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Prove that graphs with no K4 minor are 2-degenerated.
Prove that graphs with no K4 minor are 2-degenerated.
I can think about a counterexample for this statement.
Consider a vertex with 3 vertices adjacent to it, and these 3 vertices are not pairwise adjacent.
This graph has no K4 minor, but it is not 2-degenerated.
It's "2-degenerate" not "2-degenerated", and your example is: if you put the vertices in an order that puts the degree-3 vertex first, then every vertex has at most 2 neighbors that come before it.
|
Steven Fitzgerald
Steven Fitzgerald is a serial killer who appeared in Season Three of Criminal Minds.
Background
In Heat
Profile
Modus Operandi
Real-Life Comparison
Known Victims
* 2008:
* February: Robert Feeney
* February-March: Benjamin
* March-April:
* Unnamed victim
* Paul Hayes
* Daniel Brown
* April 28: Detective Charles Luvet
* April 29: Deacon Rogers
* April 30: Michael Aldridge
Appearances
* Season Three
* "In Heat"
|
About birational map between curves of the form $y^{2}=g(x)$
I'm trying to solve the following exercise but I'm stuck after trying for a long time.
Suppose that $g(x)=ax^{4}+bx^{3}+cx^{2}+dx+e\in{k[x]}$ and similarly $g'(x)=a'x^{4}+b'x^{3}+c'x^{2}+d'x+e'\in{k[x]}$. Assume that $C:y^{2}=g(x)$ and $C':y^{2}=g'(x)$ are nonsingular curves (of genus 1) and that there is an $k$-isomorphism $\phi:C\rightarrow{C'}$. The problem is to find explicitly what is $\phi$.
In the proof there are three steps that I don't understand. First, one should take a root $\xi$ of $g(x)$. Then the claim is that $\phi$ should map the point $(\xi,0)$ to a point of the form $(\xi',0)$ where $\xi'$ is a root of $g'(x)$. My quetion is why this happens? Why the image is not a point of the form $(a,b)$ with $a$ not a root of $g'(x)$ and $b\neq{0}$?.
Now once we know that the image of $(\xi,0)$ is of the form $(\xi',0)$, then it follows that $\phi$ maps the roots of $g(x)$ bijectively onto the roots of $g'(x)$. This is ok. But then it follows that $g(x)=\lambda^{2}(\gamma{x}+\delta)^{4}g'(\frac{\alpha{x}+\beta}{\gamma{x}+\delta})$ for some $\alpha,\beta,\gamma,\delta,\lambda\in{k}$. Why this happens?? There must be some bilinearity involved as a consequence of the bijection between roots of $g(x)$ and $g'(x)$ but I can't clearly see what is happening here.
Finally, we should have that $\begin{bmatrix} \alpha & \beta \\ \gamma & \delta \end{bmatrix}$ is an invertible matrix and then from this I am supposed to find $\phi$. My guess is that $\phi$ is of the form $(x,y)\mapsto(\frac{\alpha{x}+\beta}{\gamma{x}+\delta},\frac{\lambda^{-1}y}{(\gamma{x}+\delta)^{2}})$ or something like this but I'm not even sure if this makes sense (due to $(\gamma{x}+\delta)^{2}$).
I will deeply appreciate any help about this.
The model of the affine curves $E: y^{2} = g(x)$ is reminiscent of the fact that they are ramified coverings of the projective line $\mathbb{P}^{1}$ ramified at four points (this is well known: look at the image of the rational function $y/x$) and the ramification points are the roots of $g(x)$ and it is unramified at infinity.
So if we had an isomorphism $\phi$ then it would take the ramification points to ramification points (this is because the map $\phi$ is an isomorphism of varieties not just abstract curves). This answers your first question why roots should go to roots.
The map $\phi$ induces a map on the underlying $\mathbb{P}^{1}$ as follows. for any point in $p \in \mathbb{P}^{1}$ choose a point $q$ lying in $E : y^{2} = g(x)$ (there will be two choices) and then look at $\phi(q)\in E^{\prime} : y^{2}= g^{\prime}(x)$ and then map it down to the $\mathbb{P}^{1}$ that is covered by $E^{'}$; because $\phi$ is an isomorphism you can revert this process so the induced map is an isomorphism of $\mathbb{P}^{1}$ so it is, in explicit co-ordinates, a standard transformation of $PGL_{2}$. Writing this in the coordinates $[x:y]$ will give you the relations between $g(x)$ and $g^{\prime}(x)$.
Thank you for your answer. I solved my question about 2 weeks ago but the idea was essentially the same as yours (the explicit map induced by the element of $PGL_{2}$ was more difficult to find though)
You are welcome.
|
// beware of multiplicity!
// https://www.stucox.com/blog/the-good-and-bad-of-level-4-media-queries/#multiplicity
import {
get_usage_observations,
has_seen_tab_key_usage,
has_seen_touch_usage,
} from './event-listeners'
/////////////////////
function _get_relevant_media_queries() {
const result = {}
// https://developer.mozilla.org/en-US/docs/Web/CSS/Media_Queries/Using_media_queries
;[
// https://developer.mozilla.org/en-US/docs/Web/CSS/@media/any-hover
'(any-hover: none)',
'(any-hover: hover)',
// https://developer.mozilla.org/en-US/docs/Web/CSS/@media/any-pointer
'(any-pointer: none)',
//'(any-pointer: coarse)',
'(any-pointer: fine)',
// https://developer.mozilla.org/en-US/docs/Web/CSS/@media/orientation
//'(orientation: portrait)',
//'(orientation: landscape)',
].forEach(mq => {
result[mq] = window.matchMedia(mq).matches
})
return result
}
const relevant_media_queries = _get_relevant_media_queries()
///////
// https://developer.mozilla.org/en-US/docs/Web/CSS/@media/any-hover
// https://www.stucox.com/blog/you-cant-detect-a-touchscreen/
function has_any_hover() {
// from more trustable to less trustable:
// if a MQ is true, it should be reliable
if (relevant_media_queries['(any-hover: hover)']) {
return true
}
if (relevant_media_queries['(any-hover: none)'])
return false
if (relevant_media_queries['(any-pointer: fine)']) {
// assume the user has a mouse, so can hover
return true
}
if (relevant_media_queries['(any-pointer: none)']) {
// assume the user has no mouse
return false
}
if ('ontouchstart' in window || has_seen_touch_usage) {
// assume touchscreen = no pointer = no hover
return false
}
return undefined
}
/*
// https://www.stucox.com/blog/you-cant-detect-a-touchscreen/
function has_any_touch(window = window) {
const from_MQ = window.matchMedia('(any-hover: hover)')
const from_
}
// https://www.stucox.com/blog/you-cant-detect-a-touchscreen/
function has_any_pointer(window = window) {
const from_MQ = window.matchMedia('(any-hover: hover)')
const from_
}
*/
function uses_tab() {
return has_seen_tab_key_usage
}
/////////////////////
function get_debug_snapshot() {
return {
relevant_media_queries,
usages: get_usage_observations(),
has_any_hover: has_any_hover(),
uses_tab: uses_tab(),
}
}
/////////////////////
export {
has_any_hover,
uses_tab,
get_debug_snapshot,
}
|
ABC Kids XD on ABC
Schedules
* 8:00am Kick Buttowski: Suburban Daredevil
* 8:30am Star vs. The Forces of Evil
* 9:00am Randy Cunningham: 9th Grade Ninja
* 9:30am Accidentally Adventures
* 10:00am Livin' The Life With The Stereotypes
* 10:30am The Adventures of Julie Kane
* 11:00am Zeke and Luther
* 11:30am I'm In The Band
* 12:00pm Kickin' It
* 12:30pm Lab Rats
|
using System;
using System.Collections.Generic;
using System.Linq;
using System.Text;
using System.Reflection;
namespace Manos.Mvc
{
public class MvcApp : ManosApp
{
public MvcApp()
{
// Create services
ControllerService = new ControllerService(this);
ViewService = new ViewService(this);
// Document root is the current directory
DocumentRoot = System.IO.Directory.GetCurrentDirectory();
// Default session state provider
SessionStateProvider = new InMemorySessionStateProvider();
// Allocate server key
ServerKey = Guid.NewGuid().ToString();
}
public string ServerKey
{
get;
set;
}
// Map a path to the document root
public string MapPath(string path)
{
if (!path.StartsWith("/"))
throw new ArgumentException("Mapped paths must begin with a slash");
path = System.IO.Path.Combine(DocumentRoot, path.Substring(1));
path = path.Replace('/', System.IO.Path.DirectorySeparatorChar);
return path;
}
// The document root folder
public string DocumentRoot
{
get;
set;
}
// Route a static content folder
public void RouteStaticContent(string route_prefix, string content_folder=null)
{
// If content folder not specified assume same as the route prefix
if (content_folder == null)
content_folder = route_prefix;
// Setup routing to static content module
Route(route_prefix, new StaticContentModule(route_prefix, MapPath(content_folder)));
}
public ISessionStateProvider SessionStateProvider
{
get;
set;
}
public ControllerService ControllerService
{
get;
private set;
}
public ViewService ViewService
{
get;
private set;
}
}
}
|
How to export to csv the output of every iteration when scraping with a loop in python
I am very new to Python. I am trying to scrape a website and I have created a small code for this:
select = Select(character.find_element_by_id('character-template-choice'))
options = select.options
for index in range(0, len(options) - 0):
select.select_by_index(index)
option1 = character.find_elements_by_class_name('pc-stat-value')
power = []
for c in option1:
power.append("Power:" + c.text)
option2 = character.find_elements_by_class_name(
'unit-stat-group-stat-label')
skills = []
for a in option2:
skills.append(a.text)
option3 = character.find_elements_by_class_name(
'unit-stat-group-stat-value')
values = []
for b in option3:
values.append(b.text)
test = [power, skills, values]
print(test)
df = pd.DataFrame(test).T
df.to_csv('test2.csv', index=False, header=False)
The issue I have is when I try to export "test" list of lists to csv I only get the last iteration. I want to get the data for every iteration but I don't know how to do so. Can someone help me?
Thank you
Looks like you're subscribing your test file each for index in range(0, len(options) - 0): iteration. Don't you mean to write all the test after this for loop?
Thanks @ArthurPereira that was a mistake in the code I saw after I posted. I corrected it now. In this way the csv will only capture the last iteration. What I need is the csv file to capture the output of every iteration not only the last. I don't know what I need to change so that I don't overwrite the csv with every iteration
Now you are overwriting power, skills, values every iteration and only appending the last one to test. You have to append this three to your list each iteraton if you want to get then all.
Yes. I don't know how....Thus I am asking what i need to change :)
You will need to append these three list every iteration to get then all in the end:
select = Select(character.find_element_by_id('character-template-choice'))
options = select.options
test = [] # Create empty list
for index in range(0, len(options) - 0):
select.select_by_index(index)
option1 = character.find_elements_by_class_name('pc-stat-value')
power = []
for c in option1:
power.append("Power:" + c.text)
option2 = character.find_elements_by_class_name(
'unit-stat-group-stat-label')
skills = []
for a in option2:
skills.append(a.text)
option3 = character.find_elements_by_class_name(
'unit-stat-group-stat-value')
values = []
for b in option3:
values.append(b.text)
test.append([power, skills, values]) # Add a list of lists to your test
print(test)
df = pd.DataFrame(test).T
df.to_csv('test2.csv', index=False, header=False)
This will give you a list test with power, skills, values inside one list for iteration.
Thank you so much. That works great. I had tried to put the test list before the loop, but I didn't know I could append like the way you showed me. As I said I am new to Python, started as a hobby 2 weeks ago. This is my first code so still a lot to learn.
I'm glad it worked for you, and if this or any answer solves your question please consider accepting it by clicking the check-mark. This indicates to the wider community that you've found a solution and gives some reputation to both the answerer and yourself. There is no obligation to do this.
|
Silicone condensation reaction
ABSTRACT
A new silicone condensation reaction, the condensation between an alkoxy silane or siloxane or a dihydric phenol and an organo-hydrosilane or siloxane and catalysts therefore is described and claimed.
The present invention relates to a new condensation reaction between compounds containing the hydrogen bonded directly to silicon (organo-hydrosilanes or organo-hydrosiloxanes) and alkoxy-silane or siloxane which leads to the formation of siloxane bond and release of hydrocarbons as a by-product or dihydric phenols which leads to the formation of polyaryloxysilanes or polyaryloxysiloxanes
BACKGROUND OF THE INVENTION
Two general processes can be applied for synthesis of organosiloxane polymers; ring opening polymerization of cyclic siloxanes and poly condensation. The poly condensation reaction between organofunctional silanes or oligosiloxanes leads to the formation of siloxane bond and elimination of a low molecular byproduct. The poly condensation of low molecular weight siloxanol oils is the most common method synthesis of polyorganosiloxanes and has been practiced for several years. The byproduct of this process is water. Unfortunately this method cannot be used for the synthesis of well-defined block organosiloxane copolymers. In that case the non-hydrolytic condensation processes can be employed. Many of such reactions are known and are frequently used:
- 1) the reaction of an organohalosilane with an organoalkoxysilane, ≡Si—X+R—O—Si≡→≡Si—O—Si≡+RX; - 2) the reaction of organohalosilanes with organoacyloxysilanes, ≡Si—X+RCOO—Si≡→≡Si≡O—Si≡+RCOX; - 3) the reaction of organohalosilanes with organosilanols, ≡Si—X+HO—Si≡→≡Si—O—Si≡+HX; - 4) the reaction of organohalosilanes with metal silanolates, ≡Si—X+Metal—O—Si≡→≡Si—O—Si≡+Metal X; - 5) the reaction of organo-hydrosilanes with organosilanols, ≡Si—H+HO—Si≡→≡Si—O—Si≡+H₂; - 6) the self-reaction of organoalkoxysilanes, ≡Si—OR+RO—Si≡→≡Si—O—Si≡+ROR - 7) the reaction of organoalkoxysilanes with organoacyloxysilanes, ≡Si—OR+R′COO—Si≡→≡Si—O—Si≡+R′COOR - 8) the reaction of organoalkoxysilanes with organosilanols, ≡Si—OR+HO—Si≡→≡Si—O—Si≡+ROH - 9) the reaction of organoaminosilanes with organosilanols, ≡Si—NR₂+HO—Si≡→≡Si—O—Si≡+NR₂H; - 10) the reaction of organoacyloxysilanes with metal silanolates, ≡Si—OOR+Metal—O—Si≡→≡Si—O—Si≡+MetalOOR; - 11) the reaction of organoacyloxysilanes with organosilanols, ≡Si—OOR+HO—Si≡→≡Si—O—Si≡+HOOR; - 12) the reaction of organooximesilane with organosilanols, ≡Si—ON=OR₂+HO—Si≡→≡Si—O—Si≡+HN=OR₂; - 13) the reaction of organoenoxysilane with organosilanols, ≡Si—O(C=CH₂)R+HO—Si≡→≡Si—O—Si≡+CH₃COR;
Those reactions can also be used for the formation of siloxane networks via a crosslinking process. Many of the above processes require the presence of catalyst such as prot ic acids, Lewis acids, organic and inorganic bases, metal salts and organometalic complexes. (See, for example, (a) “The Siloxane Bond” Ed. Voronkov, M. G. ; Mileshkevich, V. P. ; Yuzhelevskii, Yu. A. Consultant Bureau, New York and London, 1978; and (b) Noll, W. “Chemistry and Technology of Silicones”, Academia Press, New York, 1968).
It is also well known in silicon chemistry that the organosilanol moiety will react with a hydrogen atom bonded directly to silicon (organo-hydrosilane) to produce a hydrogen molecule and the silicon-oxygen bond, (See, “Silicon in Organic, Organometallic and Polymer Chemistry” Michael A. Brook, John Wiley & Sons, Inc. , New York, Chichester, Weinheim, Brisbane, Singapore, Toronto, 2000). Although the uncatalyzed reaction will run at elevated temperatures, it is widely known that this reaction will run more readily in the presence of a transition metal catalyst especially noble metal catalysts such as those comprising platinum, palladium, etc. , a basic catalyst such as an alkali metal hydroxide, amine, etc. , or a Lewis acid catalyst such as a tin compound, etc. Recently it has been reported that organo-boron compounds are extremely efficient catalysts for the reaction between an organo-hydrosilanes and organosilanols (WO 01/74938 A1). Unfortunately, the by-product of this process is dangerous, highly reactive hydrogen.
Another useful class of materials, polyaryloxysilanes (PAS) have long been materials of commercial interest. In addition to the property benefits expected for any silicone copolymer, such as good low temperature flexibility, high temperature stability PAS also exhibit excellent flammability characteristics.
These polymers are commonly prepared by the reaction of bis-phenols with α, ω-di functional silanes, typically, α, ω-dichlorosilanes or α, ω-diaminosilanes. Reaction of bis-phenols with α, ω-dichlorosilanes requires the use of a stoichiometric amount of an acid acceptor, usually a tertiary amine. As the ether linkage in these polymers is susceptible to hydrolysis, particularly in the presence of acid or base, the amine and its salts must be completely removed from the polymer for optimal stability. The α, ω-diaminosilanes do not require an acid scavenger during the preparation of the polymer, but these intermediates themselves are prepared by the reaction of chlorosilanes with amines in the presence of an acid acceptor.
In spite of the foregoing developments, there is a continuing search for new condensation reactions that will improve reaction's selectivity and safety of the poly condensation process.
SUMMARY OF THE INVENTION
The present invention provides a new condensation process for forming a silicon-oxygen bond comprising reacting an organosilane or siloxane compounds bearing at least one hydrosilane functional group with an organoalkoxysilane or siloxane compounds containing at least one alkoxysilane functional group and release of hydrocarbon as a byproduct, in the presence of a Lewis acid catalyst. The present invention also provides for the formation of silicon-oxygen bond by reacting a compound comprising both at least one hydrosilane functionality and at least one an alkoxysilane moiety and releases hydrocarbon as a byproduct in the presence of a Lewis acid catalyst.
