces 94.
Plate 96 has a predetermined width d₂ sufficiently large that the plate will provide secure overlying contact with cross bar 74 when, as in FIG. 7, the cross bar is of its predetermined minimum length. In this Figure, the shortfall in the length of cross bar 74 is exaggerated for emphasis over what is likely to be encountered in the actual construction of storage racks in accordance with the present invention. However, it is preferred that even small variations in the length of the cross bars such as are likely to be found in actual construction be adjusted for, as the end bracket of this invention does.
As will be seen from FIG. 7, the width of plate 96 is such that even though the cross bar of predetermined minimum length may not fully reach the right-hand edge of flange 98, still end bracket 76 overlaps the end of bar 74 by a distance d₃ that is sufficiently large that there is a secure contact between the end bracket and cross bar.
In the embodiment shown, main rectangular plate 96 is stiffened by depressed portion 97 extending longitudinally of the plate.
Downwardly Extending Flanges
Rigid flanges 98 extend rigidly downward from each end of main rectangular plate 96 to embrace the end of cross bar 74. As seen in FIG. 9, the internal distance between the two downwardly extending flanges 98 is substantially equal to width d₁ of the end of cross bar 74.
Each flange 98 preferably has a width substantially equal to width d₂ of main rectangular plate 96. This dimension provides a secure contact between downwardly extending flanges 98 and side walls 100 of cross bar 74.
Supporting Tongue
As best seen in FIGS. 7-9, thin, flat, rigid, supporting tongue 78 extends rigidly outward from one side of main rectangular plate 96. It extends for a predetermined distance sufficiently large that the tongue extends a distance d₄ beyond cross bar end 104 even when the cross bar is of its predetermined maximum length. In FIG. 8 the amount by which wood cross bar 74' exceeds the standard length for such bars is again exaggerated for emphasis.
The distance tongue 78 extends outward from main rectangular plate 76 is preferably substantially less than predetermined width d₂ of the rectangular plate.
As explained above, tongue 78 (like the remainder of end bracket 76) is formed of steel of a thickness not much more than about 1/16". The decking of the shelf is supported at all times by contact with main rectangular plates 96 of brackets 76 at the ends of cross bars 74 (or 74'), and with tongues 78 extending outward from the ends of cross bars 74 (or 74'). When a sufficiently heavy load is stored on shelf decking 72, the decking bows downward in the lengthwise direction between end brackets 76 of adjacent cross bars 74 (74'), and at the same time bows downward between end brackets 90 at opposite ends of each individual cross bar (FIGS. 5 and 6). In this latter condition, the decking is supported not only (1) by main rectangular plates 96 and tongues 78, but also (2) by substantial intervening portions of steps 82 in steel step ledge beams 84, and (3) by substantial intervening portions of top surfaces 94 of cross bars 74 (or 74').
Inwardly Extending Fingers
Rigid finger 106 extends rigidly inward at the bottom of each flange 98. The fingers of each pair of opposing fingers 106 confine the end of wood cross bar 92 between them.
Base 108 of finger 106 is positioned at a distance d₅ from main rectangular plate 96 that is substantially equal to the predetermined minimum thickness of the cross bar. Free end 110 of finger 106 is positioned at a distance d₆ from main rectangular plate 96 that is substantially equal to the predetermined maximum thickness of the cross bar. (These dimensions can be observed in FIGS. 6 and 7, and are specifically deisgnated in FIG. 10.) As a result of these dimensions, each finger 106 extends at a relatively small obtuse angle from the flange with which it is associated.
The indicated orientation of each finger 106 means that end bracket 76 can be easily and securely attached to a wood cross bar no matter where its thickness falls between the predetermined maximum and minimum thickness of the bars with which the end bracket of this invention is designed to be used. Cross bars 74 and 74' in FIGS. 7 and 8 are of the predetermined minimum thickness; as is seen in those Figures, base 108 of each finger 106 is in tight contact with bottom surface 94 (or 94') of cross bar 74 (or 74') even though free end 110 is not. Cross bar 74" in FIG. 10 is of the maximum predetermined thickness; in that Figure, free end 110 of finger 106 is in tight contact with bottom surface 94" of cross bar 74", base 108 and the rest of finger 106 have dug into the wood cross bar to compress the portion of the bar underlying the finger and thereby increase still further the security of attachment of the end bracket to the cross bar.
In the embodiment shown, each finger 106 extends inward from its associated flange 98 from directly beneath the side of main rectangular plate from which supporting tongue 78 extends outwardly (to the right in FIGS. 7 and 8). This means that if end bracket 76 must be forced on the cross bar because it is of the maximum predetermined thickness (as explained just above in connection with FIG. 10), the finger will be forced for only the minimum distance.
Hook Members
As shown in FIG. 9, at least one rigid hook member 112 extends inward at the bottom of each flange 98 for fixedly securing end bracket 76 to the cross bar. This is accomplished by driving hook 112 into position 112' within wood cross bar 74 (or 74' or 74" )after end bracket 76 has been pushed onto the end of the cross bar.
Each hook member 112 has a rigid shank 114 that is connected (as best seen in FIG. 9) at its base to flange 98. Each of these shanks carries at its free end a rigid, tapered tip 116 that is rigidly oriented at acute angle 118 to its shank.
The base of shank 114 of each hook member 112 is positioned at a distance d₅ from main rectangular plate 96 that is substantially equal to the predetermined minimum thickness of the cross bar. The free end of tapered tip 116 is normally positioned at distance d₆ from main rectangular plate 96 that is substantially equal to the predetermined maximum thickness of the cross bar.
As seen in FIG. 10, after end bracket 76 is placed on the wood cross bar, the free end of tapered tip 116 is driven into the wood cross bar to secure end bracket 76 in its final condition on the end of the cross bar. Because of acute angle 118, when hook tip 116 is driven into the end of the wood cross bar, a portion of the cross bar within the space encompassed by tapered tip 116 positioned at acute angle 118 to its shank 114 is embraced to produce a still firmer connection between end bracket 76 and the cross bar to which it is secured.
As pointed out above, the described construction of the end bracket and storage rack of this invention means that the bracket can be securely attached to a wood cross bar of any thickness between its predetermined maximum and minimum thicknesses at any of several positions to accommodate a cross bar of any length between its predetermined maximum and minimum lengths.
The above detailed description has been given for clearness of understanding only. No unnecessary limitations should be understood therefrom, as modifications will be obvious to those skilled in the art.
I claim:
1. A bracket for the end of one of several wood cross bars that support the shelf decking in a storage rack, said cross bar having:(i) predetermined maximum and minimum lengths, (ii) two major surfaces of a predetermined width, and (iii) predetermined maximum and minimum thicknesses, which end bracket comprises:(a) a rigid main rectangular plate for overlying contact with one of said cross bar major surfaces with its long dimension oriented transverse to the cross bar, said rectangular plate having a predetermined width sufficiently large that the plate will provide a secure overlying contact with said cross bar end when the cross bar is of its predetermined minimum length; (b) a thin, flat, rigid, supporting tongue extending rigidly outward from one side of said main rectangular plate for a predetermined distance sufficiently large that said tongue will extend a substantial distance beyond said cross bar end when the cross bar is of its predetermined maximum length; (c) a rigid flange extending rigidly downward from each end of said main rectangular plate for embracing one of said cross bar ends in a position in which said tongue extends outward from said cross bar a substantial distance beyond the end of the bar; (d) a rigid finger extending rigidly inward at the bottom of each of said flanges for confining said cross bar end, said finger extending at a relatively small obtuse angle to said flange, with the base of said finger being at a distance from said main rectangular plate substantially equal to said predetermined maximum thickness of said cross bar and the free end of said finger being at a distance from said rectangular plate substantially equal to said predetermined maximum thickness of said cross bar; and(e) at least one rigid hook member extending inward at the bottom of each of said flanges for fixedly securing said end bracket to said cross bar by driving said at least one hook into the cross bar, each of said hooks having a rigid shank connected at its base to said flange, said shank carrying at its free end a rigid, tapered tip, said tip being rigidly oriented at an acute angle to said shank, the base of said shank being at a distance from said main rectangular plate substantially equal to said predetermined minimum thickness of said cross bar and the free end of said tapered tip being normally at a distance from said main rectangular plate substantially equal to said predetermined maximum thickness of said cross bar, whereby said end bracket can be securely attached to a cross bar of any thickness between said predetermined maximum and minimum thicknesses at any of several positions to accommodate a cross bar of any length between said predetermined maximum length and said predetermined minimum length, and each of said hook tips, which tips are rigidly oriented at an acute angle to their respective hook shanks, can be driven into said wood cross bar ends to embrace a portion of said cross bar within the space encompassed by the tapered tip positioned at said acute angle to its shank.
2. The end bracket of claim 1 in which said predetermined distance said tongue extends outward from one side of said rectangular plate is smaller than said predetermined width of the rectangular plate.
3. The end bracket of claim 1 in which each of said downwardly extending flanges is of substantially the same width as said main rectangular plate.
4. The end bracket of claim 1 in which said rigid fingers extend inward from said flanges directly beneath the side of said main rectangular plate from which said supporting tongue extends.
5. A storage rack including a rectangular shelf decking member, a pair of horizontal, parallel, step ledge beams, and a plurality of wood cross bars, in which:(a) the end bracket of claim 1 is attached to both ends of each wood cross bar, with (i) said main rectangular plate, (ii) said downwardly extending flanges, and (iii) said fingers all embracing said cross bar end securely; (b) said hook members are driven securely into the cross bar; (c) said thin, flat, rigid, outwardly extending supporting tongue of each of said end brackets rests, at both ends of each of said cross bars, on a step of one of said pair of horizontal, parallel step ledge beams; and (d) said shelf decking (i) is supported by continued contact with said tongues, and (ii) when bowed downward slightly by a load stored thereon, is supported by said steps and said cross bars.
|
CCXXX GENERAL SUMMARY OF SCIENTIFIC AND
to the fact that the extraordinary impulse given to the iron producing industries of the country during the years imme diately preceding the panic called into existence a large number of new furnaces, many of which were of the largest size and constructed upon the most approved plans. The furnaces which made 2,854,558 tons of iron in 1872 were mostly small, and, owing to the excitement and recklessness of those times, not so managed as to produce the best results. " When we consider," says the secretary, " that the lessened number of furnaces which made 2,868,278 tons in 1873 in cluded all the large and improved new furnaces, and when we consider that there were almost as many furnaces in blast in 1874 as in 1873, that as a rule the best furnaces in the country were running in 1874, while the poorest stood idle, and that, from motives of enforced economy and by reason of increased skill, the management of most of the furnaces in blast in that year was such as to produce the largest possible yield, we need no longer wonder that the production of 1874 was only 178,865 tons less than the product of 1873." The number of new furnaces completed in 1874 was 38, against 50 in 1873, and 41 in 1872. No less than 46 stacks are re ported as being in course of erection in 1875, while other new furnaces are projected. The district showing the great est increase of production during 1874 was the miscellaneous coal and coke district of Ohio. The district showing the greatest decrease during 1874 was the Lehigh anthracite re gion of Pennsylvania. Utah Territory made her first pig iron in 1874 200 tons of charcoal. After a Ions: rest, Ore gon, with one furnace, made 2500 tons of charcoal iron in 1874. Texas made 1012 tons of charcoal iron in 1874. South Carolina, with eight furnaces, and Minnesota, with one fur nace, made no iron in that year.
The total imports of pig-iron into the United States in 1874 were 61,165 net tons, against 154,708 net tons in 1873, 295,967 net tons in 1872, and 245,535 net tons in 1871.
The total exports of pig-iron from the United States to all countries in 1874 were 16,039 net tons, against 10,103 net tons in 1873, and 1477 net tons in 1S72.
The following table affords an oversight of the growth of the pig-iron branch of the iron trade of the United States from 1854 to 1874, compiled from the association's statistics:
|
FINAL EXAM Question 1. What is the name of the regional airline brand name for Delta Air Lines that utilizes both Atlantic Southeast Airlines and Endeavor Air?
----
Answer: Delta Connection
Q: FINAL EXAM Question 1. Which is a constituency in Lincolnshire that was served by Sir Richard Winfrey as a member of Parliament from 1923-1924?
A: Gainsborough
Question: FINAL EXAM Question 1. The English actor, whose career has included roles on stage, television, and film, as well as starred in the 1997 comedy action film Masterminds, was born when?
Answer: born 13 July 1940
[Q]: FINAL EXAM Question 1. Who wrote an autobiography published by White Mountain Castle Publishing about his adventure in Hawaii?
****
[A]: Daniel Keauhou Matsu "Danny" Yamashiro
input: Please answer the following: FINAL EXAM Question 1. Are both Super Furry Animals and Juliette and the Licks rock bands?
++++++++++
output: yes
FINAL EXAM Question 1. Are Ixia and Billbergia both flowering plants?
----
Answer:
no
|
import { CascaderOption } from './nz-cascader-definitions';
export function isChildOption(o: CascaderOption): boolean {
return o.isLeaf || !o.children || !o.children.length;
}
export function isParentOption(o: CascaderOption): boolean {
return !!o.children && !!o.children.length && !o.isLeaf;
}
|
Pauline Dixon
Pauline Dixon is a Professor of International Development and Education at Newcastle University in North East England. She is the Co-Director of the Global Challenges Academy and the Newcastle University Lead for the Global Challenges Summit. She is the PI for the Women in Development Network and is currently a Co-Investigator on the Water and Sanitation Hub funded by UKRI GCRF.
Career background
Dixon has been involved in multiple projects predominately focusing on researching the role of school choice and potential solutions for achieving Education For All in Asia and Africa. Her work is closely linked to the philosophy of Professor James Tooley, who she has worked with on various funded John Templeton Foundation projects. Between 2003–2005 both explored the nature and existence of private schools for the poor in India, resulting in multiple academic articles and exposing an under the radar network of schools throughout the developing world. Following the success of the project both Tooley and Dixon lead on further Templeton funded research that aimed to look at 'education in conflict zones' with a focus on African schools (2011-2013). Her last research project was funded by the ESRC focusing on Dar es Salaam, Tanzania and identifying high ability and creative children in poor areas of the Kinondoni District.
In conjunction with her work in India she has worked as an advisor and education consultant for the British-based charity Absolute Return for Kids (ARK), where she helped initiate the ASPIRE programme (Allow Synthetic Phonics to Improve Results in English).
Dixon delivers keynote speeches and presentations around the world including at Capitol Hill, Washington D.C., University of Connecticut, Brown University, Free Market Foundation of South Africa, Johannesburg, Waterloo Global Science Initiative, and Panama City. She also delivers talks in Europe including at Uppsala University, Riksdagen, Zurich, Liechtenstein, Durham, Glasgow, London, and Vienna. She has also presented the research findings to government officials in India and Africa. She gave a TEDx talk at Glasgow in 2012 "How Private Schools are Serving the Poorest".
Prizes and awards
* The Times Literary Supplement Books of the Year for "International Aid and Private Schools for the Poor: Smiles, Miracles and Markets" Edward Elgar, 29 November 2013.
* Luminary Award from the Free Market Foundation of South Africa. Honours individuals making a unique contribution to the advancement of mankind. Awarded 2013.
* First place Winners – EG West Centre for their research in Asia and Africa. The 2006 Templeton Freedom Prize for Excellence in Promoting Liberty in Free Market Solutions to Poverty. Presented in Colorado Springs, USA April 2006.
* Don Lavoie Memorial Graduate Student Essay Contest Winner 2003 for "Regulation of Private Schooling for Low-Income Families in India: An Austrian Economic Approach"
* 2001 winner to attend the ‘Advanced Seminar in Austrian Economics’, in New York City.
Publications
Dixon, P., Egalite, A.J., Humble, S., Wolf, P. (2019) Experimental results from a four-year targeted education voucher program in the slums of Delhi, India. World Development 2019, 124, 104644.
Humble, S., Dixon, P., Mpofu, E. (2018) Factor Structure of the Torrance Tests of Creative Thinking Figural Form A in Kiswahili speaking children: multidimensionality and influences on creative behaviour. Thinking Skills and Creativity, 27, 33-44.
Humble, S., Dixon, P., Schagen, I. (2018) Assessing intellectual potential in Tanzanian children in poor areas of Dar es Salaam. Assessment in Education: Principles, Policy and Practice, 25(4), 399-414.
Dixon, P., Humble, S., and Counihan, C. (2015) Eds., Handbook of International Development and Education, Cheltenham UK and MA, USA, Edward Elgar.
Dixon, P. (2014) International Aid and Private Schools for the Poor: Smiles, Miracles and Markets, Worldwide Paperback edition: MA, USA and Gloucestershire, UK. Edward Elgar.
Wolf, P., Egalite, A.J., and Dixon, P. (2015) Private School Choice in Developing Countries: Experimental Results from Delhi, India, In Dixon, P., Humble, S., and Counihan, C., (Eds.) The Handbook of International Development and Education, MA, USA, Edward Elgar.
Dixon, P., Humble, S., and Marshall, P. (2015) International aid and schooling for the poor, In, Dixon, P., Humble, S., and Counihan, C., (Eds.) The Handbook of International Development and Education, MA, USA, Edward Elgar.
Dixon P, Schagen I, Seedhouse P. The impact of an intervention on children's reading and spelling ability in low-income schools in India. School Effectiveness and School Improvement 2011, 22(4), 461–482.
|
Email updates
Keep up to date with the latest news and content from BMC Research Notes and BioMed Central.
Research article
Identifying microRNA/mRNA dysregulations in ovarian cancer
Gregory D Miles12*, Michael Seiler3, Lorna Rodriguez1, Gunaretnam Rajagopal15 and Gyan Bhanot12345
Author Affiliations
1 The Cancer Institute of New Jersey, New Brunswick, NJ, USA
2 Department of Bioinformatics and Systems Biology, Boston University, Boston, MA, USA
3 BioMaPS Institute, Rutgers University, Busch Campus, Piscataway, NJ, USA
4 Department of Molecular Biology & Biochemistry; Department of Physics, Rutgers University, Piscataway, NJ, USA
5 Institute for Advanced Study, Simons Center for Systems Biology, Princeton, NJ, USA
For all author emails, please log on.
BMC Research Notes 2012, 5:164 doi:10.1186/1756-0500-5-164
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1756-0500/5/164
Received:11 November 2011
Accepted:27 March 2012
Published:27 March 2012
© 2012 Miles et al; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC), revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA).
Methods
TCGA Microarray data was normalized and samples whose class labels (tumour or normal) were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA.
Results
We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from indirect regulatory mechanisms.
Conclusions
Our findings identify novel microRNA/mRNA relationships that can be verified experimentally. We identify both generic microRNA/mRNA regulation mechanisms in the ovary as well as specific microRNA/mRNA controls which are turned on or off in ovarian tumours. Our results suggest that the disease process uses specific mechanisms which may be significant for their utility as early detection biomarkers or in the development of microRNA therapies in treating ovarian cancers. The positively correlated microRNA/mRNA pairs suggest the existence of novel regulatory mechanisms that proceed via intermediate states (indirect regulation) in ovarian tumorigenesis.
Background
Ovarian cancers have a high mortality rate and few treatment options and the failure rate is high [1]. In spite of significant advances in detection and effort to reduce recurrence rates, the five year survival rate has remained relatively unchanged for over 50 years [2].
The Cancer Genome Atlas (TCGA) [3] is a public database which provides multi-modal, patient matched data, including microRNA and mRNA expression levels as well as clinical data (survival, recurrence and treatment), for large cohorts in several cancers, including serous cystadenocarcinoma (the most common type of ovarian cancer). In this paper, we apply a validated method [4] to identify statistically significant microRNA/mRNA regulations which are disrupted in serous cystadenocarcinoma using patient matched data from TCGA. Although mRNA and microRNA dysregulations in ovarian cancer have been identified in various studies [5-15], regulatory mRNA targets of microRNA have not been established. Our analysis proceeds as follows:
We first identify those mRNA or microRNA which can individually and robustly distinguish ovarian cancer samples from normal ovary samples based on expression level. We then identify putative mRNA potentially regulated by the microRNA by matching microRNA/mRNA using seed sequence complementarity from TargetScan http://www.targetscan.org webcite). Finally, we look for a significant correlation/anti-correlation signature between patient matched microRNA/mRNA in tumor samples or normal samples. This procedure allows us to identify microRNA/mRNA regulations which are common (maintained) between tumor and normal tissue as well as microRNA/mRNA regulations that are disrupted in carcinogenesis [4].
Using several statistical tests (Students T-test with FDR correction, unpaired t-test without FDR correction, and Mann-Whitney test with FDR correction), K-Means Clustering [16] and principal component analysis [17], our analysis found 18 microRNA and 49 mRNA which best distinguish tumour from normal. Using seed sequence matches between all putative pairs between these sets (from TargetScan) and Pearson correlation at significance p < 0.05 and < 0.1 (one tailed test) in the tumour and normal samples, respectively, we found forty microRNA/mRNA pairs of potential interest, including fifteen pairs anti-correlated across all tumour samples and seven pairs anti-correlated across the normal samples. Within the anti-correlated pairs, one pair: hsa-miR-140-3p/RAD51AP1, was anti-correlated in both tumour and normal samples with opposite expression levels in tumor/normal, implying the dysregulation of a direct microRNA/mRNA mechanism. In addition, we also identified microRNA/mRNA pairs that were correlated or anti-correlated in the tumour samples but not in the normal samples, suggesting a de novo gain of microRNA function in tumours. Also present were microRNA/mRNA regulations present in normal samples but not in tumour samples, indicating a de novo loss of microRNA function in tumours. Interestingly, there are also pairs identified which show positive correlation in both tumour and normal samples, implying the potential existence of indirect pathways or intermediate regulatory mechanisms with a possible role in ovarian tumorigenesis.
Methods
TCGA data
The Cancer Genome Atlas (TCGA) is a central bank for multidimensional experimental cancer data, including MicroRNA and cDNA microarray data. These data were obtained from the Data Access Matrix within the TCGA data portal (http://cancergenome.nih.gov/dataportal/data/access/ webcite). cDNA microarray experiments measuring mRNA expression were run on the Affymetrix HG-U133A platform (22,277 probesets). microRNA experiments were performed on the Agilent 8 × 15 K Human microRNA-specific microarray V2 platform measuring the expression of 821 microRNAs. Of the 386 TCGA microRNA data samples (378 tumours and 8 normals) and 294 mRNA data samples (including one cell line experiment, which was eliminated), filters were applied such that only samples withboth microRNA/mRNA data were retained. When this was done, we were left with 290 samples (282 tumors, 8 normals). Outliers were then removed as described below, leaving a final cohort of 264 samples (258 tumors, 6 normals).
Identification of samples with matched microRNA/mRNA data
The TCGA dataset consisted of 386 samples with microRNA expression data (378 tumours and 8 normals) and 294 samples with mRNA expression data (including one cell line experiment). Of these, we retained only samples which had data for both microRNA and mRNA levels. This resulted in a reduced dataset with 290 total samples (282 tumours, 8 normals). Further removal of samples with ambiguous class labels with respect to consensus ensemble clustering reduced this to 258 tumour samples and 6 normals (see below).
Normalization
The mRNA expression data was normalized using MAS5.0 summarization. We then standard normalized the data: The mean of the summarized intensities for each gene across all experiments was subtracted from the individual intensity for that same gene within a given experiment (per-gene mean subtraction). This value was then divided by the standard deviation of the summarized intensities for each gene across all experiments.
We further normalized the data by performing a 75th percentile shift using GeneSpring GX 11.0 (Agilent Technologies, Inc., Santa Clara, CA, USA). In order to compare our data with previous literature [5], these values were then per-gene mean subtracted and divided by the per-gene standard deviation (similar to the mRNA normalization) to produce normalized measurable microRNA expression values.
Removal of samples with ambiguous class labels
An ambiguous tumour/normal sample is defined as one that does not robustly cluster with members of its labelled class (tumour or normal). Such samples were identified and eliminated using both mRNA and microRNA data. This was done by using consensus ensemble K-means clustering, using the public software ConsensusCluster (http://code.google.com/p/consensus-cluster/ webcite). mRNA expression data for the 290 samples (282 tumours and 8 normals) was clustered via unsupervised K-Means consensus clustering into two classes [18]. Most of the tumour samples clustered in a manner consistent with their labels (tumours with tumours and normal with normal) across the dataset. However, 20 samples clustered in an ambiguous way (sometimes with normal and sometimes with tumours) and were eliminated (Figure 1), leaving 270 samples for to be analysed for their microRNA levels.
Figure 1. Identifying ambiguous samples using mRNA levels. K-means clustering yielded two distinct subclusters which may represent subtypes that will be addressed in the future. The 20 samples which did not cluster well with either group were classified as ambiguous samples and removed.
We found that microRNA levels varied over a much smaller range than mRNA levels. Hence a similar analysis of the microRNA data required that uninformative microRNA be removed first. We therefore eliminated microRNA whose expression had little or no variation across tumour/normal sample clusters, retaining only those whose expression levels could significantly distinguish tumour samples from normal samples. This was done using three statistical tests:
a) A Students' unpaired t-test with a Benjamini Hochberg FDR multiple testing correction (p < 0.05) between the tumour and normal samples within GeneSpring GX 11.0;
b) A Mann-Whitney test with a Benjamini Hochberg FDR multiple testing correction (p < 0.05) between the tumour and normal samples within GeneSpring GX 11.0;
c) A Students' unpaired T-test without a multiple testing correction (p < 0.05).
Only microRNA that passed all three tests were retained, which resulted in a robust subset of 127 microRNA (Figure 2 and Additional file 1: Table S1) whose expression levels significantly separated tumour samples from normal samples. Consensus ensemble K-means clustering into two clusters using expression levels of these 127 microRNA was performed on the 270 samples that remained after analysis of the mRNA data (see above). This identified six additional samples that did not retain consistent cluster membership across bootstrap samplings of the data. These six samples were also removed.
Figure 2. MicroRNAs that separate tumour from normal. The intersection of three separate statistical tests yielded 127 microRNA that more significantly differentiate tumour from normal samples. The tests included an unpaired T-test (p < 0.05) with a Benjamini Hochberg FDR multiple testing correction and an unpaired Mann-Whitney test (p < 0.05) with a Benjamini Hochberg FDR multiple testing correction from within GeneSpring GX 11.0, and a Student's t-test (p < 0.05). Data for these 127 microRNA were subsequently used for further clustering of the samples and SNR analysis to uncover the top microRNA which differentiate tumour and normal samples.
Additional file 1. Table S1 MicroRNAs separating tumour from normal samples. 127 microRNAs are significantly differentially expressed and robustly separate tumour samples from normal samples.
Format: XLSX Size: 10KB Download file
These two analyses on mRNA and microRNA levels identified our final sample set of 264 samples (258 tumours and 6 normals) which are listed in Additional file 2: Table S2. We note in that our analysis showed that two of the TCGA samples which are labelled as "normal" (TCGA-01-0628-11 and TCGA-01-0631-11) consistently clustered with the tumour samples, suggesting that they might contain a significant contamination from the tumour. These were eliminated from further analysis.
Additional file 2. Table S2 Samples used for analysis. This table identifies the 258 tumor samples and 6 normal samples with matched microRNA/mRNA data from the TCGA sample set which were retained for analysis ambiguous samples were removed using consensus ensemble clustering (see Methods for details).
Format: XLSX Size: 12KB Download file
Identifying optimal microRNA and mRNA to distinguish tumour from normal
After removal of these ambiguous samples, the ConsensusCluster software was used to perform principal component analysis (PCA) using expression levels of the 127 microRNAs. PCA analysis was performed 43 times, using the six remaining normal samples and six randomly selected tumour samples (without replacement) as input. The first two principal component eigenvectors (PC1 and PC2) from these 43 runs were averaged. Figure 3 shows the PCA plot obtained on projecting the samples onto the two averaged eigenvectors. A robust subset of 18 microRNA was identified as those which appeared most often (35 times out of 43) in these datasets as significantly able to distinguish tumour from normal using a signal-to-noise ratio (SNR) test using SNR > 0.5 as a cutoff. These 18 microRNAs with the most significant values of this eigen-score across the 43 datasets were retained for further analysis. A similar procedure was used for the mRNA, once again validating (using PCA) that the normal samples indeed separate from the tumour samples (Figure 4). Furthermore, upon iterating 43 times once again, the SNR filtering provided 53 genes that were most informative in separating tumour from normal samples in a robust manner, with each gene appearing in at least 20 of the 43 lists generated by ConsensusCluster.
Figure 3. PCA on robust microRNA data reveals distinct separation. PCA was executed using only the expression data from the 127 microRNA represented in Figure 1. A clear separation between tumour and normal samples validates the effectiveness of the methods used to generate this microRNA list.
Figure 4. PCA on mRNA data reveals clear separation. PCA was executed using gene expression data. A clear separation between the tumour and normal samples indicates the presence of selected genes that robustly distinguish ovarian tumour from the normal samples.
Identifying mRNA targets of microRNA
TargetScan (http://www.targetscan.org webcite) was used to obtain putative mRNA targets for all 18 microRNAs that best distinguished tumour samples from normals. In the 18 × 53 matrix of microRNA/mRNA pairs, we retained those where the microRNA had a seed sequence in TargetScan which was identified as either 'conserved' or 'poorly conserved'. For each such microRNA/mRNA pair, we computed the Pearson rank correlation function separately within the normal and tumour samples. We retained those which had a p-value significance (http://danielsoper.com/statcalc3/calc.aspx?id = 44 webcite) < 0.5 for this statistic in tumour samples, and < 0.1 in the normal samples.
Results
At the time of this study, the TCGA ovarian cancer data set consisted of 282 tumour samples and 8 non-matching normal samples with both microRNA and mRNA expression data available. The microRNA data consists of expression levels for 821 microRNA measured on an Agilent 8 × 15 K Human miRNA-specific microarray platform. The gene expression levels were measured on the Affymetrix GeneChip Human Genome HG-U133A array platform consisting of 22,277 probes. Clinical and survival data were also available for all samples, including: age, days to death (if applicable), days to last follow-up, days to tumour progression, days to tumour recurrence, and age at initial pathologic diagnosis. As described in the Methods section (above), after normalizing, removing ambiguous samples and finding the optimum set of microRNA and mRNA, we were left with 258 tumor samples, 6 normals, 18 microRNA and 53 mRNA.
Of the 18 microRNA that robustly distinguished tumours from normals, nine (hsa-miR-183*, hsa-miR-15b*, hsa-miR-15b, hsa-miR-590-5p, hsa-miR-18a, hsa-miR-16, hsa-miR-96, hsa-miR-18b, and dmr_285) were up-regulated and nine (hsa-miR-145*, hsa-miR-143*, hsa-miR-34b*, hsa-miR-140-3p, hsa-miR-145, hsa-miR-139-5p, hsa-miR-34c-3p, hsa-miR-133a, and hsa-miR-34c-5p) were down-regulated in tumour compared to normal. K-means clustering using only these 18 microRNA levels confirmed that these microRNA clearly separate tumour from normal samples (Figure 5).
Figure 5. A separate cluster for normal samples implies significance of 18 microRNA. We K-means clustered (k = 3) all samples using microRNA expression data exclusively from the 18 microRNA in Table 1. The results are consistent with our expectation that these 18 microRNA best separate the cancerous samples from normal ovarian tissue.
Of the 53 mRNA probes which robustly separated tumour from normal samples, 44 (BUB1, TPX2, CDC25C, ASPM, C1orf112, KIF23, CENPA, HJURP, CCNA2, TTK, CCNB2, C12orf48, BIRC5, RAD51AP1, RACGAP1, MELK, KIFC1, NCAPG, EXO1, KDM2A, EHMT2, DNA2, E2F3, C8orf30A, FAM64A, CORO1B, HEATR3, NCAPH, PSMB2, ERCC6L, KIF15, ESPL1, RANGAP1, KIF11, SCAMP5, NUSAP1, GINS1, ZWINT, ASF1A, an unannotated probe 217205_at, and two probes each for TOP2A and AURKA) were up-regulated and 9 (DNAH3, C6, ADH6, SERPINA6, GCLC, DNAI1, SPARCL1, and two probes for DNAH9) were down-regulated in tumour compared to normal. K-means clustering of using only data from these 53 mRNA confirmed that these mRNA clearly separate tumour from normal samples (Figure 6). We note that the sub-clusters in Figure 6 suggests the presence of two (or more) distinct disease subtypes within the tumour samples. We will further explore these potential disease subclasses in a subsequent paper. Figure 7 shows a heat map of the data projected on the 53 genes that best separate tumour samples from normal samples, and shows that they define a highly accurate signature for this separation.
Figure 6. A distinct cluster containing only normal samples implies significance of 53 mRNAs. Using SNR, 53 genes were isolated that best separate tumour from normal samples We K-means clustered (k = 3) all samples using expression data from these genes. The above results are consistent with our expectations that these 53 genes separate the cancerous samples from normal ovarian tissue well.
Figure 7. Heat map of 53 differentially expressed genes in tumours. Heat map of 53 genes isolated using SNR across 43 iterations. Hierarchical clustering was used to generate the heat map, revealing oncogenic behaviour in the top subcluster and tumour-suppressor activity within the bottom subcluster.
Of the 18 × 53 possible microRNA/mRNA pairs, 69 pairs showed seed sequence complementarity and conservation in TargetScan. The Pearson Rank test at p < 0.5 identified 21 significant pairs (Table 1) in the tumour samples. Of these, fifteen pairs (including nine mRNA) showed a significant anti-correlation signal while six showed a significant positive correlation signal. A similar analysis of the normal samples, at p < 0.1, identified nineteen significant pairs (Table 2) of which seven (with six distinct mRNA) exhibited anti-correlation and twelve were positively correlated.
Table 1. Anti-correlated and positively correlated mRNA/microRNA pairs in the tumour and/or the normal samples
Table 2. Anti-correlated and positively correlated mRNA/microRNA pairs in the tumour and/or the normal samples
We found that of the fifteen microRNA/mRNA pairs anti-correlated in tumour, one (hsa-miR-140-3p/RAD51AP1) was anti-correlated and fourteen either showed no correlation or were positively correlated across the normal samples. Furthermore, of the six positively correlated pairs in tumours, three showed no correlation and three showed positive correlation within the normal samples, implying a potential indirect mechanism of ovarian tumorigenesis. Of the seven pairs anti-correlated in normal samples, all (except miR-140-3p/RAD51AP1) showed no correlation across the tumour samples, implying a potential de novo loss in microRNA function in tumours. Of the twelve pairs which are positively correlated in normal samples, two show anti-correlation within the tumour samples, implying a potential de novo gain in microRNA function in tumours. The remaining ten pairs, which are positively correlated in normal samples, showed either a positive correlation or no correlation in tumour samples. These are of interest because they suggest some novel indirect mechanisms in ovarian tumorigenesis.
Discussion
The methods we applied find potential functional relationships that are good candidates for experimental validation. Many of these microRNA/mRNA pairs impact critical cellular functions that are frequently dysregulated in cancer. For instance, RAD51AP1, a gene that functions in double-stranded DNA repair, is also positively expressed in cervical cancer [19] and breast cancer cell lines [20], cancers that exhibit high expression homogeneity with malignant ovarian carcinomas. Our analysis shows that RAD51AP1 is also up-regulated in ovarian cancers. Furthermore, hsa-mir-140-3p, a potential regulator of RAD51AP1 according to our anti-correlation analysis, has been previously shown to be down-regulated in ovarian cancer [20], a finding which we confirm. Interestingly, the anti-correlated relationship exhibited with this pair is also present in the normal samples. This suggests that if RAD51AP1 is acting as an oncogene in ovarian tumours then targeting hsa-mir-140-3p may be a way to target RAD51AP1.
The E2F transcription factor 3 (E2F3), a gene that is up-regulated in serous ovarian carcinomas, regulates crucial cell cycle and tumour suppressor genes [21-30]. We find that this gene is over-expressed in ovarian tumours. Moreover, hsa-miR-145, a microRNA that is highly down-regulated in ovarian cancer [5,8,9], shows significant expression anti-correlation with E2F3 in normal samples, indicating potential transcriptional repression by hsa-miR-145 in normal cells but loss of this function in tumours. Another potential regulator of E2F3, hsa-miR-139-5p, is also predicted to target Topoisomerase IIα (TOP2A), a gene encoding an enzyme which is involved in altering DNA topology, including chromosome condensation, chromatid separation and the relief of torsional stress occurring in transcription and replication. TOP2A has also been shown to be overexpressed in ovarian tumours [31] and is currently a common target in ovarian cancer clinical trials. Glutamate-cysteine ligase (GCLC), an enzyme of glutathione synthesis predicted to be regulated by hsa-miR-133a in tumours (in a de novo gain of microRNA function) and by hsa-miR-140-3p (in a de novo loss of microRNA function), has been shown to be an anti-apoptotic gene that is positively expressed in ovarian cancer cell lines [32,33].
In addition to many of the genes above which have normal microRNA regulation disrupted by a loss of microRNA function (Table 1) in tumours, several genes regulated by microRNAs with de novo gains in function exist as well. Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), or Survivin, is a protein predicted to be regulated by hsa-miR-96 that inhibits caspase activation [34] leading to negative regulation of apoptosis [35]. Furthermore, increased presence of this protein has been shown to decrease apoptosis in cisplatin-sensitive ovarian carcinoma cells [35], a finding that is consistent with the up-regulation of this gene within the TCGA tumour data set. Additionally, another gene found to be up-regulated in tumours in our dataset, Rac GTPase-activating protein 1 (RACGAP1) is an enzyme whose overexpression has also been associated with serous ovarian carcinoma [30].
We also found six positively correlated microRNA/mRNA pairs with matching seed sequences in tumour and eleven pairs in normal. We reasoned that a likely explanation for this lies in an intermediate regulatory mechanism that is probably anti-correlated with the microRNA of interest. Consequently, it is important to note that some of the positively correlated genes/microRNA pairs also impact important cellular functions frequently dysregulated in cancer. Also noteworthy is that three of the pairs show positive correlation in both the tumour and normal samples. This finding suggests that while regulation of gene expression by these microRNA is indirect, physiological differences between tumour and normal samples is directly dependent on the changes in expression by these microRNA and the downstream effects they have on the target mRNA they are paired with. For instance, nucleolar and spindle associated protein 1 (NUSAP1), is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization [36] that is positively correlated with hsa-miR-18a in normal but not in tumour. It has also been previously shown to be positively regulated in cervical carcinoma [19,36]. Another gene of potential interest is cell division cycle 25 homolog C (CDC25C), a critical gene involved in cell division that dephosphorylates cyclin B-bound CDC2 (CDK1) and triggers entry into mitosis [37]. It might also have a role in suppressing p53-induced growth arrest and has been shown to be overexpressed in ovarian cancer cell lines [27,38]. Finally, GINS complex subunit 1 (GINS1), which was shown to be significantly positively correlated with hsa-miR-18a and hsa-miR-18b in both tumour and normal samples (and positively correlated with hsa-miR590-5p in normal samples), represents a key component of the GINS complex that is essential for initiation of DNA replication and is positively regulated in serous ovarian carcinoma [39]. Interestingly, hsa-miR-18a, which possesses a significant positive correlation with GINS1 (along with NUSAP1) has shown to be highly up-regulated in serous ovarian carcinoma both previously [10] and within our analysis.
Hsa-miR-16, mentioned previously to be anti-correlated in tumours with several potential mRNA targets including E2F3, C8ORF30A, and SCAMP5, is significantly positively correlated with CDC25C. Should seed sequence complementarity and conservation between these positively correlated pairs be purely coincidental, the relationships between the pairs of positively correlated entities suggest an elaborate mechanism by which these oncogenes/tumour suppressors operate. Further wet-lab validation may show this to be a significant ovarian cancer biomarker. This finding may further elucidate a broader cancer pathway involving CDC25C and some of its target tumour suppressor and cell cycle genes.
Conclusions
Using microRNA/mRNA expression data for 258 tumor samples and six normal samples from TCGA, we have uncovered forty mRNA/microRNA regulation which meet the following criteria: a) These pairs have seed sequence complementarity b) They are able to clearly differentiate ovarian tumours from normal ovary by their expression levels; c) They exhibit a strong anti-correlation or correlation signature within either the tumour samples, the normal samples, or both.
The novelty of our finding is that we have significantly reduced the space of possible dysregulated microRNA/mRNA pairs (based on seed sequence complementarity alone) to a robust subset which may potential represent functional relationships. Such a possibility can be tested experimentally on ovarian cancer cell lines knock down and/or knock in assays. If in addition, some of these dysregulations are associated with survival pathways for the tumor or with resistance to therapy, it opens up the possibility of patient specific targeted therapy.
Availability of supporting data
All expression data is available for download at The Cancer Genome Atlas Data Portal (http://tcga-data.nci.nih.gov/tcga/tcgaHome2.jsp webcite).
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
GM obtained the data, performed most of the analysis, implemented the methods, interpreted the results, and wrote the manuscript, MS performed portions of the analysis, suggested alternative interpretations/analyses to perform, GB, LR, GR helped design and supervise the study. All authors have read and approved the final manuscript. The authors declare that they have no conflict of interest with any of the contents of this manuscript.
Acknowledgements
We thank NIH/NCI for allowing us access to the TCGA datasets. Without this access, the present work would not have been possible.
References
1. Society AC: Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010. PubMed Abstract
2. Siegel R, Ward E, Brawley O, Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths.
CA: a cancer journal for clinicians 2011, 61(4):212-236. Publisher Full Text
3. Comprehensive genomic characterization defines human glioblastoma genes and core pathways
Nature 2008, 455(7216):1061-1068. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
4. Liu H, Brannon AR, Reddy AR, Alexe G, Seiler MW, Arreola A, Oza JH, Yao M, Juan D, Liou LS, et al.: Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma.
BMC Syst Biol 2010, 4:51. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
5. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, et al.: MicroRNA signatures in human ovarian cancer.
Cancer Res 2007, 67(18):8699-8707. PubMed Abstract | Publisher Full Text
6. Dahiya N, Sherman-Baust CA, Wang TL, Davidson B, Shih Ie M, Zhang Y, Wood W, Becker KG, Morin PJ: MicroRNA expression and identification of putative miRNA targets in ovarian cancer.
PLoS One 2008, 3(6):e2436. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
7. Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV, et al.: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN.
Cancer Res 2008, 68(2):425-433. PubMed Abstract | Publisher Full Text
8.
Proc Natl Acad Sci USA 2008, 105(19):7004-7009. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
9.
Clin Cancer Res 2008, 14(9):2690-2695. PubMed Abstract | Publisher Full Text
10. Wyman SK, Parkin RK, Mitchell PS, Fritz BR, O'Briant K, Godwin AK, Urban N, Drescher CW, Knudsen BS, Tewari M: Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries.
PLoS One 2009, 4(4):e5311. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
11. Laios A, O'Toole S, Flavin R, Martin C, Kelly L, Ring M, Finn SP, Barrett C, Loda M, Gleeson N, et al.: Potential role of miR-9 and miR-223 in recurrent ovarian cancer.
Mol Cancer 2008, 7:35. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
12. Berchuck A, Iversen ES, Lancaster JM, Pittman J, Luo J, Lee P, Murphy S, Dressman HK, Febbo PG, West M, et al.: Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers.
Clin Cancer Res 2005, 11(10):3686-3696. PubMed Abstract | Publisher Full Text
13. Hartmann LC, Lu KH, Linette GP, Cliby WA, Kalli KR, Gershenson D, Bast RC, Stec J, Iartchouk N, Smith DI, et al.: Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy.
Clin Cancer Res 2005, 11(6):2149-2155. PubMed Abstract | Publisher Full Text
14. Lancaster JM, Dressman HK, Whitaker RS, Havrilesky L, Gray J, Marks JR, Nevins JR, Berchuck A: Gene expression patterns that characterize advanced stage serous ovarian cancers.
J Soc Gynecol Investig 2004, 11(1):51-59. PubMed Abstract | Publisher Full Text
15. Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, Libermann TA, Cannistra SA: Gene expression signature with independent prognostic significance in epithelial ovarian cancer.
J Clin Oncol 2004, 22(23):4700-4710. PubMed Abstract | Publisher Full Text
16. MacQueen JB: Some Methods for classification and Analysis of Multivariate Observations. In Proceedings of 5-th Berkeley Symposium on Mathematical Statistics and Probability. Volume 1. Berkeley, University of California Press; 1967::281-297.
17. Pearson K: On Lines and Planes of Closest Fit to Systems of Points in Space.
Philosophical Magazine 1901, 2(6):559-572.
18. Seiler M, Huang CC, Szalma S, Bhanot G: ConsensusCluster: a software tool for unsupervised cluster discovery in numerical data.
OMICS 2010, 14(1):109-113. PubMed Abstract | Publisher Full Text
19. Rosty C, Sheffer M, Tsafrir D, Stransky N, Tsafrir I, Peter M, de Cremoux P, de La Rochefordiere A, Salmon R, Dorval T, et al.: Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma.
Oncogene 2005, 24(47):7094-7104. PubMed Abstract | Publisher Full Text
20.
Breast Cancer Res 2005, 7(6):R1058-R1079. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
21. Macleod K, Mullen P, Sewell J, Rabiasz G, Lawrie S, Miller E, Smyth JF, Langdon SP: Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer.
Cancer Res 2005, 65(15):6789-6800. PubMed Abstract | Publisher Full Text
22. Ye D, Mendelsohn J, Fan Z: Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225.
Oncogene 1999, 18(3):731-738. PubMed Abstract | Publisher Full Text
23. Zhang D, Vuocolo S, Masciullo V, Sava T, Giordano A, Soprano DR, Soprano KJ: Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression.
Oncogene 2001, 20(55):7935-7944. PubMed Abstract | Publisher Full Text
24. Todd MC, Sclafani RA, Langan TA: Ovarian cancer cells that coexpress endogenous Rb and p16 are insensitive to overexpression of functional p16 protein.
Oncogene 2000, 19(2):258-264. PubMed Abstract | Publisher Full Text
25. Ma S, Yang Y, Wang C, Hui N, Gu L, Zhong H, Cai Z, Wang Q, Zhang Q, Li N, et al.: Endogenous human CaMKII inhibitory protein suppresses tumor growth by inducing cell cycle arrest and apoptosis through down-regulation of the phosphatidylinositide 3-kinase/Akt/HDM2 pathway.
J Biol Chem 2009, 284(37):24773-24782. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
26. Masamha CP, Benbrook DM: Cyclin D1 degradation is sufficient to induce G1 cell cycle arrest despite constitutive expression of cyclin E2 in ovarian cancer cells.
Cancer Res 2009, 69(16):6565-6572. PubMed Abstract | Publisher Full Text
27. Selvendiran K, Tong L, Vishwanath S, Bratasz A, Trigg NJ, Kutala VK, Hideg K, Kuppusamy P: EF24 induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by increasing PTEN expression.
J Biol Chem 2007, 282(39):28609-28618. PubMed Abstract | Publisher Full Text
28. Li P, Li C, Zhao X, Zhang X, Nicosia SV, Bai W: p27(Kip1) stabilization and G(1) arrest by 1,25-dihydroxyvitamin D(3) in ovarian cancer cells mediated through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1-Cullin-F-box protein/Skp2 ubiquitin ligase.
J Biol Chem 2004, 279(24):25260-25267. PubMed Abstract | Publisher Full Text
29. Humbert PO, Verona R, Trimarchi JM, Rogers C, Dandapani S, Lees JA: E2f3 is critical for normal cellular proliferation.
Genes Dev 2000, 14(6):690-703. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
30. Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, Ramoth LR, Rosen DG, Liu J, Hellstrom I, et al.: Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis.
Clin Cancer Res 2004, 10(10):3291-3300. PubMed Abstract | Publisher Full Text
31. Chekerov R, Klaman I, Zafrakas M, Konsgen D, Mustea A, Petschke B, Lichtenegger W, Sehouli J, Dahl E: Altered expression pattern of topoisomerase IIalpha in ovarian tumor epithelial and stromal cells after platinum-based chemotherapy.
Neoplasia 2006, 8(1):38-45. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
32. Godwin AK, Meister A, O'Dwyer PJ, Huang CS, Hamilton TC, Anderson ME: High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis.
Proc Natl Acad Sci USA 1992, 89(7):3070-3074. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
33. Botta D, Franklin CC, White CC, Krejsa CM, Dabrowski MJ, Pierce RH, Fausto N, Kavanagh TJ: Glutamate-cysteine ligase attenuates TNF-induced mitochondrial injury and apoptosis.
Free Radic Biol Med 2004, 37(5):632-642. PubMed Abstract | Publisher Full Text
34. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC: IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs.
Cancer research 1998, 58(23):5315-5320. PubMed Abstract | Publisher Full Text
35. Dan HC, Jiang K, Coppola D, Hamilton A, Nicosia SV, Sebti SM, Cheng JQ: Phosphatidylinositol-3-OH kinase/AKT and survivin pathways as critical targets for geranylgeranyltransferase I inhibitor-induced apoptosis.
Oncogene 2004, 23(3):706-715. PubMed Abstract | Publisher Full Text
36. Raemaekers T, Ribbeck K, Beaudouin J, Annaert W, Van Camp M, Stockmans I, Smets N, Bouillon R, Ellenberg J, Carmeliet G: NuSAP, a novel microtubule-associated protein involved in mitotic spindle organization.
J Cell Biol 2003, 162(6):1017-1029. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
37. Hoffmann I, Clarke PR, Marcote MJ, Karsenti E, Draetta G: Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis.
Embo J 1993, 12(1):53-63. PubMed Abstract | PubMed Central Full Text
38. Arafa elSA, Zhu Q, Barakat BM, Wani G, Zhao Q, El-Mahdy MA, Wani AA: Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway.
Cancer research 2009, 69(23):8910-8917. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
39. Donninger H, Bonome T, Radonovich M, Pise-Masison CA, Brady J, Shih JH, Barrett JC, Birrer MJ: Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways.
Oncogene 2004, 23(49):8065-8077. PubMed Abstract | Publisher Full Text
|
# lv2-ui – prototype for an ui crate for rust-lv2
**This repo is no longer maintained!**
The development has been transferred to
[rust-lv2](https://github.com/RustAudio/rust-lv2) itself. See
https://github.com/RustAudio/rust-lv2/pull/75
[rust-lv2](https://github.com/RustAudio/rust-lv2) are Rust bindings to write
[LV2 Plugins](https://lv2plug.in). This crate aims to eventually fill the gap
in rust-lv2 for LV2 GUIs.
## Status
Very early prototype stage. There is one example plugin, which is a simple
amplifier with a UI to set the gain and enable and disable the plugin.
## Example plugins
As in a Rust crate only one library is allowed, LV2 plugins with a GUI have to
come in two crates, one for the DSP part of the plugin, and one for the GUI.
The simple amplifier plugin can be found in the following two repos
* DSP: [ampmeter-rs.lv2](https://github.com/johannes-mueller/ampmeter-rs.lv2)
* UI: [ampmeter-rs-ui.lv2](https://github.com/johannes-mueller/ampmeter-rs-ui.lv2)
Look in those repose on how to build and install the example plugins.
## Todo
Still a lot
* LV2 UI feature discovery
* Atom ports [done]
* Many things still need to be done the right way
* Implement macro rules for the descriptor structs and port collections
* For sure a lot more
* Integrate into rust-lv
* Write actual plugins to test convenient usage
* Write the two example plugins eg-sampler and eg-scope for the lv2 book
Eventually this repo will hopefully disappear and become a part of rust-lv2.
|
Functional PCA for stationary signal
I just came across this technique:
https://en.wikipedia.org/wiki/Functional_principal_component_analysis
As far as I understand, if projects a signal onto a functional subspace that describe the "modes" with largest variation. These modes $f(t)$ are eigenfunctions of the correlation $G(s,t)=E[X(s)X(t)]$. I was just wondering if for stationary signals, where $G(s,t)$ depends only on $s-t$, this framework is equivalent to a Fourier decomposition on some discrete selected frequencies $\omega_k$.
My conjecture comes from the fact that in reciprocal space the operator $G(s,t)$, depending
only on time differencies, should be multipicative, even if than I am a bit confused on how to find the frequencies, if this is the case.. Maybe in such a case we have an infinite number of eigenvectors ($e^{i\omega t}$), each one with a different eigenvalue ( equal to $\tilde G(\omega)$ ) ? But than how can such a PCA version be useful ?
If the statement, or one variation of it, is true, is there some Python/R framework implementing this ?
As the eigenfunctions are derived from the data themselves they are non-parametric while Fourier polynomials would be purely parametric. I would think that we can accept wavelets as a middle ground (and there are quite a few publications on that, e.g. Morris & Carroll (2006), Pigoli & Sangalli (2012), etc.), if you want to explore a basis that explores localisation both in time and frequency.
|
Cam strip
FIG. 1 is a top view thereof;
FIG. 2 is a front view thereof;
FIG. 3 is a back view thereof;
FIG. 4 is a left side view thereof;
FIG. 5 is a right side view thereof;
FIG. 6 is a bottom view thereof; and,
FIG. 7 is a perspective view thereof.
The ornamental design for a cam strip, as shown and described.
|
package ggc.app.partners;
/** Messages for partner menu interactions. */
interface Message {
/** @return string prompting for a partner identifier. */
static String requestPartnerKey() {
return "Identificador do parceiro: ";
}
/** @return string prompting for a partner name. */
static String requestPartnerName() {
return "Nome do parceiro: ";
}
/** @return string prompting for an address. */
static String requestPartnerAddress() {
return "Endereço do parceiro: ";
}
/** @return string prompting for a product identifier. */
static String requestProductKey() {
return "Identificador do produto: ";
}
}
|
var prevScrollpos = window.pageYOffset;
window.onscroll = function() {
var currentScrollPos = window.pageYOffset;
if (prevScrollpos > currentScrollPos) {
document.getElementById("navbar").style.top = "0";
} else {
document.getElementById("navbar").style.top = "-50px";
}
prevScrollpos = currentScrollPos;
}
var sideFide = false;
function generalFunc() {
var gen = document.querySelector(".general").clientWidth;
var page = document.querySelector(".page").clientWidth;
var sideEl = document.querySelector(".sidenav");
var side = sideEl.clientWidth;
var wind = document.documentElement.clientWidth;
if (((page - gen) / 2) < side) {
sideEl.classList.add("shadow");
} else {
sideEl.classList.remove("shadow");
}
console.log(gen >= wind);
if (gen >= wind && (sideFide != true)) {
window.onresize = null;
console.log(1)
sideFide = true;
hiddenSide(sideEl, 1, 0);
}
if (sideFide && gen < wind) {
sideFide = false;
console.log(2)
window.onresize = null;
wisibleSide(sideEl, 0, -325);
}
}
function hiddenSide(elem, curent, position) {
if (curent >= 0) {
let newPos = position - 32.5;
elem.style.right = newPos + "px";
elem.style.opacity = curent - 0.1;
setTimeout(() => { hiddenSide(elem, curent - 0.1, newPos) }, 50);
} else {
window.onresize = function() { generalFunc() };
}
}
function wisibleSide(elem, curent, position) {
if (curent <= 1) {
let newPos = position + 32.5;
elem.style.right = newPos + "px";
elem.style.opacity = curent + 0.1;
setTimeout(() => { wisibleSide(elem, curent + 0.1, newPos) }, 50);
} else {
window.onresize = function() { generalFunc() };
}
}
window.onresize = function() { generalFunc() };
|
Talk:Mycena nargan/GA1
GA Review
The edit link for this section can be used to add comments to the review.''
rev Reviewer: Rcej (Robert) - talk 04:39, 17 December 2010 (UTC)
Nice :) Thingies:
* Mention/src unknown edibility in Descr.
* I've mentioned, but haven't been able to specifically source "unknown" yet. Have pinged Casliber for help, and am hoping it's mentioned in one of his Australian field guides. Sasata (talk) 03:01, 18 December 2010 (UTC)
* Refs number 6 and 8 appear to have dead links. Rcej (Robert) - talk 08:23, 17 December 2010 (UTC)
* Updated one link, but had to remove the other, as it seems to have disappeared off the web. As a nice consolation prize, I was able to add another photo from a fungus lover from Down Under who kindly released one of his pics for our cause :) Sasata (talk) 03:01, 18 December 2010 (UTC)
* Pass! And kudos to Mr. Leithhead! Rcej (Robert) - talk 05:27, 18 December 2010 (UTC)
Results of review
* GA review (see here for criteria)
The article Mycena nargan passes this review, and has been promoted to good article status. The article is found by the reviewing editor to be deserving of good article status based on the following criteria:
* 1) It is reasonably well written.
* a (prose): b (MoS):
* 1) It is factually accurate and verifiable.
* a (references): b (citations to reliable sources): c (OR):
* 1) It is broad in its coverage.
* a (major aspects): b (focused):
* 1) It follows the neutral point of view policy.
* Fair representation without bias:
* 1) It is stable.
* No edit wars, etc.:
* 1) It is illustrated by images, where possible and appropriate.
* 1) Overall:
* Pass/Fail:
* 1) It is illustrated by images, where possible and appropriate.
* 1) Overall:
* Pass/Fail:
* 1) Overall:
* Pass/Fail:
|
# Automatically loads json files with an associated class for loading fixture
module JSONHelper
class << self
# Uhuhuh! What a cache!
def cache
@cache ||= {}
end
def cache_or_load(path)
cache[path] ||= begin
file = File.read(path)
JSON.parse(file)
end
end
def load_file(name)
path = File.expand_path("../../json/#{name}", __FILE__)
cache_or_load(path)
end
end
# TODO: Better way to deal with this.
# Declaring a class for each one was too much.
# With this, it works, but is too meta, I think.
class Generic
include FootballApi::Symbolizer
def self.get(name)
new.get(name)
end
def get(name)
file_name = "#{File.basename(self.class.name.underscore)}.json"
fixtures = ::JSONHelper.load_file(file_name)
fixtures = self.class.custom_deep_symbolic_hash(fixtures)
fixtures[name.to_sym] && fixtures[name.to_sym].clone
end
end
Dir[File.expand_path('../../json/*.json', __FILE__)].each do |file_name|
klass_name = "#{File.basename(file_name, '.json').camelize}"
JSONHelper.const_set(klass_name, Class.new(Generic))
end
end
|
How to add private fields to json
I have a class with private fields and I want them in the JSON string that later I will write into a text file.
like so
class User
{
private string userEmail;
private string userPassword;
public bool isconnected;
}
class WriteToFile
{
public Dictionary<string,User> write(){
if (File.Exists(path))
{
File.WriteAllText(path, string.Empty);
string json = JsonConvert.SerializeObject(dictionary);
File.WriteAllText(path, json);
}
}
}
I would like that in the json variable will contain the dictionary that his value is the User object WITH his PRIVATE fields.
(Also if you can write a function that will be in the WriteToFile class, not in other class)
Thanks!
Declare your private properties with JsonProperty
public class User
{
[JsonProperty]
private string userEmail = "@abc";
[JsonProperty]
private string userPassword = "def";
public bool isconnected = true;
}
|
Thymoquinone (TQ) loaded NLC NLC showed improved entrapment efficiency and drug loading, along with enhanced site-specific internalization via EPR. In addition, the TQ-NLC showed enhanced apoptosis and anti-metastatic effect as compared to free TQ. [312] Gambogic acid (GA) loaded NLC, functionalized with dimeric c (RGD) GA-cRGD-NLC showed enhanced tumor site accumulation, enhanced encapsulation along with improved stability. In addition, GA-cRGD-NLC (0.25 µg/mL) showed increased cytotoxicity, as compared to untargeted GA-NLC (0.5 µg/mL) [313] Citral loaded NLC Citral-NLC showed increased internalization in the tumor cells and improved entrapment efficiency. Moreover, citral-NLC showed superiority in apoptosis, migration, invasion, and wound healing assay, as compared to free citral. [309]
Nanomedicine: From Pre-Clinical Design to Clinical Practice
Nanomedicines are able to modulate the biodistribution of the drug as well as target them to the desired site, thereby improving the balance between efficacy and toxicity. In the pre-clinical studies, it was observed that nanoparticles inhibit the growth of cancer as well as prolong the survival rate as compared to the non-formulated drugs, however, in the clinical studies, the patients obtain benefit from nanoparticles only because of altered or decreased side effects. Hence, it leads to an increased number of preclinical studies compared to a smaller number of nanomedicines approved for clinical practice. Thus, to tackle the clinical challenges in the right way, a certain protocol was established [314].
It was observed that the national competent authority announced a clinical trial authorization, which stated that the content of the protocol and its format must comply with the Community guideline on Good Clinical Practice (CPMP/ICH/135/95). To administer any nanoparticle in humans, various steps have to be followed. The first step is the preparation of IMPD, which involves the compilation of all information associated with the drug substance (Part S), and the investigational medical product under test (Part P), where the drug substance can be natural, or synthetic, and the product is the nanoformulation of the drug. The second step is to complete the Investigator's Brochure, which contained five chapters, assembling both clinical and non-clinical information relevant to the human subject. The first chapter includes a mini-review of the biological properties of the product (nanoformulation) and their effect on the human. The second chapter includes a summary of IMPD Part S and P. The third chapter involves the results of all pre-clinical analyses (in vitro and in vivo pharmacology; biodistribution, PK, dosimetry, and toxicity studies). The fourth chapter deals with a summary of all results and data previously obtained in humans with the administration of the investigated nanoformulation. The last chapter offers the investigators guidance in summarizing the information necessary for clinical practice (clinical indications, dose, administration route, contraindications, special warnings, and reference safety information). Finally, a study protocol was to be prepared, indicating the justification for the rationale, summary and procedure of the trial, eligibility criteria, the treatment regimen administered to the volunteers, and the efficacy assessment. In addition to these, the study protocol should also include information concerning the safety assessment, regulatory issues, quality control, legal consideration, and funding and insurance issues [315].
Toxicity of Nanoparticles
Nanoparticles are comprised of different types of materials with specific chemical structure, solubility, size, morphology, and surface charge, which may influence the toxicity of the nanoparticles [316]. It was further observed that the nanoparticles exhibit a certain level of toxicity due to their small size and increased surface area, as their nano dimension can lead to irreversible oxidative strain, protein denaturation, agitation of asthmatic and allergic reactions, etc. [317]. On further analysis of the nanoparticles, it was observed that the toxicity of the liposomes and dendrimers are mainly due to their small particle size and surface charge. For example, it was observed that the cationic liposomes interact with serum proteins, lipoproteins, and extracellular matrix, which leads to either aggregation or expulsion of drugs before entering the target site, which results in systemic toxicity. Also, dendrimers with a positive charge like amino-terminated PAMAM dendrimers destabilize the cell membrane, resulting in cell lysis. Such side effects could be overcome by optimizing the factors responsible for nanoparticle preparation, which in turn controls the size and surface functionalization, thereby modifying the surface charge. However, the polymeric nanoparticles seemed to exhibit less toxicity as the polymers used are biodegradable and are easily eliminated from the body with no residual materials. It was further observed that the toxicity of the nanoparticles is also associated with their composition. Due to the presence of silver, the silver nanoparticles generate ROS, which can destroy the blood-brain barrier and form neuronal degeneration and brain edema [318]. Also, there is evidence that states that the carbon nanotubes (both SWCNT and MWCNT) can induce oxidative stress and cytotoxicity [316].
Research evidence demonstrated that nanoparticles are also responsible for inducing allergic reactions. However, it was observed that nanoparticles induce allergic reactions by acting as adjuvant instead of hapten, which activates a certain type of cytokines, antibodies, and cells favoring allergic sensitization to environmental allergens [319]. From various studies, it was observed that lipid-based nanoparticles like liposomes, lipid micelles, nanoemulsion, SLN, and NLC can activate the complement system via classic and alternative pathways. Such activation further results in the development of complement activation-related pseudoallergy, an acute hypersensitivity. Hence, it was concluded that the factors responsible for activation of the complement system include surface charge (positive/negative), an increment in size from 70 nm to 300 nm, composition of lipid-based nanoparticles, and their amount in the formulation and functionalization of the surface with anionic PEG-PE. The common symptoms of complement activation-related pseudoallergy are shortness of breath, flushing, dyspnea, rash, chest and back pain, and distress [320].
Conclusions
TNBC remains an aggressive type of breast cancer with a poor prognosis due to the discrepancy in its molecular and genomic profiling. Although chemotherapy has been the backbone of TNBC treatment, certain developments have occurred with the targeted therapy. This has led to the emergence of two PARP inhibitors: olaparib and talazoparib, as approved by the FDA in 2018. However, these drugs were restricted to patients who suffered from BRCA1/2 mutation, which comprised only 10-15% of the TNBC population. However, a lot of recent advancements have been made in the advancement of novel nanocarrier-based delivery systems, which could offer a ray of hope in improving the treatment and health options among patients suffering from TNBC. Nanoparticles provide plenty of opportunities in improving the biopharmaceutical attributes of the drug, their bioavailability, and targetability, drug loading capacity, ability to administer drug combination, and limiting off-target toxicities and MDR due to their versatility in terms of morphology, surface characteristics, and material of their fabrication. In recent times, much focus has been given to the utilization of biocompatible and green technologies for the preparation of nanoparticles. The novel nanotechnologies are further amalgamated with various other disciplines like synthetic chemistry, molecular biology, formulation development, molecular imaging, etc., to develop a better understanding between the components of the nanoparticles and their association with the cellular environments in vivo. To conclude, there arises an expectation that nano-cavalries loaded with drugs, genes, or endogenous factors will soon become an element of the armamentarium for the treatment of TNBC and aid to manage the peril and commit to improved patient survival.
Future Perspective
This review has discussed various types of nanoparticles optimized for the therapeutic delivery of drugs and to overcome the heterogenous physiological barriers found across the patients suffering from TNBC. It was observed that nanoparticles exist in many shapes and sizes, ranging from inorganic nanoparticles to polymer-based nanoparticles. It was further observed that a few of the polymer-based nanoparticles or inorganic nanoparticles showed significant in vivo results for clinical application. Our view suggests that such nanoparticles can induce certain toxicity in humans, which is not observed in the case of lipid-based nanoparticles, and urges the evaluation of the substantial preclinical studies with utmost caution. In our opinion, lipid-based nanoparticles, more specifically SLN and NLC, will make a substantial impact on the treatment and management of TNBC.
|
Display X distinct random node sets using XSLT 1.0
I've got a simple xsl code to display some dynamically xml.
<xsl:template match="/">
<xsl:for-each select="NewDataSet/Vehicle">
<div class="item">
<xsl:value-of select="ManufacturerName" /><br />
<xsl:value-of select="Model" /><br />
<xsl:value-of select="Colour" /><br />
£<xsl:value-of select='format-number(Price, "###,###,##0.")' />
</div>
</xsl:for-each>
</xsl:template>
What I'd like to be able to do is display X number of random distinct node sets instead of all of them. Is this possible using xslt 1.0?
Thanks.
Your question is not quite clear. What exactly do you mean by "random distinct node sets"? And what does this have to do with grouping? -- Also, which XSLT 1.0 processor are you using?
Sorry. I just assumed some sort of grouping would need to be used. So the code above displays a node groups within NewDataSet/Vehicle, one after the other. I was just wondering if it's possible to pick, say, 6 of these groups at random and just display them. I might be using the word distinct out of play too, because there are no duplicates in the xml, so just 6 random groups might be more accurate. The xml is fed from .net so it's Microsoft's MSXML processor.
There's no random() function in XSLT 1.0 - see: http://stackoverflow.com/a/25869149/3016153 and http://stackoverflow.com/a/6607235/3016153
Here is an example that shows how to pick N random nodes out of a given node-set.
You must have a method to generate a random number between 0 and 1 (not including 1) to make this work. In this example, the EXSLT math:random() extension function is used for this purpose. If you are using the MSXML processor, replace this with an extension function as shown here: https://stackoverflow.com/a/6607235/3016153
XML
<list>
<item id="1">001</item>
<item id="2">002</item>
<item id="3">003</item>
<item id="4">004</item>
<item id="5">005</item>
<item id="6">006</item>
<item id="7">007</item>
<item id="8">008</item>
<item id="9">009</item>
<item id="10">010</item>
<item id="11">011</item>
<item id="12">012</item>
</list>
XSLT 1.0
<xsl:stylesheet version="1.0"
xmlns:xsl="http://www.w3.org/1999/XSL/Transform"
xmlns:math="http://exslt.org/math"
extension-element-prefixes="math">
<xsl:output method="xml" version="1.0" encoding="UTF-8" indent="yes"/>
<xsl:template match="/list">
<output>
<xsl:call-template name="pick-random">
<xsl:with-param name="node-set" select="item"/>
<xsl:with-param name="quota" select="5"/>
</xsl:call-template>
</output>
</xsl:template>
<xsl:template name="pick-random">
<xsl:param name="node-set"/>
<xsl:param name="quota"/>
<xsl:param name="selected" select="dummy-node"/>
<xsl:choose>
<xsl:when test="count($selected) < $quota and $node-set">
<xsl:variable name="set-size" select="count($node-set)"/>
<xsl:variable name="rand" select="floor(math:random() * $set-size) + 1"/>
<!-- recursive call -->
<xsl:call-template name="pick-random">
<xsl:with-param name="node-set" select="$node-set[not(position()=$rand)]"/>
<xsl:with-param name="quota" select="$quota"/>
<xsl:with-param name="selected" select="$selected | $node-set[$rand]"/>
</xsl:call-template>
</xsl:when>
<xsl:otherwise>
<xsl:copy-of select="$selected"/>
</xsl:otherwise>
</xsl:choose>
</xsl:template>
</xsl:stylesheet>
Result (of an example run)
<?xml version="1.0" encoding="UTF-8"?>
<output>
<item id="1">001</item>
<item id="3">003</item>
<item id="8">008</item>
<item id="10">010</item>
<item id="12">012</item>
</output>
Note: This method preserves the internal order of the selected items.
This is fantastic. I need to have a play with it some more, but this seems to do exactly what I was after. Big thanks..!!!
|
Tah Muhl
Tah Muhl can refer to:
* Tah Muhl Shrine, an Ancient Shrine in the Eldin region.
* Tah Muhl, the Monk who designed the eponymous Shrine.
|
//
// UIImageView+ImageFetcher.swift
// LruCache
//
// Created by to4iki on 9/14/16.
// Copyright (c) 2015 to4iki. All rights reserved.
//
import Foundation
extension UIImageView {
public func fetch(url: URLLiteralConvertible) {
ImageFetcher.sharedInstance.fetch(url) {
self.image = $0
}
}
}
|
/**
* Markdown-Link in parens: ([ts2fable](http://fable.io/ts2fable/))
* Markdown-Link in two parens: (([ts2fable](http://fable.io/ts2fable/)))
* Markdown-Link in brackets: [[ts2fable](http://fable.io/ts2fable/)]
* Markdown-Link in two brackets: [[[ts2fable](http://fable.io/ts2fable/)]]
* Markdown-Link in braces: {[ts2fable](http://fable.io/ts2fable/)}
* Markdown-Link in two braces: {{[ts2fable](http://fable.io/ts2fable/)}}
*
* JSDoc-Link in parens: ({@link http://fable.io/ts2fable/ ts2fable})
* JSDoc-Link in two parens: (({@link http://fable.io/ts2fable/ ts2fable}))
* JSDoc-Link in brackets: [{@link http://fable.io/ts2fable/ ts2fable}]
* JSDoc-Link in two brackets: [[{@link http://fable.io/ts2fable/ ts2fable}]]
* JSDoc-Link in braces: {{@link http://fable.io/ts2fable/ ts2fable}}
* JSDoc-Link in two braces: {{{@link http://fable.io/ts2fable/ ts2fable}}}
*/
export interface I1 {}
|
[Question] When mapping string that contains comma it's wrapped with additional quotes
Hi there,
Thanks for the lib, works great and fast :) But lately I've been struggling with one issue I don't know if it's intended or not but for instance when I'm using IVariableLengthWriter when I map string property that contains a comma an example: "XYZ XXX, S.L" - it becomes "\"XYZ XXX, S.L\"" so it adds two extra characters.