Thus the present invention provides for a process for forming a silicon to oxygen bond comprising: (a) reacting a first silicon containing compound said first silicon containing compound comprising a hydrogen atom directly bonded to a silicon atom with (b) a second silicon containing compound said second silicon containing compound comprising an alkoxy group bonded to a silicon atom, in the presence of (c) a Lewis acid catalyst thereby forming a silicon to oxygen bond. The present invention also provides for a process for forming an silicon to oxygen bond comprising: (a) selecting a compound comprising both at least one hydrogen atom directly bonded to a silicon atom and at least one an alkoxy group bonded to a silicon atom in said compound and (b) reacting the hydrosilane functional group with the alkoxysilane group, in the presence of (c) a Lewis acid catalyst thereby forming a silicon to oxygen bond. The present invention also provides for a process for forming a silicon to oxygen bond comprising: (a) selecting a compound comprising at least one hydrosilane functional group and a second compound serving as a source of oxygen such as water, alcohol, aldehydes, ethers, and esters (b) reacting the hydrosilane functional group with the a second compound, in the presence of (c) a Lewis acid catalyst thereby forming a silicon to oxygen to carbon bond which subsequently reacts with the residual hydrosilane functional group to form new silicon to oxygen bond.
The present invention also provides for a process for forming a silicon to oxygen bond that is part of a polyaryloxysilane or polyaryloxysiloxane comprising: (a) selecting a compound comprising at least two hydrosilane functional groups and a second compound comprising at least one of a diphenolic compound or dialkyl ether of a diphenolic compound (b) reacting the hydrosilane functional group with the a second compound, in the presence of (c) a Lewis acid catalyst thereby forming a silicon to oxygen to carbon bond.
The processes of the present invention further provide for means to produce compositions: siloxane foams, hyper branched silicone polymers, cross-linked siloxane networks and gels therefrom as well as other silicone and siloxane molecules exemplified herein.
DETAILED DESCRIPTION OF THE INVENTION
The present invention represents the discovery of a new type of non-hydrolytic condensation reaction for silicon bearing molecules. Generally, the reaction may be characterized as a condensation reaction between an organo hydrosilane or siloxane compounds bearing at least one hydrosilane moiety with an organoalkoxysilane or siloxane compounds containing at least one alkoxysilane moiety or functionality in the following exemplary embodiment: the reaction of (M_(a)D_(b)T_(c)Q_(d))_(e)(R²)_(f)(R³)_(g)SiOCH₂R¹ and HSi(R⁴)_(h)(R⁵)_(i)(M_(a)D_(b)T_(c)Q_(d))_(j)yields a compound containing a new silicon-oxygen bond (M_(a)D_(b)T_(c)Q_(d))_(e)(R²)_(f)(R³)_(g)Si OSi(R⁴)_(h)(R⁵)_(i)(M_(a)D_(b)T_(c)Q_(d))_(j) and hydrocarbon (CH₃R¹) as the products. The subscripts a, b, c and d are independently zero or positive number; e, f, g, h, i, j are zero or positive number subject to limitation that e+f+g=3; h+i+j=3; j=0, 1, 2; i=0, 1, or 2 subject to the limitation that i+j≦2. The other molecular components have standard definitions as follows:
- - M=R⁶R⁷R⁸SiO_(1/2); - D=R⁹R¹⁰SiO_(2/2); - T=R¹¹SiO_(3/2); and - Q=SiO_(4/2) or drawn as structures (without any implied limitations of stereochemistry):
The R¹ substituent is hydrogen or is independently selected from the group of one to sixty carbon atom monovalent hydrocarbon radicals that may or may not be substituted with halogens (halogen being F, Cl, Br and I), e. g. non limiting examples being fluoroalkyl substituted or chloroalkyl substituted, substituents R², R⁴, R⁶, R⁷, R⁸, R⁹, R¹⁰, and R¹¹ are independently selected from the group of one to sixty carbon atom monovalent hydrocarbon radicals that may or may not be substituted with halogens (halogen being F, Cl, Br and I), e. g. non limiting examples being fluoroalkyl substituted or chloroalkyl substituted and R³ and R⁵ are independently selected from the group consisting of hydrogen, one to sixty carbon atom monovalent alkoxy radicals, one to sixty carbon atom monovalent aryloxy radicals, one to sixty carbon atom monovalent alkaryloxy radicals and halogen.
Condensation of molecules that bear both functionalities, one (≡SiOCH₂R¹) and one (H—Si≡), on the same molecular backbone will lead to a formation of linear polymers unless the condensation reaction is conducted with a highly diluted substrate, in which case cyclic condensation products would be expected. Molecules that bear more than one (≡SiOCH₂R¹) and only one (H—Si≡) functionalities on the same molecular backbone as well as molecules that bear one (≡SiOCH₂R¹) and more than one (H—Si≡) functionalities on the same molecular backbone are examples of AB_(x) molecular structures. The condensation of these AB_(x) compounds will lead to a formation of complex hyper branched condensation polymers. The examples of such AB_(x) molecular structures include but are not limited to:
Condensation of siloxane oligomers and polymers that bear more than one (≡SiOCH₂R¹) functional group with the siloxane oligomers and polymers having more than one (H—Si≡) functionality is also possible and will lead to a formation of the cross-linked network. A preferred structure of the polymers with (≡SiOCH₂R¹) groups has the following formula:
where G is OCH₂R¹; R¹, R², R⁴ has been defined before, m=0, 1, 2 . . . 5000; n=0,1,2 . . . 1000; o=1, 2, 3; p=0, 1, 2, 3; r=0, 1, 2 with limitation that r+o=2 for internal siloxane and p+o=3 for terminal siloxane units.
A preferred structure of the polymer with (≡Si—H) groups has the following formula:
where R¹, R², R⁴ has been defined before, m=0, 1, 2 . . . 1000; n=0, 1, 2 . . . 100; t =0, 1, 2, 3 s=0, 1, 2, 3 with the limitation that t+s=2 for internal siloxane units and t+s=3 for terminal siloxane units.
Other preferred compounds with (≡Si—H) groups are:
- - Cyclic siloxanes: where R² has been defined before and u=1, 2, 3 . . . 8; or branched siloxane: where R² has been defined before and v=0, 1; w=3, 4
Condensation of siloxane oligomers and polymers that bear more than one (≡SiOCH₂R¹) moiety and more than one (H—Si≡) functionality is also possible and will lead to formation of a cross-linked network.
Condensation of diphenolic compounds and compounds with compounds having two H—Si≡ functionalities will lead to the formation of polysilylarylethers:
where Ar represents a typical bis-phenol species as described herein, R² has been defined previously, n=0-400 and m= about 10-200
The above reactions are generally accomplished in the presence of an appropriate catalyst. The catalyst for this reaction is preferably a Lewis acid catalyst. For the purposes herein, a “Lewis acid” is any substance that will take up an electron pair to form a covalent bond (i. e. , “electron-pair acceptor”). This concept of acidity also includes the “proton donor” concept of the Lowry-Bronsted definition of acids. Thus boron trifluoride (BF₃) is a typical Lewis acid, as it contains only six electrons in its outermost electron orbital shell. BF₃ tends to accept a free electron pair to complete its eight-electron orbital. Preferred Lewis acid catalysts include such catalysts as FeCl₃, AlCl₃, ZnCl₂, ZnBr₂, BF₃. The ability of any particular Lewis acid to catalyze the new reaction of the present invention will be a function of acid strength, steric hindrance of both the acid and the substrate and solubility of the Lewis acid and the substrate in the reaction medium. Generally the following Lewis acids: FeCl₃, AlCl₃, ZnCl₂, ZnBr₂, and BF₃ are only sparingly soluble in siloxane solvents and this low solubility tends to interfere with the ability of these particular Lewis acid catalysts to catalyze the desired reaction. Lewis acid catalysts having a greater solubility in siloxane media are more preferred and preferable catalysts include Lewis acid catalysts of formula (I) MR¹² _(x)X_(y) (I) wherein M is B, Al, Ga, In or Tl; each R¹² is independently the same (identical) or different and represent a monovalent aromatic hydrocarbon radical having from 6 to 14 carbon atoms, such monovalent aromatic hydrocarbon radicals preferably having at least one electron-withdrawing element or group such as —CF₃, —NO₂ or —CN, or substituted with at least two halogen atoms; X is a halogen atom; x is 1, 2, or 3; and y is 0, 1 or 2; with the proviso that x+y=3, more preferably a Lewis acid of Formula (II) BR¹³ _(x)X_(y) (II) wherein each R¹³ are independently the same (identical) or different and represent a monovalent aromatic hydrocarbon radical having from 6 to 14 carbon atoms, such monovalent aromatic hydrocarbon radicals preferably having at least one electron-withdrawing element or group such as —CF₃, —NO₂ or —CN, or substituted with at least two halogen atoms; X is a halogen atom; x is 1, 2, or 3; and y is 0, 1 or 2; with the proviso that x+y=3, and is most preferably B(C₆F₅)₃.
The condensation reaction between the (≡Si—H) moiety and the (≡—SiOR) moiety has some limitations, it appears that when three electron withdrawing substituents are on the silicon containing (≡Si—H) bond such as for example—OR, siloxane substituents or X (X=halogen) the reaction kinetics are slowed, sometimes to the point of inhibition of the reaction. Also the condensation reaction appears to require an alkoxy silane of the following structure (≡Si—O—CH₂—R¹) wherein R¹ is C₁₋₆₀ alkyl, C₁₋₆₀ alkoxy, C₂₋₆₀ alkenyl, C₆₋₆₀ aryl, and C₆₋₆₀ alkyl-substituted aryl, and C₆₋₆₀ arylalkyl where the alkyl groups may be halogenated, for example, fluorinated to contain fluorocarbons such as C₁₋₂₂ fluoroalkyl. The preferred alkoxy group is methoxy and ethoxy group.
The process of the present invention utilizes a Lewis acid catalyst concentration that ranges from about 1 part per million by weight to about 10 weight percent (based on the total weight of siloxanes being reacted); preferably from about 10 part per million by weight (wppm) to about 5 weight percent (50,000 wppm), more preferably from about 50 wppm to about 10,000 wppm and most preferably from about 50 wppm to about 5,000 wppm.
The condensation reaction can be done without solvent or in the presence of solvents. The presence of solvents may be beneficial due to an increased ability to control viscosity, rate of the reaction and exothermicity of the process. The preferred solvents include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, as well as oligomeric cyclic diorganosiloxanes.
The condensation reaction between the (≡Si—H) moiety and the (≡SiOCH₂R¹) moiety can be conducted at an ambient or at an elevated temperature depending on the chemical structures of reagents and catalysts, concentration of catalyst and used solvent.
In some cases it is desirable to blend siloxane oligomers or polymers that bear at least one (≡SiOCH₂R¹) moiety with the siloxane oligomers or polymers having at least one (H—Si≡) functional group and Lewis acid catalyst. Subsequently the condensation reaction may be activated by heat. To extend the pot life of such a fully formulated mixture, the addition of a stabilizing agent is recommended. The stabilizing additives that are effective belong to the group of nucleophiles that are able to form a complex with Lewis acids. These stabilizing additives, preferably nucleophilic compounds, include but are not limited to ammonia, primary amines, secondary amines, tertiary amines, organophosphines and phosphines.
In yet another embodiment, a polyaryloxysilane or polyaryloxysiloxane is produced from a reaction of stoichiometric amounts of an organohydrosilane or siloxane compound bearing at least two hydrosilane moieties, such as but not limited to 1,1,3,3-tetramethyldisiloxane or diphenylsilane, with a diphenolic compound or an dialkyl ether of a diphenolic compound. Compounds being such diphenolic or diphenolic ethers include but are not limited to: bis-phenol A, hydroquinone and dialkyl ethers of hydroquinone, resorcinol, bi phenol and dialkyl ethers of bi phenol and compounds of the like. Preferably, the dipenolic compound is 4,4′bi phenol and substituted 4,4′bi phenol. Additionally, the diphenolic compound, or species, may include, but is not limited to the following:
- - 4-bromoresorcinol - 4,4′-dihydroxybiphenyl ether - 4,4-thiodiphenol - 1,6-dihydroxynaphthalene - 2,6-dihydroxynaphthalene - bis(4-hydroxyphenyl)methane - bis(4-hydroxyphenyl)diphenylmethane - bis(4-hydroxyphenyl)-1-naphthylmethane - 1,1-bis(4-hydroxyphenyl)ethane - 1,1-bis(4-hydroxyphenyl)propane - 1,2-bis(4-hydroxyphenyl)ethane - 1,1-bis(4-hydroxyphenyl)-1-phenylethane - 1,1-bis(3-methyl-4-hydroxyphenyl)-1-phenylethane - 2-(4-hydroxyphenyl)-2-)3-hydroxyphenyl)propane - 2,2-bis(4-hydroxyphenyl)butane - 1,1-bis(4-hydroxyphenyl)isobutane - 1,1-bis(4-hydroxyphenyl)decane - 1,1-bis(3,5-dimethyl-4-hydroxyphenyl)cyclohexane - 1,1-bis(3,5-dibromo-4-hydroxyphenyl)cyclohexane - 1,1-bis(4-hydroxyphenyl)cyclohexane - 1,1-bis(4-hydroxyphenyl)cyclododecane - 1,1-bis(3,5-dimethyl-4-hydroxyphenyl)cyclododecane - trans-2,3-bis(4-hydroxyphenyl)-2-butene - 4,4-dihydroxy-3,3-dichlorodiphenyl ether - 4,4-dihydroxy-2,5-dihydroxy diphenyl ether - 2,2-bis(4-hydroxyphenyl)adamantane - α, α′-bis(4-hydroxyphenyl)toluene - bis(4-hydroxyphenyl)acetonitrile - 2,2-bis(3-methyl-4-hydroxyphenyl)propane - 2,2-bis(3-ethyl-4-hydroxyphenyl)propane - 2,2-bis(3-n-propyl-4-hydroxyphenyl)propane - 2,2-bis(3-isopropyl-4-hydroxyphenyl)propane - 2,2-bis(3-sec-butyl-4-hydroxyphenyl)propane - 2,2-bis(3-t-butyl-4-hydroxyphenyl)propane - 2,2-bis(3-cyclohexyl-4-hydroxyphenyl)propane - 2,2-bis(3-allyl-4-hydroxyphenyl)propane - 2,2-bis(3-methoxy-4-hydroxyphenyl)propane - 2,2-bis(3,5-dimethyl-4-hydroxyphenyl)propane - 2,2-bis(2,3,5,6-tetramethyl-4-hydroxyphenyl)propane - 2,2-bis(3-5-dichloro-4-hydroxyphenyl)propane - 2,2-bis(3,5-dibromo-4-hydroxyphenyl)propane - 2,2-bis(2,6-dibromo-3,5-dimethyl-4-hydroxyphenyl)propane - α, α-bis(4-hydroxyphenyl)toluene - α, α, α′, α′-Tetramethyl-α, α′-bis(4-hydroxyphenyl)-p-xylene - 1,1-dichloro-2,2-bis(4-hydroxyphenyl)ethylene - 1,1-dibromo-2,2-bis(4-hydroxyphenyl)ethylene - 1,1-dichloro-2,2-bis(5-phenoxy-4-hydroxyphenyl)ethylene - 4,4′-dihydroxybenzophenone - 3,3-bis(4-hydroxyphenyl)-2-butanone - 1,6-bis(4-hydroxyphenyl)-1,6-hexanedione - ethylene glycol bis(4-hydroxyphenyl)ether - bis(4-hydroxyphenyl)ether - bis(4-hydroxyphenyl)sulfide - bis(4-hydroxyphenyl)sulfoxide - bis(4-hydroxyphenyl)sulfone - bis(3,5-dimethyl-4-hydroxyphenyl)sulfone - 9,9-bis(4-hydroxyphenyl)fluorene - 2,7-dihydroxypyrene 6,6′-dihydroxy-3,3,3′, 3′-tetramethylspiro(bis)in dane(“spirobiin dane Bisphenol”) - 3,3-bis(4-hydroxyphenyl)phthalide - 2,6-dihydroxydibenzo-p-dioxin - 2,6-dihydroxythianthrene - 2,7-dihydroxyphenoxathiin - 2,7-dihydroxy-9,10-dimethylphenazine - 3,6-dihydroxydibenzofuran - 3,6-dihydroxydibenzothiophene - 2,7-dihydroxycarbazole.
The dihydric phenols may be used alone or as mixtures of two or more dihydric phenols. Further illustrative examples of dihydric phenols include the dihydroxy-substituted aromatic hydrocarbons disclosed in U.S. Pat. No. 4,217,438.
This reaction is generally accomplished in the presence of a Lewis acid catalyst, such as those described herein. Preferably the Lewis acid catalyst is B(C₆F₅)₃. This process may occur at room temperature or at elevated temperatures. The catalyst concentration is the same as described previously.
In yet another embodiment, the organoalkoxysilane or siloxane compound containing at least one alkoxysilane moiety or functionality is produced from a reaction of the organohydrosilane or siloxane compounds bearing at least one hydrosilane moiety with a source of oxygen. The source of oxygen may be any compound that reacts with the organohydrosilane or siloxane compounds bearing at least one hydrosilane moiety to produce an organoalkoxysilane or siloxane compound containing at least one alkoxysilane moiety or functionality.
The organohydrosilane or siloxane compounds bearing at least one hydrosilane moiety or functionality are generally those silanes and siloxanes of the strictures provided above. The oxygen source preferably includes any molecule that could be reduced in the presence of a (≡Si—H) moiety and a catalyst. Compounds being such oxygen sources include but are not limited to alcohols, ethers, aldehydes, carbonates and esters. Preferably, the oxygen source is any alkyl ether, alkyl alcohol alkyl or aryl aldehyde, alkyl ester, more preferably the oxygen source is a dialkyl ether, such as diethyl ether, alkyl ester such as methyl acetate, ethyl acetate, alkyl carbonate such as dimethyl carbonate.
The above reaction is generally accomplished in the presence of an appropriate catalyst. The catalyst for this reaction is preferably the same type of catalyst as described previously, namely the Lewis acid catalysts described herein and more preferably, B(C₆F₅)₃. The above reaction can be accomplished in ambient conditions or at elevated temperature. The catalyst concentration is the same as described previously. This reaction yields an organoalkoxysilane or siloxane compound containing at least one alkoxysilane moiety or functionality, such as those described herein.
In yet another embodiment, the new siloxane bond is produced from a two step reaction of the organohydrosilane or siloxane compounds bearing at least one hydrosilane moiety with less than molar equivalent (compared to Si—H functionality) of a source of oxygen. The source of oxygen may be any compound that reacts with the organohydrosilane or siloxane compounds bearing at least one hydrosilane moiety to produce an organoalkoxysilane or siloxane compound containing at least one alkoxysilane moiety or functionality. The produced organoalkoxysilane or siloxane compound is subsequently reacting with the residual organohydrosilane or siloxane compound to form a new siloxane bond. The final resultant product is the compound as described herein, namely a compound containing a new silicon-oxygen bond (M_(a)D_(b) T_(c)Q_(d))_(e)(R²)_(f)(R³)_(g)Si OSi(R⁴)_(h)(R⁵)_(i) (M_(a) D_(b)T_(c)Q_(d))_(j) and hydrocarbon (CH₃R¹) as the products. When less than molar equivalent of the compound comprising oxygen e.g in the case of diethylether 0.5 molar equivalent is preferable, a high molecular weight siloxane results. In order to obtain low molecular weight siloxane, the oxygen source is provided at an amount that is higher than the molar equivalent preferable.
The above reaction is generally accomplished in the presence of an appropriate catalyst. The catalyst for this reaction is preferably the same type of catalyst as described previously, namely the Lewis acid catalysts described herein and more preferably, B(C₆F₅)₃. The above reaction can be accomplished in ambient conditions or at elevated temperature. The catalyst concentration is the same as described previously.
Further, as described for a previous embodiment, reaction of siloxane oligomers and polymers that bear more than two (H—Si≡) functionality with less than molar equivalent, preferentially with 0.5 molar equivalent (compared to Si—H functionality) of a source of oxygen is also possible and will lead to a formation of the cross-linked network.
The compositions produced according to the method or process of this invention are useful in the field of siloxane elastomers, siloxane coatings, insulating materials and cosmetic products. The condensation reaction of (≡Si—H) terminated dimethylsiloxane oligomers with alkoxy-terminated diphenylsiloxane oligomers leads to a formation of regular block siloxane copolymers with beneficial thermo-mechanical properties. The crosslinked material produced via condensation of siloxane oligomers and polymers that bear more than one (≡SiOCH₂R¹) moiety with the siloxane oligomers and polymers having more than one (H—Si≡) functional group will lead to a formation of novel siloxane coatings and siloxane foams. A low cross-link density network frequently has the ability to be swollen by lower molecular weight siloxanes or hydrocarbons thereby forming a gel. Such gels have found utility as silicone structurants for cosmetic compositions. Hyper branched siloxane polymers may be prepared by reacting the self-condensation of molecule that bears more than one (≡SiOCH₂R¹) and one (H—Si≡) functionalities in the presence of Lewis acid.
It is to be noted that silicon is a tetravalent element and for purposes of descriptive convenience herein, not all four bonds of the silicon atom have been described in some of the abbreviated chemical reaction scenarios used to explain the reaction chemistry involved in the formation of non-hydrolytic silicon oxygen bonds. Where silicon is hypovalent or hypervalent in terms of its customary stereochemistry, the full structure has been indicated.
Experimental
1. Reaction of MD^(H) ₂₅D₂₅M with Me₂Si(OEt)₂.
A 50 ml flask was charged with 7.5 g of MD^(H) ₂₅D₂₅M (0.057mol of Si—H) and 3 g of Me₂Si(OEt)₂ (0.02 mol). The resulting low viscosity homogenous fluid was heated to 100 g for 1 hr. No reaction was observed. This example demonstrates that the reaction requires appropriate catalysis.
2. Reaction of MD^(H) ₂₅D₂₅M with MeSi(OEt)₃ in the Presence of B(C₆F₅)₃
A 50 ml flask was charged with 7.5 g of MD^(H) ₂₅M (0.057 mol of Si—H) and 3 g of MeSi(OEt)3 (0.02 mol). The reagents were mixed to form a low viscosity homogenous fluid. 1000 ppm of B(C₆F₅)₃ as a 1.0 wt % solution in methylene chloride, was added to the flask. The resulting mixture was stable at room temperature for several hours. After heating to 80° C. a very violent reaction occurred with rapid evolution of gas. The reaction mixture turned into foam in few seconds. This example shows that addition of a suitable bora ne catalyst, B(C₆F₅)₃, promotes an rapid reaction between Si—H and SiOR. Conceivably this system could be used to make a siloxane foam.
3. Self Condensation of (CH₃)₂Si(H)(OC₂H₅)
A 50 ml flask was charged with 10 g of dry toluene and 5.0×10⁻⁶ moles of B(C₆F₅)₃. The resulting mixture was heated to 50° C. Next 5.2 g (0.05 moles) of (CH₃)₂Si(H)(OEt) was added dropwise over a period of 30 minutes. The exothermic reaction with gas evolution stared after addition of first few drops of alkoxy silane. The rate of addition was adjusted to keep the reaction mixture temperature below 90° C. After addition was completed, the resulting mixture was heated at 50° C. for an additional 60 minutes. The proton NMR showed 100% conversion of Si—H and 90% conversion of Si—OEt. Si²⁹ NMR indicated the formation of linear alkoxy-stopped siloxane oligomers along with small amounts of D₃ (hexamethylcyclotrisiloxane) and D₄ (octamethyl cyclotetrasiloxane). This low temperature process may also be carried out a room temperature.
4. Self Condensation of (CH₃)Si(H)(OCH₃)₂
A 50 ml flask was charged with 10 g of dry toluene and 5.0×10⁻⁶ moles of B(C₆F₅)₃. The resulting mixture was heated to 50° C. Next 5.3 g (0.05 moles) of (CH₃)Si(H)(OCH₃)₂ was added dropwise over a period of 30 minutes. The exothermic reaction with gas evolution started after the addition of the first few drops of alkoxy silane. The rate of addition was adjusted to keep a mixture temperature below 90° C. After addition was completed, the resulting mixture was heated at 50° C. for an additional 60 minutes. The proton NMR showed 100% conversion of Si—H and 50% conversion of Si—OCH₃. Si₂₉ NMR indicated formation of hyper branched siloxane oligomers with Si—OCH₃ end groups.
5. Self Condensation of HSi(OC₂H₅)₃
A 50 ml flask was charged with 10 g of dry toluene and 5.0×10⁻⁶ moles of B(C₆F₅)₃. The resulting mixture was heated to 50° C. Next 7.9 g (0.05 moles) of HSi(OC₂H₅)₃ was added drop wise over a period of 30 minutes. The reaction temperature did not change, any gas evolution was observed. After addition of alkoxysilane was completed the resulting mixture was heated at 50° C. for an additional 60 minutes. The proton NMR showed 0% conversion of Si—H.
6. Condensation of (CH₃O)₂Si(C₆H₅)₂ with H—Si(CH₃)₂—O—Si(CH₃) ₂—H
A 50 ml flask was charge with 10 g of dry toluen and 5.0×10⁻⁶ moles of B(C₆F₅)₃.
The resulting mixture was heated to 50° C. Next a mixture of 4.88 g (0.02 moles) of (CH₃O)₂Si(C₆H₅)₂ and 2. 68 g (0.02 moles) of H—Si(CH₃) ₂—O—Si(CH₃)₂—H was added drop wise over a period of 30 minutes. The exothermic reaction with gas evolution stared after addition of the first few drops. After addition was completed the resulting mixture was heated at 50° C. for an additional 60 minutes. The proton NMR showed 100% conversion of Si—H and 100% conversion of Si—OCH₃. Si²⁹ NMR indicated formation of cyclic compound (Si(C₆H₅)₂—O Si(CH₃)₂—O—Si(CH₃)₂—O)—and linear oligomers.
7. Condensation of (CH₃O)₂Si(C₆H₅)₂ with H—Si(CH₃)₂—Cl
A 50 ml flask was charged with 10 g of dry toluene, 2.93 g (0.03 moles) of HSi(CH₃)₂—Cl and 5.0×10⁻⁶ moles of B(C₆F₅)₃ and cooled down to 20° C. Next a mixture of 3 g (0.012 moles) of (CH₃O)₂Si(C₆H₅)₂ and 3.0 g of toluene was added drop wise over a period of 30 minutes. The exothermic reaction with gas evolution stared after addition of the first drop. After addition was completed the resulting mixture was heated at 50° C. and low boiling components were stripped by application of a partial vacuum. The proton NMR showed 100% conversion of Si—H and formation of chloro-stopped siloxane (ClSi(CH₃)₂—O—S(C₆H₅)₂—O—Si(CH₃)₂Cl). Si₂₉ NMR confirmed formation of this compound.
8. Condensation of ((CH₃)₂CHO)₂SiC₂H₃ with H—Si(CH₃)₂—O—Si(CH₃) ₂—H
A 50 ml flask was charged with 10 g of dry toluene and 5.0×10⁻⁶ moles of B(C₆F₅)₃. The resulting mixture was heated to 50° C. Next a mixture of 4. 64 g (0.02 moles) of (iPrO)₃SiVi and 1.34 g (0.01 mol) of H—Si(CH₃)₂—O—Si(CH₃)₂—H was added drop wise over a period of 5 minutes. The reaction temperature did not change, and no gas evolution was observed. After addition of regents was completed the resulting mixture was heated at 50° C. for additional 60 min. The GC analysis did not show formation of siloxane oligomers. Example 8 shows that sterically hindered alkoxysilanes such as isopropoxysilane or t-butyloxysilane do not react with Si—H in the presence of B(C6F₅)₃ The condensation reaction requires the presence of —O—CH₂—R¹ alkoxide moiety attached to silicon atom.
9. Reaction of MD^(H) ₂₅D₂₅M with MeSi(OMe)₃ in the Presence of B(C₆F₅)₃
A 10 ml flask was charged with 1.25 g of MD^(H) ₂₅D₂₅M (0.01 moles of Si—H) and an appropriate amount of MeSi(OMe)3. The reagents were mixed to form a low viscosity homogenous fluid. Next 160 ppm of B(C₆F₅)₃ was added. The cure kinetics of the above mixture was evaluated by differential scanning calorimetry (DSC: Perkin Elmer). The observed pot life, peak temperature and Delta H are presented in the following table: SiH/ Peak Delta Pot life/ Exp. # Formula SiOR temp H J/g min 091-c 884466-MeSi(OMe)3 0.63 53.4 561 >360 091-d 884466-MeSi(OMe)3 1.8 61.5 174 45 091-e 884466-MeSi(OMe)3 1 57.4 310 >360 10. Reaction of MD^(H) ₂₅D₂₅M with OctylSi(OMe)₃ in the Presence of B(C₆F₅)₃
A 10 ml flask was charged with 1.25 g of MD^(H) ₂₅D₂₅M (0.01 moles of Si—H) and appropriate amount of (C₈H₁₇)Si(OMe)₃. The reagents were mixed to form a low viscosity homogenous fluid. Next 160 ppm of B(C₆F₅)₃ was added. The cure kinetics of the above mixture was evaluated by differential scanning calorimetry (DSC: Perkin Elmer). The observed pot life, peak temperature and Delta H are presented in the following table: SiH/ Peak Delta Pot life/ Exp. # Formula SiOR temp H J/g min 091-f 884466-Oct Si(OMe)3 1 47.5 745 20 O91-g 884466-Oct Si(OMe)3 0.66 62 196 20 091-h 884466-Oct Si(OMe)3 1.25 36.7 490 10
Examples 9 and 10 show that a mixture of Si—H siloxane with alkoxysilane in the presence of a catalytic amount of B(C₆F₅)₃ is stable at room temperature for a period ranging from 10 min to more than 6 hours. The room temperature stable mixture can be quickly reacted at slightly elevated temperature. These experiments indicate that the mixtures from examples 9 and 10 could be used to produce thin siloxane coatings at a low temperature (below 80° C. ). Such properties would be useful for low temperature paper release coatings and applications thereof.
11. Preparation of 1,4-bis(disilyl)benzene with Diethylether.
A 50 ml 3-neck flask equipped with a stir bar, condenser, thermometer and rubber septum seal was evacuated and then filled back with nitrogen. The flask was charged via glass syringe with 10 ml toluene, 9.88 g(0.0515 mols) of 1,4-bis(dimethylsilyl)benzene and 0.0015 g of B(C6F5)3. 3.7 g (0.05 mols) of diethylether were added dropwise via glass syringe over a period of three hours. The condensation reaction started after addition of a few drops of diethylether. The start reaction was indicated by an increase of the temperature of the reaction mixture from 25° C. to 32° C. and release of gaseous byproduct. At the end of the additional step, an additional 0.001 g of catalyst was added. After one hour of mixing at 25° C. , the reaction mixture was poured to 100 ml of methanol. The precipitation of polymeric material was observed immediately. The polymeric fraction was subsequently dried on the vacuum line to yield 10 g (95%) of white crystalline solid. GPC analysis indicated a Mw of 26000 and Mw/Mn of 2.3.
12. Reaction of 1,1,3,3-tetramethyldisiloxane (TMDS) with ethyl acetate
A solution of TMDS, 2.00 g (14.9 mmol) in 10 ml of ethyl acetate was added slowly to a solution of B(C₆F₅)₃, 10.0 mg (0.0195 mmol) in 35 ml of ethyl acetate. Upon initial addition, no gas evolution was noted but when about 50% of the TMDS had been added, rapid gas evolution accompanied by a strong exothermic reaction occurred. When addition of the silane was complete and gas evolution had ceased volatiles were removed under vacuum affording 2.42 g of an oil. Analysis of this oil by ¹H and Si NMR and by GC-MS indicated it to be a mixture of cyclic siloxanes and ethoxy-capped linear siloxanes having an average composition of about 3 silicon atoms per ethoxy group.
13. Reaction of 1,1,3,3-tetramethyldisiloxane (TMDS) with Methyl Acetate
A solution of TMDS, 2.00 g (14.9 mmol) in 10 ml of methyl acetate was added slowly to a solution of B(C₆F₅)₃, 10.0 mg (0.0195 mmol) in 35 ml of methyl acetate. Upon initial addition, no gas evolution was noted but when about 50% of the TMDS had been added, rapid gas evolution accompanied by a strong exothermic reaction occurred. When addition of the silane was complete and gas evolution had ceased volatiles were removed under vacuum affording an oil. Analysis of this oil by H and Si NMR and by GC-MS indicated it to be a mixture of cyclic siloxanes and a mixture of methoxy and ethoxy-capped linear siloxanes (methoxy/ethoxy˜1/1).
14. Reaction of 1,1,3,3-tetramethyldisiloxane (TMDS) with Dimethyl Carbonate
A solution of TMDS, 2.00 g (14.9 mmol) in 10 ml of dimethyl carbonate was added slowly to a solution of B(C₆F₅)₃, 10.0 mg (0.0195 mmol) in 35 ml of dimethyl carbonate. Upon initial addition, some gas evolution was noted accompanied by a strong exothermic reaction. When addition of the silane was complete and gas evolution had ceased volatiles were removed under vacuum affording 1.1 g of an oil. Analysis of this oil by H and Si NMR and by GC-MS indicated it to be a mixture of short linear methoxy stopped siloxanes the main component of which is 1,5-dimethoxy-1,1,3,3,5,5-hexamethyltrisiloxane.
15. Preparation of poly-2,6,2′,6′-tetramethylbiphenoxy-1,1,3,3, tetramethyldisiloxanyl Ether
To a stirred mixture of 24.2 g (0.1 mol) of tetramethylbi phenol and 55 mg (0.0001 mol) of tris-pentafluorophenyl boron in 60 ml of CH₂Cl₂ was added over 50 minutes a solution of tetramethyldisiloxane in 40 ml of CH₂Cl₂. Gas evolved vigorously with each drop of silane added and the mixture became viscous near the end of the addition. The polymer was isolated as a gummy mass by precipitation into isopropyl alcohol. The molecular weight of the polymer was determined by gel permeation to be; Mw=108,000/Mn=51,800. The Tg of the polymer is 54° C. by DSC. A thin film of the polymer, obtained by compression molding at 150° C. did not ignite when exposed to a burning match.
The foregoing examples are merely illustrative of the invention, serving to illustrate only some of the features of the present invention. The appended claims are intended to claim the invention as broadly as it has been conceived and the examples herein presented are illustrative of selected embodiments from a manifold of all possible embodiments. Accordingly it is Applicants' intention that the appended claims are not to be limited by the choice of examples utilized to illustrate features of the present invention. As used in the claims, the word “comprises” and its grammatical variants logically also subtend and include phrases of varying and differing extent such as for example, but not limited thereto, “consisting essentially of” and “consisting of. ” Where necessary, ranges have been supplied, those ranges are inclusive of all sub-ranges there between. It is to be expected that variations in these ranges will suggest themselves to a practitioner having ordinary skill in the art and where not already dedicated to the public, those variations should where possible be construed to be covered by the appended claims. It is also anticipated that advances in science and technology will make equivalents and substitutions possible that are not now contemplated by reason of the imprecision of language and these variations should also be construed where possible to be covered by the appended claims. All United States patents referenced herein are herewith and hereby specifically incorporated by reference.
1. A process for forming a silicon to oxygen bond comprising: a) reacting a first silicon containing compound said first silicon containing compound comprising a hydrogen atom directly bonded to a silicon atom with i) at least one compound comprising oxygen, said compound selected from the group consisting of alcohol, ester, aldehyde, ether, carbonate and combinations and mixtures thereof and ii) a Lewis acid catalyst, thereby forming a second silicon containing compound, said second silicon containing compound comprising an alkoxy group bonded to a silicon atom; and b) reacting the formed second silicon containing compound comprising an alkoxy group bonded to a silicon atom with the residual first silicon containing compound thereby forming a silicon to oxygen bond.
2. The process of claim 1 wherein the Lewis acid catalyst comprises a compound of the formula: MR¹² _(x)X_(y) wherein M is selected from the group consisting of B, Al, Ga, In and Tl; each R¹² is independently selected from the group of monovalent aromatic hydrocarbon radicals having from 6 to 14 carbon atoms; X is a halogen atom selected from the group consisting of F, Cl, Br, and I; x is 1, 2, or 3; and y is 0, 1 or 2; subject to the requirement that x+y=3.
3. The process of claim 2 where M is boron.
4. The process claim 2 wherein each R¹² is C₆F₅ and x=3.
5. The process of claim 1 wherein the concentration of the Lewis acid catalyst ranges from about 10 wppm to about 50,000 wppm.