After writing to a file I have: "XYZ XXX, S.L" instead of just XYZ XXX, S.L
I ran some tests and I'm pretty sure the case is when string contains comma.
Why is that?
P.S.: forgot to mention that in file each written value is delimited by ; and end values are wrapped with "
Here is example that I want to achieve:
"000000";"COMPANY ";"XYZ XXX, S.L"
hello @rekosko !
Thanks for the lib, works great and fast :)
Thank you for using it! and glad to know that it is helping to solve people real problems! it was the reason since the beginning
I ran some tests and I'm pretty sure the case is when string contains comma.
yes, it is because of the comma char. In your cenario the two extra quotes around the value does not change the field content, just ensure to the consumers of the file that it is a single value. So it should not be a problem in pratice. Is it being a real problem in your cenario?
The reason: In many scenarios csv users/libraries does not compliant with RFC 4180 standard. It defines that quoted char is " and field separator is , but in many cases we need to build something using different values, like in yours using ; value.
So libraries usually should use a safe approach to guarantee that what is being write to a file can be read by another library/user, even in a different programming language. In RecordParser I choose to play safe and quote any text that contains one of the following values inside its inner content:
user defined field separator
, (comma character)
\n (line break character)
\r (carriage return character)
a possible workaround would be you removing the edge quotes in the "custom property converter". something like following
FuncSpanTIntBool func = (Span<char> dest, ReadOnlySpan<char> value) =>
{
// not a quoted value
if (value.Length < 3)
return JustCopy(dest, value);
// is it a quoted value? if no, just copy
if (value[0] != '"')
return JustCopy(dest, value);
// ok, we got a quoted value. lets check its inner content
var innerContent = value.Slice(1, value.Length - 2);
// does it contains any char that we judge ok to quote? if so, we are ok
if (innerContent.ContainsAny(";\n\t\""))
return JustCopy(dest, value);
// ok, we got a quoted value that does not have any char that we judge ok to quote
// lets go ahead just with its inner content
return JustCopy(dest, innerContent);
static (bool, int) JustCopy(Span<char> dest, ReadOnlySpan<char> value) =>
value.TryCopyTo(dest)
? (true, value.Length)
: (false, 0);
};
var writer = new VariableLengthWriterBuilder<(string Name, DateTime Birthday, string Surname)>()
.Map(x => x.Name, 0, func)
.Map(x => x.Birthday, 1, "yyyy.MM.dd")
.Map(x => x.Surname, 2, func)
.Build(";");
var instance = ("foo,bar,baz", new DateTime(2020, 05, 23), "Company xyz");
Span<char> destination = stackalloc char[100];
// Act
var success = writer.TryFormat(instance, destination, out var charsWritten);
// Assert
var result = destination.Slice(0, charsWritten);
@leandromoh thank you very much for giving me the solution to my problem :) I did something similar with my custom converter but just used value.Trim('"') instead.
So in the end you proved me that this is the way to go in my case. Once again thanks :)
|
/**
* Test cases for ComponentEntityManager class.
*
* Requires node.js and it's nodeunit module.
* To run those tests: nodeunit tests/test_component-entity-manager.js
*
* @author Adrian Gaudebert - [email protected]
*/
var cem = require('../component-entity-manager'),
PositionComponent = require('./components/position');
UnitComponent = require('./components/unit');
function prepareManager() {
var myGE = new cem.ComponentEntityManager();
myGE.c('Position', PositionComponent);
myGE.c('Unit', UnitComponent);
return myGE;
}
exports['add-component'] = function (test) {
// One component case
var myGE = new cem.ComponentEntityManager();
myGE.c('Position', PositionComponent);
test.deepEqual(myGE.getComponentsList(), ['obj', 'Position'], 'Bad list of components');
// Two components case
myGE.c('Unit', UnitComponent);
test.deepEqual(myGE.getComponentsList(), ['obj', 'Position', 'Unit'], 'Bad list of components');
test.done();
}
exports['create-entity'] = function (test) {
// Preparing
var myGE = prepareManager(),
pos = myGE.e('Position');
// Testing default values
test.equal(pos.x, 0, 'Bad value for attribute `x`');
test.equal(pos.y, 0, 'Bad value for attribute `y`');
test.equal(pos.z, 0, 'Bad value for attribute `z`');
test.equal(pos.attack, undefined, 'Attribute `attack` should not exist');
test.equal(pos.unknownattribute, undefined, 'Attribute `unknownattribute` should not exist');
pos.x = 12;
test.equal(pos.x, 12, 'Bad value for attribute `x`');
pos.set('x', 13);
test.equal(pos.x, 13, 'Bad value for attribute `x`');
pos.x++;
test.equal(pos.x, 14, 'Bad value for attribute `x`');
test.equal(pos.get('x'), 14, 'get() method returns wrong result for attribute `x`');
// Testing an other entity
var unit = myGE.e('Unit');
test.equal(unit.x, 0, 'Bad value for attribute `x`');
test.equal(unit.y, 0, 'Bad value for attribute `y`');
test.equal(unit.z, 0, 'Bad value for attribute `z`');
test.equal(unit.attack, 10, 'Bad value for attribute: attack');
test.equal(unit.speed, 1, 'Bad value for attribute: speed');
// Testing methods
pos.x = 0;
test.ok(pos.isAtOrigin(), 'Cannot call method isAtOrigin() of Position entity');
test.ok(unit.isAtOrigin(), 'Cannot call method isAtOrigin() of Unit entity');
test.ok(unit.canReach(), 'Cannot call method canReach() of Unit entity');
test.done();
}
exports['get-entity'] = function (test) {
// Preparing
var myGE = prepareManager(),
pos = myGE.e('Position');
// Testing with one entity
test.deepEqual(myGE.get('Position'), [pos], 'Bad list of entities');
//~ test.deepEqual(myGE.get(pos.id), [pos], 'Bad entity'); // Not ready yet
// Testing with two entities
var unit = myGE.e('Unit');
test.deepEqual(myGE.get('Unit'), [unit], 'Bad list of entities');
test.deepEqual(myGE.get('obj Unit'), [unit], 'Bad list of entities');
test.deepEqual(myGE.get('obj Position Unit'), [unit], 'Bad list of entities');
test.deepEqual(myGE.get('Position'), [pos, unit], 'Bad list of entities');
test.deepEqual(myGE.get('obj Position'), [pos, unit], 'Bad list of entities');
test.deepEqual(myGE.get('obj'), [pos, unit], 'Bad list of entities');
//~ test.deepEqual(myGE.get(unit.id), [unit], 'Bad entity'); // Not ready yet
test.done();
}
|
Vizuna
The Protector of Jungle was the elder of the villagers who resided in the rainforests of Okoto.
Biography
* Coming soon...
Personality and Traits
* Coming soon...
Powers and Equipment
Set Information
* Coming soon...
|
npx wrangler pages publish build
$ npx wrangler pages publish build
Using cached values in 'node_modules/.cache/wrangler'. This is used as a temporary store to improve the developer experience for some commands. It may be purged at any time. It doesn't contain any sensitive information, but it should not be commited into source control.
X [ERROR] X [ERROR] Received a malformed response from the API
<html>
<head><title>502 Bad Gateway</title></head>
<body>
<center><h1>502 Bad Gateway</h1></cente... (length = 155)
POST /accounts/*********************/pages/projects/admin/file -> 502 Bad Gateway
If you think this is a bug, please open an issue at: https://github.com/cloudflare/wrangler2/issues/new
🌏 Uploading... (17/25)
It seems like this might also be related to #960. I was able to publish fine earlier, however using wrangler pages publish now I also see a combination of the error above or this:
✨ Success! Uploaded 95 files (6.83 sec)
✘ [ERROR] ✘ [ERROR] Received a bad response from the API
An unknown error occurred [code: 8000000]
If you think this is a bug, please open an issue at: https://github.com/cloudflare/wrangler2/issues/new```
Thank you for reporting this - we are working on stability improvements for publishing Pages projects through Wrangler
I'm running into this as well with no feedback other than this.
🌍 Uploading... (82/82)
✨ Success! Uploaded 82 files (10.28 sec)
✘ [ERROR] ✘ [ERROR] Received a bad response from the API
An unknown error occurred [code: 8000000]
If you think this is a bug, please open an issue at:
https://github.com/cloudflare/wrangler2/issues/new
I'm receiving a similar error:
Compiled Worker successfully.
🌍 Uploading... (188/188)
✨ Success! Uploaded 0 files (188 already uploaded) (0.58 sec)
✘ [ERROR] A request to the Cloudflare API (/accounts/********************************/pages/projects/website/deployments) failed.
An unknown error occurred [code: 8000000]
If you think this is a bug, please open an issue at: https://github.com/cloudflare/wrangler2/issues/new/choose
I receive this error pretty consistently both locally and in CI. Occasionally it flakes and succeeds.
It seems to have gotten worse after adding a _redirects file, not sure if that is related.
We see an error when we're trying to redeploy a previously deployed version (when we want to revert a live defect from our CI tool)
our assumption is that cloudflare recognises it as a previously deployed version and throws an error. How would you suggest we handle triggering a re-release of an older version from a CI pipeline?
I did some logging in the Wrangler code hoping to find some more info about the error, but it seems to be a Internal Server Error.
Let me know if there's anything I can do to help!
Updating to wrangler 2.0.14 has had no effect on success rates. Today for example, using the CLI in a GitHub Action succeeded only 3 times out of 12 attempts. Wrangler does seem smarter about not re-uploading files, which at least makes it fail faster with the "unknown error" afterwards:
> wrangler pages publish dist --project-name XXXXX --branch "main"
🌍 Uploading... (215/215)
✨ Success! Uploaded 0 files (215 already uploaded) (0.40 sec)
✘ [ERROR]A request to the Cloudflare API (/accounts/***/pages/projects/XXXXX/deployments) failed.
An unknown error occurred [code: 8000000]
If you think this is a bug, please open an issue at: https://github.com/cloudflare/wrangler2/issues/new/choose
Error: Process completed with exit code 1.
I'm not 100% sure if it is, but for me this issue appears to be fixed 😁
Hiya! Sorry for the issues. We have since fixed these so I'm closing it for now. Please do update wrangler to optin.
If you'll still see instances of this, please feel free to open or reopen this one. Cheers!
|
1. Why Study Acute HIV Infection? {#sec1-diagnostics-07-00013}
In light of the 90-90-90 United Nations Joint Program on HIV/AIDS (UNAIDS) targets, identifying the estimated 19 million human immunodeficiency virus (HIV) positive individuals worldwide who are unaware of their HIV status remains a priority \[[@B1-diagnostics-07-00013],[@B2-diagnostics-07-00013]\]. Early detection of HIV infection is key to saving public health costs \[[@B3-diagnostics-07-00013]\], and diagnosis of acute HIV infection (AHI) is gaining global attention. Acute infection is generally defined as the period of infection which precedes seroconversion, when RNA is detectable in the blood but antibodies are not \[[@B4-diagnostics-07-00013]\]. AHI is thought to contribute disproportionately to new infections, with modeling estimates suggesting that acute and early HIV infection account for up to 50% of all forward transmissions \[[@B5-diagnostics-07-00013],[@B6-diagnostics-07-00013]\]. The benefits to detecting HIV during early infection include earlier treatment initiation (now WHO recommended), resulting in reductions in viral load \[[@B7-diagnostics-07-00013]\]. Detection during AHI has public health implications for reducing forward transmission of HIV, in addition to management of symptoms of acute retroviral syndrome and lowering the viral set point \[[@B8-diagnostics-07-00013]\]. The additional value of detecting AHI must be taken into consideration, for ensuring timely treatment and controlling the spread of HIV.
2. Problems Encountered in Detecting AHI {#sec2-diagnostics-07-00013}
Compared to detecting established HIV (post-seroconversion), there are many challenges unique to the detection of acute HIV infection. Due to the lack of detectable HIV antibodies in the blood during AHI, many diagnostic technologies are rendered ineffective. This is of particular importance for high prevalence resource-limited settings, which rely heavily on rapid tests to detect antibodies to HIV. A recent study in South Africa demonstrated that a substantial number of individuals in the acute and early stage of HIV infection are misdiagnosed as negative upon initial screening with rapid antibody point of care tests \[[@B9-diagnostics-07-00013]\], highlighting the need for rapid tests which can detect HIV earlier, preferably in outreach settings.
Efforts to detect AHI have so far focused on identifying HIV RNA or p24 antigen, both of which appear in the blood prior to HIV antibodies. RNA is detectable even earlier than p24 antigen (5--7 days earlier), thus nucleic acid amplification testing (NAAT) is still the most sensitive method of detecting AHI \[[@B10-diagnostics-07-00013]\]. However, NAAT is not practical technology for many settings as it is expensive, and generally requires complex laboratory equipment and skilled technicians to perform.
Early infant diagnosis (EID) faces similar challenges for detecting acute HIV, and a point of care NAAT (Alere™ q HIV 1/2 Detect) has been developed for the purpose of EID \[[@B11-diagnostics-07-00013]\]. This device may have potential to detect AHI at point of care, yet its performance is currently being reviewed. Field evaluations in a broad spectrum of patients are needed to determine its accuracy, effectiveness and implementation potential for AHI.
Fourth generation laboratory assays detect p24 antigen in addition to HIV antibodies. These assays are highly accurate and less expensive than NAAT, but have encountered barriers to being developed in a rapid, point of care format.
Detection of p24 antigen is challenging due to is its tendency to form immune complexes with antibodies in the blood, a barrier which has been largely overcome with the use of ultrasensitive heat dissociation techniques; however these techniques are difficult to implement into a rapid, point of care diagnostic test prototype \[[@B12-diagnostics-07-00013],[@B13-diagnostics-07-00013]\]. Difficulties in sensitive detection of p24 antigen have been seen with the first FDA-approved fourth generation rapid test: the Determine HIV 1/2 Ag/Ab Combo test (Alere) \[[@B14-diagnostics-07-00013]\].
Our previous work evaluated the overall performance of the Determine HIV Combo rapid test (Alere) in a systematic review and meta-analysis \[[@B15-diagnostics-07-00013]\]. We found that while the Determine HIV Combo test's sensitivity to detect HIV antibodies was impressive, it was not able to detect p24 antigen with high sensitivity (thus unable to diagnose AHI) \[[@B15-diagnostics-07-00013]\]. These findings were largely congruent with a similar review, which investigated rapid fourth generation tests in field evaluations \[[@B16-diagnostics-07-00013]\]. While the accuracy of the Determine HIV Combo test for detecting AHI was disappointing, our quality assessment of studies highlighted the numerous challenges for conducting high quality diagnostic evaluations of rapid fourth generation tests.
To follow up on our prior meta-analysis, we aim to describe weaknesses in past evaluations of fourth generation rapid tests, evaluate if improvements have been made in recent studies, and address what is needed to improve future evaluations of rapid diagnostic tests for AHI.
2.1. Weaknesses and Biases Observed in Study Evaluations {#sec2dot1-diagnostics-07-00013}
We identified numerous weaknesses and biases in study design and conduct, that were recurring across a total of 17 studies evaluating the Determine HIV Combo test published over a period of four years (2010--2014) \[[@B15-diagnostics-07-00013]\]. Many of these problems are known to span diagnostic accuracy studies in the field of HIV and sexually transmitted infections. These problems include failure to perform sample size calculations for a defined primary end point, poor selection of study population, and biases such as verification and incorporation biases (especially lack of blinding, and use of complex reference testing algorithms).
The most frequent sources of bias in the evaluation of the Determine HIV Combo rapid test, as described in our meta-analysis and QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) summary \[[@B17-diagnostics-07-00013]\], were risk of biases in patient selection (i.e., case-mix due to case-control study design) and interpretation of the index test due to lack of blinding. While the former poses specific challenges in the context of fourth generation evaluations, the interpreter of an index test in any diagnostic evaluation should always be blinded to the reference standard results. Reviewer bias (due to lack of blinding) is more common in case control studies, but it can also occur in cross-sectional studies depending on the study procedure and time frame (i.e., if the reference standard is conducted before the index test). While the Determine Combo rapid test was designed to be simple to interpret, there is still some subjectivity in its interpretation and blinding should be reported in any diagnostic evaluation.
We have outlined below the various biases and limitations in study design which have specific implications in evaluations for fourth generation combination (antigen/antibody) tests.
2.2. Impact of Spectrum Bias in Selecting a Study Design {#sec2dot2-diagnostics-07-00013}
Spectrum bias has the potential to have a severe impact on accuracy estimates in a study. This bias can occur in case-control studies when patients or blood samples are selected based on HIV status, resulting in a case mix of patients/samples that is not representative of the target population. Patients/samples included in this type of analysis are often at extremes of the disease spectrum (i.e., well characterized and clearly positive or negative), which tends to over-estimate test accuracy. This is critical to keep in mind when evaluating fourth generation combination tests (e.g., the Determine HIV Combo rapid test), which can detect markers for HIV at different stages: p24 antigen and HIV antibody.
An individual who obtains a positive band for p24 antigen, HIV antibody, or both, is considered HIV positive. An individual who obtains a negative result for both p24 antigen and HIV antibody is considered HIV negative. Calculating an "overall" accuracy estimate for this kind of test, therefore, is actually an average of the performance of the two components in a study population, weighted to the proportion of individuals/samples which are antigen or antibody positive. Investigators must therefore be careful of the case mix of patients they recruit, if the sensitivities of the antigen and antibody components are different.
Spectrum bias was observed in the evaluations of Determine HIV Combo rapid test, which has a highly sensitive antibody component but low sensitivity for the antigen component and was evaluated in populations with varying case mixes. Using the evaluations of this test as an example, we noted that cross-sectional studies tended to have a higher proportion of patients in the established/post-seroconversion stage than patients in the acute phase (due to the narrow time frame for detecting AHI), resulting in a higher overall sensitivity. In order to increase the sample size to evaluate the p24 antigen component, many case-control studies specifically sought out p24 antigen positive samples, which naturally overestimates the prevalence of p24 antigen that would be found even in the highest prevalence setting, precipitating spectrum bias. In these cases, the overall performance of the Determine HIV Combo rapid test was more heavily weighted to the antigen component of the test (compared to field evaluations), resulting in a lower overall sensitivity.
Spectrum bias can be avoided with careful sampling, to ensure that patients/samples represent the full spectrum of disease that would be expected in a population. When previously stored blood/plasma specimens are included, randomizing the selection of these samples can mitigate this risk. In an observational cross-sectional study, a consecutive or random sampling strategy should be considered.
2.3. Impact of Imperfect Reference Standard Bias on Accuracy Estimates {#sec2dot3-diagnostics-07-00013}
Selecting an appropriate reference standard for evaluating the accuracy of fourth generation tests such as the Determine HIV Combo test is particularly challenging, as the Determine Combo test provides independent results for p24 antigen and HIV antibody. The various assays used as reference standards (or as part of reference testing algorithms) for the Determine Combo test were third and fourth generation enzyme immunoassays (EIA), third generation rapid tests, NAAT, Western Blot, and p24 antigen assays. If the accuracy of each test component of the Determine Combo is to be evaluated separately (as was the case), then an appropriate reference standard must be selected which can accurately identify the true presence or absence of p24 antigen or HIV antibody, independently. For example, using a third generation test as the sole reference standard is only suitable when evaluating the performance of the antibody component of a fourth generation test, by nature they cannot detect p24 antigen. This was the case for the evaluation conducted by Bhowan and colleagues, where the reference standard algorithm consisted of two third generation rapid tests in parallel \[[@B18-diagnostics-07-00013]\]. A fourth generation assay was only used in cases where the reference tests were discordant, or the Determine Combo rapid test was discordant with the third generation tests. As such, only the antibody component of the test could be evaluated---the investigators were not able to evaluate the overall performance of the assay, nor its ability to detect acute infections. Additionally, NAAT should be used with caution as a reference standard, as there is a 5-day window when RNA is detectable but p24 is not, meaning sensitivity for the p24 antigen component will be underestimated. For example, in the study by Patel et al. \[[@B19-diagnostics-07-00013]\], the Determine Combo rapid test was compared to NAAT, likely estimating a lower overall sensitivity than had it been compared to a fourth generation assay, as there may have been infections that were NAAT positive but not yet p24 antigen positive. Nevertheless, it may be acceptable to use NAAT as a reference standard if the objective of the study is to evaluate Determine Combo test's sensitivity to detect AHI in general (rather than p24 antigen). Authors should clearly state this distinction in their study objectives, and interpretation of results.
For estimating the overall accuracy, an appropriate reference standard for the Determine HIV Combo test would be a highly accurate fourth generation laboratory assay (e.g., Abbott Architect Combo assay). Conway and colleagues evaluated the Determine Combo rapid test against a fourth generation laboratory assay, with additional supplementary testing for positive specimens (with HIV antibody test, sensitive p24 assay and Western Blot), and samples were classified as acute if they were p24 antigen positive but antibody negative \[[@B20-diagnostics-07-00013]\] This allowed for proper estimation of overall sensitivity as well as each independent test component (p24 and HIV antibody).
Lastly, the choice of statistical methods also plays a role in evaluating test performance. For example, advanced Bayesian statistical methods can help overcome limitations in Frequentist statistical methods typically used for correcting biases due to imperfect reference standards and incorrect verification \[[@B21-diagnostics-07-00013],[@B22-diagnostics-07-00013]\].
Given the biases frequently seen in the studies evaluating the Determine Combo, addressing the question of test suitability for detecting acute HIV becomes complicated. The following questions remain: is the accuracy (e.g., sensitivity, specificity) more likely to be over or under-estimated in light of these biases, and can they feasibly be avoided in studies of diagnostic accuracy?
We ask these questions again in the context of a new fourth generation rapid test for HIV developed by Alere, the Alere HIV Combo test \[[@B23-diagnostics-07-00013]\] which is anticipated to be an improvement upon the Determine HIV Combo rapid test.
3. The Alere HIV Combo Test: A Summary of Evaluations {#sec3-diagnostics-07-00013}
Since our review of the Determine Combo rapid test, four published studies have evaluated the new Alere HIV Combo test \[[@B24-diagnostics-07-00013],[@B25-diagnostics-07-00013],[@B26-diagnostics-07-00013],[@B27-diagnostics-07-00013]\]. All four studies are case-control designs. The studies were conducted in Switzerland (this study did not compute accuracy estimates e.g., sensitivity, specificity) \[[@B27-diagnostics-07-00013]\], United Kingdom \[[@B24-diagnostics-07-00013]\], Japan \[[@B25-diagnostics-07-00013]\], and the Netherlands \[[@B26-diagnostics-07-00013]\]. So far, the Alere HIV Combo test has shown improvements in p24 antigen sensitivity compared to the Determine HIV Combo rapid test \[[@B24-diagnostics-07-00013],[@B25-diagnostics-07-00013]\]. Nevertheless, these studies have fallen victim to some of the same design flaws (outlined below) which were identified in the Determine HIV Combo rapid test evaluations.
We critiqued three studies (excluding the full text in Japanese for lack of translation) using the validated QUADAS-2 method \[[@B15-diagnostics-07-00013],[@B17-diagnostics-07-00013]\]. Limitations and biases in these studies have been outlined in [Table 1](#diagnostics-07-00013-t001){ref-type="table"}.
Risk of bias in patient selection due to the use of a case-control design was expected in the initial evaluations, as there are distinct advantages to evaluating the performance of a novel test using a case-control study, under "ideal" (i.e., laboratory controlled) environment before undertaking field evaluations. Two out of the three studies failed to mention blinding of reference standard results when interpreting the index test \[[@B24-diagnostics-07-00013],[@B27-diagnostics-07-00013]\], the third study acknowledged that the interpretation was unblinded (but did not provide any explanation) \[[@B26-diagnostics-07-00013]\].
The evaluation by Fitzgerald and colleagues restricted their samples to those which were (by reference standard) either HIV negative, p24 antigen positive, or HIV antibody positive, but did not include any samples which were positive for both p24 antigen and HIV antibody by reference standard, putting this evaluation at risk of spectrum bias. This evaluation missed a key group of individuals whose antibodies may not yet be picked up by a second or third generation antibody assay, but could be captured as positive through the p24 antigen component of the Alere HIV Combo test.
3.1. Recommendations {#sec3dot1-diagnostics-07-00013}
High quality studies, especially field evaluations, evaluating the Alere HIV Combo (or any similar fourth generation rapid test) in the future will be essential to diagnosing AHI in low and middle income settings. Quality issues can be avoided during the design stage of research studies. To avoid the biases which plagued evaluations of the Determine HIV Combo rapid test, we propose the following recommendations for future evaluations of Alere HIV Combo.
The use of a cross-sectional study design is recommended. It is essential to understand how a diagnostic test, particularly rapid and point of care tests, will perform outside of a controlled environment, in field settings. The advantages of using cross-sectional designs compared to case-control studies involve avoiding spectrum bias, obtaining generalizable results, and a more realistic indication of how a diagnostic test is likely to perform once it has been implemented in a health care setting. Cross-sectional studies (even with large sample sizes) may face difficulty recruiting sufficient numbers of patients with acute HIV infection to evaluate the performance of fourth generation rapid tests (such as Determine HIV Combo) during AHI \[[@B28-diagnostics-07-00013]\]. However, a recent study from the US was able to overcome this challenge in identifying acute infections by implementing a more sensitive test algorithm; in this study the Architect Ag/Ab fourth generation assay was used in addition to pooled RNA testing to identify acute infections \[[@B29-diagnostics-07-00013]\].
In contrast, there are advantages to using a case-control design when initially investigating a novel test or perfecting a prototype, for achieving an adequately large sample size of p24 positive specimens. The short window period of acute HIV detection (2--4 weeks) makes it challenging to capture a sufficient sample size of acute specimens (p24 antigen or RNA positive, but antibody negative). It is understandable as to why many researchers turn to a case-control design over a cross-sectional design, particularly in early evaluations where achieving perfection of device prototype becomes the guiding principle for future studies. Regardless of study design, researchers should make efforts to include all types of samples from participants of varying risk profiles, in different stages of HIV infection, not just those which are very clearly positive.
Finally, STARD is a reporting checklist for diagnostic accuracy studies \[[@B30-diagnostics-07-00013]\]; QUADAS-2 is a useful tool for understanding how biases can occur due to flaws in study design, and is frequently used to assess study quality when conducting systematic reviews of diagnostic accuracy studies \[[@B17-diagnostics-07-00013]\]. Both STARD and QUADAS-2 guidelines are practical and can be consulted while designing study protocols so that potential issues in quality are identified ahead of time.
3.2. Other Considerations {#sec3dot2-diagnostics-07-00013}
While we wait for the results of future high quality studies evaluating new tests for acute HIV infection, it is worth mentioning alternative approaches. These approaches are being used to identify acutely infected individuals in resource-limited settings, which may prove useful in the absence of a high performing fourth generation rapid point of care test. One such approach being used in sub-Saharan Africa is targeted screening of individuals, based on signs and symptoms associated with AHI (e.g., symptoms of acute retroviral syndrome such as fever, or receiving discordant rapid HIV test results) \[[@B31-diagnostics-07-00013]\] This approach involves the creation of a risk score algorithm, where only high-risk patients undergo laboratory testing for AHI, and has been shown to perform well and reduce the number of patients undergoing resource-intensive testing for AHI. Other risk score algorithms may be useful in different populations (including high income settings), such as the Denver risk score which has been validated in previous studies \[[@B32-diagnostics-07-00013]\].
4. Conclusions {#sec4-diagnostics-07-00013}
To conclude, a highly sensitive fourth generation combo rapid test has the potential to improve the detection of acute infections, however overall study quality (including sampling methodology, study design, statistical methods and reference standard algorithms) needs to be improved in future evaluations. When designing studies to evaluate a novel device, the correct population (case mix) should be targeted to avoid spectrum bias, and investigators should take special care to blind reference standard results when interpreting the index test results. Being mindful of biases and all the key items mentioned above, will not only improve the quality of evaluation, but raise the standard of diagnostic studies for detection of AHI.
Nitika Pant Pai acknowledges the support of FRSQ Salary Award Junior 2, and operating grants Canadian Institute for Health Research (CIHR): HIB-131558 Fonds de Recherche Santé.
Nitika Pant Pai and Megan Smallwood participated in the conception, drafting, critique of content.
The authors declare no conflict of interest.
::: {#diagnostics-07-00013-t001 .table-wrap}
Quality assessment of studies evaluating the Alere human immunodeficiency virus (HIV) Combo test.
Study Authors Year of Publication Sample Size QUADAS-2 Domains \*
------------------- --------------------- ------------- --------------------- --------- ----- -----
Ottiger et al. 2015 38 high unclear low low
Fitzgerald et al. 2016 120 high unclear low low
Van Tienen et al. 2017 89 high high low low
\* Risk: high, low, or unclear.
|
using System.Collections;
using System.Collections.Generic;
using System.Linq;
using UnityEngine;
public class EnvironmentManager : MonoBehaviour
{
public List<EnvironmentObject> environments;
[SerializeField] float rotateAngle = 90;
void Start()
{
foreach (EnvironmentObject item in FindObjectsOfType<EnvironmentObject>().ToList())
{
environments.Add(item);
}
}
public void CreateEnvironmentObject(GameObject env, int _cost)
{
EnvironmentObject e = Instantiate(env).GetComponent<EnvironmentObject>();
e.creationTime = Time.time;
e.cost = _cost;
AddEnv( e );
e.StartPlacing();
}
public void RotateEnv(EnvironmentObject e)
{
if(!e.isStatic)
e.transform.RotateAround(e.transform.position, e.transform.up, rotateAngle);
}
public void RemoveEnv(EnvironmentObject e)
{
environments.Remove(e);
}
public void AddEnv(EnvironmentObject e)
{
environments.Add(e);
}
public List<EnvironmentObject> GetEnvironments()
{
return environments;
}
}
|
Board Thread:Anything Goes/@comment-26335978-20171124172930/@comment-28272355-20171126171131
Pretty much hide the body
WWYD if you slipped on the floor because of someone's blood?
|
Minimum per cent, of crude protein. Minimum per cent, of crude fat. Maximum per cent, of crude fiber.
Feed Control Officials
Meal is the clean, sound, ground product of the entire grain, cereal or seed which it purports to represent. Provided, that the following meals, qualified by their descriptive names are to be known as, viz : Corn germ meal is a product in the manufacture of starch, glucose and other corn products and is the germ layer from which a part of the corn oil has been extracted. Cotton-seed meal is the meal obtained from the cotton-seed kernel after extraction of part of the oil and contains not less than 38.50 per cent, of crude protein. Linseed meal is the ground residue after extraction of part of the oil from ground flaxseed. Bolted corn meal is the entire ground product of corn, bolted.
IOS ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
lies in its outer circumference just beneath the hull. If the meal is derived from any other cereal, the source must be designated. Corn bran is the outer coating of the corn kernel. Gluten feed is a product obtained in the manufacture of starch and glucose from corn and is a mixture of gluten meal and corn bran to which may be added the residue resulting from the evaporation of the so-called "steep-water." If derived from any other cereal, the source must be designated.
thereto.
Cracklings are the residue after extracting the fats and oils from the animal tissue. If it bears a name descriptive of its kind, composition or origin, it must correspond thereto.
Digester tankage is meat scraps from edible carcasses which have been inspected and passed as satisfactory for human consumption, especially prepared for feeding purposes through tanking under live steam, drying under high heat and suitable grinding.
Distillers' dried grains are the dried residue from cereals obtained in the manufacture of alcohol and distilled liquors. The product shall bear a designation indicating the cereal predominating.
be designated.
Cotton-seed feed shall be a mixture of cotton-seed meal and cotton-seed hulls containing less than 38.50 per cent, of crude protein and shall be plainly marked "mixture of cotton-seed meal and cotton-seed hulls."
The Federal Law. — The national pure food law also protects the purchaser of feeds. All feeds that enter into interstate trade are subject to the requirements of this law. The manufacturers of feeds are required to sell goods as represented to satisfy this law. Example, a manufacturer cannot sell a feed manufactured in Texas, in Arkansas, labelled pure wheat bran that contains any thins: other than wheat bran, nor can he sell a feed of a stated chemical analysis and have it fall materially below it.
Low Grade By-Product Feeds. — Some states, as heretofore stated, do not permit the sale of feeds below certain standards. There is considerable difference of opinion as to the advisability of such prohibition. Some claim such feeds should be eliminated so as to furnish all purchasers with feeds of a so-called high or standard grade. Others claim that a manufacturer should be permitted to sell low grade feeds provided the ingredients that make up the feed are stated and there are no injurious or poisonous materials present. We all know that oat hulls, corn cobs, screenings, cotton seed hulls, etc., contain some nutritious material and many claim that should the consumer wish to buy feeds containing any of these substances it is his own privilege and legitimate, when they are stated as being present. Other points
FEED STUFF EAWS AND FEED ADULTERANTS III
that are worth considering are, that the prices of grains are getting higher and the population of this country is increasing so that the feeder may be forced in the future to utilize the wastes and low grade by-products to a certain extent.
Adulteration of Feeds. — If it were not for the protection our feed laws give us, we would find it hard to purchase good standard products. A manufacturer could easily adulterate his feed and sell it for the genuine article if he knew it would not be subject to inspection and analysis. For instance, a manufacturer could easily introduce ground cotton seed hulls into his cotton seed meal and sell the product with any guarantee he pleased. He could sell this mixed product under the name of cotton seed meal, when in reality it is cotton seed meal and ground cotton seed hulls (cotton seed feed). Of course the manufacturer could afford to sell the mixed product at a lower price than pure cotton seed meal, but for the nutrients received the purchaser would perhaps pay much more than for cotton seed meal. Many of the laws permit manufacturers to sell low grade products provided they are not injurious, but require that the true name or a trade name be employed. Perhaps the manufacturer would not care to put out a mixture of cotton seed meal and cotton seed hulls and label it so, but he would rather give it a trade or brand name, as Cracker Feed.
Values of Low Grade Feeds. — The purchasers of low grade feeds should know their values. The Experiment Stations or the State Boards of Agriculture are continually sending out bulletins which comment and set forth the values of commercial feeds so there is no excuse for a feeder, in states having feed laws, allowing a spurious article to be sold to him. In all feeds the principles as cited are true. It is unfortunate but possible, for manufacturers to put out feeds that resemble standard products, which are badly adulterated. These adulterated feeds are generally ground so fine that the casual observer would not notice the adulteration.
Feed Adulterants. — In some of our molasses feeds, wheat admixtures, corn and oat feeds, feed mixtures, cotton seed feeds, mixed oats and barley, and similar mixtures, materials are often
112 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
added which are inferior. These inferior materials are called adulterants. As a general rule adulterants are added to feeds that command high prices and so are disposed of for more than they would bring if sold unmixed.
Sweepings,
elevator dust, brushings, grain screenings and other wastes are used to some extent in our feeds, but there is such variation in the composition of these materials that the analyses are not given in the table. Corn pith, corn stalks, straws, corn husks, etc., are sometimes used. Weed seeds are objectionable because they sometimes injure the palatability of the feed to which they are added, and they are a source of disseminating objectionable weeds when they are added to a feed unground. Unground weed seeds often pass through the animal undigested. Some states do not permit the use of adulterants as previously explained.
Suggestion: Require the students to secure a copy of the State Feed Stuff Law and if your state has no law have them obtain the law from some other state. The students should read it thoroughly and write a criticism of it.
A FEW REMARKS ABOUT FEED STUFFS
Valuation of Feed Stuffs. — It is impossible to arrive at money values of feed stuffs as we can with fertilizers. The constituents in mixed fertilizers, namely, nitrogen, phosphoric acid and potash may be purchased singly, but when we purchase feed stuffs we get protein, fats and carbohydrates and cannot purchase any one of these nutrients alone, except occasionally carbohydrates from cane molasses. There are products on the market as sugar, starch, oils, protein substances, etc., which may contain single nutrients but these products are too expensive to feed live stock.
There have been many attempts made to secure a money valuation for protein, fats and carbohydrates but so far all have been unsuccessful. Should corn be taken as a basis and values established, these values when applied to the nutrients in cotton seed meal are all out of proportion to the selling price of this feed. The same principle applies with the nutrients of other feeds. If we calculate on the digestible nutrients or dry matter in feeds, the results secured have no comparative relation. The heat values of feed stuffs may be determined but a money value cannot be placed on the heats of combustion, because the nutrients act in another capacity as repair material, which value cannot be ascertained in this way.
Rebates and Comparative Unit Values. — In some sections of the country the purchaser buys feed stuffs on the chemical analyses and when they fail to reach the guarantee, rebates are demanded to make up for the deficiencies. In Louisiana the writer received so many communications requesting the settlement of rebates on feeds failing to reach their guarantees, that the following method was worked out and is used in the calculation of rebates.
The nutrients considered are protein, fat and carbohydrates (nitrogen free extract). To secure a basis of comparison of values, according to composition, one pound of protein is considered of the same value as two and one-half pounds of carbo-
114 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
hydrates, and one pound of fat is considered to be worth as much as two and a quarter pounds of carbohydrates. Therefore, to secure the total number of units on which the value is based, we multiply the protein content by 2.50 and the fat content by 2.25 and add these products to the carbohydrate content.
Example. — Let us suppose a commercial feed is sold for $32 per ton and guaranteed to contain 14 per cent, of protein, 4 per cent, of fat and 60 per cent, of carbohydrates. By analysis we find 12.30 per cent, of protein, 3.80 per cent, of fat and 62 per cent, of carbohydrates. Then the percentages of protein, fat and carbohydrates as guaranteed, multiplied by their respective unit values will give the unit values guaranteed of each of these nutrients. The addition of these will give us the total unit value guaranteed. In other words, 14 (the per cent, of protein guaranteed) multiplied by 2.50 (the unit value for protein) gives us 35.00 (or the unit value of protein guaranteed).
60 (the per cent, of carbohydrates guaranteed) multiplied by 1. 00 (the unit value of carbohydrates) gives us 60.00 (or the unit value of carbohydrates guaranteed).
In other words:
104 : 101.30 = 32 : X 104 X = 3241.60 X = 31.17, or the actual price that should be paid per ton. $32 — $31.17 = $0.83, the rebate per ton.
Impossible to Consider Digestibility. — It is impossible to consider the digestibilities of the nutrients in the several mixed feeds, because of the enormous expenditure of money and work necessary to determine these percentages. Again the primary products that go to make up these feeds are often changing. For example, a mixed feed will be inspected that is made up of corn, rice bran, rice polish, cotton seed meal, and cane molasses. In a month from the above inspection, the same company will change the ingredients of this same brand of feed, so that it consists of corn, wheat bran, alfalfa and cane molasses, and the guarantee and the name of the brand will remain unchanged. Under such conditions it is impossible to consider anything except the chemical analysis. The market prices, demand, ease of obtaining, location, etc. of the available primary products seem to determine the ingredients that are used in mixed feeds.
No Other Feed Should be Considered in Settlement. — Some agents have tried to settle rebates by figuring a mixed feed as valuable as some other feed as oats for example. Oats may be selling for $36 per ton and his feed for $32 per ton, and yet the per cent, of protein, fat and carbohydrates may be about the same in the two feeds. When a feed is sold to contain a given per cent, of protein, fat and carbohydrates for a fixed price, the rebate should be calculated on this basis and no other feed should be considered in the settlement.
Values Only Approximate. — The ■> student should understand that the unit values for protein, fat and carbohydrates as given are only approximate, but are used by the trade in certain sections, in settling rebates, and seem to give general satisfaction.
I l6 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
deficiencies in others. It may be said that such is permissible within reasonable limits. The manufacturers of feeds intend to guarantee their products as true to the actual composition as possible. Most of the manufacturers try to give a little more nutrients than guaranteed, so that the feed will meet the guarantee under reasonable conditions. Sometimes a feed will run above the guarantee in one nutrient and low in the other two, or it may run above in two nutrients and low in one ; but it hardly ever falls below the guarantee in all three nutrients. If the chemical analysis approximates the guarantee, the system as laid down for figuring rebates is permissible. The composition of the feed stuffs found on the American market will usually come within reasonable limits of their guarantees.
How to Buy a Feed. — You have learned that many of our feeds vary considerably in composition and therefore do not buy cotton seed meal, linseed meal, wheat bran, etc. just because they are so named. In purchasing feed stuffs consult the standards as given for the several feeds in the previous sections, and send for a bulletin from your State Experiment Station or from the State Board of Agriculture, which may contain analyses of the products you intend to buy. After familiarizing yourself with what the feed should contain, ask your feed dealer for the guarantee, i. e. the chemical analysis and weight of the package. If the feed or feeds you want to purchase are below the standards as set forth in your state bulletin or in the table of standards in this book, do not purchase. There are many dealers and merchants who purchase the cheapest feeds possible, regardless of their value, and sell these inferior feeds to their customers for nearly as high a price as high class feeds bring. They do this to make greater profits.
Before purchasing any feed the purchaser should know the kind of feed that is needed for his economical use. If considerable molasses, corn, roughage (native hay, corn stover, etc.) are on hand, a feed rich in protein should be secured. For example, if plenty of carbohydrate feeds are on hand, as corn and grass hay, it would be a waste of money to purchase a feed rich in carbohydrates and in all probability the results of feeding such
combinations would be unsatisfactory. The selling price and the name of a feed do not indicate its suitability for the needs of the purchaser. Often the cheapest feeds are the most expensive for the nutrients received and sometimes the reverse is true.
Il8 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
The liays from grasses, dry fodders, straws, and cane molasses would probably be considered as carbohydrate feeds although it must be remembered that they do not contain as much protein as the feeds included in Class V.
This table may be found useful in the selection of feeds. Classes I and II are especially rich in protein and may be classed as protein feeds. Classes III and IV may be termed protein and carbohydrate feeds. Class V includes the carbohydrate feeds.
Conversion Factors. — Some products are used for fertilizer and feed, and when sold may be guaranteed to contain only nitrogen or ammonia. The following factors will be useful in obtaining equivalents of nitrogen, ammonia and protein:
Example.— Cotton-seed meal, carrying 6.58 per cent, of nitrogen, is equivalent to cotton-seed meal containing 6.58 X T -2i54 or 8 -°° P er cent ammonia and 6.58 X 6.25 or 41.12 per cent, protein. A feed containing 15 per cent, protein is equivalent to a feed containing 15 X -^945 or 2 -9 2 P er cent, ammonia and 15 X • 16 or 2.40 per cent, nitrogen.
Condimental Feeds. — There are a great many of these feeds sold in this country. They are made up of mixtures of sulphur, salt, saltpeter, Epsom salts, Glauber's salts, sodium bicarbonate, fenugreek seeds, fennel seeds, ginger, turmeric, gentian powder, charcoal, red and black peppers, ground bone, Venetian red, anise, oyster shells and similar products, generally with some feed as a basis, in varying proportions. These feeds generally carry
The following is taken from Bui. 106, Mass. Exp. Station.
"Cost and Selling Price Compared. — None of the mineral drugs Used in these feeds except nitre, cost much over a cent a pound, and the vegetable drugs vary in price from 3 to 12 cents a pound. The cost of condimental feeds rarely exceeds 2 to 3 cents a pound. The retail prices vary from 6 to 25 cents a pound, depending on the \ brand and quantity purchased. Condition powders are much higher priced, from 30 cents to $1 a pound.
Value. — "The food value of these feeds has been shown by experiments to be no greater than that of ordinary grains of which they are largely composed. Their medicinal value depends largely upon the aromatic seeds and roots used as a tonic for the stomach, on charcoal as an absorbent, and on the purgative effect of the Epsom or Glauber's salts. The quantity recommended to be fed daily is usually so small (one ounce or less) that very little effect can be expected unless the material is fed for a considerable length of time. While it is probably true that some of these stock foods may prove beneficial under certain conditions, it is also true that most of them are heterogeneous mixtures and evidently put together by parties quite ignorant of the principles of animal physiology, pathology and veterinary medicine.
"Dr. Paige, very pointedly expresses the most advanced views of the veterinary profession when he says, animals in a state of health do not need condition powders or tonic foods. There is in the body of a healthy animal a condition of equilibrium of all body functions. The processes of digestion and assimilation are at their best. All that is required to maintain this condition of balance, is that the animal be kept under sanitary conditions and receive a sufficient supply of healthful nutritive food and pure water. While tonics may improve the appetite so that the animal will temporarily consume and digest more food, should this increased quantity of nutrients consumed not be appropriated by the tissues of the body, harm may result from thus over-loading
Treatment. — Bartlett of the Maine Experiment Station recommends the following when a tonic is required. "Pulverized gentian, one pound ; pulverized ginger, ]/\ pound ; pulverized saltpeter, *4 pound; pulverized iron sulphate, ]/ 2 pound. Mix and give one tablespoonful in the feed once a day for ten days, omit for three days, then give ten days more. The cost of this tonic is 20 cents a pound."
to take any chances with tonics.
Experiments conducted at other Experiment Stations on condimental feeds and condition powders have demonstrated that the economical feeder cannot afford to purchase them.
Suggestion : Take the class to a feed store or feed stores, and have the students examine the commercial feeds on sale. Require them to copy the guarantees, selling prices, names of the feeds and addresses of the manufacturers or jobbers. Have them compare the data obtained with the standards as set forth in the state bulletin or in this book. Let them figure the cost of the feeds per ton and classify them. Take the class around to the feed and drug stores and see what condimental feeds are for sale. Make a list of them and ascertain their prices. Have them figure the ton prices of these feeds.
AND THE NUTRITIVE RATIO.
Composition of Feeds. — We have already stated the meaning and functions of the nutritive elements contained in plants and animals. The next thing- is to become more familiar with the composition and digestibility of feeds. The chemist has already worked out these for us and he expresses the composition as follows :
The above analysis is very simply translated. It means that in every 100 pounds of corn grain, there are 10.3 lbs. of protein, 5 lbs. of fat, 70.4 lbs. of nitrogen free extract, 2.2 lbs. of fiber, 10.6 lbs. of water and 1.5 lbs. of ash. Or there are 10.6 lbs. of water and 89.4 lbs. of dry matter.
Digestibility of Feeds. — Knowing the composition of feeds, it is now necessary to become acquainted with the actual amounts of the nutrients (protein, fat, nitrogen free extract and fiber), that the animal can assimilate. The digestibility of any food is determined by analyzing and finding its chemical composition, namely the per cent, of protein, ether extract, nitrogen free extract, fiber, water and ash, and feeding weighed portions of this food to animals for a given period and at regular intervals. The feces or manure is collected, weighed and analyzed. The difference between the dry matter fed and the dry matter cast off as manure, is taken as digestible. This procedure seems very simple but it requires a great deal of work, and the results received are not always satisfactorily accurate.
122 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
that nitrogenous compounds present in wastes that are passed oft' in the processes of digestion, such as the wastes from mucus, bile, digestive juices, etc., have no connection with the protein of the food in the experiment. It seems that the smaller the per cent, of protein in the food, as in hay or straw for example, the greater are the amounts of these waste products in the manure. The writer conducted some digestion experiments on Bermuda and lespedeza (Japan clover) hays of low quality, and found in some cases when other feeds as cotton-seed meal, corn chops and molasses were fed with these hays, a negative digestibility for the protein of these hays. It is reasonable to suppose that some of the protein in these hays was digested. The digestibility of fat is difficult to arrive at because the wastes from the bile, which are present in the feces, are soluble in ether, which extracts matter that is calculated as fat. The digestibility of the same kind of feed is perhaps influenced by several factors such as season, climate, fertilizer, curing, handling, etc., so that the digestibility of a feed may vary with these conditions.
From the foregoing we can readily understand that the digestibilities as given in Table I are perhaps not always accurate, yet they serve in giving us an approximate value of feed stuffs.
The Per Cent. Digestible is often spoken of as the coefficient of digestibility. In order to acquaint the student with a full understanding of digestibility let us take the digestibility of corn for example.
That is, in 100 lbs. of the grain of corn, j6 per cent, of the 10.3 lbs. of protein is digestible, 86 per cent, of the 5 lbs. of fat is digestible, 93 per cent, of the 70.4 lbs. of nitrogen free extract is digestible and 58 per cent, of the 2.2 lbs. of fiber is digestible. We can represent this in another way by stating the total pounds of digestible nutrients in 100 lbs. of corn grain.
The digestible fiber is generally added to the digestible nitrogen free extract and called digestible carbohydrates. In this case then the digestible carbohydrates of corn grain would be 65.5 -(- 1.3 — 66.8 lbs. As mentioned previously the water is not considered a nutrient as it can be supplied so much cheaper by itself. The ash is also omitted because most of our feeds contain enough of this substance for the needs of the animal.
Necessity of Composition and Digestibility. — There are several feeds which have practically the same chemical composition but different percentages of digestibility. Therefore to ascertain the real feeding value of a feed the composition and digestibility should be known.
Nutritive Ratio. — The ratio between the digestible protein and the digestible carbohydrates -+- the digestible fats, is called the nutritive ratio. This ratio is obtained in the following manner. The per cent, of digestible fat is multiplied by 2.25, to reduce it to terms of carbohydrates. It was previously explained that the fuel value of fat is 2.25 times that of carbohydrates. This product is then added to the per cent, of digestible carbohydrates which gives us the total carbohydrates. This sum is divided by the per cent, of digestible protein,
Nutritive ratio in this case is 1 : 9.8.
Table of Composition and Digestible Nutrients. — The composition and digestible nutrients of feed stuffs are given in Table' I. The results in this table are the work of Foreign and American investigators.
Suggestion : Make the students determine the coefficients of digestibility of several feeds. Assume some percentages of digestibility for protein, fat and carbohydrates and have the students work out the nutritive ratios. If a cow is fed 6 lbs. of corn and cob meal a day what per cent, of protein, fat, and carbohydrates does it digest?
FEEDING STANDARDS.
The amount of digestible protein, digestible fat and digestible carbohydrates required per day for animals of 1,000 lbs. live weight, for different purposes, is called the "Feeding Standard."
The table of feeding standards is based on the work of foreign investigators and is arranged after Armsby. American investigators think that these standards call for more protein than is required for our conditions and hence a reduction is sometimes recommended to secure the best results. However, the prices of protein and carbohydrates, which will be taken up later, have a great deal to do with the make up of a ration.
Henry in his valuable book on "Feeds and Feeding," says: "Standards are arranged to meet the requirements of farm animals under normal conditions. The student should not accept the statements in the standards as absolute, but rather as data of a helpful nature, to be varied in practice as circumstances suggest.
"The statements in the column headed "Dry Matter" should be regarded as approximate only, since the digestive tract of the animal readily adapts itself to variations of 10 per cent, or more from the standard of volume.
"The standards are for animals of normal size. Those of small breeds will require somewhat more nutrients, amounting in some cases to 0.3 of a pound of nitrogenous and 1.5 pounds of non-nitrogenous digestible nutrients daily for 1,000 pounds of live weight of animals.
"Narrowing the nutritive ratio in feeding full grown animals is for the purpose of lessening the depression of digestibility, to enliven the temperament, or to increase the production of milk at the expense of laying on fat.
"The different standards given for the same class of animals according to performance illustrate the manner and direction in which desirable changes should be made.
position.
"The standards for growing animals contemplate only a moderate amount of exercise; if much is taken, add 15 per cent., — (mostly non-nitrogenous nutrients) — to the ration. If no exercise is taken, deduct 15 per cent, from the standard."
Explanation of Table II. — The table on feeding standards is divided into two parts, A and B. Table A gives the amounts of dry matter and digestible nutrients required per day for farm animals under all conditions of work and rest. This table is based on 1,000 lbs. live weight. Table B is similar to Table A, except that the standards are based on the weights of the animals as mentioned. To make this clearer, the first standard in Table A is for "oxen at rest in stall." The standard reads 17.5 lbs. dry matter, 0.7 lbs protein, 8.3 lbs. carbohydrates and fat, 9.0 lbs. total, with a nutritive ratio of 1 : 11.9. This standard is for oxen, weighing 1,000 lbs., at rest in the stall. The first standard in table B is for growing cattle 2-3 months old weighing 150 lbs. The standard reads 3.3 lbs. dry matter, 0.6 lbs. protein, 2.8 lbs. carbohydrates and fat, 3.4 lbs. total, with a nutritive ratio of 1 : 4.6. This standard is figured on growing cattle weighing 150 lbs.
The digestible carbohydrates, fiber and fat are included in the column, carbohydrates and fat. The fat is reduced to terms of carbohydrates and the digestible fiber is added to the carbohydrates because it is considered of equal value.
A study of the table reveals a difference in the standards for the same class of animal according to the purpose for which the animal is fed. These standards therefore may be called feed requirements. The feed requirements may be considered for maintenance, growth, work, milk production and fattening.
Maintenance Requirements. — We learned that no matter how still an animal might be, a supply of food is necessary to keep the animal alive. The amount of dry matter and digestible nutrients
1: 6.5
required to keep the animal alive, which is producing and' doing nothing, without a loss or gain in weight, is called the maintenance requirement. It is then the amount of nutrients required to maintain the animal body. The feeding standard for "oxen at rest in stall" is an example of a maintenance requirement.
Growth Requirements. — In the composition of farm animals we found that the young animal contains a larger percentage of water than the mature animal, and a gain in weight of the young animal shows less dry matter and more water than with the mature animal. We also learned that the dry matter of the young animal contains more protein and less fat than that of the mature animal. Hence the requirements for growth show a larger proportion of protein to carbohydrates than for the older animals. The following standards per 1,000 lbs. live weight, illustrate this point.
140 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
Work Requirements. — A working animal requires protein to repair the broken down tissues and carbohydrates and fats to produce energy. Therefore the harder an animal has to work the more protein and carbohydrates are needed. The protein
Milk Production Requirements. — The protein requirements for milk production are not entirely satisfactory for all parts of this country, and this will be discussed later. Suffice it to say that milk contains nitrogenous compounds, and enough protein must
essary functions of the animal body.
Fattening Requirements. — In the production of fat, carbohydrates and fat of feed stuffs are mainly used. Hence the ration for fattening animals should contain a considerable proportion of non-nitrogenous substances. Too much of an excess of carbohydrates and fats is undesirable as such excess interferes with digestion. A small proportion of the ration should consist of digestible protein which aids in the digestion and consumption of fattening rations. Kellner recommends 1 pound of digestible protein to 8-10 pounds of carbohydrates and fat.
SECTION XXIII.
— Referring to Table i (Composition and Digestible Nutrients) and Table II (Feeding Standards) and knowing the meaning of the terms as set forth in the preceding pages, it will now be a simple matter of arithmetic and judgment to compute or balance any ration.
Let us suppose, for example, that we have a horse or a mule at home ploughing. Ploughing all day is hard or heavy work. Now if we turn to Table II we find that the standard for a horse weighing 1,000 lbs. heavily worked is as follows:
This means that if our horse at home doing heavy work, weighs 1,000 lbs., the requirement will be 23 lbs. of dry matter, 2.3 lbs. of digestible protein, and 14.3 lbs. of digestible carbohydrates to satisfy its needs for a day of 24 hours.
Let us suppose we have the following feed stuffs at home: Cotton-seed meal, corn (shelled), wheat bran and timothy hay. To figure our ration let us try 2 lbs. of cotton-seed meal, 6 lbs. of shelled corn, 6 lbs. of wheat bran and 10 lbs. of timothy hay. We must now find the total dry matter, digestible protein, digestible carbohydrates and fat, in each of the above feeds that make up our ration. Referring to Table I we find that 100 lbs. of cotton-seed meal contain 91.8 lbs. of dry matter, 37.2 lbs. of digestible protein, 16.9 lbs. of digestible carbohydrates and 12.2 lbs. of digestible fat. Then as 2 lbs. of cotton-seed meal are included in our trial ration we get the amounts of digestible nutrients as stated.
In the same way we arrive at the digestible amounts contained in 6 lbs. of shelled corn, 6 lbs. of wheat bran and 10 lbs. of timothy hay. Then we add together the dry matter and digestible nutrients in the cotton-seed meal, shelled corn, wheat bran and timothy hay and compare the result with the standard.
To reduce the fat to terms of carbohydrates we must multiply by 2.25. 0.804 X 2.25 = 1.809. 11-038 -f- 1.809 — i 2 -847 ^s. total digestible carbohydrates. 12.847 (total digestible carbohydrates) -r- 2.218 (digestible protein) = 5.8. That is, the nutritive ratio is 1: 5.8. This trial ration is stated as follows:
Balancing the Ration. — This trial ration is not entirely satisfactory. It is almost correct for dry matter and near enough to the standard in protein. It is too low in carbohydrates. We must correct the ration to make it more nearly approximate the standard. Let us add 3 lbs. of timothy hay and see what effect it has on balancing the ration.
It is practically impossible to get the exact amounts as laid down in the standard. The above ration is perhaps nearer the standard than one will ordinarily approximate.
If animals weigh more or less than 1,000 lbs. it is necessary to increase or decrease the amounts of the feed proportionately. The nutritive ratio, however, should remain the same. In the above example suppose the horse weighs 1,200 lbs., then we would increase the amounts of feed one-fifth. That is, instead of feeding 2 lbs. of cotton-seed meal, 6 lbs. of shelled corn, 6 lbs. of wheat bran and 13 lbs. of timothy hay we would feed 2.4 lbs. of cotton-seed meal, 7.2 lbs. shelled corn, 7.2 lbs. of wheat bran and 15.6 lbs. of timothy hay. If the animal weighed less than 1,000 lbs. the ration should be proportionately reduced. Sometimes the individuality of the animal must be considered. Dairy cattle weighing 700 lbs. giving 25 lbs. of milk need more feed than dairy cattle weighing the same but only giving 15 lbs. of milk.
HOW TO BALANCE A RATION
Narrow Ration. — A narrow ration is one in which the proportion of protein is large as compared to the carbohydrates. A ration having a nutritive ratio less than 1 : 5.5 is considered narrow.
Nutritive ratio 1:2.9
The protein in the above ration is high as compared to the carbohydrates. Nitrogenous ration is another name sometimes applied to a narrow ration because of the predominance of nitrogenous substances (protein).
Wide Ration. — A wide nutritive ratio is one where the proportion of carbohydrates is large as compared to the protein. Such a ration has a nutritive ratio of more than 1 : 8.0
Nutritive ratio 1:12.4
This style of ration is sometimes called carbonaceous on account of the high proportion of carbohydrates, but the term is incorrect because protein as well as carbohydrates contains carbonaceous compounds.
AMOUNTS OF ROUGHAGE AND CONCENTRATES TO FEED.
Amounts of Roughage and Cencentrates to Feed. — In compounding rations for live stock it is necessary that the proper amounts of roughage and concentrates accompany each other. It is practically impossible to state just the amounts of roughage and grain to furnish animals for different purposes, as available feeds and prices influence the make up of the ration. The following considerations therefore are only approximate.
Milch Cows. — In rations for milch cows we should aim to supply 12-14 lbs. of dry matter from roughage and the balance with 8-12 lbs. of grain. Sometimes as high as 50 lbs. of silage are fed to milch cows but usually 30 to 40 lbs. are sufficient.
Fattening Cattle do well on 2 lbs. of grain to 1 lb. of roughage. 8 to 10 lbs. of roughage and 15 to 18 lbs. of grain per 1,000 lbs. live weight are perhaps sufficient for this class of animal.
Horses or Mules. — For horses or mules 10 to 12 lbs. of hay are usually enough. 1 lb. of roughage to 100 lbs. live weight is a crude method of estimating the quantity of roughage for a horse or mule. A horse or mule weighing 1,200 lbs. would therefore receive, according to this method, 12 lbs. of hay.
When the concentrates of a ration are carbohydrate in character, the roughage should be nitrogenous (legumes for example) and should the concentrates be nitrogenous the roughage should be relatively high in carbohydrates (grass hay for example). In other words the roughage and concentrates should be complements of each other.
There is an excess of 20.7 lbs. of dry matter and a waste of 9.29 lbs. of carbohydrates in such a ration. A horse could not perform hard work with this ration as it would be impossible for this class of animal to consume such a large quantity of hay.
30.091
This combination is unsatisfactory because it exceeds the dry matter standard by 25 lbs. and there is a waste of 15.7 lbs. of carbohydrates. Both of these feeds are proportionately high in carbohydrates.
is proportionately high in carbohydrates and the alfalfa is relatively high in protein. These feeds are then complements of each other. This ration should prove satisfactory as the total feed is not too large in amount and the roughage is within the limit of the requirements for a horse.
A ration of oats alone is not suitable because of the excess of concentrate. Roughage is required for the best results. Such a ration would prove too expensive for the economical feeder.
150 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
The ration as it now stands is properly balanced. It is not enough too high in dry matter to affect its usefulness and the protein and carbohydrates are sufficiently close.
7. Generally a variation from the standard shows a predominance of carbohydrates and dry matter but sometimes an excess of protein is employed. The following ration illustrates a predominance of protein :
This ration shows a waste of 0.8 of a pound of protein which is generally the most expensive nutrient in feed stuffs. The roughage in this ration is also a little high. The carbohydrates agree with the standard.
Feeding Standards are Guides. — It must be understood that the feeding standards are only guides and the intelligent feeder will often find it necessary to change the standard to suit his conditions. In other words the feeder must use the feeding standards to approximate the requirements of his live-stock from the feeds that are available and cheapest.
The following table is given to enable the feeder to compound rations easily. In making rations for animals, large amounts of the grain portion can be mixed at one time. This saves the trouble of mixing and calculating at every feeding. The measure of roots, molasses, hay, fodder and ensilage can be determined once and fed accordingly without any inconvenience.
Suggestion : — Compute a ration for a moderately worked horse weighing 1,000 lbs. from cotton-seed meal, wheat bran and molasses (cane). Criticize this ration.
1 The data on wheat mixed feed was taken from Bui. 112, Massachusetts Experiment Station ; the data on alfalfa meal, cottonseed hulls, molasses and rice products were worked out by the writer ; the remaining data came from Farmers' Bui. 222.
HOW TO IMPROVE AND REDUCE THE COST OF RATIONS. 1
A Common Ration. — A herd of milch cows is receiving the following ration per day of 24 hours, per 1,000 lbs. live weight; 5 lbs. of cotton-seed meal, 3 lbs. of wheat bran, 10 lbs. of red clover hay (medium) and 15 lbs. of corn stover. Let us figure this ration and find out if it is properly balanced for the herd of dairy cows. Turn to Table I and find that the following amounts of digestible nutrients are present in 100 lbs. of each feed stuff.
Then as 5 lbs. of cotton-seed meal are in the ration, we multiply the amounts of dry matter, digestible protein, digestible carbohydrates and digestible fat as given above for cotton-seed meal, by 5. Or
digestible carbohydrates. The ration is also too narrow.
Improving the Ration. — Let us try to improve this ration by supplying less of the nutrients and particularly less protein. By consulting Table I we learn that cotton-seed meal has more digestible protein than any of the other feeds in this ration. Suppose then we reduce the amount of cotton-seed meal to 3 lbs. Then the ration will be as follows :
154 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
How to Reduce the Cost of a Ration. — John Smith has a large farm and he is feeding his 15 horses which weigh 1,000 lbs., that are doing hard work, the following ration.
Cost of the Ration. — Let us learn what it is costing John Smith to feed his horses. The following are the market prices of some of the feeds which are available to John Smith.
Corn and cob meal 22.00
Oats cost $35 per ton of 2,000 lbs. One pound of oats costs $0.0175. Then 8 lbs. will cost 8 X 0.0175 = $0.14. In a similar way the cost of the shelled corn, wheat bran and timothy hay are calculated.
COST OF RATIONS
It is costing John Smith $0,361 per day per horse. Or it is costing him 15 X $0,361 = $5,415 for his 15 horses per day. We will now substitute some other feeds and see if we cannot reduce John Smith's feed bill.
A Cheaper Ration. — Oats, shelled corn and timothy hay are the expensive feeds in this ration, considering the nutrients they furnish. By perusing Table I we find that cotton-seed meal contains a high per cent, of digestible protein. We can substitute this feed for oats. Shelled corn and corn and cob meal contain about the same amounts of dry matter and digestible carbohydrates, so we may substitute corn and cob meal for shelled corn. The shelled corn is richer in digestible protein than the corn and cob meal but we can get this nutrient cheaper from our wheat bran. The crab grass hay is of about the same nutritive value as timothy hay. It is also cheaper so we will use crab grass hay in place of timothy hay. A balanced ration from these feeds would be as stated.
i :6.2
Compared to the Standard. — This ration is better than the one John Smith is feeding. It comes nearer the standard. The dry matter and carbohydrates in John Smith's ration approximate the standard but the protein is too low and his ration is too wide. The dry matter in this second ration is a little high, but animals can take care of an excess of dry matter within certain limits as previously explained. The protein and carbohydrates in the
T56 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
balanced ration are very close to the standard. The nutritive ratio very closely approximates the standard nutritive ratio. The Saving 1 . — At the market prices the new ration will cost,
In other words this ration will cost John Smith $0,293 per day per horse. The ration of John Smith's costs $0,361 per day per horse. This new ration will save John Smith $0,361 — $0,293 = $0,068 per day per horse. On 15 horses the saving will be 15 X $0,068 = $1.02 per day. In a year the savingwill amount to 365 X $1.02 = $372.30. This example just cited is not exceptional. There are many farmers, livery men and other feeders who throw away money every year because of a poor selection of feeds and still they do not always get the best returns. This second ration, as it more closely approximates the standard, is indeed a better one, besides being cheaper than John Smith's ration.
Suggestion: — Select a few rations fed in the county and have the students ascertain the market values of the feeds and reduce the cost and improve these rations as much as possible.
NUTRIENTS IN FEED STUFFS
Table III which follows, is given to save the student considerable work in figuring rations. It gives the dry matter and the digestible nutrients in i, 2, 3, 4, 5, 7, and 10 pounds of several feed stuffs commonly used.
In Table I the composition and digestible nutrients of feed stuffs are given but in figuring rations from Table I a great deal of work is necessary. The figures in Table I are based on 100 lbs. of material so in obtaining data for any amount less than 100 lbs. involves a chance for error.
Use of Table III. — Let us suppose we wish to feed a ration composed of 5 lbs. of oats, 10 lbs. of alfalfa hay and 4 lbs. of corn (grain) per day. By referring to Table III we find that these quantities of the stated feeds carry the following amounts of dry matter and digestible nutrients.
The digestible fat as given in the table must be reduced to carbohydrates to get the total carbohydrates. It is only necessary to do this once, however, after the amounts for the ration have been added, as was done above.
If amounts other than those given in the table are desired it is only necessary to multiply, divide or add some of those given. For example, if the amounts of dry matter and digestible nutrients for 6 lbs. are wished we would multiply the amounts given for 3 lbs., by 2. If 9 lbs. are wanted, add the amounts
for 4 and 5 lbs. or multiply the amounts for 3 lbs., by 3. If Y? lb. is needed, take 1/10 of 5 lbs. or divide the amounts for 1 lb., by 2. For 50, 100, 200, 300 lbs., etc., a simple multiplication will give the amounts required.
A Ration Computed by Using Table III. — Let us figure a ration by using this table. Supposing we have some cattle we wish to fatten for the market. The standard, Table II, for the preliminary period for fattening cattle of 1,000 lbs. live weight is :
Our ration is too low in carbohydrates to be satisfactory. Corn and cob meal contains a larger percentage of carbohydrates than the other feeds included in this ration. Therefore we will use 15 lbs of corn and cob meal. The protein in our trial ration is almost equal to that of the standard and by using 15 lbs. of corn and cob meal the protein will be too high. Let us try reducing the amount of alfalfa hay to 14 lbs. and compare our ration to the standard.
This ration is very close to the standard.
Suggestion : — Compute a ration for farm work horses averaging 1,200 lbs., doing heavy farm work, from oats, linseed meal, corn and cob meal and timothy hay. How much of each concentrate would be required to last 15 horses of this weight for a month?
STANDARDS FOR MUCH COWS.
Wolff's standard for milch cows, which has been generally used, has been found to be unsatisfactory for American feeders. Many investigations have been conducted to determine the requirements for milch cows in this country.
Adjust the Ration to the Cow's Needs. — Haecker in Minnesota Bui. 79, says : "It has long since been recognized that because of the difference in composition of the various kinds of feed stuffs no single standard of composition for all feeds would be practical, and yet, while there is as great a difference in the composition of milks as there is in feed stuffs, there has been no adjustment of the nutrients in the ration to the quantity and character of the solids contained in the milk yielded, though such an adjustment is simple and practicable. If in formulating a ration it is deemed necessary in economic milk production, to take note of the fact that one feed stuff contains 12 per cent, protein and another 20 per cent., is it not equally important in our attempt to adjust the ration to the needs of the cow in milk production to also take into account the fact that one cow may give milk containing 3 per cent, fat while that of another may contain twice as much? It would seem quite as consistent to feed an animal food regardless of its composition as to feed an assumed balanced ration regardless of the composition of the product which is to be elaborated from the nutrients in the food.
"Great stress has been placed upon the fact that the nutrients in milk have a nutritive ratio of approximately one to five, and that therefore the ration for a milch cow should have a similar nutritive ratio ; apparently overlooking the fact that only 50 per cent, of the ration is used in milk production and the balance for maintenance of body. If note is taken of the fact that about half the ration is used for maintenance and that the maintenance ration has a nutritive ratio of one to ten. it becomes apparent that for the production of milk of average quality by an animal of average milk producing powers the nutritive ratio of the ration should be approximately 1 : 7.5. But since animals
vary in productive powers, and since this variation is not in proportion to weight of body, it follows that if rations are adjusted to the actual requirements of animals the nutritive ratio of the rations will also vary."
A New World Record.
"It remained for the Missouri College of Agriculture at Columbia, Missouri, to raise and develop the Champion Dairy Cow of all the world. Missouri Chief Josephine, a Holstein-Friesian cow
finished her six months test on July 18th, producing 17,008.8 pounds, an average of 93.4 pounds of milk daily for 182 days. This is equivalent to 46.7 quarts, or 11.6 gallons every day. Her highest record for one day was 1 10.2 pounds. This record is the more remarkable because no special preparation had been made for this test and Josephine has done her full duty in the regular dairy herd of the University, having had five calves in five and one-half years.
STANDARDS FOR MILCH COWS 175
Not only has this record smashed all previous worlds records for milk production, but the per cent, of butter fat is increasing daily, so that, barring accidents this cow will undoubtedly produce more butter during a period of twelve months than any other cow that has ever been tested in the world.
This cow is but one of a number of remarkable cows owned by the University of Missouri and maintained solely for the instruction of its students -in Agriculture and for investigational purposes. Only twenty Jersey cows in the history of the world have produced more than 700 pounds of butter in one year. Five of these cows, or 25 per cent, of the total number are owned and were bred by this Missouri institution. The College owns more than 300 pure bred and registered animals, belonging to 17 distinct breeds.
The table on page 176 of standards for milch cows has been compiled from Haecker's work, giving the requirements for cows weighing 1,000 lbs. producing the stated quantities of milk of stated butter fat.
Maintenance and Milk Production Requirements. — The standards in the table include the requirements for maintenance and milk production and are based on 1,000 lbs. live weight. Investigations have demonstrated that the maintenance per 100 lbs. live weight, namely, 0.07 of a pound of digestible protein, 0.7 of a pound of digestible carbohydrates and 0.01 of a pound of digestible fat, which is given at the head of the preceding table, are ample for maintaining the average cow.
To compute the maintenance requirements for any live weight, say 600, 700 or 800 lbs., simply multiply the maintenance for 100 lbs. by 6, 7 or 8 as the case may be. For milk production requirements, divide the production of milk by 10 and multiply the standard for each additional 10 lbs. by this result. The standard required would be the sum of the maintenance and milk production requirements.
ing 850 lbs.
Use of the Table. — Let us make this clearer by computing the standard for a cow weighing 850 lbs. producing 23 lbs. of milk daily, testing 5 per cent, butter fat.