6. The process of claim 1 wherein said process is stabilized by the addition of a compound selected from the group consisting of ammonia, primary amines, secondary amines, tertiary amine and organophosphines.
7. The process of claim 1 wherein said process is activated by heat.
8. The process of claim 1 wherein the compound comprising oxygen is an ether.
9. The process of claim 8 wherein the ether is diethylether.
10. The process of claim 1 wherein said silicon to oxygen bond is part of at least one of a polyaryloxysilane.
11. A process of for the preparation of a cross-linked siloxane network utilizing the method of claim 1 wherein said first silicon containing molecule comprises more than two hydrogen atoms directly bonded to more than one silicon atom and said second compound comprising oxygen, further comprising the steps of reacting the first silicon containing compound and said second compound comprising oxygen in the presence of Lewis acid catalyst.
12. A siloxane foam composition prepared by the method of claim
11. 13. A siloxane coating composition prepared by the method of claim
11. 14. A cross-linked siloxane network prepared by the method of claim
11. 15. A siloxane composition prepared by the method of claim 11, said siloxane composition comprising a polyaryloxysiloxane.
16. The composition of claim 14 swollen by lower molecular weight siloxanes or hydrocarbons thereby forming a gel.
17. The composition of claim 14 swollen by lower molecular weight siloxanes or hydrocarbons thereby forming a gel.
18. A process for forming a silicon to oxygen bond comprising: a) reacting a first silicon containing compound said first silicon containing compound comprising a hydrogen atom directly bonded to a silicon atom with i) at least one compound comprising oxygen, said compound selected from the group consisting of alcohol, ester, aldehyde, ether, carbonate and combinations and mixtures thereof and ii) a Lewis acid catalyst having the formula B(C₆F₅)₃, thereby forming a second silicon containing compound, said second silicon containing compound comprising an alkoxy group bonded to a silicon atom; and b) reacting the formed second silicon containing compound comprising an alkoxy group bonded to a silicon atom with the residual first silicon containing compound thereby forming a silicon to oxygen bond.
19. The process of claim 18 wherein the compound comprising oxygen is an ether.
20. The process of claim 19 wherein the ether is diethylether.
21. A process for forming a silicon to oxygen bond that is part of at least one of a polyaryloxysilane and a polyaryloxysiloxane comprising: a) reacting a silicon containing compound said silicon containing compound comprising at least two hydrogen atoms directly bonded to at least one silicon atom with i) at least one selected from the group consisting of a diphenolic compound and an alkyl ether of a diphenolic compound, and ii) a Lewis acid catalyst, thereby forming a silicon to oxygen bond, said silicon to oxygen bond a part of at least one of a polyaryloxysilane compound and a polyaryloxysiloxane compound.
22. The process of claim 21 wherein the diphenolic compound is tetramethyldiphenol.
23. The process of claim 21 wherein the first silicon containing compound comprising at least two hydrogen atoms is diphenylsilane.
|
American Horror Story: Bitchcraft
Notes & Trivia
* This episode is rated TV-MA.
* Production code number: 3ATS01.
* This episode had a special running time of 75 minutes.
* "Bitchcraft" aired in the United Kingdom on October 29th, 2013.
* This is the first horror genre work for actor Ameer Baraka.
Allusions
* The song that Fiona Goode dances to while using drugs is "In a Gadda Da-Vida" by Iron Butterfly.
|
INTRODUCTORY REMARKS.
The first Cattle Show of the Essex Agricultural Society was held, two years after its incorporation, at Topsfield, October 5th, 1820, From that time to the present, there have been nearly every year, shows in the county, under the direction of the Society. These have been held at different points, and of late, two or three years successively at the same place, so as to equalize the benefits to be derived from them.
It has been the judgment of the Society, that this Itinerating system of holding its Shows is better adapted to the wants of Essex,^ than that of establishing itself at some central part of the county^ and having grounds and buildings of its own, as is the case in some other counties. The question of a change in this respect, is often started, many contending that the interests of the Society and the agricultural community would be promoted by it.
One thing however is certain, that there is no diminution in the interest manifested by the public in attending our Annual Fairs. On the contrary, Cattle Show days here, as elsewhere, are the most popular holidays of the year.
A more important question to be determined is, how to give a right direction to these Shows so that they will not degenerate into occasions of mere amusement ; how best to sustain them so as to be productive of the most progress in agriculture ; how to call out, not only admiring throngs of spectators, but earnest crowds of competitors ; how to fill our show-pens with stock, surpassing in the different points of excellence such as has heretofore been exhibited ; how to induce our farmers to attempt oftener and more systema.t 4
|
Priming-cup for gas-engines.
R. G. DU BOIS.
PRIMING CUP'FOR GAS ENGINES. APPLICATION FILED MN. 16, 1915.
Patented July 18, 1916.
Ill/ [/5 IV TOR BHESA Gr. DU-BQIS, OF EAST ORANGE, NEW JERSEY.
rename-cor ron ens-ENGINES.
Specification of Letters Patent. Patented July 18, 1916.
Application filed January 16, 1915. Serial No. 2,520.
To all whom it may concern Be it known that I, Rrrnsn Gr. DU 1301s, a citizen of the United States, and resident of East Orange, in the county of Essex and State of New Jersey, have invented certain new and useful Improvements in Priming- Cups for Gas-Engines, of which the following is a specification.
This invention relates to priming cups for gasolene engines, and the object sought to be attained is to provide means which will automatically operate to close the cup and exclude dust after the valve therein is closed, thereby keeping the cup clean and leaving no deposit of dust to be washed down through the cup into the engine cyllnder every time the latter is primed.
To this end my invention consists in the peculiar features and combinations of parts to be more fully described hereinafter and pointed out in the claims.
In the accompanying drawings: Figure 1 represents a side elevation of my invention as applied to an ordinary form of prim lng cup wherein the parts are shown in closed adjustment; Fig. 2 a similar view in section showing the cup open, dotted lines indicating the closed position. Fig. 3 is a top view as when the oil valve is open and my cover removed, Fig. t front elevation showing the parts in closed position, and Fig. 5 a modification showing the cover supported by one arm, the yoke form of manipulating lever being dispensed with.
The reference numeral 1 represents the bowl or cup proper, and 2 the neck.
3 is a tapered valve passing transversely through the neck and provided with a hole 3 and held in its seat by a spring 4 encircling an extension 5. The spring and valve are held by a cross-pin 6.
7 is a screw-threaded shank adapted to enter the end of an engine cylinder, and 8 are wrench faces.
All of the above features are common to the art.
I have found in practice that considerable quantities of road dust and grit will accumulate in the cup and will be washed down into the engine cylinder whenever gasolene or oil is poured through the cup during the priming operation. This difficulty I overcome by providing a device which automatically closes the bowl of the cup whenever the valve is closed and opens the former whenever the valve is opened. This device consists of a cover .9 on the free end of a manipulating lever or yoke 10 and arranged so as to swing over and close the bowl. The lower ends 11 and 12 of downwardly ex tending arms 13 and 11 of the yoke 10 are fixed by pin 16 to turn with the valve 3, a handle 15 at the top of the yoke serving to give greater leverage and facilitate manipulation. The cover 9 is formed integral with the arms 13 andl-it for convenience in manufacture and to prevent torsional strain. The top edge 17 of the bowl 1 and the underside 18 of the cover are curved in conformity with the arc of the circle in which the cover swings during the opening and closing operations of the valve in order to more perfectly close the cup against dust and dirt.
In Fig. 5'the left hand'arm 13 shown in the other views is dispensed with and only a single lever 19 is used. A cover 20 is attached integrally to the free end of the lever 19. This cover projects laterally or at right angles to the lever 19 and swings over the mouth 21 of cup 22 in the same way that the cover 9' does in the principal views. A handle 23 is off-set relatively to the center of the cup in order to bring the handle more nearly in line with the lever 19 and thereby reduce torsional strain on the latter during manipulation. The; lever 19 is fixed to turn with a tapered valve 2 1 by a pin 25, and when the lever is in the raised position shown it turns the oil hole 26 in the valve across the oil duct 27 in the cup and stops the flow of oil or gas, at the same time bringing the cover 9 over the mouth of the cup 22 to protect it from dust and dirt.
Thus constructed the operation of my de vice is as follows: Normally the bowl of the priming cup remains closed as shown in Figs. 1, 4t and 5. When parts of the cup are in such position the manipulating lever stands upright and the oil hole 3 lies crosswise of the duct 4 and the cover 9 is over the mouth of the cup. When it is desired to prime the engine the cup is opened by manually grasping the handle 15 and turning the lever 10 down into the horizontal position shown in Fig. 2. This action carries the cover 9 with the lever 10 and uncovers the cup, thereby bringing the transverse hole 3 into coincidence with the oil duct 4? for the reception of gasolene; and as the cup has been protected by the cover, the interior will be left clean and no extraneous matter washed" down into an engine cylinder to do damage.
Although I have shown the preferred form of carrying out my invention it is apparent that innumerable variations might be con trived without escaping the essence of my device.
W'Vhat I claim is:
l. A priming cup for internal combustion engines and the like comprising a bowl having a member with a discharge duct from the bowl, a rotary valve for opening and closing said duct, and an exterior arm provided with a cover for said bowl, said. arm being movable with the valve to pass the cover over the rim of the bowl to closed position as the valve closes the duct and to opened position as the valve opens the duct, the rim of the bowl forming oppositely located convex portions each extending approximately half way around said rim, the under surface of said cover being correspondingly curved to pass over the top edge of the rim completely around the same when the cover is in closed position.
2. A priming cup for internal combustion engines and the like comprising a bowl having a stem with a discharge duct from the bowl, a valve turn able for opening and closing said duct and provided with an exterior arm having a laterally extending cover for the top of said bowl, the rim of said bowl forming oppositely located semi-circular convex portions, the under surface of said cover being correspondingly curved to pass over said rim and to fit the same completely around the bowl when the e ov r is in closed position.
3. A priming cup for internal combustion engines and the like comprising a bowl having a discharge outlet, the open end of said bowl being convex ed throughout its width from one edge portion thereof to the opposite edge portion thereof, a cover for said open end of the bowl having its under surface correspondingly conoaved to pass over the edge of the bowl and fit the same completely around said open end to close the bowl, a valve to close and open said outlet, and a radial arm carrying said cover and moving with said valve to close and open said end of the bowl as the valve closes and opens said outlet.
Signed at New York, in the county of New York and State of New York this 15 day of January A. D. 1915.
RHESA G. DU BOIS.
Witnesses FRED E. TASKER, JAMES A. RIDGWAY.
Washington, I). G.
|
How to display background pictures
I simply want to be able to "Insert" background pictures while displaying text in front of it.
I'm new to c# so if possible, keep it simple.
Insert background pictures to where? A form? A picturebox? A website?
Use the background image property, or add a picture box/control and place a label on top of it, if the label is behind the picture control then move the text label in-front of the picture box
You can try setting BackGroundImage property from your code behind if this property is exposed by the control.... -
control.BackgroundImage = Image.FromFile("C:\filename.jpg");
I'm guessing you're using the console applications but you cant change the background image on that, if you want to make a program you could try using windows form applications, you can design what you want the user to see and set background images. Change the "BackgroundImage" property, and then import the image you want to use. I'm also new to c# so I know how you feel. Also to impove image quality change it to a bitmap (bmp), its much clearer than a jpeg
To change the background of a form go to the properties of the form and click BackgroundImage
If you want to change it during runtime with code
Make a class called background
class Background
{
public static string background_file;
}
This is the class
this.BackgroundImage = new Bitmap("file_in_debug_folder");
This will change the background on the current form
Background.background_file = "$this.BackgroundImage-blue.bmp";
This will change the variable in the class to the file location "$this.BackgroundImage-blue.bmp" but this will be changed to the name of your file in the debug folder
|
2006-04-18 Herald-Sun: community church
'Community' the word for outreach church
* By DAWN BAUMGARTNER VAUGHAN : The Herald-Sun
* dvaughan@heraldsun
* Apr 18, 2006 : 8:06 pm ET
DURHAM -- No denomination is attached to the name of this Lincoln Street church.
For the kids, it is a time to learn and have fun.
For their parents, it is knowledge that their children are in a safe, positive environment.
Lucas says all the church's programs benefit from partnerships with others.
First Chronicles has a lot going on.
|
In the original article, there was a mistake in the legend for **Table 1** as published: important citations were not included for the referenced studies. The correct legend appears below.
**Table 1** **∣** **Site characteristics for each year and location that samples were randomly selected from for chemical analysis. Raw quinoa seed sent for analysis was grown in 2016 and 2017 in western Washington as part of two separate experimental designs** **(**[@B1], [@B2]**)**.
In the original article ***(Hinojosa et al., 2019; Kellogg and Murphy*** ***2019)***was not cited in the article. The citation has now been inserted in ^**\*\***^***Methods*** ***Section***^**\*\***^, ^**\*\***^***Study Region*** ***and Field Trials***^**\*\***^, ^**\*\***^***Paragraph*** ***one***^**\*\***^ and should read:
^**\*\***^**Raw quinoa seed sent for analysis was grown in 2016 and 2017 in western Washington as part of two separate experimental designs** **(**[@B1], [@B2]**). Site characteristics for all locations are summarized in Table 1. In 2016, F5:F6 advanced breeding lines and control varieties were planted on three organic farms in Chimacum (Finnriver Farm; 48°0\'29"N 122°46\'12"W), Quilcene (Dharma Ridge Organic Farm; 47°55\'04.0"N 122°53\'23.2"W) and Sequim (Nash\'s Organic Produce; 48°08\'31"N 123°07\'19"W) on the Olympic Peninsula. Control varieties included Cherry Vanilla (Wild Garden Seed, Philomath, OR, US), CO407Dave (PI 596293, USDA Plant Introduction, Ames, Iowa) and Kaslaea (Ames 13745, USDA Plant Introduction, Ames, Iowa). At each location, advanced breeding lines and control varieties were planted in single hand-sown plots that measured 4.9 m in length and 40.64 cm from center and were seeded at a rate of 4 g row m**^**−1**^ **in an augmented randomized complete block design (ARCBD). An ARCBD uses control varieties to account for field variation by replicating control varieties across blocks; control varieties can be used as covariates to make spatial adjustments across blocks. This design is useful for evaluating advanced breeding lines when seed quantity is low, land and other resources are limited, and when many advanced breeding lines must be evaluated**.^**\*\***^
The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
[^1]: Edited and reviewed by: Michael Erich Netzel, The University of Queensland, Australia
[^2]: This article was submitted to Nutrition and Sustainable Diets, a section of the journal Frontiers in Nutrition
|
#include <SoftwareSerial.h>
#define ssRX 2
#define ssTX 3
SoftwareSerial nss(ssRX, ssTX);/*
Fade
This example shows how to fade an LED on pin 9
using the analogWrite() function.
This example code is in the public domain.
*/
int led = 13; // the pin that the LED is attached to
int brightness = 0; // how bright the LED is
int fadeAmount = 5; // how many points to fade the LED by
int delayTime = 1000;
// the setup routine runs once when you press reset:
void setup() {
// declare pin 9 to be an output:
pinMode(led, OUTPUT);
nss.begin(9600);
}
// the loop routine runs over and over again forever:
void loop() {
// set the brightness of pin 9:
// reverse the direction of the fading at the ends of the fade:
analogWrite(led, brightness);
int i = 0;
while(i < delayTime){
nss.println(brightness);
i++;
}
//delay(delayTime);
brightness = 255;
analogWrite(led, brightness);
i=0;
while(i < delayTime){
nss.println(brightness);
i++;
}
brightness = 1;
}
|
248 THE VOYAGE OF H.M.S. CHALLENGER. really belonged to Conocrinus. But as he did not place the latter type among the Apiocrinidee together with Bourgueticrinus and Bugeniacrinus, it would seem that he had either abandoned it altogether, or else entirely misunderstood its real character and affinities ; and in the absence of figures or original specimens his account of it would be absolutely unintelligible. Rhizocrinus was first described by Sars in 1864,’ and more fully in 1868°; and though he was led to consider the anchylosed basals as a top stem-joint, this error was corrected by Pourtalés and myself before a fresh diagnosis of Conocrinus was given by de Loriol.? This indeed was only provisional, in default of better knowledge, and owing to Meneghini’s failure to find the interbasal sutures in a section through the lower part of the calyx,‘ just as in a recent Rhizocrinus or Bathycrinus (Pl. VIla. fig. 13), de Loriol was led to consider it probable that the basals “ n’existent pas et sont intimement soudées, de maniére 4 former comme une seule piece centro-dorsale.” He thus fell into exactly the same error as had been made by Sars and Ludwig respecting the recent Rhizocrinus lofotensis. Zittel,? however, who had satisfied himself regarding the presence of interbasal sutures in Conocrinus pyriformis, recognised the identity of this genus with Rhizocrinus, but did not adopt the latter name on the ground that ‘Nach den Regeln der Prioritiit gebiihrt dem Namen Conocrinus, d’Orb. die Prioritit, wenn gleich die Gattungsdiagnose @’Orbigny’s unyollstiindig und theilweise unrichtig ist.” It seems to me, however, that this is stretching the rules of priority to the widest possible limit, or even beyond it ; and that definitions which are incorrect, meaningless, and altogether incomplete have no claim whatever to recognition. Liitken remarked in 1864 that the distinction of Conocrinus from Bourgueticrinus was still a matter of uncertainty ; while d’Orbigny’s own countrymen Hébert and Munier-Chalmas did not adopt his generic name for the new type which they described as Bourgueticrinus suesst ; and although it was subsequently referred by de Loriol to Conocrinus, and carefully described, the genus Rhizocrinus had meanwhile become thoroughly well established and universally recognised by zoologists. Both Sars and de Loriol were in error as to the composition of the calyx in this type ; and a correct definition of Conocrinus was not given until the publication of Zittel’s Paleontology in 1879; while even as early as 1868,° and subsequently more fully in 1874,’ Pourtalés had correctly pointed out the characteristic features of Sars’s genus Rhizocrinus, especially as regards the presence of basals, which had been supposed to be either absent altogether, or else modified into a kind of rosette. According to Sars* “Ce qui est remarquable et characteristique pour la tige du Rhizocrinus, c’est son sommet 1 Forhandl. Vidensk. Selsk., p. 127. 2 Crinoides vivants, pp. 38, 39. 3 Swiss Crinoids, p. 191. * Loc. cit., p. 50. 5 Paleeontologie, p. 392. & Bull. Mus. Comp. Zodl., vol. i., No. 7, p. 129. 7 Ill. Cat. Mus. Comp. Zodl., No. 8, pp. 27, 28. * Crinoides vivants, p. 4.
|
User talk:Naruto Wikia Editor
Welcome
* Here are several other pages that can help you with where to begin-
* Special:Upload - A page that provides you a form for uploading images easily.
Always sign in before you edit – This is so that we can recognize you!
|
It's July and it's getting hot, just like the deals at Appalachian Wireless. All month get the Samsung Galaxy S8 for just a penny with a two-year agreement. But don't wait because the deal ends soon. Better service, bigger savings. That's today's Appalachian Wireless. It's important to stay fit this summer, but it's also important to take precautions when exercising in the summer heat. Local fitness guru Tammy Hall has more. Sometimes when people are needing to exercise in this type of weather, well, even in winter weather, you have to have a black back-up plan. You have to be aware of weather forecasts and weather alerts and heat alerts especially. Also wear appropriate clothing, wear sunscreen, drink plenty of fluids is one of the main things to avoid getting cramps or heat stroke. But having a back-up plan is very important because the weather right now that we have been having in the last two weeks, the humidity is so high it was even hard to breathe, especially if anyone has breathing problems such as asthma. In midday sun it is hotter and it's the most, those are the most dangerous rays of sunshine that comes down sunlight on you which is going to be very hot in midday, either early morning or at night. And two, you can bring that inside. And they need to be aware of some of our Apple Watches or some of the Fitness Watches. We can tell your heart rate, your heart rate also. Some of them have blood pressure now I've noticed. And that is something to be aware of and always make sure at any type of exercise inside or outside that you stretch and warm up because muscles are easy to tear. And doing yoga, which is one of my favorites, yoga is a good thing to do before you do any type of running, jogging or actually getting on any machines that are inside because our muscles have to stretch in order to work properly. Reporting in Pikeville, I'm Polly Hopkins for EKB News.
|
<?php namespace Anomaly\PagesModule\Entry\Form;
use Anomaly\Streams\Platform\Ui\Form\FormBuilder;
/**
* Class EntryFormBuilder
*
* @link http://pyrocms.com/
* @author PyroCMS, Inc. <[email protected]>
* @author Ryan Thompson <[email protected]>
*/
class EntryFormBuilder extends FormBuilder
{
/**
* The form options.
*
* @var array
*/
protected $options = [
'locking_enabled' => false,
];
}
|
initialise models in MODEL_REGISTRY to make PyTorch modules work
Codecov Report
All modified and coverable lines are covered by tests :white_check_mark:
Project coverage is 90.23%. Comparing base (8061cee) to head (8fca5a2).
Additional details and impacted files
@@ Coverage Diff @@
## main #184 +/- ##
=======================================
Coverage 90.23% 90.23%
=======================================
Files 42 42
Lines 1925 1925
=======================================
Hits 1737 1737
Misses 188 188
:umbrella: View full report in Codecov by Sentry.
:loudspeaker: Have feedback on the report? Share it here.
|
[Congressional Record (Bound Edition), Volume 147 (2001), Part 15]
[Extensions of Remarks]
[Page 21820]
PATRIOTIC POEM WRITTEN BY SARAH BETH SOENDKER
______
HON. IKE SKELTON
of missouri
in the house of representatives
Tuesday, November 6, 2001
Mr. SKELTON. Mr. Speaker, I am proud to share with the Members of the
House this excellent poem written by 11-year old Sarah Beth Soendker,
of Polo, Missouri. She is the granddaughter of Mr. and Mrs. Carl
Soendker, of Lexington, Missouri. She wrote the poem in remembrance of
the victims of the attack on America. The fine poem is set forth as
follows:
An American Promise
We will stand tall if our soldiers die, if war starts again
or if our hearts cry.
We will stand tall if our country should lose, if our men go
to war, that's our news.
We will stand tall if our houses are burned, or if our
country is attacked, we will still not be ruined.
We may be trapped in this world of sin, but at least we still
have our pride, our courage and we can win!
An American Promise that we will make, we'll hold the flag
high and this flag we won't let them take!
Sarah has also had two poems published in the 2000-01 editions of
``Anthology of Poetry by Young Americans.''
____________________
|
import DOM from 'src/ui/dom/dom';
import { mount } from 'enzyme';
import mockManager from '../../../setup/managermocker';
import Filter from 'src/core/models/filter';
import FilterMetadata from '../../../../src/core/filters/filtermetadata';
describe('range filter component', () => {
DOM.setup(document, new DOMParser());
let COMPONENT_MANAGER, defaultConfig, setStaticFilterNodes;
const metadataFormatters = {
greaterThanEqual: min => `≥ ${min}`,
lessThanEqual: max => `≤ ${max}`,
inclusiveRange: (min, max) => `${min} - ${max}`
};
beforeEach(() => {
const bodyEl = DOM.query('body');
DOM.empty(bodyEl);
DOM.append(bodyEl, DOM.createEl('div', { id: 'test-component' }));
setStaticFilterNodes = jest.fn();
const mockCore = {
setStaticFilterNodes: setStaticFilterNodes,
filterRegistry: {
setStaticFilterNodes: setStaticFilterNodes
}
};
COMPONENT_MANAGER = mockManager(mockCore);
defaultConfig = {
container: '#test-component'
};
});
it('renders correctly for default values', () => {
const component = COMPONENT_MANAGER.create('RangeFilter', defaultConfig);
const wrapper = mount(component);
expect(component._range.min).toEqual(0);
expect(component._range.max).toEqual(10);
const minInputs = wrapper.find('input[data-key="min"]');
expect(minInputs).toHaveLength(1);
expect(minInputs.props().value).toEqual('0');
const maxInputs = wrapper.find('input[data-key="max"]');
expect(maxInputs.props().value).toEqual('10');
expect(maxInputs).toHaveLength(1);
});
it('correctly renders title, minLabel, maxLabel', () => {
const config = {
...defaultConfig,
title: 'Flowers for m[A]chines',
minLabel: 'or not to [B]e',
maxLabel: 'meaningless [C]ode'
};
const component = COMPONENT_MANAGER.create('RangeFilter', config);
const wrapper = mount(component);
expect(wrapper.find('legend').first().text()).toEqual(config.title);
const labelEls = wrapper.find('label');
expect(labelEls).toHaveLength(2);
expect(labelEls.at(0).text()).toEqual(config.minLabel);
expect(labelEls.at(1).text()).toEqual(config.maxLabel);
});
it('correctly creates filter nodes on change', () => {
const config = {
...defaultConfig,
field: 'yorha',
title: 'Flowers for m[A]chines',
initialMin: -1,
initialMax: 1
};
let min = config.initialMin;
let max = config.initialMax;
const { field, title } = config;
const component = COMPONENT_MANAGER.create('RangeFilter', config);
let filter = Filter.inclusiveRange(field, min, max);
let metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.inclusiveRange(min, max)
});
min = component._range.min;
max = component._range.max;
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
// Clear the min value
min = '';
component._updateRange('min', min);
filter = Filter.lessThanEqual(field, max);
metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.lessThanEqual(max)
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(1);
// Set the min value again
min = 0;
component._updateRange('min', min);
filter = Filter.inclusiveRange(field, min, max);
metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.inclusiveRange(min, max)
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(2);
// Clear the max value
max = '';
component._updateRange('max', max);
filter = Filter.greaterThanEqual(field, min);
metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.greaterThanEqual(min)
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(3);
// Set the max value again
max = 2;
component._updateRange('max', max);
filter = Filter.inclusiveRange(field, min, max);
metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.inclusiveRange(min, max)
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(4);
// Clear both values
min = '';
max = '';
component._updateRange('max', min);
component._updateRange('min', max);
filter = Filter.empty();
metadata = new FilterMetadata({
fieldName: title
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(6);
// Set both values, finally done!
min = -1;
max = 0;
component._updateRange('min', min);
component._updateRange('max', max);
filter = Filter.inclusiveRange(field, min, max);
metadata = new FilterMetadata({
fieldName: title,
displayValue: metadataFormatters.inclusiveRange(min, max)
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
expect(setStaticFilterNodes.mock.calls).toHaveLength(8);
});
it('correctly creates filter node when min equals max', () => {
const config = {
...defaultConfig,
field: 'yorha',
title: 'Flowers for m[A]chines',
initialMin: 0,
initialMax: 0
};
const min = config.initialMin;
const { field, title } = config;
const component = COMPONENT_MANAGER.create('RangeFilter', config);
const filter = Filter.equal(field, min);
expect(component._buildFilter()).toEqual(filter);
const metadata = new FilterMetadata({
fieldName: title,
displayValue: min
});
expect(component.getFilterNode().getFilter()).toEqual(filter);
expect(component.getFilterNode().getMetadata()).toEqual(metadata);
});
});
|
[]() []()
# alekny-mastercomfig-preset
A custom preset for [mastercomfig](https://www.mastercomfig.com/)
#### What is this?
This custom preset is based on the mastercomfig "medium low"-preset, changes include:
* Enabling shadows=medium (because they are still visible through walls in a lot if situations)
* Setting textures and lod to high (just looks a lot better)
* Enabling phong shading (make australiums look gold and shiny)
* Enabling sprays
* Setting Bandwidth to 6Mbps (make the most out of good connections)
* Enabling Killstreak-Sheens
* Enabling outlines on objectives like the cart in pl
* Enabling HUD-Playermodel
* Adding some cool net_graph settings when pressing and holding "tab"
* Force mat_queue_mode 2
#### Screenshots
[Click Me!](https://imgur.com/a/G83cp8d)
#### Install Instructions
Download the latest [release](https://github.com/alekny/alekny-mastercomfig-preset/releases) and place "alekny-mastercomfig-preset.vpk" into your "tf/custom" folder together with any mastercomfig preset vpk.
NOTICE: This will override any existing preset!
#### Preset Update Instructions
Download the latest [release](https://github.com/alekny/alekny-mastercomfig-preset/releases) and replace it with your existing "alekny-mastercomfig-preset.vpk".
I will design it to work with the latest stable version of mastercomfig. However it will very likely work with older versions as well.
#### Mastercomfig Update Instructions
Just update your mastercomfig vpk and leave "alekny-mastercomfig-preset.vpk" where it is.
Enjoy :>
[My Minisign Pubkey](https://pastebin.com/raw/ybSfH5yW) (FP: 9CBE19476D63187B)
[My PGP Pubkey](https://keys.openpgp.org/search?q=D05F3280EFA67D05CCEF199C802F8B63CFBFB38C) (FP: D05F3280EFA67D05CCEF199C802F8B63CFBFB38C)
|
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 181
Search results for: 6-DOF robots
181 Creation of a Care Robot Impact Assessment
Authors: E. Fosch-Villaronga
Abstract:
This paper pioneers Care Robot Impact Assessment (CRIA), a methodology used to identify, analyze, mitigate and eliminate the risks posed by the insertion of non-medical personal care robots (PCR) in medical care facilities. Its precedent instruments [Privacy and Surveillance Impact Assessment (PIA and SIA)] fall behind in coping with robots. Indeed, personal care robots change dramatically how care is delivered. The paper presents a specific risk-sector methodology, identifies which robots are under its scope and presents some of the challenges introduced by these robots.
Keywords: Ethics, Impact Assessment, Law, Personal Care Robots.
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180 A New Center of Motion in Cabling Robots
Authors: A. Abbasi Moshaii, F. Najafi
Abstract:
In this paper a new model for center of motion creating is proposed. This new method uses cables. So, it is very useful in robots because it is light and has easy assembling process. In the robots which need to be in touch with some things this method is so useful. It will be described in the following. The accuracy of the idea is proved by two experiments. This system could be used in the robots which need a fixed point in the contact with some things and make a circular motion.
Keywords: Center of Motion, Robotic cables, permanent touching.
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179 Robust Stabilization of Rotational Motion of Underwater Robots against Parameter Uncertainties
Authors: Riku Hayashida, Tomoaki Hashimoto
Abstract:
This paper provides a robust stabilization method for rotational motion of underwater robots against parameter uncertainties. Underwater robots are expected to be used for various work assignments. The large variety of applications of underwater robots motivates researchers to develop control systems and technologies for underwater robots. Several control methods have been proposed so far for the stabilization of nominal system model of underwater robots with no parameter uncertainty. Parameter uncertainties are considered to be obstacles in implementation of the such nominal control methods for underwater robots. The objective of this study is to establish a robust stabilization method for rotational motion of underwater robots against parameter uncertainties. The effectiveness of the proposed method is verified by numerical simulations.
Keywords: Robust control, stabilization method, underwater robot, parameter uncertainty.
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178 Self-protection Method for Flying Robots to Avoid Collision
Authors: Guosheng Wu, Luning Wang, Changyuan Fan, Xi Zhu
Abstract:
This paper provides a new approach to solve the motion planning problems of flying robots in uncertain 3D dynamic environments. The robots controlled by this method can adaptively choose the fast way to avoid collision without information about the shapes and trajectories of obstacles. Based on sphere coordinates the new method accomplishes collision avoidance of flying robots without any other auxiliary positioning systems. The Self-protection System gives robots self-protection abilities to work in uncertain 3D dynamic environments. Simulations illustrate the validity of the proposed method.
Keywords: Collision avoidance, Mobile robots, Motion-planning, Sphere coordinates, Self-protection.
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177 Navigation of Multiple Mobile Robots using Rule-based-Neuro-Fuzzy Technique
Authors: Saroj Kumar Pradhan, Dayal Ramakrushna Parhi, Anup Kumar Panda
Abstract:
This paper deals with motion planning of multiple mobile robots. Mobile robots working together to achieve several objectives have many advantages over single robot system. However, the planning and coordination between the mobile robots is extremely difficult. In the present investigation rule-based and rulebased- neuro-fuzzy techniques are analyzed for multiple mobile robots navigation in an unknown or partially known environment. The final aims of the robots are to reach some pre-defined goals. Based upon a reference motion, direction; distances between the robots and obstacles; and distances between the robots and targets; different types of rules are taken heuristically and refined later to find the steering angle. The control system combines a repelling influence related to the distance between robots and nearby obstacles and with an attracting influence between the robots and targets. Then a hybrid rule-based-neuro-fuzzy technique is analysed to find the steering angle of the robots. Simulation results show that the proposed rulebased- neuro-fuzzy technique can improve navigation performance in complex and unknown environments compared to this simple rulebased technique.
Keywords: Mobile robots, Navigation, Neuro-fuzzy, Obstacle avoidance, Rule-based, Target seeking
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176 Energy Management Techniques in Mobile Robots
Authors: G. Gurguze, I. Turkoglu
Abstract:
Today, the developing features of technological tools with limited energy resources have made it necessary to use energy efficiently. Energy management techniques have emerged for this purpose. As with every field, energy management is vital for robots that are being used in many areas from industry to daily life and that are thought to take up more spaces in the future. Particularly, effective power management in autonomous and multi robots, which are getting more complicated and increasing day by day, will improve the performance and success. In this study, robot management algorithms, usage of renewable and hybrid energy sources, robot motion patterns, robot designs, sharing strategies of workloads in multiple robots, road and mission planning algorithms are discussed for efficient use of energy resources by mobile robots. These techniques have been evaluated in terms of efficient use of existing energy resources and energy management in robots.
Keywords: Energy management, mobile robot, robot administration, robot management, robot planning.
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175 Representations of Childcare Robots as a Controversial Issue
Authors: Raya A. Jones
Abstract:
This paper interrogates online representations of robot companions for children, including promotional material by manufacturers, media articles and technology blogs. The significance of the study lies in its contribution to understanding attitudes to robots. The prospect of childcare robots is particularly controversial ethically, and is associated with emotive arguments. The sampled material is restricted to relatively recent posts (the past three years) though the analysis identifies both continuous and changing themes across the past decade. The method extrapolates social representations theory towards examining the ways in which information about robotic products is provided for the general public. Implications for social acceptance of robot companions for the home and robot ethics are considered.
Keywords: Acceptance of robots, childcare robots, ethics, social representations.
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174 Deadline Missing Prediction for Mobile Robots through the Use of Historical Data
Authors: Edwaldo R. B. Monteiro, Patricia D. M. Plentz, Edson R. De Pieri
Abstract:
Mobile robotics is gaining an increasingly important role in modern society. Several potentially dangerous or laborious tasks for human are assigned to mobile robots, which are increasingly capable. Many of these tasks need to be performed within a specified period, i.e, meet a deadline. Missing the deadline can result in financial and/or material losses. Mechanisms for predicting the missing of deadlines are fundamental because corrective actions can be taken to avoid or minimize the losses resulting from missing the deadline. In this work we propose a simple but reliable deadline missing prediction mechanism for mobile robots through the use of historical data and we use the Pioneer 3-DX robot for experiments and simulations, one of the most popular robots in academia.
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173 Designing a Robust Controller for a 6 Linkage Robot
Authors: G. Khamooshian
Abstract:
One of the main points of application of the mechanisms of the series and parallel is the subject of managing them. The control of this mechanism and similar mechanisms is one that has always been the intention of the scholars. On the other hand, modeling the behavior of the system is difficult due to the large number of its parameters, and it leads to complex equations that are difficult to solve and eventually difficult to control. In this paper, a six-linkage robot has been presented that could be used in different areas such as medical robots. Using these robots needs a robust control. In this paper, the system equations are first found, and then the system conversion function is written. A new controller has been designed for this robot which could be used in other parallel robots and could be very useful. Parallel robots are so important in robotics because of their stability, so methods for control of them are important and the robust controller, especially in parallel robots, makes a sense.
Keywords: 3-RRS, 6 linkage, parallel robot, control.
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172 Distributed Coverage Control by Robot Networks in Unknown Environments Using a Modified EM Algorithm
Authors: Mohammadhosein Hasanbeig, Lacra Pavel
Abstract:
In this paper, we study a distributed control algorithm for the problem of unknown area coverage by a network of robots. The coverage objective is to locate a set of targets in the area and to minimize the robots’ energy consumption. The robots have no prior knowledge about the location and also about the number of the targets in the area. One efficient approach that can be used to relax the robots’ lack of knowledge is to incorporate an auxiliary learning algorithm into the control scheme. A learning algorithm actually allows the robots to explore and study the unknown environment and to eventually overcome their lack of knowledge. The control algorithm itself is modeled based on game theory where the network of the robots use their collective information to play a non-cooperative potential game. The algorithm is tested via simulations to verify its performance and adaptability.