Multiply the standard for each additional 10 lbs. of 5 per cent, butter fat milk (0.54 lb. protein, 2.48 lbs., carbohydrates and 0.18 lb. fat) by 2.3 which gives us the milk production requirement.
As previously stated the standards in the table are on the basis of 1,000 lbs. live weight. Therefore to compute the standard for a cow of this weight (1,000 lbs.) it is not necessary to figure the maintenance and milk production requirements, as this work has already been done and is included in the table.
A Ration. — The following ration for a cow weighing 1,000 lbs. producing 25 lbs. of milk daily, testing 4 per cent, butter fat, illustrates how feed stuffs may be compounded to meet the standards as laid down in this table.
poses.
A Narrow Nutritive Ratio is Sometimes Economical. — Dairymen have learned by practical experience that Haecker's standards are too wide (that is there is too high a proportion of carbohydrates and fat to protein) for the most economical production of milk where protein is cheap and carbohydrates relatively expensive. In all probability Haecker's table is suitable for the Northwest and other sections where protein is expensive and carbohydrates comparatively cheap. Prof. E. L. Jor-
178 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
dan of the Louisiana State University and the writer adapted the following table from Haecker's work to meet the demands of feeders who wish to employ narrow rations for milch cows.
Woll of the Wisconsin Experiment Station says : "At the prices of feeding stuffs in the North Central States it will not, as a general rule, pay to feed a narrower ratio to dairy cows than 1 : 6.0 and we find that the cows in our University herd fed according to our best judgment receive on the average rations with a nutritive ratio of about 1 : 6.5 to 7.0. The heavier producers in the herd naturally receive more grain feed than the low producers and their rations, therefore, have a narrower nutritive ratio, but it is very rarely that we find it necessary to go below 1 : 6.0. The starchy feeds are cheaper than the protein feeds with us and unless the cow has an exceptional productive capacity a medium or somewhat wide nutritive ratio is more economical than a narrow one."
Suggestion : A gallon of milk weighs 8.6 lbs. Compute two rations for a cow weighing 825 lbs. producing 2 Y / 2 gallons of milk a day, testing 4 per cent, butter fat, according to the standards in the two tables in this section, from mixed hay, corn meal, linseed meal and wheat bran.
COMPUTATION OF RATIONS ACCORDING TO ENERGY VALUES.
The tables given in the foregoing pages on composition, digestible nutrients and standards are those commonly used in compounding rations. Armsby of the Pennsylvania Experiment Station and G. Kuhn and Kellner of the Mockern Experiment Station of Germany have been conducting investigations as to the protein and energy values of feeds, and the requirements of animals, by means of the respiration apparatus.
The following table of digestible protein and energy values is taken from Farmers' Bui. 346. The energy value represents the production value, or the value of the feed stuffs cited for the production of gain in fattening animals. The protein represents what is available for repair material.
The Feed Requirements given in Table V may not be absolutely accurate but they are perhaps as near to the true requirements as those we are accustomed to using. The intelligent feeder can compound rations from this table that will meet
COMPUTATION OF RATIONS
the requirements of his animals. The requirements for swine have not been worked out. The per cent, of digestible protein, being true protein (crude protein minus the amides) will be smaller in amount than the digestible protein of the standards given in Table II.
Energy, therms 4.95 6.00
The difference between 875 and 1,000 is the same as the difference between 750 and 875. Therefore the maintenance requirement for a cow weighing 875 lbs. is :
How to Compute the Ration. — Let us suppose cotton-seed meal, corn meal, wheat middlings, oat hay and rye straw are available. Our previous study has taught us that we should endeavor to supply 12 to 14 pounds of dry matter from roughage, as roughage generally is our cheapest source of feed. We have been taught that the amount of roughage should be limited because an animal can only properly consume a certain amount of roughage. Rye straw and oat hay are the feeds which are available as roughage.
Let us see what 8 lbs. of rye straw will furnish :
92.9 X °-°8 = 7-43 2 pounds dry matter 0.63 X °-°S = -°5°4 pound digestible protein 20.87 X °-°8 — 1.6696 therms of energy value
Eight pounds of rye straw furnish 7.432 lbs. of dry matter. By a simple calculation we find that 6 lbs. of oat hay will furnish the remaining dry matter required from roughage. The amounts for oat hay are arrived at in the same way as for rye straw.
I.6696
We must supply the difference between what we have figured for roughage and the requirement (1.7 lbs. digestible protein and 12.975 therms of energy value) with the available concentrates (cotton-seed meal, corn meal and wheat middlings).
184 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
Addition of Concentrates. — Let us try 3 lbs. of cotton-seed meal, 3 lbs. of corn meal and 2 lbs. of wheat middlings and add these to our roughage. The amounts for the concentrates are calculated in a similar manner from Table IV as illustrated for rye straw.
in therms of energy value.
Balancing the Ration. — In order to bring the energy value to the requirement we must add some corn meal, as this feed stuff contains a relatively larger proportion of therms than the other available concentrates. We must reduce the quantity of cotton-seed meal because an addition of corn meal will make the protein too high. We will try 6 lbs. of corn meal and 2 lbs. of cotton-seed meal and compare the ration to the requirement.
lS6 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
doing medium work, weighing 1,200 lbs. computed from timothy hay, oats, corn and wheat bran would be calculated as follows. Table V gives maintenance and work requirement for a horse doing medium work weighing 1,000 lbs. as,
Requirement 1,200 1.68
We must aim to allow a limited amount of roughage to a horse because this class of animal is not capable of consuming large amounts of this kind of feed stuff. The following ration approximates the requirement.
Rations for Fattening Cattle. — In computing rations for fattening cattle the maintenance requirement should be added to the average gain in live weight per day. Example : A farmer has a bunch of cattle weighing 1,000 lbs. which he wishes to fatten for the market. These cattle should make an average gain of 2 lbs. a day and weigh about 1,500 lbs. when ready for sale.
According to Table V, 1 pound gain in live weight for fattening cattle requires 3.5 therms of energy value. The cattle gain 2 lbs. a day, hence (2 X 3.5) = 7 therms, or the requirement of energy value. The maintenance should be calculated on the average live weight of the cattle for the period, namely 1,250 lbs.
Total requirement 0.60 14.00
The digestible protein requirement is not given for 1 pound gain live weight, so that in computing a ration of this nature it will be necessary to balance the energy value. The digestible protein will then be much higher than is included in the requirement, but if the energy value is balanced by the employment of the proper amounts of roughage and concentrates the digestible protein will be near enough for good results.
Suggestion : Require the class to compute a ration for a flock of sheep averaging 135 lbs. live weight and 16 months of age, from potatoes, gluten feed, corn, clover hay and oat straw, according to energy values.
FEED AND CARE OF DAIRY COWS.
Requirements. — The ration for a dairy cow should supply the proper amounts of nutrients for good milk production and for the needs of the animal body. It should be palatable and adaptable. The ration should be as cheap as possible and should not contain enough feed to disturb the digestive equilibrium of the animal.
Amount of Feed. — As already stated the amount of nutrients should be controlled by the quantity of milk produced, and its butter fat content. A cow producing 15 lbs. of milk should not receive as much digestible feed as one giving 25 lbs. of milk, and of two cows producing equal quantities of milk, the one producing the higher fat content should receive the more non-nitrogenous food.
The dairy cow when producing a good flow of milk is a hard working animal. Hence the larger the yield of milk the greater should be the proportion of concentrates to roughage. A dry cow is a lightly worked animal and a suitable ration may consist of much less grain and more roughage than for a cow in milk. A pregnant cow needs nitrogenous food to support the calf in utero and a suitable ration may be furnished with some well cured leguminous hay and carbohydrate roughage as corn stover, good grass hay, or straw. When the roughage is inferior, grain should be supplied in small amounts. A ration for a dairy cow should be made up of more than two feeds as an animal does better and enjoys variety just as people do.
Cows usually prefer their feed in a dry condition and by supplying the feed in this way, the mangers are easily kept clean. The general practice is to feed dairy cows in the morning and late afternoon, with a little roughage, such as hay, at noon time. The cows should be fed and milked regularly. With some cows (usually fresh young cows) uniformity in the milking time is necessary for the best returns.
FEED AND CARE OF DAIRY COWS 189
ly influence the amount of grain that should be fed per day. For cows weighing 800 lbs. producing 20 to 22 lbs. of milk testing 5 per cent fat, 7 to 8 lbs. of grain should suffice. When the price of grain is high it is sometimes economical to reduce the grain portion of the ration to 5 to 6 lbs. When the grain is reduced the feeds grown on the farm may be fed to advantage. Cows weighing 1,100 to 1,200 lbs. should receive sometimes as high as 11 to 12 lbs. of grain, depending upon their ability to consume it to good advantage. Whenever heavy feeds such as corn meal, middlings, etc. form a part of the ration, bulky feeds such as wheat bran, dried brewers' grains, corn and cob meal, etc. should be included.
be considered.
Corn (Grain). — This grain is used very extensively in American dairy rations because it may be successfully grown in most all sections of the United States. It is relished by cattle. It is relatively high in carbohydrates and when supplemented with another feed to complete the ration, the latter must necessarily supply roughage and be nitrogenous in character. When whole corn grain is fed some of it passes through the animal undigested and for this reason it is well to grind it and feed it as corn meal.
Corn and Cob Meal, when ground fine, is very satisfactory for dairy cattle. When the expense of grinding is not too great it may be used profitably. It is practically equal to corn meal in feeding value for dairy cows because of its bulkiness and looseness, which permits of its being readily acted upon by the digestive juices.
eliminated.
Corn By-Products. — Corn bran, corn germ meal, gluten feed, gluten meal, grano-gluten and hominy meal are used a great deal by feeders of dairy cattle. Gluten feed and gluten meal are very popular with the eastern feeders as a source of protein.
IQO ELEMENTARY TREATISE ON STOCK EEEDS AND FEEDING
to corn meal and should be mixed with other grain in forming" a ration, because it is sticky when masticated. The by-products are superior to ground wheat for dairy cows.
Wheat bran, wheat middlings or shorts and red dog flour are the wheat by-products fed in dairy rations. Wheat bran is especially desirable. This feed runs high enough in fiber to give bulk and it contains a high ash content and a fair protein percentage for a concentrate. Wheat bran is used in more dairy rations perhaps than any other concentrate. With heavy corn meal it makes a good combination as corn is rather deficient in ash and fiber. Bran seems to aid digestion, has a cooling effect, and is a mild laxative. It is one of the best feeds for dairy cows just after calving, because at that time the cow is generally constipated and feverish.
Middlings are much heavier than bran so they are not as good a complement for corn meal as bran. Middlings are more suitable than bran for animals of small capacity.
Six to eight pounds of bran and from four to six pounds of middlings may be fed daily to dairy cows. Dark feeding flour (red dog) is excellent dairy feed when the price is within the limit of the feeder. It is a heavy feed and therefore should be accompanied with some light concentrate.
Barley. — Ground barley may be fed profitably to dairy cows ; at the rate of 3 to 5 lbs., in certain sections when the price is low. Barley should always be ground. It has about the same feeding- value as corn. It is often fed with oats. It contains more digestible protein than corn and less than oats. Wheat bran, or roots, or oats, should accompany barley as this latter feed counteracts the laxative effect of these feeds.
are sufficient.
Rye Meal should be fed in conjunction with ground oats, wheat bran, corn meal, etc., and should never be supplied in quantities of more than 3 pounds a day. An excess of this feed
mary to feed less than 3 pounds a day.
Oats. — Ground oats make excellent feed for cows in milk. The selling price regulates the extent of its use in dairy feeding. It may form the whole grain part of the ration and when mixed with corn meal, wheat bran, ground barley or rye meal, an excellent ration may be completed with hay and stover. Oats is easily digested and bulky and may be fed economically when the price is slightly higher than corn.
Pea Meal and ground oats when mixed together offer a suitable feed. About ]/z pea meal together with % oats or bran is an ideal feed. This concentrate is fed in far northern sections with good success
Vegetable Oil By-Products. — Linseed meal, cotton-seed meal and cotton-seed hulls are used considerably for dairy herds. Cotton-seed is sometimes fed but at the present prices it is more advisable to sell it to the oil mills. It is a good feed. Linseed meal and cotton-seed meal are both used to furnish protein in rations. A study of Table I shows these feeds to contain high protein contents. Practical feeders advise that not over 4 pounds of cotton-seed meal be furnished per day and that some other grain accompany it in a ration.
Linseed meal is very popular in the foreign countries where it is used a great deal for feeding. This foreign demand has caused the employment of this feed to be too expensive for supplying the protein of dairy rations in some sections. Three to four pounds of this concentrate give excellent results with dairy cows.
Cotton-seed hulls, which are very light and bulky, furnish excellent roughage in dairy rations. Too much hulls are not desirable and 12 to 14 pounds a day are enough. The price of this feed must be considered by the feeder. There is a great variation in the composition of this feed, depending on the amount of broken kernels present. They are generally fed near the oil mills.
192 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
dairy cattle. About 25 pounds of wet brewers' grains may be fed successfully at points near the breweries. Their large water content and liability to ferment prohibit transportation and storage. Malt sprouts, dried brewers' grains and dried distillers' grains are used to supply protein and may make up 2 to 5 pounds of a day's ration.
The Massachusetts Agricultural Experiment Station, Bui. 94 says, "After taking into consideration the digestible nutrients contained in the several by-products (alcoholic), the mechanical condition and palatability, together with the results of different trials with dairy animals, the following general statements may be made with regard to the relative value of the several feed stuffs.
Sugar By-Products. — Cane, beet and sorghum molasses and beet pulp are used in feeding dairy cows. Cane molasses is especially palatable and digestible and 4 to 5 pounds a day may be fed with good results to furnish carbohydrate concentrate. Beet molasses is not so palatable as cane molasses but may be used to the extent of 2 pounds mixed with other feed per day. Sorghum molasses is used in mixed feeds and may be fed in sections where available at the rate of 2 to 4 pounds a day. Molasses is a good tonic and conditioner and may often be used to advantage in disposing of unpalatable roughage. The wet beet pulp may be fed in close proximity to the sugar factory, but it will not stand storing and becomes too expensive when transported. The New York (Geneva) Experiment Station estimates that pound for pound, the dry matter of beet pulp is
EEED AND CARE OE DAIRY COWS 193
equal to that of corn silage, or approximately, 2 tons of wet beet pulp equal i ton of corn silage. Wet beet pulp seems to give results far above what its chemical composition shows. In other words it has a beneficial physiological effect for milk production. The Colorado Experiment Station recommends 50 pounds as a maximum 1 in daily rations. In their investigations the following ration was used :
than for dairy cows.
Corn Fodder and Stalks. — Corn stover, the whole corn plant, corn leaves, etc., furnish desirable feed that may be used to make up part of the ration for milch cows. On account of the wide distribution of the corn plant, this roughage is found in dairy rations of many sections. These feeds are comparatively high in carbohydrates so that leguminous hays are excellent to complete the roughage portion of rations containing any of them.
Grass Hays. — Timothy, Kentucky blue grass, meadow fescue, red top, Hungarian grass and other millets, orchard grass, prairie grasses, tall oat grass, Bermuda, crab, Canadian blue grass, Italian rye grass, rescue grass, teosinte, velvet grass, Russian broom, Western rye grass, Texas blue grass, oat, etc., are fed as roughage to dairy cattle. These furnish relatively large proportions of carbohydrates and when fed should be accompanied with grains rich in protein to form a balanced ration.
Timothy hay commands such a high market price that it is only occasionally that the feeder can economically use it. It is usually more profitable to sell this hay as the market price is generally far above its feeding value for. dairy cows. Oats and vetch, oats and peas, wheat and vetch, oats, peas and vetch and similar combinations are grown and furnish good roughage for cows in milk.
194 ELEMENTARY TREATISE ON STOCK EEEDS AND FEEDING
Great care should be exercised in harvesting grasses. They should be cut before they become too woody and lose color. In curing, the green color and aroma should be maintained as much as possible.
Straws. — The straws from rye, barley, buckwheat, wheat, oats and rice are sometimes used in furnishing part of the roughage of dairy rations. Oat straw when bright, may be used to advantage. Many feeders use a small amount of oat straw to furnish a part of the roughage. As a general rule straws are, too woody and stiff to be used to any considerable extent for feeding dairy cows in milk.
Legumes. — Alfalfa, clovers, Canada field pea, cowpea, soy bean and peanut vine are the principal leguminous plants used in dairy rations. Alfalfa and the clovers are par excellence for supplying roughage. Cowpea, peanut vine, soy bean and Japan clover (lespedeza) are fed in the South where they are easily grown. All the legumes are nitrogenous and make excellent roughage for carbohydrate concentrates. Clover hay is fed more in dairy rations than any other leguminous hay. It is greatly relished by dairy cattle.
Legumes should be harvested before they are mature to have the best feeding value. They are usually highest in feeding value just when in blossom. Great care should be taken in curing these natural feeds as the shattering of the leaves and other fine parts, results in large losses of protein. Rain and dew also injure these feeds.
Methods of Curing. — There are different methods employed in the successful curing of these crops. Some farmers cut this class of forage late in the afternoon so that very little wilting takes place before the dew falls. The next day the hay is cured as rapidly as possible and stored away before night. Another system requires that the forage be cut in the morning just after the dew has dried off. It should not be disturbed until afternoon when it is cocked before the dew falls. The cocks should be covered with caps to prevent rain injury, and allowed to stand until the sweating process is over. The cocks are then
passes off and stored away before the dew falls.
Silage. — This is one of the best fodders for dairy cows. It furnishes succulent feed that exerts a beneficial physiological effect which tends to increase milk production. In winter it is very acceptable when green feeds are not to be had. It is variable in composition depending upon the nature of the crop or crops used, the condition of growth, and with corn the maturity of the ears. When corn is harvested at too early a stage it contains a great deal of water which tends to produce the so-called sour silage. Sweet silage is obtained from the more mature corn and may be fed in larger quantities than sour silage. As high as 50 pounds per day are sometimes fed but 30 to 40 pounds are usually sufficient. Some dry roughage as leguminous hay should be fed with it.
Corn and Legumes Make Valuable Silage. — The following from Bui. 101, Illinois Experiment Station is valuable data relative to silage. "Corn not only produces a large quantity of nutritious feed that is easily placed in the silo, but it is of such a nature as to pack readily and keep well. The large southern varieties of ensilage corn, which give enormous yields in tons per acre, have been recommended for silage ; but such varieties do not produce much grain and the total nutrients are usually less than from ordinary field corn. The best results are obtained with some variety that will give a good yield of grain, and by planting somewhat thicker than for a grain crop. Under average conditions a larger tonnage of feed can usually be obtained per acre by combining corn, sorghum and cowpeas or soy beans, but even with this combination the greater part of the crop should be corn. When either peas or beans are grown with corn and the entire crop is put into the silo, the feeding value is greater, ton for ton, than that of corn alone. This is a much more economical method of obtaining protein than by purchasing it in high priced concentrates, as gluten feed, cotton-seed meal, linseed meal, etc.
I96 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
Harvesting Corn and Cowpeas.— "If cowpeas are planted at the same time as the corn and in the rows with it, they will usually make a fair growth. Since the vines will run up the corn stalks, the entire crop can be cut with the binder the same as corn alone, making- practically no extra work in filling the silo. The only difficulty in harvesting corn and cowpeas with the corn binder is that, if the corn is missing for a rod in the row,
there is nothing to carry the peas back into the binder and it is likely to clog. Where there is a fairly uniform stand of corn, all can be readily bound together. As the stalks of soy beans are much stiffer than those of cowpeas, no difficulty is experienced in cutting them with corn."
According to King: 1 "The weight of corn silage increases with the depth below the surface, with the amount of water in the silage, and with the diameter of the silo. In silos of small diameters the amount of surface in the wall is so much greater in proportion to the silage contained that the friction on the sides has more influence in preventing the settling of the silage.
"Capacity of Silos. — The capacities of silos increase more rapidly than do their depths, so much that a silo 36 feet deep will contain nearly five times as much silage as one only onethird that depth; and when it is remembered that there is less necessary loss with deep silage the importance of depth will be appreciated.
"Doubling the diameter of the silo increases its capacity a little more than four times, while trebling its diameter increases its capacity nine-fold. It is evident, therefore, that the cost of storage decreases rapidly with increase in the size of the silo."
The Horizontal Feeding Area. — Silage must be removed from the top and not sliced or cut down vertically as is often practiced in feeding hay from the mow or stack, because the entrance of air will rapidly spoil it. It is considered that at least 1.2 inches should be removed per day from the top to prevent molding. Two inches of corn silage weigh 5 lbs. per square foot at the top and 10 lbs. at the bottom, or an average of 7.5 lbs. for the silo. The daily requirement for a cow, at this rate, would be about 5 square feet surface area. The feeding area should not be so large that enough cannot be fed per day to prevent deterioration.
200 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
The table 1 which follows gives the diameters and depths of silos of two types which hold enough silage for 180 days, feeding 2 or 3.2 inches a day, allowing each cow 40 lbs.
This table 2 gives the number of cows in herd and tonnage of silage for both 180 and 240 days of feeding of 40 pounds of silage per cow, also acreage of corn estimated to fill the silo and the dimensions of the silo itself. The diameters given are such that at least 2 inches in depth of silage will be taken off daily.
FEED AND CARE OE DAIRY COWS
Roots and Tubers. — Carrots, beets, sweet potatoes, Irish potatoes, turnips, rutabagas, etc., are feeds that exert a beneficial effect on dairy cows. Irish and sweet potatoes usually command too high a price to warrant using them as feed. However, when the market price is low it sometimes pays to feed them. Beet (mangel) sugar-beet, rutabagas, carrots, and turnips are often fed with profit. These feeds increase milk pro-
duction far above what would be expected from their chemical composition. In northern sections where corn is easily grown it is perhaps more economical to make silage than to grow roots for feeding. The Nebraska Experiment Station found sugar beets to have about the same feeding value as corn silage. The Colorado Experiment Station found that one ton of beets is equivalent to two tons of beet pulp. A great deal more dry matter may be produced on the same area by growing corn,
202 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
than roots. In southern localities roots may be grown in the winter when land is often idle, and harvested in time to plant corn and other summer crops. Roots should be sliced before feeding. They seem to exert a cooling effect on animals. The mangel is probably the most profitable root crop to feed.
Pasturage. — When dairy cows are receiving plenty of green pasture grass, the production of milk generally increases and under such conditions it is not necessary to feed any roughage. Sometimes a small amount of grain (2 lbs.) fed occasionally at the afternoon feeding is beneficial. If the pasturage is scant the cows will require sufficient feed to supplement it.
Soiling. — Some farms have not the acreage to support the number of cows the dairyman wishes to keep by pasturing. On other farms the pastures become poor at certain times. On such farms green crops are cut and fed fresh to the animals. There is a great deal of labor involved in handling green crops in this way and for this reason soiling is not popular in some sections. In furnishing green crops to cows, the dairyman must arrange so that green feed may be furnished continuously. Oats, rye, alfalfa, clovers, oats and peas, sorghum, corn, etc., are popular soiling crops.
Salt. — This should be allowed the cows regularly. If the cows are on pasture a sheltered box containing rock salt or pulverized salt is helpful. Some feeders mix a little pulverized salt or common salt in the feed, but care must be taken not to add too much and make the feed unpalatable. About % to 1 ounce of salt a day should be given regularly.
Water. — A good artesian well or other pure water should be supplied the animals at a place near or in the barn, so that the cows will not be forced to go a long distance in severe weather. They should be allowed all they wish as milk requires a great deal of water for a good production. If the water is not at the animals' disposal it should be supplied regularly two or three times a day. If a trough or other vessel is used, the feeder should make sure that it is kept clean.
shade during the hot days.
Exercise. — In the cold winters cows should get several hours of exercise daily, to keep up milk production. Often it is too disagreeable to exercise the cows outside, and a change to some roomy, well ventilated, covered enclosure, which is bedded with straw and horse manure and sprinkled with some material such as land plaster, makes a desirable place for the animals to rest and exercise.
Kindness. — The dairy cow is generally a nervous animal and should always be treated gently for best results. Dairy cattle like people do not enjoy harsh and abusive treatment. To keep up a good flow of milk the cows should be quiet and contented and any treatment that tends to make them nervous, results in lessening milk production.
Rations for Dairy Cows. — In the Wisconsin Experiment Station Bui. 38, Woll gives statistics on ioo American dairy rations. Some of the data from this bulletin is given for the student because it represents actual practice of some of the leading American dairymen.
corn meal, 2.9 lbs. bran, 1.4 lbs. oil meal.
New Hampshire — 11.7 lbs. clover and witch grass hay, 3.3 lbs. oat straw, 10 lbs. meadow hay, 2 lbs. shorts, 2 lbs. corn and cob meal, 1 lb. ground pease, 1 lb. oats, 1 lb. barley
6 lbs. oats, 2 lbs. oil meal.
New York — 9 lbs. clover hay, 9 lbs. timothy hay, 5 lbs. corn fodder, 5 lbs. oat and pea straw, I lb. oats, 1 lb. buckwheat middlings, 1 lb. corn, 1 lb. rye bran, 1 lb. wheat bran, 1.6 lbs. cottonseed meal.
3 lbs. corn and cob meal, 1 lb. bran, 8 lbs. roots.
Pennsylvania — 10 lbs. clover hay, 5 lbs. timothy hay, 2 l / 2 lbs. corn fodder, 6 l / 2 lbs. corn meal, 2 lbs. oats, 3.2 lbs. bran, i 1 /? lbs. oil meal, 15 lbs. carrots.
lbs. malt sprouts.
Wisconsin — 22 lbs. corn silage, 4 lbs. clover hay, 4 lbs. timothy hay, 2 lbs. oat straw, 2 lbs. corn stalks, 6 lbs. wheat screenings, 2 lbs. malt sprouts, 2 lbs. oil meal, 1 lb. wheat bran.
lbs. turnips, 1.3 lbs. pea meal, 2.5 lbs. oats, 1.3 lbs. barley.
In the 100 rations were included 3 succulent feeds, 18 coarse dry fodders, 27 concentrates, 6 kinds of roots and tubers, and 1 miscellaneous (skim milk). Of these 55 feeds several were used in many rations. The list that follows shows the number of times the most popular feeds were employed.
As previously stated the width of a profitable dairy ration depends upon the cost of the feeds locally. In some sections wider or narrower rations than the above may be best for certain conditions. The feeds that go to make up a ration are influenced by market prices of those that are available. Hence it is impossible to state the best ration for dairy cows. The nutritive ratio of most of the dairy rations fed in America is much wider than the Wolff standard given in Table II. From the foregoing data the student should experience little trouble in selecting feeds and compounding a ration suitable to the conditions of his home.
Suggestion: — Is there any objection to feeding a ration to a milch cow composed of linseed meal, wheat bran, gluten feed and alfalfa hay? Require the students to make a list of the available feeds in the locality; their prices; and require them to compute the cheapest rations possible for milch cows.
Have one of the students explain the construction of a silo, the way the crop is prepared for siloing and the appearance of the silage after it has been in the silo for some time. Examine some silage and allow the students to taste it. If there is a silo in the vicinity a trip to it may prove profitable.
FEED AND CARE OF FATTENING CATTLE.
Requirements. — We have learned that fattening animals require enough protein to repair the wastes, and carbohydrates must be supplied to increase body weight. Hence the carbohydrates should predominate in rations for fattening animals.
The amount of protein required will depend upon the age of the animal. Mature animals require very little protein and a wide nutritive ratio is satisfactory for the laying on of fat. The width of the ration will be influenced by the available feeds and market values, and the cost per pound of increase in live weight. In some sections where alfalfa is cheap and abundant, a suitable ration would necessarily be narrower than one where carbohydrate roughage and grains are economical. The addition of protein from some nitrogenous concentrate as linseed meal, gluten feed, cotton-seed meal, etc., tends to increase the efficiency of fattening rations and makes them more palatable. Sometimes it is cheaper to supply most of the protein from some protein roughage.
A fattening ration should not only be palatable but should be easily digestible, hence rough fodders are not suitable. A variety of materials should make up the ration.
Cattle should average 2 lbs. gain in live weight per day during the fattening period. The gain of course depends upon the age of the animals. Experiments have shown that young animals gain faster than those more mature. During the first part of the fattening period cattle gain more than at the latter part and the longer the fattening period the more feed is required to produce a given gain in weight. It is considered that 12 to 13 lbs. of dry matter are required for 1 pound of gain. The animals should be allowed all the roughage they will eat.
Corn is the best grain feed for fattening cattle. In this country it is used more than any other single grain for this purpose. Because of its high content of starch it is admirably suited for producing fat.
208 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
Snapped Corn. — This is the unhusked ear which is snapped or broken from the stalk. It is the most popular feed in the West and produces excellent results. Some feeders fatten their cattle on this feed alone, claiming that the husk and cob furnish sufficient roughage. Farmers who practice this method of feeding often leave the stalks in the field allowing the cattle to eat what they wish of them. It is better to harvest the stalks and use them as roughage, for there is a great deal of waste and loss of nutrients by allowing the stalks to remain in the field. Cattle fed snapped corn sometimes become troubled with sore mouths. In such cases the animal should be fed a mixture of corn and cob meal and wheat bran or some other easily masticated grain mixture until the soreness disappears. In feeding snapped corn the cattle should receive some leguminous roughage such as clover, alfalfa, cowpea, soy bean, etc.
Shocked Corn. — This is a very satisfactory feed for fattening cattle. The harvester cuts and ties the fodder corn into bundles and the corn is then put in shock at a small expense. It is well preserved for winter feeding by this procedure and the husk prevents the ear corn from becoming too hard for cattle to masticate. Shocked corn is more easily preserved than snapped corn because in storing the latter it is hard to keep up a free circulation of air. This shocked corn is placed in sheltered feed racks with enough space between the racks to permit the animal free use of the head. Sometimes the bundles are scattered over a field. The cattle eat some of the fodder in this method. Pigs should follow cattle to pick up the wastes and droppings as some of the corn kernels pass through the animal undigested. This indirect
the corn and the profits are derived from selling the pigs.
Protein is Desirable. — It is often profitable to limit the amount of shocked corn in a steer's ration and supplement it with corn and cob meal, shelled corn, and some protein concentrate as linseed meal, gluten feed, gluten meal, cotton-seed meal, etc. Sometimes wheat bran may be used instead of a protein concentrate when the market value is low. When nitrogenous
enous concentrates may be reduced.
Husked Corn is sometimes fed. It is cheaper and more desirable to feed snapped or shocked corn than husked corn. Husked corn becomes exceedingly dry and hard and has the tendency to produce sore mouths and gums when fed in large quantities. It is often practical to crush corn to make it more easily masticated.
Corn Meal seems to be favored by Eastern feeders. Larger gains are made with meal than with unground grain. Of course corn meal is a heavier feed than the whole ear and care must be exercised in its use. For Western and Southern feeders it is no doubt cheaper to feed the whole unground ear because of the expense of grinding.
Corn and Cob Meal. — Experiments have demonstrated that corn and cob meal is equal in feeding value to corn meal. This feed is more bulky than corn meal and hence it is easily attacked by the digestive fluids.
Corn Stover is always a cheap roughage on the farm. It should supply at least one-half the roughage when available. Alfalfa or clover make excellent complements of stover to complete the roughage of a ration. It is often desirable to cut up the stover or shred it to insure a larger consumption. The cost of course will determine the practicability of such practice.
Corn Silage. — When the farm is equipped with a silo it pays to allow the cattle about 10 to 15 lbs. a day during the preliminary and middle periods of fattening. Silage seems to help the cattle in the preliminary and middle periods of fattening by supplying water and bulk, by increasing the appetite and by producing a cooling and laxative effect. It is perhaps unprofitable to construct a silo just for feeding fattening cattle.
2IO ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
with dry feed and the increase in profits amounted to $3~$8 per steer. The cotton-seed meal gave better results than oil meal and tended to produce a firmer flesh with silage.
Wheat Bran. — When the market price permits, wheat bran may be utilized for giving bulk to a ration. It seems to produce a slight laxative action and possess cooling properties which are desirable. When corn meal is fed, wheat bran is especially valuable in the ration.
Protein Concentrates. — Linseed meal, gluten feed, gluten meal, cotton-seed meal, etc., may often be used to advantage in furnishing protein to fattening animals. A little protein especially from linseed meal seems to give a finish to beef and often reduces the fattening period. This is helpful on a declining market. Linseed meal or oil cake at the rate of 2 to 4 lbs. a day is exceedingly beneficial for the finishing period. Cotton-seed and cotton-seed meal are good beef producing feeds. 3 to 4 lbs. of cotton-seed meal is sufficient per day.
Roots are valuable in the preliminary period of fattening, but should not be fed during the finishing period, because they produce soft flesh. 10 to 20 lbs. of roots per day are ample. Roots should always be sliced or pulped before feeding. In fattening rations the feeds are generally heat producing and roots seem to exert a cooling effect which is beneficial. In the corn belt it is cheaper to feed silage because twice as much dry matter can be obtained from equal areas by growing corn than roots. The mangel is the best root crop for steers and it produces a higher tonnage than the other roots.
Beet pulp has been shown by experiments to be a good feed for fattening cattle. With alfalfa as an adjunct, in sections where alfalfa is cheap, beet pulp may be fed profitably for fattening cattle.
Straw. — Flax straw, when flaxseed is present, may be used in fattening cattle. Oat straw is sometimes profitably utilized for supplying half the roughage. If hay is available it is perhaps better to feed the hay. Wheat straw has been found to be unsatisfactory because as much energy is expended in preparing it
Molasses. — When the price of this feed is low it may be used to furnish part of the carbohydrates of a ration. On account of its increasing price it is not within the reach of many of our feeders.
Kaffir Corn may be successfully fed in the arid regions where corn is not profitably grown, for feeding steers. The Kansas Experiment Station found that Kaffir corn was a little below corn in feeding value. Where Kaffir corn is available, the stover may be fed as is practiced in feeding corn. Kaffir corn should be ground or soaked before feeding because of the hardness of the grains.
Leguminous Hays. — Alfalfa, clover, cowpea, soy bean, etc., may often be used to advantage in furnishing the greater part of the nitrogenous portion of a fattening ration. It is often very profitable to utilize these hays in this way. Of course the market value will influence the extent of their use.
Grass Hays. — Most of the grass hays are suitable for fattening cattle. When corn stover is available it is cheaper to feed the stover and sell or save the hay for other live stock. Sometimes a part of the roughage may be profitably supplied in the form of hay. In Western sections prairie hay is often cheap and can most profitably be utilized as roughage for fattening cattle. Timothy hay is more profitable to sell than to feed cattle at the present market value. It is low in digestible nutrients and cattle cannot use it economically at the present price it carries.
Oats is sometimes used in fattening cattle. It is not high enough in carbohydrates to furnish the whole of the grain and should be supplemented with corn. The market value often makes the use of oats unprofitable.
as corn it may be fed.
Barley should always be ground before being fed. It is perhaps a little below corn for fattening value and not so well liked. When accompanied with corn is perhaps the better way of feeding it.
Summer Pasturing. — Cattle fed on grain and hay during the winter cannot be pastured on green grass entirely without causing shrinkage. For this reason some farmers make the change from hay to grass gradually. There are two methods used in turning steers to grass. One is to wait until the grass gets a good growth and accustom the steers to the change by allowing them a few hours a day on pasture, gradually increasing the period until they become used to it By following this method the heavy feeding of grain is still followed and may be reduced when the cattle are on full pasture.
Another method is to turn the cattle to pasture when the first blades appear. By doing this the cattle cannot gorge themselves with grass and by the time the grass is abundant the cattle will be accustomed to it. The objection to this method of turning to pasture is that the grass does not have a chance to get a good start because of the continual cropping.
Size of Pasture. — Most American feeders prefer one large pasture to several small pastures. One large pasture does away with the trouble of changing the steers, offers a greater variety of grasses for grazing, and gives the animals more freedom and contentment.
Grain on Grass. — The kind of grain to feed on grass depends upon the grasses that make up the pasture. If clovers, alfalfa, or other nitrogenous legumes predominate, corn may make up the entire grain portion. If timothy, Kentucky blue grass, meadow fescue, or other grasses relatively high in carbohydrates are abundant, a little oil meal, cotton-seed meal, gluten feed, gluten meal, etc., should be mixed with the corn for the best results. Cattle fed in this way should be ready for market in the summer.
FEED AND CARE OF FATTENING CATTLE 213
Preparing for the Fall Market. — When cattle are to be marketed in the fall it is not necessary to feed grain in the early summer. In the fall when the corn is ripe, shocked or snapped corn may be distributed over the pasture or fed in a rack in the field. It is desirable to feed a small quantity, 3 to 4 lbs., of corn at first, gradually increasing to a full feed of 15 lbs. a day. The cattle may be fed in this way until ready for market which will usually be sometime before the winter sets in. An addition of a protein concentrate is desirable in this system of fattening.
Water and Salt. — A plentiful supply of pure water should be supplied to cattle in the lot twice a day. In pastures a good spring will often furnish the water for range feeders. In cold weather it is beneficial to take the chill from water with some form of heater to cause cattle to drink enough water.
As with dairy cattle, rock salt or pulverized salt should be placed in a sheltered box in the feed lot. When the steers are kept in barns or feed lots, ^4 to i 1 /* ounces a day will be enough. Some feeders add common salt to the grain but it is necessary not to supply too much and make the feed unpalatable.
Shelter. — In the summer when the flies are troublesome fattening cattle often fail to gain unless they are taken to some dark, cool enclosure for a short time each day during the worst periods and fed some grain. Every pasture should have some trees to furnish shade. When cattle are fattened for the fall market a shelter should be provided in the pasture to protect the cattle during the cold fall rains.
Bedding induces the cattle to rest when they are kept in a feed lot or barn. Often a feed lot becomes muddy and a liberal supply of straw as bedding provides comfort and contentment.
Rations for Fattening Cattle. — There are many rations that may be computed for fattening cattle. The feeder should aim to utilize the cheap coarser feeds, by-products and wastes. By so doing, feed stuffs that ordinarily would go to waste or bring low prices on the market, may be profitably converted into beef. The amount of feed in a fattening ration will depend upon the age, weight, appetite and capacity of the animal. A feeder must
some cheap rations from these feeds. What differences would be made in feeding cattle during the different periods of fattening? What could be done to economize an animal's food during cold weather ?
FEED AND CARE OF HORSES.
Requirements. — A horse or mule requires digestible nutrients to furnish the energy required for walking, pulling loads, trotting, etc., and for the repair of the tissues. The degree of work determines the amount of digestible nutrients needed. A horse or mule doing light, medium or heavy work will require different amounts and proportions of digestible nutrients. See Table II.
engaged in light work.
"7. The proportion of protein to carbohydrates (nutritive ratio) required, by horses doing moderate work should be about 1 : 7 or 8, and for horses doing heavy work as 1 : 5 or 6."
It has been previously remarked that a horse or mule cannot consume as much roughage as ruminants. The stomach of a horse is small and 10 to 14 lbs. of roughage is enough for a day's ration.
Oats is the best grain for horses. This feed is used to a large extent in this country. The high cost of oats has sometimes induced feeders to substitute other feeds. Oats may make up
corn, wheat, bran, barley and similar feeds.
There is no food that will take the place of oats for horses. The presence of the hull makes the feed light enough for the digestive juices to permeate freely. Oats should be ground for horses with poor teeth. Oats is a well balanced feed.
Barley is sometimes mixed with oats, or fed alone. On the Pacific slope, barley is fed a great deal to horses. Crushing or grinding barley helps in the mastication. Sometimes linseed meal or wheat bran is mixed with barley when fed to horses.
Wheat. — Ground wheat, mixed with oats or bran, is sometimes used as horse feed. Wheat requires some bulky feed to supplement it, because when fed alone it becomes sticky in the mouth. The market value of wheat generally prohibits its use as a horse feed.
Corn is fed extensively in the South and West. It is fed on the ear, shelled, or ground fine. Corn and cob meal because of its bulk is better for horses than corn meal when fed alone. When corn meal is fed it should be diluted with some bulky feed like wheat bran. Corn is more of a fattening feed than oats and it causes the animal to sweat freely, but may be used to good advantage as part of a ration. Corn is a very satisfactory feed in cold weather for horses because of its heat producing power. Corn runs low in ash and protein and must be supplemented with feeds running high in these constituents.
Kaffir Corn. — When this feed is ground it may be used for horses. This feed is not as valuable as corn but may be often profitably fed in semi-arid sections where corn cannot be grown successfully.
Cotton-Seed Meal. — As much as 2 lbs. of this feed per day may be fed to a horse or mule weighing 1.000 lbs. doing hard work. It is not desirable to feed too much cotton-seed meal to horses although a moderate daily amount, 1 to 2 lbs., mixed with other grains, seems to give good results. There is a great variation in the chemical composition of cotton-seed meal as manufactured and the feeder should try to secure meal carry-
is generally ample.
Dried Brewers' Grains. — Experiments have shown this product to be a more economical feed for horses than oats at the present prices, in some sections, and of equal feeding value. This feed is not as palatable as oats and corn but may be successfully fed with mixtures as bran and corn.
Wheat Bran is often used to lighten rations composed of heavy concentrates. It has a slight laxative effect. Some feeders use it daily in their rations while others feed it two or three times a week.
Molasses. — Cane and beet molasses are both fed to furnish carbohydrates. Cane molasses is more palatable than that from the beet and is used considerably in feeding horses in some sections. The amount of cane molasses to feed per day depends upon the feeds that make up the ration and the market price of this carbohydrate feed. As high as 12 to 14 lbs. a day have been fed with satisfaction but a smaller quantity, 4 to 8 lbs., is perhaps sufficient. This feed is used in sections of the South where it is available, and is increasing in popularity in the East where it is imported from tropical countries, notably Porto Rico.
but may be used when mixed with other feeds.
Timothy Hay is the best roughage for horses. The feeding value is not as high as some other hays, but this feed is usually free from dust and objectionable weeds, is easily handled without loss of nutrients, is relished, is well cured and seems to give better results than any other roughage on the American market for horses. On account of its bulk it serves as a good roughage for concentrates. Timothy hay is for roughage what oats is for grain in horse feeding.
2l8 ELEMENTARY TREATISE ON STOCK EEEDS AND FEEDING
heaves. Well cured clover hay, however, is a good source of roughage and when used the protein supplied by the grain should be reduced. It is a good complement of starchy concentrates. Clover hay is liable to lose some of its leaves and other fine parts, which are rich in protein, when carelessly handled.
Alfalfa Hay. — The same objections are raised to alfalfa hay as to clover hay. Well cured alfalfa hay is fed successfully in limited quantities to horses. Corn or some other carbohydrate feed should supplement alfalfa in the ration. Alfalfa is liked by horses and they are liable to eat too much unless the supply is limited. The Utah Experiment Station has used alfalfa hay for supplying the entire roughage of rations for horses.
factory roughage for moderately worked horses.
Corn Fodder is a valuable and cheap roughage for horses. It may be fed with corn and bran, corn and oats, and other combinations. It should be harvested before the leaves die because this part of the corn plant is relished by horses. For hard working horses the stalk should be cut or shredded to render mastication more easy. It may be used to supply the whole or part of the roughage and on account of its cheapness is worthy of consideration by all horse feeders.
Corn Silage may be fed to idle horses. When used for feeding- working: horses the amount should be small. It is a succulent feed and increases the appetite. It is somewhat bulky for the hard working horse.
Millet Hay. — The exclusive use of millet as roughage has been claimed to increase the action of the kidneys, produce lameness and swelling of the joints, and render bones soft. For these reasons millet is not a safe feed for horses, although it may sometimes furnish a part of the ration.
Grass Hays. — As previously stated, timothy hay is the best grass hay for horses. Sometimes other grass hays are available and when well cured and free from dust may economically furnish the roughage for horses.
FEED AND CARE OF HORSES 2IQ,
may be fed when free from dust and well cured. The supplementing of any leguminous hay with grain of course offers a chance of reducing the protein in the grain portion.
Straw in good condition may be used for idle horses, but when fed to working horses only a small amount should be given. It is not so valuable as hay and therefore a larger quantity of grain should accompany its use. Oat straw is the best. Barley, rice and wheat straws may also be utilized but rye straw is of little value.
Cotton-Seed Hulls. — In the South this material is sometimes used in feeding idle horses. On account of its bulk, a working horse has not time to thoroughly masticate it, and when fed to hard working horses it should be used in small amounts to •furnish a part of the roughage. The feed cannot generally be fed profitably at points far from the oil mills.
Boots are not generally fed in America to horses and mules. Sweet potatoes are sometimes used in the South at the rate of 3 lbs. to i lb. of grain. Horses are especially fond of carrots. They are excellent feed for horses fed dry feed. They seem to keep the digestive organs in good tone and increase the appetite. Not over 10 to 15 lbs. a day should be allowed and they should be sliced or pulped.
Watering. — Horses should be watered regularly with pure water. In the winter it is good practice to warm the water when it is too cold. Horses require different quantities of water depending on the atmospheric conditions, the work performed and the nature of the feed.
For horses of 1,200 lbs., 60 to 70 lbs. of water are considered average daily amounts, with variations of 30 to 100 lbs. There is some difference of opinion as to the best time to water the horse. It has been found that it makes no difference as long as the horses are watered regularly and with judgment. Hard working horses may be watered to advantage before feeding. Some advocate watering before and after feeding.
Bedding. — It is almost needless to say that horses to be kept in good condition should have a good clean bed of straw to rest on. Horses, like people, require a comfortable bed in order to
pulverized form.
Wintering Working Horses. — In the winter when there is practically no work for the horse comfortable quarters should be provided. Coarse roughage as corn stover, straw, etc. may be
used to advantage until spring time. About 6 or 7 weeks before the working period sets in the horses should be given a light grain ration and exercised to fit them for work.
tion, Bui. 115, says:
"A feeder may have all the information necessary concerning feeding standards, balanced rations, nutritive ratios, etc., and yet be cannot possibly secure the maximum of good results from the
intelligent system in the feeding of his animals.
"Animals under domestication, such as the live stock of the farm, and more particularly the work horses and mules, are living under artificial conditions in respect to their feeding, and are solely at the mercy of the intelligence, or otherwise, of their owners for the manner, or system, in which their food is supplied to them.
"Under natural conditions, the horse, or mule, owing to the anatomical arrangement of its digestive organs, and its physiological requirements, feeds quite often, but partakes of little at a time. The main reason for this is, the relatively small capacity of its stomach — not more, perhaps, than from 14 to 17 quarts — the short time it takes for the stomach to empty itself, and hence the necessity for frequent replenishment.
In order to obtain the most satisfactory results, under domestication, or during work, it is reasonable to presume that the animal's natural method of feeding should be approximated as closely as practicable. During the working season on the plantation or farm this would suggest that the day's ration, or the amount of food required by the animal in twenty-four hours, should be divided into at least three feeds. Some animals may, and do, become habituated to a lesser number of feeds per day with, apparently, satisfactory results. But it is a risky method, because, instead of getting as close as practicable to the animal's natural way of feeding, it is getting further away from it.
"After an opportunity, during the past twenty years, of studying and observing the conditions under which many of our work animals are fed, we have no hesitancy in saying that lack of system in feeding is responsible for the major portion of the loss of valuable animals from colic, inflammation of the bowels, etc.
"Many who lose valuable horses and mules on the plantations and farms from digestive troubles are wont to place the blame on the kind or class of feed the animals have been given ; while, in reality, the blame properly belongs to the unnatural and unintelligent manner in which they receive their feed. A properlybalanced ration of the very best quality of oats, when fed in-
222 ELEMENTARY TREATISE ON STOCK EEEDS AND FEEDING
telligently and systematically, may not induce a case of colic during the natural lifetime of the animal. But if the entire day's ration of oats is fed at one time, instead of its being divided into three parts, it is liable to so derange the digestive apparatus as to set up a fatal case of flatulent colic, because the digestive organs in the horse or mule are not constructed, nor prepared, to "handle" such an excessive quantity of food material all at once. In such a case, are we to blame the oats for the trouble, or the unintelligent manner in which they were fed to the animal? And so it is with other kinds and classes of concentrated feeds ; they require system in their administration to prevent indigestion, colic, etc., and to produce the best results in the capacity of the animal for work.
"A point of very great importance for the owner or feeder to bear in mind, therefore, is, that an animal's food may be properly balanced as to its digestible nutrients ; it may be correct as to quantity and nutritive ratio ; in fact, be perfect in every particular, so far as supplying the needs of the animal is concerned ; and yet, if an intelligent system is not employed in the feeding of it, the otherwise perfect requirements may be altogether vitiated."
Rations for Horses and Mules. — A few rations fed in different parts of the country are given below. These rations are given to illustrate the several concentrates and roughage employed by practical feeders. Many combinations may be compounded into balanced rations for horses and mules doing different kinds of work. Of course the make up of a ration is controlled by the market values of the available feeds. By studying the text in this section the student should have no trouble in compounding rations for all classes of horses and mules, no matter what degree of work they may be required to perform. A variety of feeds in a ration is satisfactory.
Suggestion : Make a list of concentrates that may replace each other for feeding a horse. Why should not a horse in the stable doing no work be fed the same as when working? What will be the result if the horse's ration is not cut down when idle? What is the cheapest balanced ration that can be fed to a horse in your locality? How many times a day are the horses fed in your county? Do you think you could improve upon the system of feeding as practiced in your town?
FEED AND CARE OF SHEEP.
Requirements. — The natural food of sheep is plants. They have four stomachs as is the case with cattle and therefore they are able to consume comparatively large quantities of roughage. They seem to be able to digest and assimilate the nutrients in roughage quite completely as is noticed by the fineness of the
particles in their manure. The requirements of sheep are somewhat similar to the requirements of cattle. Sheep require a little more protein per pound of live weight than cattle, perhaps because of wool production. Fattening lambs also require protein to produce growth. As a rule sheep require more digestible nutrients per pound live weight and make larger gains per unit of digestible nutrients than steers.
226 ELEMENTARY TREATISE ON STOCK EEEDS AND FEEDING
is scant sheep crop the grass very close to the ground and sometimes injure pastures in this way, but when good pasturage is allowed them no injury is done. Sheep will eat weeds that other classes of live-stock refuse.
Pasturing. — In the spring when the grass begins to come up the ewes and lambs should be put on pasture for a few hours a day, gradually lengthening the period until they become accustomed to the change from dry to green feed. Alfalfa, clover, rape, and rape and corn, make fine pastures for sheep.
Alfalfa Pasture. — By pasturing on alfalfa in the fall after two or three cuttings have been harvested good gains may be made for preparing lambs for the early winter market. Good gains are made on alfalfa alone but the addition of shelled corn increases the rapidity of gain. Alfalfa is nitrogenous in character and corn makes an excellent grain to feed with it. In feedingcorn a little should be supplied at first, 34 of a pound, and gradually increased until i pound a day is supplied. When oats and bran are cheap they may be fed in place of some of the corn.
Clover Pasture. — After the hay has been harvested and the second growth has a good stand the crop may be pastured by lambs. As with alfalfa grain should be supplied lambs that are to be sold in the late fall or early winter.
Rape Pasture. — This plant is becoming popular for pasturing sheep. It may be pastured the whole summer or for preparing lambs for fall shipment. Sometimes it is cut green and fed in racks. The Wisconsin Experiment Station considers rape as worth $14.48 to $20 per acre depending on the season. As with alfalfa and clover, grain is desirable for preparing lambs for the fall market. If fed some hay and turned to pasture partly filled, bloating should not take place.
EEED AND CARE OE SHEEP 227
mature, the lambs are turned into the field and allowed to eat both crops. In this way many of the lambs are fattened quickly. The lambs should be watched and as soon as they become fat they should be taken from the pasture. Sometimes a few lambs have to be finished in the feed lot.
Wintering Fattening Quarters. — Sheep because of their heavy coat of wool do not require as warm quarters as cattle. Therefore a shelter should be provided that offers plenty of fresh air and protection from severe weather. A southern exposure is to be preferred. Plenty of bedding is desirable which should be renewed and supplied in sufficient quantities to keep the animals comfortable. The quarters should be well drained and kept as dry as possible to prevent disease such as foot rot.
Feeding Racks. — The roughage and grain should be supplied daily and separately. The hay should be placed in racks large enough so that all the sheep may feed at the same time. It should only be furnished in quantities sufficient for a feed as sheep do not relish hay that remains in the hayrack. Grain should be placed in troughs wide enough so that the feed cannot be eaten rapidly. This may be accomplished by providing a wide bottom to the grain trough thus distributing the grain. As with hay only grain enough for a feed should be given.
Salt. — Sheep require salt and there should always be a supply on hand. This may be furnished by nailing several boxes about the feed lot or by a separate trough which should be kept for this purpose.
Water. — Sheep do not drink as much water as other classes of live-stock. The amount of water consumed varies with the nature of the feed and temperature. From 4 to 6 quarts daily are considered average amounts. A supply of pure fresh water in suitable watering troughs should be in the feed lot.
Fattening Winter Lambs. — When the lamps are taken from the pasture to the feed lot only a moderate amount of grain should be given. This may be increased gradually until they are on a full ration. The kind of roughage will determine the amount and character of grain to use. Should straw, corn stover, or grass hay be the roughage, a protein concentrate must be pro-
228 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
vided as part of the grain ration. If alfalfa, other nitrogenous hay be the roughage, shelled supply the grain. It is not necessary to grind because they are so constructed that they can hard grains. When their teeth become poor it them on ground grains and market them.
months for February trade. These lambs are called hot-house lambs or winter lambs and usually weigh about 45 lbs. The Dorset is considered the best breed for supplying early lambs, because of the hereditary tendency towards liberal milk production which fattens lambs early. The Dorset-Merino crossbreed and Hampshire are also used for producing hot-house lambs, the former being more desirable because of heavier milk production.
FEED AND CARE OF SHEEP 229
fall markets than for summer trade. Lambs gain more per pound of feed than mature sheep and there is more money made in fattening lambs than mature sheep.
Corn is the best fattening feed for lambs. Experiments have shown that about 500 lbs. of corn and 400 lbs. of clover hay produced 100 lbs. of gain in live weight. Shelled corn is the form in which this material is utilized for sheep. The amount of shelled corn in a ration depends upon the character of the roughage and the market value of corn.
Shock Corn. — In some sections the whole stalk of corn is fed to sheep. Enough shocked corn for a day's ration is placed in the feed rack. The lambs eat the grain, leaves, and more tender parts of the stalk. Some nitrogenous roughage as alfalfa, clover, cowpea, etc., makes an excellent fattening food with shocked corn. If nitrogenous hay is not available some protein concentrate should be used.
Oats produce growth in lambs and for a fattening ration corn should be added. It is not always profitable to feed oats but this is an excellent feed when the market price is low.
Barley is often fed in sections where corn is hard to grow. It may be used in fattening lambs. Barley is not as valuable as corn for sheep feeding but may be fed unground with other feeds.
Wheat is not as good as corn for fattening and an addition of corn helps a ration containing wheat. Wheat is a better feed for producing growth than corn because of its higher content of protein.
Wheat Screenings may often be fed at a profit to sheep. This material contains shrunken grains of wheat, weed seeds and other wastes obtained in preparing wheat, as it comes from the farm, for manufacturing flour. This feed is usually sold at a low price and sheep seem to be fond of it. The feeding value of this by-product is variable.
Wheat Bran is not a profitable sheep feed. It is too bulky for so small an animal and does not possess sufficient fattening qualities to be of material value for fattening lambs. It is sometimes fed in small quantities mixed with other grains.
23O ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
Speltz or Emmer grows well in semi-arid regions and it has about the same composition as barley. Alfalfa hay fed with speltz makes a good sheep feed. The Colorado Experiment Station got better returns by feeding speltz than barley and found it to be as valuable as corn in that section. The South Dakota Experiment Station found barley to be more valuable than speltz and a mixture of barley or corn and speltz to be better than speltz alone.
Protein Concentrates. — Linseed meal, gluten meal, gluten feed and cotton-seed meal may often be used in rations deficient in protein. When grass hay, stover, etc., are used as roughage a mixture of a protein concentrate with shelled corn gives good results. The proportion of protein concentrate to corn or other carbohydrate concentrate should depend to some extent on the prices of these grains, although too large a proportion of protein concentrate should be avoided.
Protein Roughage. — Clover, alfalfa and cowpea hays are suitable roughage to supplement corn in completing a sheep ration. These crops can be grown on the farm and the necessary protein for the growth and repair of the animal body may be supplied much more cheaply than from protein concentrates. Should the supply of protein roughage be limited it could be used with straw, corn stover or grass hay. Some protein concentrate would be necessary under such conditions but not so much as if no protein roughage were utilized.
Corn Leaves are eaten by sheep with great relish. They are not so valuable as the leguminous hays. Sheep do not eat the coarser parts of the corn stalk very much even when shredded or ground.
Corn Silage fed in limited quantities tends to keep sheep in good health and is excellent during the early period of fattening. It would not pay to build a silo just to furnish ensilage to sheep but on dairy farms the available silage may be furnished to lambs in daily amounts of 1 to 2 lbs. together with about
grain, the dry grain may be reduced when it is fed.
Grass Hays. — Lambs fed on grass hays should receive some protein concentrate to balance the ration. Most of the grass hays are suitable. Millet hay is not favored by sheep feeders because it sometimes produces scours.
Roots like silage furnish succulence, keep the digestive tract in good condition, and increase the appetite. In the European countries and Canada roots are used a great deal in feeding sheep. The feeding of roots in the United States is not as profitable as feeding silage in sections where corn may be grown extensively. In the South it ought to prove profitable to raise roots in the winter for sheep feeding, as the land is often idle during the winter and roots are off the land in time to plant the summer crops. Some dry roughage should be fed with roots. Roots are especially desirable during seasons when sheep are off from pasture. Mangels and sugar beets are popular roots for feeding sheep. Two to 4 lbs. a day are sufficient.
Wet Beet Pulp may be utilized at points near sugar factories. The laxative effect of beet pulp may be eliminated by using a little dry roughage as straw or stover. On account of the large amount of water in beet pulp it is not desirable in large quantities when finishing lambs.
Dried Beet Pulp is a fattening food suitable for sheep. The market price of this feed will determine whether or not it can be profitably used. It is not as valuable as corn.
Straw. — When other roughage is scarce, straw may be fed as part of the roughage. Straw is inferior to hay as feed and when other roughage is available straw is undesirable. Sometimes a feeder may use straw entirely to furnish roughage, in which case the grain must be increased to balance the ration. Oat straw is better than wheat, rye, or barley straw.
Feeding Period, Rate of Grain, Etc. — Lambs fed grain on pasture should be ready for market in 5 to 8 weeks after being placed in the feed lot. The total feeding period for sheep and lambs when preparing for market should not last over 15 weeks and often in 12 to 14 weeks they are ready.
According to Lawes
and Gilbert: "Sheep on good fattening food, such as oil cake or corn, with chaff and roots, will consume weekly about 4.75 lbs. oil cake, 4.75 lbs. of hay, and about 70 lbs. of roots, for every 100 lbs. of their live weight.
"When fed as above, they will consume every week about 1 / 7 of their own weight of the dry substance of food ; that is, after deducting the moisture it contains.
"Sheep well fed and under cover will increase about 2 per cent, upon their weight ; that is to say, 100 lbs. live weight will increase from 1.75 lbs. to 2 lbs. per week.
FEED AND CARE OF SWINE.
Swine like horses have but one stomach, therefore they are not adapted to consuming as large quantities of roughage as the ruminants, cattle and sheep. Grain is very desirable for pigs and from equal weights of such feed pigs will gain more than
the ruminants. Swine generally are made to utilize the wastes from the kitchen and the dairy and because of the many wastes that would ordinarily be thrown away, the raising of pork is usually very profitable.
Requirements. — The requirements for pork production include plenty of bone making material (ash) and a fair supply of protein. It was formerly customary to feed very wide rations and market the animals very fat at the age of about 15 months, weighing 300 to 400 lbs. Such hogs are suitable for the packing houses. Local demand at present often calls for pigs of
236 ELEMENTARY TREATISE ON STOCK FEEDS AND FEEDING
150 to 250 lbs. of rather lean pork, which may be produced in a few months, the age depending upon whether they are grain or pasture fed. A nutritive ratio of I : 6.5 or 7 is suitable for the production of lean pork. As with other animals the gain in live weight from feed is greater in the earlier stages of the fattening period and so it is more profitable to market pigs when 5 to 8 months old than when 15 months old. This early marketing also gives quicker returns. The following table from Henry's "Feeds and Feeding - ' illustrates this point:
The average weight of 34,400,000 market hogs for the year ending March 1, 1908 was 226.58 lbs., costing the packers $5.52 per 100 lbs. 1 This shows that 225-230 lbs. is about the average weight of the market hog of to-day.
quick production of fat.
Shelled corn, corn meal and corn on the cob are about of equal feeding value for swine ; corn meal being perhaps slightly superior. If shelled corn is very hard, causing sore mouths, it should either be soaked in water for a day or so or else ground to a meal. Sometimes grinding is too expensive but is preferable when practicable. Corn meal should always be soaked with
FEED AND CARE OF SWINE 237
water just before feeding to render it more palatable. Corn is often profitably fed without the addition of any other grain when pigs (are on good leguminous pasture or rape. The amount of corn to use in the ration depends upon the age of the pigs. Young pigs require more protein and ash, to supply nutrients to furnish growth, than mature animals. Corn alone does not contain enough protein and ash to supply the needs of young pigs, therefore it is necessary to supplement it with materials rich in protein and ash, and use it in smaller proportions for young pigs. Wood ashes, bone meal, etc., are often fed pigs that are kept in pens, to furnish sufficient ash to form strong bones, especially when corn is the only grain fed. Swine on pasture do not generally require to be supplied bone forming materials as they secure an ample supply from the pasture.
|
package com.tvd12.ezyfox.testing.codec;
import com.tvd12.ezyfox.codec.EzyMessageHeader;
import com.tvd12.ezyfox.codec.EzyMessageReader;
import com.tvd12.ezyfox.exception.EzyZeroRequestSizeException;
import com.tvd12.test.assertion.Asserts;
import com.tvd12.test.util.RandomUtil;
import org.testng.annotations.Test;
import static org.mockito.Mockito.mock;
public class EzyMessageReaderTest {
@Test
public void readSizeErrorDueToZero() {
// given
ZeroSizeEzyMessageReader instance = new ZeroSizeEzyMessageReader();
Object buffer = new Object();
int maxSize = RandomUtil.randomSmallInt();
// when
Throwable e = Asserts.assertThrows(() ->
instance.readSize(buffer, maxSize)
);
// then
Asserts.assertEqualsType(e, EzyZeroRequestSizeException.class);
}
private static class ZeroSizeEzyMessageReader extends EzyMessageReader<Object> {
@Override
protected int getSizeLength() {
return 4;
}
@Override
protected int remaining(Object buffer) {
return 5;
}
@Override
protected byte readByte(Object buffer) {
return 0;
}
@Override
protected int readMessageSize(Object buffer) {
return 0;
}
@Override
protected void readMessageContent(
Object buffer,
byte[] content,
int offset,
int length
) {}
}
}
|
Maurice Levy v. United States
No. 5427.
Invoice dated Paris, France, September 18, 1936.
Certified September 22, 1936.
Entered at New York October 2, 1936.
Entry No. 745083.
(Decided September 9, 1941)
Styauss & Hedges (Hadley S. King of counsel) for the plaintiff.
Paul P. Rao, Assistant Attorney General (Daniel I. Auster, special attorney), for the defendant.
Olivek, Presiding Judge:
This appeal to reappraisement has been submitted for decision upon the following stipulation of counsel for the parties'hereto:
It is hereby stipulated and agreed by and between the attorneys for the parties ¿hereto, subject to the approval of the court, that the merchandise covered by the instant appeal to reappraisement consists of bottles similar in all material respects to the merchandise the subject of United States v. Guerlain, Inc., decided in C. A. D. 146.
It is further stipulated and agreed that the said merchandise was appraised upon the cost of production under Section 402 (f) of the Tariff Act of 1930.
It is further stipulated and agreed that the issue with respect to said merchandise •covered by the instant appeal to reappraisement is the same as the issue involved in the case of United States v. Guerlain, Inc., supra.
It is further stipulated and agreed that the invoice prices plus the cost of cases •and packing are equal to the costs of materials, fabrication, manipulation or other processes employed in manufacturing or producing such merchandise, plus the usual general expenses (not less than ten per centum), plus the cost of all containers, coverings and other costs, charges and expenses incident to placing the -merchandise in condition packed ready for shipment to the United States and plus an addition for profit (not less than eight per centum) equal to the profit which ■ordinarily is added to the cost of merchandise of the same character by manufacturers or producers in the country of manufacture who are engaged in the manufacture of merchandise of the same class or kind.
It is further affirmed by the undersigned, Hadley S. King, member of the firm of Strauss & Hedges, counsel for the plaintiff, that the reappraisement covered by this stipulation has been examined by him and that said reappraisement has been duly signed and filed in the statutory time. The instant reappraisement is submitted on this stipulation.
On. the agreed facts, I find the cost of production, as that value is. defined in section 402 (f) of the Tariff Act of 1930, to be the proper basis for the determination of the value of the merchandise here involved, and that as to the bottles such values are the invoice prices plus the cost of cases and packing.
Insofar as the appeal relates to all other merchandise it is hereby dismissed. Judgment will be rendered accordingly.
|
Saurfang, Warrior
Objectives
Report to High Overlord Saurfang at Razor Hill in Durotar.
Description
I have already sent word. Saurfang awaits your arrival,.
Rewards
You will receive:
* 1,370 XP
* 1,370 XP
Progression
* 1) A Blood-Caked Scroll
* 2) Battle-Hardened Relics
* 3) Saurfang, Warrior
|
Value of Apoptotic, Antiapoptotic, and Cell Proliferation Markers in the Treatment of Graves' Disease
To better understand the genesis of autoimmunity in Graves' disease (GD), it is essential to study the mechanism of apoptosis and cell proliferation in thyroid cells and intrathyroidal lymphocytic infiltrate of GD patients. Methods. A cross sectional, observational study performed by evaluating histopathological samples of thyroidectomy products from GD patients using immunohistochemistry. New histological sections were prepared for immunohistochemical analysis with markers of cell proliferation, antiproliferation, apoptosis, and antiapoptosis. Results. Patients with GD who underwent radioiodine therapy (RIT) had a lower lymphocytic expression level of p27Kip1, and those who took beta-blockers had higher expression levels of BID (BH3-interacting domain) and a lower Ki-67 expression level in thyrocytes than those who did not. The association of a shorter diagnostic time with a lower expression level of MCL-1 in thyroid cells suggests that the hyperthyroid state was related to a lower antiapoptotic effect on thyrocytes. In comparison to patients with GD not using antithyroid drugs (ATD), we found a lower expression level of BID in lymphocytes for those who used ATD. Conclusion. In GD, the hyperthyroid state was associated with a lower antiapoptotic effect on thyroid cells. RIT, beta-blockers, and thionamide act by stimulating apoptosis of thyrocytes by intrathyroidal lymphocytes.
Introduction
Graves' disease (GD) is an autoimmune thyroid disease that involves [1,2] autoreactivity against thyrocytes by antibodies, lytic granules released from cytotoxic T-lymphocytes (CTLs), and apoptosis and the inappropriate presence of death receptors that activate apoptotic pathways [3][4][5]. Death receptors and their ligands, as Fas or CD95 and Fas ligand (FasL), are inactive in a normal thyroid. However, under proinflammatory conditions, proapoptotic molecules are activated [6,7]. Thyrocytes from GD patients express lower Fas levels creating an antiapoptotic environment. FasL-positive GD thyrocytes appear to induce Fas-mediated apoptosis of lymphocytes [8,9]. BCL-2 (B-cell lymphoma/leukemia 2) is an antiapoptotic molecule from the BCL-2 protein family. Other molecules of the family participate in the control of apoptosis: antiapoptotic MCL-1 (myeloid cell leukemia 1) and proapoptotic BID (BH3-interacting domain). In patients with GD, cytokines promote humoural immunity predominance and upregulate BCL-2 in thyrocytes, which escape from apoptosis. However, this safety is not present in GD intrathyroidal lymphocytes [7,[10][11][12]. MCL-1 is relevant for the survival of cell lineages of lymphocytes, stem cells, and neutrophils [13,14]. BID has lower expression levels in normal thyroid cells. However, when thyroid cells are exposed to inflammatory cytokines, there is BID overexpression. In mice with BID overexpression, the risk of developing autoimmune thyroiditis, induced by known factors such as iodine, was higher than in controls [10,15,16].
Autoimmune thyroid diseases and their clinical characteristics are distinguished by an imbalance between the degree of apoptosis and cell proliferation. Ki-67 and p27Kip1 proteins are markers related to cell proliferation in thyroid cells. Ki-67 is a nuclear protein produced in dividing cells that is used as a marker to identify active dividing cells. Doganay et al. [17] determined Ki-67 major expression in the follicles adjacent to lymphocytic infiltrate associated with regenerative hyperplasia; and some authors observed higher expression levels of Ki-67 in GD than nodular goiter [18,19]. p27Kip1 is a regulator of cyclindependent kinase activity and an inhibitor of G1-S cell cycle progression. Fang et al. [20], in a study with mice presenting with autoimmune disease, found that cell proliferation occurs by downregulating antiproliferative molecules, p21 and p27. The need for clarification regarding the development of autoimmune thyroid disease in hyperthyroidism justifies studies on the mechanisms of cell protection and death of thyrocytes and intrathyroidal lymphocytes in GD, as well as the action of thionamides. This study is aimed at evaluating antiapoptotic, proapoptotic, and cell proliferation markers in GD by using histopathological samples of thyroidectomy products in a representative number of patients associated with clinical and laboratory variables, as well as medications.
Study Design.
The study was carried out at the University of Campinas Teaching Hospital. Paraffin blocks of thyroidectomy products with anatomopathological and clinical diagnoses of GD and normal thyroid were selected. New sections were prepared for the immunohistochemical analysis of markers of apoptosis (Fas, Fas ligand, and BID), antiapoptosis (BCL-2, MCL-1), cell proliferation (Ki-67), and antiproliferation (p27Kip1) in thyroid cells and intrathyroidal lymphocytic infiltrate, as well as an evaluation of the lymphocytic infiltrate pattern in haematoxylin-eosin (HE) stained cells by an experienced pathologist. Clinical and laboratory parameters such as age, sex, serum thyroidstimulating hormone (TSH) and free levothyroxine (FT4) concentrations, and antithyroperoxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies were collected, retrospectively, by reviewing the chart.
The institutional review board approved the study under the opinion number 783.083, and no competing financial interests exist.
Patients.
We selected 67 individuals from an iodine area who underwent thyroidectomy between 1996 and 2015 and whose specimens were maintained by the tissue bank of the hospital; 53 were GD patients, and 14 had normal thyroid samples in the control group. Out of 67 individuals studied, 52 were female. The clinical diagnosis of GD was confirmed based on the presence of goiter, hyperthyroidism, or euthyroidism using thionamide, with at least one of the antithyroid serum antibodies in high concentrations. The indications of thyroidectomy were difficult disease control even in optimized therapy or serious adverse reactions due to the use of antithyroid drugs such as hepatitis drug, cutaneous reaction, or agranulocytosis. We included in the GD sample, eight patients who were not using ATD at the time of surgery. Among patients with GD, 54.72% were smokers, 88.68% were using thionamide at the time of surgery, 84.91% had exophthalmos, and only 11.33% underwent previously radioiodine therapy. In the control group, the indications of thyroidectomy were thyroid infiltrative malignant neoplasm of larynx or suspicion of thyroid neoplasia. The inclusion criteria were the absence of antithyroid antibodies, euthyroidism, and normal thyroid tissue by anatomopathological analysis. If there were thyroid neoplasia in the sample, that case was excluded.