Keywords: Distributed control, game theory, multi-agent learning, reinforcement learning.
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171 Intelligent Swarm-Finding in Formation Control of Multi-Robots to Track a Moving Target
Authors: Anh Duc Dang, Joachim Horn
Abstract:
This paper presents a new approach to control robots, which can quickly find their swarm while tracking a moving target through the obstacles of the environment. In this approach, an artificial potential field is generated between each free-robot and the virtual attractive point of the swarm. This artificial potential field will lead free-robots to their swarm. The swarm-finding of these free-robots dose not influence the general motion of their swarm and nor other robots. When one singular robot approaches the swarm then its swarm-search will finish, and it will further participate with its swarm to reach the position of the target. The connections between member-robots with their neighbors are controlled by the artificial attractive/repulsive force field between them to avoid collisions and keep the constant distances between them in ordered formation. The effectiveness of the proposed approach has been verified in simulations.
Keywords: Formation control, potential field method, obstacle avoidance, swarm intelligence, multi-agent systems.
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170 Localization of Mobile Robots with Omnidirectional Cameras
Authors: Tatsuya Kato, Masanobu Nagata, Hidetoshi Nakashima, Kazunori Matsuo
Abstract:
Localization of mobile robots are important tasks for developing autonomous mobile robots. This paper proposes a method to estimate positions of a mobile robot using a omnidirectional camera on the robot. Landmarks for points of references are set up on a field where the robot works. The omnidirectional camera which can obtain 360 [deg] around images takes photographs of these landmarks. The positions of the robots are estimated from directions of these landmarks that are extracted from the images by image processing. This method can obtain the robot positions without accumulative position errors. Accuracy of the estimated robot positions by the proposed method are evaluated through some experiments. The results show that it can obtain the positions with small standard deviations. Therefore the method has possibilities of more accurate localization by tuning of appropriate offset parameters.
Keywords: Mobile robots, Localization, Omnidirectional camera.
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169 Cooperative Multi Agent Soccer Robot Team
Authors: Vahid Rostami, Saeed Ebrahimijam, P.khajehpoor, P.Mirzaei, Mahdi Yousefiazar
Abstract:
This paper introduces our first efforts of developing a new team for RoboCup Middle Size Competition. In our robots we have applied omni directional based mobile system with omnidirectional vision system and fuzzy control algorithm to navigate robots. The control architecture of MRL middle-size robots is a three layered architecture, Planning, Sequencing, and Executing. It also uses Blackboard system to achieve coordination among agents. Moreover, the architecture should have minimum dependency on low level structure and have a uniform protocol to interact with real robot.
Keywords: Robocup, Soccer robots, Fuzzy controller, Multi agent.
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168 Task Planning for Service Robots with Limited Feedback
Authors: Chung-Woon Park, Jungwoo Lee, Jong-Tae Lim
Abstract:
In this paper, we propose a novel limited feedback scheme for task planning with service robots. Instead of sending the full service robot state information for the task planning, the proposed scheme send the best-M indices of service robots with a indicator. With the indicator, the proposed scheme significantly reduces the communication overhead for task planning as well as mitigates the system performance degradation in terms of the utility. In addition, we analyze the system performance of the proposed scheme and compare the proposed scheme with the other schemes.
Keywords: Task Planning, Service Robots, Limited Feedback, Scheduling
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167 Adaptive Motion Planning for 6-DOF Robots Based on Trigonometric Functions
Authors: Jincan Li, Mingyu Gao, Zhiwei He, Yuxiang Yang, Zhongfei Yu, Yuanyuan Liu
Abstract:
Building an appropriate motion model is crucial for trajectory planning of robots and determines the operational quality directly. An adaptive acceleration and deceleration motion planning based on trigonometric functions for the end-effector of 6-DOF robots in Cartesian coordinate system is proposed in this paper. This method not only achieves the smooth translation motion and rotation motion by constructing a continuous jerk model, but also automatically adjusts the parameters of trigonometric functions according to the variable inputs and the kinematic constraints. The results of computer simulation show that this method is correct and effective to achieve the adaptive motion planning for linear trajectories.
Keywords: 6-DOF robots, motion planning, trigonometric function, kinematic constraints
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166 Designing a Football Team of Robots from Beginning to End
Authors: Maziar A. Sharbafi, Caro Lucas, Aida Mohammadinejad, Mostafa Yaghobi
Abstract:
The Combination of path planning and path following is the main purpose of this paper. This paper describes the developed practical approach to motion control of the MRL small size robots. An intelligent controller is applied to control omni-directional robots motion in simulation and real environment respectively. The Brain Emotional Learning Based Intelligent Controller (BELBIC), based on LQR control is adopted for the omni-directional robots. The contribution of BELBIC in improving the control system performance is shown as application of the emotional learning in a real world problem. Optimizing of the control effort can be achieved in this method too. Next the implicit communication method is used to determine the high level strategies and coordination of the robots. Some simple rules besides using the environment as a memory to improve the coordination between agents make the robots' decision making system. With this simple algorithm our team manifests a desirable cooperation.
Keywords: multi-agent systems (MAS), Emotional learning, MIMO system, BELBIC, LQR, Communication via environment
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165 Formation Control of Mobile Robots
Authors: Krishna S. Raghuwaiya, Shonal Singh, Jito Vanualailai
Abstract:
In this paper, we study the formation control problem for car-like mobile robots. A team of nonholonomic mobile robots navigate in a terrain with obstacles, while maintaining a desired formation, using a leader-following strategy. A set of artificial potential field functions is proposed using the direct Lyapunov method for the avoidance of obstacles and attraction to their designated targets. The effectiveness of the proposed control laws to verify the feasibility of the model is demonstrated through computer simulations
Keywords: Control, Formation, Lyapunov, Nonholonomic
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164 Attribute Based Comparison and Selection of Modular Self-Reconfigurable Robot Using Multiple Attribute Decision Making Approach
Authors: Manpreet Singh, V. P. Agrawal, Gurmanjot Singh Bhatti
Abstract:
From the last decades, there is a significant technological advancement in the field of robotics, and a number of modular self-reconfigurable robots were introduced that can help in space exploration, bucket to stuff, search, and rescue operation during earthquake, etc. As there are numbers of self-reconfigurable robots, choosing the optimum one is always a concern for robot user since there is an increase in available features, facilities, complexity, etc. The objective of this research work is to present a multiple attribute decision making based methodology for coding, evaluation, comparison ranking and selection of modular self-reconfigurable robots using a technique for order preferences by similarity to ideal solution approach. However, 86 attributes that affect the structure and performance are identified. A database for modular self-reconfigurable robot on the basis of different pertinent attribute is generated. This database is very useful for the user, for selecting a robot that suits their operational needs. Two visual methods namely linear graph and spider chart are proposed for ranking of modular self-reconfigurable robots. Using five robots (Atron, Smores, Polybot, M-Tran 3, Superbot), an example is illustrated, and raking of the robots is successfully done, which shows that Smores is the best robot for the operational need illustrated, and this methodology is found to be very effective and simple to use.
Keywords: Self-reconfigurable robots, MADM, TOPSIS, morphogenesis, scalability.
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163 Posture Stabilization of Kinematic Model of Differential Drive Robots via Lyapunov-Based Control Design
Authors: Li Jie, Zhang Wei
Abstract:
In this paper, the problem of posture stabilization for a kinematic model of differential drive robots is studied. A more complex model of the kinematics of differential drive robots is used for the design of stabilizing control. This model is formulated in terms of the physical parameters of the system such as the radius of the wheels, and velocity of the wheels are the control inputs of it. In this paper, the framework of Lyapunov-based control design has been used to solve posture stabilization problem for the comprehensive model of differential drive robots. The results of the simulations show that the devised controller successfully solves the posture regulation problem. Finally, robustness and performance of the controller have been studied under system parameter uncertainty.
Keywords: Differential drive robots, nonlinear control, Lyapunov-based control design, posture regulation.
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162 Lane Changing and Merging Maneuvers of Carlike Robots
Authors: Bibhya Sharma, Jito Vanualailai, Ravindra Rai
Abstract:
This research paper designs a unique motion planner of multiple platoons of nonholonomic car-like robots as a feasible solution to the lane changing/merging maneuvers. The decentralized planner with a leaderless approach and a path-guidance principle derived from the Lyapunov-based control scheme generates collision free avoidance and safe merging maneuvers from multiple lanes to a single lane by deploying a split/merge strategy. The fixed obstacles are the markings and boundaries of the road lanes, while the moving obstacles are the robots themselves. Real and virtual road lane markings and the boundaries of road lanes are incorporated into a workspace to achieve the desired formation and configuration of the robots. Convergence of the robots to goal configurations and the repulsion of the robots from specified obstacles are achieved by suitable attractive and repulsive potential field functions, respectively. The results can be viewed as a significant contribution to the avoidance algorithm of the intelligent vehicle systems (IVS). Computer simulations highlight the effectiveness of the split/merge strategy and the acceleration-based controllers.
Keywords: Lane merging, Lyapunov-based control scheme, path-guidance principle, split/merge strategy.
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161 Novel Mobile Climbing Robot Agent for Offshore Platforms
Authors: Akbar F. Moghaddam, Magnus Lange, Omid Mirmotahari, Mats Høvin
Abstract:
To improve HSE standards, oil and gas industries are interested in using remotely controlled and autonomous robots instead of human workers on offshore platforms. In addition to earlier reason this strategy would increase potential revenue, efficient usage of work experts and even would allow operations in more remote areas. This article is the presentation of a custom climbing robot, called Walloid, designed for offshore platform topside automation. This 4 arms climbing robot with grippers is an ongoing project at University of Oslo.
Keywords: Climbing Robots, Mobile Robots, Offshore Robotics, Offshore Platforms, Automation, Inspection, Monitoring.
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160 Intelligent Condition Monitoring Systems for Unmanned Aerial Vehicle Robots
Authors: A. P. Anvar, T. Dowling, T. Putland, A. M. Anvar, S.Grainger
Abstract:
This paper presents the application of Intelligent Techniques to the various duties of Intelligent Condition Monitoring Systems (ICMS) for Unmanned Aerial Vehicle (UAV) Robots. These Systems are intended to support these Intelligent Robots in the event of a Fault occurrence. Neural Networks are used for Diagnosis, whilst Fuzzy Logic is intended for Prognosis and Remedy. The ultimate goals of ICMS are to save large losses in financial cost, time and data.
Keywords: Intelligent Techniques, Condition Monitoring Systems, ICMS, Robots, Fault, Unmanned Aerial Vehicle, UAV, Neural Networks, Diagnosis, Fuzzy Logic, Prognosis, Remedy.
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159 An AR/VR Based Approach Towards the Intuitive Control of Mobile Rescue Robots
Authors: Jürgen Roßmann, André Kupetz, Roland Wischnewski
Abstract:
An intuitive user interface for the teleoperation of mobile rescue robots is one key feature for a successful exploration of inaccessible and no-go areas. Therefore, we have developed a novel framework to embed a flexible and modular user interface into a complete 3-D virtual reality simulation system. Our approach is based on a client-server architecture to allow for a collaborative control of the rescue robot together with multiple clients on demand. Further, it is important that the user interface is not restricted to any specific type of mobile robot. Therefore, our flexible approach allows for the operation of different robot types with a consistent concept and user interface. In laboratory tests, we have evaluated the validity and effectiveness of our approach with the help of two different robot platforms and several input devices. As a result, an untrained person can intuitively teleoperate both robots without needing a familiarization time when changing the operating robot.
Keywords: Teleoperation of mobile robots, augmented reality, user interface, virtual reality.
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158 Walking Hexapod Robot in Disaster Recovery: Developing Algorithm for Terrain Negotiation and Navigation
Authors: Md. Masum Billah, Mohiuddin Ahmed, Soheli Farhana
Abstract:
In modern day disaster recovery mission has become one of the top priorities in any natural disaster management regime. Smart autonomous robots may play a significant role in such missions, including search for life under earth quake hit rubbles, Tsunami hit islands, de-mining in war affected areas and many other such situations. In this paper current state of many walking robots are compared and advantages of hexapod systems against wheeled robots are described. In our research we have selected a hexapod spider robot; we are developing focusing mainly on efficient navigation method in different terrain using apposite gait of locomotion, which will make it faster and at the same time energy efficient to navigate and negotiate difficult terrain. This paper describes the method of terrain negotiation navigation in a hazardous field.
Keywords: Walking robots, locomotion, hexapod robot, gait, hazardous field.
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157 Analytical Approach of the In-Pipe Robot on Branched Pipe Navigation and Its Solution
Authors: Yoon Koo Kang, Jung wan Park, Hyun Seok Yang
Abstract:
This paper determines most common model of in-pipe robots to derive its degree of freedom in order to compare with the necessary degree of freedom required for a system to move inside pipelines freely in order to derive analytical reason for losing control of in-pipe robots at branched pipe. DOF of most common mechanism in in-pipe robots can be calculated by considering the robot as a parallel manipulator. A new design based on previously researched in-pipe robot PAROYS has been suggested, and its possibility to overcome branched section has been simulated.
Keywords: Branched pipe, Degree of freedom, In-pipe robot, Parallel manipulator.
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156 A Universal Approach for the Intuitive Control of Mobile Robots using an AR/VR-based Interface
Authors: Juergen Rossmann, Andre Kupetz, Roland Wischnewski
Abstract:
Mobile robots are used in a large field of scenarios, like exploring contaminated areas, repairing oil rigs under water, finding survivors in collapsed buildings, etc. Currently, there is no unified intuitive user interface (UI) to control such complex mobile robots. As a consequence, some scenarios are done without the exploitation of experience and intuition of human teleoperators. A novel framework has been developed to embed a flexible and modular UI into a complete 3-D virtual reality simulation system. This new approach wants to access maximum benefits of human operators. Sensor information received from the robot is prepared for an intuitive visualization. Virtual reality metaphors support the operator in his decisions. These metaphors are integrated into a real time stereo video stream. This approach is not restricted to any specific type of mobile robot and allows for the operation of different robot types with a consistent concept and user interface.
Keywords: 3-D simulation system, augmented reality, teleoperation of mobile robots, user interface.
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155 Fuzzy Separation Bearing Control for Mobile Robots Formation
Authors: A. Bazoula, H. Maaref
Abstract:
In this article we address the problem of mobile robot formation control. Indeed, the most work, in this domain, have studied extensively classical control for keeping a formation of mobile robots. In this work, we design an FLC (Fuzzy logic Controller) controller for separation and bearing control (SBC). Indeed, the leader mobile robot is controlled to follow an arbitrary reference path, and the follower mobile robot use the FSBC (Fuzzy Separation and Bearing Control) to keep constant relative distance and constant angle to the leader robot. The efficiency and simplicity of this control law has been proven by simulation on different situation.
Keywords: Autonomous mobile robot, Formation control, Fuzzy logic control, Multiple robots, Leader-Follower.
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154 Pipelines Monitoring System Using Bio-mimetic Robots
Authors: Seung You Na, Daejung Shin, Jin Young Kim, Seong-Joon Baek, Bae-Ho Lee
Abstract:
Recently there has been a growing interest in the field of bio-mimetic robots that resemble the behaviors of an insect or an aquatic animal, among many others. One of various bio-mimetic robot applications is to explore pipelines, spotting any troubled areas or malfunctions and reporting its data. Moreover, the robot is able to prepare for and react to any abnormal routes in the pipeline. Special types of mobile robots are necessary for the pipeline monitoring tasks. In order to move effectively along a pipeline, the robot-s movement will resemble that of insects or crawling animals. When situated in massive pipelines with complex routes, the robot places fixed sensors in several important spots in order to complete its monitoring. This monitoring task is to prevent a major system failure by preemptively recognizing any minor or partial malfunctions. Areas uncovered by fixed sensors are usually impossible to provide real-time observation and examination, and thus are dependent on periodical offline monitoring. This paper proposes a monitoring system that is able to monitor the entire area of pipelines–with and without fixed sensors–by using the bio-mimetic robot.
Keywords: Bio-mimetic robots, Plant pipes monitoring, Mobile and active monitoring.
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153 Social Assistive Robots, Reframing the Human Robotics Interaction Benchmark of Social Success
Authors: Antonio Espingardeiro
Abstract:
It is likely that robots will cross the boundaries of industry into households over the next decades. With demographic challenges worldwide, the future ageing populations will require the introduction of assistive technologies capable of providing, care, human dignity and quality of life through the aging process. Robotics technology has a high potential for being used in the areas of social and healthcare by promoting a wide range of activities such as entertainment, companionship, supervision or cognitive and physical assistance. However such close Human Robotics Interaction (HRI) encompass a rich set of ethical scenarios that need to be addressed before Socially Assistive Robots (SARs) reach the global markets. Such interactions with robots may seem a worthy goal for many technical/financial reasons but inevitably require close attention to the ethical dimensions of such interactions. This article investigates the current HRI benchmark of social success. It revises it according to the ethical principles of beneficence, non-maleficence and justice aligned with social care ethos. An extension of such benchmark is proposed based on an empirical study of HRIs conducted with elderly groups.
Keywords: HRI, SARs, Social Success, Benchmark, Elderly care.
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152 Minimizing of Target Localization Error using Multi-robot System and Particle Filters
Authors: Jana Puchyova
Abstract:
In recent years a number of applications with multirobot systems (MRS) is growing in various areas. But their design is in practice often difficult and algorithms are proposed for the theoretical background and do not consider errors and noise in real conditions, so they are not usable in real environment. These errors are visible also in task of target localization enough, when robots try to find and estimate the position of the target by the sensors. Localization of target is possible also with one robot but as it was examined target finding and localization with group of mobile robots can estimate the target position more accurately and faster. The accuracy of target position estimation is made by cooperation of MRS and particle filtering. Advantage of usage the MRS with particle filtering was tested on task of fixed target localization by group of mobile robots.
Keywords: Multi-robot system, particle filter, position estimation, target localization.
Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1292
|
Talk:Just Dance 2018/@comment-30297252-20170912111016/@comment-28121720-20170914234635
And lets us not forget Rockabye, a song about Single Mothers.
|
Socket
FIG. 1 is a top plan view of a socket showing our new design;
FIG. 2 is a front elevational view thereof;
FIG. 3 is a right side view thereof;
FIG. 4 is a rear elevational view thereof;
FIG. 5 is a left side view thereof;
FIG. 6 is a bottom plan view thereof;
FIG. 7 is a perspective view thereof;
FIG. 8 is a second perspective view thereof; and,
FIG. 9 is a third perspective view thereof.
CLAIM The ornamental design for a socket, as shown.
|
MAINT: Test old and new Sphinx versions
This is a proposal-by-PR:
Test the oldest supported sphinx in tests (I don't think it's being done currently?)
Test the latest sphinx dev version (should help catch stuff like #1404)
Refactor test install step into a script (DRY)
No idea if this has been discussed so far but it seemed quick enough to just do it and see what people thought :)
FYI we use a dev test against NumPy/SciPy/matplotlib etc. in MNE-Python and find bugs in their dev branches fairly frequently. As a maintainer it's easy enough to know when a dev failure can be safely ignored for the time being...
Looks like it's already showing a problem with the pyproject.toml / minimum reqs, assuming I'm interpreting correctly that sphinx==4.2 is meant to be the minimum required version:
ERROR: Cannot install pydata-sphinx-theme, pydata-sphinx-theme[doc]==0.13.4.dev0 and sphinx==4.2 because these package versions have conflicting dependencies.
The conflict is caused by:
The user requested sphinx==4.2
pydata-sphinx-theme[doc] 0.13.4.dev0 depends on sphinx>=4.2
ablog 0.11.0rc2 depends on sphinx>=5.0.0
I'll bump the minimum to 5.0 in this PR but someone should make sure that's the right thing to do!
... I guess it's just a min required for the doc run, so I'll revert that part. But it means the doc run will never test the oldest sphinx version (maybe okay?)
... also added concurrency to the GitHub actions build so that pushing repeated commits (like I did here) cancels previous ones in the same PR
thank you @larsoner this was on my mental TODO list (I hadn't managed to even open an issue about it yet)
note to self: the sphinx dev dependency clash is coming from myst-nb which requires sphinx < 6
note to self: the sphinx dev dependency clash is coming from myst-nb which requires sphinx < 6
@choldgraf looks like the last release was in April, might be time for another that doesn't pin to an ancient Sphinx version :)
All green other than macos taking ages to start. Old (now 5.0) and dev versions now tested in both pytest and doc-build jobs (when using the branch from https://github.com/jdillard/sphinx-sitemap/pull/70 which seems okay until they cut a new version), ready for review/merge from my end
|
Nguyen Du Park Residences Ltd
5 contracts, total value $1,186,074.33
Procurement methods: limited 5 contracts, 100.00%,
Categories
Category Contracts Count Total Contract Value
Lease and rental of property or building 3 $736,776.09
Residential rental 2 $449,298.24
Agencies
Agency Contracts Count Total Contract Value
Austrade 5 $1,186,074.33
Contracts
Contract Notice Number Contract Description Total Contract Value Agency Contract Start Date Supplier
164607-A2 Residential lease: Ho Chi Minh City $573,407.37Austrade 2007-11-21 Nguyen Du Park Residences Ltd
3306951-A1 Residential Lease Ho Chi Minh City $328,458.24Austrade 2015-10-31 Nguyen Du Park Residences Ltd
1195491 Residential Lease Agreement Renewal: Ho Chi Minh City $124,143.00Austrade 2012-11-21 Nguyen Du Park Residences Ltd
881941 Residential Lease - Vietnam $120,840.00Austrade 2012-11-21 NGUYEN DU PARK RESIDENCES LTD
2726821 Renewal of Residential Lease Agreement $39,225.72Austrade 2014-11-21 Nguyen Du Park Residences Ltd
|
undefined output in a simple JavaScript
I am very new to all of this and I recently started learning JavaScript. To test my learning I made this simple script, Rock, paper, and scissors. It is something very similar to Codecademy project. The problem I am having is with the output, which comes out as 'undefined' and I can't figure out, what's giving this output, can someone please help?
const getUserChoice = userInput => {
userInput = userInput.toLowerCase();
if (userInput === 'rock') {
return 'Rock'
} else if (userInput === 'paper') {
return 'Paper' }
else if (userInput === 'scissors') {
return 'Scissors'}
else if (userInput === 'bomb') {
return 'Bomb'
} else {
return 'Please input a valid choice!'
}
}
const getComputerChoice = () => {
const numbers = (Math.floor(Math.random() * 3))
switch (numbers) {
case 0 : return "Rock";
break;
case 1 : return "Paper";
break;
case 2 : return "Scissors";
break;
}
}
const determineWinner = (userChoice, computerChoice) => {
if (userChoice === computerChoice) {
return 'It\'s a tie!!';
}
if (userChoice === 'rock') {
if (computerChoice === 'paper') {
return 'The Computer has won the game!!';
} else {
return 'Congratulation You have won the game!!';
}
}
if (userChoice === 'scissors') {
if (computerChoice === 'rock') {
return ('The Computer has won the game!!');
} else {
return ('Congratulations You have won the game!!');
}
}
if (userChoice === 'scissors') {
if (computerChoice === 'paper') {
return 'Cogratulations You have Won the game!!';
} else {
return 'The Computer has won the game!!';
}
}
if (userChoice === 'bomb') {
return 'Congratulation you Won!!'
}
};
const playGame = () => {
var userChoice = getUserChoice('rock')
var computerChoice = getComputerChoice()
console.log('You picked: ' + userChoice);
console.log('The computer picked: ' +computerChoice)
console.log(determineWinner(userChoice, computerChoice));
}
playGame()
What is undefined? Please show your whole output. If the method does not reach a return, it will return undefined, btw
Hey, apparently someone figured it out. Thanks for the help though!!
Your userChoice and computerChoice are both capitalized. You are checking them against lowercase strings. Also, you're checking for scissors twice and not checking for paper.
const getUserChoice = userInput => {
userInput = userInput.toLowerCase();
if (userInput === 'rock') {
return 'Rock'
} else if (userInput === 'paper') {
return 'Paper'
} else if (userInput === 'scissors') {
return 'Scissors'
} else if (userInput === 'bomb') {
return 'Bomb'
} else {
return 'Please input a valid choice!'
}
}
const getComputerChoice = () => {
const numbers = (Math.floor(Math.random() * 3))
switch (numbers) {
case 0:
return "Rock";
break;
case 1:
return "Paper";
break;
case 2:
return "Scissors";
break;
}
}
const determineWinner = (userChoice, computerChoice) => {
if (userChoice === computerChoice) {
return 'It\'s a tie!!';
}
if (userChoice === 'Rock') {
if (computerChoice === 'Paper') {
return 'The Computer has won the game!!';
} else {
return 'Congratulation You have won the game!!';
}
}
if (userChoice === 'Paper') {
if (computerChoice === 'Rock') {
return ('The Computer has won the game!!');
} else {
return ('Congratulations You have won the game!!');
}
}
if (userChoice === 'Scissors') {
if (computerChoice === 'Paper') {
return 'Cogratulations You have Won the game!!';
} else {
return 'The Computer has won the game!!';
}
}
if (userChoice === 'Bomb') {
return 'Congratulation you Won!!'
}
};
const playGame = () => {
var userChoice = getUserChoice('rock')
var computerChoice = getComputerChoice()
console.log('You picked: ' + userChoice);
console.log('The computer picked: ' + computerChoice)
console.log(determineWinner(userChoice, computerChoice));
}
playGame()
You only check for Rock and Sciccors in your determine winner method
const getUserChoice = userInput => {
userInput = userInput.toLowerCase();
if (userInput === 'rock') {
return 'Rock'
} else if (userInput === 'paper') {
return 'Paper' }
else if (userInput === 'scissors') {
return 'Scissors'}
else if (userInput === 'bomb') {
return 'Bomb'
} else {
return 'Please input a valid choice!'
}
}
const getComputerChoice = () => {
const numbers = (Math.floor(Math.random() * 3))
switch (numbers) {
case 0 : return "Rock";
break;
case 1 : return "Paper";
break;
case 2 : return "Scissors";
break;
}
}
const determineWinner = (userChoice, computerChoice) => {
if (userChoice === computerChoice) {
return 'It\'s a tie!!';
}
if (userChoice === 'Rock') {
if (computerChoice === 'Paper') {
return 'The Computer has won the game!!';
} else {
return 'Congratulation You have won the game!!';
}
}
if (userChoice === 'Scissors') {
if (computerChoice === 'Rock') {
return ('The Computer has won the game!!');
} else {
return ('Congratulations You have won the game!!');
}
}
if (userChoice === 'Paper') {//You mean paper here
if (computerChoice === 'Rock') {
return 'Cogratulations You have Won the game!!';
} else {
return 'The Computer has won the game!!';
}
}
if (userChoice === 'bomb') {
return 'Congratulation you Won!!'
}
};
const playGame = () => {
var userChoice = getUserChoice('rock')
var computerChoice = getComputerChoice()
console.log('You picked: ' + userChoice);
console.log('The computer picked: ' +computerChoice)
console.log(determineWinner(userChoice, computerChoice));
}
playGame()
Welcome to programming then! Comment above is true - when you post, do try to be really specific about exactly what problem you're seeing. Makes it much easier to help you.
With that said though, I think from looking at the code above I can see what you mean. It's often helpful when debugging to walk through how your code will run:
playGame() is called
getUserChoice is called with the parameter 'rock'
userChoice is assigned 'Rock' *note uppercase
determineWinner is called with 'Rock' as userChoice
'Rock' does not trigger ANY of the if statements, and determineWinner does not return anything
So from following those steps its actually quite easy to see why determineWinner is undefined when you log it out... it doesn't return anything. The point of your getUserChoice function appears to be standardizing the inputs. But those standardized inputs are not being used properly later. You could consider storing those possible values in an array and then returning the lowercase value from that function?
Hope this helps - good luck!
Hey, thanks for the help and from next time I will make sure to keep this in mind before posting something :)
The values you chose are capitalized, so, for example, you want to check if userChoice === 'Rock' instead of userChoice === 'rock'
Fixed:
const getUserChoice = userInput => {
userInput = userInput.toLowerCase();
if (userInput === 'rock') {
return 'Rock'
} else if (userInput === 'paper') {
return 'Paper' }
else if (userInput === 'scissors') {
return 'Scissors'}
else if (userInput === 'bomb') {
return 'Bomb'
} else {
return 'Please input a valid choice!'
}
}
const getComputerChoice = () => {
const numbers = (Math.floor(Math.random() * 3))
switch (numbers) {
case 0 : return "Rock";
break;
case 1 : return "Paper";
break;
case 2 : return "Scissors";
break;
}
}
const determineWinner = (userChoice, computerChoice) => {
if (userChoice === computerChoice) {
return 'It\'s a tie!!';
}
if (userChoice === 'Rock') {
if (computerChoice === 'Paper') {
return 'The Computer has won the game!!';
} else {
return 'Congratulation You have won the game!!';
}
}
if (userChoice === 'Scissors') {
if (computerChoice === 'Rock') {
return ('The Computer has won the game!!');
} else {
return ('Congratulations You have won the game!!');
}
}
if (userChoice === 'Scissors') {
if (computerChoice === 'Paper') {
return 'Cogratulations You have Won the game!!';
} else {
return 'The Computer has won the game!!';
}
}
if (userChoice === 'Bomb') {
return 'Congratulation you Won!!'
}
};
const playGame = () => {
var userChoice = getUserChoice('rock')
var computerChoice = getComputerChoice()
console.log('You picked: ' + userChoice);
console.log('The computer picked: ' +computerChoice)
console.log(determineWinner(userChoice, computerChoice));
}
playGame()
|
related to Marble Maze Game
I am working on the project of marble maze game in j2me.I am facing the problem related to the movement and controlling of the ball.
The code i am using is
private SensorConnection sensor;
Data[] data;
double value[] = new double[3];
double PreValueX1, PreValueX2, PreValueY1, PreValueY2;
double CurrentValX, CurrentValY;
int ballX,ballY;
Sensor = (SensorConnection) Connector.open("sensor:acceleration");//To open connection
public void run() {
while(true){
try {
data = compass.getData(1);/
} catch (IOException ex) {
ex.printStackTrace();
}
for (int i = 0; i < data.length - 1; i++) {
value[i] = data[i].getDoubleValues()[0];/Get data For X and Y axis
}
CurrentValX = value[0];
CurrentValY = value[1];
if (CurrentValX < PreValueX1) {
left = false;
right = true;
} else if (CurrentValX > PreValueX1) {
left = true;
right = false;
}
if (CurrentValY < PreValueY1) {
down = false;
up = true;
} else if (CurrentValY > PreValueY1) {
down = true;
up = false;
}
if (right == true) {
ballX += 10;
} else if (left == true {
ballX -= 10;
}
if (down == true ) {
ballY += 10;
} else if (up == true ) {
ballY -= 10;
}
CurrentValY = PreValueY1;
CurrentValX = PreValueX1;
dodraw();
repaint();
}
//Function used to draw the image of ball
dodraw(){
ballSprite.setPosition(ballX, ballY);
ballSprite.paint(g);//Graphics==g
}
Now the problem here i am facing is if I decrement the speed
eXample :-by writting ballx+=4;ballY+=4 OR ballx-=4;ballY-=4,Then I get the control over my ball
And if my keep my speed as 10 then i don't get control over my ball.
In short i can able to get only one thing speed or control.
But i want to do both speed and control.
Fix your code formatting. Also, what mobile OS?
For a more realistic behaviour, you should store the motion vector of your marble and modify it each frame according to the sensor data and add it to the marble's position every frame. .
You could go the full simulation way, using the equations for Kinmatics to calculate your marble's speedvector.
|
Hose coupling
HOSE COUPLING Filed Dec. 28. 1940 ya j@ the end of the hose Patented Nov. 3, 1942 UNITED STATES PATENT OFFICE HosE COUBLING Arthur L. Parker,cleveland, ohio Application December 28, 1940, Serial No. 372,158
Claims.
The present invention relates to new and useful improvements in couplings for joining fluid conduits, and more particularly to improvements in a coupling for connecting hose sections to various types of conduits.
According to the present invention, the coupling generally includes a clamping assembly for one end of the hose section. This clamping'assembly has associated therewith an inner tubular portion on which the end of the hose section is placed and against which the hose iis clamped.This tubular portion extends beyond the clamping assembly and is adapted tobe clamped in communication with a suitable conduit so that communication between the hose section and the conduit is afforded through the tubular portion.
An object of the present invention is to provide a coupling of the above type which is constructed and arranged so that the hose section can be quickly connected to a conduit without twisting either the conduit orthe hose section.
A further object of the invention is to provide a coupling of the above type wherein a tubular member affording communication between the hose section and the connected conduit is adapted to be clamped in communication with the conduit by means which eliminates the hecessityof twisting either the conduit or the hose section.
A still further object of the invention is to provide a coupling of the above type which is simple in construction and which affords fluid tight communication with a minimum number of parts.
end of the hose. The sleeve member I3 may also be provided with a wrench engaging'portion I1.
A clamping member in the form of a y sleeve I8 is threaded ly connected tothe outer threads I5 on the sleeve member I3 and is provided at the free end thereof with an inwardly directed portion I9 having an inclined inner camming surface 20. l When the sleeve members I3, I8 .are tightened relative to one another, the camming surface 20 is adapted to engage one edge of a split clamping ring 2 I, the opposite edge of which abutsagainst the end of the sleeve member I3. Thus, tightening of the sleeve members I3, I8 will effect a tight clamping of the hose` against the tubular member .by the clamping ring 2| but clamping movement of the sleeve I8 is limited so as to prevent excessive contraction of the ringI2| and resultant damage to the hose@ The inner threads I4 on the sleeve member I3 are for the purpose of providing an additional gripping surface between the clamping assembly and the hose in that compression of the hose by the clamping ring 2| will tend to force the hose material into engagement with the threads I4.
A s1eeve 22 surrounds the tubular member II and is provided at .one end thereof with an outwardly directed' ange 23. which is disposed betweenthe inner'end of the hose I0 and the inner surface of the shoulder I6 onthe sleeve member I3. The opposite end of the sleeve 2,2 is provided with an outwardly directed head or The above and other objects of the invention shoulder portion 24 which is provided with a more fully pointed out.
In the accompanying drawing:
Figure 1 is a longitudinal section showing one form of coupling with the hose section secured in communication with a conduit.
Figure 2 is a similar longitudinal section showing a modified form of coupling.
' Figure 3 is a similar longitudinal section showing a still furthermodication.
Referring more in detail to the accompanying drawing, and particularly to Figure l, one end of a flexible hose I0 is placed over one end of a tubular member Il, the opposite end of which extends beyond the end ofis provided with an outwardly ared end portion I2. A sleeve member I3 is disposed around ternal and external threads I4, I5, respectively,
Y will in part be obvious and will be hereinafter 40 which is in communication with the tubular member II and with the hose section I0.The adapter 26 may be provided with external threads 21 for connection with a suitable ii uid conduit. The adapter 26 is also provided with external threads 28 which are adapted to thread the hose and 24 on the sleeve 22.
I0 and is provided with inedly engage internal threads on a clamping nut member 29. The nut member 29 is provided with an inwardly directed shoulder 3Il which is adapted to engage the shoulder or head portion The adjacent end of the adapter ing surface 3| against which the inner surface of the ared end I2 of the tubular member II" is adapted -to beclamped when the nut member and with an inwardly extending radial shoulder 29 is tightened relative to the adapter 26.
26 is provided with an inclined clamp sleeve v2a terminates short I -but is provided with the head or shoulder por extending annular. flange adapter 26 by tightening the nut 2l relative to the adapter. There is a metal to metal contact between the shoulders 24 and 3l so that the nut29 can be tightened without turning or twisting of the hose I or the adapter-2i. The i lange 23 on the sleeve v 22, being disposed within -the shoulder I6 on the sleeve member Il, serves to prevent separation of the clamping assembly for the hose section and also the clamping assembly for the end of the tubular member II.