2.3. Laboratory Evaluation. Serum TSH concentrations were measured by the electrochemiluminescence (EIA) method-a sandwich technique used in the Elecsys TSH immunoassay analyser (Roche), and a range of 0.4 to 4.5 μIU/mL was considered normal. The concentrations of FT4 were measured by the EIA method-the competition principle used in the Elecsys FT4 immunoassay analyser (Roche), with a normal range of 0.9 to 1.8 ng/mL. Anti-TPO and anti-Tg antibodies were measured by EIA, the competition principle used in the Elecsys anti-TPO and anti-Tg (Roche) immunoassay analyser, with normal values lower than 35 μIU/mL and 115 μIU/mL, respectively.
Tissue Specimens.
We selected 10% formalin-fixed paraffinembedded blocks of 67 thyroidectomies. We performed new histological sections for lymphocytic infiltrate evaluation and immunohistochemical analysis with proliferation, antiproliferation, cell apoptosis, and antiapoptotic markers.
2.5. Immunohistochemistry. The selected paraffin blocks were submitted to 4 μm slices in a Leica® RM2125RT microtome. Tissue sections were deparaffinized in xylene and dehydrated in graded ethanol series, washed with distilled water, and then placed in a pressure cooker in Tris-EDTA buffer pH 8.9 for 5 minutes at 95°C (CD 95, Fas ligand, Ki-67, and BCL-2) or citrate buffer pH 6.0 (BID, MCL-1, and p27). Endogenous peroxidase and nonspecific binding were blocked with 0.3% hydrogen peroxide in methanol for 15 minutes. After rinsing in phosphate-buffered saline at pH 7.2, 10% bovine serum (Wako, Osaka, Japan) was applied for 20 minutes. Sections were then incubated with primary antibodies overnight at 4°C. The primary antibodies and positive controls within each marker used are shown in Table 1.
Anti-MCL-1 monoclonal antibody detects the long chain of MCL-1 protein (37 kDa), called isoform 1, and is defined as an antiapoptotic protein [21]. A second-generation peroxidase-based detection system (Advance, Dako) was used to visualize antigen-antibody reactions.
2.6. Immunohistochemical Evaluation. All analyses were performed under light microscopy (Eclipse E200, Nikon Instruments Inc., NY, USA). Two blinded observers, one pathology expert in thyroid (IBS) and the first author (JCV), reviewed all thyroid slides at different times individually (Cohen's kappa = 0.628 − substantial agreement), and cases with inconsistent scores were reevaluated to achieve a consensus score. An evaluation of semiquantitative and visual immunohistochemistry (IHC) was done in follicular epithelium and lymphoid follicles, in each case, in at least three representative tissue areas, and different cut-off points were used for each marker, based on the extent of expression at 40x magnification (calculating the percentage of immunoreactive cells of at least 500 cells). For cell proliferation evaluation, we used Ki-67 and p27kip1, with nuclear positivity on thyrocytes and lymphocytes. For apoptosis, we used BID, Fas, and FasL with cytoplasm positivity in thyroid cells and cytoplasm or nuclear membrane positivity in lymphocytes. For antiapoptosis, we used BCL-2 and MCL-1, with cytoplasm positivity in thyroid cells and lymphocytes. It was considered strong expression of Fas/FasL when a minimum of 50% of cells were clearly positive. The staining intensity of Ki-67 was scored as expression less than 1% and greater than 1%. The marker BID was evaluated and classified as expression lower and greater than 50%. For BCL-2, the staining was divided into no or weak reactivity (0-25%) and positive (>25%). For p27Kip1, the expression was classified into three groups: no expression (0%), weak positivity (1 to 25%), and strong (>25%) positivity. MCL-1 protein expression was classified as strong positivity (>20%) and weak positivity (<20%).
Most patients (77.36%) underwent total thyroidectomy due to the difficulty of controlling hyperthyroidism.
Relationship between Lymphocytic Infiltrate and the
Presence of Antibodies in Graves' Disease. We could observe that as lymphocytic infiltrate (Figure 1) in GD becomes more pronounced, the frequency of antibody positivity ( Figure 2) increases and, in the case of antithyroglobulin antibody, it was significant: those with negative lymphocytic infiltrate did not have antibody positivity and among those with severe lymphocytic infiltrate, all had antibody positivity (p = 0 0003).
Proliferation and Antiproliferation Cell Markers
(1) Analysis of Graves' Disease Patients and the Control Group. The immunostaining results of proliferative cell markers in GD patients and the control group are summarized in Table 2 and Figure 1.
(2) Analysis of Graves' Disease Patients. We could observe that six patients with Graves' disease who submitted to radioiodine therapy (RIT) presented lower lymphocytic expression of the p27 marker (<25%) and those who took beta-blockers, such as propranolol, had lower Ki-67 expression in thyrocytes than those who did not (Table 3).
Proapoptotic Markers
(1) Analysis of Graves' Disease Patients and the Control Group. Patients with GD using ATD have a higher expression of the proapoptotic marker BID in thyrocytes (expression greater than 50% in 72% of cases of each disease), whereas in the control group, the expression was less than 50% in most individuals, 64% (p = 0 0318).
(2) Analysis of Graves' Disease Patients. Patients with GD using beta-blocker drugs have higher expression of the proapoptotic marker BID in thyroid cells (p = 0 0432), as shown in Table 4. If we divided these patients according to the use of ATD, those who were not using ATD had higher expression of the proapoptotic marker BID (greater than 50%) in intrathyroid lymphocytes (p = 0 0094), as shown in Table 4.
Antiapoptotic Markers
(1) Analysis of Graves' Disease Patients and Control Group. The antiapoptotic marker MCL-1 is expressed more in thyrocytes (expression greater than 20%) in cases of GD using ATD (95.45%) than that in control subjects (64.29%), with a p value of 0.0117.
(2) Analysis of Graves' Disease Patients. The expression levels of antiapoptotic markers BCL-2 and MCL-1 in intrathyroid lymphocytes are lower in patients who took beta-blocking drugs at the time of thyroidectomy, as shown in Tables 5 and 6. It was also observed that the lowest expression of MCL-1 protein (<20%) in intrathyroid lymphocytes occurred in patients with the largest thyroid volume (mean 97.92 cm 3 ), despite having a large standard deviation (±82.61 cm 3 ) with p = 0 0229.
Discussion
GD pathophysiology involves dysregulation of apoptosis and lymphocytic infiltration, in addition to the result of the balance between proapoptotic and antiapoptotic factors, as well as proliferative and antiproliferative factors in thyroid cells and intrathyroidal lymphocytes [22].
When analysing the expression of markers between GD patients and the control group, we found that Ki-67 (proliferation) and p27Kip1 (antiproliferation) expression in intrathyroidal lymphocytes was lower in the control group than that in GD patients using antithyroid drugs (ATD). Studies have shown a tendency toward apoptosis of intrathyroidal lymphocytes in patients with GD who take ATD and exhibit less cell proliferation, with an elevation of the p27Kip1 marker and its regulator Ki-67 [23]. BID expression in thyrocytes was greater in patients with GD using antithyroid drugs than that in the control group, showing the proapoptotic effect of these drugs. The MCL-1 marker exhibited higher expression in thyrocytes of patients with GD using ATD than that in the control group, indicating that there is strength in the body to prevent apoptosis of these cells, promoted by the marker of apoptosis BID, as cited above.
According to the literature [24], we found a positive association between patients who received radioiodine treatment and the lowest expression of marker p27 in intrathyroidal lymphocytes; that is, lymphocytes cause a greater inflammatory reaction, increased apoptosis in thyrocytes, and a reduction of goiter volume. Patients with GD use medications such as thionamide, beta-blockers, and iodine solution to control thyrotoxicosis and prepare for surgery. In our study, the use of beta-blockers was associated with the greater expression of BID (proapoptotic) and lesser expression of Ki-67 (cell proliferation) in thyrocytes [25], suggesting that these medications may stimulate apoptosis of thyrocytes, reducing the cell proliferation rate and helping in disease control.
We divided GD patients into two groups: with and without the use of ATD at the time of surgery. The expression of BID in intrathyroidal lymphocytes was lower in patients using ATD, suggesting that they had less lymphocytic apoptosis, which stimulates less activity of thyrocytes and may be another disease control mechanism of ATD. In relation to MCL-1 in GD, patients with the lowest expression of this marker in lymphocytes are those with the largest goiters; those using beta-blockers also had lower expression of MCL-1 and BCL-2 in lymphocytes. If MCL-1 or BCL-2 is decreased in lymphocytes, they survive less and have less stimulating thyrocyte apoptosis, leading to a greater goiter volume. There are already studies evaluating melanoma and thyroid carcinoma [25,26] showing the reduction of BCL-2 and MCL-1 expression in people using propranolol.
The higher proportion of positive detectable antithyroid antibodies found in patients with GD with more prominent lymphocytic infiltrate suggests that a larger lymphocytic infiltrate and activation of T cells led to a higher recruitment of B cells and the development of immune response via antithyroid antibodies [27].
The study limitations were as follows: the impossibility to show a predominance of one marker over another. We evaluated the expression of markers separately, and there was a lower number of individuals in the control group due to the lower indication of thyroidectomy in these cases. The strengths were as follows: the study was carried out with anatomopathological findings, thyrocytes, and intrathyroidal lymphocytes; the study contained many patients and immunohistochemical markers, as well as an evaluation of drugs in use and their effects on apoptotic mechanisms and cell proliferation.
In conclusion, the recognition of thionamides as immunomodulatory drugs, with alteration of the lymphocytic infiltrate in patients who use them, and RIT as a lymphocyte sparer represents significant findings obtained from this study. We believe that these findings in the immunohistochemical expression of cell antiproliferation (p27Kip1 on intrathyroidal lymphocytes), apoptotic (BID on thyroid cells and intrathyroidal lymphocytes), and antiapoptotic (MCL-1 on thyroid cells and intrathyroidal lymphocytes) markers may be relevant in the development of new drugs and a better understanding of the pathophysiology of these diseases. Additionally, understanding the role of beta-blockers, more specifically propranolol, in GD has been poorly explored in thyroid studies, although it has been described as an important aid in melanoma cells and cardiac cells. Therefore, the greater BID (apoptotic) expression in the thyrocytes and lower expression of MCL-1 (antiapoptotic) in lymphocytes may lead to the routine use of these drugs in therapy for Graves' disease, changing its indication. Further studies are needed to better understand the pathophysiology of these diseases and
|
Ruth McCALL, Appellant, v. ALABAMA BRUNO’S, INC., Appellee.
No. 93-936.
District Court of Appeal of Florida, First District.
June 29, 1994.
Michel L. Stone, of Stone & Sutton, and Marvin A. Urquhart, Jr., Panama City, for appellant.
Thomas R. Jenkins, of Bozeman, Jenkins & Matthews, Pensacola, for appellee.
BARFIELD, Judge.
We find that summary judgment for the defendant grocery store owner, Alabama Bruno’s, Inc., was inappropriate in this negligence action arising out of a slip and fall accident, because the store owner was not entitled to judgment in its favor as a matter of law.
Ruth McCall fell in the area between the aisles and the check-out lanes, where the floor had recently been cleaned by a floor cleaning service, United Maintenance (UM), using a machine that used water to scrub the floor. It is undisputed that the store was open to the public 24 hours a day every day, that UM cleaned the floors every night from about 10:00 PM to about 6:00 AM, that the cleaning machine was still operating when the accident occurred at about 6:30 AM, that UM was supposed to place “wet floor” warning signs in the area it was cleaning, and that there were no warning signs in the area immediately after the fall (from which it may reasonably be inferred that there were no warning signs in the area at the time McCall fell). The depositions indicated that there was a puddle of dirty water on the floor where McCall fell, and that store personnel knew that the cleaning machine sometimes left water behind and had several times had trouble getting UM to keep “wet floor” signs down.
The complaint alleged that the store owner failed to maintain the premises in a safe condition, failed to make the premises safe when it knew or should have known of the hazard, and failed to warn McCall of a dangerous condition of which it was aware or should have been aware. The store owner asserted, inter alia, that it was not in actual possession and control of the portion of the premises where the accident occurred, and that McCall’s injuries resulted from the acts of a third party independent contractor for which it had no liability. The trial court found that “the general rules of slip and fall cases apply” and that under Schaap v. Publix Supermarkets, Inc., 579 So.2d 831 (Fla. 1st 1991), “the plaintiff must prove that the defendant had actual or constructive notice of the condition.” It noted that motions for summary judgment should be carefully scrutinized, particularly in personal injury cases, citing Brooks v. Phillip Watts Enterprises, Inc., 560 So.2d 339 (Fla. 1st DCA), rev. denied, Phillip Watts Enterprises, Inc. v. Brooks, 567 So.2d 435 (Fla.1990); but found that there were no material facts in dispute and that the store owner was entitled to judgment as a matter of law, citing Bennett v. Mattison, 382 So.2d 873 (Fla. 1st DCA 1980).
Resolution of this case turns on which rules of law apply. Florida follows the general rule that the employer of an independent contractor is not liable for the contractor’s negligence because the employer has no control over the manner in which the work is done, but it also recognizes exceptions to the general rule which may generally be divided into three categories: 1) negligence in selecting, instructing, or supervising the contractor; 2) non-delegable duties arising out of some relation toward the public or the particular plaintiff; and 3) work which is specially, peculiarly, or “inherently” dangerous.
When the owner of a store employs an independent contractor to do work on the premises while they are open to the public and the work involves an unreasonable risk of harm to members of the public unless reasonable care is exercised in supervising the activities of the contractor, the store owner has a duty to supervise the equipment and methods of the contractor. The store owner is therefore liable for physical harm caused to a member of the public by its failure to use reasonable care to protect the public against unreasonably dangerous conditions created by the contractor, if the store owner had a reasonable opportunity to ascertain the improper equipment or methods of the contractor and to secure the substitution of safe equipment or methods.
Also, when a store owner hires an independent contractor to do work which it “should recognize as likely to create, during its progress, a peculiar unreasonable risk of physical harm to others unless special precautions are taken,” it has a duty to provide for such precautions in the contract or otherwise. And even if the store owner has provided for such precautions, it remains subject to liability for physical harm caused to others by the contractor’s failure to exercise reasonable care to take such precautions. “Peculiar” does not mean that the risk must be one which is abnormal to the type of work done, or that it must be an abnormally great risk, but instead refers to a special, recognizable danger arising out of the work itself. In order for the vicarious liability rules to apply,
... it is not essential that the work which the contractor is employed to do be in itself an extra-hazardous or abnormally dangerous activity, or that it involve a very high degree of risk to those in the vicinity. It is sufficient that it is likely to involve a peculiar risk of physical harm unless special precautions are taken, even though the risk is not abnormally great. A “peculiar risk” is a risk differing from the common risks to which persons in general are commonly subjected by the ordinary forms of negligence which are usual in the community. It must involve some special hazard resulting from the nature of the work done, which calls for special precautions ....
Restatement (Second) of Torts § 416 cmt. d. The peculiar risk need not be one which will necessarily and inevitably arise in the course of the work, no matter how it is done, so long as it is a risk which the store owner should recognize as likely to arise in the course of the ordinary and usual method of doing the work, or the particular method which it knows that the contractor will adopt.
The Restatement states that the rules imposing vicarious liability on employers for the acts of independent contractors arise “in situations where, for reasons of policy, the employer is not permitted to shift the responsibility for the proper conduct of the work to the contractor” and that it is commonly stated that “the employer is under a duty which he is not free to delegate to the contractor.” Such nondelegable duties have been found under Florida law to be imposed by statute, contract, or common law, and to arise out of “inherently dangerous activity” or activity involving “inherently dangerous elements,” or out of the creation of an “inherently dangerous condition.”
There is a close relation between the above stated exception and the rule stated in section 427 of the Restatement;
One who employs an independent contractor to do work involving a special danger to others which the employer knows or has reason to know to be inherent in or normal to the work, or which he contemplates or has reason to contemplate when making the contract, is subject to liability for physical harm caused to such others by the contractor’s failure to take reasonable precautions against such danger.
The comment to section 416 indicates that the two rules “have been applied more or less interchangeably in the same types of cases, and frequently have been stated in the same opinion as the same rule, or as different phases of the same rule.” It explains that the rule stated in section 416 is more commonly applied “where the employer should anticipate the need for some specific precaution, such as a railing around an excavation in a sidewalk,” while the rule stated in section 427 is more commonly applied “where the danger involved in the work calls for a number of precautions, or involves a number of possible hazards, as in the ease of blasting, or painting carried on upon a scaffold above a highway.” The comments to section 427 indicate that the exception is not limited to highly dangerous activities, but that it applies “where the harm results from the negligence of the contractor in failing to take precautions against the danger involved in the work itself, which the employer should contemplate at the time of the contract,” and further,
... It is not necessary that the work call for any special skill or care in doing it. It is sufficient that work of any kind involves a risk, recognizable in advance, of physical harm to others which is inherent in the work itself, or normally to be expected in the ordinary course of the usual or prescribed way of doing it, or that the employer has special reason to contemplate such a risk under the particular circumstances under which the work is to be done.
Without a transcript of the hearing on the motion for summary judgment, it is impossible to assess the context in which the trial court concluded that there were no genuine issues of material fact and that the store owner was entitled to summary judgment as a matter of law. However, considering the pleadings, affidavit, and depositions presented to the trial court, and drawing all possible inferences in favor of the party against whom the summary judgment was sought, Moore v. Morris, 475 So.2d 666 (Fla.1985), we find that the evidence presented created a jury question as to whether the store exercised reasonable care to assure that the floor was safe for public passage or properly marked with “wet floor” signs, and that the trial court’s conclusion was therefore erroneous.
The summary judgement is REVERSED and the ease is REMANDED for further proceedings consistent with this opinion.
ALLEN and WOLF, JJ., concur.
. Schaap v. Publix Supermarkets, Inc. involved a slip and fall on a cookie in a grocery store that had a policy of giving children cookies. The trial judge granted summary judgment for the store, finding that the fact that it had a cookie club was not enough, in and of itself, to establish a causal connection between Schaap's slipping and a breach of duly by the store, and that there was no evidence to indicate how long the cookie had been there. This Court affirmed, stating that a plaintiff must generally prove that the owner of the premises had actual or constructive notice of the dangerous condition, that constructive notice may be inferred from either the length of time a substance has been on the floor or the fact that the condition occurred with such frequency that the owner should have known of its existence, and that the owner may also be liable if its agent or employee caused the dangerous condition, or if its method of operation was inherently dangerous. It found that the Schaaps had not proffered evidence that would sufficiently prove either element of the “method of operation” theory they asserted: 1) either that the method of operation was inherently dangerous or the particular operation was being conducted in a negligent manner, and 2) that the floor condition was created as a result of the negligent method of operation.
. Brooks v. Phillip Watts Enterprises, Inc. involved a slip and fall on a "wet damp” area as the plaintiff entered a grocery store on a rainy day; there were no “wet floor” warning cones, which were usually placed at the front door when it rained. The trial court granted summary judgment for the store, finding Brooks had failed to prove that any of the store employees had actual or constructive notice that there was water on the floor when the accident occurred. This Court reversed, finding that the trial court “failed to exercise the caution appropriate to a determination of a motion for summary judgment in negligence cases” and that:
This evidence is sufficient for a factfinder to determine constructive notice existed of the dangerous condition on either of two theories: (1) the water was on the floor for a sufficient period of time that in the exercise of ordinary care (such as regular inspection), appellee should have known of the condition, or (2) the condition occurred with regularity and was therefore foreseeable.
560 So.2d at 342.
. Bennett v. Mattison involved a slip and fall on a wet spot in an apartment building hallway leading to a beach-front patio. This Court reversed a directed verdict for the apartment building owners, finding that they had been put on notice that the hallway was slippery and dangerous when wet and that others had slipped, creating a jury question as to whether they had exercised reasonable care to guard against a foreseeable danger. We noted that the owners could not be charged with either actual or constructive notice of the precise water which caused Bennett’s fall, but we found that the Bennetts were entitled to submit the case to the jury on the theory that the owners failed to take reasonable care 1) by not preventing water from coming onto the floor; 2) by not having an inspection procedure to discover water on the floor and clean it up; or 3) by not making the floor less slippery when water came to be on it.
. Restatement (Second) of Torts § 409 (1965) and comments.
. Id. § 415 and comments; Maldonado v. Jack M. Berry Grove Corp., 351 So.2d 967 (Fla.1977). See also Maule Industries, Inc. v. Messana, 62 So.2d 737 (Fla.1953); Breeding's Dania Drug Co. v. Runyon, 2 So.2d 376 (Fla. 1941).
. Restatement (Second) of Torts § 413.
. Id. § 416 and comments.
. Id. § 413 cmt. b and § 416 cmt. b.
. Id. § 416 cmt. e.
. Id. Chapter 15, Topic 2, Introductory Note.
. E.I. Strickland Const. v. Dept. of Agriculture and Consumer Services of Florida, 515 So.2d 1331 (Fla. 5th DCA 1987).
. See Emelwon, Inc. v. U.S., 391 F.2d 9 (5th Cir.), cert. den., Florida v. Emelwon, Inc., 393 U.S. 841, 89 S.Ct. 119, 21 L.Ed.2d 111 (1968); Midyette v. Madison, 559 So.2d 1126 (Fla.1990); Channell v. Musselman Steel Fabricators, Inc., 224 So.2d 320 (Fla.1969); Schaap v. Publix Supermarkets, Inc.; Fisherman’s Paradise, Inc. v. Greenfield, 417 So.2d 306 (Fla. 3d 1982); Atlantic Coast Dev. v. Napolean Steel, 385 So.2d 676 (Fla. 3d DCA 1980); Florida Freight Terminals, Inc. v. Cabanas, 354 So.2d 1222 (Fla. 3d DCA 1978); Florida Power & Light Company v. Price, 170 So.2d 293 (Fla.1964); Ross v. Heitner, 156 So.2d 869 (Fla. 3d DCA 1963).
|
<Tr> <Th> Clarke, Fred Fred Clarke (2) </Th> <Td> 000000001903 - 05 - 07 - 0000 May 7, 1903 </Td> <Td> Pittsburg Pirates </Td> <Td> National League </Td> <Td> Cincinnati Reds </Td> <Td> </Td> </Tr> <Tr> <Th> Freeman, Buck Buck Freeman </Th> <Td> 000000001903 - 06 - 21 - 0000 June 21, 1903 </Td> <Td> Boston Red Sox </Td> <Td> American League </Td> <Td> Cleveland Naps </Td> <Td> </Td> </Tr> <Tr> <Th> Dougherty, Patsy Patsy Dougherty </Th> <Td> 000000001903 - 07 - 29 - 0000 July 29, 1903 </Td> <Td> Boston Red Sox </Td> <Td> American League </Td> <Td> New York Highlanders </Td> <Td> </Td> </Tr> <Tr> <Th> Bradley, Bill Bill Bradley </Th> <Td> 000000001903 - 09 - 24 - 0000 September 24, 1903 </Td> <Td> Cleveland Indians </Td> <Td> American League </Td> <Td> Washington Senators </Td> <Td> </Td> </Tr>
How many consecutive games have the astros hit a double
|
250 CLASS XV.
LlNN^US quotes them). This species I'etains the tail veiy long, and is smaller when adult than before the loss of the tail ; hence Merian and Seba fell into the mistake that it undergoes a retrograde metamorphosis into a fish ; it is met with in Surinam.
Rana L. (exclusive of manj species). Membrane of tympanum distinct. Anterior feet cloven, posterior palmate. Tongue oblong, posteriorly deeply eraarginate, free, exsertile. Two lateral vocal sacs in males, emerging externally in some when distended with air.
Sp. Rana esculenta L., Ecesel Hist. Ranar. Tab. 13 — 16, Sturm Deutschl. Faun., Amphib. Heft i., Dadd. Rain., Gren. et Crap. PI. 15, fig. i, Bell Hist. Brit. Rept. sec. ed. London, 1849, p. no; the green frog, der griine WasserfroscJi ; green above, with black spots, under-surface of body whitish ; the vocal sacs in this species become visible externally (see above, p. 221). The croak, very loud and especially by night, is heard at a great distance. This species is very common in Holland, but in England is confined to par ticular localities. — Rana temporaria L., Rcesel 1. 1. Tab. i. — viii. Sturm 1. 1. Daud. pi. 13, fig. 2, Bell 1. 1. p. 89; the hrownfrog; yellow-brown or reddish ; a dark brown longitudinal spot behind the eyes, which passes obliquely over the membrane of tympanum and ends in a point backwards. In this species the vocal sacs do not pass out externally. Rana temporaria contains, according to Steenstrup, two species, oxyrliinus and platyrhinus. The last is the most common {Bericht der i^te Versamml. der deutschen Naturf or seller, in Kiel.). See also Thomas Ann. des Sc. nat. 4ifeme s^rie, Tom. IV. 1855, p. 365. These animals make only a growling sound, especially when uneasy and in pairing time ; at this time only do they live in water, at other times they keep on land. A very large species of this genus occurs in the East Indies, Rana ciUipora Dum. and Bibr., Rana sapaiiue Keinw. M. S., Dactylethra henghalensis! Lesson Illustr. de Zool. PI. 47, and one still larger in North America, Ratia mugiens Merr., the Bidl-frog of Catesbt. Most of the species of the genus Rana of modern writers are from the eastern hemisphere.
On some other sub-genera, here omitted, cons. Dumeril and BiBRON 1. 1. Vol. VIII. In habit, and especially in the small and slender fore feet, Lejytohrachium TsCHum differs from the rest of the Ranee.
|
NATIONAL STATE BANK v. FEDERAL RESERVE BANK OF NEW YORK; Community Guardian Bank; Uniport Company, Inc.; Sang B. Lee Federal Reserve Bank of New York, Appellant.
No. 92-5189.
United States Court of Appeals, Third Circuit.
Argued Sept. 22, 1992.
Decided Nov. 24, 1992.
Thomas C. Baxter, Jr. (argued), New York City, Robert B. Silverman, Silverman & Rozier, Lakewood, N.J., for appellant.
Mark E. Herrera, Scott C. Pyfer (argued), Patterson & Weir, Westmont, N.J., for appellee.
Present: MANSMANN and ROTH, Circuit Judges and RESTANI, Court of International Trade Judge .
. Honorable Jane A. Restani, Judge, United States Court of International Trade, sitting by designation.
RESTANI, Judge.
Defendant-appellant, the Federal Reserve Bank of New York (“the N.Y.Fed”), appeals from the district court’s grant of summary judgment in favor of plaintiff-appellee National State Bank (“NSB”). The district court held that defendant N.Y.Fed breached its duty of ordinary care in presenting two checks for payment and in failing to notify NSB within a reasonable time that the checks had been lost. Because we find that NSB did not meet its initial burden of demonstrating the absence of a genuine issue of fact in its motion for summary judgment, we reverse the district court’s order and remand for trial.
I.
This case involves apportionment of liability resulting from an alleged check kiting scheme. A brief overview of check kiting and the United States check collection system is therefore appropriate. A check kiter is a person who first draws a check on a fictitious account or on an account with insufficient funds to cover the amount of the check. The bank in which the account is supposedly located is the payor bank. The kiter then deposits the check in an account in a second bank, the depositary bank. The depositary bank does not learn that the check cannot be covered by funds in the account in the payor bank until after the kiter, or the kiter’s accomplice, has withdrawn the money from the depositary bank. See Northpark Nat’l Bank v. Bankers Trust Co., 572 F.Supp. 524, 526 (S.D.N.Y.1983).
In order to understand why the depositary bank may not learn that the check has been dishonored until after the funds have been withdrawn, we must take a look at the check collection system in the United States. This system depends in large part on our Federal Reserve banks. The regional banks of the Federal Reserve System, as collecting banks, receive checks from depositary banks and physically transmit these checks to the payor banks. The N.Y.Fed, for example, collects and processes nearly eight million checks daily. While checks are in transit, the collecting banks extend provisional credit to the depositary banks and make provisional debits to the accounts of the payor banks. See Greater Buffalo Press, Inc. v. Federal Reserve Bank of N.Y., 866 F.2d 38, 39-40 (2d Cir.1989) (overview of the check collection process). If, when a payor bank physically receives a check, there are insufficient funds in the account on which it is drawn to cover it, the payor bank will notify the depositary bank that the check has been dishonored. This usually will occur within a matter of a day or two. However, if the transaction has proceeded normally and there are funds in the payor bank to cover the check, the payor bank will not generally advise the depositary bank that final payment has been made on a particular check.
It is on the occasions when there is a delay in transmitting a check or in giving notice of its dishonor that a check kiter may create an opportunity to withdraw funds from an account in the depositary bank even though there are insufficient funds in the account in the payor bank. Under our banking system, the payor and depositary banks maintain reserves in the collecting bank in their respective regions. The provisional debits and credits are made by the collecting bank against those reserves. Unless the depositary bank is notified that a check has been lost or dishonored, the depositary bank will assume within a short period of time that the provisional credit is final. By creating a situation in which there will be a delay in notification, the check kiter may succeed in withdrawing funds from the depositary bank before that bank learns of the scam.
In this case, Mr. Sang Lee, the President of Uniport Co., was allegedly involved in a check kiting scheme. Mr. Lee had accounts with plaintiff NSB and with Community Guardian Bank (“CGB”), not a party to this action. On or about November 27, 1989, Mr. Lee deposited at NSB two checks in the amount of $35,800. These checks were drawn on Mr. Lee’s account at CGB.
NSB sent the checks to the N.Y.Fed which then took two provisional actions, crediting NSB with the deposit and debiting CGB. Approximately three months later, on March 9, 1990, the N.Y.Fed informed NSB that CGB had never received the checks. There is no evidence in the record to suggest that the N.Y.Fed’s delay in notifying NSB of the loss of the checks was caused by the check kiting scheme. At the time of oral argument, the parties still had no knowledge as to what happened to those two checks. Sometime after the loss was discovered, the N.Y.Fed reversed both the provisional credit to NSB and the provisional debit to CGB.
Unfortunately, by the time the N.Y.Fed reversed the provisional credit to NSB, NSB was no longer able to cover the loss of this credit from the funds in Mr. Lee’s NSB account. This is so because during the three month delay between the time the checks were sent and NSB received the notice that they had been lost, NSB and CGB had concluded that Mr. Lee was attempting to defraud them. On February 20,1990, NSB closed Mr. Lee’s account and sent the remaining funds in it to CGB, where Mr. Lee’s account was overdrawn. In return, CGB agreed to hold NSB harmless for any liability arising out of the payment of these funds to CGB.
In the fall of 1990, CGB declared bankruptcy and closed its doors. For this reason, NSB could no longer turn to CGB to cover its loss on the Lee account. NSB was able to recover only $3,000 from Mr. Lee personally. Therefore, NSB sued the only remaining source of recovery, the N.Y.Fed, for $32,800, the balance of its loss. On March 4, 1992, the district court granted summary judgment in favor of NSB. In an unpublished opinion, the trial judge stated,
the Court finds that Federal Reserve [of N.Y.] breached its duty of ordinary care in the presentment of the two checks. The Court further finds, as a matter of law, that a delay of more than three months in notifying plaintiff that the checks were lost in transit was an unreasonable length of time.
Nat’l State Bank v. Fed. Reserve Bank of N.Y., Civ. No. 91-3777, at 9 (D.N.J. Mar. 4, 1992) (“Memorandum & Order”), Joint Appendix (“Joint App.”) at 115. The N.Y.Fed appeals.
II.
In this ease, federal jurisdiction is based on 12 U.S.C. § 632, which provides, “all suits ... to which any Federal reserve bank shall be a party shall be deemed to arise under the laws of the United States.” 12 U.S.C. § 632 (1988). Thus, the district court had federal question jurisdiction under 28 U.S.C. § 1331 (1988), and appellate jurisdiction is proper under 28 U.S.C. § 1291 (1988).
The standard of review for a grant of summary judgment is plenary. Resolution Trust Corp. v. Gill, 960 F.2d 336, 340 (3d Cir.1992). On review, this court will apply the same test used by the district court, namely, whether the movant has met its initial burden of showing the absence of a genuine issue of material fact. The evidence must be viewed in the light most favorable to the non-moving party. O’Donnell v. United States, 891 F.2d 1079, 1081-82 (3d Cir.1989). Once the initial burden has been met, the moving party will prevail only if the evidence would support a directed verdict in its favor. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 251, 106 S.Ct. 2505, 2511, 91 L.Ed.2d 202 (1986).
III.
The issue of whether plaintiff NSB satisfied its initial burden on summary judgment presents two questions. First, did the district court correctly decide that the N.Y.Fed breached its duty of ordinary care in presenting the checks? Second, did the district court correctly find that a three month delay between collection of the checks and notification of loss was unreasonable as a matter of law?
On a summary judgment motion, the movant must show that “there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law.” Fed.R.Civ.P. 56(c). Once the movant satisfies this initial burden, then the non-movant must respond with information to the contrary or it will lose. Fed.R.Civ.P. 56(e).
To prove that no genuine factual issues exist, a movant must present a factual scenario without any “unexplained gaps.” Adickes v. S.H. Kress & Co., 398 U.S. 144, 158, 90 S.Ct. 1598, 1609, 26 L.Ed.2d 142 (1970); accord O’Donnell, 891 F.2d at 1082. Where the movant is the defendant, or the party without the burden on the underlying claim, the movant has no obligation to produce evidence negating its opponent’s case. The moving party merely has to point to the lack of any evidence supporting the non-movant’s claim. Celotex Corp. v. Catrett, 477 U.S. 317, 323-25, 106 S.Ct. 2548, 2552-54, 91 L.Ed.2d 265 (1986).
Where the party moving for summary judgment is the plaintiff, or the party who bears the burden of proof at trial, the standard is more stringent. The Third Circuit has stated that “where the movant bears the burden of proof at trial and the motion does not establish the absence of a genuine factual issue, the district court should deny summary judgment even if no opposing evidentiary matter is presented.” Gill, 960 F.2d at 340.
In the case before us now, the party bringing the summary judgment motion is the plaintiff NSB, who bears the burden of proof at trial. To determine whether NSB should have prevailed on its summary judgment motion, we must consider whether NSB satisfied its initial burden of production. If it did not, the sufficiency of the N.Y.Fed’s response is not an issue.
IV.
A.
We first turn to the question of whether NSB has established the N.Y.Fed’s duty of care in presenting the two checks. The applicable statute, New Jersey’s version of the Uniform Commercial Code (“U.C.C.”), provides that “[a] collecting bank must use ordinary care in ... presenting an item.” N.J.Stat.Ann. § 12A:4-202(l)(a). NSB argues that the N.Y.Fed, as a collecting bank, breached its duty of ordinary care by losing the checks before it had the opportunity to present them to the paying bank.
Ordinary care, in the sense used by the U.C.C., “is not intended to refer to a standard of care unique to the banking world.” U.S. Fidelity & Guaranty Co. v. Federal Reserve Bank of N.Y., 590 F.Supp. 486, 491 (S.D.N.Y.1984). Nevertheless, sound banking practice will be considered when a court examines the surrounding facts and circumstances of alleged negligence. Id. at 499.
The principal piece of evidence upon which NSB relies to establish the N.Y.Fed’s breach of ordinary care is the affidavit of Carole N. Marshall, an assistant vice president of NSB. The affidavit states only, “it is my belief that the Federal Reserve [of New York] lost the original Checks, having failed to deliver the Checks to Community Guardian Bank [CGB] for collection.” Joint App. at 62. Ms. Marshall does not explicitly rely either on her expertise as a banker or on the standards of the banking industry in reaching that conclusion.
The affidavit also lacks any supporting factual evidence for Ms. Marshall’s conjecture that the N.Y.Fed lost the checks. The documents which she cites show only that CGB never received the original checks (although it later received photocopied duplicates). Joint App. at 62, 70-71. NSB’s brief states that the N.Y.Fed might have lost the checks or it might have presented them to CGB later than it should have. Appellee’s Brief at 12. Equally plausible is the N.Y.Fed’s contention that CGB lost the checks. Joint App. at 86, 91. It is also possible that the mail carrier lost them.
These significant factual disputes bear directly on the issue of whether the N.Y.Fed breached its duty of ordinary care in presenting the checks to CGB. There is no evidence in the record as to who lost the checks — the N.Y.Fed, CGB, or the mail carrier. If there is no evidence that the N.Y.Fed lost the checks, then it cannot be held liable for breach of the duty of presentment.
Therefore, the district court’s statement that “[w]hat happened to the checks after Federal Reserve [of N.Y.] received them is ... irrelevant” is incorrect. Memorandum & Order at 8. Summary judgment against the N.Y.Fed for breaching its duty of ordinary care in presenting the checks is improper.
B.
Summary judgment was also granted on the ground that “as a matter of law, ... a delay of more than three months in notifying plaintiff that the checks were lost in transit was an unreasonable length of time.” Memorandum & Order at 9. The district court apparently measured the delay from when NSB sent the checks to the N.Y.Fed to when NSB received notification of loss.
The statute, in contrast, requires the delay to be measured from when the collecting bank, in this case the N.Y.Fed, first learned of the loss. The record contains no indication of when the N.Y.Fed learned of CGB’s failure to receive the checks. The N.Y.Fed’s notification form says only that the checks have “been reported not received.” Joint App. at 69. Plaintiff NSB admitted at oral argument that it neglected to request this information in discovery.
The time that the N.Y.Fed learned of the loss is a material fact. With no evidence on this point in the record, NSB can hardly claim that there are no genuine issues of material fact. NSB failed to meet its initial burden, and therefore the N.Y.Fed had no obligation to respond. Under the law of this circuit, when the movant who bears the burden of proof at trial does not establish the absence of a genuine factual issue, summary judgment is inappropriate even when the non-movant submits no evidence at all. Gill, 960 F.2d at 340. Even if NSB did not bear the burden of proof at trial, there is still an “unexplained gap” in its version of events which requires a denial of summary judgment. Adickes, 398 U.S. at 158, 90 S.Ct. at 1609.
V.
Summary judgment below was granted on two grounds: 1) that the N.Y.Fed breached its duty of ordinary care in presenting the checks and 2) that the N.Y.Fed breached its duty of timely notification of the checks’ loss. Summary judgment was improper because the NSB failed to produce sufficient evidence to meet its initial burden on either ground.
Because we hold that the district court’s order of summary judgment should be reversed, we do not reach the issue of whether the district court should have allowed the N.Y.Fed further discovery before requiring it to respond to the motion for summary judgment.
. See also Anchorage Assocs. v. Virgin Islands Bd. of Tax Review, 922 F.2d 168, 175 (3d Cir.1990) (where movant has burden of proof and non-movant does not respond at all, court must still find that movant is entitled to prevail as matter of law). Justice Brennan’s dissent in Celotex recommended that where the movant bears the burden of persuasion at trial, the movant must produce enough evidence to justify a directed verdict in its favor in order to meet its initial burden. 477 U.S. at 331, 106 S.Ct. at 2556 (Brennan, J., dissenting); see also William W. Schwarzer et al., The Analysis and Decision of Summary Judgment Motions, 139 F.R.D. 441, 477 (1991).
. NSB argues that the N.Y.Fed bears the burden of establishing that it presented the checks to CGB "seasonably." Appellee’s Brief at 12-13. NSB relies on the somewhat ambiguous statutory provision that "[a] collecting bank taking proper action before its midnight deadline ... acts seasonably; taking proper action within a reasonably longer time may be seasonable but the bank has the burden of so establishing.” N.J.Stat.Ann. § 12A:4-202(2) (West 1991). The New Jersey courts, however, have held that the plaintiff bears the burden of proof under § 12A-.4-202. Hoke v. Pioneer State Bank, 167 N.J.Super. 410, 400 A.2d 1217, 1219 (Ct.App.Div.1979).
. "[A] bank is not liable ... for loss or destruction of an item in transit or in the possession of others." N.J.Stat.Ann. § 12A:4-202(3).
. Mr. Lee deposited the checks at NSB on November 27, 1989 and NSB received notification on March 9, 1990. Memorandum & Order at 2.
. "A collecting bank must use ordinary care in ... notifying [a check’s] transferor of any loss or delay in transit within a reasonable time after discovery thereof.” N.J.Stat.Ann. § 12A:4-202(l)(e).
.The fact that the N.Y.Fed is more likely to know when it learned of the loss makes no difference because NSB could easily have requested the information during discovery. The New York Fed has no obligation to prove its opponent’s case. See Celotex, 477 U.S. at 324, 106 S.Ct. at 2553.
|
System and method for combined heat and electric power generation
ABSTRACT
A system for combined heat and electric power generation, preferably including a heat reservoir and one or more electric generators, each preferably including a heat source and an energy converter. A method for combined heat and electric power generation, preferably including activating an electric generator, deactivating the electric generator, and/or providing heat from a heat reservoir.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application Ser. No. 62/971,796, filed on 7 Feb. 2020, and of U.S. Provisional Application Ser. No. 63/133,953, filed on 5 Jan. 2021, each of which is incorporated in its entirety by this reference.
STATEMENT OF GOVERNMENT SUPPORT
This invention was made with government support under Grant Number DE-SC0019568 awarded by the Department of Energy. The government has certain rights in the invention.
TECHNICAL FIELD
This invention relates generally to the energy conversion field, and more specifically to a new and useful system and method for combined heat and electric power generation in the energy conversion field.
BACKGROUND
Many typical heating systems convert high-temperature heat sources, such as combustion-based heat sources, into lower-temperature heat outputs, thereby introducing thermodynamic inefficiencies. Many typical electric power generators produce waste heat that goes unused, also introducing thermodynamic inefficiencies. Thus, there is a need in the energy conversion field to create a new and useful system and method for combined heat and electric power generation.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1A is a schematic representation of an embodiment of a system for combined heat and electric power generation.
FIG. 1B is a schematic representation of an example of the embodiment depicted in FIG. 1A.
FIG. 1C is a schematic representation of a specific example of the example depicted in FIG. 1B.
FIG. 2A is a schematic representation of an embodiment of an electric generator of the system.
FIG. 2B is a schematic representation of an example of the embodiment depicted in FIG. 2A.
FIG. 3A is a schematic representation of an embodiment of a method for combined heat and electric power generation.
FIG. 3B is a schematic representation of an example of the embodiment depicted in FIG. 3A.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following description of the preferred embodiments of the invention is not intended to limit the invention to these preferred embodiments, but rather to enable any person skilled in the art to make and use this invention.
1. Overview.
A system 100 for combined heat and electric power generation preferably includes one or more electric generators 101 and a heat reservoir 130 (e.g., as shown in FIGS. 1A-1B). The electric generator 101 preferably includes a heat source 110 and an energy converter 120. The system 100 can optionally include an electrical storage module 140 and/or any other suitable elements. However, the system 100 can additionally or alternatively include any other suitable elements in any suitable configuration.
A method 200 for combined heat and electric power generation is preferably performed using the system 100, but can additionally or alternatively be performed using any other suitable systems. The method 200 preferably includes generating both heat and electric power (e.g., concurrently generating both heat and electric power), such as described below in more detail (e.g., regarding functionality of the system 100). However, the method 200 can additionally or alternatively include any other suitable elements performed in any suitable manner.
Embodiments of the system and/or method may confer one or more benefits. First, some embodiments may enable efficient implementations of combined heat and electric power generation at small power scales. Mechanical generators are typically far less efficient at smaller power scales, such as 200-1000 W or less, than they can be at larger power scales (e.g., many kW or more), but non-mechanical (or substantially non-mechanical) electric power generators, such as those described herein, can exhibit significantly higher efficiencies. Second, in some embodiments, the use of a heat reservoir can offer one or more synergies with elements of the electric power generator. For example, the heat reservoir can optionally function as a temperature control element for one or more elements of the electric power generator, such as a cesium reservoir of a thermionic energy converter. Third, in some embodiments, the heat rejection portion (e.g., the cold side) of the electric power generator described herein may be able to tolerate a wide range of temperatures without significant reduction in electric power generator efficiency. Accordingly, such an electric power generator may be especially well suited for thermal coupling to a variable-temperature heat reservoir such as described herein. However, the system and/or method can additionally or alternatively confer any other suitable benefits.
2. System.
2.1 Heat Reservoir.
The heat reservoir 130 preferably functions to store heat rejected by the electric generator 101, and/or to provide heat (e.g., as hot water, space heating, and/or for other residential, commercial, and/or industrial uses, etc.) when desired (e.g., desired by a user of the system). The heat reservoir 130 can include any suitable elements for accepting, retaining, and/or dispensing heat, preferably at slightly elevated temperatures compared to room temperature, such as 25-200° C. (e.g., 35-120° C., 20-60° C., 50-100° C., 45-80° C., 90-150° C., etc.), but additionally or alternatively at any other suitable temperature(s).
In one embodiment, the heat reservoir includes a hot water reservoir (e.g., as shown in FIG. 1). In this embodiment, the heat reservoir can be substantially analogous to a typical water heater (e.g., residential or commercial water heater), except that heating of the water is preferably achieved using heat received from the electric generator 101 (e.g., rather than using heat generated directly by a heating module of a typical water heater, such as one or more burners, electrical resistive elements, heat pumps, etc.). The reservoir preferably includes an inlet, which can accept unheated water (and/or water of any other suitable temperature) to refill the reservoir, and an outlet, which preferably provides heated water from the reservoir. The reservoir preferably defines a cavity (e.g., which receives water at the inlet and/or provides water at the outlet) configured to store water (e.g., heated water), more preferably wherein the reservoir includes thermal insulation configured to reduce heat loss from the stored water to the surrounding environment. The inlet and/or outlet can be connected to a building water system (e.g., inlet connected to a pressurized cold water source, and outlet acting as a pressurized hot water source, wherein the hot water pressure is preferably maintained by the pressurization of the cold water source), but can additionally or alternatively be configured in any other suitable manner.
The hot water reservoir temperature can be allowed to vary over a wide range. For example, the temperature can vary between a minimum temperature (e.g., a desired water delivery temperature or minimum acceptable water delivery temperature) and a maximum temperature (e.g., temperature limit set by practical considerations, such as to prevent localized boiling of water in the reservoir). In one example, the minimum temperature can be 30-60° C. (e.g., 45-55° C., such as 50° C., etc.) and the maximum temperature can be 80-100° C. (e.g., 90-95 or 95-100° C., etc.).
The reservoir temperature can vary and/or be controlled based on system operation criteria, such as demand for heat (e.g., hot water) delivery from the reservoir. To maximize system efficiency, the electric generator 101 is preferably substantially always active, if the heat demand allows. However, if the reservoir is at or near the maximum temperature, it may be inefficient and/or unsafe to allow the generator to reject heat to the reservoir. In such circumstances, the generator is preferably deactivated to avoid such inefficient/and or unsafe conditions. The electric generator 101 can have a duty cycle greater than a threshold amount (e.g., 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 40-50%, 50-60%, 60-75%, 75-85%, 85-95%, and/or 95-100%, etc.), preferably greater than 50%, but alternatively any other suitable duty cycle. The reservoir and/or electric generator are preferably configured (e.g., sized) appropriately to enable such a duty cycle (e.g., to maximize the duty cycle while avoiding or minimizing times at which the reservoir temperature is less than the minimum temperature). For example, based on typical demand (e.g., residential demand) for hot water and electric power, the electric generator may be sized such that it can provide 10-75% (e.g., 20-40%) of the total electric power demand (e.g., for a residence), but can alternatively have any other suitable size.
In one example, the system is controlled such that while the reservoir temperature is below a first threshold temperature, the electric generator 101 is activated (e.g., wherein fuel is burned at the heat source 110 and electricity is generated at the energy converter 120). Under such operation, the electric generator can gradually heat the reservoir using its rejected heat, thereby enabling efficient system operation. The first threshold temperature is preferably a temperature less than the maximum temperature, but can alternatively be equal to the maximum temperature, greater than the maximum temperature, or any other suitable temperature. The first threshold temperature can be defined based on the maximum (and/or minimum) temperature, such as less than the maximum temperature by an absolute amount (e.g., 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-1, 1-2, 2-5, 5-10, 10-20, and/or 20-50° C., etc.), by a relative amount (e.g., 0.1, 0.2, 0.5, 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-0.3, 0.3-1, 1-2, 2-5, 5-10, 10-20, and/or 20-30% of the maximum temperature; 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-1, 1-2, 2-5, 5-10, 10-20, and/or 20-50% of the difference between the minimum and maximum temperatures; etc.), and/or by any other suitable amount.
In this example, if the reservoir temperature reaches a second threshold temperature, the electric generator is preferably deactivated, thereby preventing overheating of the reservoir. The second threshold temperature is preferably a temperature greater than the first temperature, such as substantially equal to the maximum temperature or less than the maximum temperature by a smaller threshold amount (e.g., to allow for additional heat transfer after the generator is deactivated), but can alternatively be greater than the maximum temperature, less than the first threshold temperature, or any other suitable temperature. The second threshold temperature can be defined based on the maximum temperature and/or the first threshold temperature, such as less than the maximum temperature by an absolute amount (e.g., 0.2, 0.5, 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-1, 1-2, 2-5, 5-10, 10-20, and/or 20-50° C., etc.) or by a relative amount (e.g., 0.1, 0.2, 0.5, 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-0.3, 0.3-1, 1-2, 2-5, 5-10, 10-20, and/or 20-30% of the maximum temperature; 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-1, 1-2, 2-5, 5-10, 10-20, and/or 20-50% of the difference between the minimum and maximum temperatures; etc.), greater than the first threshold temperature by an absolute amount (e.g., 0.2, 0.5, 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-1, 1-2, 2-5, 5-10, 10-20, and/or 20-50° C., etc.) or by a relative amount (e.g., 0.1, 0.2, 0.5, 1, 2, 3, 5, 10, 15, 20, 25, 30, 0-0.3, 0.3-1, 1-2, 2-5, 5-10, 10-20, and/or 20-30% of the first threshold temperature; 5, 10, 15, 20, 25, 30, 40, 50, 65, 75, 85, 90, 95, 0-1, 1-2, 2-5, 5-10, 10-20, 20-35, 35-50, 50-70, 70-80, 80-90, and/or 90-100% of the difference between the first threshold temperature and the maximum temperature; etc.), and/or by any other suitable amount.
In this example, once the reservoir temperature drops back below the first threshold (e.g., due to heat output such as hot water use, due to heat losses, etc.), the electric generator is preferably reactivated such as described above (e.g., and then deactivated upon reaching the second threshold, and so on, continuing the cycle, such as shown by way of example in FIGS. 3A-3B). Accordingly in this embodiment, the duty cycle of the electric generator can be maximized, given the overall constraints of the system.
Additionally or alternatively, the electric generator may be controlled based on electricity demand, such as being activated to satisfy electricity demand (e.g., provide surge power within a facility, such as residence, in which the system is installed; provide surge power to the electric power grid; etc.), and/or based on other criteria, such as responding to external signals (e.g., electricity pricing signals, electricity demand signals, system control signals, etc.). In one example, the electric generator (and/or any other suitable elements of the system) may be controlled by and/or based on external signals, such as control signals received from a utility provider, utility regulator, government entity, and/or other controlling entity. However, the electric generator can additionally or alternatively be controlled in any other suitable manner.
Additionally or alternatively, the system may include one or more backup heat rejection elements, which can function to accept heat (e.g., from the electric generator), such as if the heat reservoir cannot (e.g., has reached and/or is projected to reach a threshold temperature such as the maximum temperature). For example, the electric generator can reject heat to the heat reservoir when the heat reservoir is in condition to accept the heat (e.g., analogous to the operation mode described above), but can also run, rejecting heat to the backup heat rejection element(s) at other times (e.g., at all times, under certain circumstances such as when electricity demand is high, etc.).
The heat reservoir can include a temperature control element (e.g., at the outlet), which can function to enable a more consistent heat output temperature (e.g., hot water temperature). For example, the temperature control element can mix heated water output from the reservoir with unheated water, thereby achieving a desired output temperature. In a specific example, the temperature control element includes a thermostatic valve that controls the mixing of the heated and unheated water such that a substantially constant output temperature is maintained.
In some embodiments, the heat reservoir can additionally or alternatively include heat storage materials other than water. For example, the heat reservoir can include one or more phase change materials (PCMs) (e.g., waxes, fatty acids, salt hydrates, etc.) configured to store and release heat (e.g., wherein heat is stored by melting the PCM, and can be released by solidification of the PCM). In examples, the additional storage material(s) (e.g., the PCM) can release heat to the heated water reservoir, and/or can release heat to directly satisfy external heat demands (e.g., to heat water to be delivered to a user as hot water, to provide space heating such as via radiative and/or forced air heating, etc.).
In a first embodiment, the additional storage material (e.g., the PCM) is thermally coupled (e.g., in direct contact with, arranged near such as separated by a thermally conductive element, coupled by a heat exchanger, etc.) to the hot water reservoir. For example, the additional storage material can be at substantially the same temperature as the water in the reservoir, and can function to increase the heat capacity of the heat reservoir. In examples, the heat received by the heat reservoir can be received primarily by the water (e.g., which can then heat the additional storage material), primarily by the additional storage material (e.g., which can then heat the water), or substantially received by both (e.g., received concurrently by both; received controllably by one or the other, such as received by the water reservoir or by both when the water is sufficiently below a threshold temperature such as the maximum temperature, and received only by the additional storage material otherwise; etc.).
In a second embodiment, the additional storage material (e.g., the PCM) may receive heat from the other elements of the system, and may reach (e.g., occasionally reach, be maintained at, etc.) substantially higher temperatures than the water (e.g., reaching temperatures higher than a maximum water temperature in the system, higher than a water boiling temperature such as 100° C., etc.), wherein the additional storage material can then provide heat to the water, such as by being thermally coupled to the water reservoir, by being operable to be thermally coupled to the water reservoir (e.g., by a controllable heat exchanger, which can be controlled to transfer heat to the water reservoir, such as only when heat is demanded and/or only when the water is below a threshold temperature, etc.). In a variation of this embodiment, the heat reservoir does not include a heated water reservoir. For example, the heat reservoir can be thermally coupled to a water supply line and can be configured to heat water as it flows through the supply line (e.g., heat water when flow is detected, such as flow above a threshold flow rate, and stop heating water when little or no flow is detected), such as in a manner analogous to an on-demand water heater. However, the additional storage material(s) can additionally or alternatively be included in the heat reservoir in any other suitable manner.
In some variations, the heat reservoir can include a backup heat source (e.g., burner, electrically resistive element, heat pump, etc.), which can function to directly heat the reservoir (e.g., not intermediated by the electric generator). In such variations, the backup heat source can be activated in response to demand for heating that exceeds the heat output of the electric generator (e.g., the electric generator is active and is rejecting heat into the heat reservoir, but the heat provided by the electric generator is insufficient to maintain an acceptable temperature within the heat reservoir and/or to provide heating at an acceptable temperature). For example, if the heat reservoir goes below (or is projected to go below, such as based on the present heat fluxes, based on projected heat demand, etc.) a third threshold temperature (e.g., minimum temperature, temperature within a threshold range of the minimum temperature, such as less than 1, 2, 5, 10, or 20° C. above or below the minimum temperature, etc.), the backup heat source can be activated (e.g., while keeping the electric generator on, activated instead of the electric generator, etc.). In this example, the backup heat source can remain on until the heat reservoir is sufficiently above the minimum temperature and/or the third threshold temperature (e.g., more than 1, 2, 5, 10, or 20° C. above the minimum temperature and/or the third threshold temperature), until the heating demand ceases or lessens (e.g., lessens to such an extent that the electric generator alone can provide sufficient heating for the heat reservoir), until determining that the electric generator alone is projected to be able to provide sufficient heating, and/or until any other suitable criteria are satisfied.
However, the heat reservoir 130 can additionally or alternatively include any other suitable elements in any suitable arrangement.
2.2 Electric Generator.
As described above, the electric generator 101 preferably includes a heat source 110 and an energy converter 120. The heat source 110 preferably functions to provide a heat input to the energy converter 120 (and/or to the heat reservoir 130).
The heat source is preferably a burner, more preferably a recuperating burner. However, the heat source can alternatively include any other suitable chemical energy input, radio thermal input, and/or any other heat input and/or other element operable to heat the energy converter. The heat source (e.g., burner) preferably delivers heat (e.g., heat of combustion) to the energy converter. The heat can be delivered radiatively, convective ly, conductive ly, and/or in any other suitable manner. For example, the heat source can produce a flame near and/or incident upon the energy converter.
The burner preferably includes an exhaust (e.g., condensing exhaust) configured to deliver additional heat to the energy converter and/or heat reservoir. For example, heat can be delivered at high temperature from both the burner and the exhaust to the energy converter, and additional heat can be delivered at lower temperature (e.g., from a condensing portion of the condensing exhaust) to the heat reservoir.
However, the heat source 110 can additionally or alternatively include any other suitable elements.
The heat source is preferably operable between two or more modes, which can include an active mode, in which the heat source consumes significant fuel (e.g., consumes fuel at more than a threshold rate, at substantially its maximum consumption rate, etc.) and/or generates significant heat, and an inactive mode, in which the heat source consumes substantially less fuel than in the active mode (e.g., consumes fuel at substantially less than the threshold rate, less than 1, 2, 5, 10, 20, or 50% of the threshold rate, etc.; consumes no or substantially no fuel, such as only consuming fuel to maintain a pilot light; etc.) and/or generates substantially less heat than in the active mode (e.g., generates substantially no heat, generates heat at less than a threshold amount of the rate at which it generates heat in the active mode, such as less than 1, 2, 5, 10, 20, or 50% of the rate, etc.). The heat source is preferably operated in the active mode when the energy converter is activated (e.g., wherein operating the heat source in the active mode causes activation of the energy converter), and is preferably operated in the inactive mode when the energy converter is not activated (e.g., wherein operating the heat source in the inactive mode causes deactivation of the energy converter), but can additionally or alternatively be operated in any other suitable manner, and/or can additionally or alternatively be operable in any other suitable modes.
The energy converter 120 preferably functions to convert a heat input (e.g., received from the heat source) into an electrical power output (e.g., provided to an external load 14) and to reject waste heat to the heat reservoir. The energy converter is preferably a solid state device, such as a thermionic energy converter (TEC), thermoelectric device, thermo photovoltaic device, and/or any other suitable solid state energy converter. In some variations, the energy converter can additionally or alternatively accept one or more chemical fuel inputs (e.g., to be converted into the electrical power output); for example, the energy converter can be (or include) one or more fuel cells. In some such variations (e.g., in which the converter accepts chemical fuel input and not heat input), the energy converter may not include a hot region and cold region as described below; rather, it may reject heat (e.g., heat resulting from and/or otherwise associated with conversion of chemical fuel potential energy into electric energy) into one or more heat rejection regions, which a person of skill in the art will recognize are preferably arranged in the system and/or are preferably used in a manner analogous to the cold region (e.g., wherein the heat rejection region is thermally coupled to the heat reservoir and provides heat to the heat reservoir). However, the system can additionally or alternatively include any other suitable type of energy converter.
The converter is preferably non-mechanical (e.g., having no or substantially no moving parts, having moving parts only in auxiliary elements such as heat rejection elements, etc.), but can alternatively be any other suitable converter. In some embodiments in which the converter includes a TEC, the TEC can include one or more elements such as described in U.S. patent application Ser. No. 16/715,705, filed 16 Dec. 2019 and titled “System and Method for Work Function Reduction and Thermionic Energy Conversion”, U.S. patent application Ser. No. 16/883,762, filed 26 May 2020 and titled “System and Method for Thermionic Energy Conversion”, and/or U.S. patent application Ser. No. 17/155,638, filed 22 Jan. 2021 and titled “Small Gap Device System and Method of Fabrication”, each of which is herein incorporated in its entirety by this reference (e.g., as shown in FIGS. 2A-2B).
In a first embodiment (e.g., designed for residential applications, such as single-family or small multi-unit dwellings), the energy converter can have a power scale (e.g., input power accepted or output electrical power generated) less than 1000 watts, preferably less than 500 watts (e.g., 10-50, 50-100, 100-200, 150-250, 250-350, and/or 350-500 W, etc.). In examples of this embodiment, the energy converter can include an active area on the order of single square inches (e.g., 1-10 square inches, such as 1-2, 2-5, or 5-10 square inches). In a second embodiment (e.g., designed for commercial, industrial, and/or large multi-unit residential applications), the energy converter may have a power scale greater than 1 kW (but alternatively less than 1 kW) and/or an active area greater than 10 square inches (but alternatively less than 10 square inches), preferably sized approximately proportional to the heating demand of the application (e.g., with similar proportionality as in the first embodiment described above). However, the converter can alternatively have any other suitable scale.
The energy converter 120 preferably defines a heat input region 121 (e.g., hot region) configured to accept a heat input from the heat source, and a heat rejection region 122 (e.g., cold region) configured to reject waste heat to the heat reservoir (e.g., as shown in FIG. 2B). For a TEC, the hot region is preferably the emitter (and/or a thermal coupling region that transfers heat to the emitter) and the cold region is preferably the collector (and/or a thermal coupling region that transfers heat from the collector). In some examples, these regions are substantially parallel planar regions (e.g., opposing each other across a thickness of the converter). In some examples, in which the TEC includes one or more elements such as described in U.S. patent application Ser. No. 16/883,762, filed 26 May 2020 and titled “System and Method for Thermionic Energy Conversion”, which is herein incorporated in its entirety by this reference (e.g., the TEC defines a cavity in which it receives heat), the hot region 121 can include one or more elements such as described in U.S. patent application Ser. No. 16/883,762 regarding the ‘emitter module 100’ (e.g., the ‘inner shell 120’), and/or the cold region 122 can include one or more elements such as described in U.S. patent application Ser. No. 16/883,762 regarding the ‘collector module 200’ (e.g., the ‘electron collector 210’ and/or the ‘cooling element 230’), such as wherein the ‘collector module 200’ rejects heat to the heat reservoir (e.g., in addition to or instead of rejecting heat to the ‘airflow module 13’). However, these regions can alternatively have any other suitable shape and/or arrangement.
The energy converter can output the generated electrical power to one or more electrical elements, such as electrical systems (e.g., building-scale electrical system, utility-scale electric grid, etc.), electrical storage modules 140, and/or any other suitable elements. Additionally or alternatively, a subset of (or all of) the generated electrical power can be used to power the system 100 (e.g., enabling system operation to continue during an electric grid outage). However, the generated electrical energy can additionally or alternatively be used in any other suitable manner.
The cold region 122 is preferably thermally coupled to the heat reservoir. This coupling is preferably a direct coupling (e.g., thermally conductive coupling, preferably via low thermal resistance elements). However, the thermal coupling can additionally or alternatively be intermediated by elements such as heat exchangers, coupling fluids (e.g., a forced air coupling), and/or any other suitable thermal couplings. In some examples, the thermal coupling may be configured to present a high thermal resistance between the cold region and the heat reservoir (e.g., to prevent localized boiling of the fluid in the heat reservoir, to aid more even heating of the heat reservoir, etc.). In some examples, the heat source exhaust can also reject heat to the reservoir. For example, the heat source exhaust can provide high-temperature heat output to the hot region 121, and provide and lower-temperature heat output (e.g., from a later heat exchange stage, such as a condensing stage) to the reservoir 130. However, the electric generator can additionally or alternatively deliver heat to the heat reservoir in any other suitable manner.
In some examples, the energy converter is a TEC that includes a cesium reservoir. In some such examples, the cesium reservoir is preferably maintained within a particular temperature range, such as a range between 140 and 400° C. (e.g., 140-180, 180-230, 200-250, 220-280, 230-270, 250-300, 260-320, and/or 320-400° C.). In such examples, the cesium reservoir can optionally be thermally coupled to the heat reservoir, wherein the heat reservoir can act as a thermal ballast which assists in maintaining the cesium reservoir within the desired temperature range (e.g., preventing the cesium reservoir from overheating). However, the cesium reservoir can additionally or alternatively be configured in any other suitable manner.
The energy converter 120 can additionally or alternatively include any other suitable elements in any suitable arrangement.
In some examples, the electric generator 101 can include one or more elements such as described in U.S. patent application Ser. No. 16/883,762, filed 26 May 2020 and titled “System and Method for Thermionic Energy Conversion”, which is herein incorporated in its entirety by this reference (e.g., the electric generator 101 can include the system of U.S. patent application Ser. No. 16/883,762, wherein the heat source 110 is such as described regarding the power input 12 of U.S. patent application Ser. No. 16/883,762, the energy converter 120 is such as described regarding the TEC 11 of U.S. patent application Ser. No. 16/883,762, and/or the electric generator 101 optionally includes one or more airflow modules 13 and/or other elements as described in U.S. patent application Ser. No. 16/883,762). In a specific example, the electric generator 101 includes a burner (e.g., recuperating burner) arranged within a heating cavity defined by a TEC, such as described in U.S. patent application Ser. No. 16/883,762 (e.g., as shown in FIG. 2B).
However, the electric generator 101 can additionally or alternatively include any other suitable elements in any suitable arrangement.
2.3 Electric Storage Module.
The system can optionally include one or more electric storage modules 140. The electric storage module can function to store energy received from the electric generator (e.g., for later use, such as for on-demand electric power). The electrical storage module 140 can include one or more batteries (preferably secondary batteries), capacitors (e.g., super capacitors), and/or any other suitable electrical storage elements. In some embodiments, the electric storage module can deliver electric power to satisfy demand (e.g., provide surge power within a facility, such as residence, in which the system is installed; provide power within a facility in which it is installed if the electric power grid is not currently delivering power; provide power to other elements of the system 100, such as providing power to start and/or operate the electric generator 101; provide surge power to the electric power grid; etc.) and/or respond to external signals (e.g., electricity pricing signals, system control signals, etc.). Additionally or alternatively, However, the electrical storage module can additionally or alternatively include any other suitable elements in any suitable arrangement, and/or can have any other suitable functionality.
2.4 Arrangements.
The system preferably includes one or more electric generators 101 thermally coupled to the heat reservoir 130. In some such examples, in which the heat reservoir includes a hot water tank, the electric generators can be arranged near the bottom of the hot water tank, such as at or near the base of an upright cylindrical tank (e.g., as shown in FIG. 1C).
The electric generators are preferably arranged spaced out from each other along one or more boundaries (e.g., faces) of the heat reservoir. For example, the electric generators can define a substantially planar array at the reservoir base. In one example, the system includes 4-12 (e.g., six) electric generators arranged in a ring (preferably with substantially equiangular spacing, such as about a central axis of the heat reservoir). In variations, the system can include multiple rings (e.g., concentric rings), each ring including the same or differing numbers of electric generators (e.g., inner rings with fewer electric generators and outer rings with greater numbers of electric generators, such as to establish substantially equidistant spacing between electric generators of all rings), and/or can include a single central electric generators at the center of a ring defined by some or all other electric generators. However, the electric generators can alternatively have any other suitable arrangement.
The heat reservoir 130 can include one or more thermally conductive elements, which may facilitate thermal coupling of the electric generators to the heat reservoir. These thermally conductive elements can function to distribute heat received from the electric generators over a larger portion of the reservoir (e.g., facilitate more even heating of the heat reservoir). For example, a heat reservoir with a hot water tank can include a high-conductivity interface between the tank base and the electric generators. Such an interface can function to deliver heat to the water more evenly across the entire base, rather than the more localized heating that could result from direct heat transfer from the electric generators to the water. The heat reservoir can optionally include one or more elements to promote more even heat distribution within the reservoir, such as convection elements configured to enable and/or promote mixing of water in a hot water tank. By promoting convection within the heat reservoir, these elements can help prevent localized over-heating (e.g., boiling) within the reservoir.
In some examples, each electric generator 101 has a separate exhaust system. The electric generator exhaust preferably provides additional heat to the hot region 121 of the generator (e.g., as described in U.S. patent application Ser. No. 16/883,762, filed 26 May 2020 and titled “System and Method for Thermionic Energy Conversion”, which is herein incorporated in its entirety by this reference), but alternatively may not provide additional heat to the hot region (or may only provide such heat indirectly). In some such examples, these multiple exhausts can be combined and/or brought close to each other wherein this combined exhaust can provide further heat rejection to the heat reservoir (e.g., wherein the combined exhaust runs through the reservoir, such as along a central axis of the reservoir).
However, the system can additionally or alternatively include any other suitable elements in any suitable arrangement.
3. Method.
As described above, the method 200 for combined heat and electric power generation is preferably performed using the system 100, but can additionally or alternatively be performed using any other suitable system. In some embodiments, the method 200 can include: activating an electric generator, deactivating the electric generator, and/or providing heat from a heat reservoir (e.g., as shown in FIG. 3A).
The electric generator is preferably activated such as described above regarding the system (e.g., based on one or more criteria, such as criteria associated with heat reservoir temperature and/or heat demand, etc.). When the electric generator is activated, the heat input preferably operates in the active mode, generating heat and providing some or all of the generated heat to the energy converter (e.g., TEC). In response to receiving this heat, the energy converter preferably generates an electric power output (which can be provided to an electric system, such as described above regarding the system), thereby generating waste heat (e.g., at a lower temperature than the heat it receives), which it preferably provides to the heat reservoir (e.g., thereby increasing the temperature of an energy storage material in the heat reservoir, such as a fluid stored within and/or flowing through the heat reservoir).
The electric generator is preferably deactivated such as described above regarding the system (e.g., based on one or more criteria, such as criteria associated with heat reservoir temperature and/or heat demand, etc.). When the electric generator is deactivated, the heat input preferably operates in the inactive mode (e.g., not providing significant heat to the energy converter). Accordingly, while the electric generator is deactivated, the energy converter will typically not generate significant electric power output and will typically not provide significant heat output to the heat reservoir.
Providing heat from the heat reservoir is preferably performed such as described above regarding the system (e.g, regarding the heat reservoir). In embodiments in which the heat reservoir includes a fluid heat storage material, the fluid can be heated (e.g., by heat received from the electric generator, by heat generated by a backup heat source, by heat received from other elements of the heat reservoir such as from other heat storage materials, etc.) while retained within the reservoir, while passing through the reservoir, and/or while outside the reservoir (e.g., while flowing past a heat exchanger of the reservoir). The heated fluid is preferably delivered to one or more heated fluid demand ers (e.g., provided upon and/or in response to demand for the heated fluid). For example, opening of a hot water valve (e.g., faucet) can cause water to flow (e.g., from the heat reservoir outlet) through the valve (e.g., out the faucet). In this example, additional water can flow into the reservoir via the inlet (and this additional water can then be heated, preferably in the same manner as described above). In an alternate variation, the fluid may flow in a loop (e.g., when a flow controlling valve is open, at all times, etc.), such as wherein the heated fluid exits the reservoir via the outlet, flows to a heat demander to which it transfers some of its heat (e.g., by flowing through a heat exchanger), and then flows back into the reservoir via the inlet. In examples, the heat demand ers (e.g., heated fluid demand ers) can include hot water outlets, space heating systems, other heat users such as described above regarding the system, and/or any other suitable elements.
The electric generator is preferably activated and deactivated such that it has a duty cycle (e.g., time activated divided by total time) greater than a threshold amount (e.g., 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 40-50%, 50-60%, 60-75%, 75-85%, 85-95%, and/or 95-100%, etc.), preferably greater than 50%, but alternatively any other suitable duty cycle (e.g., as described above regarding the system). In some examples, activation and/or deactivation is performed based on threshold temperatures and/or heat fluxes, wherein the thresholds can be predetermined, dynamically determined, constant, vary based on factors such as time of day, historical usage, and/or anticipated usage, and/or can be determined in any other suitable manner.
However, activating the electric generator, deactivating the electric generator, and/or providing heat from the heat reservoir can additionally or alternatively be performed in any other suitable manner. Further, the method 200 can additionally or alternatively include any other suitable elements performed in any suitable manner.
Although omitted for conciseness, the preferred embodiments include every combination and permutation of the various system components and the various method processes. Furthermore, various processes of the preferred method can be embodied and/or implemented at least in part as a machine configured to receive a computer-readable medium storing computer-readable instructions. The instructions are preferably executed by computer-executable components preferably integrated with the system. The computer-readable medium can be stored on any suitable computer readable media such as RAMs, ROMs, flash memory, EEPROMs, optical devices (CD or DVD), hard drives, floppy drives, or any suitable device. The computer-executable component is preferably a general or application specific processing subsystem, but any suitable dedicated hardware device or hardware/firmware combination device can additionally or alternatively execute the instructions.
The FIGURES illustrate the architecture, functionality and operation of possible implementations of systems, methods and computer program products according to preferred embodiments, example configurations, and variations thereof. In this regard, each block in the flowchart or block diagrams may represent a module, segment, step, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block can occur out of the order noted in the FIGURES. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
As a person skilled in the art will recognize from the previous detailed description and from the figures and claims, modifications and changes can be made to the preferred embodiments of the invention without departing from the scope of this invention defined in the following claims.
We claim:
1. A method for combined heat and electric power generation, comprising: at a heat reservoir, while a heat reservoir temperature of the heat reservoir is greater than a minimum temperature, heating a fluid; providing the heated fluid to an external heat demand element; while the heat reservoir temperature is less than a threshold temperature, activating an electric generator thermally coupled to the heat reservoir, wherein, while the electric generator is activated: a heat source of the electric generator generates heat and provides the heat to a solid-state energy converter of the electric generator; the solid-state energy converter generates an electric power output; and the solid-state energy converter rejects waste heat to the heat reservoir; after activating the electric generator, while the heat reservoir temperature is greater than the threshold temperature, deactivating the electric generator.
2. The method of claim 1, wherein the heated fluid is water.
3. The method of claim 2, wherein the external heat demand element comprises a domestic hot water faucet fluidly coupled to the heat reservoir by a hot water pipe, wherein providing the heated fluid to the external heat demand element is performed automatically in response to opening of the domestic hot water faucet.
4. The method of claim 2, wherein the threshold temperature is less than 100° C.
5. The method of claim 1, further comprising determining that the heat reservoir temperature is less than the threshold temperature, wherein activating the electric generator is performed in response to determining that the heat reservoir temperature is less than the threshold temperature.
6. The method of claim 5, further comprising, while the electric generator is active, determining that the heat reservoir temperature is greater than a second threshold temperature greater than the threshold temperature, wherein deactivating the electric generator is performed in response to determining that the heat reservoir temperature is greater than the second threshold temperature.
7. The method of claim 1, wherein a duty cycle of the electric generator, defined as a ratio between time in which the electric generator is active to total time, is greater than 30%.
8. The method of claim 7, wherein the duty cycle is greater than 60%.
9. The method of claim 1, wherein the heat source comprises a burner that, while the electric generator is activated, generates the heat by combusting fuel.
10. The method of claim 9, wherein, while combusting fuel, the burner generates an exhaust, wherein the exhaust transfers heat to the heat reservoir.
11. The method of claim 1, wherein the solid-state energy converter comprises a thermionic energy converter.
12. A system for combined heat and electric power generation, comprising: a heat generator operable between: an active mode, in which the heat generator consumes fuel at greater than a threshold rate and generates heat; and an inactive mode, in which the heat generator consumes fuel at substantially less than the threshold rate; a solid-state electric generator comprising a heat input region and a heat rejection region, the heat input region thermally coupled to the heat generator; and a heated water reservoir thermally coupled to the heat rejection region of the solid-state electric generator, the heated water reservoir defining a cavity configured to store heated water, the cavity defining a water input and a heated water output; wherein the solid-state electric generator is configured to: accept heat from the heat generator at the heat input region; generate an electric power output; and provide waste heat to the heated water reservoir at the heat rejection region.
13. The system of claim 12, further comprising a thermostatic mixing valve configured to receive heated water at a varying heated water temperature from the heated water output, receive water at a temperature lower than the varying heated water temperature, and mix the water and heated water to produce intermediate-temperature water of a substantially fixed temperature.
14. The system of claim 12, wherein the solid-state electric generator comprises a thermionic energy converter (TEC).
15. The system of claim 14, wherein: the TEC defines a cavity, wherein the heat input region bounds the cavity and the heat rejection region opposes the cavity across the heat input region; and the heat generator comprises a burner arranged within the cavity, wherein, in the active mode, the burner generates the heat by combusting the fuel.
16. The system of claim 15, wherein: the solid-state electric generator further comprises a second TEC defining a second cavity; the heat generator further comprises a second burner arranged within the second cavity; and the system further comprises an exhaust manifold, the exhaust manifold comprising: a merged exhaust tube extending through and thermally coupled to the heated water reservoir; a first exhaust tube extending from the burner to the merged exhaust tube; and a second exhaust tube extending from the second burner to the merged exhaust tube.
17. The system of claim 12, wherein the heat generator comprises a burner arranged within the cavity, wherein, in the active mode, the burner generates the heat by combusting the fuel.
18. The system of claim 17, wherein the burner is a recuperating burner.
19. The system of claim 17, wherein: the burner comprises an exhaust manifold extending from the burner through the cavity of the heated water reservoir; and while combusting the fuel, the burner generates an exhaust, wherein the exhaust transfers heat to the heated water reservoir via the exhaust manifold.
20. The system of claim 19, wherein: the solid-state electric generator comprises a plurality of generator modules; the heat generator comprises a set of burners, the set of burners comprising the burner, wherein each burner of the set is associated with a respective generator module of the plurality; and each burner of the set comprises a respective exhaust tube of the exhaust manifold.
|
---
title: Start annotation
type: guide
order: 102
---
## Quickstart
To start annotating your data, you have to
- [Import your data](/guide/tasks.html)
- Select any of predefined annotation _project_ template on **Setup** page.
<div style="margin:auto; text-align:center; width:100%"><img src="/images/setup-page.png"/></div>
For more advanced configuration, please address to [this section](#Labeling-config).
## Command line arguments
Label Studio app is a highly configurable engine for any of your annotation ideas. Most of the configuration part you can carry on web UI, but sometimes it becomes easier to set up something once on the launch.
To look over all possible parameters you can specify on Label Studio launch, run:
```bash
label-studio start --help
```
## Labeling interface
Let's explore the complex example of multi-task labeling which includes text + image + audio data objects:
<br>
<img src="/images/labeling.png">
* Labeling interface is implemented using JavaScript + React and placed to separated repository [Label Studio Frontend](https://github.com/heartexlabs/label-studio-frontend). Label Studio has integrated Label Studio Frontend build.
* Labeling interface is highly configurable: you can enable or disable some parts of it (completions panel, predictions panel, results panel, controls, submit & skip buttons).
### Instructions
Most of the actions described in this section are similar for all the data objects (images, audio, text, etc.).
### Choices, TextArea and other simple tags
Such tags have straightforward labeling mechanics. It’s intuitive for users, so let’s talk about more complex things below.
### Add region
1. Select label you want to add (if you use Tag without labels like Polygon, just go to 2)
2. Click on your data object (image, audio, text, etc)
### Change label
You can change the label of the existing region:
1. Select entity (span, bounding box, image segment, audio region, etc)
2. Select a new label
### Delete entity
1. Select entity
2. Press Backspace or go to Results panel and remove selected item
### Add relation
You can create relations between two results with
* direction
* and labels ([read more about relations with labels](/tags/relations.html))
<br>
<img src="/images/screens/relations.png">
1. Select a first region (bounding box, text span, etc)
2. Click on "Create Relation" button
3. Select the second region
4. **Optionally**: After the relation is created you can change the direction by click on the direction button
4. **Optionally**: [If you've configured labels](/tags/relations.html), click on the triple dots button and add your predefined labels
### Hotkeys
Use hotkeys to improve your labeling performance. Hotkeys help is available in the labeling settings dialog.
<table>
<tr><th>Key</th><th>Description</th></tr>
<tr><td>ctrl+enter</td><td>Submit a task</td></tr>
<tr><td>ctrl+backspace</td><td>Delete all regions</td></tr>
<tr><td>escape</td><td>Exit relation mode</td></tr>
<tr><td>backspace</td><td>Delete selected region</td></tr>
<tr><td>alt+shift+$n</td><td>Select a region</td></tr>
</table>
## Project structure
**Project** is a directory where all annotation assets are located. It is a self-contained entity: when you start Label Studio for the first time e.g. `label-studio start ./my_project --init`,
it creates a directory `./my_project` from where its launched.
If you want to start another project, just remove `./my_project` directory, or create a new one by running `label-studio start /path/to/new/project --init`.
**Project directory** is structured as follows:
```bash
├── my_project
│ ├── config.json // project settings
│ ├── tasks.json // all imported tasks in a dict like {task_id: task}
│ ├── config.xml // current project labeling config
│ ├── completions // directory with one completion per task_id stored in one file
│ │ ├── <task_id>.json
│ ├── export // stores archives with all results exported form web UI
│ │ ├── 2020-03-06-15-23-47.zip
```
> Warning: It is not recommended to modify any of the internal project files. For importing tasks, exporting completions or changing label config please use web UI or command line arguments (see `label-studio start --help` for details)
## Labeling config
Project labeling config is an XML file that consists of:
- **object tags** specifying input data sources from imported tasks,
- **control tags** for configuring labeling schema (how annotation result looks like),
- **visual tags** applying different user interface styles.
<a class="button" href="/tags">Check Available Tags</a>
#### Example
Here an example config for classifying images provided by `image_url` key into two classes:
```html
<View>
<Image name="image_object" value="$image_url"/>
<Choices name="image_classes" toName="image_object">
<Choice value="Cat"/>
<Choice value="Dog"/>
</Choices>
</View>
```
### Setup labeling config from file
It is possible to initialize a new project with predefined `config.xml`:
```bash
label-studio my_new_project start --init --label-config config.xml
```
### Setup labeling config from UI
You can also use the web interface at [`/setup`](http://localhost:8080/setup) to paste your labeling config. Using web UI you also get a live update while you're editting the config.
## Sampling
You can define the way of how your imported tasks are exposed to annotators. Several options are available. To enable one of them, specify `--sampling=<option>` as command line option.
#### sequential
Tasks are ordered ascending by their `"id"` fields. This is default mode.
#### uniform
Tasks are sampled with equal probabilities.
#### prediction-score-min
Task with minimum average prediction score is taken. When this option is set, `task["predictions"]` list should be presented along with `"score"` field within each prediction.
#### prediction-score-max
Task with maximum average prediction score is taken. When this option is set, `task["predictions"]` list should be presented along with `"score"` field within each prediction.
### Setup labeling config from API
You can configure your labeling config via server API. Check [Backend API page](api.html) for more details.
|
DELIMITER $$
CREATE PROCEDURE usp_get_holders_full_name()
BEGIN
SELECT
CONCAT(a.first_name, ' ', a.last_name) AS 'full_name'
FROM account_holders AS a
ORDER BY
full_name ASC,
a.id ASC;
END $$
DELIMITER ;
CALL usp_get_holders_full_name();
|
import React from "react";
let emptyState = {
name: '',
budget: '',
}
class CategoryForm extends React.Component {
constructor(props){
super(props);
this.state = this.props.category ? this.props.category : emptyState;
let memberFunctions = Object.getOwnPropertyNames(CategoryForm.prototype);
for(let functionName of memberFunctions){
if(functionName.startsWith('handle')){
this[functionName] = this[functionName].bind(this);
}
}
}
//--------------------------------------------------
// Member Functions
//--------------------------------------------------
handleChange(event) {
let{name, value} = event.target;
this.setState({
[name] : value
});
}
handleSubmit(event) {
event.preventDefault();
this.props.onComplete(this.state);
this.setState(emptyState);
}
//--------------------------------------------------
// Hooks
//--------------------------------------------------
componentWillReceiveProps(nextProps) {
if(nextProps.category)
this.setState(nextProps.category);
}
//--------------------------------------------------
// Render
//--------------------------------------------------
render() {
let buttonText = this.props.category ? 'update category' : 'create category';
return (
<form onSubmit={this.handleSubmit} className="category-form">
<input
type="text"
name="name"
placeholder="category name"
value={this.state.name}
onChange={this.handleChange}
/>
<input
type="number"
name="budget"
placeholder="$ 0"
value={this.state.budget}
onChange={this.handleChange}
/>
<button type="submit"> {buttonText} </button>
</form>
);
}
}
export default CategoryForm;
|
Standing Committee C
[Mr. Frank Cook in the Chair]
Private Hire Vehicles (Carriage of Guide Dogs etc.) Bill
Frank Cook: Before we begin our formalities, I have an announcement about clause 5.
When the Bill was introduced, the House authorities considered that expenditure would arise from the provisions of the Bill, thus requiring a money resolution. An expenses clause was consequently included in the measure as clause 5.
Since Second Reading there have been further discussions, including some with the Department that will have to implement the Bill. It is now considered that any expenditure that arises will be minimal, so a money resolution is no longer needed. Clause 5 is therefore redundant and should be left out of the Bill. As a consequence, when we reach clause 5, I shall put the question on clause stand part forthwith with the intention that it should be negatived.
Clause 1 - Carrying of guide dogs, hearing dogs and other assistance dogs
Neil Gerrard: I beg to move amendment No. 1, in page 1, line 4, leave out from beginning to end of line 19 and insert—
'37A Carrying of assistance dogs in private hire vehicles
(1) It is an offence for the operator of a private hire vehicle to fail or refuse to accept a booking for a private hire vehicle—
(a) if the booking is requested by or on behalf of a disabled person, or a person who wishes a disabled person to accompany him; and
(b) the reason for the failure or refusal is that the disabled person will be accompanied by his assistance dog.
(2) It is an offence for the operator of a private hire vehicle to make an additional charge for carrying an assistance dog which is accompanying a disabled person.
(3) It is an offence for the driver of a private hire vehicle to fail or refuse to carry out a booking accepted by the operator of the vehicle—
(a) if the booking was made by or on behalf of a disabled person, or a person who wishes a disabled person to accompany him; and
(b) the reason for the failure or refusal is that the disabled person is accompanied by his assistance dog.
(4) A person who is guilty of an offence under this section is liable on summary conviction to a fine not exceeding level 3 on the standard scale.'.
Frank Cook: With this it will be convenient to take the following: New Clause 1—Carrying of guide dogs, hearing dogs and other assistance dogs: Scotland—
'In section 20 of the Civic Government (Scotland) Act 1982 (c. 45) (regulations relating to taxis and private hire cars and their drivers) the following subsection is inserted after subsection (2A)—
''(2AA) The Scottish Ministers may by regulations make such provision as appears to them to be necessary or expedient in relation to the carrying in private hire cars of disabled persons (within the meaning of section 1 (2) of the Disability Discrimination Act 1995 (c. 50)) and such provision may in particular prescribe—
(a) requirements as to the carriage of guide dogs, hearing dogs and other categories of dogs;
(b) a date from which any such provision is to apply and the extent to which it is to apply; and
(c) the circumstances in which an exemption from such provision may be granted in respect of any private hire car or private hire car driver, and in this subsection ''guide dog'', ''hearing dog'' and ''other categories of dog'' have the same meaning as in subsection (2A) above.
(2AB) Regulations under subsection (2AA) above shall be made by statutory instrument subject to annulment in pursuance of a resolution of the Scottish Parliament.''.'.
Neil Gerrard: I welcome you to the Chair, Mr. Cook. I hope that we shall have a productive and not too onerous morning considering the amendments. I thank my colleagues who have given up their time to take part in the Committee. Although we shall not deal with contentious issues, it is important for the Committee to meet and to consider and agree to the amendments.
Clause 1 is the most important part of the Bill and amendment No. 1 is the major issue that we shall consider this morning. The Bill will amend the Disability Discrimination Act 1995, which places a duty on the drivers of licensed taxis to take guide dogs and other assistance dogs and not to make an extra charge for doing so. Nothing was done about private hire vehicles in the 1995 Act and the clause will extend the provisions of that Act to private hire vehicles. I shall not go through the principles behind it; the key point is that people who have assistance dogs rely on private hire vehicles more than most of us, for the obvious convenience of having door-to-door transport.
Private hire vehicles are already licensed in some parts of the country through local authorities, many of which include in their licensing requirements a statement that guide dogs and other assistance dogs should be carried, but the provision is patchy. The intention is therefore to ensure that it is consistent throughout the country. There is an anomaly in London, where there is no licensing for drivers at present, although I hope that there will be in the near future.
In the Bill as drafted, clause 1 essentially copied the provisions in the Disability Discrimination Act 1995 for licensed taxis and applied them to private hire vehicles. To make that work properly, however, we must recognise that the hiring of private hire vehicles works differently from the hiring of taxis. A taxi is generally hired on the street, with the person hailing it and the taxi taking the fare. If the taxi refused to take a fare that involved a guide dog, the driver would be committing an offence. The contract is between the person taking the taxi and the driver; no other person is involved.
The situation is different for private hire vehicles, which cannot be legally hailed on the street, and which are generally booked through an operator. Someone
rings the operator, books the private hire vehicle and waits for the operator to send out a driver. Two people are involved in providing the service, and amendment No. 1 will cover both. Subsection (1) of the proposed new section will make it an offence for the operator to refuse to accept the booking if it is requested for a disabled person and the reason for the failure or refusal is the assistance dog accompanying the person. We cannot force operators to accept bookings, as there may be other reasons for refusing the booking. For example, they may not be prepared to send a driver that distance. However, an operator cannot refuse a booking because an assistance dog is involved.
Subsection (2) of the proposed new section is identical to one of the subsections in the original draft and will make it an offence to make an additional charge for carrying a dog, and subsection (3) will make it an offence for the driver to refuse to carry out the booking once the operator has accepted it. Both operator and driver are covered, which is necessary given the mechanisms in place for private hire vehicles. That is the reason for the major amendment to the original draft—to ensure that we cover both the operator and the driver involved in the contract, not just the driver.
I shall refer briefly to new clause 1. It will allow the Bill to be extended to Scotland. To do that, we had to consider our relationship with the Scottish Parliament and its powers. Since Second Reading, approaches have been made from the Scottish Parliament and Ministers to make it clear that they want to be able to extend the Bill's provisions to Scotland, and new clause 1 will allow Scottish Ministers to introduce a statutory instrument to do that. The Bill will then cover England, Wales and Scotland, although that still leaves a gap: Northern Ireland. Interest has been expressed from Northern Ireland, but it has not been possible to get the necessary technical agreement from the Northern Ireland Assembly to allow us to introduce an amendment. I hope that we shall be able to do that on Report. By then, the necessary resolution should have been passed by the Northern Ireland Assembly, and amendments covering Northern Ireland should have been tabled.
That is the reasoning behind the first group of amendments, which constitute the major change. Many of the amendments that we shall come to later are relatively technical and tidy up the legislation. The key change is to ensure that both operator and driver are covered—not just the driver, as would have been the case with the original draft of the Bill.
Tim Boswell: May I echo the sentiments that have been expressed about enjoying serving under your chairmanship, Mr. Cook? It is always a constructive experience, and I hope that it will be a reasonably brisk one, as usual.
I should like to place on the record my gratitude to the hon. Member for Walthamstow (Mr. Gerrard), who introduced the Bill. It is good in principle and, like the amendment, has been presented in a characteristically exemplary and clear fashion. The hon. Gentleman supplied additional material and has obviously had a constructive working relationship
with the Department. That is the right way to proceed, because we all have to understand that, with private Members' legislation, the aspiration is one thing, the delivery another. Delivery is terribly important, although the wider principle is the greater one.
I have a general point to raise about disability issues. A number of hon. Members, particularly on the Government Benches, have been very much involved, as I have, in the all-party disability group. My experience in this place is that, on disability issues, it is quite difficult to put any significant distance between members of individual parties. Our only worry is that not all our colleagues from all parties take the same interest in the issue as we do—but enough of self-congratulation. This is a very sensible Bill, and we shall approach it in that spirit.
I hope that the hon. Gentleman will understand that, if I raise any queries, I do so not as some sort of pettifogging exercise, but in an attempt to get the legislation absolutely right, within a framework that we find perfectly acceptable. I have only two or three comments to make on what he has rightly said is the substantive clutch of amendments.
I think that my first point solves itself, but it would be useful to consider it for a moment. It concerns what might be termed ''mixed motives'' in turning down a booking. An example—not a particularly happy one, in view of recent discussions—is the primary purpose rule for immigration. An operator or driver might have more than one motive. To put it more seriously, if a case went to court, there could be a rather messy evidential argument about whether the main motive for turning down a booking was the presence of a guide dog.
To put it another way, if someone was maliciously inclined and happy to cock a snook at the legislation, they might try to find a pretext for turning down a booking. They might have done so because they did not like the dog, but they might say that they had gone over their hours, they were out of their normal range or whatever. One assumes that, if push ever came to shove and there were proceedings in court, the matter would be sorted out perfectly well and the extent of the bearing of the different motives would be explored. However, it is worth at least pausing to consider whether the expression used is correct. I say that not as a lawyer but as someone who is always anxious that we get legislation right.
My second concern relates to the respective duties of the operator and the driver, which the hon. Gentleman has properly set out. I consider that they mesh perfectly, because they are parallel duties. The operator is told that he cannot turn down a booking on the grounds of disability, and the driver is told the same. I do not think that it is necessary to have anything securing that in the driver's contract of employment or engagement with the operator, because certain compliances with the law are implicit in any such arrangement. A driver who signs a contract with the operator is required to comply with road traffic laws and not to exceed speed limits. I am unsure whether the difficulty needs to be tied up explicitly.
I come now to a more substantive concern. I am sure that the hon. Gentleman is right to tie the provisions to the operator in the first instance because of the booking system, which represents the interface with the customer. It will be a nice legal matter, but the contract with the customer resides with the operator—not the driver—whose responsibility it is to provide a transport service from A to B.
It is not clear in amendment No. 1 whether anything about the disability has to be disclosed in the initial booking conversation. Two circumstances are possible. In the first, the disabled person might say that he requires an assistance dog to travel with him, leaving the operator in no doubt. If the operator then told the client to get stuffed, it would be a clear breach of the proposed law. Alternatively, it might simply be assumed with nothing expressly said about it, in which case the operator might find himself in difficulty.
The biggest difficulty applies to circumstances where the operator is a single-vehicle operation. For perfectly good reasons, the vehicle might be subject to an exemption certificate. It is unlikely to happen—most private hire firms are not like that—but it is not impossible. An owner-driver could take the message on the phone. If the operator has to take a booking and cannot turn it down on the grounds of a person's disablement or requirement of a dog's assistance, but has no vehicle available to discharge the service, will it cause a difficulty that amounts to an unreasonable burden? The driver might turn up at the person's home and say, ''Good Lord, I didn't know that you had a dog with you''; no other vehicle might be available. In those circumstances, would the operator be obliged to secure another vehicle, perhaps through hire, or would the obligation have been discharged by virtue of the operator's not discriminating against the person?
The legislation is all about discrimination and about motive. We want to stop private hire firms and their drivers using a person's need for an assistance dog to turn down a booking. That is not in doubt. I am worried, however, that we could create difficulties for an operator who, with the best of motives, genuinely cannot meet the requirements.
Hugo Swire: In support of my hon. Friend, I would argue that the onus should fall on the person booking the vehicle to declare the need for a dog's assistance. The driver turning up for the journey might have an allergy and be unable to stay in the same vehicle as the animal. In those circumstances, he could legitimately refuse to accept the fare.
Tim Boswell: My hon. Friend assists the Committee in making that point. No one is trying to overturn the substance of the legislation, which is to stop wilful discrimination against disabled people who need the assistance of a dog. That is not at issue. I hope, however, that the hon. Member for Walthamstow will reflect on the spirit of what my hon. Friend and I have said and try to ensure that an operator does not stumble into a position that had not been anticipated and for which no easy recourse is available. I am not asking for a categorical answer now, but I hope that he
will reflect further and ensure that the duties are fair. There is an implied duty on the client to declare their need for assistance up front if they are reasonably to expect that it will be available when they need it.
Tom Clarke: I take it that this is the appropriate time to discuss new clause 1.
Frank Cook: Indeed.
Tom Clarke: Thank you, Mr. Cook. I join my hon. Friend the Member for Walthamstow and the hon. Member for Daventry (Mr. Boswell) in welcoming you to the Chair. Given our visit to North Korea some time ago, I may refer to you as ''our great Chairman'' or ''our dear leader''.
In common with my colleagues, I am delighted with the progress that my hon. Friend the Member for Walthamstow has made with this excellent Bill, and with the time that he has taken to consult everyone affected by its implications. As one of its sponsors, I thought that Scotland would be included at some point. Following the discussions that my hon. Friend mentioned, I am delighted that it will be included as a result of the new clause.
My brief questions are technical, and if my hon. Friend the Minister does not have the answers today, perhaps he will be willing to write to members of the Committee. Can we assume that our colleagues in the Scottish Executive, who represent the Scottish Parliament, supported the measure, and were 100 per cent. in favour of including Scotland? I very much hope that they were.
Proposed subsection (2AB) states:
''Regulations under subsection (2AA) above shall be made by statutory instrument subject to annulment in pursuance of a resolution of the Scottish Parliament.''
Have the Scottish Executive expressed any views yet? Does the reference to annulment mean annulment of the statutory instrument put before the Scottish Parliament, or the right later to repeal a statutory instrument that has already been approved? I hope that the Minister will be able to see the distinction. If not, perhaps the advice given to him will clarify it. It would be welcome if ''annulment'' means what I think it means: that a statutory instrument put before the Scottish Parliament will be approved and will therefore apply to Scotland. As my hon. Friend the Member for Walthamstow said during consideration of the Disability Discrimination Act 1995, in which my hon. Friend the Member for Kingswood (Mr. Berry) was also involved, this is an evolutionary measure that would develop, and is another indication of the improvements that we can make in partnership with the Scottish Parliament.
I hope that my technical questions were not too difficult; if they were, perhaps the letter will serve to satisfy me in due course.
Sandra Gidley: I congratulate the hon. Member for Walthamstow on bringing the Bill to this stage. I fully support its aims and wish him every success with it. However, it needs to be as watertight as possible. The hon. Gentleman obviously appreciates
that, as he has tabled amendments. The hon. Member for Daventry has got me thinking. I hope that he will not think me pedantic, but I have been trying to think of different scenarios and how they may or may not be covered by the Bill's provisions. One scenario concerned me slightly. I should like to share it with the Committee to see whether there is a problem, and if so, how we can get round it.
Some local education authorities hire vehicles to transport young people to school or college. Presumably the Bill would cover those vehicles. Small private hire firms are often used. A driver can say no if he has an exemption certificate, but what would happen if another passenger who had an allergy to dogs was included in the contract? Would that be a basis for refusing the contract? I have only just thought of that point. It is a possible, if unlikely, scenario and it would be useful to cover it.
David Jamieson: May I say how pleased I am to be sitting under your careful and watchful eye, Mr. Cook? I am particularly pleased to be able to support my hon. Friend the Member for Walthamstow to ensure that his Bill can deliver its desired aims. It is a pleasure to be here not just with my hon. Friend but with other right hon. and hon. Friends who have long fought on disability issues.
My right hon. Friend the Member for Coatbridge and Chryston (Mr. Clarke) has a distinguished record in this area. My hon. Friend the Member for Kingswood and I shared an office many years ago. He had a private Member's Bill, which, alas, was unsuccessful, and I had one the following year, on an entirely different issue, which was successful, so I know how difficult it is to pilot private Member's legislation through the House. Again, I congratulate my hon. Friend the Member for Walthamstow on his work. My hon. Friends the Members for Leyton and Wanstead (Harry Cohen), for Halifax (Mrs. Mahon), for Bristol, North-West (Dr. Naysmith) and for St. Helens, North (Mr. Watts) have a keen interest in this subject, and, if I can spare his blushes, I know that the hon. Member for Daventry has followed these matters with interest for many years.
Much was said on Second Reading about the difference that assistance dogs can make to the lives of so many disabled people. Being unable to use local transport services with their dogs, a companion whom many describe as a lifeline, must create problems for many disabled people. One correspondent who wrote to the Department said:
''Imagine how you would feel if you couldn't get a minicab when you needed one, particularly if you cannot drive a car. Imagine how it feels to be told you are not allowed into a club, restaurant, pub, theatre or a shop purely because you rely on a guide dog to help you around. These problems affect guide dog owners every day.''
Imagining is all that many of us can do, but for many disabled people it is a daily experience. I am delighted to see that this piece of legislation will help to plug a small but important gap in what people would see as discrimination.
In some parts of the country the situation with private hire vehicles has changed in response to the campaigns orchestrated by the Guide Dogs for the Blind Association and the Royal National Institute for the Blind. Many local licensing authorities have already introduced their own requirements under existing legislation for drivers of private hire vehicles to carry assistance dogs, but unfortunately that has not given us the national coverage that we so much want. The Bill ensures that the provision is uniform throughout the country. Disabled people who use assistance dogs are uncertain about the policy when they move from one area to another. I am therefore particularly pleased to be associated with this Bill, which will tackle that aspect of discrimination against disabled people and give them the confidence to travel around the country.
The amendments in this group bring the Bill into line with private hire legislation, which, strange as it may seem to the man in the street, is significantly different from that applying to licensed taxis. The role of the operator is, perhaps, the most significant difference. With taxis, a hiring is made directly between a passenger and a driver, but with licensed private hire vehicles it is, of course, the operator who accepts the booking. It was therefore important to ensure that there would be duties relating to an operator to ensure that they did not turn down a booking purely on the grounds that an assistance dog would accompany the passenger, and the amendments address that particular concern.
My right hon. Friend the Member for Coatbridge and Chryston asked about the important Scottish aspect of the Bill. He asked whether the Scots were 100 per cent. in favour of it, and I understand that they certainly were. There is a technicality here, which he probably understands better than I. I believe that the Sewel motion has not yet been approved by the Scottish Parliament.
Mr. Clarke indicated assent.
David Jamieson: My right hon. Friend is nodding—no one else in the Committee is doing so—because he clearly understands the Sewel motion. Perhaps he will explain it to me, sometime. However, the Bill will be enacted in the Scottish Parliament.
Tom Clarke: My hon. Friend is explaining clearly exactly what is going on, and I am grateful to him for doing so. The Sewel motion relates to Lord Sewel, who, as a Minister at the Scottish Office, was involved in drawing up the Scotland Act 1998. In due course, he worked with the Scottish Executive. What my hon. Friend has said so far certainly pleases me, and I am delighted by the news that he has given me.
David Jamieson: I am glad that my news has been good news to my right hon. Friend. I am also glad that he has explained the Sewel motion to me and the rest of the Committee. It was indeed the intention that the
Bill be enacted in Scotland as well. It would have created some disappointment in the House had that not been so.
I know that both Government and Opposition Members and, in particular, disability organisations welcome the legislation. I therefore hope that the Committee will accept the amendments in order to deliver the benefits for disabled people that we all want.
Neil Gerrard: I thank my colleagues for their contributions. The hon. Member for Daventry raised a number of important points. We want to ensure that the Bill is right and that things work properly, and I understand his motives for raising those points.
One difficulty is that we are dealing with a complex relationship. There is a passenger with a dog, an operator and a driver, and there are various forms of licensing involving operators, drivers and cars. It is a complex mixture to try to work through and it is difficult to find a phrase that will cover every single possible scenario that one might think of.
The hon. Gentleman raised the question of mixed motives. It would be difficult for a driver to make a false excuse. Once an operator had taken a booking and passed it to a driver by saying, ''Go to this address and pick this person up,'' and the driver had agreed, it would be a fairly flimsy excuse if the driver then told the passenger, ''I am not taking you'' and refused to carry a dog. It would not be difficult for a court to see through such an excuse if the matter were pursued.
The Bill is anti-discrimination legislation. We are saying that a driver or operator will be in trouble if they do not take from a person with a guide dog a booking that they would otherwise have taken. One can always envisage circumstances in any dispute or court case where establishing motives is not simple, but courts are used to taking such decisions.
In many cases, drivers do not have a contract of employment with operators. Certainly in London, which I am familiar with, many of the drivers are virtually self-employed. In some cases, if they have a contract with the operator, they pay the operator to provide them with work, which is a rather odd form of contract. When the driver is licensed, there is the possibility that, in addition to court action, the licensing authority may take a dim view of the driver not abiding by the conditions of the licence. In the case of exemption certificates, it is the driver who will have such a certificate, not the vehicle.
With regard to the information that a person should give when making a booking, it is difficult to see how one could in the legislation impose a duty to disclose on the person making the booking. One would have thought that it would be common sense for someone to do so when making a booking. If we pass the legislation, no doubt the Guide Dogs for the Blind Association and other organisations dealing with assistance dogs will want to tell their members that the legislation is in place and ensure that they are aware of it.
Hugo Swire: I am grateful to the hon. Gentleman for addressing those points. However, does he accept that, because many of the vehicles are privately owned cars, drivers should have some warning that they are going to pick up a dog? They could then make the necessary arrangements by putting down some protection for what may, when they clock off work, revert to their family car. I should also like the hon. Gentleman to address the question of compensation. I fully accept that the firm has no right to charge more for taking an animal, but what happens—as it must from time to time—if a dog soils, or in some way damages, the car? Is that something that could be addressed?
Neil Gerrard: I am sure that we could all be in that situation if we took a dog in a car, but it is difficult to see how one would deal with compensation.
It would make sense, and associations would encourage their members to make it clear, for people to know when they are taking a booking that a dog is to be carried. There will also be a process of education, and drivers getting used to the idea of taking dogs. We should remember that that is already happening in a fair number of local authorities. We are not introducing provisions that are completely new, but bringing consistency throughout the country. I am not aware of any real problems that have arisen in the local authorities where the licensing requirement is already in place. Operators, drivers and passengers soon become familiar with the new regime.
Tim Boswell: I am grateful to the hon. Gentleman, who has addressed the points made helpfully and in a good spirit. To respond, I would ask him to think about the comments of my hon. Friend the Member for East Devon (Mr. Swire). It may reassure the Committee if I say that in all my experience of guide dogs, including that of a right hon. Member in this House, the concerns that people have about their continence, or their ability to influence the environment, are nearly always ill placed. Of course, something can go wrong, but the dogs nearly always slot into situations with the least of problems. The legislation will allow us to prevent people from using the excuse of some theoretical inconvenience when there is no problem at all.
Neil Gerrard: That is very helpful. Every time that I have come across guide dogs they have been well behaved and gentle. A dog that is not reasonably well behaved would be unsuitable as a guide dog or assistance dog.
There are bound to be problems, for example, with a person who has a single-car business and is covered by an exemption certificate. Someone may make a booking and have the unfortunate experience of such a driver turning up who cannot take the individual because of his exemption. That would be an inconvenience and a fresh booking would have to be made. However, the number of such occasions will be small; we know that exemption certificates that have been issued to licensed taxis are very few, and I do not expect huge numbers of exemption certificates to be issued in this case. I cannot remember the exact number, but we have something in the order of 6,000
assistance dogs of one sort or another. We also have about 150,000 private hire vehicles, so we will not be placing a huge burden on operators and drivers.
I understand the point about passengers and allergies. That is a difficult problem. Anyone with an allergy could get into a private vehicle after someone else had just been in it with a dog, or after someone had been in it wearing perfume; it would be terribly difficult to legislate against such possibilities. On the issue of local authority hire vehicles, local authorities that are hiring vehicles would in most cases have contracts with the companies from which they hire. It should be possible, through those contracts, for local authorities to think about the various possibilities and ensure that they do not create a difficulty where one should not exist. In most cases in which there are contracts with local authorities, the contract will be the mechanism through which problems are dealt with, rather than through legislation, which cannot cover every single possibility that we think of.
I have tried to address some of the concerns, and I shall reflect on the points that have been made. The amendment will work, but I shall reconsider some points because we do not want to produce something that does not work properly.
Amendment agreed to.
Neil Gerrard: I beg to move amendment No. 2, in page 1, line 21, leave out from 'to' to end of line 22 and insert
'issue a certificate of exemption to a driver in respect of subsection (3) it must do so.'.
Frank Cook: With this it will be convenient to take the following amendments: No. 3, in page 2, line 1, after 'issue', insert 'a'.
No. 4, in page 2, line 10, leave out from beginning to 'if' in line 11 and insert—
'( ) No offence is committed by a driver under subsection (3)'.
Amendment No. 2 follows on from amendment No. 1 because in the original draft of the Bill, in which a duty was on the driver, the word ''person'' was used in relation to the exemption certificate being given on medical grounds. Clearly, the only person that might be concerned would be the driver. We now have references in clause 1 to both ''operator'' and ''driver'' so we must make it clear to whom precisely the exemption refers. The amendment clarifies that the driver and not the operator is eligible for an exemption certificate.
It would dignify amendment No. 3 to call it a technical amendment. A word was left out because of a drafting error—it is as simple as that. Amendment No. 4 just tidies up and makes it clear that a driver is not committing an offence if he has an exemption certificate by replacing the original phrase ''exempt from the duties.'' These are fairly small, technical and
tidying-up amendments to ensure that amendment No. 1, which we have already discussed, fits in with the rest of clause 1.
Amendment agreed to.
Amendments made: No. 3, in page 2, line 1, after 'issue', insert 'a'.
No. 4, in page 2, line 10, leave out from beginning to 'if' in line 11 and insert—
'( ) No offence is committed by a driver under subsection (3)'.—[Mr. Gerrard.]
Neil Gerrard: I beg to move amendment No. 5, in page 2, line 17, leave out from beginning to end of line 20.
Frank Cook: With this it will be convenient to take the following amendments: No. 6, in page 2, line 22, leave out from beginning to 'which' in line 24 and insert
(a) has been trained to guide a blind person;
(b) has been trained to assist a deaf person;
(c) has been trained by a prescribed charity to assist a disabled person who has a disability'
No. 7, in page 2, line 28, leave out from 'objects' to end of line 33.
No. 8, in page 2, line 33, at end insert
''driver'' means a person who holds a licence granted under—
(a) section 13 of the Private Hire Vehicles (London) Act 1998 (c. 34) (''the 1998 Act'');
(b) section 51 of the Local Government (Miscellaneous Provisions) Act 1976 (c. 57) (''the 1976 Act''); or
(c) an equivalent provision of a local enactment;
''licensing authority'', in relation to any area of England and Wales, means the authority responsible for licensing private hire vehicles in that area;
''operator'' means a person who holds a licence granted under—
(a) section 3 of the 1998 Act;
(b) section 55 of the 1976 Act; or
(c) an equivalent provision of a local enactment;
''private hire vehicle'' means a vehicle licensed under—
(a) section 6 of the 1998 Act;
(b) section 48 of the 1976 Act; or
(c) an equivalent provision of a local enactment.'.
Neil Gerrard: The amendments deal with definitions. The Bill includes definitions for guide dog, hearing dog and assistance dog. These tidying-up amendments define them all as ''assistance dog.'' The definition includes guide dogs and hearing dogs but also other working dogs. That is quite important, although it covers a relatively small numbers of dogs. There are several other categories of working dogs and they would all be swept up in the definition of assistance dog.
One of the amendments deletes the reference in the Bill to the yellow jacket. There are two reasons for doing that. First, not all assistance dogs wear yellow jackets. Many do—probably the majority—but certain assistance dogs wear red rather than yellow, and some owners of assistance dogs tend not to put a jacket but perhaps just a coloured harness on the dog.
Secondly, private hire vehicles are often booked by telephone. It does not make sense to have a clause in the Bill that says that the dog must be wearing a yellow
jacket when one hires a vehicle. How the operator would be able to distinguish over the phone whether a dog is wearing a yellow jacket is difficult to envisage. I know that videophones are on the way, but they are not here yet and they may not be universally used. Therefore, it makes sense to take out the reference to a yellow jacket so that we do not unintentionally introduce a nonsense. Amendment No. 6 uses the term ''prescribed charity'' rather than ''specified charity'' and brings the paragraph into line with the terms in the rest of the Disability Discrimination Act 1995.
Amendment No. 8 is another technical amendment and contains a series of definitions of phrases such as ''driver'', ''licensing authority'' and ''operator''. I was rather surprised about some of the provisions, including the references to three pieces of legislation: ''the 1998 Act'', ''the 1976 Act'' and
''an equivalent provision of a local enactment''.
Those are necessary to cover London and the rest of the country, while the
''equivalent provision of a local enactment''
refers only to the constituency of my hon. Friend the Minister. There is apparently some local enactment for Plymouth that must be included so that the definitions can apply throughout the country.
The amendments are mainly technical. We must remove the yellow jacket reference and ensure that the definition of assistance dog covers all the categories of dog that might be involved.
Tim Boswell: I start with a general and positive point. Dogs for the Disabled is an admirable charity and is located by a whisker in my constituency. I thoroughly enjoy visiting the people there and seeing how they train dogs to do remarkable things for disabled people. There is no suggestion from the Opposition of any covert, let alone overt, opposition to the intentions of the hon. Gentleman or his Bill. His amendments are well placed, but in the spirit of my earlier remarks I want some further assurances.
Although it should perhaps be incumbent on me to know the Disability Discrimination Act, I confess that I have not checked it cover to cover. After all, there is a limit to the extent to which one can check multiple cross-references, unless one is a draftsperson, to check that it has been conceived correctly. Will the hon. Gentleman assure me that the substance of the regime for private hire vehicles covered by the legislation will be the same as that for taxis?
Mr. Gerrard indicated assent.
Tim Boswell: The hon. Gentleman nods, which is helpful. Having said that, and in the knowledge that I do not have the text in front of me, I shall ask him a couple of specific points about the drafting of the amendments. He referred to a ''prescribed charity'', and I presume the DDA specifies the charities that that covers and that the Secretary of State may make an order to prescribe them as such. I am not a lawyer, but there is always the potential that a list that specifies one type may be held to exclude another. There is a slight
difficulty in singling out assistance dogs for blind people, those for deaf people and other assistance dogs, as a dog may have an obligation to cover the multiple disabilities of an individual who, for example, was blind and had locomotive disabilities. No one wants to see a situation in which a dog that qualifies to do two jobs is somehow disqualified under the arrangements by a legal accident.
I do not want to make a meal of this for the Committee, as these are matters on which the hon. Gentleman and his advisers may want to reflect, but my final point concerns amendment No. 6, which relates to dogs that are trained to guide blind persons. They are what most people would think of typically as ''guide dogs''.
Paragraph (b) refers to the special category of assistance to deaf people and paragraph (c), the third category, to general assistance. A slightly different standard of approval of what is being done is required in the different cases. For example, it is not clear from the proposal whether the blind person referred to is a registered blind person. There are more people who are visually impaired than there are those who have no sight at all. The definition of a deaf person, and the appropriate amount of training, are also not clear from the provision.
The third category, training by a prescribed charity, does not define the amount of training or the nature of the assistance given, but it appears to impose a slightly different sort of test. For example, it is not clear why, given the role of the Royal National Institute for the Blind in respect of visual impairment or of the Royal National Institute for Deaf People in respect of hearing loss, they could not all be swept up within the single category of prescribed charities, which would make it simpler.
My point of substance is that, whenever categories are broken down and different ones proposed, it may involve two separate interests or two slightly different methods of handling a situation, and that may have unfortunate legal consequences, which we neither seek nor fully anticipate. However, the amendment is more straightforward than the clause and is therefore a welcome simplification. Assuming that it is accepted, I shall be happy to consider it again on Report.
In the spirit of my earlier remarks, I ask the hon. Gentleman to reflect on whether the amendment really optimises the proposal and to ensure that nothing has been overlooked which would help to make its implementation clearer and better.
Neil Gerrard: I take the hon. Gentleman's point; we do not want to leave loopholes in the Bill. The meaning of ''prescribed'' is as in the Disability Discrimination Act. The Secretary of State has the power, through statutory instruments, to define the organisations covered. I do not want the Bill to include a list that would have to be amended in primary legislation, if for example, new organisations were to be included.
Dual-purpose dogs should not be a problem provided that they come within one of the categories. It would make no difference if they fell within two of the categories.
With the amendments, the section will still include references to the disabled person having a disability that consists of epilepsy or otherwise affects his mobility or manual dexterity. Those phrases will remain in the measure, which is pretty much a catch-all one. I understand what the hon. Gentleman said about definitions and creating loopholes, but I do not think that there are any in the proposal. However, before Report I will ensure that the Bill contains no unnecessary loopholes.
Amendment agreed to.
Amendments made: No. 6, in page 2, line 22, leave out from beginning to 'which' in line 24 and insert
(a) has been trained to guide a blind person;
(b) has been trained to assist a deaf person;
(c) has been trained by a prescribed charity to assist a disabled person who has a disability'
No. 7, in page 2, line 28, leave out from 'objects' to end of line 33.
No. 8, in page 2, line 33, at end insert
''driver'' means a person who holds a licence granted under—
(a) section 13 of the Private Hire Vehicles (London) Act 1998 (c. 34) (''the 1998 Act'');
(b) section 51 of the Local Government (Miscellaneous Provisions) Act 1976 (c. 57) (''the 1976 Act''); or
(c) an equivalent provision of a local enactment;
''licensing authority'', in relation to any area of England and Wales, means the authority responsible for licensing private hire vehicles in that area;
''operator'' means a person who holds a licence granted under—
(a) section 3 of the 1998 Act;
(b) section 55 of the 1976 Act; or
(c) an equivalent provision of a local enactment;
''private hire vehicle'' means a vehicle licensed under—
(a) section 6 of the 1998 Act;
(b) section 48 of the 1976 Act; or
(c) an equivalent provision of a local enactment.'.—[Mr. Gerrard.]
Clause 1, as amended, ordered to stand part of the Bill.
Clause 2 ordered to stand part of the Bill.
Clause 3 - Forgery and false statements
Neil Gerrard: I beg to move amendment No. 9, in page 2, line 39, leave out from '(1)(a)' to the end and insert
', for ''section 36 or 37'' there is substituted ''section 36, 37 or 37A''.'.
Frank Cook: With this we may take the following amendments: No. 10, in page 2, line 40, leave out from '(1)(b)' to the end and insert
', for ''section 36(9)(b) or (37)(8)(b)'' there is substituted ''section 36(9)(b), 37(8)(b) or 37A(8)(b)''.'.
No. 11, in clause 4, page 2, line 42, leave out '67' and insert '68'.
No. 12, in clause 4, page 2, line 43, leave out from 'authority''' to end of line 7 on page 3 and insert
', after ''authority'' there is inserted '', except in section 37A,''.'.
Neil Gerrard: Briefly, these are purely technical amendments to ensure that the correct references to appropriate sections appear in the Act. It applies to the original sections 36 and 37 of the Disability Discrimination Act 1995 and to clause 1 of the Bill, which will become section 37A of the Act.
Amendment No. 11 simply corrects a drafting error: the reference to section 67 of the 1995 Act should have been to section 68. Amendment No. 12 brings in the correct reference to the new section 37A, which will be created by clause 1. As I said, they are purely technical amendments.
Amendment agreed to.
Amendment made: No. 10, in page 2, line 40, leave out from '(1)(b)' to the end and insert
', for ''section 36(9)(b) or (37)(8)(b)'' there is substituted ''section 36(9)(b), 37(8)(b) or 37A(8)(b)''.'.—[Mr. Gerrard.]
Clause 3, as amended, ordered to stand part of the Bill.
Clause 4 - Interpretation
Amendments made: No. 11, in page 2, line 42, leave out '67' and insert '68'.
No. 12, in page 2, line 43, leave out from 'authority''' to end of line 7 on page 3 and insert
', after ''authority'' there is inserted '', except in section 37A,''.'.—[Mr. Gerrard.]
Clause 4, as amended, ordered to stand part of the Bill.
Clause 5 - Expenses
Frank Cook: I now remind members of the Committee of my advice at the opening of the sitting.
Clause 5 disagreed to.
Clause 6 - Short title, commencement and extent
Neil Gerrard: I beg to move amendment No. 14, in page 3, line 14, leave out from 'Act' to end of line 18 and insert
'(apart from this section) comes into force on such day as the Secretary of State or, in relation to section (Carrying of guide dogs, hearing dogs and other assistance dogs: Scotland) the Scottish Ministers, may by order made by statutory instrument appoint.
(3) Different days may be appointed for different purposes and different areas.'.
Frank Cook: With this we may take amendment No. 15, in page 3, line 19, leave out subsection (4) and insert—
'(4) Any amendment by this Act of an enactment has the same extent as the enactment amended.'.
Neil Gerrard: The final group of amendments deal with commencement. I refer particularly to the reference in amendment No. 14 to
''Different days may be appointed for different purposes and different areas.''
London is behind the rest of the country. [Interruption.] I wish that my hon. Friends would not read more into that remark than I intended. It related purely to the legislation. The rest of the country already has licensing regimes through local authorities. We do not have them in London, but Transport for London is progressing matters. We have got to the point where operators are licensed, and hopefully drivers will be licensed by the end of the year. That is out of our hands, and depends on Transport for London. We do not want the rest of the country to have to wait until the legislation is brought into force merely because there is a delay in getting the licensing provisions in place for London. Licensing for London is a large exercise. It is not being carried out borough by borough, or local authority by local authority, but for the whole of London through the Public Carriage Office. We will get there, but the provision allows us to ensure that the legislation can be enforced as soon as possible in other parts of the country. We can apply the legislation to London once we have the licensing provisions.
Amendment agreed to.
Amendment made: No. 15, in page 3, line 19, leave out subsection (4) and insert—
'(4) Any amendment by this Act of an enactment has the same extent as the enactment amended.'—[Mr. Gerrard.]
Question proposed, That the clause, as amended, stand part of the Bill.
Neil Gerrard: This is the last clause that we will consider, and I want to reiterate my thanks to hon. Members who have given up their time to help the Committee, and for the constructive way in which the Bill was considered. I thank the Minister and his officials who worked so helpfully through the amendments that were necessary to produce a Bill that will work. I also thank the Guide Dogs for the Blind Association and the RNIB. The Bill was produced through my contacts with them, and they have been of great support and assistance to me throughout my attempt to get the Bill to this stage. I hope that it will reach Report and will soon be on the statute book.
David Jamieson: I offer my congratulations to my hon. Friend the Member for Walthamstow on the way in which he has handled the Bill, which has been exemplary. I know how difficult private Members' legislation is. It follows a precarious and difficult route through the House, and my hon. Friend has done extremely well to have got this far.
I am delighted to have been associated with the Bill. I was not the Minister who originally had charge of it, but there have been unforeseen rearrangements in the Department over the past fortnight, and happy circumstances meant that I could be associated with it. I, too, thank the officials who have given excellent advice throughout the Bill's consideration. We wish it safe passage through its later stages in the House.
Tim Boswell: It would be churlish if Opposition Members made no comment. I simply want to reiterate the thanks and praises that have been lavished on the hon. Member for Walthamstow for what by all accounts has been a common and worthwhile endeavour, and the thanks for all the support that he has received. Support often has to be earned, and he has gone to great pains to liaise with people to try to get the legislation right. I welcome the Committee's emphasis on ensuring that the legislation is not merely right in theory, but works in practice. We are nearly there, and I do not anticipate any further difficulties. This morning's discussion will have helped to eliminate any remaining difficulties or concerns.
Question put and agreed to.
Clause 6, as amended, ordered to stand part of the Bill.
New Clause 1 - Carrying of guide dogs, hearing dogs and other assistance dogs: scotland
'In section 20 of the Civic Government (Scotland) Act 1982 (c. 45) (regulations relating to taxis and private hire cars and their drivers) the following subsection is inserted after subsection (2A)—
''(2AA) The Scottish Ministers may by regulations make such provision as appears to them to be necessary or expedient in relation to the carrying in private hire cars of disabled persons (within the meaning of section 1 (2) of the Disability Discrimination Act 1995 (c. 50)) and such provision may in particular prescribe—
(a) requirements as to the carriage of guide dogs, hearing dogs and other categories of dogs;
(b) a date from which any such provision is to apply and the extent to which it is to apply; and
(c) the circumstances in which an exemption from such provision may be granted in respect of any private hire car or private hire car driver,
and in this subsection ''guide dog'', ''hearing dog'' and ''other categories of dog'' have the same meaning as in subsection (2A) above.
(2AB) Regulations under subsection (2AA) above shall be made by statutory instrument subject to annulment in pursuance of a resolution of the Scottish Parliament.''.'.—[Mr. Gerrard.]
Brought up, read the First and Second time, and added to the Bill.
Bill, as amended, to be reported.
Committee rose at twenty minutes to Twelve o'clock.
Gidley, Sandra Jamieson, Mr. Mahon, Mrs. Naysmith, Dr. Swire, Mr. Watts, Mr.
|
---
description: >-
Let us introduce you our public Discord Bot for the cdc-bot.js community! With
the bot you have all needed developer tools you need to learn and to use
cdc-bot.js.
---
# Our Tools-Bot
Default bot prefix: `-`
Try out our slash commands to interact with the bot.
Invite the bot to your servers by clicking here: [https://dsc.gg/developer-tools](https://dsc.gg/developer-tools)
## Features:
* List of all functions
* Information about usage and details of each function
* List of all command types
* List of all permission names
* List of all events
* List of all client setup options
* List of all options for guildUpdateCommands
* List of all options for userUpdateCommands
* List of all options for presenceUpdateCommands
* List of all options for channelCreate/Update/DeleteCommands
* List of all options for emojiCreate/Update/DeleteCommands
* List of all options for roleCreate/Update/DeleteCommands
* discord.js documentation tools
* hex color preview and random color generator
* Parse MS into time
* Parse time into MS
|
/**
* Copyright (c) 2020-2021 Philippe Lieser
*
* This software is licensed under the terms of the MIT License.
*
* The above copyright and license notice shall be
* included in all copies or substantial portions of the Software.
*/
// @ts-check
///<reference path="./dkimHeader.d.ts" />
///<reference path="../mozilla.d.ts" />
///<reference path="../mozillaDom.d.ts" />
/* eslint-env worker */
/* global ChromeUtils, Components, ExtensionCommon */
"use strict";
/** @type {{ExtensionParent: ExtensionParentM}} */
const { ExtensionParent } = ChromeUtils.import("resource://gre/modules/ExtensionParent.jsm");
/** @type {{ExtensionSupport: ExtensionSupportM}} */
const { ExtensionSupport } = ChromeUtils.import("resource:///modules/ExtensionSupport.jsm");
/**
* Base class for DKIM tooltips
*/
class DKIMTooltip {
/**
* Creates an instance of DKIMTooltip.
*
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DKIMTooltip
*/
constructor(document, element) {
// whether a separator should be added before the warnings
this._warningsSeparator = false;
if (element) {
// @ts-ignore
this.element = element;
return;
}
/** @type {DKIMTooltipElement} */
// @ts-ignore
this.element = document.createXULElement("tooltip");
// A box containing the warnings
this.element._warningsBox = document.createXULElement("vbox");
}
/**
* Set the warnings for the tooltip
*
* @param {String[]} warnings
* @memberof DKIMTooltip
*/
set warnings(warnings) {
// delete old warnings from tooltips
while (this.element._warningsBox.firstChild) {
this.element._warningsBox.removeChild(this.element._warningsBox.firstChild);
}
if (!this.element.ownerDocument) {
throw Error("Underlying element of DKIMTooltip does not contain ownerDocument");
}
if (this._warningsSeparator && warnings.length > 0) {
const sep = this.element.ownerDocument.createXULElement("separator");
sep.setAttribute("class", "thin");
this.element._warningsBox.appendChild(sep);
}
// add warnings to warning tooltip
for (const w of warnings) {
const des = this.element.ownerDocument.createXULElement("description");
des.textContent = w;
this.element._warningsBox.appendChild(des);
}
}
}
/**
* Tooltip showing the DKIM warnings.
*
* @extends {DKIMTooltip}
*/
class DKIMWarningsTooltip extends DKIMTooltip {
/**
* Creates an instance of DKIMWarningsTooltip.
*
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DKIMTooltip
*/
constructor(document, element) {
super(document, element);
if (element) {
return;
}
this.element.appendChild(this.element._warningsBox);
}
}
/**
* Tooltip showing both the DKIM result and the warnings.
* The tooltip contains the label "DKIM:".
*
* @extends {DKIMTooltip}
*/
class DkimResultTooltip extends DKIMTooltip {
/**
* Creates an instance of DkimResultTooltip.
*
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DKIMTooltip
*/
constructor(document, element) {
super(document, element);
this._warningsSeparator = true;
if (element) {
return;
}
// Outer box and label
const outerBox = document.createXULElement("hbox");
const outerBoxLabel = document.createXULElement("label");
outerBoxLabel.setAttribute("value", "DKIM:");
// The inner box, containing the DKIM result and optional the warnings
const innerBox = document.createXULElement("vbox");
innerBox.setAttribute("flex", "1");
// The DKIM result
this.element._value = document.createXULElement("label");
this.element.appendChild(outerBox);
outerBox.appendChild(outerBoxLabel);
outerBox.appendChild(innerBox);
innerBox.appendChild(this.element._value);
innerBox.appendChild(this.element._warningsBox);
}
/**
* Set the DKIM result
*
* @param {String} val
* @memberof DKIMTooltip
*/
set value(val) {
if (!this.element._value) {
throw Error("Underlying element of DkimResultTooltip does not contain _value");
}
this.element._value.textContent = val;
}
}
/**
* The content that is shown inside the DkimHeaderRow.
*/
class DKIMHeaderField {
/**
* Creates an instance of DKIMHeaderField.
*
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DKIMHeaderField
*/
constructor(document, element) {
if (element) {
// @ts-ignore
this.element = element;
this._dkimWarningTooltip = new DKIMWarningsTooltip(document, this.element._dkimWarningTooltip);
return;
}
/** @type {DKIMHeaderFieldElement} */
// @ts-ignore
this.element = document.createXULElement("hbox");
this.element.id = DKIMHeaderField._id;
this.element.classList.add("headerValueBox");
this.element.setAttribute("context", "copyPopup");
// @ts-ignore
this.element.style.MozBoxAlign = "center";
// DKIM result
this.element._dkimValue = document.createXULElement("description");
this.element._dkimValue.classList.add("headerValue");
// DKIM warning icon
this._dkimWarningTooltip = new DKIMWarningsTooltip(document);
this.element._dkimWarningTooltip = this._dkimWarningTooltip.element;
this.element._dkimWarningTooltip.id = "dkim-verifier-header-tooltip-warnings";
this.element._dkimWarningIcon = document.createXULElement("image");
this.element._dkimWarningIcon.classList.add("alert-icon");
this.element._dkimWarningIcon.setAttribute("anonid", "dkimWarningIcon");
this.element._dkimWarningIcon.setAttribute("tooltip", "dkim-verifier-header-tooltip-warnings");
this.element._dkimWarningIcon.style.maxWidth = "1.2em";
this.element._dkimWarningIcon.style.maxHeight = "1.2em";
this.element._dkimWarningIcon.style.marginLeft = "1ex";
/**
* Create element for ARH result
*
* @param {String} anonid
* @param {String} labelValue
* @returns {{box: XULElement, value: XULElement}}
*/
function createArh(anonid, labelValue) {
const box = document.createXULElement("hbox");
box.setAttribute("anonid", anonid);
const label = document.createXULElement("description");
label.classList.add("headerValue");
label.setAttribute("style", "text-align: right");
label.textContent = labelValue;
const value = document.createXULElement("description");
value.classList.add("headerValue");
box.appendChild(label);
box.appendChild(value);
return {
box: box,
value: value,
};
}
// ARH result
this.element._arhDkim = createArh("arhDkim", "DKIM:");
this.element._arhSpf = createArh("spf", "SPF:");
this.element._arhDmarc = createArh("dmarc", "DMARC:");
const separator = document.createXULElement("separator");
separator.setAttribute("flex", "1");
this.element.appendChild(this.element._dkimValue);
this.element.appendChild(this.element._dkimWarningTooltip);
this.element.appendChild(this.element._dkimWarningIcon);
this.element.appendChild(this.element._arhDkim.box);
this.element.appendChild(this.element._arhSpf.box);
this.element.appendChild(this.element._arhDmarc.box);
this.element.appendChild(separator);
this.reset();
}
/**
* Set the DKIM result
*
* @param {String} val
* @memberof DKIMHeaderField
*/
set value(val) {
this.element._dkimValue.textContent = val;
}
/**
* Set the DKIM warnings
*
* @param {String[]} warnings
* @memberof DKIMHeaderField
*/
set warnings(warnings) {
if (warnings.length > 0) {
this.element._dkimWarningIcon.style.display = "";
} else {
this.element._dkimWarningIcon.style.display = "none";
}
this._dkimWarningTooltip.warnings = warnings;
}
/**
* Set the SPF result
*
* @param {String} val
* @memberof DKIMHeaderField
*/
set spfValue(val) {
if (val) {
this.element._arhSpf.box.style.display = "";
} else {
this.element._arhSpf.box.style.display = "none";
}
this.element._arhSpf.value.textContent = val;
}
/**
* Set the DMARC result
*
* @param {String} val
* @memberof DKIMHeaderField
*/
set dmarcValue(val) {
if (val) {
this.element._arhDmarc.box.style.display = "";
} else {
this.element._arhDmarc.box.style.display = "none";
}
this.element._arhDmarc.value.textContent = val;
}
/**
* Set the DKIM result from the ARH
*
* @param {String} val
* @memberof DKIMHeaderField
*/
set arhDkimValue(val) {
if (val) {
this.element._arhDkim.box.style.display = "";
} else {
this.element._arhDkim.box.style.display = "none";
}
this.element._arhDkim.value.textContent = val;
}
reset() {
this.value = DKIMHeaderField.resetValue;
this.warnings = [];
this.spfValue = "";
this.dmarcValue = "";
this.arhDkimValue = "";
}
/**
* Get the DKIM header field in a given document.
*
* @static
* @param {Document} document
* @returns {DKIMHeaderField}
* @memberof DKIMHeaderField
*/
static get(document) {
const element = document.getElementById(DKIMHeaderField._id);
if (!element) {
throw Error("Could not find the DKIMHeaderField element");
}
return new DKIMHeaderField(document, element);
}
}
DKIMHeaderField.resetValue = "Validating…";
DKIMHeaderField._id = "expandedDkim-verifierBox";
/**
* The DKIM row shown in the e-mail header.
*/
class DkimHeaderRow {
/**
* Creates an instance of DkimHeaderRow.
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DkimHeaderRow
*/
constructor(document, element) {
this.document = document;
if (element) {
this.element = element;
return;
}
this.element = document.createElement("tr");
this.element.id = DkimHeaderRow._id;
const headerRowTitle = document.createElement("th");
const headerRowTitleLabel = document.createXULElement("label");
headerRowTitleLabel.classList.add("headerName");
headerRowTitleLabel.textContent = "DKIM";
headerRowTitle.appendChild(headerRowTitleLabel);
const headerRowValue = document.createElement("td");
const dkimHeaderField = new DKIMHeaderField(document);
headerRowValue.appendChild(dkimHeaderField.element);
this.element.appendChild(headerRowTitle);
this.element.appendChild(headerRowValue);
}
/**
* Set whether the DKIM heder should be shown
*
* @param {boolean} show
* @returns {void}
* @memberof DkimHeaderRow
*/
show(show) {
if (show) {
this.element.style.visibility = "";
} else {
this.element.style.visibility = "collapse";
}
// Trigger the OnResizeExpandedHeaderView() function from Thunderbird
// to recalculate the height on the expandedHeaderView element.
const defaultView = this.document.defaultView;
if (defaultView) {
const window = defaultView.window;
window.dispatchEvent(new window.Event('resize'));
}
}
/**
* Get the DKIM header row in a given document.
*
* @static
* @param {Document} document
* @returns {DkimHeaderRow}
* @memberof DkimHeaderRow
*/
static get(document) {
const element = document.getElementById(DkimHeaderRow._id);
if (!element) {
throw Error("Could not find the DkimHeaderRow element");
}
return new DkimHeaderRow(document, element);
}
/**
* Add the DKIM header row to a given document.
*
* @static
* @param {Document} document
* @returns {void}
* @memberof DkimHeaderRow
*/
static add(document) {
const headerRow = new DkimHeaderRow(document);
headerRow.show(false);
const expandedHeaders2 = document.getElementById("expandedHeaders2");
if (!expandedHeaders2) {
throw Error("Could not find the expandedHeaders2 element");
}
expandedHeaders2.appendChild(headerRow.element);
}
/**
* Remove the DKIM header row from a given document.
*
* @static
* @param {Document} document
* @returns {void}
* @memberof DkimHeaderRow
*/
static remove(document) {
const headerRow = DkimHeaderRow.get(document);
if (headerRow) {
headerRow.element.remove();
}
}
}
DkimHeaderRow._id = "expandedDkim-verifierRow";
/**
* The favicon shown before the from address.
*/
class DkimFavicon {
/**
* Creates an instance of DkimFavicon.
*
* @param {Document} document
* @param {XULElement|void} element - optional underlying element, will be created if not given
* @memberof DkimFavicon
*/
constructor(document, element) {
if (element) {
// @ts-ignore
this.element = element;
this._dkimTooltipFrom = new DkimResultTooltip(document, this.element._dkimTooltipFromElement);
return;
}
/** @type {DKIMFaviconElement} */
// @ts-ignore
this.element = document.createXULElement("description");
this.element.id = DkimFavicon._id;
this.element.classList.add("headerValue");
this.element.setAttribute("tooltip", DkimFavicon._idTooltip);
// dummy text for align baseline
this.element.textContent = "";
this.element.style.setProperty("min-width", "0px", "important");
this.element.style.width = "1.5em";
this.element.style.height = "1.5em";
this.element.style.backgroundSize = "contain";
this.element.style.backgroundPosition = "center center";
this.element.style.backgroundRepeat = "no-repeat";
// DKIM tooltip
this._dkimTooltipFrom = new DkimResultTooltip(document);
this.element._dkimTooltipFromElement = this._dkimTooltipFrom.element;
this.element._dkimTooltipFromElement.id = DkimFavicon._idTooltip;
this.element.setAttribute("tooltip", DkimFavicon._idTooltip);
this.reset();
}
/**
* Set the DKIM result.
*
* @param {String} val
* @memberof DkimFavicon
*/
set value(val) {
this._dkimTooltipFrom.value = val;
}
/**
* Set the DKIM warnings.
*
* @param {String[]} warnings
* @memberof DkimFavicon
*/
set warnings(warnings) {
this._dkimTooltipFrom.warnings = warnings;
}
/**
* Sets the url to the favicon. Empty string to reset it.
*
* @param {String} faviconUrl
* @return {void}
* @memberof DkimFavicon
*/
setFaviconUrl(faviconUrl) {
this.element.style.backgroundImage = `url('${faviconUrl}')`;
if (faviconUrl) {
this.element.style.display = "";
} else {
this.element.style.display = "none";
}
}
reset() {
this.setFaviconUrl("");
this.value = DKIMHeaderField.resetValue;
this.warnings = [];
}
/**
* Get the DKIM favicon in a given document.
*
* @static
* @param {Document} document
* @returns {DkimFavicon}
* @memberof DkimFavicon
*/
static get(document) {
const element = document.getElementById(DkimFavicon._id);
if (!element) {
throw Error("Could not find the DkimFavicon element");
}
return new DkimFavicon(document, element);
}
/**
* Add the DKIM favicon to a given document.
*
* @static
* @param {Document} document
* @returns {void}
* @memberof DkimFavicon
*/
static add(document) {
const headerRow = new DkimFavicon(document);
/** @type {MozMailMultiEmailheaderfield|null} */
// @ts-ignore
const expandedFromBox = document.getElementById("expandedfromBox");
if (!expandedFromBox) {
throw Error("Could not find the expandedFromBox element");
}
expandedFromBox.longEmailAddresses.prepend(headerRow.element);
// The tooltip is reused, and wherefore can not defined directly under the favicon
expandedFromBox.longEmailAddresses.prepend(headerRow._dkimTooltipFrom.element);
}
/**
* Remove the DKIM favicon from a given document.
*
* @static
* @param {Document} document
* @returns {void}
* @memberof DkimFavicon
*/
static remove(document) {
const favicon = DkimFavicon.get(document);
if (favicon) {
favicon.element.remove();
favicon._dkimTooltipFrom.element.remove();
}
}
}
DkimFavicon._id = "dkimFavicon";
DkimFavicon._idTooltip = "dkim-verifier-header-tooltip-from";
/**
* DKIM specific modifications of the from address:
* - Highlighting of the from address (text & background color)
* - Show DKIM tooltip
*/
class DkimFromAddress {
/**
* Get the element containing the from address (without the following star)
* @static
* @param {Document} document
* @returns {XULElement?}
*/
static _getFromAddress(document) {
/** @type {MozMailMultiEmailheaderfield?} */
// @ts-ignore
const expandedFromBox = document.getElementById("expandedfromBox");
if (!expandedFromBox) {
console.debug("DKIM: from address not found (no expandedfromBox)");
return null;
}
/** @type {XULElement?} */
// @ts-ignore
const mailEmailadress = expandedFromBox.emailAddresses.firstChild;
if (!mailEmailadress) {
console.debug("DKIM: from address not found (no firstChild)");
return null;
}
/** @type {XULElement|undefined} */
// @ts-ignore
const emailValue = mailEmailadress.getElementsByClassName("emaillabel")[0];
if (!emailValue) {
console.debug("DKIM: from address not found (no emaillabel)");
return null;
}
return emailValue;
}
/**
* Set the text and background color of the from address.
* @param {Document} document
* @param {string} color
* @param {string} backgroundColor
* @returns {void}
*/
static setHighlightColor(document, color, backgroundColor) {
const emailValue = this._getFromAddress(document);
if (!emailValue) {
return;
}
emailValue.style.borderRadius = "3px";
emailValue.style.color = color;
emailValue.style.backgroundColor = backgroundColor;
}
/**
* Set whether the DKIM heder should be shown
*
* @param {Document} document
* @param {boolean} show
* @returns {void}
*/
static showTooltip(document, show) {
const emailValue = this._getFromAddress(document);
if (!emailValue) {
return;
}
if (show) {
// save current tooltip if set
const tooltiptext = emailValue.getAttribute("tooltiptext");
if (tooltiptext) {
emailValue.setAttribute("tooltiptextSaved", tooltiptext);
}
emailValue.removeAttribute("tooltiptext");
// set DKIM tooltip
emailValue.setAttribute("tooltip", DkimFavicon._idTooltip);
} else {
if (emailValue.getAttribute("tooltip") === DkimFavicon._idTooltip) {
// remove DKIM tooltip
emailValue.removeAttribute("tooltip");
// restore saved tooltip
const tooltiptextSaved = emailValue.getAttribute("tooltiptextSaved");
if (tooltiptextSaved) {
emailValue.setAttribute("tooltiptext", tooltiptextSaved);
emailValue.removeAttribute("tooltiptextSaved");
}
}
}
}
/**
* Reset the DKIM specific modifications of the from address.
* @param {Document} document
* @returns {void}
*/
static reset(document) {
this.setHighlightColor(document, "", "");
this.showTooltip(document, false);
}
}
/**
* A listener on gMessageListeners that resets the DKIM related header elements.
*
* Functions will be called in the following order:
* 1. onStartHeaders
* 2. onBeforeShowHeaderPane (optional)
* 3. onEndHeaders
*/
class DkimResetMessageListener {
/**
* Creates an instance of DkimResetMessageListener.
* Should not be called directly, use the static register() instead.
*
* @param {Window} window
* @memberof DkimResetMessageListener
*/
constructor(window) {
this.window = window;
}
/**
* Create and register a DkimResetMessageListener.
*
* @static
* @param {Window} window
* @returns {void}
* @memberof DkimResetMessageListener
*/
static register(window) {
if (DkimResetMessageListener._mapping.has(window)) {
console.error("MessageListener.register(): already registered");
}
const messageListener = new DkimResetMessageListener(window);
DkimResetMessageListener._mapping.set(window, messageListener);
window.gMessageListeners.push(messageListener);
}
/**
* Unregister a DkimResetMessageListener.
*
* @static
* @param {Window} window
* @returns {void}
* @memberof DkimResetMessageListener
*/
static unregister(window) {
const listener = DkimResetMessageListener._mapping.get(window);
if (!listener) {
console.error("MessageListener.unregister(): could not find a listener for the window");
return;
}
const pos = window.gMessageListeners.indexOf(listener);
if (pos !== -1) {
window.gMessageListeners.splice(pos, 1);
} else {
console.error("MessageListener.unregister(): could not find the listener");
}
DkimResetMessageListener._mapping.delete(window);
}
/**
* Reset the header in a specific document.
*
* @static
* @param {Document} document
* @returns {void}
*/
static reset(document) {
const dkimHeaderField = DKIMHeaderField.get(document);
dkimHeaderField.reset();
const dkimFavicon = DkimFavicon.get(document);
dkimFavicon.reset();
DkimFromAddress.reset(document);
}
onStartHeaders() {
const document = this.window.document;
DkimResetMessageListener.reset(document);
}
// eslint-disable-next-line no-empty-function
onEndHeaders() { }
// eslint-disable-next-line no-empty-function
onEndAttachments() { }
}
/** @type {Map<Window, DkimResetMessageListener>} */
DkimResetMessageListener._mapping = new Map();
// eslint-disable-next-line no-invalid-this
this.dkimHeader = class extends ExtensionCommon.ExtensionAPI {
/**
* @param {ExtensionCommon.Extension} extension
*/
constructor(extension) {
super(extension);
this.id = `${extension.id}|dkimHeader`;
this.windowURLs = [
"chrome://messenger/content/messenger.xhtml",
"chrome://messenger/content/messageWindow.xhtml",
];
DKIMHeaderField.resetValue = extension.localeData.localizeMessage("loading");
extension.callOnClose(this);
this.open();
}
open() {
ExtensionSupport.registerWindowListener(this.id, {
chromeURLs: this.windowURLs,
onLoadWindow: window => {
DkimResetMessageListener.register(window);
this.paint(window);
},
});
}
close() {
ExtensionSupport.unregisterWindowListener(this.id);
for (const window of ExtensionSupport.openWindows) {
if (this.windowURLs.includes(window.location.href)) {
DkimResetMessageListener.unregister(window);
this.unPaint(window);
}
}
}
/**
* Add the DKIM specific elements to the window.
*
* @param {Window} window
* @returns {void}
*/
paint(window) {
const { document } = window;
DkimHeaderRow.add(document);
DkimFavicon.add(document);
}
/**
* Remove the DKIM specific elements from the window.
*
* @param {Window} window
* @returns {void}
*/
unPaint(window) {
const { document } = window;
DkimHeaderRow.remove(document);
DkimFavicon.remove(document);
}
/**
* Get the Document for a specific message shown in a tab.
* Returns null if a different message is shown.
*
* @param {number} tabId
* @param {number} messageId
* @returns {Document?}
*/
getDocumentForCurrentMsg(tabId, messageId) {
const target = ExtensionParent.apiManager.global.tabTracker.getTab(tabId);
const window = Components.utils.getGlobalForObject(target);
const msg = this.extension.messageManager.convert(
window.gFolderDisplay.selectedMessage);
if (msg.id !== messageId) {
return null;
}
return window.document;
}
/**
* @param {ExtensionCommon.Context} context
* @returns {{dkimHeader: browser.dkimHeader}}
*/
// eslint-disable-next-line no-unused-vars
getAPI(context) {
return {
dkimHeader: {
showDkimHeader: (tabId, messageId, show) => {
const document = this.getDocumentForCurrentMsg(tabId, messageId);
if (!document) {
return Promise.resolve(false);
}
const dkimHeaderRow = DkimHeaderRow.get(document);
dkimHeaderRow.show(show);
return Promise.resolve(true);
},
showFromTooltip: (tabId, messageId, show) => {
const document = this.getDocumentForCurrentMsg(tabId, messageId);
if (!document) {
return Promise.resolve(false);
}
DkimFromAddress.showTooltip(document, show);
return Promise.resolve(true);
},
setDkimHeaderResult: (tabId, messageId, result, warnings, faviconUrl, arh) => {
const document = this.getDocumentForCurrentMsg(tabId, messageId);
if (!document) {
return Promise.resolve(false);
}
const dkimHeaderField = DKIMHeaderField.get(document);
dkimHeaderField.value = result;
dkimHeaderField.warnings = warnings;
if (arh.dkim) {
dkimHeaderField.arhDkimValue = arh.dkim;
}
if (arh.spf) {
dkimHeaderField.spfValue = arh.spf;
}
if (arh.dmarc) {
dkimHeaderField.dmarcValue = arh.dmarc;
}
const favicon = DkimFavicon.get(document);
favicon.value = result;
favicon.warnings = warnings;
favicon.setFaviconUrl(faviconUrl);
return Promise.resolve(true);
},
highlightFromAddress: (tabId, messageId, color, backgroundColor) => {
const document = this.getDocumentForCurrentMsg(tabId, messageId);
if (!document) {
return Promise.resolve(false);
}
DkimFromAddress.setHighlightColor(document, color, backgroundColor);
return Promise.resolve(true);
},
reset: (tabId, messageId) => {
const document = this.getDocumentForCurrentMsg(tabId, messageId);
if (!document) {
return Promise.resolve(false);
}
DkimResetMessageListener.reset(document);
return Promise.resolve(true);
},
},
};
}
};
|
Aguaranteedpokertournamentisatournamentwheretheprizepoolisguaranteedbythepokerroom.
A guaranteed poker tournament is a tournament where the prize pool is guaranteed by the poker room.
ChristianisProjectManagerandadvisesonPRforourITandconsumerclients.
Christian is Project Manager and advises on PR for our IT and consumer clients.
MASTERTENToffersyoumaximumservicelife.
MASTERTENT offers you maximum service life.
Andyes,thispluginwillalsobeconvenienttohighlighteditedpictures,andsoshowyourtalent,alwaysintheformofaslider.
And yes, this plugin will also be convenient to highlight edited pictures, and so show your talent, always in the form of a slider.
|
Apparatus for implementing the function of a virtual container-11 and a tributary unit group-2 in a synchronous digital hierarchy
ABSTRACT
An apparatus for implementing the integrated function of virtual container-11(VC-11) and tributary unit group-2(TUG-2) is configured to transmit and receive a DS-1 network signal and a TUG-2 system signal through a synchronization process in a synchronous multiplexing structure. Data between a network and a system is converted by using only one Tx buffer and one receiving buffer in a transmitter and a receiver respectively. An input of a Tx FIFO buffer is a DS-1 signal of 1.544 Mbps, and an output thereof is a TU-11 frame of 1.728 Mbps including spaces for a path overhead and a pointer. An input of a RX FIFO buffer is the TU-11 signal of 1.728 Mbps in which the path overhead and the pointer are eliminated, and an output thereof is the DS-1 signal of 1.544 Mbps.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an apparatus for implementing the integrated function of VC-11 (Virtual Container-11) and TUG-2 (Tributary Unit Group-2) in a synchronous multiplexing structure accommodating the ITU-T recommendation for a synchronous digital hierarchy and, more particularly, to an apparatus for simplifying a circuit and reducing the area of a chip by using one transmitting data buffer and one receiving data buffer in a transmitter and a receiver, respectively.
2. Discussion of Related Art
A synchronous digital hierarchy (SDH) is a hierarchical digital transmission structure which is standardized so as to multiplex and process payload signals of various hierarchies and to transmit the multiplexed and processed signals through a communication network. A synchronous multiplexing structure provides various advantages such as simplifying multiplexing and demultiplexing simplifying an access to a low speed hierarchical signal, improving operation and maintenance function, and in the future, facilitating an extension to the broadband communication. The ITU-T has published G.707, G.708, G709, G781, G783, G784, etc as the recommendation for such a SDH.
A SDH system is based on a SONET (Synchronous Optical NETwork) system of U.S. Currently, STM-1 in the 155.520 Mbps, STM-4 of 622.080 Mbps, STM-16 of 2.488320 Gbps, etc. are adopted as standards by the ITU-T. Each hierarchical signal of North America and Europe is multiplexed and transmitted in this system.
A VC-11 circuit converts the digital signal DS-1 signal of the North American Standard to VC-11 data format. A TUG-2 circuit multiplexes the VC-11 data by a factor of 4 and transmits the multiplexed data to an upper hierarchy. In this case, since a FIFO (First-In First-Out) buffer is generally used at two points in which a path overhead byte is inserted to construct VC-11 data and a pointer byte is inserted to construct TU-11 (Tributary Unit-11)data, transmitter and receiver circuits are complicated, and the area of the chip increases.
A structure to synchronize the network in the SDH system is described in a paper entitled "Network Synchronization - A Challenge for SDH/SONET ?", IEEE Commun. Mag., vol. 31, no. 9, Sep. 1993, pp. 42-50, Michael J. Klein & Ralph Urban sky. This structure is proposed to synchronize the network between TU and TUG in the SDH system. However, this structure is uneconomical in that two elastic buffers are used and other additional circuits should be added.
Another structure for the network synchronization in the SDH system for multiplexing European digital transmission data is disclosed in European Patent No. EP 0 503 732 A2, "Ubertragungs system fur die digital Synchron-Hier archie", Philips. The above patent using only one buffer memory describes a synchronous structure when a DS-nE signal of a European transmission speed is multiplexed to the SDH system.
SUMMARY OF THE INVENTION
An object of the present invention is to provide an apparatus for implementing the integrated function of VC-11 and TUG-2 in a synchronous multiplexing structure which can simplify a circuit and reduce the area of a chip.
Another object of the present invention is to provide an apparatus for synchronizing DS-1 and TU-11 when multiplexing a DS-1 signal of an American Standard transmission speed to a TUG-2 signal of an SDH system.
To achieve these and other advantages and in accordance with the purpose of the present invention, as embodied and broadly described, the apparatus for implementing the integrated function of VC-11 and TUG-2 in a synchronous multiplexing structure for synchronizing a DS-1 network signal and a TUG-2 system signal and transmitting the synchronized signal includes: a B8ZS decoder for decoding a DS-1 network TX signal of 1.544 Mbps coded to a B8ZS code to network data; a TX signal write clock generator for generating a write clock used for writing the network data decoded from the decoder; a TX signal read clock generator for generating a read clock used for reading the network data stored in TX FIFO; TX FIFO a buffer for writing the DS-1 network data decoded from the decoder in synchronization with the read clock, and for generating the DS-1 network data of a TU-11 frame structure of 1.728 Mbps including spaces for a path overhead and a pointer in synchronization with the write clock; a bit stuffing controller for generating a control signal for constantly maintaining a difference between the write and read clocks of the TX FIFO buffer; a pointer generator for generating 1-byte data by adjusting a pointer value by a pointer adjusting signal when the difference between the read and write clocks is one byte; an overhead generator for generating an overhead for a lower hierarchy path; a frame former for receiving the DS-1 network data generated from the TX FIFO buffer, the overhead generated from the overhead generator and the pointer value generated from the pointer generator, and for forming TU-11 frame data; a TX clock generator for receiving a transmitting clock of 6.912 MHz, for transmitting a clock needed to read data to the TX signal read clock generator, and for generating a frame transmitting clock of 2 KHZ; and a TUG-2 multiplexer for multiplexing the TU-11 frame data formed from the TU-11 frame former and from three external TU-11 frame formers, and for transmitting the multiplexed data with a speed of 6.912 Mbps.
Further, the apparatus for implementing the integrated function of VC-11 and TUG-2 in a synchronous multiplexing structure for synchronizing a network signal of DS-1 and a system signal of TUG-2 and for receiving the synchronized signal includes: a loopback controller for receiving, at a normal mode, RX data of 6.912 MHz, and for receiving, at a test mode, TX data through feedback to confirm whether the TX and RX data are equal; a TUG-2 demultiplexer for demultiplexing multiplexed TUG-2 system frame data received through the loopback controller to four independent data; four TU-11 frame de formers for deforming each frame of four demultiplexed data, and for extracting a path overhead, a pointer value, and a TU-11 signal in which the path overhead and the pointer value are eliminated; a path overhead processor for interpreting the path overhead extracted from one of the TU-11 frame de formers, and for implementing a unique function; a pointer processor for interpreting the pointer value extracted from one of the TU-11 frame de formers, and for generating a control signal according to the state of the pointer value; an RX clock generator for generating various clocks necessary for operation of a receiver by using an RX clock of 6.912 MHz and a receiving frame clock of 2 KHz applied from the exterior; an RX data write clock generator for receiving the clock generated from the RX clock generator, and for generating a write clock used for writing TU-11 system data of 1.728 Mbps in which the path overhead and the pointer are eliminated according to control signals of the overhead processor and the pointer processor; an RX data read clock generator for generating a read clock used for reading data from a clock obtained by dividing a bit leaked clock by a factor of four; a clock comparator for comparing the write clock with the read clock to constantly maintain a clock difference, and for generating a bit leaking request signal when there is a clock difference; a bit leaking processor for bit leaking a 6.912 MHz input clock by the bit leaking request signal generated from the clock comparator, and for dividing the bit leaked clock by a factor of four; RX FIFO buffer for storing the TU-11 data in which the path overhead and the pointer are eliminated in synchronization with the write clock, and for converting the stored TU-11 data to DS-1 data in synchronization with the read clock; and a B8ZS coder for coding the DS-1 data generated from the RX FIFO buffer to a B8ZS code, and for transmitting the DS-1 signal with a speed of 1.544 Mbps.
The write clock and the read clock may vary according to the capacity of the transmitting and receiving buffers.
BRIEF DESCRIPTION OF THE ATTACHED DRAWINGS
The accompanying drawings, which are included to provide a further understanding of the invention and are integrated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention. In the drawings:
FIG. 1 illustrates a synchronous multiplexing structure;
FIG. 2 is a block diagram of VC-11 and TUG-2 according to the present invention;
FIG. 3 illustrates mapping a DS-1 signal to a VC-11 signal;
FIG. 4 illustrates aligning a VC-11 signal to a TU-11 signal;
FIG. 5 illustrates multiplexing a TU-11 signal to a TUG-2 signal;
FIG. 6 illustrates a configuration of a lower hierarchy path overhead; and
FIG. 7 illustrates a configuration of a pointer.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENT
Reference will now be made in detail to the preferred embodiments of the present invention, examples of which are illustrated in the accompanying drawings.
An apparatus according to the present invention constructs a TUG-2 frame by multiplexing 1.544 Mbps data which is a DS-1 signal on the basis of the ITU-T recommendation for a SDH. By using only one transmitting buffer and one receiving buffer in a transmitter and a receiver respectively, a difference in construction and speed of data between a network signal of DS-1 and a system signal of TUG-2 is converted. A TUG-2 signal of 6.912 Mbps has 108 bytes per frame of 125 us as indicated in FIG. 5 and shows a structure multiplexed to A, B, C and D by interleaving a TU-11 signal of 27 bytes.
FIG. 1 shows a synchronous multiplexing structure, and the apparatus for implementing the integrated function of VC-11 and TUG-2 is connected thereto. A VC-11 circuit converts a DS-1 signal of a North American Standard to VC-11 data shown in FIG. 3. A TUG-2 circuit multiplexes the VC-11 data to 4:1 and transmits the multiplexed data to an upper layer from a lower layer.
The construction and operation of the apparatus according to the present invention will now be described with reference to FIGS. 2 to 7.
Referring to FIG. 2, the apparatus for implementing the integrated function of VC-11 and TUG-2 includes a transmitter 100 for converting a DS-1 network signal into a TUG-2 system signal by use of one TX FIFO buffer 120, and a receiver 200 for converting the TUG-2 system signal transmitted from the transmitter 100 to the DS-1 network signal by use of one RX FIFO buffer 260.
The transmitter 100 receives the DS-1 network TX signal of 1.544 Mbps and generates a TU-11 frame of 1.728 Mbps including spaces for a path overhead and a pointer by use of the TX FIFO buffer 120. The receiver 200 receives the TU-11 system signal of 1.728 Mbps in which the path overhead and the pointer are eliminated and generates the DS-1 network signal of 1.544 Mbps by use of the RX FIFO buffer 260. A bit leaking (BL) processor 290 of the receiver 200 adjusts a clock difference between a network and a system. A clock comparator 280 compares a write clock with a read clock. If the clock comparator 280 generates a control signal for the clock difference, the BL processor 290 implements bit leaking for a 6.912 MHz clock received from a DS-1 network and divides the bit leaked clock by a factor of four to be used as an RX FIFO read clock.
An input signal from a subscriber is 1.544 Mbps data coded to a B8ZS code and corresponds to the DS-1 network signal.
A B8ZS decoder 110 decodes a B8ZS input signal to a binary bit. During decoding, the B8ZS decoder 110 checks whether or not a code rule is violated. The TX FIFO buffer 120 writes input data by a TX FIFO write clock of 1.544 MHz synchronized with the B8ZS input signal, and reads data by an output clock of a transmitting clock generator 180 synchronized with a multiplexer, i.e., by a TX FIFO read clock of 1.728 MHz. The TX FIFO write clock is generated from a TX FIFO write clock generator 121 receiving a transmitting clock of 1.544 MHz from the DS-1 network. The TX FIFO read clock is generated from a TX FIFO read clock generator 122 using 1.728 MHz generated from the transmitting clock generator 180. The output data of the TX FIFO buffer 120 includes DS-1 data and has a perfect frame structure with spaces which can insert a lower hierarchy path overhead and a pointer value.
When a difference between the write clock generated from the TX FIFO write clock generator 121 and the read clock generated from the TX FIFO read clock generator 122 is 1 byte, a bit stuffing controller 130 generates a control signal for constantly maintaining the clock difference. A pointer generator 160 generates an incremental or decremental pointer adjusting signal according to the control signal generated from the bit stuffing controller 130, and generates substantially 1-byte data by adjusting a pointer value. A lower level pointer includes V1, V2, V3 and V4 bytes. Theses bytes are positioned at the first byte of each part when equally dividing a TU-11 frame of 500 us by four. Therefore, each Vn byte appears by 1 every 500 us frame.
The pointer is constructed as shown in FIG. 7. The first four bits of the V1 and V2 bytes, indicated by four N's, designate a new data flag, and the next two bits indicated by two S's represent a data size. The last 10 bits alternatively interleaved by I and D bits indicate an address and show a start address of a corresponding VC frame and a state when it is adjusted. The V3 byte is used to adjust a sub-position. The V4 byte is for preparation.
An overhead generator 150 generates an overhead for a lower hierarchy path of BIP (bit interleaved parity)-2 etc. and transmits the overhead inserted into a V5 byte of the VC-11 frame to a TU-11 frame former 140. As shown in FIG. 6, the V5 byte transmitting the lower hierarchy path overhead consists of a bit interleaved even number checking bit BIP-2, a far end block error indicating bit FEBE, a path tracking bit PT, a signal indicating bit Ln, a far end receive failure bit FERF, etc.
Meanwhile, the VC-11 circuit maps the DS-1 signal transmitted from the FIFO buffer 120 to a VC-11 signal of 104 bytes consisting of a path overhead byte V5, four information bytes 24I*, four fixed bytes R* and information and fixed byte Wn, as shown in FIG. 3.
The TU-11 frame former aligns the mapped VC-11 signal to a TU-11 signal. That is, four TU-11 frame formers 140-143 receive the DS-1 data generated from the TX FIFO buffer 120, the overhead generated from the overhead generator 150 and the pointer value generated from the pointer generator 160, and construct a perfect TU-11 frame. That is, as shown in FIG. 4, each TU-11 frame former, 140 for example, forms the VC-11 signal consisting of the path overhead byte V5 of one byte and C-11 of 103 bytes to the TU-11 frame of 108 bytes in which four pointer bytes V1-V4 are interleaved to four VC-11 signals each having 26 bytes. The four formed TU-11 frame data are multiplexed by a TUG-2 multiplexer 170 to 4:1, as shown in FIG. 5. The multiplexed data is supplied to an upper circuit. The four TU-11 data are sequentially interleaved one byte by one byte. The output data of the TUG-2 multiplexer 170 is transmitted to the upper circuit with a transmission speed of 6.912 Mbps.
The receiver 200 is opposite to the transmitter 100 in operation. A loopback controller 210 of the receiver 200 receives RX data of 6.912 Mbps at a normal mode. At a test mode, the TX data generated from the TUG-2 multiplexer 170 is fed back to the RX path 210 for judging an error of the circuit by checking whether the transmitting and RX data are equal. A TUG-2 demultiplexer 220 demultiplexes the data multiplexed to 4:1 to four independent data. Four TU-11 frame de formers 230-234 deform each frame for four data and extract transparent data, the path overhead and the pointer value. The transparent data indicates data in which the path overhead and the pointer value are eliminated, and represents non-modulated data. The transparent data out of the output data of the TU-11 frame de former 230, for example, is supplied to the RX FIFO buffer 260. The path overhead for a lower hierarchy path of BIP-2 etc. is interpreted by an overhead processor 240 to implement each unique function. A pointer processor 250 receiving the point value interprets the pointer value and judges the state of the point. The pointer processor 250 generates a control signal according to a judged result.
An RX clock generator 270 generates various clocks necessary for the operation of the receiver 200 by using an RX clock of 6.912 MHz and a receiving frame clock of 2 KHz. An RX FIFO write clock generator 261 supplies a write clock to the RX FIFO buffer 260 according to control signals of the overhead processor 240 and the pointer processor 250 by using a 1.728 MHz clock generated from the RX clock generator 270. The RX FIFO buffer 260 functioning as a data buffer is needed when the VC-11 frame and the DS-1 frame differ from each other in structure and when the pointer is adjusted. The clock comparator 280 monitors the write clock and the read clock and maintains a clock difference at a constant level. If there is a clock difference, the clock comparator 280 generates a bit leaking request signal. When the bit leaking request signal is generated from the clock comparator 280, the BL processor 290 processes bit leaking for a 6.912 MHz input clock generated from the DS-1 network and generates a 6.176 MHz clock. Moreover, the BL processor 290 divides the 6.176 MHz clock by a factor of four and generates a 1.544 MHz clock.
An RX FIFO read clock generator 262 reads data from the RX FIFO buffer 260 by using the 1.544 MHz clock generated from the BL processor 290 as the read clock. The read clock and the write clock of the RX FIFO buffer 260 are not equal. When the pointer adjusting signal is generated, there is a severe clock difference of one byte. Therefore, the clock comparator 280 monitors the write clock and the read clock in order to constantly maintain the clock difference. A B8ZS coder 295 codes the TU-11 signal which is the system signal of 1.728 Mbps supplied to the RX FIFO buffer 260 to a B8ZS code, and transmits the B8ZS coded signal with a speed of 1.544 Mbps.
As described above, the inventive apparatus accommodates the ITU-T recommendation associated with the synchronous multiplexing structure and implements the function of VC-11 and TUG-2. By using a TX and RX data buffer in the transmitter and the receiver respectively, a circuit configuration is simplified and the area of a chip is reduced. Further, the present invention has a wide application to the development of an ASIC (Application Specific Integrated Circuit) for SDH.
It will be apparent to those skilled in the art that various modifications and variations can be made in the apparatus of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.
What is claimed is:
1. An apparatus for implementing an integrated function of Virtual Container-11 (VC-11) and Tributary Unit Group-2 (TUG-2) in a synchronous multiplexing structure for synchronizing a DS-1 network signal and a TUG-2 system signal and transmitting the synchronized signal, said apparatus comprising:a B8ZS decoder for decoding a DS-1 network transmitting signal of 1.544 Mbps coded to a B8ZS code to network data; a transmitting signal write clock generator for generating a write clock used for writing the network data decoded from said decoder; a transmitting signal read clock generator for receiving a transmitting clock, and for generating a read clock used for reading the network data decoded from said decoder; transmitting data storing means for writing the DS-1 network data decoded from said decoder in synchronization with said write clock, and for generating the DS-1 network data of a Tributary Unit-11 (TU-11) frame structure of 1.728 Mbps including spaces for a path overhead and a pointer in synchronization with said read clock; a bit stuffing controller for generating a control signal for constantly maintaining a difference between said write and read clocks of said transmitting data storing means; a pointer generator for substantially generating one-byte data by adjusting a pointer value by utilizing a pointer adjusting signal when the difference between said read and write clocks is one-byte; an overhead generator for generating an overhead bit for a lower hierarchy path; frame formers for receiving the DS-1 network data generated from said transmitting data storing means, the overhead generated from said overhead generator and the pointer value generated from said pointer generator, and for forming TU-11 frame data; a transmitting clock generator for receiving a transmitting clock of 6.912 MHz, for transmitting a clock needed to read data to said transmitting signal read clock generator, and for generating a frame transmitting clock of 2 KHz; and a TUG-2 multiplexer for multiplexing the TU-11 frame data formed form said TU-11 frame formers, and for transmitting the multiplexed data with a speed of 6.912 Mbps.
2. The apparatus as claimed in claim 1, wherein said transmitting data storing means uses a first-in first-out buffer.
3. The apparatus as claimed in claim 1, wherein said read clock and write clock supplied to said transmitting data storing means are different from each other.
4. An apparatus for implementing an integrated function of Virtual Container-11 (VC-11) and Tributary Unit Group-2 (TUG-2) in a synchronous multiplexing structure for synchronizing a network signal of DS-1 and a system signal of TUG-2 and receiving the synchronized signal, said apparatus comprising:a loopback controller for receiving, in a normal mode, RX data of 6.912 Mbps, and for receiving, in a test mode, transmitting data as feedback to confirm whether the transmitting and RX data are equal; a TUG-2 demultiplexer for demultiplexing multiplexed TUG-2 system frame data received through said loopback controller into independent data; TU-11 frame de formers for deforming each frame of the independent demultiplexed data, and for extracting a path overhead, a pointer value, and a TU-11 signal in which the path overhead and the pointer value are eliminated; a path overhead processor for interpreting the path overhead extracted by one of said TU-11 frame de formers, and for implementing each corresponding function thereof; a pointer processor for interpreting the pointer value extracted by one of said TU-11 frame de formers, and for generating a control signal according to a judged result of the pointer value; an RX clock generator for generating various clocks necessary for an operation of a receiver by using an RX clock of 6.912 MHz and a receiving frame clock of 2 KHz applied from without; an RX data write clock generator for receiving the clock generated from said RX clock generator, and for generating a write clock used for writing TU-11 system data of 1.728 Mbps in which the path overhead and the pointer are eliminated according to control signals of said overhead processor and said pointer processor; an RX data read clock generator for generating a read clock used for reading data from a clock obtained by dividing a bit leaked clock by a factor of four; a clock comparator for comparing said write clock with said read clock to constantly maintain a clock difference, and for generating a bit leaking request signal when there is a clock difference; a bit leaking processor for bit leaking a 6.912 MHz input clock by said bit leaking request signal generated from said clock comparator, and for dividing the bit leaked clock by a factor of four; RX data storing means for storing the TU-11 data in which the path overhead and the pointer are eliminated in synchronization with said write clock, and for converting the stored TU-11 data to DS-1 data in synchronization with said read clock; and a B8ZS coder for coding the DS-1 data generated from said RX data storing means to a B8ZS code, and for transmitting the B8ZS coded signal with a speed of 1.544 Mbps.
5. The apparatus as claimed in claim 4, wherein said RX data storing means uses a first-in first-out buffer.
6. The apparatus as claimed in claim 4, wherein said read clock and write clock supplied to said RX data storing means are different from each other.
|
Thread:<IP_ADDRESS>/@comment-22439-20160726222252
<!Hi, I'm an admin for the community. Welcome and thank you for your edit to Natsuki Subaru!
Enjoy your time at !
|
Skeleton bony; anterior vertebrae distinct, without Weberian ossicles; ventral fins abdominal, rarely wanting; all fins soft-rayed, although the first dorsal ray is in a few forms somewhat stiffened and spine-like; no adipose fin; pectoral arch suspended from the skull; mesocoracoid wanting (this character constituting the only important distinction between these fishes and the Isospondyli); opercular bones well developed; air-bladder with a distinct duct. Four families; species numerous and widely distributed, chiefly in habiting fresh or brackish waters of both hemispheres.
THE MUDFISHES
Body oblong, broad anteriorly and compressed behind; head somewhat flattened; scales cycloid, covering head and body; lateral line wanting; skeleton osseous; anterior vertebrae simple; no spines in fins; ventrals ab dominal; dorsal fin posterior; caudal rounded; no mesocoracoid; gill-mem branes little connected; branchiostegals 6 to 8; pseudobranchise hidden, glandular; gill-rakers little developed; mouth moderate, premaxillary not protractile; lateral margin of upper jaw formed by the maxillaries, which are toothless and without distinct supplemental bone; premaxillaries, lower jaw, vomer, and palatines with bands of villiform or cardiform teeth, stomach without blind sac; no pyloric ceeca; air-bladder simple, with distinct duct; oviparous fishes.
|
require 'spec_helper'
require 'csv'
module Pris
module Halebop
describe Zones do
let(:country_map) { CSV.read("./spec/example_data/halebop_country_map.csv", headers: :first_row) }
let(:subject) { Zones.new(country_map) }
describe "#[]" do
it "returns the zone of the given country" do
expect(subject["Finland"]).to eq("zone_1_eu")
end
end
end
end
end
|
Find the numbers that would satisfy an upper index, that would lead it to be divisible by 3
\begin{equation}\displaystyle{\sum_\limits{i=0}^n}i\end{equation}
Find the values of n for which the summation is divisible by 3. If Possible write a general formula.
This is a puzzle I know that 2 works and 5, 6 and so on
You can use $\displaystyle \sum_{ i =0}^{n} i = \frac{n(n+1)}{2}$. Then the problem effectively reduces to finding all $n$ such that $6$ divides $n(n+1)$.
You should have figured out that $\sum\limits_{i=0}^n i = \dfrac{n(n+1)}{2}$. Now... what happens if $n$ is divisible by $3$ or if $n+1$ is divisible by $3$?
First, this is equivalent to:
$\sum_{i = 1}^{n}i = 1 + 2 + ...+ (n - 1) + n$
Using the formula for the sum of an arithmetic series:
$1 + 2 + ...+(n-1)+n = \frac{n(n + 1)}{2}$
Obviously this is an integer, because one of $n$ and $n+1$ must be even (divisible by $2$).
Now, we need $\frac{n(n+1)}{2}$ to be divisible by $3$. This is true if and only if one of $n$ and $n + 1$ is divisible by 3. In other words, $n$ must be a multiple of $3$ or one less than a multiple of $3$. Using modular expressions for compactness, the solution set is
$\boxed{\big\{n : n\equiv 0\pmod{3} \text{ or }n\equiv 2\pmod{3}\big\}}$
\begin{align*}
\begin{cases}
S = 1 & + & 2 & + & 3 & + & \ldots & + & n\\\\
S = n & + & (n-1) & + & (n-2) & + & \ldots & + & 1
\end{cases} \Longrightarrow 2S = n(n+1) \Longrightarrow S = \frac{n(n+1)}{2}
\end{align*}
|
Mongo time-series inserts using c# produce exception after short time
I want to test if mongo db can have a collection up to 50 000 000 000.
So I insert 10K elements every second using method:
public async Task InsertManyAsync(List<DBRoutLine> list)
{
await _collRouts.InsertManyAsync(list);
}
Data looks like this:
namespace DbLayer.Models
{
public class DBRoutLineMeta
{
[BsonId]
[BsonRepresentation(BsonType.ObjectId)]
public string id { get; set; }
public int counter { get; set; }
}
[BsonIgnoreExtraElements]
public class DBRoutLine
{
[BsonId]
[BsonRepresentation(BsonType.ObjectId)]
public string id { get; set; }
public DBRoutLineMeta meta { get; set; } = new DBRoutLineMeta();
public DateTime timestamp { get; set; } = DateTime.UtcNow;
public string some_data { get; set; } = DateTime.Now.ToString();
}
}
id members not required actually but I have them, just for testing.
So I've got exception like this:
"A bulk write operation resulted in one or more errors. WriteErrors: [ { Category : "DuplicateKey", Code : 11000, Message : "E11000 duplicate key error collection: TSTest.system.buckets.TSTable dup key: { _id: ObjectId('634e87301297fa65b7df9923') }" } ]."
after sometime. It can be also like this:
"time-series insert failed: TSTest.TSTable :: caused by :: Expected
And it will never recover from error even if I recreate connection to mongo server. Only application restart helps to insert records again.
Test code:
using DbLayer.Models;
using DbLayer.Services;
using MongoDB.Bson;
Console.WriteLine("Hello, World!");
var service = new RoutService();
try
{
CancellationTokenSource tokenSource = new CancellationTokenSource();
CancellationToken token = tokenSource.Token;
var list = new List<DBRoutLine>();
for (int i = 0; i < 10000; i++)
{
DBRoutLine line = new DBRoutLine();
list.Add(line);
}
Task task = Task.Run(async () => {
int max_counter = await service.GetMaxCount();
bool recover = false;
while (!token.IsCancellationRequested)
{
try
{
if (!recover)
{
foreach (DBRoutLine line in list)
{
line.meta.counter = ++max_counter;
line.id = ObjectId.GenerateNewId().ToString();
line.meta.id = line.id;
}
}
var t1 = DateTime.Now;
await service.InsertManyAsync(list);
var t2 = DateTime.Now;
max_counter = await service.GetMaxCount();
var t3 = DateTime.Now;
Console
.WriteLine(
$"{max_counter}->Insert:{(int)(t2 - t1).TotalMilliseconds}, GetMax:{(int)(t3 - t2).TotalMilliseconds}");
recover = false;
}
catch(Exception ex)
{
recover = true;
await Task.Delay(3000);
Console.WriteLine(ex.Message.ToString());
service = new RoutService();
max_counter = await service.GetMaxCount();
}
}
}, token);
Console.WriteLine("Press any key to stop emulation\n");
Console.ReadKey();
tokenSource.Cancel();
Task.WaitAll(task);
}
catch (Exception ex)
{
Console.WriteLine(ex.Message);
}
Service code:
using DbLayer.Models;
using MongoDB.Bson;
using MongoDB.Driver;
namespace DbLayer.Services
{
public class RoutService:IDisposable
{
private readonly IMongoCollection<DBRoutLine> _collRouts;
private readonly MongoClient _mongoClient;
private readonly string CollName = "TSTable";
public RoutService(
)
{
var ConnectionString = "mongodb://mongoservice:27017";
_mongoClient = new MongoClient(
ConnectionString);
var mongoDatabase = _mongoClient.GetDatabase(
"TSTest");
var filter = new BsonDocument("name", CollName);
var options = new ListCollectionNamesOptions { Filter = filter };
if (!mongoDatabase.ListCollectionNames(options).Any())
{
var createOptions = new CreateCollectionOptions();
var timeField = nameof(DBRoutLine.timestamp);
var metaField = nameof(DBRoutLine.meta);
createOptions.TimeSeriesOptions =
new TimeSeriesOptions(timeField, metaField, TimeSeriesGranularity.Minutes);
mongoDatabase.CreateCollection(
CollName,
createOptions);
}
_collRouts =
mongoDatabase.GetCollection<DBRoutLine>(
CollName
);
CreateIndexes();
}
private void CreateIndexes()
{
{
IndexKeysDefinition<DBRoutLine> keys =
new IndexKeysDefinitionBuilder<DBRoutLine>()
.Descending(d => d.meta.counter);
var indexModel = new CreateIndexModel<DBRoutLine>(
keys, new CreateIndexOptions()
{ Name = "counter" }
);
_collRouts.Indexes.CreateOneAsync(indexModel);
}
////////////////////////////////////////////////
{
IndexKeysDefinition<DBRoutLine> keys =
new IndexKeysDefinitionBuilder<DBRoutLine>()
.Ascending(d => d.meta.id);
var indexModel = new CreateIndexModel<DBRoutLine>(
keys, new CreateIndexOptions()
{ Name = "id" }
);
_collRouts.Indexes.CreateOneAsync(indexModel);
}
}
public async Task InsertManyAsync(List<DBRoutLine> list)
{
await _collRouts.InsertManyAsync(list);
}
public async Task<int> GetMaxCount()
{
var last = await _collRouts
.Find(i=> i.meta.counter > 0)
.SortByDescending( i => i.meta.counter).FirstOrDefaultAsync();
if (last == null)
{
return 0;
}
return last.meta.counter;
}
public void Dispose()
{
}
}
}
project repository:
github.com/pruginkad/TestMongo
Please share your code
Does it ever create any records? It seems you are specifying a field in class DBRoutLine called id of type string. I can't see where you are setting a specific value, but since you have decorated it with [BsonId] I believe it maps t the _id field which must be unique. Try setting it to a unique value.
https://github.com/pruginkad/TestMongo
no id is not a problem. In time-series collection it's not required actually. I even deleted it to try but still the same problem. I can insert about 10 000 000 records before the exception occurs. So the code works, the problem in mongo I believe or in some settings which required for connection. Or c# driver bug, otherwise mongo developer could run into the same problem
Ok, I found the bug. I changed timestamp only once when I created List of documents.
in this code:
foreach (DBRoutLine line in list)
{
line.meta.counter = ++max_counter;
line.id = ObjectId.GenerateNewId().ToString();
line.meta.id = line.id;
line.timestamp = DateTime.UtcNow;//missing line
}
I had to update timestamp, my mistake.
Anyway it's kind of strange that exception happen after every 17M documents and disappear after restart of mongo db
|
**2. Bariatric surgery methods**
### **2.1 Roux-en-Y gastric bypass (RYGB)**
The surgical treatment that is still considered a standard technique and widely used for the treatment of morbid obesity is RYGB [6, 7]. In RYGB, a small gastric pouch attaches to the small intestine and bypasses the stomach, duodenum, and proximal jejunum [8]. Recently, RYGB is the second most common operation worldwide, sleeve gastrectomy (SG) preceded that [9]. Although RYGB frequency is surpassed worldwide by sleeve gastrectomy (SG), long-term results in weight reduction, remission of comorbidities also changing quality of life, are well documented and make the RYGB a common bariatric procedure [6, 7, 10]. For these good results, identifiable factors are mostly a combination of mechanisms of action, which include mild malabsorption by bypassing a reasonable part of the jejunum, mechanical restriction of calorie intake due to the small gastric pouch, and hormonal changes like a decrease in the production of ghrelin, early secretion of PYY and changes in various incretin levels, such as GLP1 [11]. For patients with gastroesophageal reflux disease, many are seen as the gold standard treatment and it is recommended as the first method of choice for patients with type 2 diabetes mellitus [12]. Hepatic hypersensitivity to insulin has been shown to improve within a week after RYGB, and after months, after major weight loss, insulin sensitivity in adipose tissue and skeletal muscle also improves [13]. However, due to changes in intestinal anatomy after LRYGB, the internal hernia can occur through the Petersen space mesenteric defect or the mesenteric jejunojonostomy defect during follow-up [10]. After LRYGB, a frequent complication is small bowel obstruction [14]. Fasting bile acid levels increase after RYGB but do not increase after SG [15]. Long-term complications may occur. Re-interventions are sometimes needed. In very rare cases, a return to normal anatomy may be due to severe dumping syndrome, gastric bypass malnutrition, excessive
weight loss, postprandial hypoglycemia, or recurrent marginal ulcers [9]. Long-term complications, such as anemia, may not be diagnosed by non-bariatric specialists. Anemia causes include folate, iron, and B12 deficiency. Bleeding marginal ulcers, and selenium, copper, and vitamin A deficiency are the less common causes [16].
|
Implement new slider in Android 13 media player via Jetpack Compose
Is there a way to set the stroke of Bezier curves in Android canvas? And also how do I animate the shift of slider track. Image of the desired slider.
I opened the Material 3 slider implementation in Jetpack Compose. And there you can change the slider track with any other Compose function. The shift of the Bezier curve along the Y axis did not give the desired result. And the mathematical shift of the curve along the normal is too complicated an operation for a small interface element. I think there is a much simpler way to implement such a slider.
https://github.com/galaxygoldfish/waveslider
See this post and this library
|
SUMProduct or Sum if to only count values in multiple rows
I want to use sumproduct to count multiple rows if the formula finds a match in a particular column. I'm using the following formula:
=SUMPRODUCT(('CPT Utilization'!C:C="IMRT Treatments Commercial")*('CPT Utilization'!AD:AO))+SUMPRODUCT(('CPT Utilization'!C:C="IMRT TX to Medicare plans (G Codes)")*('CPT Utilization'!AD:AO))+SUMPRODUCT(('CPT Utilization'!C:C="Daily Treatments Commercial Plans")*('CPT Utilization'!AD:AO))+SUMPRODUCT(('CPT Utilization'!C:C="Daily TX to Medicare plans (G codes)")*('CPT Utilization'!AD:AO))
It works fine, except currently there are no values for columns AE:AO, as those are future months, and they are displaying as #DIV/0, which is giving my formula total a #DIV/0. Is there a way to count the columns only when they have a total. So when AE has a 4, it will count it, but not if it is displaying #Div/0?
In a hidden cell, I've put a formula that will display the columns if a certain month is entered. For example, when February is typed it, the formula displays AD:AE. I tried linking that formula into my sumif, but it is pulling like this: ")*('CPT Utilization'!G15)).
G15 is on another sheet, so that is not working correctly.
If you don't mind.. you may accept the answer like this. It'll remove this question from SO 'unanswered' list. || Alternatively if the example doesn't work for you.. please share the details here. ( :
If you want the Count not the Sum you can use ISNUMBER like the following:
=SUMPRODUCT(('CPT Utilization'!C:C="IMRT Treatments Commercial")(ISNUMBER('CPT Utilization'!AD:AO)))+SUMPRODUCT(('CPT Utilization'!C:C="IMRT TX to Medicare plans (G Codes)")(ISNUMBER('CPT Utilization'!AD:AO)))+SUMPRODUCT(('CPT Utilization'!C:C="Daily Treatments Commercial Plans")(ISNUMBER('CPT Utilization'!AD:AO)))+SUMPRODUCT(('CPT Utilization'!C:C="Daily TX to Medicare plans (G codes)")(ISNUMBER('CPT Utilization'!AD:AO)))
In this case if in 'CPT Utilization'!AD:AO there is text or #Div/0 it will not be included.
|
#!/bin/sh
ROOT=$(cd `dirname $0` && pwd)/..
cd $ROOT
lein cljsbuild clean
lein cljsbuild once prod
echo "Finalizing chessground.js"
(cat $ROOT/libs/interact.js; cat $ROOT/scripts/wrapper.beg.txt; cat $ROOT/generated-prod/chessground.prod.js; cat $ROOT/scripts/wrapper.end.txt) > $ROOT/scripts/chessground.tmp.js
$ROOT/node_modules/.bin/uglifyjs $ROOT/scripts/chessground.tmp.js -o $ROOT/chessground.js
rm $ROOT/scripts/chessground.tmp.js
|
DICOTYLEDONS
flowers. The plant is sickly for want of the necessary light. A dense forest produces the same effect. There is so much shade that hardly any herb can grow in it. How many plants die there for want of light! How many seeds fall there to the ground and germinate, but cannot grow further, perishing miserably in the dark thicket!
The seed of a liana has to germinate under such disadvantages and would cer tainly suffer the same miserable death, if it were not provided with certain qualities that other plants lack. Above all, the liana is distinguished by an unusually quick growth, by which it brings its foliage to the top of trees in a very short time. The darkness and the damp air in the jungle are advantageous to quick growth. It is as if the plant in its youth had no other aim than this, and as if everything else about its growth was subservient to this one end: it does not form many leaves; it does not produce branches; the stem does not grow in width; it only grows in length. The stem thus becomes so slender and weak that it cannot stand upright by itself. What may now be its fateV Shall it yet die in the struggle for existence?
It Avould certainly die, if it had not the wonderful ability to use as its support the very giant tree in its vicinity which threat ened to be the cause of its death and to clioke it. The Elephant Climber climbs the tree by winding roun<l it. The leatless tip of the slender stem moves spirally until it finds something to grasp, round which it then winds in the direction opposite to that in which the hands of a clock move. If the stem cannot find any support, it sinks down to the ground, striking new roots
|
Is gorm supported for snowflakedb ?
Your Question
We are using GORM for managing our MySQL DBs and tables. We are also using Snowflake and until now we were using the native SQL queries. Snowflake as a SQL driver - https://github.com/snowflakedb/gosnowflake
So the question is, if we use gorm to manage our Snowflake DBs and tables, are there any potential issues that we should be aware of?
The document you expected this should be explained
Expected answer
I haven't used the Snowflake database, maybe you can give it a try, and we also accept pull request for other databases support.
Thank you.
@jinzhu I am working on a snowflake driver for gorm here: https://github.com/omixen/gorm-snowflake
Some notes:
It is still work in progress
There is note on what features supported/supported due to Snowflake limitations
The issue page has list of unit tests that are currently broken due to either SF limitation or one of the decision I made (e.g. not quoting/accepting case-insensitive names)
There will be a PR going into this repo later with minor changes and skip-tests to accommodate SF.
Unfortunately, SF is cloud based and we can't have a test environment, unless we can get an open source instance.
which I can try to ask.
Should we re open this issue?
|
Hello, how can I help you today?
I am having an issue with my subscription. For some reason it was removed from my account.
Glad to help. May I have your full name please?
Joseph Banter
thanks Joseph.
How did you hear about this issue?
My wife told me
got it.
I am going to check my system about this problem.
the system shows that nothing has changed in your account and there are no extra charges. So you have nothing to worry about. Your wife might have misheard the news.
Weird. Are you sure?
Yes. Can you see the service properly activated on your account now?
hold on, let me check Ok. I see it now
Great. Is there anything else that I can help you with?
No. That's it. thank you
Have a nice day!
|
Generate types inside a theme package
When developing a theme, types are generated inside a playground. This makes it hard to properly link types while developing a theme. To improve this, types could also be generated inside the theme package to prevent issues with hoisting or circular type references.
Things to consider:
Types are generated using the AIK utility addDts. This utility only generates types inside a user project, this issue would require a custom utility (or an upstream addition to AIK) for type generation inside a package
Where are these types generated inside a package? virtual.d.ts?
I am going to take over this issue and rename it, I worded it poorly and didn't explain exactly why I created it. Generating types inside the theme's package may have some advantages, but I don't know of any right now.
The real issue here is that theme authors need Content Collections types while developing inside a package.
This is a bit complicated because we need to generate the Content Collection types inside a playground and hoist them somehow so that authors have type safety when creating theme packages.
TLDR: Typically, types flow downwards from packages to users. We need to pass types upwards from a user to a package.
|
Add a script for searching for Cody commits by JetBrains version
By running pnpm run canhaz nnnn where nnnn is a sourcegraph/cody commit, this script will print which JetBrains versions contain that commit. You must set the CODY_DIR environment variable to a sourcegraph/cody repo; this script will fetch commits in that repo.
This reads version tags from the repo containing the working directory. If you need to fetch version tags, run the command mentioned in the script first.
Test plan
This adds a script, it does not affect the product.
$ CODY_DIR=~/dev/cody pnpm run canhaz 343d9cfe7539806f447f23e0f9a4be70dcf713c3
> @ canhaz C:\Users\DominicCooney\dev\jetbrains\scripts
> ts-node canhaz.ts "343d9cfe7539806f447f23e0f9a4be70dcf713c3"
This script checks whether a given JetBrains release contains a specific Cody commit.
To fetch version git tags from origin, run:
git fetch origin 'refs/tags/v*:refs/tags/v*'
Using sourcegraph/cody repo in C:/Users/DominicCooney/dev/cody
✔️ v7.0.6-nightly
✔️ v7.0.6
✔️ v7.0.5-nightly
✔️ v7.0.4-nightly
✔️ v7.0.4
✔️ v7.0.3-nightly
✔️ v7.0.2-nightly
✔️ v7.0.2
✔️ v7.0.1-nightly
✔️ v7.0.1
✔️ v7.0.0-nightly
✔️ v7.0.0
✔️ v6.0.38-nightly
✔️ v6.0.37-nightly
✔️ v6.0.36-nightly
✔️ v6.0.35-nightly
❌ v6.0.34-nightly
❌ v6.0.34
❌ v6.0.33-nightly
✔️ v6.0.32-nightly
✔️ v6.0.31-nightly
❌ v6.0.30-nightly
❌ v6.0.29-nightly
❌ v6.0.28-nightly
❌ v6.0.27-experimental
oh this is so nice!! thank you dominic 😍
but it only searches on the main branch right? I know we don't often fork but it could be helpful
|
Sylvania
110 Drawing.
UNITED STATES PATENT OFFICE.
FRANK G. BREYEB, ALBERT E. HALL, AN'D GEORGE B. WALTZ, 0F PALMERTON, PENN- SYLVANIA, ASSIGNORS TO THE NEW JERSEY ZINC COMPANY, OF NEW YORK, N. Y.,
A CORPORATION OF NEW JERSEY.
PRODUCTION OF METAL OXIDS AN D OTHER COMPOUNDS 0]? METALS.
To all whom it may concern Be it known that we, FRANK G. BREYER, ALBERT E. HALL, and GEORGE R. WALTZ, all citizens of the United States, residing at Palmerton, Pennsylvania, have invented certain new and useful Improvements in the Production of Metal Ox ids and other Compounds of Metals; and we do hereby declare the following to be a full, clear, and exact description of the invention, such as will enable others skilled in the art to which ita pertains to make and use the same.
T is invention relates to the production of metal oxids or other compounds of metals volatilized by the WV ether ill process.
Metallic oxids, such, for example, as zinc oxid and leaded zinc oxid, as well as other compounds of metals volatilized by the Wether ill process, such, for example, as basic lead sulfate or sublimed lead, have heretofore been more or less extensively produced by the so-called \Vet her ill process. In speaking of metals volatilized by the \Vet her ill process, we intend to describe and cover such metals as are volatilizable at the temperatures attainable in the \Vet her ill' process, and for the sake of brevity, we shall hereinafter designate these metals as volatilizable metals. In the case of certain of such metals, the final or desired compound or compounds thereof are the result of a sequence of actions in which the metallif er ous materials of the charge are reduced, the reduced metal volatilized and then oxidized or otherwise compounded, while in other cases a metal compound may be directly volatilized, with or without subsequent oxidation or compounding.
By the expression \Vet heril] process as we have used the same herein is to be understood the furnacing step of the process for produc ing metal oxids or other compounds of volatilizable metals in which a charge of the metallif er ous mater lal mixed with a red uc ing agent and spread on an ignited bed of fuel is subjected to a combustion supporting blast oi draft and brought to a sufficiently high temperature to reduce the metallif er ous materials and volatilize the reduced metal or metals (and (or) to volatilize a metal or a metal compound or compounds) without bringing the charge to a condition where it becomes rmpervious to the blast or draft, the entire charge being supported on a furnace hearth Specification of Letters Patent.
Application filed July 12, 1919. Serial No. 310,440.
Patented Nov. 18, 1919.
or grate designed to hold it without letting any considerable part drop through, and the worked-off material being discharged as a clinker or sinter. The furnacing step is independent of the subsequent treatment of the laden furnace gases and of the collection of the metal compound or compounds.
As a typical example of the VVet her ill process, as heretofore usually practised, we will briefly describe the customary procedure in the commercial production of zinc oxid, including leaded zinc oxid. The furnacing step is generally carried out in a furnace having a broad expanse of horizontal grate or hearth roofed over with an arch, and associated with appropriate instrumentalities for permitting the passage there through and into the charge, by either a blast or draft, of a combustion supporting gas. It is customary to first charge upon the furnace grate or hearth a layer of buckwheat anthracite coal (which is thereupon ignited, usually by the residual heat of the furnace) and by means of a forced blast or draft of air to bring this initial layer of coal to well-developed combustion. Upon this layer of bed coal is then charged the customary mixture or working charge characteristic of the 'ether ill process, that is to say, a mixture of finely divided red uc ing coal with the finely divided zincif er ous (or zincif er ous and plumbif er ous) material, such as zine silicate, roasted zinc blends, roasted so-called mixed sulfids of zinc and lead, spelter retort residues, or other red uci ble zinc-containing or zinc-and lead containing material at the disposal of the operator. The forced air draft is continued, and, when the familiar flames of greenish tint, known as zinc candles, begin to make their appearance above the upper surface of the charge, indicating that the reduction and volatilization of the zinc and its oxidation to the form of fume is well under way, the products of combustion carrying the zinc oxid fume and other volatilized metallic compounds are conveyed through the customary cooling fines, etc., to the bag-room wherein, in a cooled condition, they filter through the bags and pass oif into the atmosphere, leaving the fume collected in the interior of the bags, from which it is removed at convenient intervals. The furnace operation is continued until the production of fume therefrom in appreciable quantitv ceases, whereupon the residual charge, which is, to a large extent, sintered together, is broken up by long-handled rabble s and pried up and lifted or scraped out through the furnace doors into a receiving pit, or the like, preparatory to the starting of a new operation. The coal or other carbonaceous material of the charge serves the two-fold purpose of furnishing a red uc ing agent for effecting the reduction of the metallif er ous materials of the charge and of furnishing, by combustion, the necessary degree of heat to bring these materials to the red uc ing temperature characteristic of the process.
As thus ordinarily practised, the above described furnace operation is attended with certain defects interfering with its full efficiency. Prominent among these defects is the inevitable tendency to the formation of blow-holes or craters at various regions of the charge. lVorking or rab bling of the charge to break up these blow-holes involves considerable labor, and, in addition, the formation of blow-holes causes waste of fuel and inefliciency in the recovery of values. A further defect of the above-described furnace operation is that the forced draft tends to project into the free space above the charge more or less dust, and thus dusting is further aggravated by the rab bling operations. This dust contaminates the fume and damages its color and marketability. These and many of the other defects of the above-described furnace operation as heretofore generally practised are overcome to a very remarkable extent by modifying the heretofore customary practice in accordance with the improvements described in the application for Letters Patent of the United States of Frank G. Breyer, James A. Sing master and Albert E. Hall, Serial No. 270,179, filed January 8, 1919. These improvements consist in supply ing either or both the bed fuel and the working) charge to the furnace hearth in the form of rique ts. The improved results attendant upon this modification in the prior customary practice are described in detail in the aforementioned application.
We have discovered that a further decided improvement in the efficiency of the aforementioned furnace operation can be secured by appropriately modifying the relative proportions of fuel, including red uc ing agent. in the working charge and bed fuel in accordance with the principles hereinafter explained. Thus, briefly, we have discovered that when the greater proportion of the total fuel of the charge is placed in the form of brique ts in the bed fuel, rather than in the working charge as has heretofore been customary, a very complete working-ofi' of the volatilizable metal values is effected, The relatively deep bed of fuel brique ts when in full combustion imparts to the superposed working charge a hi hly red uc ing atmosphere and a sufficient y hi h and very uniform temperature where y 90% or more of the volatilizable metals may be recovered from the metallif er ous material of the charge, as compared with recoveries of about under the heretofore customary furnace practice with unbrique ted charges and recoveries of from 80 to 85% with brique ted charges as described in the aforementioned Breyer-Sing master-Hall application.
The residual charge from the hereinbefore described furnace operation (with unbrique ted charges) consists of a more or less sintered mass containing the ash of the consumed fuel, unconsumed fuel and the worked-off metallif er ous material. These various materials are more or less mixed together and their mixed condition seriously prejudices subsequent treatment of the residue and the separation and recovery there from of such valuable materials as it usually contains. When this heretofore customary practice is modified by supply ing the usual working charge mixture to the furnace hearth in the form of brique ts, the worked off charge is still a mixture of ash, unconsumed fuel and worked-ofl' metallif er ous material. By pla ein the greater proportion of the total fue of the charge in the bed fuel in the form of brique ts, and by supply ing the working charge, with its correspondingly reduced content of fuel and red uc ing agent, in the form of brique ts, we very materially reduce the amount of combustible material associated with the metallif er ous material of the working charge and thereby enable the working charge brique ts to retain for the most part their original form and shape, whereby the Worked-off ore or metallif er ous bri ue ts may be readily separated from the clinkered residue of the bed fuel brique ts. At the same time, the amount of ash associated with the worked off ore brique ts is of such small amount that these worked-off brique ts can be subsequently treated for the recovery of further metallic values without serious difficulty.
In the customary commercial practice of the \Vet her ill process, the total carbonaceous material in the entire charge, including the bed fuel and the Working charge mixture, is several times greater than the theoretical amount required to reduce the compounds of a the volatilizable metals in the charge. It has heretofore been the general practice to place the greater proportion of the total carbonaceous material of the entire charge in the working charge mixture. For. example. when operating with the well known Franklin furnace zinc oxid ores. it is customary to place from about fifteen (15) to twenty-five (25) per cent. of
the total carbonaceous material of the entire charge in the bed fuel, while the remaining eighty-five (85) to seventy-five (75) per cent. of the total carbonaceous material is mixed with the ore to form the Working charge. In general terms, the layer of bed fuel is approximately one inch in depth of thickness, while the working charge mixture is spread over the ignited bed fuel in a layer from about five (5) to seven (7) inches in depth or thickness.
\Ve have discovered that a very considerable proportion of the carbonaceous or other combustible material can be withdrawn from the working charge and placed in the bed fuel when the bed fuel is supplied to the fur nace hearth in the form of brique ts. Thus, for example, when operating with Franklin furnace zinc oxid ores, we have obtained excellent results by placing from about seventy-five (75) to eighty-five (85) per cent. of the total carbonaceous material of the entire charge in the bed fuel and supply ing this bed fuel to the furnace hearth in the form of brique ts. The remaining twenty-five (25) to fifteen (15) per cent. of the total carbonaceous material is then admixed with the ore to form the workin charge. The working charge is also pre erably brique ted and spread on the ignited bed fuel brique ts.
In carrying out the invention, the brique ted bed fuel is charged onto the furnace hearth in any appropriate manner, ignited and brought to full combustion by passing a combustion-supporting gas, such as air, into the bed fuel brique ts. The working charge is then spread onto the ignited bed of fuel brique ts, and the resulting efliuent is withdrawn from the furnace and appropriately treated for the removal and collection of the metallic compounds contained therein. In working with Franklin furnace zinc oxid ores, we have secured very satisfactory results by charging the brique ted bed fuel in a layer of approximately five (5) to six (6) inches in depth or thickness, and spreading onto the ignited layer of these bed fuel brique ts a layer of workin charge brique ts of approximately four (4 to five (5) inches in depth or thickness.
\V hen the compounds of the volatilizable metals of the working charge have been worked-off to the desired extent. the residual charge may be withdrawn or discharged from the furnace in any suitable manner. This residual charge consists of a relatively thin layer of clinker on which rests the worked-off ore brique ts. During the process the bed fuel brique ts undergo substantial ly f complete combustion, and are discharged as a clinkered ash. On the other hand, the physical form of the brique ted working charge is not materially altered and for the most part the worked-oil ore brique ts retain their original shape with only incipient fusion.
The bed fuel brique ts may be prepared by compressing finely divided coal, together with a suitable binder, such, for example, as the concentrated waste sulfite liquor of the sulfite paper pulp industry. Various forms and grades of carbonaceous material are available for the bed fuel brique ts. Thus, for example, anthracite coal below the No. 3 buckwheat size, such as No. 4 buckwheat, colliery washings, dirt oo al, dust coal, as well as coke breeze, may be utilized in the production of the bed fuel brique ts. The bed fuel brique ts are of such size and shape as to materially reduce the resistance to the combustion supporting gas, and nevertheless to supply such a substantial ly uniform substratum for the support of the superposed working charge as to give free access therethrough and practice. ly equal distribution thereto of the combustion supporting gas. To this end, the bed fuel brique ts, as well as the working charge brique ts, should be of substantial ly uniform size, and preferably of such shape that they roll or tumble easily over one another. Thus, we have found the so-called pil low block, eggette, rounded pil low block, over-stuffed il low, and simllar shapes well suited to t e purposes of the invention.
While the working charge consisting of a mixture of the metallif er ous material and an appropriate red uc ing agent maybe supplied to the ignited la 'er of bed fuel brique ts in an unbrique ted orm, we prefer to briquet the working charge because of the many attendant advantages. Furthermore, we wish it to be understood that the metallif er ous material may be brique ted alone, without briqueting the red uc ing agent, or the red uc ing agent may be brique ted alone without briqueting the metallif er ous material, or the red uc ing agent and the metallif er ous material may be separately brique ted. However, our preferred practice is to briquet a mixture of the metallif er ous material and the red uc ing agent.
The red uc ing agent of the working charge may be of any suitable kind, and while we. now prefer to employ carbonaceous material as the red uc ing agent, it will be understood by those skilled in the art that red uc ing agents other than carbonaceous materials are available for the purpose of the invention. One of the advantages of employing a brique ted red uc ing agent in any of the forms hereinbefore described is that it permits the use of carbonaceous materials of cheaper grades and finer mesh, such as anthracite coal of finer mesh than No. 3 buckwheat, colliery washings, dust coal, coke breeze and the like.
The bed fuel brique ts and the working charge brique ts may be prepared in any suitable binder, such as concentrated waste sulfite liquor of 30 Baum, mold in the mixture into brique ts of the desire size and shape, and drying or baking the brique ts at a temperature of approximately 200 C., so as to impart to them the desirable amount of resistance to crumbling and breaking so that they may be freely subjected to the rough handling incident to storing them, conveying them to the fur nace, and incident to char ing them into the furnace either by han or otherwise. In the case of the brique ted metallif er ous material, it is also desirable that the brique ts possess such resistance to crumbling and breakin as to substantial ly maintain their form uring the entire furnacing operation, so that they are for the greater part discharged from the furnace in substantial ly their original physical form.
When practising the Wether ill process in accordance with the principles of our present invention, the residual charge consists of a more or less clinkered coal ash, resulting from the combustion of the bed fuel brique ts, and a residue, resulting from the workingoif of the metallif er ous charge. When, as 1n the preferred embodiment of the invention, the metallif er ous material of the working charge is supplied to the furnace hearth in the form of brique ts, this residue contains the worked-off ore brique ts in substantial ly their original physical form. Some of the working charge brique ts will almost inevitably become broken or crushed in the preliminary handling and furnacing operation, but these brique ts for the greater part retain their original physical form. After the furnacing operation, these brique ts are remarkably hard and almost coke-like in their physical characteristics, and are readily separated from the clinkered coal ash of the bed fuel brique ts.
This ca ability of readily separating the worked-o metallif er ous or ore brique ts from the ash of the fuel brique ts is of especial advantage when the worked-oil ore brique ts are to be subjected to further treatment for the recovery of valuable metals not volatilizable by the lVet her ill process. As a result of practising the \Vet her ill process in accordance with our present invention, this advantage is greatly augmented by the fact that the worked-off metallif er ous brique ts contain at most only a relatively small amount of ash. \V here the working charge brique ts consist of a mixture of metallif er ous material and carbonaceous red uc ing agent, the worked-oft" brique ts will contain, in addition to the worked-ofl metallif er ous material, the ash from the consumed carbonaceous red uc ing agent as well as the unconsumed portion of the red uc ing agent. The ash is composed principally of silica and alumina, and is generally objectionable in any subsequent treatment of the worked-off metallif er ous brique ts. Thus, for example, in those instances in which the worked-off metallif er ous brique ts are smelted in a blast furnace for the production of spiegeleisen a certain amount of fiuxing agents is necessary for slagging off the ash present in the worked-ofl' metallif er ous brique ts, and when this amount of ash is relatively large an objectionably large amount of fluxing agent is required, with the resultant production of an objectionably large amount of slag. By the practice of our present invention the main bulk, for example, around eighty-five (85) per cent. of the ash of the total carbonaceous material of the charge is in the clinker resulting from the combustion of the bed fuel brique ts, and the worked-oft metallif er ous brique ts are consequently contaminated with only a relatively small amount of ash. On account of this relatively slight ash contamination of the worked-off metallif er ous brique ts, as well as on account of their physical properties, these brique ts are peculiarly well adapted for subsequent treatment in blast furnaces. In addition to retaining their original form, these brique ts are moreover of a porous character, due to the removal of the volatilizable metals therefrom, and this porous property of the worked-off brique ts is also of advantage in their subsequent treatment.
As a typical instance of the practice of the invention, we will briefly describe a articular charge and the manner of wor ing the same. The charge was made up of the well known Franklin furnace zinc oxid ores and dust coal. Approximately eight -five (85) per cent. of the total coal of the c ar e was brique ted with concentrated waste sul te liquor as the binder, in the manner previously described. The remaining fifteen (15) per cent. of the total coal was mixed with the ore (in the proportion of about ninety (90) parts of ore to ten (10) parts of coal dust) to which was added about three (3) per cent. of concentrated waste sulfite liquor as a binder and the mixture was then brique ted and the brique ts baked, as pre- .viously described. The fuel brique ts were first charged onto the perforated hearth of the present day customary type of zinc oxid furnace and ignited by the residual heat of the preceding furnacing operation. A thin layer of fuel brique ts was first charged, and after these had been well ignited, the remainder of the fuel brique ts were charged, produc ing a layer of bed fuel of about six (6) inches in depth. When this layer of bed fuel had reached full combustion, the brique ted working charge was spread thereon, produc ing a superposed layer of working charge brique ts of about five (5) inches in depth. During these operations, a blast of air was maintained through the perforated grate, and when active reduction of the zincif er ous material of the charge began, the efliuent from the furnace was conducted to the oxid drums and thence to the bag-room in the usual manner. The temperature of the charge was maintained at from about 1100 C. to about 1250 C., and the fume emitting period was of substantial ly four hours duration.
The residual charge consisted of a more or less clinkered coal ash of about three-fourths (i to one and one-half (1%) inches in thickness, resulting from the combustion of the fuel bri nets, and worked-ofi' metallif er ous or ore rique ts retaining for the greater art their original form with only incipient Fusion. This residual charge was withdrawn from the furnace by hand and the worked-01f ore brique ts separated from the remainder of the residual charge for subsequent treatment.
The zinc oxid produced was of a very high grade, free from grit or specks and very bright. The recovery of zinc was remarkably high, being about ninety (90) per cent. on the original zinc content of the raw ore.
While we have hereinbefore specifically described the invention by reference to the production of zinc oxid, including leaded zinc oxid, we wish it to be understood that the invention is applicable to the production of other metal compounds of the volatilizable metals. In particular, we contemplate the production of basic lead sulfate or sublimed lead by the method of the invention. In general, the procedure for the production of sublimed lead is substantial ly the same as hereinbefore described, substituting, of course, an appropriate plumbif er ous material for the zincif er ous material. Thus, for example, the bed fuel is brique ted in the manner hereinbeforedescribed, and contains the bulk or greater proportion of the total carbonaceous or other combustible material of the entire charge. The working charge consists of a mixture of finely divided galena or native lead sulfid and carbonaceous material preferably brique ted as hereinbefore described. The workin charge is spread on the ignited layer of fied fuel brique ts and upon reaching the reaction temperature. the lead sulfid is reduced and (or) volatilized and subsequently oxidized to lead sulfate and lead oxid thus forming the so-called basic lead sulfate.
The eflluent containing the sublimed lead is withdrawn from the furnace and the metallic product collected in any appropriate manner. The worked-oil plumbif er ous brique ts containing as they do a relatively small amount of contaminating ash may be advantageously subjected to any appropriate subsequent treatment for the recovery of the non-volatilizable metals of the original metallif er ous material. As the source of plumbif er ous material, we may use a high grade of native lead sulfid suitably crushed and jigged to free it from accompanying gangue material, or we may use lead sulfid concentrates, such as flotation concentrates, or other appropriate plumbif er ous-containing material, with proper additions of sulfur in the form of pyrite, galena, brimstone or other suitable sulfur carrying agents, whenever there is a lack of sulfur in the char to properly sulfate the fume.
The re atively deep layer of bed fuel, when in complete combustion, provides a substantial ly incandescent sub-stratum of carbonaceous material of appreciable depth upon which rests the metallif er ous material of the working charge. By appropriately controlling the amount of combustion supporting gas introduced into the bed fuel, complete utilization of the oxygen of such gas can be effected during its passage through the bed fuel and the superposed metallif er ous material can be subjected to a strong and effective red uc ing atmosphere. This red uc ing atmosphere may be so controlled as to materially reduce the amount of red uc ing agent in the Working charge, and in certain instances may even eliminate the necessity of ad mixing any red uc ing agent with the metallif er ous material of the working charge.
We clailii:
1. In t e production by the Wether ill process of i metal oxids vor other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together with the steps of spreading on the ignited layer of bed fuel brl que ts a working charge containing metallif er ous material and a red uc ing agent; substantial ly as described.
2. In the production by the Wether ill process of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatii'ely deep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing metallif er ous material and a brique ted red uc ing agent; substantial ly as described.
3. In the production by the lVet her ill. process of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together process of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge composed of a brique ted mixture of metallif er ous material and a red uc ing agent; substantial ly as described.
5. In the production by the Wether ill process of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth-a layer of bed fuel containin the greater part of the total combustib e material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing metallif er ous material and a red uc ing agent; substantial ly as described.
6. In the production by the Wether ill process of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a layer of bed fuel containing the greater part of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing metallif er ous material and a brique ted red uc ing agent; substantial ly as described.
7. In the production by the Wether ill process of metal oxids or other compounds of volatilizable metals, the step of su plying to the furnace hearth a la er of be fuel containing the greater part 0 the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing brique ted metallif er ous material and .a reduc ing agent; substantial ly as described.
8. In the production by the Wether ill of metal oxids or other compounds of volatilizable metals, the step of sugplying to the furnace hearth a layer-of be fuel contain the greater part of the total combustlble material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge composed of a brique ted mixture of metallif er ous material and a red uc ing agent; substantial ly as described.
9. In the production bythe Wether ill process of metal oxids or other compounds of volatilizable metals, the step of supply in to the furnace hearth a layer of bed fue containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing metallif er ous material and a brique ted red uc ing agent; substantial ly as described, a
11. In the production by the Wether ill process of metal oxide or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a layer of bed fuel containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containin brique ted metallif er ous material and a re uc ing agent; substantial ly as described.
12. In the production by the Wether ill process of metal oxids or other compounds of volatilizable metals, the step of su plying to the furnace hearth a layer of bed containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the i ited layer of bed fuel brique ts a working 0 arge composed of a brique ted mixture of metallif er ous material and a red uc ing agent; substantial ly as described.
13. In the production of sublimed lead by the lVethenll process, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing plumbif er ous material and a red uc ing agent; substantial ly as described.
14. In the roduction of sublimed lead by the Wether ill process, the step of sup lying to the furnace hearth a relatively eep layer of bed fuel in the form of brique ts, together with the etc of spreading on the ignited layer of bed fiiel brique ts a working charge containing plumbif er ous material and a brique ted red uc ing agent; substantial ly as described.
15. In the roduction of sublimed lead by the Wether ill process, the step of sup ly mg to the furnace hearth a relatively eep fuel layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working c arge containin brique ted plumbif er ous material and a re uc ing agent; substantial ly as described.
16. In the production of sublimed lead by the Wetherlll process, the step of sup lying to the furnace hearth a relatively d eep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a workin charge composed of a brique ted mixture 0 plum if er ous material and a red uc ing agent; substantial ly as described.
17. In the production of sublimed lead by the Wether ill process, the step of sup lying to the furnace hearth a la er of bed uel containing the greater part 0 the total combustible material of the'en-tire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing plumbif er ous material and a red uc ing agent; substantial ly as described.
18. In the production of sublimed lead by the Wether ill process, the step of supply ing to the furnace hearth a layer of bed fuel containing the greater part of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing lumbif er ous material and a brique ted resuc ing agent; substantial l as described.
19. In the roduction o sublimed lead by the Wetheril process, the step of supply ing to the furnace hearth a layer of bed fuel containing the greater part of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge oontainin brique ted plumbif er ous material and a re uc ing agent; substantial ly as described.
20. In the production of sublimed lead by the Wether ill process, the step of supply in to the furnace hearth a layer of bed fue containing the greater art of the total combustible mater lal of t e entire charge in the form of brique ts, together with the step of s reading on the ignited layer of bed fuel brique ts a working char composed of a brique ted mixture of plum if er ous material and a red uc ing agent; substantlally as described.
21. In the roduction of sublimed lead by the Wetheril process, the step of supply m to the furnace hearth a layer of bed fue containing from about 75% to about 85% of the total combustible material of the en-- tire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge charge containing containing plumbif er ous material and a red uc in agent; substantial ly as described.
22. n the production of sublimed lead by the Wether ill process, the step of supp y lng to the furnace hearth a layer of bed uel containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ig; nited layer of bed fuel rigue ts a workin lumbi er ous materia and a brique ted re uc ing agent; substantial ly as described.
23. In the roduction of sublimed lead by the Wetheril process, the step of supply in to the furnace hearth a layer of bed hi5 containing from about 75% to about 85% of .the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing plumbif er ous material and a brique ted red uc ing agent; substantial ly as described.
24. In the production of sublimed lead by the Wether ill process, the step of supply ing to the furnace hearth a layer of bed fuel containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique tsa working charge composed of a brique ted mixture of plumbif er ous material and a red uc ing agent; substantial ly as described.
25. In the production of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of be fuel brique ts a working charge containing metallif er ous material; substantial ly as described.
26. In the production of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel, together with the step of spreading on the ignited layer of bed fuel a working charge containing brique ted metallif er ous material; substantial ly as described.
27. In the production of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge conta1nmg br1- que ted metallif er ous material; substantlally as described.
28. In the production of metal oxids or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel, together posed of a brique ted mixture of metallif er ous material and a red uc ing agent; substantial ly as described.
29. In the production of metal oxide or other compounds of volatilizable metals, the
step of supply ing to the furnace hearth a layer of bed fue containing in excess of 25% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the'ignited layer of bed fuel rique ts a working charge containing metallif er ous material; substantial ly as described.
30. In the production of metal oxide or other compounds of volatilizable metals, the step of supslying to the furnace hearth a layer of be fuel containin in excess of 25% of the total combustib e material of the entire charge in the form of brique ts, together with the ste of spreading on the ignited layer of bed el brl acts a working c arge containing briquet inetallif er ous material; substantial ly as described.
31. In the product lon of metal oxide or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a layer of bed fuel containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the etc of spreading on the ignited layer of bed e1 bri ue ts a workin charge containing metalhfer ous materia substantial l as described.
32. In the production of metal oxide or other compounds of volatilizable metals, the step of supply ing to the furnace hearth a layer of bed fuel containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel bri nets 0. a Working charge containing bri u metallif er ous material; substantial y as described.
33. In the reduction of sublimed lead by the Wetherilfprocess, the step of supply to the furnace hearth a relatively deep la er of bed fuel in the form of brique ts, toget er with the step of spreading on the ignited layer of bed fuel brique ts a working charge containin plumbif er ous mater al; substantial ly as escribed.
34. In the production of sublimed lead by the Wether ill process, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel, together with the etc of spreading on the ignited layer of bed us] a working charge containing brique ted plum'bif erone material; substantial ly as described.
35. In the production of sublimed lead by the Wether ill rocess, the step of supply ing to the furnace earth a relatively deep la er of bed fuel in the form of brique ts, toget er with the step of spreading on the layer of bed fuel brique ts a working c arge containin brique ted plumbif er ous material; substantia y as (1 bed.
36. In the production of.suhlimed lead by the Wether ill process, the step of supply ing to the furnace hearth a relatively deep layer of bed fuel, together with the etc of spreading on the igm ted layer of bed el a working char composed of a brique ted mixture of, p umbif er ous material and a red uci agent substantial ly as described.
7 In the production of sublimedlead by the Wether ill process, the step of en plying to the furnace hearth a layer of bed fh el containing in excess of 25% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fuel brique ts a working charge containing plumbif er ous material; substantial ly as described. y
1138. Inhthel 1productionhof sublimed lead 15y teWeteri rocessiteste osu in to the heart a'lay r of containing in excess of 25% of the total eom bustible material of the entire charge in the form of b 'que ts, together spreading on the ignited layer of bed fuel brique ts a working charge containing brique ted plumbif er ous material; substantial ly as described.
39. In the roduction of sublimed lead by the Wether ill process, the step of en plyingto the furnace hearth a layer of bed el containing from about 75% to about 85% of the total combustible material of the entire charge in the form of britglue ts, together with the etc of spreading on e ignited layer of bed fue brique ts a working charge containing plumbif er ous material; substantial ly as described.
40. In the production of sublimed lead by the Wether ill process, the step-of supply ing to the furnace hearth a layer of bed fue containing from about 75% to about 85% of the total combustible material of the entire charge in the form of brique ts, together with the step of spreading on the ignited layer of bed fllel brique ts a working charge containing brique ted plumbif er ous materia substantial ly as described.
41. In a process for volatilizing and oxidizing metal values involving the blowing of air into a bed containing combustible material and a mixture of the metal-bearing material and a red uc ing agent under conditions which will leave the worked-off charge as a clinker and which will produce a volatile fume, the step of supply ing the combustible material in the form of a relatively deep layer of brique ts; substantial l as described.
42. In a process for volatihzing and oxidizing metal values involving the blowing of air into a bed containing combustible ma with the step of terial and a mixture of the metal-bearing material and a combustible red uc ing agent under conditions which will leave the worked-off charge as a clinker and which will produce a volatile fume, the step of supply ing the combustible material in the form of a relatively deep layer of brique ts containing the greater part of the total combustible material of the entire charge; substantial ly as described.
43. In a process for volatilizing and oxidizing metal values involvin the blowing of air into a bed containin t e metal-bean ing material and combustib e material under conditions which will leave the worked-off charge as a clinker and which will produce a volatile fume, the step of supply ing at least part of the combustible material in the form of a relatively dee layer of brique ts; substantial ly as descri ed.
44. In a process for produc ing sublimed lead involving the blowing of air into a bed containing combustible material and a mixture of the metal-bearing material and a combustible red uc ing agent under conditions which will leave the worked-oil? charge as a clinker and which will produce a volatile fume, the step of supply ing the combustible material in the form of a relatively deep layer of brique ts containing the greater part of the total combustible material of the entire charge; substantial ly as described.
45. In a process for produc ing sublimed lead involving the blowing of air into a bed containing the metal-bearing material and combustible material under conditions which will leave the Worked-ofi' charge as a clinker and which will produce a volatile fume, the step of supply ing at least part of the com bustible material in the form of a relatively dee layer of brique ts; substantial ly as des'cri ed.
In testimony whereof We afl ix our signatures.
FRANK G. BREYER. ALBERT E. HALL. GEORGE R. WALT Z.
It is hereby certified that in Letters Patent No. 1,322,090, granted November 18, 1919, upon the application of Frank G. Breyer, Albert E. Hall, and George Waltz, of Pel merton, Pennsylvania, for an improvement in Production of Metal Oxide andother Compounds of Meta. errors appear in the printed specification requiring correction as follows: Page 2, line 30, for the word thus read this; page 6, line 49, claim 8, after the word Wether ill insert the word process; page 7, lines 100, 108, 116, 125, claims 25, 26, 27, 2s, and page 8, lines 6,.16, 2e, 36, claims 29, 30, 31, 32, after the word production insert the words by the Wetter-ill process;
same page, line 48, claim 33, for the word "supply reed supply ing; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Ofice.
Signed and sealed this 30th day of December, A. D., 1919.
M. H. GOULSTON, Acting Commissioner of Patents.
[emu]
|
Modular anti-seismic protection device to be used in buildings and similar constructions
ABSTRACT
This invention is a modular anti-seismic protection device to be used in buildings and similar constructions. It discloses a modular base, which is to be laid on the ground below a building's foundation plate, to dampen, dissipate, and cancel out seismic waves.
PRIORITY REFERENCES
This application claims foreign priority benefits to Spanish Foreign Application Number 200002303 filed Sep. 22, 2000, and to PCT International Application Number PCT/ES01/00036 filed Feb. 8, 2001.
BACKGROUND
Several potential solutions have been devised to dampen or render harmless the effects of earthquakes. Most are based upon the use of elastic elements to absorb seismic waves.
For example, a German Patent (DE-3446831) describes an elastic body to be used as a support for constructions, in the form of a shaped strip with inner seatings that run lengthways in two rows and are staggered crosswise. The layout of the strip and the elastomeric material it is made of is designed to enable it to absorb considerable vertical stress. A similar structure is described in another German patent (DE-3935354).
Along the same lines, an English Patent (GB-2,120,167) describes a deformable structure consisting of two plates separated by an abscission layer containing material, such as foam, which becomes compressed under pressure. Alternatively, this structure can take the form of a honeycomb, subjecting the aforementioned plates to a process of elastic deformation bringing them closer together.
Likewise, a French Patent (2,510,645) describes a cell that acts against earthquakes. The cell is prismatic, eight-sided in shape, and is designed to fit in juxtaposition with other similar cells. It is designed to dampen momentary and vertical excessive stresses, such as those caused by an earthquake.
Another French Patent (2,391,324) also describes a system for protection against earthquakes. It consists of a steel plate that separates the construction itself from the foundation, in order to prevent cracks appearing in the foundation from spreading to the building.
A similar system is disclosed in PCT WO98/57013. The difference is that an isolating elastomeric support is used instead of a steel plate. This support is rigid and consists of inlaid pre-stressed fibres laid horizontally inside it.
Likewise, another PCT WO96/30602 describes a system for protecting buildings. In this system, buildings are founded on a flat structure suspended by hydraulic jacks to dampen seismic vibrations.
Similarly, a U.S. Pat. No. (4,959,934) describes an elastoplastic damper to be used in a structure, to absorb the vibrations that buildings are subjected to during seismic movements. The damper comprises a piece, which looks like a block or sheet of metal, with a number of separated openings that cover the whole surface to give it elastic deformability.
Another U.S. Pat. No. (4,555,433) describes an element for acoustic absorption. It comprises small plates and hollows that look like a small bowl, arranged in the form of a grid. If an element of this type is given the right structural rigidity, it can be used as a means for damping the vibrations caused by earthquakes, instead of being used as a means for damping acoustic vibrations.
Yet another U.S. Pat. No. (4,782,913) describes a construction element with acoustic properties. It is equipped with a core that either has a grille or is cellular. This device can absorb most acoustic waves, and if it is properly structured, is designed to be able to dampen the vibrations caused by earthquakes.
Likewise, a European Patent (EP 0889179) describes a construction bridge for absorbing shocks. The construction bridge consists of a series of horizontal parts arranged in series, with vertical parts supporting them, linked by means of absorbers that dampen the shock waves caused by an earthquake.
Another European Patent (EP 0481146 A1) describes a composite construction to cope with seismic movements. It is composed of a series of modules that are supported on the ground without foundations, and which support each other without any type of vertical connection. In such manner, each module can move in an unrestricted way crosswise with respect to the adjacent modules.
SUMMARY
The invention's disclosed modular anti-seismic protection device, to be used in buildings and similar constructions, utilizes a series of special features that provide advantages over the prior art.
In one aspect, a device providing an elastically deformable layer to protect against seismic waves, includes a layer of a plurality of modules, wherein each module comprises a first upper part attached to a second lower part. Further included is a circular flexible object disposed between the first upper part and the second lower part.
In another aspect, a device providing an elastically deformable layer to protect against seismic waves, includes a layer of a plurality of modules, wherein each module comprises a first upper part attached to a second lower part. Further included is a circular flexible object disposed within each module between the first upper part and the second lower part. Additionally, a block is disposed within each module. Each block is attached to both the first upper part and the second lower part in each module. Each module also includes granular material disposed within the module.
In yet another aspect, a method of constructing a modular anti-seismic protection device, to be used in buildings and similar constructions, to provide an elastically deformable layer to protect against seismic waves, is provided. A plurality of arranged modules, wherein each module comprises a first upper part and a second lower part, and a plurality of circular flexible objects are provided. At least one of said circular flexible objects is disposed between said first upper part and said second lower part in each of said modules. The first upper part is then attached to the second lower part in each of the modules.
The present invention, together with further objects and advantages, will be best understood by reference to the following detailed description taken in conjunction with the accompanying drawings.
DESCRIPTION OF THE DRAWINGS
To supplement the description that is being given and to make it easier to understand the characteristics of the invention, a set of drawings are enclosed. These drawings are illustrative in nature and in no way limiting, and show an example of one of the best ways to put this invention to practical use.
FIG. 1 shows one embodiment of a side elevation view and a diametrical cross-section of a module forming part of the modular anti-seismic protection device used in buildings and similar constructions. The embodiment shows the module at a time when there is no seismic wave activity.
FIG. 2 shows a plan view of the object in FIG. 1.
FIG. 3 shows a view of the object in FIGS. 1 and 2 when there is seismic wave activity.
FIG. 4 shows a plan view of one embodiment of the modular anti-seismic device. As shown, a plurality of modules are arranged side by side at the base of a building before work begins on laying the concrete foundation.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
As shown in FIG. 4, the modular anti-seismic protection device, to be used in buildings and similar constructions, is made up of a number of modules 1 which are positioned on the same plane and adjacent to each other with their sides in contact. As shown in FIGS. 1-3, each module 1 is structured with two parts of material 2 and 2′, which may be plastic and identical, preferably joined to each other by means of a block 3. The block 3 is held in place by two retaining devices 4 and 4′ disposed within the parts 2 and 2′. To hold the block 3 in place, two retaining nuts, which may be plastic, may be inserted into pockets within the parts 2 and 2.′
A circular flexible object 5, which may have a hollow interior and may be a car tire, is inserted between the parts 2 and 2′, held in place by the block 3, before the parts are joined together. Granular material is inserted into the space left between the parts 2 and 2′. This forms a system 6 with a hydraulic effect. The granular material is inserted through a hole 7, made in the part 2, equipped with a cover seal for safety purposes.
As shown in FIG. 4, a number of modules 1 are placed on the same plane, lying on the ground where a building is to be constructed. The modules are laid at the bottom of the excavation works that have been dug for the foundations. This guarantees an even arrangement, which may be hexagonal, for the plastic parts 2 and 2′. The modular layout has two flat, parallel and largely unbroken surfaces, between which the circular flexible objects 5 are inserted at a tangent to each other. The circular flexible objects 5 may be arranged in the form of a quincunx, leaving small triangular voids with curved sides, in such a way that the slabs or foundation plates 10 can then be laid on this modular but continuous surface. The structure of the building is then constructed on those slabs or foundation plates 10.
In the event of seismic movement, the upward movement that the lower plastic plate 2′ is subjected to, forces the modules 1 against the weight of the building, causing the granular material 6 contained within the circular objects 5 to move horizontally. This subjects the modules to radial deformation, as can be seen in an exaggerated way in FIG. 3. Because the circular flexible objects 5 are arranged tangentially, the deformation takes place towards the voids in the triangular layout, and the size of these spaces is sufficient to absorb the deformation, giving rise to an elastic effect. As soon as the impact of the seismic wave has been dampened, the modules 1 return to the original positions they were in before the earthquake occurred.
Although the present invention has been described with reference to preferred embodiments, those skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention. As such, it is intended that the foregoing detailed description be regarded as illustrative rather than limiting and that the appended claims, including all equivalents thereof, are intended to define the scope of the invention.
What is claimed is:
1. A device comprising: a layer of a plurality of modules arranged in the same plane tangentially between the ground and a foundation of buildings, wherein each module comprises a first upper part attached to a second lower part, and a circular flexible object disposed between said first upper part and said second lower part, wherein said layer is elastically deformable to protect against seismic waves.
2. The device of claim 1 wherein said circular flexible object is a tire.
3. The device of claim 1 wherein said first upper part and said second lower part are plastic.
4. The device of claim 1 further comprising a block, disposed between said first upper part and said second lower part, wherein said block is attached to both of said first upper part and said second lower part.
5. The device of claim 4 further comprising means for securing said block to both of said first upper part and to said second lower part.
6. The device of claim 5 wherein said means for securing is an interlocking bolt and nut.
7. The device of claim 1 wherein said plurality of modules are polygonal.
8. The device of claim 1 wherein said plurality of modules are arranged between the ground and the foundation of a building.
9. The device of claim 1 further comprising granular material disposed within said circular flexible object.
10. The device of claim 9 wherein said granular material is plastic.
11. A device comprising: a layer of a plurality of modules arranged in the same plane tangentially between the ground and a foundation of buildings, wherein each module comprises a first upper part attached to a second lower part, and said layer is elastically deformable to protect against seismic waves; a circular flexible object disposed within each module between said first upper part and said second lower part; a block disposed within each module, wherein said block is attached to both of said first upper part and said second lower part in each module; and granular material disposed within each module.
12. The device of claim 11 wherein said circular flexible object is a tire.
13. A method of constructing a modular anti-seismic protection device, to be used in buildings, to provide an elastically deformable layer to protect against seismic waves, comprising: providing a plurality of arranged modules arranged in the same plane tangentially between the ground and a foundation of buildings, wherein each module comprises a first upper part and a second lower part, and providing a plurality of circular flexible objects; disposing at least one of said circular flexible objects between said first upper part and said second lower part in each of said modules; and attaching said first upper part to said second lower part in each of said modules. attaching said first upper part to said second lower part in each of said modules.
14. The method of claim 13 further comprising disposing granular material within each module.
15. The method of claim 13 wherein said circular flexible objects are tires.
16. The method of claim 13 wherein said plurality of modules are polygonal.
17. A device comprising: a layer of a plurality of modules, wherein each module comprises a first upper part attached to a second lower part, and a tire disposed between said first upper part and said second lower part, wherein said layer is elastically deformable to protect against seismic waves.
18. A device comprising: a layer of a plurality of modules, wherein each module comprises a first upper part attached to a second lower part, and said layer is elastically deformable to protect against seismic waves; a tire disposed within each module between said first upper part and said second lower part; a block disposed within each module, wherein said block is attached to both of said first upper part and said second lower part in each module; and granular material disposed within each module.
19. A method of constructing a modular anti-seismic protection device, to be used in buildings, to provide an elastically deformable layer to protect against seismic waves, comprising: providing a plurality of arranged modules, wherein each module comprises a first upper part and a second lower part, and providing a plurality of circular flexible objects; disposing at least one of said circular flexible objects between said first upper part and said second lower part in each of said modules; attaching said first upper part to said second lower part in each of said modules; and disposing granular material within each module.
20. A method of constructing a modular anti-seismic protection device, to be used in buildings, to provide an elastically deformable layer to protect against seismic waves, comprising: providing a plurality of arranged modules, wherein each module comprises a first upper part and a second lower part, and providing a plurality of tires; disposing at least one of said tires between said first upper part and said second lower part in each of said modules; and attaching said first upper part to said second lower part in each of said modules.
21. A method of constructing a modular anti-seismic protection device, to be used in buildings, to provide an elastically deformable layer to protect against seismic waves, comprising: providing a plurality of arranged polygonal modules, wherein each polygonal module comprises a first upper part and a second lower part, and providing a plurality of circular flexible objects; disposing at least one of said circular flexible objects between said first upper part and said second lower part in each of said polygonal modules; and attaching said first upper part to said second lower part in each of said polygonal modules.
|
package br.com.zup.nossoCartao.fatura.fatura;
import br.com.zup.nossoCartao.fatura.transacao.Transacao;
import org.hibernate.annotations.UpdateTimestamp;
import javax.persistence.*;
import javax.validation.constraints.NotNull;
import java.math.BigDecimal;
import java.time.LocalDate;
import java.util.List;
import java.util.UUID;
@Entity
@Table(
name = "faturas"
)
public class Fatura {
@Id
@GeneratedValue(strategy = GenerationType.IDENTITY)
private Long internalId;
@Transient
private UUID externalId = UUID.randomUUID();
@NotNull
private BigDecimal limite;
@NotNull
private BigDecimal saldo;
private String cartaoId;
private LocalDate criadaEm = LocalDate.now();
@UpdateTimestamp
private LocalDate atualizadaEm;
@OneToMany(cascade = CascadeType.ALL)
private List<UltimaTransacao> transacoes;
private Fatura() {
}
public Fatura(@NotNull String cartaoId, @NotNull BigDecimal limite, @NotNull BigDecimal saldo, List<UltimaTransacao> transacoes) {
this.cartaoId = cartaoId;
this.limite = limite;
this.saldo = saldo;
this.transacoes = transacoes;
}
public UUID getExternalId() {
return externalId;
}
public BigDecimal getLimite() {
return limite;
}
public BigDecimal getSaldo() {
return saldo;
}
public List<UltimaTransacao> getTransacoes() {
return transacoes;
}
public void setTransacoes(List<UltimaTransacao> transacoes) {
this.transacoes = transacoes;
}
public void atualizaSaldo(BigDecimal contabilizacao) {
this.saldo = this.saldo.subtract(contabilizacao);
}
@Override
public String toString() {
return "Fatura{" +
"internalId=" + internalId +
", externalId=" + externalId +
", limite=" + limite +
", saldo=" + saldo +
", cartaoId='" + cartaoId + '\'' +
", criadaEm=" + criadaEm +
", atualizadaEm=" + atualizadaEm +
", transacoes=" + transacoes +
'}';
}
}
|
Uncaught TypeError: Object #<Object> has no method 'datepicker'
I want to use jQuery Datepicker in my website. However when I use the same I get the following error.
Uncaught TypeError: Object # has no method 'datepicker'
I've googled on this for quite sometime. All of these say that the problem could be due to loading jquery twice. I have checked and this isn't the case.
I load the jQuery scripts in the following way.
<script type="text/javascript" src="http://xxxx/wp-includes/js/jquery/jquery.js"></script>
<script type="text/javascript" src="http://xxxx/wp-includes/js/jquery/ui/jquery.ui.core.min.js"></script>
<script type="text/javascript" src="http://xxxx/wp-includes/js/jquery/ui/jquery-ui.min.js"></script>
<script type="text/javascript" src="http://xxxx/wp-includes/js/jquery/ui/jquery.ui.datepicker.min.js"></script>
...
...
<input type="text" id="arrival-date-10">
<input type="text" id="departure-dat-14">
....
<script type="text/javascript">
jQuery(document).ready(function(){
$("#arrival-date-10").datepicker();
$("#departure-date-14").datepicker();
});
</script>
I get the error in line $("#arrival-date-10").datepicker();
Please can someone help me?
Partha
What happens if you use jQuery(document).ready(function($){ instead?
JS questions are not on-topic for this site. That said, you've already received plenty of useful answers below (and one spot-on in the comment above this one).
This line shouldn't be in there:
<script type="text/javascript" src="http://xxxx/wp-includes/js/jquery/ui/jquery-ui.min.js"></script>
In a standard WordPress install, no such file exists. This makes me wonder how you are adding the scripts to the theme in the first place. Are you using wp_enqueue_styles? If not, there is a VERY good chance that you are indeed adding two versions of jQuery.
You may be having a jQuery conflict. Give it a try in noconflict mode like so:
<script type="text/javascript">
(function($) {
$(document).ready(function(){
$("#arrival-date-10").datepicker();
$("#departure-date-14").datepicker();
});
})(jQuery);
</script>
I wonder if this wouldn't be better asked on Stack Overflow instead, it's not really a WordPress question (unless you're asking how to properly enqueue scripts).
|
from itertools import izip, count
from numpy import inf, zeros, array, isneginf, hstack, zeros_like
from numpy.linalg import norm
from numpy.core.umath import sqrt
__author__ = 'danielv'
try:
from cvxoptCuttingPlane import proximalIteration
def proximalCuttingPlaneStream(f, g, x0, lowerBound=None, stepSize=1.):
n = x0.shape[0]
xk = yk = ykn = x0
bko = f(x0)
bestLowerBound = -inf if lowerBound is None else lowerBound
if lowerBound is None:
A, Z, b = zeros((n, 0)), zeros((n, 0)), zeros(0)
#A,Z,b = zeros((n,1)),zeros((n,1)),array([-10e12])
else:
A, Z, b = zeros((n, 1)), zeros((n, 1)), array([lowerBound])
while (True):
newLowerBound = yield yk
# If a lower bound is added or improved by client, update the constraints.
if (not (newLowerBound is None)):
if isneginf(bestLowerBound):
A = hstack((zeros((n, 1)), A))
Z = hstack((zeros((n, 1)), Z))
b = hstack((newLowerBound, b))
if newLowerBound > bestLowerBound:
bestLowerBound = newLowerBound
b[0] = bestLowerBound
# Compute a new cutting plane through xk.
ak = g(xk)
zk = xk
bk = f(xk)
if bk < bko: # Serious step: next turn we'll change the reference point.
ykn = xk
bko = bk
stepSize = stepSize * 2
else:
stepSize = stepSize / 2
''' Update function approximation (currently grows without bound).'''
A = hstack((A, ak.reshape(n, 1)))
Z = hstack((Z, zk.reshape(n, 1)))
b = hstack((b, array([bk])))
xk = proximalIteration(yk, 1. / stepSize, A, Z, b)
#xk = proximalIteration(yk, 1. / (k + 1), A, Z, b)
yk = ykn
except ImportError:
pass
def sgdStream(gradf_t, w0, stepsizes):
w = w0
for alpha, grad in izip(stepsizes, gradf_t):
yield w
w = w - alpha * grad(w)
def averageStream(stream):
aw = stream.next()
yield aw
for n,w in enumerate(stream, start=2):
aw = (w + aw * (n-1)) / float(n)
yield aw
def averageLateWeightingStream(stream):
aw = stream.next()
yield aw
for n, w in enumerate(stream, start=2):
aw = (2*w + aw * (n-1)) / float(n + 1)
yield aw
def regularizedDualAveragingStream(gradf_t, prox, w0, L, gamma):
""" Essentially Algorithm 3 (Accelerated RDA method) from the paper
Dual Averaging Methods for Regularized Stochastic Learning and Online Optimization by Lin Xiao, JMLR 2010.
- L is the Lipschitz constant for the gradients.
- prox(g,C) is a function that solves the proximal operator argmin_w {<g,w> + Psi(w) + C*h(w)}, where Psi is the regularization function and h is a strongly convex localizer (e.g. squared distance from a minimizer of Psi).
- gradf_t is a sequence of instances of an unbiased estimators for gradients of the base function. For example, each may correspond to a different random minibatch of data points.
- w0 is the minimizer of h. """
w = w0
v = w
A = 0
gt = zeros_like(w)
yield w
for t, gradf in izip(count(1.), gradf_t):
alpha_t = t / 2
beta_t = gamma * ((t + 1) ** 1.5) / 2
# Calculate coefficients
A += alpha_t
theta_t = alpha_t / A
# Compute the query point
u = (1 - theta_t) * w + theta_t * v
# Query stochastic gradient, update weighted average gradient
gt = (1 - theta_t) * gt + theta_t * gradf(u)
# Solve for the exploration point
v = prox(gt, (L + beta_t) / A)
# Interpolate for w
w = (1 - theta_t) * w + theta_t * v
yield w
def fastGradientProjectionStream(f, g, gradf, proxg, x0, initLip=None):
'''The (fast) proximal gradient method requires a gradient of f, and a prox
operator for g, supplied by gradf and proxg respectively.'''
if initLip is None:
Lipk = 1.
else:
Lipk = initLip
eta = 2.
xko = x0
xk = x0
yk = x0
tk = 1
yield xk
def F(x):
return f(x) + g(x)
Fxko = F(xko)
def Q(Lip, px, x):
"""Value at px, where smooth part is approximated quadratically around x"""
d = (px - x).flatten() # treat all matrices as vectors
return f(x) + gradf(x).flatten().dot(d) + Lip * (norm(d) ** 2) / 2 + g(px)
def P(Lip, x):
"""Gradient step and projection"""
return proxg(Lip, x - gradf(x) / Lip)
'''Non standard extension: expanding line search to find an initial estimate of Lipschitz constant'''
for k in range(10):
pyk = P(Lipk, yk)
Fpyk = F(pyk)
Qpykyk = Q(Lipk, pyk, yk)
#print "Fpyk = %s; Q(%s ** -1...) = %s" % (Fpyk, Lipk ** -1, Qpykyk)
if Fpyk > Qpykyk:
#print "stop increase"
break
if Fpyk < Fxko:
yield pyk
yk = pyk
Lipk /= eta ** 4
#print "increased step size to %s" % Lipk ** -1
'''Step size now must be too large, decrease at least one step.'''
Lipk *= eta
'''Start standard algorithm'''
xk = pyk
while True:
'''Decrease step size until approximation is valid.'''
while True:
pyk = P(Lipk, yk)
Fpyk = F(pyk)
Qpykyk = Q(Lipk, pyk, yk)
#print "Fpyk = %s; Q(%s ** -1...) = %s" % (Fpyk, Lipk ** -1, Qpykyk)
if Fpyk <= Qpykyk:
#print "stop step size decrease"
break
Lipk *= eta
#print "decreased step size to %s" % Lipk ** -1
zk = pyk
tkn = (1 + sqrt(1 + 4 * (tk ** 2))) / 2
if Fpyk <= Fxko: # Fpyk is F(zk)=F(pyk); Fxko is F(xko)
xk = zk
Fxk = Fpyk
else:
xk = xko
Fxk = Fxko
yk = xk + (zk - xk) * tk / tkn + (xk - xko) * (tk - 1) / tkn
Fxko = Fxk
xko = xk
tk = tkn
yield xk
def projectedSubgradientStream(sgf, proj, x0, theta=1.):
""" Minimize a function f whose subgradient is sgf over
a convex set of radius theta and orthogonal projection operator proj,
starting at x0. """
theta = float(theta)
xk = x0
# Using optimal step size for fixed number of iterations
for k in count(1):
yield xk
gk = sgf(xk)
'Theoretically motivated step size, sometimes decays too slowly'
tk = sqrt(2 * theta / k) / norm(gk)
uncon = xk - tk * gk
xk = proj(uncon)
|
Obesity and nonalcoholic fatty liver disease (NAFLD) are comorbid conditions which are increasingly prevalent throughout the world \[[@B1]\]. Several dietary factors have been implicated as causative, including excessive sucrose, fructose and fat \[[@B2]-[@B4]\]. The human diet has changed greatly during the past four decades, with the introduction of partially-hydrogenated vegetable oils (*Trans* fats), which began replacing natural fats and oils in processed foods during the 1960s. *Trans* fat (TFA) has no nutritional value, and has been associated with major health deficits \[[@B5]\]. In 1994, it was estimated that TFA consumption could be linked to the approximately 20,000 fatalities from heart disease annually in the United States alone \[[@B6]\]. Increased abdominal adiposity has been shown to result from TFA-feeding in monkeys \[[@B7]\]; and increased visceral fat and hepatic lipid accumulation together with impaired insulin sensitivity were noted in rats consuming a low fat diet supplemented with 4.6% elaidic acid (*Trans*-18.1), which is the predominant lipid found in hydrogenated vegetable oils \[[@B8]\]. Furthermore, we have previously investigated the changes in hepatic and adipose tissue gene expression which accompany the increased adiposity and hepatic steatosis induced by TFA supplementation, and noted significant dysregulation in several key transcription factors controlling energy metabolism \[[@B9]\].
In addition to extending the shelf life of foods and reducing production costs, processed foods can be rendered more palatable by the use of food additives to preserve flavor and enhance taste \[[@B10]\]. Two of the most commonly consumed food additives are monosodium glutamate (MSG) which enhances flavor when combined with another savory odor \[[@B11]\]; and the low-calorie artificial sweetener aspartame \[[@B12]\], used to replace dietary sugar and fructose. However in rodents, neonatal injections of high doses of MSG promotes obesity and growth hormone defects together with hyperinsulinemia and elevated corticosteroid levels in adulthood \[[@B13]-[@B16]\]. This hypothalamic model of obesity may also be induced in the offspring of pregnant dams orally ingesting MSG \[[@B17]-[@B19]\]; and studies with radiolabeled ^3^H-glutamate have shown that glutamate given orally to pregnant mice can subsequently be detected in the maternal and fetal brains, livers and kidneys \[[@B20]\]. The mechanism behind the neuroendocrine disturbance caused by MSG is believed to involve glutamate-induced degeneration of those areas of the immature neonatal brain which are insufficiently protected by a mature blood--brain barrier, including regions which regulate growth and energy metabolism \[[@B13]-[@B19]\].
MSG has previously been demonstrated to cause hepatic microsteatosis and a NASH-type phenotype in rodents exposed to MSG neonatally \[[@B21]\]. We have previously shown that the combination of TFA and MSG can further modulate hepatic and adipose tissue gene expression, by increasing the transcription of genes involved in lipid mobilization and storage, together with an attenuation of the expression of several lipid catabolizing genes \[[@B9]\]. In both tissues, transcription factor Srebp1c was increased by TFA consumption; whereas in the adipose tissue, expression of the key transcription factor Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc1a) was reduced by 50% in TFA-fed mice, and reduced further to 25% by the combination of TFA and MSG. Ppargc1a is a potent transcriptional activator of glucose and lipid metabolism linking nutritional and hormonal signals and energy metabolism; and Ppargc1a-null mice develope systemic dyslipidemia and hepatic steatosis \[[@B22]\].
The low-calorie dipeptide artificial sweetener aspartame (ASP) is rapidly metabolized upon ingestion into its metabolic components phenylalanine, aspartate and methanol, in the ratio of 50:40:10 w/w/w \[[@B23]\]. Recently, chronic consumption of aspartame by mature rodents has been shown to cause hepatocellular injury and a reduction in hepatic antioxidant defense capacity \[[@B24]\]. Additionally, we have utilized a rodent model in order to investigate the interactive effects of chronic exposure to ASP and MSG, either alone or in combination \[[@B25]\]. We demonstrated that C57Bl/6 J mice exposed to ASP both *in utero* via the mother's diet, and subsequently throughout the first five months of life, developed hyperglycemia and reduced insulin tolerance; and that the combination of ASP and MSG appeared to interact in further modulating insulin sensitivity in young C57Bl/6 J mice. Throughout the study, animal exposed to ASP and MSG were maintained on a Standard Chow diet, which has a relatively low fat content, (typically of between 5-10%), however this may not accurately reflect current dietary trends in the human population \[[@B26]\]. We were therefore interested to know how consumption of ASP and MSG might affect the physiology and gene expression of animals consuming a TFA -enriched diet, since in processed foods and restaurant fare, TFA, MSG and aspartame may frequently be consumed together in the same meal. Since TFA \[[@B7]-[@B9],[@B27]\], ASP \[[@B24]\] and MSG \[[@B9],[@B21]\] have all been implicated in hepatic dysfunction, our aim was to examine the development of hepatic steatosis, adiposity and changes in hepatic and adipose tissue gene expression in response to ASP and MSG, or a combination of both, in animals maintained on a TFA -enriched diet.
Because exposure to nutritional and environmental challenges during critical periods of early development can markedly effect metabolism in later life \[[@B28]\], and since differentiation of the rodent neuroendocrine system regulating energy homeostasis begins during gestation and continues for a significant period of time after birth \[[@B29]\], our study animals were exposed to these dietary manipulations *in utero* via the mother's diet and throughout the first five months of life, using an experimental design similar to our previous NAFLD studies \[[@B9],[@B30]\]. Concentrations of ASP and MSG used throughout this study were comparable with the Acceptable Daily Intake for both substances \[[@B31],[@B32]\], which we believe makes our experimental paradigm an appropriate model for examining the interaction between commonly-consumed food additives. To our knowledge this is the first article to address the effect of these additives on hepatic and adipose tissue gene expression in a rodent nutrigenomics model.
Materials and methods
Animals and diets
Our study animals were bred from C57Bl/6 J mice obtained from The Jackson Laboratory (Maine, USA). Female breeders were housed and fed a standard chow diet until 6 weeks of age whereupon they were placed on one of 4 different dietary regimens for an adjustment period of 3 weeks prior to mating as described previously \[[@B9],[@B30]\]. The four diet regimens used in this study were: \[[@B1]\]**TFA control diet**: consisting of 20% (w/w) Partially Hydrogenated Vegetable Shortening (Test Diet \#5C4M containing 8.68% w/w *Trans* fatty acids; Test Diet Purina, USA), with *ad lib* drinking water \[[@B2]\]. **MSG + TFA diet**: TFA diet with *ad lib* drinking water containing 0.75 g/L of L -Glutamic acid monosodium salt hydrate (MSG catalog G1626 Sigma Aldrich) \[[@B3]\]. **ASP + TFA diet**: TFA diet with *ad lib* drinking water containing 0.25 g/L Asp-Phe methyl ester (aspartame, ASP, catalog A5139 Sigma Aldrich) \[[@B4]\]. **ASP + MSG + TFA diet:** TFA diet with *ad lib* drinking water containing 0.25 g/L aspartame and 0.75 g/L monosodium glutamate (see Additional file [1](#S1){ref-type="supplementary-material"} for diet composition). Following mating, the 4 groups of breeder dams were maintained on their respective diets throughout the gestation, birth and nursing period. The offspring used in the following experiments were weaned onto the same maternal dietary regimen at 4 weeks of age and maintained on their respective diets for the duration of the study. Male offspring (n = 15 per diet group) were housed 3 to a cage in an identical manner as described above. Average body weight was assessed at 6 & 17 weeks of age. Percentage weight change between these two time-points was calculated as follows:
{\%\mspace{9mu}{weight}\mspace{9mu}{change}\mspace{9mu} =} & {\quad({weight}\mspace{9mu}{at}\mspace{9mu} 17\mspace{9mu}{weeks} -} \\
& \left. \quad{weight}\mspace{9mu}{at}\mspace{9mu} 6\mspace{9mu}{weeks})/{weight}\mspace{9mu}^{*}100 \right. \\
mean ASP and MSG consumption were calculated from the amount of aspartame-water and MSG-water consumed, and expressed in mg per Kg body weight. At the conclusion of the study (20 weeks of age), overnight-fasted subjects were euthanized with a mixture of xylazine and ketamine, and the blood was collected for analysis of serum components. Concomitantly, the liver and the visceral fat (epididymal fat pads, together with adipose tissue associated with the reproductive organs and omental-mesenteric fat associated with the digestive organs) was carefully excised, rinsed in PBS buffer, blotted dry and weighed to the nearest 0.01 g. Tissues were either snap-frozen in liquid nitrogen for RNA isolation and hepatic lipid quantitation, or immediately placed in 5× volume of formalin for histological analysis. The breeding and care of the animals were in accordance with the protocols approved by the Animal Care and Use Committee of the King Faisal Specialist Hospital & Research Centre.
Measurement of fasting serum glucose, hormone, and lipid profile
Overnight fasting blood glucose was measured from the tail vein of the 6-week and 17-week old experimental subjects using the Ascensia Contour glucometer (Bayer HealthCare, IN, USA). Additionally, total cholesterol (T-CHOL), and HDL-C concentrations were also measured in overnight fasted 17-week old mice using the Reflovet Plus instrument (Roche, F. Hoffmann-La Roche Ltd, Basel, Switzerland) as described in our previous studies \[[@B9],[@B30]\]. A panel of murine hormones and cytokines relating to the metabolic syndrome (amylin, C-peptide, gastric inhibitory peptide GIP, insulin, leptin, MCP-1, resistin, and TNFα) were simultaneously analyzed using the Multiplex bead-based Mouse metabolic assay catalog\# MMHMAG-44 K (Millipore, Billerica, MA, USA), according to manufacturer's instructions. Samples and standards were processed using the Luminex 100/200 system with related xPONENT^®^ software (version 3.1; Luminex Corporation, Austin, TX, USA). A five-parameter logistic regression model with weighting was used to create standards curves (pg/mL) and calculate the mean of sample concentration from each triplicate. Homeostatic Model Assessment Index (HOMA-IR) values, a measure of insulin resistance, were calculated according to the established formula: (fasting serum glucose mM) **\*** (fasting serum insulin μIU/ml)/22.5 \[[@B33]\].
Liver and adipose tissue histology, and hepatic triglyceride quantitation
Formalin-fixed, paraffin-embedded liver and visceral cavity adipose tissues from each of the experimental subjects were processed, and 4 μm-thick serial sections were cut and stained with hematoxylin and eosin (H&E: liver) or trichrome (adipose tissue) according to standard laboratory procedures. After mounting with glycerol gelatin, images were captured using Axio Vision Rel4.5 software (Carl Zeiss). Levels of mouse liver triglyceride (Tg) were quantified using the Triglyceride Determination Kit TRO100 with appropriate triglyceride standards (Sigma Aldrich, MO, USA). Frozen liver samples from 20-week old mice were first powdered under liquid nitrogen and 120 mg of the frozen liver powder was weighed into 2 ml chloroform: methanol mix (2:1 v/v) and incubated for 2 hours at room temperature with continuous shaking. Following the addition of 0.2 vols H~2~O, vortexing and centrifuging at 2500 g, the lower phase chloroform containing the lipids was collected and dried under vacuum in a rotary evaporator for 5--6 hr. The dried pellets were resuspended in the reaction buffer provided in the Kit. Results were expressed as mean Tg (mg /g tissue) ± SEM, n = 15 per diet group.
Animals (n = 15 per diet group) were euthanized at 20 weeks of age by xylazine/ketamine intramuscular injection, and the liver and adipose tissues were rapidly removed and rinsed in PBS buffer as described above. After weighing, the tissues were snap-frozen for RNA extraction as described previously \[[@B9],[@B30]\]. Total RNA was prepared using Qiagen RNeasy Kit (Qiagen, CA, USA) according to the manufacturer's instructions and stored at −80°C. RNA integrity was measured using a 2100 Bioanalyzer instrument and an RNA 6000 Nano LabChip assay (Agilent Technologies, CA, USA). RNA concentrations were determined by absorption at 260-nm wavelength with an ND-1000 spectrometer (Nanodrop Technologies, DE, USA).
Gene expression analysis
Gene expression in these samples was analyzed using 12 GeneChip (R) Mouse Gene 1.0 ST arrays representing 28,853 genes. We used 3 chips per diet group, and applied pooled RNA from 5 mice per chip (see Figure [1](#F1){ref-type="fig"} for design of the microarray experiments). Targets were prepared and microarrays were processed as described in the Affymetrix GeneChip Whole Transcript Expression Analysis manual using the Ambion WT expression kit and Affymetrix WT Terminal Labeling Kit as per manufacturers' instructions. Briefly, approximately 250 ng of total RNA was used to synthesize double-stranded DNA with random hexamers tagged with a T7 promoter sequence. The cDNA was used as a template for *in vitro* transcription. In the second cycle cDNA synthesis, random primers were used in reverse transcription to convert the cRNA into single-stranded DNA, which was fragmented, labeled, and hybridized to the array for 17 hours, then washed and stained using the Fluidics 450 station (Affymetrix, Santa Clara, CA). Arrays were scanned using the Affymetrix 3000 7G scanner and GeneChip Operating Software version 1.4 to produce.CEL intensity files. This software also provided summary reports by which array QA metrics were evaluated including average background, average signal, and 3′/5′ expression ratios for spike-in controls, β-actin, and GAPDH. Microarray data was deposited at the MIAME compliant NCBI gene expression hybridization array data repository (GEO: <http://ncbi.nlm.nih.gov/geo>) under accession \#GSE38444 and GSE38445 (expression data from liver and adipose tissue respectively).
::: {#F1 .fig}
**Functional relationship networks of PPAR and PPAR-interacting DEGs responsive to ASP + MSG.** IPA-generated networks depict PPAR-interacting DEGs in **(a)** Liver &**(b)** Adipose (P \< 0.01, stringency ≥ ± 1.4-fold change in expression).
Confirmation of microarray results was performed by quantitative PCR (qPCR) as previously described \[[@B30]\]. Total RNA (2 μg) was reverse transcribed using SuperScript II reverse transcriptase (Invitrogen, CA, USA). Subsequently, qPCR reactions were performed in triplicate using SYBR-Green 1 master mix (Roche Diagnostics IN, USA) and 10 ng cDNA as template. No template and no reverse transcriptase controls were included and products were analyzed by gel electrophoresis. Real time qPCR values for each target gene were calculated as a ratio of target gene expression level to GAPDH expression level in the same specimen. Statistical significance was assessed using a two-tailed t test assuming unequal variance of the biological replicates. Intron-spanning gene specific primers were designed using Primer 3 software and sequences are provided in Additional file [2](#S2){ref-type="supplementary-material"}: Table S2. DEGs that differed significantly (P \< 0.01) in their regulation between the diet groups' microarray analysis were selected, based on their biological relevance, and validated with the same samples by qPCR analysis. Ratios of expressions between the diet comparisons were calculated from the microarray data set and Pearson correlation analysis between the qPCR and microarray data were calculated.
Morphological and biochemical data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's test. Differences were considered significant at P \< 0.05. For identification of differentially expressed genes (hereafter termed DEGs), microarray analysis was performed using the Partek Genomic suite software version 6.3 (Partek, MO, USA) as previously described \[[@B9],[@B30]\]. Probe set data were summarized and background adjusted using the GC-Robust Multi-Array (GCRMA) algorithm \[[@B34]\], as implemented in the microarray analysis software package. The GC-RMA algorithm is based on a linear additive model, and assumes that *Y*~*gij*~ = *O*~*gij*~ + *N*~*gij*~ + *S*~*gij*~, where *Y*~*gij*~ is the perfect match probe intensity value for probe *j* in probeset *g* on array *i*. *O*~*gij*~ is the corresponding "optical noise" due to laser scanning errors, *N*~*gij*~ is the corresponding "non-specific binding noise," and *S*~*gij*~ is a quantity proportional to the actual abundance of target transcript in a sample, which allows for estimation of the "true" expression value. This method is used to reduce discrepancies in hybridization patterns from each of the three chips per diet group that might result from variables in target amplification, hybridization conditions, staining or probe array lot. All data were normalized using non-linear transformation termed Quantile Normalization to improve the linearity, normality & homoscedasticity of the data, which was further filtered to remove noise and extreme expression values. Additionally, all probesets without unique Entrez gene identifiers were removed from the analysis. We used a one-way ANOVA to test for diet interactions without correction for multiple testing. A significance value of 0.05 indicated that the gene was differentially regulated by diet. See Figure [1](#F1){ref-type="fig"} for the design and analysis of the microarray experiments. In order to identify genes regulated in response to dietary manipulation, we used the False Discovery Rate (FDR) method \[[@B35]\] in which p-values were adjusted simultaneously across multiple subgroup comparisons. Contrasts were included in the model based on the comparison of interest. All further sub-lists were created using genes that passed the FDR adjusted ANOVA p-value as well as fold change criteria. A significance value of 0.05 indicated that the gene was differentially regulated by diet with a stringency of 1.4-fold change in expression values. For identification of diet-induced differentially expressed genes we considered the comparison of three conditions (TFA versus ASP + TFA; TFA versus MSG + TFA; and TFA versus ASP + MSG + TFA). All resultant genes and expressed sequence tags (ESTs) meeting the criteria for ASP- and MSG-induced differential expression were classified as relatively upregulated or downregulated compared to TFA. Genes fulfilling these criteria were ascribed genome-wide significance using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) annotation \[[@B36]\]. Ingenuity Pathways Analysis (IPA: <http://www.ingenuity.com>) was used for detection of gene ontology, canonical pathways analysis, with significant transcripts in diet groups compared to control. Networks of biologically related genes were also created using IPA. Heat maps of the gene/ESTs expression data were generated using Matlab (version 7.6, The MathWorks, Inc. USA) and Partek.
A combination of aspartame and MSG in a *Trans* fat diet promotes hyperglycemia, and increases adiposity and hepatic steatosis
The experimental design is outlined in Additional file [3](#S3){ref-type="supplementary-material"}. There were no significant differences in food and water intake between the 4 different diet groups (data not shown). Mean TFA consumption was 0.02 g/Kg body weight. Mean aspartame (ASP) and monosodium glutamate (MSG) consumption in the drinking water was 43.54 ± 1.42 mg/Kg body weight and 130.03 ± 5.61 mg/Kg body weight respectively. Histologically, livers presented with indications of micro- and macrosteatosis, with the ASP + MSG diet apparently resulting in the highest degree of overall steatosis compared to the other diet groups (see Additional file [4](#S4){ref-type="supplementary-material"}). Trichrome staining of adipose tissue taken from visceral depots showed a non-significant increase in the apparent size of adipose tissue cells.
Whilst there were no apparent differences in the mean body weight or weight of liver tissue between all 4 diet groups, the weight of visceral adipose tissue in the ASP + MSG + TFA diet group was significantly greater than all three other diet groups, suggesting the development of obesity (Table [1](#T1){ref-type="table"}, P = 0.001). Additionally, levels of plasma free fatty acids (FFA) were significantly elevated in both MSG-containing diet groups (MSG + TFA and ASP + MSG + TFA). These two diet groups also had the highest levels of hepatic triglyceride (TG) content indicative of hepatic steatosis (P ≤ 0.001).
::: {#T1 .table-wrap}
Body characteristics and biochemical, lipid and hormone profile of experimental subjects
**TFA** **MSG + TFA** **ASP + TFA** **ASP + MSG + TFA** **Sig.**
---------------------------- ------------------------ ------------------------- ------------------------ -------------------------- ----------
Body Weight (g)
6-week 20.07 ± 0.43 21.29 ± 0.28 20.94 ± 0.26 21.03 ± 0.32 0.06
17-week 31.58 ± 0.77 32.99 ± 0.59 31.37 ± 0.58 32.36 ± 0.87 0.31
\% Weight Change 57.58 ± 2.85 54.91 ± 1.59 50.19 ± 3.44 54.78 ± 2.38 0.27
Adipose Weight (g) 1.08^**a**^ ± 0.13 1.36^**ab**^ ± 0.09 0.98^**a**^ ± 0.16 1.67^**b**^ ± 0.14 0.001
Liver Weight (g) 1.25 ± 0.06 1.23 ± 0.05 1.30 ± 0.03 1.33 ± 0.06 0.49
Liver Triglyceride (mg/ml) 8.12^**a**^ ± 0.65 12.14^**b**^ ± 1.00 9.90^**ab**^ ± 1.16 13.33^**b**^ ± 0.84 0.001
T\_CHOL (mmol/dL) 121.60^**a**^ ± 1.34 121.67^**a**^ ± 3.25 127.0^**ab**^ ± 1.62 130.13^**b**^ ± 1.54 0.01
HDL (mmol/dL) 87.43 ± 4.08 89.39 ± 4.61 96.75 ± 1.22 98.09 ± 2.91 0.08
Free Fatty Acids (μM) 156.99^**ab**^ ± 4.59 177.36^**bc**^ ± 7.73 146.2^**a**^ ± 5.30 190.03^**c**^ ± 5.36 \<0.0001
Fasting Glucose (mg/dL)
6-week 45.00^**a**^ ± 2.10 52.03^**ab**^ ± 3.41 62.50^**b**^ ± 3.09 92.50^**c**^ ± 3.87 \<0.0001
17-week 98.53^**ac**^ ± 8.05 117.43^**ab**^ ± 10.21 81.97^**c**^ ± 6.53 132.90^**b**^ ± 8.23 \<0.001
Insulin (pg/ml) 525.5 ± 55.6 552.51 ± 56.57 539.73 ± 43.84 606.46 ± 54.50 0.75
HOMA-IR 3.65^**a**^ ± 0.38 4.67^**ab**^ ± 0.27 3.06^**a**^ ± 0.31 5.86^**b**^ ± 0.70 \<0.001
C-Peptide (pg/ml) 1761.88^**a**^ ± 200.3 1708.5^**a**^ ± 123.17 1078.42^**b**^ ± 86.51 1994.65^**a**^ ± 150.65 \<0.001
Amylin (pg/ml) 58.38 ± 5.39 58.82 ± 5.55 64.74 ± 4.24 59.75 ± 4.82 0.81
GIP (pg/ml) 129.13^**ab**^ ± 17.9 95.46^**b**^ ± 7.37 143.68^**c**^ ± 11.91 113.75^**ac**^ ± 8.69 0.04
Leptin (pg/ml) 5096.68^**a**^ ± 662.7 9073.34^**b**^ ± 1319.8 5460.9^**a**^ ± 979.17 10917.55^**b**^ ± 716.01 \<0.001
MCP-1 (pg/ml) 69.06^**a**^ ± 7.26 55.09^**a**^ ± 6.03 69.05^**a**^ ± 7.96 39.58^**b**^ ± 4.53 0.01
Resistin (ng/ml) 25.24 ± 1.64 23.12 ± 1.33 21.64 ± 1.24 25.33 ± 1.67 0.26
TNF-α (pg/ml) 11.35^**a**^ ± 1.35 7.77^**a**^ ± 1.97 9.59^**a**^ ± 1.40 30.56^**b**^ ± 11.44 0.03
*HOMA*-IR Homeostasis model of assessment of insulin resistance, *GIP* Gastric inhibitory polypeptide, *MCP*-1 Monocyte chemotactic peptide-1. Data are presented as Means ± SEM (n = 15 per diet group). Significant differences in Means are indicated using different letters *abc* for p-value of \<0.05.
Fasting blood glucose levels were highest in the ASP + MSG + TFA diet group at both 6 and 17 weeks of age (Table [1](#T1){ref-type="table"}, P \< 0.001). At 17 weeks of age, fasting blood glucose levels were markedly higher than the levels at 6 weeks; and the combination of ASP + MSG in the TFA -fed mice elevated fasting glucose to pre-diabetic levels \[[@B37]\]. Analysis of hormones and cytokines related to the development of obesity and hepatic steatosis showed that both MSG-containing diet groups had significantly higher levels of serum leptin and TNFα (MSG + TFA and ASP + MSG + TFA diet mice, Table [1](#T1){ref-type="table"}, P \<0.05). Fasting serum insulin levels were increased by 15% in ASP + MSG + TFA diet mice although this observation failed to reach statistical significance. However, the HOMA-IR index, an indicator of insulin resistance, was significantly increased by 56% in ASP + MSG + TFA diet mice (P \< 0.001). Levels of serum amylin and resistin were not significantly affected by the food additive diets. In summary, the addition of MSG to the TFA diet raised hepatic triglyceride and serum leptin levels. The combination of ASP + MSG promoted visceral adiposity, and elevated hepatic triglyceride levels, serum FFA, fasting blood glucose, TNFα and HOMA-IR index in *Trans*-fat fed mice.
We next used Pearson correlation analysis In order to further understand the mechanism behind the increased hepatic triglycerides and visceral fat observed in the ASP and MSG-fed mice. Significant correlations between levels of hepatic triglyceride content and adipose tissue weight, FFA, serum cholesterol and leptin were apparent, suggesting the possibility that the mechanism behind the lipid accumulation in the liver could be via increased adipose tissue mass and flux of FFA to the liver. HOMA-IR, a strong indicator of the development of insulin resistance, correlated with body and adipose tissue weight, fasting glucose, insulin, C-peptide, leptin and resistin (Table [2](#T2){ref-type="table"}, P \< 0.05).
::: {#T2 .table-wrap}
Correlations of HOMA-IR and hepatic triglyceride (TG) levels with markers of weight gain, adiposity and dyslipidemia
**Liver TG (mg/ml)** **HOMA-IR**
------------------------- ---------------------- --------------------
Body weight (g)
6-week .031 **.338**^**\***^
17-week **.319**^**\***^ **.575**^**\*\***^
Weight gain (%) **.355**^**\*\***^ **.387**^**\*\***^
Adipose weight (g) **.565**^**\*\***^ **.551**^**\*\***^
Liver weight (g) **.358**^**\*\***^ .174
Liver TG (mg/ml) 1 .263
T\_CHOL (mmol/dL) **.439**^**\*\***^ -.027
Free fatty acids (μM) **.361**^**\***^ .119
Fasting glucose (mg/dL)
6-week **.268**^**\***^ **.436**^**\*\***^
17-week **.428**^**\*\***^ **.693**^**\*\***^
Insulin (pg/ml) -.063 **.742**^**\*\***^
HOMA-IR .260 1
C-peptide (pg/ml) .235 **.620**^**\*\***^
Leptin (pg/ml) **.555**^**\*\***^ **.519**^**\*\***^
MCP-1 (pg/ml) **-.376**^**\***^ -.207
Resistin (ng/ml) -.044 **.403**^**\*\***^
Significant correlations are indicated in bold by \*\* at the 0.01 level and \* at the 0.05 level (2-tailed). *TG* triglyceride.
Significant correlations are indicated in bold by \*\* at the 0.01 level and \* at the 0.05 level (2-tailed). *TG* triglyceride.
Aspartame and MSG modify hepatic and adipose tissue gene expression
Microarray analysis of hepatic and adipose tissue gene expression was used in order to further examine the mechanism behind the diet-induced changes in adiposity and glucose homeostasis. We used Affymetrix Mouse Gene 1.0 ST expression arrays to determine differences in global gene/Expressed Sequence Tags (ESTs), identifying10,117 hepatic gene transcripts and almost 3 times that number (28,101) of adipose tissue transcripts, with a significant p-value of 0.05 for diet (see Additional file [3](#S3){ref-type="supplementary-material"}). In order to identify the impact of consumption of ASP, MSG or a combination of both on gene expression in *Trans* fat-fed mice, we next identified subsets of ASP-induced and MSG-induced DEGs using a false discovery rate as described by Benjamini and Hochberg, with a significance set at 0.05 and a stringency of ± 1.4-fold. We identified 8327 liver transcripts which were differentially expressed by either ASP, MSG or a combination of the two compared to the TFA-fed control, and a corresponding 11,600 adipose tissue transcripts. These DEGs were further bifurcated into either down- or up-regulated in response to the food additives (see Additional file [5](#S5){ref-type="supplementary-material"}). We identified subsets of 1715 DEGs upregulated by ASP in the liver and 2599 DEGs upregulated by ASP in the adipose tissue. In both tissues, MSG upregulated the lowest number of DEGs: 1017 in the liver and 1249 in the adipose tissue. Interestingly, the combination of ASP + MSG upregulated the highest number of DEGs in the adipose tissue (2691) compared to approximately half as many in the liver (1148). Broadly speaking, the number of ASP- and MSG-induced downregulated DEGs was similar to the number upregulated, the exception being in the adipose tissue, where MSG down-regulated approximately half the number of upregulated DEGs. In summary, in terms of global gene activation, the adipose tissue appears to be more responsive to dietary manipulation compared to the liver, and the combination of ASP + MSG induced the highest number of DEGs compared to either food additive alone.
Functional gene ontology analysis of food additive-responsive DEGs
In order to further classify the nature of the food additive-responsive gene activation in TFA -fed mice, we examined the functional gene ontologies of the diet-responsive DEGs in both liver and adipose tissue. Additional file [6](#S6){ref-type="supplementary-material"} summarizes the main significant ontologies of up- and down-regulated DEGs induced by ASP, MSG or a combination of the two, in the livers and adipose tissue of TFA -fed mice. MSG induced hepatic gene expression related to blood vessel morphology, transportation of molecules, and uptake of lipids. Conversely, genes related to RNA expression, proliferation, mitosis and xcell death were down-regulated. In adipose tissue, MSG induced genes with ontologies related to vasculogenesis, proliferation and quantity of mononuclear leukocytes, whereas genes relating to glucose metabolism disorders and Diabetes Mellitus were down-regulated (p \< 0.05).
A different pattern of gene expression ontologies was seen in ASP-treated mouse tissues, with the significant upregulation of genes involved in the organization of the cytoplasm, morphology of blood vessels and angiogenesis, and the down-regulation of genes with ontologies relating to hepatic protein metabolism, organization of peroxisomes and expression of RNA (see Additional file [6](#S6){ref-type="supplementary-material"}). ASP-induced genes relating to cell proliferation and the development of blood vessels were upregulated in the adipose tissue of TFA -fed mice; whereas down-regulated ontologies included adipogenesis and the proliferation of immune cells. Common gene ontologies significantly induced by the combination of ASP + MSG included morphology of vessels, vasculogenesis and fatty acid metabolism, whereas hepatic genes relating to hepatic expression of RNA and cell cycle progression was downregulated in all 3 cases. In adipose tissue, similarities in the ontologies of significant DEGs upregulated by both food additives included vasculogenesis, angiogenesis and response to macrophages, whereas down-regulated DEGs related to proliferation of leukocytes and the metabolism of glucose.
Generation of networks of diabetogenic peroxisome proliferator-activated receptor (PPAR) genes
Since the combination of MSG and aspartame promoted the largest changes in adiposity, blood glucose and lipid dysregulation in TFA -fed mice, we next generated networks of differentially expressed genes which were dysregulated in response to both ASP and MSG feeding. We were particularly interested in transcripts associated with the dysregulation of PPAR genes, since it is known that PPAR transcriptional activity is affected by diet and adiposity, and particularly dysregulated by diabetes \[[@B37]\]. Figure [1](#F1){ref-type="fig"}a shows networks of significant hepatic PPAR DEGs up-regulated (red) or down-regulated (green) by the combination of ASP + MSG in the livers of TFA -fed mice. Key "Master switch" transcription factor Ppargc1a expression was reduced by 1.7-fold, conversely levels of hepatic Pparα and Pparδ were modestly increased in this experimental model. Lipogenic cholesterol homeostasis transcription factor Srebf2 was upregulated 1.6-fold, together with a similar increase in cyclic AMP responsive element binding protein Creb1 (P \< 0.05). Additionally, expression of Acetyl-CoA carboxylase ß (Acacb, Acc2), an important diet-regulated enzyme involved in lipogenesis was increased 1.9-fold together with a 1.8-fold increase in carnitine palmitoyltransferase 1c (Cpt1c), one of the first enzymes in the mitochondrial ß-oxidation of long chain fatty acids. Another feature of the food-additive induced gene expression was the upregulation of PPAR target genes Acetyl CoA thioesterase (Acot1), CD36 (1.7-fold) and endothelial lipase (Lipg: 1.7-fold) which are involved in lipid hydrolysis. PPARα-related genes involved in cholesterol and phospholipid homeostasis such as the ATP-binding cassette transporters Abca1, Abcb4 and Abcd2 were upregulated approximately 1.5-fold, additionally we found a 1.7-fold upregulation of the PPARα marker genes Cyp4a10 and Cyp4a14 and acetyl-Coenzyme A acyltransferase (Acaa1b); all previously identified as being upregulated in models of diabetes. Several genes involved in cellular stress induction and protection were deregulated by ASP and MSG in TFA-fed mice, including an increase in Trp53 (p53: 1.42-fold), Car (Nr1i3; 1.43-fold), Mef2d (1.6-fold) and Hdac5 (1.5-fold); together with a decrease in hepatic nuclear factor 6 (Onecut1, 2.23-fold), hepatocyte growth factor (HGF, 1.7-fold), and Stat3 (1.5-fold).
As expected, the adipose tissue of TFA -fed mice contained many more PPAR-related DEGs in response to aspartame and MSG consumption (Figure [1](#F1){ref-type="fig"}b). The expression of adipose tissue Ppargc1a was reduced by 3.5-fold, together with a 50% reduction in the expression of PPARs α and γ, suggesting significant disruption of mitochondrial biogenesis and lipid metabolism (PPARα and PPARγ, P \< 0.05). The transcription of IPA-generated genes involved in the ß-oxidation of fatty acids and glucose were modestly down-regulated, such as rate-limiting enzymes short chain acyl-CoA dehydrogenase (Acads), very long chain acyl-CoA (Acadvl ) and dehydrogenase 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and pyruvate dehydrogenase ß (Pdhb). IPA-generated networks also linked adipogenic gene expression to Ppar transcription factor down-regulation, including increases in Creb1, Crebbp, Notch1 and Lipin1. Additionally, expression of other genes related to lipid mobilization and storage were dysregulated in this model, such as the reverse cholesterol transporter genes Abca1 and Abca3, perilipin5 (Plin5) and apolipoprotein a4 (Apoa4).
Oxidative stress-responsive sirtuins 1 and 2 (Sirt1 and Sirt2) gene were upregulated by 2.4 - 2.6-fold, together with a modest but significant increase in the transcription factor forkhead box 3 (Foxo3) and its target genes: Cdkn1b (p27^Kip1^: 1.41-fold), growth arrest and DNA damage-inducible protein 45 (GADD45b: 1.88-fold), and pro-apoptotic Trp53 (4.4-fold). This was accompanied by a 2.5-fold reduction in p53-binding and regulatory protein Mdm2, and a 1.7-fold reduction in peroxiredoxin 5 (Prdx5), known to protect against oxidative stress. Since PPARs also play an essential role in adipogenesis, we were interested to find changes in gene expression relating to adipocytes growth and differentiation in *Trans* fat-fed mice consuming both food additives. Expression of oncogenic Notch1 was increased by 2.27 fold; which was accompanied by a 1.8-fold increase in nuclear receptor co-repressor 1 (Ncor1) and a 1.6-fold increase in histone deacetylase 1 (Hdac1) expression, suggesting a significant upregulation of this evolutionary conserved intracellular signaling pathway. Furthermore levels of a novel adipocyte differentiating gene mediator (Med23) were increased nearly 3-fold.
The PPAR -downstream adipokine Thrombospondin-1 (Thbs1) was strongly activated in ASP + MSG-fed mice by 4.6-fold, suggesting the possibility of the development of inflammation in these tissues. Serum levels of TNFα were elevated by almost 3-fold in ASP + MSG-fed mice, however we did not detect a significant increase in adipose tissue TNFα gene expression. Further examination of adipose tissue gene expression revealed several important inflammatory genes which were not included in the adipose tissue PPAR networks, including a 3-fold increase in colony stimulating factor Csf1, and pro-inflammatory Interleukin-6 receptor. Expression of 12/15-lipoxygenase (Alox15), key regulator of pro-inflammatory cytokines and chemokines was upregulated by more than 3-fold; accompanied by 3-fold increases in macrophage-marker Emr1. Taken together, the PPAR-related gene networks generated here in response to aspartame and MSG consumption predominantly indicate transcriptional activity related to adipogenesis, ß-oxidation, peroxisomal and mitochondrial function, tissue matrix remodeling, lipid storage and mobilization, and inflammatory mechanisms.
Coordinated dysregulation of adipose tissue genes involved in glucose and lipid catabolism and ß-oxidation in ASP + MSG-treated mice
The highest levels of adipose tissue, glucose and plasma free fatty acids were apparent in *Trans* fat-fed mice consuming both ASP and MSG; and since analysis of PPAR-related gene networks revealed diet-induced changes in the expression of some genes involved in fatty acid oxidation, we next focused more specifically on differentially expressed genes associated with lipolysis, glycolysis, the citric acid cycle and mitochondrial oxidative phosphorylation (Ox-Phos), together with other genes with mitochondrial and peroxisomal biogenesis functions. Table [3](#T3){ref-type="table"} shows fold-changes in the expression of 60 genes with these classifications, which were dysregulated by the combination of ASP + MSG by ≥1.40-fold, and indicates that 50% of these were also dysregulated by ASP alone. For example in adipose tissue but not liver, we found significantly attenuated expression of both short-chain and very long-chain Acyl-coA dehydrogenase, which catalyze the first steps in the oxidation of free fatty acids. Expression of the trifunctional enzyme subunit Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratases α and ß (Hadha and Hadhb), which catalyzes the last three steps of mitochondrial ß-oxidation of long chain fatty acids was also significantly attenuated in *Trans* fat-fed mice consuming a combination of ASP and MSG. In addition to the 50% reduction in expression of adipose tissue PPARα, ASP + MSG-fed mice exhibited a significant reduction in Enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh), the second enzyme in the inducible peroxisomal ß-oxidation pathway. Glycolysis activator genes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (Pfkfb2 and Pfkfb4) were upregulated just over 2-fold.
::: {#T3 .table-wrap}
Diet-specific coordinated dysregulation of adipose tissue genes involved in glucose and lipid catabolism expressed as significant fold changes (P \< 0.05, stringency ≥ ± 1.4-fold change in expression)
**Symbol** **Induced by MSG** **Induced by ASP** **Induced by ASP + MSG** **Sig.**
---------------------------------------------------------------- ------------ -------------------- -------------------- -------------------------- ----------
**Mitochondrial ß-oxidation genes**
Peroxisome proliferator-activated recepto rγ, coactivator 1α Ppargc1a −1.94 −4.51 −3.49 0.048
Peroxisome proliferator-activated receptor α Ppara −1.01 −1.99 −2.03 0.052
Carnitine palmitoyltransferase 1B Cpt1b −1.99 −1.46 −1.63 0.028
Acyl-CoA dehydrogenase, short-chain Acads −1.36 −1.32 −1.57 0.024
Acyl-CoA dehydrogenase, very long chain Acadvl −1.32 −1.11 −1.67 0.036
Hydroxyacyl-CoA dehydrogenaseα Hadha −1.14 −1.31 −1.50 0.036
Hydroxyacyl-CoA dehydrogenase ß Hadhb −1.06 −1.43 −1.73 0.051
**Citric acid cycle (TCA) genes**
Aconitase 1, soluble Aco1 −1.79 −1.69 −1.67 0.003
Isocitrate dehydrogenase 2 (NADP+), mitochondrial Idh2 −1.19 −1.36 −1.44 0.022
Pyruvate dehydrogenase (lipoamide) α2 Pdha2 −1.43 −1.82 −2.36 0.004
Pyruvate dehydrogenase (lipoamide) ß Pdhb −1.30 −1.36 −1.62 0.043
Succinate dehydrogenase complex, subunit B Sdhb −1.32 −1.30 −1.44 0.001
**Mitochondrial oxidative phosphorylation genes**
NADH dehydrogenase (ubiquinone) 1 α subcomplex 5 Ndufa5 −1.14 −1.19 −1.47 0.007
NADH dehydrogenase (ubiquinone) 1 α subcomplex 12 Ndufa12 −1.21 −1.24 −1.46 0.004
NADH dehydrogenase (ubiquinone) 1ß subcomplex 2 Ndufb2 −1.12 −1.34 −1.55 0.016
NADH dehydrogenase (ubiquinone) 1ß subcomplex 6 Ndufb6 −1.11 −1.31 −1.46 0.050
NADH dehydrogenase (ubiquinone) 1ß subcomplex10 Ndufb10 1.01 −1.20 −1.76 0.010
NADH dehydrogenase (ubiquinone) Fe-S protein 1 Ndufs1 −1.62 −1.46 −2.16 0.006
NADH dehydrogenase (ubiquinone) Fe-S protein 6 Ndufs6 −1.29 −1.38 −1.53 0.037
NADH dehydrogenase (ubiquinone) flavoprotein 1 Ndufv1 −1.16 −1.27 −1.60 0.005
Succinate dehydrogenase complex, subunit B Sdhb −1.32 −1.30 −1.44 0.001
Ubiquinol-cytochrome c reductase, complex 3 subunit 6 Uqcr11 −1.44 −1.44 −1.58 0.006
COX assembly mitochondrial protein homolog Cmc1 −1.17 −2.33 −2.53 0.040
Cytochrome c oxidase subunit 7a polypeptide 1 Cox7a1 −1.34 −1.25 −1.66 0.005
Cytochrome c oxidase, subunit 7b Cox8b −1.32 −1.13 −1.58 0.047
Cytochrome c oxidase assembly homolog Cox11 −1.04 −1.32 −1.46 0.024
COX assembly mitochondrial protein homolog Cmc1 −1.17 −2.33 −2.53 0.040
Uncoupling protein 2 (mitochondrial, proton carrier) Ucp2 1.32 1.43 1.59 0.001
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 Pfkfb2 1.37 1.99 2.47 0.050
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 Pfkfb4 1.53 2.48 2.85 0.001
**Mitochondrial biogenesis & assembly**
Polymerase gamma (nuclear encoded) Polg 1.42 1.72 1.94 0.038
Transcription factor A, mitochondrial Tfam −1.38 −1.32 −2.07 0.008
Mitochondrial fission process 1 Mtfp1 −1.37 −1.30 −1.64 0.004
Tu translation elongation factor, mitochondrial Tufm −1.07 2.14 1.68 0.011
G elongation factor, mitochondrial 2 Gfm2 −1.22 −2.30 −2.46 0.034
Mitochondrial ribosomal protein L3 Mrpl3 −1.06 2.03 1.79 0.054
Mitochondrial ribosomal protein L20 Mrpl20 −1.21 −1.41 −1.62 0.024
Mitochondrial ribosomal protein S24 Mrps24 1.53 −2.99 −3.31 0.037
Mitochondrial ribosomal protein S7 Mrps7 −1.12 −1.39 −1.63 0.032
Mitochondrial ribosomal protein S12 Mrps12 −1.36 −1.40 −1.73 0.011
Mitochondrial ribosomal protein S27 Mrps27 −1.16 −1.28 −1.55 0.050
Surfeit 1 Surf1 −1.22 −1.46 −1.57 0.026
Mitochondrial inner membrane organizing system 1 Minos1 −1.02 −1.44 −1.50 0.001
Inner membrane protein, mitochondrial Immt −1.13 −1.33 −1.66 0.009
Peroxiredoxin 5 Prdx5 −1.15 −1.51 −1.70 0.029
DnaJ (Hsp40) homolog, subfamily C, member 27 Dnajc27 −1.48 −1.80 −1.51 0.047
Diablo, IAP-binding mitochondrial protein Diablo 1.14 1.51 1.63 0.007
BCL2-associated X protein Bax 1.23 1.38 1.66 0.032
Tumor protein p53 Trp53 2.13 3.57 4.39 0.004
Caspase 9 Casp9 1.44 1.86 1.70 0.034
E2F transcription factor 1 E2f1 1.52 1.73 2.60 0.025
Peroxisomal biogenesis factor 1 Pex1 −1.14 −2.02 −2.05 0.054
Peroxisomal biogenesis factor 5 Pex5 −1.29 −1.55 −1.67 0.039
Peroxisomal biogenesis factor 7 Pex7 −1.10 −1.74 −1.46 0.026
Peroxisomal biogenesis factor 11 α Pex11a −1.11 −1.40 −1.48 0.012
Peroxisomal biogenesis factor 13 Pex13 −1.17 −1.60 −1.43 0.055
Enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase Ehhadh −1.40 −1.06 −1.55 0.029
Acetyl-CoA acyltransferase 1 Acaa1a −1.32 −1.35 −1.59 0.056
ATP-binding cassette, sub-family D (ALD), member 1 Abcd1 1.29 1.69 2.09 0.051
Epoxide hydrolase 2 Ephx2 −1.17 −1.62 −1.66 0.010
**Calcium homeostasis genes**
Calcium homeostasis endoplasmic reticulum protein Cherp 1.55 2.21 2.37 0.002
Calcium homeostasis modulator 2 Calhm2 1.19 1.61 2.09 0.001
Calcium activated nucleotidase 1 Cant1 1.16 1.45 1.86 0.002
Mitochondrial calcium uniporter Ccdc109a 1.11 1.44 1.70 0.047
Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit Cacna1a 1.37 1.65 1.62 0.016
S100 calcium binding protein A8 S100a8 −1.15 −1.60 −1.57 0.033
Mitochondrial calcium uptake 1 Cbara1 −1.08 −1.80 −1.71 0.038
Calcium channel, voltage-dependent, gamma subunit 4 Cacng4 −1.26 −1.63 −1.85 0.000
Calcium binding protein 2 Cabp2 −1.26 −1.71 −1.98 0.015
S100 calcium binding protein A13 S100a13 −1.19 −2.09 −1.99 0.039
Solute carrier family 8 (sodium/calcium exchanger), member 1 Slc8a1 −1.40 −2.28 −2.01 0.042
Calcium channel, voltage-dependent, gamma subunit 8 Cacng8 −1.21 −1.87 −2.13 0.026
Calcium channel, voltage-dependent, T type, alpha 1I subunit Cacna1i −1.21 −1.38 −2.61 0.045
Calcium channel, voltage-dependent, beta 2 subunit Cacnb2 −1.56 −3.66 −2.76 0.037
Calcium channel, voltage-dependent, alpha 2/delta subunit 4 Cacna2d4 −1.77 −3.32 −3.35 0.019
Calreticulin 3 Calr3 −1.19 −1.83 −1.71 0.035
Lastly, the expression of genes involved in mitochondrial and peroxisomal biogenesis and apoptosis were affected by food additive consumption, including a 50% reduction in expression of mitochondrial transcription factor A (Tfam), a key activator of mitochondrial transcription as well as a participant in mitochondrial genome replication. Conversely, an increase in mitochondrial apoptosis was suggested by the upregulation of p53, E2F transcription factor 1, caspase 9 and Bax. In the liver, relatively few lipid catabolic genes were significantly down-regulated compared to the adipose tissue; conversely some important ß-oxidative genes such as Cpt1c were modestly upregulated.
Expression of food additive-induced DEGs common to both liver and adipose tissue
Our data show that the expression of many genes related to fatty acid catabolism where significantly down-regulated in the adipose tissue, but to a far lesser extent in the liver. The final part of our analysis aimed to shed more light on the nature of genes which were differentially regulated by the additives aspartame and MSG in both the liver and the adipose tissue of *Trans* fat-fed mice, in order to further our understanding of the mechanism(s) involved in the dyslipidemia and other metabolic disturbances. Figures [2](#F2){ref-type="fig"} and [3](#F3){ref-type="fig"} show Venn diagrams (A) and 2-D heat-maps (B) of sub-lists of DEGs considered significant only if they were up-regulated by ≥1.4-fold in response to ASP, MSG or a combination of the two additives, in both the liver and adipose tissue (Figure [2](#F2){ref-type="fig"}, P \< 0.05); or down-regulated by the same criteria (Figure [3](#F3){ref-type="fig"}, P \< 0.05). Almost twice as many genes were up-regulated than down-regulated in both tissues by the food additives, either alone (i.e. comparison ASP + TFA versus TFA, and comparison MSG + TFA versus TFA) or in combination (comparison ASP + MSG + TFA versus TFA). A total of 598 DEGs were up-regulated in all 3 comparisons, compared to only 320 down-regulated DEGs. Interestingly, aspartame alone induced the highest number of upregulated DEGs common to both tissues; followed by MSG; and the lowest number of upregulated DEGs was induced by the combination of both additives. A total of 73 DEGs common to both hepatic and adipose tissue were upregulated in response to a combination of ASP + MSG, and only 51 commonly expressed hepatic and adipose tissue DEGs were downregulated. Most notably up-regulated were a number of stress-responsive DEGs including Trp53 (p53), Notch1, phospholipase D2 (Pld2) and xanthine dehydrogenase (Xdh). Stress / remodeling proteoglycan Perlecan (Hspg2) was robustly up-regulated together with LDL-receptor related protein 1 (Lrp1), Plexin D1 (Plxnd1), Rock1, and Neurofibromatosis 1 (Nf1); all suggesting that food additive consumption may have led to an upregulation of genes involved in stress, proliferation, vasculogenesis and angiogenesis in both tissues (Figure [2](#F2){ref-type="fig"}b, P \< 0.05).
::: {#F2 .fig}
**Upregulated gene expression shared by liver and adipose tissue. (a)** Venn diagram displaying numbers of upregulated DEGs common to both liver and adipose tissue induced by either ASP, MSG or the combination of both additives. **(b)** 2-dimentional heat map of 73 upregulated DEGs common to both hepatic and adipose tissue (P \< 0.05, stringency ≥ ± 1.4-fold change in expression).
::: {#F3 .fig}
**Downregulated gene expression shared by liver and adipose tissue. (a)** Venn diagram displaying numbers of downregulated DEGs common to both liver and adipose tissue induced by either ASP, MSG or the combination of both additives. **(b)** 2-dimentional heat map of 51 downregulated DEGs common to both hepatic and adipose tissue (P \< 0.05, stringency ≥ ± 1.4-fold change in expression).
Key transcription factor Ppargc1a was significantly down-regulated in both tissues but particularly in adipose (Figure [3](#F3){ref-type="fig"}b); which was accompanied by a 2-fold reduction in hepatic expression of the Cl(−)/HCO \[[@B3]\] (−) anion exchanger 2 (Slc4a2), which is critically involved in the development of biliary cirrhosis. Two members of endocytic low density lipoprotein-related protein family (Lrp) were also down-regulated in both adipose and hepatic tissues. Expression of Lrp2, otherwise known as Megalin, was decreased 3-fold in adipose and 1.7-fold in liver tissue; whereas functionally-related Lrp4 expression was halved in both tissues. We also found a significant reduction in the expression of NADPH oxidase 1 involved in the regulation of superoxide generation, particularly in ASP + TFA diet comparisons. Fourteen genes were randomly chosen for further analyzed by qPCR based on biological relevance. Pearson correlation coefficients between the microarray analysis and qPCR were calculated. Ratios of expressions between the diet comparisons calculated from the microarray data set correlated well with the ratio calculated from the real-time PCR data (Figure [4](#F4){ref-type="fig"}, r = 0.641, P \< 0.0001). A complete list of these genes and PCR primers is given in Additional file [2](#S2){ref-type="supplementary-material"}.
::: {#F4 .fig}
**Correlation of qPCR and microarray data.** Scatter plot shows Correlation of the ratios from the microarray and real-time PCR data set. Genes that differed significantly (P \< 0.01) in their regulation between the diet groups' microarray analysis were selected and validated with the same samples by qPCR analysis. Ratios of expressions between the diet comparisons calculated from the microarray data set correlated well with the ratio calculated from the qPCR data (r = 0.641, P \< 0.0001). A complete list of these genes is shown in Additional file [2](#S2){ref-type="supplementary-material"}.
Taken together our final analysis suggests that the transcription of a number of functionally related hepatic and adipose tissue genes and transcription factors can be modulated in a similar manner by food additive consumption. These results may allow for informed speculation about the mechanisms behind the additive-induced metabolic dysregulation seen in this nutrigenomics model.
Our present data suggests that exposure to the food additives aspartame (ASP) and monosodium glutamate (MSG) as part of a *Trans* fat-enriched diet may cause metabolic dysregulation and alterations in hepatic and adipose tissue gene expression. Exposure to these additives offered continuously in the drinking water either alone or in combination, commenced *in utero* via the mother's diet and continued throughout the first five months of life. These metabolic changes were not incurred by hyperphagia since all four diet groups ingested equal amounts of food. We have previously shown that ASP exposure in C57Bl/6 J mice may promote weight gain and dysregulation of glucose homeostasis when consumed together with a standard chow diet (typically 5% dietary lipids) \[[@B38]\]. We have also demonstrated that ASP may interact with a second widely consumed food additive MSG to further imbalance glucose homeostasis in standard chow-fed animals \[[@B25]\]. The level of MSG-exposure in our model (\~130 mg/Kg bw) is considerably lower than the dosage used in the classic non-genetic MSG-obese model, in which animals are typically injected with 4 g/Kg bw MSG for a period of several days shortly after birth when the blood--brain-barrier (BBB) is still immature and vulnerable to excitotoxic damage \[[@B14]-[@B16],[@B21]\]. Nevertheless, exposure to MSG and ASP metabolites in our model began during conception and continued *in utero* and throughout life; and we hypothesize that it is this continuous exposure which resulted in the metabolic imbalances described herein.
Our early nutrigenomics studies additionally focused upon lipogenic changes in hepatic and adipose tissue gene expression incurred as a result of consumption of *Trans* Fatty Acid (TFA), either alone or in conjunction with MSG \[[@B9]\]. *Trans* fats are unsaturated fatty acids with *trans* double bonds introduced during the catalytic partial hydrogenation process in order to stabilize dietary fats and prolong their shelf-life. However, an insightful study by Yu *et al.*\[[@B39]\] showed that some TFAs such as elaidic acid are incompletely oxidized in mitochondria due to the fact that one of the metabolites (5-*trans*-tetradecenoyl-CoA) is a poorer substrate for the mitochondrial enzyme long chain acyl-CoA dehydrogenase (Acadl) than its *cis* isomer 5-*cis*-tetradecenoyl-CoA. Elaidic acid is the major fat found in hydrogenated vegetable oils, and a reduction in the oxidative capacity of mitochondria for the *trans* isomer of the elaidic acid intermediate may result in an accumulation of 5-*trans*-tetradecenoyl-CoA in the mitochondrial matrix, which could potentially increase oxidative stress. In our previous study \[[@B9]\], TFA-feeding robustly upregulated lipid biosynthetic enzymes in the adipose tissue and liver whilst also promoting increases in the transcription of mitochondrial uncoupling protein 3 (Ucp3), several mitochondrial ß-oxidation genes encoding short-, medium-, long- and very long-chain acyl co-A dehydrogenases, together with the citric acid cycle genes isocitrate dehydrogenase 3 (Idh3) and pyruvate dehydrogenase complex (Pdhx). The mechanism for this appeared to involve a 50% reduction in the expression of the transcription factor Ppargc1a, the master homeostatic transcriptional controller of mitochondrial biogenesis, oxidative phosphorylation and energy metabolism \[[@B40]\]. Interestingly, the addition of MSG further reduced the expression of adipose tissue Ppargc1a to 25% of control levels, together with attenuated expression of Idh3, Pdhx, Ucp3, and several ß-oxidation genes \[[@B9]\]. In the present study, we sought to extend our investigation of hepatic and adipose tissue gene expression to include the commonly-consumed food additive ASP, since we have previously shown that ASP may interact with MSG *in vivo* to alter glucose homeostasis, and because others have shown that ASP may disrupt hepatic antioxidant defenses \[[@B24]\].
In TFA-fed mice, the addition of either ASP or MSG alone did not increase adiposity, fasting serum glucose, cholesterol or FFA levels. However in combination, ASP + MSG significantly elevated all these parameters, and doubled fasting serum leptin and TNFα, whilst promoting insulin resistance and hepatic steatosis. These obesogenic changes were accompanied by striking alterations in gene transcription, most notably in the adipose tissue deposits which were significantly larger than those in the additive-free TFA diet group. This is of interest since white adipose tissue (WAT) was originally considered to be a passive depot of triglycerides, transcriptionally inert and sequestering or releasing fatty acids under the influence of various hormones \[[@B41]\]. However the past 15 years of research have shown that WAT is a dynamic pleiotropic endocrine organ responsive to a wide array of chemical, hormonal, neuronal and environmental signals. In TFA-fed mice, we identified over 11,000 differentially expressed adipose transcripts affected by exposure to ASP and MSG commencing *in utero,* and roughly 8,000 in liver. Others have also shown higher numbers of adipose tissue differentially expressed genes (DEGs) compared to liver, both in response to fasting \[[@B42]\], and during LPS-induced inflammation \[[@B43]\]. Most recently, high-fat feeding has been shown to induce obesogenic gene expression changes in 4 murine tissues, with adipose tissue producing the second highest number of DEGs in the following order: skeletal muscle \> adipose \> liver \> heart \[[@B44]\].
The increased hepatic triglyceride content seen in TFA-fed mice exposed to both MSG-containing diets was accompanied by an increase in the expression of acetyl-CoA carboxylase ß (Acc2) and carnitine palmitoyltransferase 1 (Cpt1). Previous studies have shown that transcription of hepatic Acc2 is markedly upregulated by increased food intake \[[@B45]\], insulin, and dexamethasone \[[@B46]\]. Unlike Acc1 which stimulates lipogenesis, Acc2 is known to inhibit lipolysis; and its structure has an N-terminal extension containing a mitochondrial-targeting motif which allows Acc2 to associate with Cpt1 on the outer mitochondrial membrane, thus regulating ß-oxidation at an early stage in the process \[[@B44]\]. High-fat diets and obesity have previously been associated with decreased expression of Ppargc1a, the dominant regulator of oxidative metabolism \[[@B41]\]; and whereas we have previously shown that Ppargc1a expression is reduced by intake of TFA compared to low-fat controls \[[@B9]\], we now demonstrate that levels of this transcription factor can be further attenuated by ASP + MSG exposure, both in the liver and particularly in the visceral adipose tissue. Expression of Ppargc1a is reduced in insulin resistant tissues \[[@B40]\], during obesity \[[@B47]\] and in type 2 diabetes \[[@B48]\]; and Ppargc1a knock-out mice exhibit hepatic steatosis due to a reduction in mitochondrial oxidative capacity and mtDNA content, together with an upregulation of lipogenic gene expression \[[@B49]\]. A large number of signaling pathways have been proposed to regulate Ppargc1a, including thyroid hormone, nitric oxide synthase, p38 mitogen activated protein kinase (p38MAPK), sirtulin and β-adrenergic stimulation, to name but a few \[[@B49]\]. Interestingly, in addition to the reduced expression of Ppargc1a in obese subjects \[[@B47]\], sustained exposure to saturated fatty acids has been shown to attenuate the expression of Ppargc1a *in vitro*\[[@B50]\]; and epigenetic studies have shown a negative correlation between Ppargc1a mRNA content and an increase in the methylation of the promoter region of Ppargc1a in the skeletal muscle of patients with type 2 diabetes \[[@B51]\].
In broad terms, diet-induced changes in hepatic gene expression tended to be less extensive, and did not mirror the coordinated reduction in adipose tissue ß-oxidative gene expression. Reduced Ppargc1a expression was accompanied by an upregulation of genes involved in lipid and cholesterol metabolism, cell stress adaptation and hepatoprotection. Additionally, levels of carnitine palmitoyltransferase (Cpt1c), an essential enzyme in the ß-oxidation of long-chain fatty acids was modestly elevated in the livers of MSG and ASP-treated mice, together with genes involved in lipid and cholesterol homeostasis. Markers of significant hepatic microsteatosis and oxidative damage have previously been noted in the livers of MSG-treated rodents \[[@B21],[@B52],[@B53]\]; some of which could be partially attenuated with antioxidant vitamins C \[[@B54]\], E \[[@B55]\] or both \[[@B56]\]. Long-term ASP exposure has also been associated with diminished liver function and impaired antioxidant defenses \[[@B24]\]. The authors of that study speculated that the hepatotoxicity could be attributed to the methanol component of metabolized ASP, since methanol is a well characterized hepatotoxin \[[@B57]\]. However in our model the relatively small amount of ASP offered in the diet would have been insufficient to raise blood methanol levels to that required to promote hepatotoxicity; rather, the increased expression of genes with hepatoprotective ontology may have been deregulated due to the increased hepatic triglyceride and serum FFA incurred by neonatal exposure to the combination of ASP and MSG.
Although our nutrigenomic evidence points to significant differences in the ontology of gene expression between the adipose tissue and the liver, for example in the differential expression of ß-oxidative genes; there were a number of common DEGs which were up- or down-regulated similarly in both tissues, and may shed more light on the mechanism for the diet-induced metabolic dysregulation. Some of the most interesting were adaptogenic, stress-responsive and oxidative DEGs such as p53, Notch1, Ppargc1a, NADPH oxidase organizer 1(Noxo1) and xanthine dehydrogenase. The transcriptional activation of p53 facilitates a diverse range of responses to metabolic challenges including the regulation of glucose homeostasis, substrate oxidation and OX-PHOS, mitochondrial integrity, autophagy and apoptosis. This assists in balancing proliferation and growth with nutrient availability, whilst attenuating metabolic stress-induced damage. In the liver, activation of p53 enhances apoptosis and promotes NAFLD-associated insulin resistance \[[@B58]\]; whilst in the adipose tissue, p53 has been termed the "guardian of corpulence" for its adaptogenic role in lipogenesis and in protecting against FFA-induced ROM and cellular stress \[[@B59]\]. Concomitant with the ASP + MSG-induced increase in p53 expression, we also noted a decrease in one of the major p53 binding and regulating proteins, Mdm2. This protein attaches to p53, promoting destabilization and removal from the nucleus, inhibiting its ability to activate transcription \[[@B60]\]. Thus our data supports the notion that there is generally an inverse relationship between Mdm2 and p53 expression via a negative feedback loop \[[@B61]\], suggesting that the diet-induced reduction in Mdm2 assists in enhancing the activation of p53. In some tissues p53 has been shown to interact with Notch1, a trans-membrane receptor molecule participating in cell to cell signaling and which has previously been implicated in the control of adipogenesis \[[@B62]\]. We observed a diet-induced increase in the expression of Notch1 in both the adipose tissue and the liver, and whereas the role of notch1 in tumorigenesis has been well documented \[[@B63]\], recent evidence also suggests that notch1 may play a role in the development of insulin resistance \[[@B64]\] and may also have several other pleiotropic functions in the liver \[[@B65]\].
The extent of visceral and hepatic fat accumulation and gene expression can be significantly modified by exposure to common food additives consumed as part of a *Trans* fat diet. The combination of aspartame and MSG promoted the highest level of visceral fat deposition and serum FFA, leptin and TNFá compared to control or either additive alone. Further studies are warranted to examine the effect of food additives, and combinations of additives on obesogenic gene expression.
All authors declare that they have no conflict of interest and have not received funding from Industry sources.
KSC conceived the study, designed the experiments and drafted the manuscript. NJM, AI, BLA, SS and RU performed the experiments. MZZ, KSC and NJM analyzed the data. FAA & MZ helped draft the manuscript. We are grateful for continuous discussions and support from FAA. All Authors read and approved the final manuscript.
###### Additional file 1
Click here for file
###### Additional file 2
qPCR Primer sequences used in the confirmatory analysis.
Click here for file
###### Additional file 3
**A: Diet groups and experimental design.** B and C: 3-D heat maps of standardized expression values of 10,117 DEGs in liver (**B**) and 28,101 DEGs in adipose tissue (**C**), with ANOVA p-value of \<0.05 for diet.
Click here for file
###### Additional file 4
**Histological examination of hepatic tissue stained with H&E (A: x40 magnification); and adipose tissue stained with trichrome (B: x20 magnification).**
Click here for file
###### Additional file 5
Diet-specific differences in the number of significant DEGs dysregulated by MSG, ASP, or the combination of ASP + MSG in liver and adipose tissue.
Click here for file
###### Additional file 6
**Diet-specific differences in the functional ontology of genes dysregulated by dietary MSG (A,B); ASP (C,D) and the combination ASP + MSG (E,F).**
Click here for file
We thank Mohammed Al-Hallaby and Sherin Shibin for technical assistance. Our gratitude goes to Mr Hakim Al-Enazi for his unparalleled help in coordinating research resources. This research was part of KFSH&RC Project \#2090 028, and supported by grant \#08-MED490-20 from the National Comprehensive Plan for Science and Technology (NCPST), Kingdom of Saudi Arabia.
|
Hot fix for initializing blob data and using template in v1.4.0
A hot fix for v1.4.0. Will create a new version v1.4.1.
Check environment variable process.env.AZURE_STORAGE exists before insert into database.
Add a property useBlob in marketplaceItem model as a flag, and only contact pai_copy related commands if useBlob is true.
Change target branch name and close this pr.
|
//
// TSSTImageView.swift
// SimpleComic
//
// Created by C.W. Betts on 10/26/15.
//
//
import Cocoa
private let stringAttributes: [NSAttributedString.Key: Any] = {
let style = NSMutableParagraphStyle()
style.lineBreakMode = .byTruncatingHead
return [.font: NSFont.labelFont(ofSize: 14),
.foregroundColor: NSColor.white,
.paragraphStyle: style.copy()]
}()
class TSSTImageView: NSImageView {
var imageName: String?
var clears: Bool = false
override func draw(_ dirtyRect: NSRect) {
if clears {
NSColor.clear.set()
bounds.fill()
}
var imageRect = rectCentered(with: image?.size ?? .zero, in: bounds)
//[NSGraphicsContext saveGraphicsState];
//[[NSGraphicsContext currentContext] setImageInterpolation: NSImageInterpolationHigh];
image?.draw(in: imageRect, from: .zero, operation: .sourceOver, fraction: 1)
if let imageName = imageName {
imageRect = imageRect.insetBy(dx: 10, dy: 10)
var stringRect = imageName.boundingRect(with: imageRect.size, attributes: stringAttributes)
stringRect = rectCentered(with: stringRect.size, in: imageRect);
NSColor(calibratedWhite: 0, alpha: 0.8).set()
NSBezierPath(roundedRect: stringRect.insetBy(dx: -5, dy: -5), cornerRadius: 10).fill()
imageName.draw(in: stringRect, withAttributes: stringAttributes)
}
//[NSGraphicsContext restoreGraphicsState];
}
}
extension NSBezierPath {
@inlinable convenience init(roundedRect aRect: NSRect, cornerRadius radius: CGFloat) {
self.init(roundedRect: aRect, xRadius: radius, yRadius: radius)
}
}
|
package cz.compling.analysis.analysator.poems.aggregation;
import cz.compling.model.Aggregations;
import cz.compling.rules.BaseRuleHandler;
import cz.compling.rules.RuleHandler;
import cz.compling.rules.RuleObserver;
import cz.compling.text.poem.Poem;
import cz.compling.text.poem.PoemModificationRule;
import cz.compling.text.poem.Verse;
import java.util.Arrays;
import java.util.Collection;
/**
*
* TODO
*
* <dl>
* <dt>Created by:</dt>
* <dd>slaha</dd>
* <dt>On:</dt>
* <dd> 2.3.14 17:59</dd>
* </dl>
*/
public class AggregationImpl implements IAggregation {
private final RuleHandler<AggregationRule> ruleHandler;
private final Poem poem;
private final Aggregations aggregations;
private boolean dirty;
public AggregationImpl(Poem poem) {
this.poem = poem;
ruleHandler = new BaseRuleHandler<AggregationRule>();
aggregations = new Aggregations();
computeAll();
dirty = false;
}
private void computeAll() {
Poem onlyLettersPoem = toOnlyLetters();
Collection<Verse> verses = onlyLettersPoem.getVerses();
final Verse[] lines = verses.toArray(new Verse[verses.size()]);
if (lines.length < 2) {
return;
}
for (int i = 0; i < lines.length - 1; i++) {
compute(i, lines);
}
aggregations.done();
}
private void compute(int baseLine, Verse[] lines) {
final String[] line1single = createChunks(lines[baseLine].toString(), 1);
final String[] line1double = createChunks(lines[baseLine].toString(), 2);
applyRules(line1single);
applyRules(line1double);
Arrays.sort(line1single);
Arrays.sort(line1double);
final int sizeA1 = line1single.length;
final int sizeB1 = line1double.length;
final Aggregations.Aggregation aggregation = aggregations.getAggregationForBaseLine(baseLine + 1);
int currentLine = baseLine + 1;
while (currentLine < lines.length) {
final String line = lines[currentLine].toString();
final String[] lineSingle = createChunks(line, 1);
final String[] lineDouble = createChunks(line, 2);
applyRules(lineSingle);
applyRules(lineDouble);
Arrays.sort(lineSingle);
Arrays.sort(lineDouble);
final int intersection1 = intersection(line1single, lineSingle);
final int intersection2 = intersection(line1double, lineDouble);
aggregation.put(
currentLine + 1,
intersection1,
sizeA1,
lineSingle.length,
intersection2,
sizeB1,
lineDouble.length);
currentLine++;
}
aggregations.done(aggregation);
}
/**
* Computes intersection of two sorted arrays of strings
*
* @param line1 first array
* @param line2 second array
*
* @return number that indicates count of the same strings on the same indexes in the arrays
*/
private int intersection(String[] line1, String[] line2) {
int matches = 0;
int i1 = 0, i2 = 0;
while (i1 < line1.length && i2 < line2.length) {
final int cmp = line1[i1].compareTo(line2[i2]);
if (cmp == 0) {
matches++;
i1++;
i2++;
} else if (cmp < 0) {
i1++;
} else {
i2++;
}
}
return matches;
}
private void applyRules(String[] line) {
String s = "";
for (int i = 0; i < line.length; i++) {
String chunk = line[i];
for (AggregationRule aggregationRule : getRegisteredRules()) {
if (aggregationRule.matchesRule(chunk)) {
chunk = aggregationRule.compareTo(chunk);
} else {
s += chunk;
}
}
line[i] = chunk.toLowerCase();
}
}
private String[] createChunks(String line, int size) {
final int chunksSize = line.length() - (size - 1);
final String[] chunks = new String[chunksSize];
for (int index = 0; index < chunksSize; index++) {
String chunk = line.substring(index, index + size);
chunks[index] = chunk;
}
return chunks;
}
private Poem toOnlyLetters() {
return poem.applyRule(new PoemModificationRule() {
@Override
public String modify(Poem poem) {
StringBuilder sb = new StringBuilder();
final String text = poem.getPlainText();
char last = 0;
for (char c : text.toCharArray()) {
if (Character.isLetter(c)) {
//..we need to be lowercase
sb.append(Character.toLowerCase(c));
} else if (c == '\n' && last != '\n') {
//..put line separator but not more than one
sb.append(c);
}
last = c;
}
return sb.toString();
}
});
}
@Override
public Iterable<AggregationRule> getRegisteredRules() {
return ruleHandler.getRegisteredRules();
}
@Override
public void registerRule(AggregationRule rule) {
ruleHandler.registerRule(rule);
dirty = true;
}
@Override
public boolean removeRule(AggregationRule rule) {
if (ruleHandler.removeRule(rule)) {
dirty = true;
return true;
}
return false;
}
@Override
public void registerRuleObserver(RuleObserver<AggregationRule> observer) {
ruleHandler.registerRuleObserver(observer);
}
@Override
public boolean unregisterRuleObserver(RuleObserver<AggregationRule> observer) {
return ruleHandler.unregisterRuleObserver(observer);
}
@Override
public Iterable<RuleObserver<AggregationRule>> getRegisteredObserves() {
return ruleHandler.getRegisteredObserves();
}
@Override
public Aggregations getAggregations() {
if (dirty) {
aggregations.clear();
computeAll();
}
return aggregations;
}
}
|
High memory usage for reductions.median but not reductions.mean
I'm attempting to median stack 200 x 4k x 4k images. I've been having trouble with the memory allocation so I tried to simplify my problem by going to 2d and was surprised to see that doing a median reduction can take 50 GB of memory and crash python.
This code works as expected in ipython. Almost no memory is used and this completes in less than a minute.
import dask.array as da
x = da.random.normal(10, 0.1, size=(100000, 100000), chunks=(10, 100000))
y = da.reductions.mean(x, axis=1)
%time z = y.compute()
CPU times: user 6min 38s, sys: 2.36 s, total: 6min 41s Wall time: 56.3 s
Running the following code causes python to crash after activity monitor showing it using more than 50 GB of RAM.
import dask.array as da
x = da.random.normal(10, 0.1, size=(100000, 100000), chunks=(10, 100000))
y = da.reductions.median(x, axis=1)
%time z = y.compute()
Anything else we need to know?:
I did also try this in regular python (as opposed to ipython) and got the same crash. The odd chunk size is an attempt to make sure each chunk has the full array necessary to compute the median in one chunk.
Environment:
Dask version: 2021.05.1
Python version: 3.8.10
IPython version: 7.22.0
Operating System: MacOS 11.3.1
Install method (conda, pip, source): conda
Mean works because the data creation and initial data reduction steps are
fused, so we create and destroy data at the same pace.
In the median case there is an intervening step, where we rechunk the array
along the axis to be reduced over to ensure that we can do the median (we
don't have a parallel median algorithm). This creates a bit of a
disconnect in the graph, and so the worker creates some data and then
doesn't immediately consume that data with the first pass of the
reduction. Instead it asks the scheduler what's next (in the distributed
case) or waits for neighboring data creation chunks to be done as well for
the eventual rechunk. The workers are eating themselves to death :)
The solution to this problem is probably to rechunk less aggressively. In
your case we don't even need to rechunk at all. We can fix this by
changing line 1586 here:
https://github.com/dask/dask/blob/eed298b2335401d2cb8e85ebb44888eb59937cf8/dask/array/reductions.py#L1569-L1588
Probably we should
Only call rechunk if any(x.numblocks[ax] > 1 for ax in axis)
Be careful about using "auto" on all other dimensions, and instead
make sure that we only reduce the size of chunks, rather than increase them
/ glom them together (which can cause scheduling artifacts)
The first task is the easiest and would solve your problem immediately.
It's a decent task for anyone with mild experience with dask array. The
second task would be good too, but is not necessary.
On Wed, Jun 9, 2021 at 3:48 PM Curtis McCully @.***>
wrote:
I'm attempting to median stack 200 x 4k x 4k images. I've been having
trouble with the memory allocation so I tried to simplify my problem by
going to 2d and was surprised to see that doing a median reduction can take
50 GB of memory and crash python.
This code works as expected in ipython. Almost no memory is used and this
completes in less than a minute.
import dask.array as dax = da.random.normal(10, 0.1, size=(100000, 100000), chunks=(10, 100000))y = da.reductions.mean(x, axis=1)%time z = y.compute()
CPU times: user 6min 38s, sys: 2.36 s, total: 6min 41s Wall time: 56.3 s
Running the following code causes python to crash after activity monitor
showing it using more than 50 GB of RAM.
import dask.array as dax = da.random.normal(10, 0.1, size=(100000, 100000), chunks=(10, 100000))y = da.reductions.median(x, axis=1)%time z = y.compute()
[image: Screen Shot 2021-06-09 at 4 32 29 PM]
https://user-images.githubusercontent.com/5331996/121426745-c66f7480-c928-11eb-8f5e-17bdf4c69a48.png
[image: Screen Shot 2021-06-09 at 4 47 17 PM]
https://user-images.githubusercontent.com/5331996/121427191-45fd4380-c929-11eb-8bdc-5ed0985ec02d.png
Anything else we need to know?:
I did also try this in regular python (as opposed to ipython) and got the
same crash. The odd chunk size is an attempt to make sure each chunk has
the full array necessary to compute the median in one chunk.
Environment:
Dask version: 2021.05.1
Python version: 3.8.10
IPython version: 7.22.0
Operating System: MacOS 11.3.1
Install method (conda, pip, source): conda
—
You are receiving this because you are subscribed to this thread.
Reply to this email directly, view it on GitHub
https://github.com/dask/dask/issues/7780, or unsubscribe
https://github.com/notifications/unsubscribe-auth/AACKZTAERPT66R2TZZLG6Q3TR7HRPANCNFSM46MZLC5A
.
For part 2 I am wondering if a different "special" string could be introduced. Something like "auto-downsample", which would behave like "auto" but only if output chunk size is smaller. I can't tell if that is too wierd.
For part 2 I am wondering if a different "special" string could be introduced. Something like "auto-downsample", which would behave like "auto" but only if output chunk size is smaller. I can't tell if that is too wierd.
I would wait until there are more requirements for that. The auto-chunking code is pretty core. I wouldn't want to add more complexity there for just this use case.
Instead, we might look at the memory of the current maximum size block (np.prod(map(max, self.chunks))) * self.dtype.itemsize) and then use that size instead of "auto". That way we'll avoid unnecessarily glomming things together.
Thanks for fixing this so quickly!
|
In this Chapter we briefly recall and summarize the main linear optics
concepts of the accelerators beam dynamics theory. In doing so we put our
emphasis on the related computational aspects: the reader will be provided with
the basic elements to write a linear optics code. To this aim, we complement
the text with few practical examples and code listings.
|
Board Thread:Trading/@comment-24837974-20140426194743/@comment-24837974-20140513121524
@MrDestiny - will consider it. Would help if u throw in a few JoL
|
HENDERSON, COHN, CATHCART, WACHMAN, AND EENN 467
per gm. of gluten, to give a conductivity of approximately 200 to 100 cc. of water. This may now be used in further study of the data upon conductivity. For this quantity, plus the electrical conduc tivity of the solution of acid or alkali added to the gluten, minus the electrical conductivity of the resulting solution, may be taken as a roughly approximate measure of the quantity of electrolyte in union with protein. It is, however, a measure which cannot be directly em ployed for comparison of the acid systems with the alkaline systems, because of the considerable difference in conductivity of hydrochloric acid and sodiun hydroxide. And of course the various salts of the original gluten are also not equal in conductivity to the acid, to the alkali, or to each other.
The results of such calculations of the conductivity of electrolytes in union with gluten are collected in Table VI. It may easily be seen that the data vary in a regular and intelhgible manner.
In the light of the above facts the swelling of gluten in solutions of acid and alkalies may now be considered. The data of Table VII in clude observations upon the weight of the wet, swollen, coherent mass, upon the weight of dry gluten contained therein, as well as calcula tions of the amount of gluten dissolved and of the ratio of wet gluten to dry material contained within it (the true swelling) .
Quantitatively the results are not at all points satisfactory. The following conclusions are possible. First, the weight of swollen gluten bears no relation to the true swelKng (hydration) because of the marked variations in the quantity of protein dissolved. Second, it Ijears no direct relation to the hydrogen ion concentration, except when quantities of gluten and solution are kept constant. Third, the chief factor in determining the weight of swollen gluten is the quan tity of protein which has been dissolved away from it. Fourth, the amount of gluten dissolved is greater the greater the acidity. Fifth, the true swelling of gluten is greater the greater the acidity. There also seems to be a tendency for the true swelling of gluten to increase as the relative quantity of gluten increases. This corresponds to a relatively greater amount of electrolyte present in the swollen mass.
|
Can I put Hardie Board siding directly over old stucco?
I just bought an old house that has five different kinds of outside wall coverings.
I was thinking I could remove the fake stones and the old wooden siding and then place strapping over top of the stucco to attach the Hardie Board to without removing the old stucco.
Several things I have read online say that I should remove the old stucco first. That seems like a lot of work for what it's worth and am trying to get an idea of what I am getting myself into before I start.
Any advice or instructions would be appreciated. Do I have to remove the old stucco? Or can I go straight over it?
Here is a photo of the house, two different types of crushed rock stucco, a white cement type stucco, fake stone, and finally and wooden planks.
I would think there would be no problem with hardie over stucco, I would be more concerned about why so many different styles, was there some type of remediation/ repair work done?
@EdBeal, that "lap siding" definitely looks like a cheap fix for work done on or from the outside.
I have some Hardie board put on new construction 25 yrs ago , excellent except steel nails were used About 5% of the nails show rust spots in the paint. I suggest aluminum nails . I go around each year with Kliz to touch-up ( Kilz matches the paint very well).
@EdBeal, It's a single story bungalow that was built in the 60's placed on top of a basement built in the 80's. Not a great setup, but the price and location are good.
For weathering in you home, it would be best to remove the stucco.
To add strapping, then the siding would place a lot of emphasis on how the windows are treated for weatherproofing. To do that properly, the stucco needs to be removed from around the windows and add thick trim and head flashing before the siding is set so the trim bridges the gap created by the strapping.
To remove the stucco, it can be removed in sheets, really heavy sheets, really heavy sheets with a bunch of nails sticking out the back side that are in really solid... with wire teeth all around the edges ready to rake the skin off of you. But doing it this way using gloves, will keep the trash to a minimum.. If a right angle grinder is used to cut the stucco, then the wire ends will be kept to a minimum.
Real stucco is 3/4" thick, and solid masonry, with expanded metal lath reinforcement. The stucco can be thicker, or thinner, but 3/4" is the norm. If you go that way, as in removing the stucco, it can be elaborated on farther.
More on adding it over the stucco. It would be best to find the studs to attach the strapping to, since when the siding is done, there will be a lot of weight hanging on each piece.
Expanded metal is a whole different ball game than wire mesh , If expanded metal stucco is left in place strapping would not be needed. But I agree the thickness for trim is an issue.
@EdBeal In my opinion, the stucco looks like it is in great shape, except for obvious places. If tied in properly, I would opt to have the stucco repaired in places rather than adding siding everywhere....
Good point about adding the flashing around the windows, I had not considered that. Probably best solution for weatherproofing would be to remove all five of the different wall coverings. I think that would be a huge job, might not even be worth it considering the wire ends etc. Thanks for the information.
You do not need to remove the stucco. I have installed Hardie Board siding right over stucco more than once with great results.
You will have to provide strapping throughout your house to support the siding. And this needs to be done where it is continuous level. This is going to provide some challenges on the area that has siding and rock. What happens to the levels once you displace the rock?
Really for your specific house where it looks to be in great shape (while maybe outdated) you probably can't determine whether you strap or go down to the studs until you start demoing different sections. I have seen rigid foam boards plus strapping used to level things.
|
Orthoptic and ophthalmic investigations
The aim of this resource is to provide a compilation of tests and investigations used by orthoptists for the purpose of investigating ocular problems.
* /Vision/
* /Stereopsis/
* /Strabismus/
* /Perimetry/
* /Anterior and posterior segment investigation/
* /Ocular imaging/
|
package com.jsoniter;
import junit.framework.TestCase;
import java.io.IOException;
import java.lang.reflect.Type;
import java.util.Date;
public class TestCustomize extends TestCase {
public void test_customize_type() throws IOException {
Jsoniter.registerTypeDecoder(Date.class, new Decoder() {
@Override
public Object decode(Type type, Jsoniter iter) throws IOException {
return new Date(iter.readLong());
}
});
Jsoniter iter = Jsoniter.parse("1481365190000");
Date date = iter.read(Date.class);
assertEquals(1481365190000L, date.getTime());
}
public void test_customize_field() throws IOException {
Jsoniter.registerFieldDecoder(CustomizedObject.class, "field1", new Decoder(){
@Override
public Object decode(Type type, Jsoniter iter) throws IOException {
return Integer.toString(iter.readInt());
}
});
Jsoniter iter = Jsoniter.parse("{'field1': 100}".replace('\'', '"'));
CustomizedObject myObject = iter.read(CustomizedObject.class);
assertEquals("100", myObject.field1);
}
}
|
SUMMARY
It is estimated that 523 bergs drifted south of 48° N. during 1948. This compares with the 49-year average, 1900 through 1948, of 433. The outstanding feature of the 1948 season was the fact that although a greater than average number of bergs drifted south of 48° N., only a few actually entered track C and only one reached track B. The one reach ing track B was a ship report and is doubtful. It was reported on June at 41°19' N., 4o°16' W. The report is considered doubtful for the follow ing reasons:
local apparent time without benefit of moonlight.
To summarize, a greater than average number of bergs drifted south of the 48th parallel. Further southward progress was impeded to the ex tent that a relatively small number, possibly 10 to 15, drifted south of westbound track C, and only one and possibly none reached track B. The relationship between this deficiency of bergs reaching southerly positions and the location of the northern boundary of the Atlantic Cur rent is discussed elsewhere in this Bulletin in the section dealing with the oceanography of the Grand Banks region.
The total amount of field ice in the St. Lawrence area was somewhat less than usual. The above comparison and those to follow are based on the monthly mean sea ice limits contained in the Ice Atlas of the Northern Hemisphere published by the Hydrographic Office of the United States Navy (H.O. No. 550). In general the deficiency of sea ice in this region was due in part to a westward displacement of the eastern limits of the sea ice dining the months of February, March, April, and May. In addition the southern limits of the sea ice were displaced to the north ward during the months of February, April, and May. March was ap proximately normal with regard to the southern limits.
In the Grand Banks region the total amount of field ice was less than usual. In February the southern limits of the sea ice were displaced ap proximately 100 miles to the north and the eastern limits were displaced to the west. Maximum westward displacement was approximately 185 miles along the parallel of 47°50' N. In March the southwestern limits were normal, but along the eastern slope of the Grand Banks the southern limits were displaced northward almost 120 miles along the 48th meridian. As a result of continued northwesterly winds of gale force in the area during the last week in March, the outer limits to the east extended to the 46th meridian, a gain of 30 miles over the monthly mean. By the
|
A Rossby Diagram
A ROSSBY DIAGRAM OF AN AIRPLANE SOUNDING AT NANKING, CHINA, AUG. 23,1937. There is a shallow layer of TM air at the surface with a sharp front at 706 meters, above which Equatorial marine air exists to the top of the sounding. This sounding was made just after a typhoon passed inland over Nanking, the warmer Em being imported aloft by the circulation of the storm. (From a paper by Tu, Bull. Amer. Met. Soc., March, 1939.) Synoptic Charts Showing Winter Cyclones (Figs. 1, 2, 6-13 from: Dorsey, Bull. Amer. Met. Soc., Oct. 1938.) OCCLUDED
Fic. 1. Deep cold air over New England was augmented by fresh Pc the next day. The warm and occluded fronts ‘in the low over Michigan are producing snow (stippled area) over a wide region and caused heavy snow in New England later the same day as it moved eastward.
Fic. 2. The low off the east coast was formed by amalgamation of two weaker lows the day before. This storm caused N W gales and heavy snow on the seaboard. In this and Figs 2-4 the effect of fresh Pc outbreaks in sweeping up old occlusions ahead of them is evident.
|
Section 2: WebGoat
Overview
How it works
WebGoat users are configured in the tomcat-users.xml configuration file.
Here is the WebGoat login page, which uses Basic Authentication:
Next is the entrance/start page; a JSESSIONID cookie is set for the session variable:
Here is an overview of the lesson menu on the left side of the page that is used for navigation:
When a WebGoat lesson is completed successfully, there are 3 different areas that denote this:
* A report card in Section 18 of WebGoat:
Lesson Table Of Contents
The Table of Contents for WebGoat 5.2 beta 1 with the numbering system used for this project is:
1. General
* 1.1 Http Basics
* 1.2 HTTP Splitting
2. Access Control Flaws
* 2.1 Using an Access Control Matrix
* 2.2 Bypass a Path Based Access Control Scheme
* 2.3 LAB: Role Based Access Control
* Stage 1: Bypass Business Layer Access Control
* Stage 2: Add Business Layer Access Control
* Stage 3: Bypass Data Layer Access Control
* Stage 4: Add Data Layer Access Control
* 2.4 Remote Admin Access
3. AJAX Security
* 3.1 LAB: Client Side Filtering
* 3.2 LAB: DOM-Based cross-site scripting
* 3.3 DOM Injection
* 3.4 Same Origin Policy Protection
* 3.5 XML Injection
* 3.6 JSON Injection
* 3.7 Silent Transactions Attacks
* 3.8 Insecure Client Storage
* 3.9 Dangerous Use of Eval
4. Authentication Flaws
* 4.1 Password Strength
* 4.2 Forgot Password
* 4.3 Basic Authentication
* 4.4 Multi Level Login 1
* 4.5 Multi Level Login 2
5. Buffer Overflows
6. Code Quality
* 6.1 Discover Clues in the HTML
7. Concurrency
* 7.1 Thread Safety Problem
* 7.2 Shopping Cart Concurrency Flaw
8. Cross-Site Scripting (XSS)
* 8.1 Phishing with XSS
* 8.2 LAB: Cross Site Scripting
* Stage 1: Stored XSS
* Stage 2: Block Stored XSS using Input Validation
* Stage 3: Stored XSS Revisited
* Stage 4: Block Stored XSS using Output Encoding
* Stage 5: Reflected XSS
* Stage 6: Block Reflected XSS
* 8.3 Stored XSS Attacks
* 8.4 Reflected XSS Attacks
* 8.5 Cross Site Request Forgery (CSRF)
* 8.6 HTTPOnly Test
* 8.7 Cross Site Tracing (XST) Attacks
9. Denial of Service
* 9.1 Denial of Service from Multiple Logins
10. Improper Error Handling
* 10.1 Fail Open Authentication Scheme
11. Injection Flaws
* 11.1 Command Injection
* 11.2 Blind SQL Injection
* 11.3 Numeric SQL Injection
* 11.4 Log Spoofing
* 11.5 XPATH Injection
* 11.6 String SQL Injection
* 11.7 LAB: SQL Injection
* Stage 1: String SQL Injection
* Stage 2: Parameterized Query #1
* Stage 3: Numeric SQL Injection
* Stage 4: Parameterized Query #2
* 11.8 Database Backdoors
12. Insecure Communication
* 12.1 Insecure Login
13. Insecure Configuration
* 13.1 Forced Browsing
14. Insecure Storage
* 14.1 Encoding Basics
15. Parameter Tampering
* 15.1 Exploit Hidden Fields
* 15.2 Exploit Unchecked Email
* 15.3 Bypass Client Side JavaScript Validation
16. Session Management Flaws
* 16.1 Spoof an Authentication Cookie
* 16.2 Hijack a Session
* 16.3 Session Fixation
17. Web Services
* 17.1 Create a SOAP Request
* 17.2 WSDL Scanning
* 17.3 Web Service SAX Injection
* 17.4 Web Service SQL Injection
18. Admin Functions
* 18.1 Report Card
19. The Challenge
* 19.1 The CHALLENGE!
Overview of lesson results
Following is an overview of the lesson results from May 21 to May 29 using WebGoat 5.2 beta 1.
Summary by category:
* (a) Not done because not applicable: 2
18.1, 19.1
* (b) Not done because not implemented: 1
5.0
* (c) Not done because developer version required: 3
2.3, 8.2, 11.7
* (d) Not successful because of bug or not doing correctly with the given solution: 9
3.1, 8.3, 8.5, 11.1, 11.5, 11.8, 16.2, 16.3, 17.4
* (e) Successful but no red "successful" message and/or green check mark: 12
1.1, 1.2, 2.2, 3.7, 4.3, 7.1, 7.2, 9.1, 11.2, 12.1, 14.1, 17.1
* (f) Successful: red "successful" message and/or green check mark: 29
Conclusion:
|
Features of Methylation and Gene Expression in the Promoter-Associated CpG Islands Using Human Methylome Data
CpG islands are typically located in the 5′ end of genes and considered as gene markers because they play important roles in gene regulation via epigenetic change. In this study, we compared the features of CpG islands identified by several major algorithms by setting the parameter cutoff values in order to obtain a similar number of CpG islands in a genome. This approach allows us to systematically compare the methylation and gene expression patterns in the identified CpG islands. We found that Takai and Jones' algorithm tends to identify longer CpG islands but with weaker CpG island features (e.g., lower GC content and lower ratio of the observed over expected CpGs) and higher methylation level. Conversely, the CpG clusters identified by Hackenberg et al.'s algorithm using stringent criteria are shorter and have stronger features and lower methylation level. In addition, we used the genome-wide base-resolution methylation profile in two cell lines to show that genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression at the genome level.
Introduction
CpG islands (CGIs), which are clusters of CpG dinucleotides in GC-rich regions, are often located in the 5 end of genes and are considered as gene markers in vertebrate genomes [1][2][3]. These CpG islands, especially promoter-associated CpG islands, play important roles in gene silencing, genomic imprinting, X-chromosome inactivation, and tumorigenesis [4]. Due to the functional importance of CpG islands in transcriptional regulation and epigenetic modifications [5], multiple algorithms have been developed to identify CpG islands in a genome or a specific sequence. Overall, these algorithms can be classified into two groups: traditional algorithms and new algorithms. Traditional algorithms are based on three features and parameters (length, GC content, and ratio of the observed over the expected CpGs (CpG O/E)) [2,4,6,7], while new algorithms are based on statistical property [8,9]. Substantial debate exists as to which algorithm performs better and in which context, such as in organisms, tissues, or developmental stages [4,8,[10][11][12]. Comparing different features of CpG islands, especially length of the predicted islands [11], our previous study suggested that Takai and Jones' algorithm is more appropriate overall for identifying promoter-associated islands of CpGs in vertebrate genomes [10]. However, the major biological patterns would remain similar regardless of the algorithm being used [13,14]. For example, the density of CpG islands is highly correlated with the number or the size of the chromosomes in mammalian genomes [13], and the number of CpG islands varies greatly among fish genomes [14]. Nevertheless, the recent study by Hackenberg et al. showed that setting the P value to 10 −20 could largely improve the performance [11]. Considering the information above, a further comparison using a similar number of CpG islands identified by different algorithms might provide us additional insights into biological features and their regulation in the cellular system. DNA methylation is an important epigenetic modification at the transcriptional regulation level, and this process is directly and substantially related to CpG islands [5,15,16]. Over 50% of human genes are associated with CpG islands in their promoter regions [3,7], while ∼15-35% of CpG islands are located in the promoter regions of genes, according to several algorithms [10,11]. Promoter-associated CpG islands have different features compared to other types of CpG islands; these features include a longer CpG island sequence, higher GC content, and higher CpG O/E ratio [6,10]. However, the correlation between the methylation of promoterassociated CpG islands and gene expression is more complex than what investigators previously thought. Several studies reported that the methylation level of promoter-associated CpG islands is negatively correlated with gene expression strength [16,17] while others observed no or weak correlations [18,19]. This difference may be due to the dynamic and complex nature of methylation in cellular systems [20][21][22][23]. Until 2009, when single-base resolution methylome data was released, studies regarding the relationship between CpG islands, methylation, and gene expression were limited. Additionally, the earlier data was often at the computational level and used features based on low-resolution data generated by array-based technology [24]. In this study, we performed an extensive investigation of the correlations between CpG islands, methylation, and gene expression by taking advantage of newly available whole genome baseresolution methylation profiling [25].
Identification of CpG Islands in the Human Genome.
We used the stringent criteria presented in Takai and Jones [4] to search CpG islands: length ≥ 500 bp, GC content ≥ 55%, and CpG O/E ratio ≥ 0.65. We also used the CpG cluster algorithm developed by Hackenberg et al. [8] to identify CpG clusters. In this study, we integrated the use of both CpG islands and CpG clusters because of their expected similarities in terms of their service as gene markers and measurement of methylation status. To identify comparable numbers of CpG clusters and CpG islands in the whole genome, we used median distance of each as the cutoff value and the P value < 10 −15 or < 10 −20 , respectively. These two P value cutoffs allowed us to obtain two sets of CpG clusters for comparison. We then downloaded CpG islands annotated by the UCSC Genome Browser (http://genome.ucsc.edu/), which were screened from the human genome by the following criteria: length > 200 bp; GC content ≥ 50%, and CpG O/E ratio > 0.6. Moreover, the UCSC algorithm searches the reference sequence one base at a time, scores each dinucleotide (+17 for CpG and −1 for others), and identifies maximally scored segments.
Sequence Data and Gene Annotation.
We downloaded the assembled human genome sequence from the National Center for Biotechnology Information (NCBI, build 36, ftp://ftp.ncbi.nih.gov/genomes/). We also extracted the Transcriptional Start Sites (TSS) for human Refseq genes from the UCSC Genome Browser (http://genome.ucsc.edu/). The promoter region was defined as −1,500 to +500 bp around the TSS, as previously described [10].
Base-Resolution Methylation Data in the Human Genome.
To evaluate the methylation status in CpG islands and CpG clusters, we downloaded the base-resolution methylation data for H1 and IMR90 cell lines in the human genome reported in Lister et al. [25], which are the first human DNA methylomes at base resolution (http://neomorph.salk .edu/human methylome/data.html). Here, we used methylation broadness [26] to evaluate the methylation level in a CpG island. The methylation broadness represents the fraction of cytosine sites detected as methylated in a given DNA segment. It can be calculated as the proportion of methylated CpG sites over the total sites in a sequence (i.e., number of methylated CpG sites/total CpG sites) [26]. A methylated CpG site is defined as the CpG site with at least one methylated read. Additionally, we obtained the methylation data in the promoter regions in the human H1 cell line from Bock et al. [27].
Gene Expression in the Human Genome.
Human gene expression data in the second version of the Gene Expression Atlas reported in Su et al. [28] was directly obtained from the author Andrew Su. There were 79 human tissues studied. Defining the expression of a gene in a specific tissue was described in previous work [29,30]. Briefly, the average difference (AD) value was required at least 200. Then, each gene was classified according to one of four groups: (1) housekeeping genes (expressed in all 79 tissues), (2) widely expressed genes (expressed in more than 80% but less than 100% of tissues), (3) moderately expressed genes (expressed in 20%-80% of tissues), and (4) narrowly expressed genes (expressed in less than 20% of genes) [31]. The expression strength was calculated by the average expression value among all 79 tissues followed by the logarithm transformation. Furthermore, we obtained separate gene expression datasets that are specifically for the human H1 and IMR90 cell lines from Lister et al. [25] and a gene expression dataset for H1 cell line from Bock et al. [27].
Features of CpG Islands Identified by Different Algorithms.
Our previous studies showed that the number of CpG islands identified by the different algorithms (e.g., Gardiner-Garden and Frommer (1987) [2], Takai and Jones (2002) [4], and CpG clusters [8]) varies greatly, either in the human genome or other vertebrate genomes [10,13,14]. Particularly, CpG clusters have several unique features (e.g., the greater number of CpG clusters identified in the human genome) that are largely dependent on the P value assigned and the length cutoff value [11]. To attain a comprehensive comparison of the performances of the major existing algorithms, in this study, our design utilized the parameters of these key algorithms so that the number of CpG islands (or clusters) would be similar and then applied this strategy to the human genome. The underlying rationale is that methylation regulation often lies in the promoter regions of genes where CpG islands are representative. Accordingly, we assigned P value 10 −15 as the cutoff to identify 37,184 CpG clusters, which is close to the number of CpG islands (37,729) identified by Takai and Jones' algorithm. Moreover, we assigned the P value 10 −20 as the cutoff to identify 25,454 CpG clusters, and this number is similar to the one identified by the UCSC Genome Browser (27,639) ( Table 1). To save space, we abbreviated the CpG islands identified by Takai and Jones' algorithm as TJ-CGIs, CpG islands identified by the USCS Genome Browser as UCSC-CGIs, CpG clusters by P value cutoff 10 −15 as CGCs-15, and CpG clusters by P value cutoff 10 −20 as CGCs-20. We further examined how the CpG clusters were associated with the promoter regions after applying these stringent P value cutoffs. Remarkably, the proportion of promoter-associated CpG clusters increased dramatically: 38.8% of all CGCs-15 and 47.6% of all CGCs-20 were promoter associated, but only 14.7% displayed association by using the default cutoff value [10]. This increase was similarly shown in Hackenberg et al. [11]. Therefore, we could obtain not only a similar number of CpG islands/clusters but also more promoter-associated CpG islands/clusters for a systematic investigation of the features of CpG islands/clusters, methylation, and gene expression in the human genome.
The average length of TJ-CGIs was 1089 bp, which was much longer than the average length of CGCs-15 (605 bp), CGCs-20 (727 bp), and UCSC-CGIs (763 bp) (Table 1). Conversely, TJ-CGIs had weaker CpG island features. For example, they had a lower GC content (60.6%) and a lower Table 1). In addition, we used box plot (with the values for maximum, minimum, median, 75% quantile, and 25% quantile) to display the distribution and features of CpG islands identified by each algorithm (Figure 1). Overall, the difference was largely due to the Hackenberg CpG cluster algorithm's tendency to identify short regions with strong CpG island features [8,10]. This comparison indicated that features of CpG islands or clusters relied on their length-the longer they are, the weaker the features they would have.
CpG islands are often located in the 5 end of genes; thus, they are considered to be gene markers [3,32]. Our previous studies showed that the features of CpG islands are different in the promoter and other regions [13,31]. Therefore, the features of promoter-associated CpG islands are more important than other genomic regions when evaluating the performance of differing CpG island/cluster algorithms. (Table 1). We observed more CpG clusters than TJ-CGIs and UCSC-CGIs in the promoter regions of genes. One main reason for this finding is that multiple CpG clusters are more likely to be identified within the same promoter region than TJ and UCSC algorithms, and several CpG clusters are often embedded within one single CpG island [10,11].
While the total number of CpG islands or CpG clusters varied among the four algorithms (ranging from 25,454 CGCs-20 to 37,729 TG-CGIs, 1.48-fold difference, Table 1), the number of promoter-associated CpG islands identified by these algorithms was actually similar (ranging from 12,115 CGCs-20 to 14,419 CGCs-15, 1.19-fold difference), confirming that CpG islands are the most important features in the promoter regions. Notably, there would be approximately 5.3-fold difference between the number of TJ-CGIs and CpG clusters when the default parameters are used in these algorithms [10]. The proportion of promoter-associated CpG islands was also very similar, that is, in a range of 35.0% (TJ-CGIs) to 47.6% (CGCs-20), 1.36-fold difference ( Table 1). Compared to the features of CpG islands at the whole genome level, the promoter-associated CpG islands showed stronger features, for example, increased length, higher GC content, and larger CpG O/E ratio (Figure 1). These observations are consistent with the previous studies [6,31], but here, we focused on a specific group of CpG clusters identified by CpG cluster algorithms using stringent criteria that are comparable to a CpG island search.
Methylation Status of CpG Islands or Clusters.
The methylation level varies within CpG islands [11]. Bock et al. [33] suggested that it should be sufficient to measure average methylation level rather than assaying every single CpG dinucleotide in a genomic region. Considering that suggestion, it would be interesting to evaluate methylation at the whole CpG island or cluster level using the highest resolution methylation data, that is, the base-resolution human methylome data, as previous studies largely relied on limited microarray-based low resolution methylation data or computational prediction [24]. Here, we applied methylation broadness, which we recently proposed and was described in Su et al. [26] to evaluate the methylation level in a CpG island or cluster. The methylation broadness is calculated as the proportion of methylated CpG sites over the total sites in a sequence (i.e., number of methylated CpG sites/total CpG sites) [26]. Since the methylation status is dynamic among different types of cells, we evaluated the methylation level in both the H1 and IMR90 cell lines in the human genome.
At the genome level, our results showed that TJ-CGIs had a higher average methylation level (mC/C ratio = 0.403) than CGCs-15 (mC/C ratio = 0.266), CGCs-20 (mC/C ratio = 0.205), and UCSC-CGIs (mC/C ratio = 0.297) in the H1 cell line. Here, mC/C denotes the ratio of methylated over unmethylated nucleotides C at the CpG sites. A similar pattern could be observed in the IMR90 cell line, as shown in Figure 2.
Promoter-associated CpG islands are thought to be mostly unmethylated or to maintain a low methylation level [18]. Compared to CpG islands across the whole genome, the methylation level of promoter-associated CpG islands decreased dramatically. In the human H1 cell line, promoterassociated TJ-CGIs had, on average, an mC/C ratio 0.177, while this ratio was 0.100 for CGCs-15, 0.084 for CGCs-20, and 0.108 for UCSC-CGIs (Figure 2(a)). Similar to our observation of the methylation pattern in CpG islands or clusters across the whole genome, promoter-associated TJ-CGIs had the highest average methylation level measured by mC/C ratio, while CpG islands or clusters identified by the other three algorithms had similar methylation levels. This difference could be related to the fact that TJ-CGIs cover longer genomic regions, some of which bear a higher methylation level. We observed a similar pattern when the methylation data in the IMR90 cell line was used (Figure 2(b)). By this measurement, our comparison suggested that the algorithm using the assigned P value cutoff 10 −20 in Hackenberg et al. [8] had the best performance to identify CpG islands or clusters with a low methylation level.
Methylation of Promoter-Associated CpG Islands and Gene
Expression. Methylation plays an important role in the regulation of gene expression [18,34]. Previous studies showed that DNA methylation typically represses gene expression [15,16]. Lister et al. [25] first displayed the correlation between the gene body methylation level and gene expression strength at the single base resolution. Here, we further analyzed the correlation between the methylation level of promoter-associated CpG islands and genes expression strength based on Lister et al. data [25]. For those genes having both expression data and methylation data in their promoter-associated CpG islands, we found a very weak negative correlation (Table 2). Moreover, we calculated Pearson's correlation coefficient between methylation of promoters and gene expression strength using Bock et al.'s [27] expression profile and methylation profile in the promoter regions across the genome in the human H1 cell line. We found a weak negative correlation between gene expression strength and methylation of promoter regions in the H1 cell line (Pearson correlation coefficient = −0.242, P < 2.2 × 10 −16 ). One possible reason for the observation of this weak correlation is that some promoter-associated CpG islands, or some promoters with methylation levels across different tissues, are negatively correlated with gene expression strength, while some others are positively correlated [35]. Following this observation, we investigated the correlation between the expression strength and methylation of promoter-associated CpG islands according to different genes categorized by their tissue expression.
We first investigated the correlation between promoterassociated CpG islands and broadness of expression. In the human H1 cell line, the average methylation level in promoter-associated TJ-CGIs in housekeeping genes was 0.125, compared to 0.139, 0.149, 0.184 in widely expressed genes, moderately expressed genes, and narrowly expressed genes, respectively (Figure 3(a)). The methylation level of CGCs-15, CGCs-20, and UCSC-CGIs was much lower than in that of TJ-CGIs. For example, the average methylation level in CGCs-15 in housekeeping genes, widely expressed genes, moderately expressed genes, and narrowly expressed genes was 0.054, 0.066, 0.077, and 0.113, respectively (Figure 3(a)). Overall, at the genome level, there was a trend that genes whose methylation level at the promoterassociated CpG islands or clusters was lower tended to express in more tissues, regardless of which specific algorithm was used. Aside from the pluripotent H1 cell line, we also examined the methylation level in the IMR90 cell line, and the conclusion remained the same (Figure 3(b)).
To further study the correlation between the methylation of promoter-associated CpG islands and gene expression strength, we used the average expression level across the 79 human tissues in the second version of the Gene Atlas dataset to represent the expression strength of a gene. In the human H1 cell line, the methylation level of the promoterassociated CpG islands in the genes with a strong expression strength (log2 expression value > 9) was much lower than those with a weak expression strength (log2 expression value < 6) (Figure 4(a)). One should note that the methylation level of promoter-associated CpG islands in genes whose expression strength values are in the range of 9-12 is similar to that of genes whose expression strength values are greater than 12. Again, a similar trend was observed when we used the methylation data from the IMR90 cell line (Figure 4(b)). Furthermore, we found a significant positive correlation between broadness of expression and expression strength (Pearson correlation r = 0.859, P < .2 × 10 −16 , Figure 5). This finding explained the consistency between broadness of expression and strength of expression.
In summary, genes with a lower methylation level at the promoter-associated CpG islands tend to express in more tissues and have stronger expression strength, while genes with a higher methylation level at the promoter-associated CpG islands tend to express in fewer tissues and have weaker expression strength.
Conclusion
In this study, we systematically investigated the features of CpG islands or clusters identified by several major algorithms in the human genome, taking advantage of recently released single-base human methylome and gene expression Atlas datasets. Because many more CpG clusters were previously found compared to the number of genes, in this study, we applied stringent criteria to generate a comparable number of CpG islands identified by the traditional Takai and Jones algorithm, or a similar number of protein-coding genes in the human genome. Our results show that Takai and Jones' algorithm tends to identify longer CpG islands, yet weaker CpG island features as well as a higher methylation level. However, this algorithm typically identifies one unique promoter-associated CpG island for a gene. Conversely, Hackenberg et al.'s algorithm is likely to identify multiple promoterassociated CpG clusters for a gene, but its CpG clusters tend to have stronger CpG island features, such as a higher GC content, higher CpG O/E ratio, and lower methylation level. This comparative study indicated that, with the appropriate, stringent cutoff value, we may identify CpG clusters that are more representative of the gene markers by uniquely mapping to the promoter regions of genes, maintaining a low methylation level, and strongly correlating gene expression among tissues. These CpG clusters may be more functional among all the CpG clusters and would be identified by the default parameters; thus, we may denote them as core CpG clusters.
Although DNA methylation has been widely thought to suppress gene expression, largely through its methylation regulation at the gene's promoter region [15,16], we found only a weak correlation between DNA methylation and gene expression strength across the whole human genome. Our results based on the gene expression broadness categories (housekeeping, widely expressed, moderately expressed, and narrowly expressed) showed that genes with a lower methylation level at the promoter-associated CpG islands tend to be expressed in more tissues and have stronger expression strength. Our results validated that the DNA methylation of promoter-associated CpG islands suppresses gene expression.
In this study, we did not take into account the missing data in the methylomes. That is, if a CpG site was not sequenced, it might be implicated as unmethylated. According to Lister et al. [25], their methylome sequencing covered 94% of the cytosines in the human genome. Considering that sequencing of gene regions has generally more coverage and higher quality than noncoding regions and our measure is the broadness of methylation in the gene regions, the effect of data missingness on our conclusions is expected to be minor. Furthermore, we applied the broadness measurement to assess methylation level in a genomic region. In this measurement, methylation of each CpG site is either methylated or unmethylated. It would be more informative by taking into account the extent of methylation at each CpG site, as such data is available from next generation sequencing. We recently proposed a deepness measurement [26], which can be combined with the broadness measurement in our future analysis.
Author's Contribution
X. Du and L. Han contributed equally to this work. grant (LM009598) from the National Library of Medicine, the Vanderbilt's Specialized Program of Research Excellence in GI Cancer Grant P50CA95103, and the VICC Cancer Center Core Grant P30CA68485 through NIH.
|
# Strapi Template Notes
This Strapi template is built using the `yarn create strapi-app tmp-app --quickstart --no-run` command to create a "Quickstart" project. There's no tagged dedicated repository for this project, rather its created between a few [Strapi packages](https://github.com/strapi/strapi/tree/master/packages) through Yarn. So, the `create` command is actually run as a part of the `update` task for `project/strapi.py`.
## `sharp`, `node-gyp`, and OSX Catalina
There is definite weirdness introduced in the most recent versions of `node-gyp`, which is used by the `create` yarn process on OSX 10.15.X Catalina. You will need XCode Command Line Tools, and likely the larger XCode app to run the `create` in the first place, even outside of template-builder. I have read that this process will also hang up on a local Node.js installation greater than 12, but have not verified myself.
This doesn't cause any problems when running the development server or building when the project has already been put together. I have only encountered it when creating the app itself from upstream in the first place.
### Common output
```
error /Users/chadcarlson/Documents/repos/github.com/platformsh/something/node_modules/sharp: Command failed.
Exit code: 126
Command: (node install/libvips && node install/dll-copy && prebuild-install) || (node-gyp rebuild && node install/dll-copy)
Arguments:
Directory: /Users/chadcarlson/Documents/repos/github.com/platformsh/something/node_modules/sharp
Output:
info sharp Detected globally-installed libvips v8.10.1
info sharp Building from source via node-gyp
/usr/local/lib/node_modules/npm/bin/node-gyp-bin/node-gyp: line 5: /usr/local/lib/node_modules/node-gyp: is a directory
Keep trying!
Oh, it seems that you encountered errors while installing dependencies in your project.
Don't give up, your project was created correctly.
Fix the issues mentionned in the installation errors and try to run the following command:
cd /Users/chadcarlson/Documents/repos/github.com/platformsh/something && yarn install
error Command failed.
Exit code: 1
Command: /usr/local/bin/create-strapi-app
Arguments: something --quickstart --no-run
Directory: /Users/chadcarlson/Documents/repos/github.com/platformsh
Output:
info Visit https://yarnpkg.com/en/docs/cli/create for documentation about this command.
```
### Relevant links
- [`node-gyp`](https://github.com/nodejs/node-gyp#on-macos)
- [Catalina Troubleshooting](https://github.com/nodejs/node-gyp/blob/master/macOS_Catalina.md)
- After considering the recommendations for local XCode installation above, the most common issue I came across was `node-gyp`s compilation of `sharp`, used by the Strapi quickstart process. Visit its [building from source](https://sharp.pixelplumbing.com/install#building-from-source) documentation for details. Very likely, the fix (after all of the above) is to set an environment variable to force compilation during `npm install/yarn`, instead of trying to use a global installation of `sharp`.
### Environment variables
After going through the above for XCode, you may need to set an enviroment variable to fix the problem with `sharp` on Catalina.
```
export SHARP_IGNORE_GLOBAL_LIBVIPS=true
```
|
<?php
use yii\db\Migration;
/**
* Class m190327_122642_tb_mt_potongan
*/
class m190327_122642_tb_mt_potongan extends Migration
{
/**
* {@inheritdoc}
*/
public function safeUp()
{
$this->createTable('tb_m_potongan', [
'id_potongan' => $this->primaryKey(),
'kode_potongan' => $this->string(50)->unique()->notNull(),
'nama_potongan' => $this->string(100)->notNull(),
'jenis_potongan' => $this->string(50)->notNull(),
'jumlah' => $this->decimal(19, 2)->notNull(),
'keterangan' => $this->text()
]);
}
/**
* {@inheritdoc}
*/
public function safeDown()
{
echo "m190327_122642_tb_mt_potongan cannot be reverted.\n";
return false;
}
/*
// Use up()/down() to run migration code without a transaction.
public function up()
{
}
public function down()
{
echo "m190327_122642_tb_mt_potongan cannot be reverted.\n";
return false;
}
*/
}
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.