In the modified form of the invention shown in Figure 2, the tubular member I Ia is formed integral with the inwardly directed shoulder ISa on the sleeve member lia. The sleeve member I8 threaded ly engages the outer threads I5a on the sleeve member Ila and the inner threads on the sleeve member I aare omitted in this form A ofthe invention. Tlghteningof the sleeve members I8, I3a relative to one another will e'ect clamping of the hose between the clamping ring 2| and the adjacent portion 'of the tubular member I I a. Since the tubular portion IIa is formed integral with the shoulder lia, the intermediate of the shoulder Iia tion 24a y which is clamped by the shoulder 3l on the nut 29,. as described in connection with the form of the invention shown in Figure 1. The flared -end I2a of the tubular member IIa is -clampedbetween the inclined surfaces at the end of the adapter 26 and the head member 24a.
In the form of the invention shown in Figure 3, the tubular member II bis shaped intermediate the ends thereof to provide an outwardly 32 whichis disposed between the inner end' of shoulder IIb on the sleeve memberI3b. The ia red -end I 2b of the tubular member I Ib is clamped betweenthe inclined surfaces on the adapter and on the head portion 24a, as described in connection with Figure 2. 'Ihe tubular member IIb is separate from the sleeve member- |311 but the fia nge 32 and the clampedend I2b serve to prevent separation of the hose from the conduit which maybe secured to the adapter 26.
From the foregoing description, it will be seen that the present invention provides a highly eficient coupling for clamping a ilexiblehose section to another il uid conduit. The clamping means for the end ofthe flexible hose includes a tubular portion which may be integral withthe clamping means .or separate therefrom. 'Ihe the hose Il and thea tubular member within the hose section against hose is clamped against the outer surface of the tubular'portion which provides il uidcommunication between the hose and an adapter which may be connected to another fluid conduit. One' end of the tubular portion extends outside of the -hose clamping means and is clamped in engage, ment with the conduit adapter. yThe clamping.
means for the hose and the clamping means for the outwardly extending end of the tubular portion are prevented from separating in the various ways illustrated. The clamping nut for clamping the flared end of the tubular portion within which the end of relative to the intermediate sleeve and It is to be clearly understood that minor changes in the details of construction and arrangement of parts may be made without departing from the scope'of the invention as set forth in the appended claims. t
I claim:
1. A coupling for joining a hose section to a fluid conduit comprising a sleeve member within which the end of the hose section is inserted, said sleeve member having an inwardly directed portion adjacent the inner endof the hose-section,
` ing the hose section against the tubular portion,
a clamping sleeve surrounding the flared end *of the tubular portion and having a tapered clamping surface engaging the outer face of theiiax'edV end of the tubular portion, the inner face of the ilared end ofthe tubular portion being adapted to abut against a tapered clamping surface on the fluid conduit to which'the hose is attached and a clamping nut engaging said ii uid conduit and having an inwardly directed shoulder engaging the shoulder on the clamping sleeve for clamping thea red end of the tubular portion between said clamping surfaces.
2'. A coupling for joining a hose section to another il uid conduit,comprising a sleeve member v within which the end of the hose section is adapted to be inserted v and said sleeve member having an inwardly4directed flange adjacent the inner end of the hose section, means providing a tubular portion disposed within said iia nge and extending within the' hose section and against which the hose section is adapted to be clamped, said tubular portion extending outwardly beyond the flange and the hose section and having an outwardly flared end, means cooperating with said sleeve member for clamping the hose section, a clamping sleeve surrounding the outer surface of the ilared end of said tubular portion and having a tapered clamping surface engaging the outer surface of the ilared end of the tubular portion and having at the opposite end thereof an outwardly directed shoulder, the inner surface of the -iia red end of said tubular portion being adapted to abut against a surface on the other il uid conduit, and a clamping nut engaging the said other il uid conduit and having an inwardly directed shoulder engaging the shoulder on said clamping sleeve for clamping the ared endof the tubular portion between said clamping surfaces and the engagement between said shoulders serving to prevent turning or twisting of the hose section during clamping of the flared end ofV the tubular portion.
3. A coupling for joining a hose section to another ii uid conduit,comprising a sleeve member l the hose section is adapted to be clampedand said sleeve member having an inwardly directed ange adjacent the inner end of the hose section, means providing a tubular portion integral with the flange on said sleeve member and extending within the hose section, said tubular portion extending beyond the end of the hose section and the flange and having tapered clamping V an outwardly iia red end, a clamping sleeve surrounding the outer surface of the ared end of said tubular portion and having a tapered clamping surface engaging the outer surface of the flared end of the tubular portion and having at the opposite end thereof an outwardly directed shoulder, the inner surface of the ared end of said tubular portion being adapted toa but against a tapered clamping surface on the other ii uid conduit, and a clamping nut engaging the said other fluid conduit and having an inwardly directed shoulder engaging the shoulder on said clamping sleeve for clamping thea red end of the tubular portion between said clamping surfaces and the engagement between said shoulders serv having an inwardly directed shoulder engaging' the shoulder on said clamping sleeve for lclampingthe flared end of the tubular portion between said clamping surfaces andthe engagement between said shoulders serving to prevent turning or twisting of the hose section during clamping of the flared end of the tubular portion.
5. A coupling for joining a hose section to another uid conduit,comprising a sleeve member within which the end of the hose section is adapted to be clamped, said sleeve member having to prevent turning or twisting of the hose section during clamping of the ared end of the tubular portion.
4. A coupling for joining a hose section to another ii uid conduit,comprising a sleeve member within which the end of the hose member is adapted to be clamped and said sleeve member having an'inwardly directed flange adjacent the inner end of the hose section, means providing a tubular portion within said ange and extending within the hose section,said tubular portion extending beyond the flange and the hose section and having an outwardly ared end, said tubular portion being folded upon itself to provide an annular ring extending outwardly and disposed between said ange andthe end of the hose section, a clamping sleeve surrounding the outer surface of the flared end of said tubular portion and having a tapered clamping surface engaging the outer surface of the flared end of the tubular portion and having at the opposite end thereof an outwardly directed shoulder, the inner surface of the flared end of said tubular portion being adapted to abut against a tapered clamping surface on `the other uid conduit, and a clamping nut engaging the said other uid conduit and ing an inwardly directed ange adjacent the inner end of the hose section, an'independent tubular member located within said flange and extending within the end of the hose section. said tubular member extending outwardly beyond the flange and the hose section and having an outwardly iia red end, a clamping sleeve surrounding the outer surface of the ared end of said tubular member and having atone end thereof a tapered clamping surface engaging the outer surface ofthe :dared end of the tubular member and having at the opposite end thereof an outwardly directed shoulder disposed between the end ofthe hose section and the ange on said sleeve member,`said clamping sleeve having an outwardlydirected shoulder located intermediate the ends thereof,
the inner surface of the ared end of said tubular f,
member being adapted to abut against a tapered clamping surface on theother uid conduit, and a clamping nut engaging the said other huidconduit and' having an inwardly directed shoulder engaging the intermediate shoulder on said clamping sleeve for clamping the iia red end of the tubular member between said clamping surfaces and the engagement between the intermediate shoulder on said clamping sleeve andthe shoulder on said clamping nut serving to prevent turning l or twisting of the hose section' during clamping of the flared end of the tubular member.
' ARTHUR L. PARKER.
|
The code you mentioned is not in my global.js or globalnav.js. Here is the link to my globalnav.js:
http://community.wikia.com/wiki/User:MeerkatMario/globalnav.js
And for my global.js:
http://community.wikia.com/wiki/User:MeerkatMario/global.js
|
Board Thread:General Discussion/@comment-27234079-20180207135359/@comment-27234079-20180226204204
Christl Rosebud wrote: Darn, still needa watch Black Panther i hear it's really freakin great
Also, Batman F'ing approves of that meme
It's really great. Hoping to see it again this weekend
|
Talk:Gold Magnet (Plantlanders)/@comment-5760976-20151219222841/@comment-5676790-20151219223444
Oh! Hah. I'll rename the page.
|
#!/usr/bin/env python
"""
script to sample lines from a file.
may 29 2014
dent earl, dearl a soe ucsc edu
"""
import os
import random
from argparse import ArgumentParser
def InitializeArguments(parser):
parser.add_argument('input', help='File to sample')
parser.add_argument('-n', '--number_of_samples', type=int,
help='Number of lines to sample')
def CheckArguments(args, parser):
if args.input is None:
parser.error('Specify input file to sample as an argument.')
if not os.path.exists(args.input):
parser.error('Input file %s does not exist!' % args.input)
if args.number_of_samples is None:
parser.error('Specify --number_of_samples')
def GetFileLength(filename):
i = 0
with open(filename) as f:
for i, line in enumerate(f, 1):
pass
return i
def PrintSamples(samples, args):
with open(args.input) as f:
for i, line in enumerate(f, 1):
if samples is None:
print line
else:
if i in samples:
line = line.strip()
print line
def main():
parser = ArgumentParser()
InitializeArguments(parser)
args = parser.parse_args()
CheckArguments(args, parser)
length = GetFileLength(args.input)
if not length:
return
if length < args.number_of_samples:
PrintSamples(None, args)
else:
samples = random.sample(xrange(length), args.number_of_samples)
PrintSamples(samples, args)
if __name__ == '__main__':
main()
|
Orthodontic appliance
Aug- 2, 1932 s. R. ATKINSON 1,869,733
ORTHODONTIA APPLIANCE Filed Jan. 25, 1950 www fg Patented Aug. 2, 1932`{EPL'SlNCER BJ. ATKINSON, QF PASADENA, CALIFORNIA olrrnononrroAPPLIANGE Application led January 25,v 1930. Serial No. 423,491.
My invention relates toan orthodontic ap-v pliancev and h as for its principal object, theV provision of relatively simple and efhcient means that is associated with the tooth encircling band and the archrwire, forlengthening the latter from time to time as conditions require.
Further objects of my invention are, to provide an arch wire adjusting device that is relatively simple in construction, inexpensive of manufacture, capable of being readily and accurately adjusted and further, to provide a device of the character referred to that will eliminate the necessity for the 'f5' cutting of threads onthe ends ofthe arch wire and which latter'in some instances are very small.
Further objects of my invention are, to provide a lengthening attachment for the ends of arch wires that will firmly hold said arch wires against rotation when properly secured to the tooth b-ands, further, to provide a device of the character referred to that will form a strong and substantial adjustable connection between the end of the arch wire and tooth encircling band and further, to provide an attachment that willVact automatically in holding the adjusting nut, that forms a part ofthe device against rotation while in service. j
lith the foregoing and other objects in view, my invention consists in certain novel features of construction and arrangement of parts that will hereinafter be more fully de-` scribed and claimed and illustrated in the accompanying drawing, in which: Y
Fig. 1 is an elevational view of a tooth band and showing my improved arch wire adjusting device applied thereto.
Figj2 is an enlarged section taken through the center of the adjustinglattachment.
Y Fig. 3 is a cross section on the line 3 3 of Fig. 2.
Fig. t is a cross sectional view v similar to Fig. 3
and showing a modified form of the attachment.
Fig. 5 is a longitudinal section of a modified form of the threaded sheath that is applied to the end of the arch wire.
Fig. 6 is a plan view of a further modied form of the threaded arch wire engaging sheath.
Fig. 7 is a cross sectional view of the arch wire sheath that forms apart ofl my in'- vention. y Y
Referring by numerals to the accompanying drawing which illustrate a practical emi bodiment of my invention, 10 designates the tooth band ofan orthodontic appliance, the v.
ends of which l bands are connected by the usual threaded pin and boltandvpermanently secured to said band, preferably at a point directly opposite the connected ends thereof is a tubular member 11, that receives the end of the usual arch wire W. l
@ne end of a substantially channel shaped sheath 12 is permanently secured, preferably b-y solder to the end of the arch v wire W that projects through the tube 1'1 and formed on the outer circular face ofthe sheath 12 are screw threads 13. This sheath extends entirely throughthe tube l1 and as said sheath is somewhat longer than the tube, the ends of said sheath project beyond the ends of said tube.
Screw-seated on' one of the projecting ends of the sheath is a nut 14that bears directly against the corresponding end of tube 1l..
In order to prevent rotation of the arch wire W within the tube the latter is provided on its inner surface with a longitudinally disposed flat face 15 that is engaged by the exposed face of that portion of the wire lV that occupies the sheath l2.
Sheath ,12 is formed of metal having a certain degree of resiliency andthe side portions of the end of said sheath that receives the nut 14 are spread apart a slight distance, as illustrated in Fig. 7 and the resulting tension acts to friction ally engage the nut so as to resist rotation thereof and thus said nut is retained against accidental removal.
Y When my improved orthodontic appliance is in use the parts are assembled, as illusvtrated in Figs. 1, 2 and 3 and the arch wire W 's retained against rotation in the tube 11 by the engagement of the exposed facel of that portion of the wire that occupies the sheath,against the flat face 15 within tube 11.
The nut 14 normally bears against the end of tube 11 and in order tolengthen the arch wire the nut 14 may be rotated on the threaded exterior of sheath 12, thereby drawing the same through the tube 11 andas the Wire IV is soldered to said sheath, said wire will be drawnlengthwise through the tube 11, thus accomplishing the desired results.
In some instances the sheath is provided with oppositely disposed flat faces, which engage correspondingly arranged flat faces within the tube11, thus holding the sheath and arch wire against rotation and Where such construction is employed, the rounded side faces of the sheath between the flat faces thereon, are threaded for the reception of the adjusting nut (see Fig. 4).
In Fig. 5, I have illustrated a modified arrangement wherein a solid wall 16 is formed at one end of the sheath 12. Where such construction is employed, the end of the arch wire `W abuts directly against the end wall 16, thereby eliminating the necessity for soldering the sheath tothe arch wire.
In Fig. 6 I have illustrated a modified form of the sheath, wherein alongitudinally disposed slot 17 is formed in the bottom of said sheath and the portions of the sheath to the sides of said slot are bent apart so as to produce tension when the parts are forced toward each other and such tension is effective in exerting pressure against the nut that is mounted on the sheath so as to prevent accidental unscrewing of said nut.
Thus it will be seen that I have provided an arch wire holding and adjusting device that is relatively simple in construction, inexpensive of manufacture and very effective in performing the functions for which it is intended.
The provision of a threaded sheath for that portion of the arch wire that passes through the tube on the tooth band, eliminates threading ofthe arch wire and the formation of a. flat face on the interior of the tube for engagement with one of the faces of the arch wire effectuallyprevents rotation of the wire relative to the tube.
The device is capable of very accurately adjusting the length of the arch wire and the sheath is constructed so as to counteract any tendency of accidental unscrewing of the adjusting nut.
It will be understood that minor changes in the size, form and construction of the various parts of my improved orthodontia appliance may be made and substituted for those herein shown and described without departing from the spirit of my invention, the scope of which is set forth in the ap-pended claims.
I claim as my invention:
1. In an orthodontia appliance, a tube adapted to be secured to a tooth band, a threaded sheath -mounted to move lengthwise through said tube and held against rotary motion, which sheath is substantially U-shape in cross section, an arch wire positioned in said U-shaped sheath andrigidly fixed thereto and a nut screw-seated on one end of said sheath and bearing against the end of said tube.
2. In an orthodontic appliance, a tube adapted to be secured to a tooth band, a threaded sheath mounted to move lengthwise through said tube and held against rotary motion, which sheath is substantially U-shape in cross section, an arch wire positioned in said U-shaped sheath andrigidly fixed thereto, a nut screw-seated on one end of said sheath and bearing against the end of said tube and the end of the sheath on which said nut is located being spread so as to produce tension there intending to hold the nut against rotation.
3. In an orthodontia appliance, the combination with an arch wire and tooth band tube, of a threaded sheath provided with a longitudinallydisposed channel in which the end of the arch wire is seated, which sheath and arch wire are rigidly connected to each other and extendlengthwise through the tooth band tube, a nut located on said threaded sheath and bearing against the end of said tube and which tube, sheath and arch wire are provided with cooperating flat faces so that said sheath and arch wire are held against rotation within said tube.
l. In an orthodontia appliance, the combination with an arch wire and tooth band tube which arch wire passes thro-ugh said tube and is held against rotation therein, of a threaded sheath provided with alongitudinally disposed channel in which a portion of said arch wire is seated, which sheath extends through the tooth band tube, said arch wire being rigidly secured to said sheath and a nut mounted on said threaded sheath and bearing against one end of said tube.
5. In an orthodontia appliance, the combination with an arch wire, of a threaded sheath rigidly secured thereto and having a longitudinallydisposed channel which receives said arch wire, a tubular support for said sheath, cooperating means on said tubular support and arch wire for preventing rotation of the arch wire within said support V and a nuts crew-seated on said sheath and engaging said tubular member.
6. In an orthodontia appliance, the combination with a tooth band and a tubular member secured thereto, of an arch wire, a threaded sheathrigidly fixed to said arch wire and extending through the tubular member on said tooth band, a nut screw seated on said threaded sheath and engaging one SPENCER R. ATKINSON.
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<?php
/*
* This file is part of the Cekurte package.
*
* (c) João Paulo Cercal <[email protected]>
*
* For the full copyright and license information, please view the LICENSE
* file that was distributed with this source code.
*/
namespace Cekurte\ComponentBundle\Controller;
use Cekurte\ComponentBundle\Service\ResourceManagerInterface;
use JMS\Serializer\SerializerInterface;
use Symfony\Bundle\FrameworkBundle\Controller\Controller;
/**
* ResourceController
*
* @author João Paulo Cercal <[email protected]>
*
* @version 2.0
*/
class ResourceController extends Controller implements ResourceControllerInterface
{
/**
* @var ResourceManagerInterface
*/
protected $resourceManager;
/**
* Init
*
* @param ResourceManagerInterface $resourceManager
*/
public function __construct(ResourceManagerInterface $resourceManager)
{
$this->resourceManager = $resourceManager;
}
/**
* @inheritdoc
*/
public function getResourceManager()
{
return $this->resourceManager;
}
/**
* Get a instance of JMS Serializer.
*
* @throws \LogicException
*
* @return SerializerInterface
*/
public function getSerializer()
{
if (!$this->container->has('jms_serializer')) {
throw new \LogicException('The JMSSerializerBundle is not registered in your application.');
}
return $this->container->get('jms_serializer');
}
}
|
Error while creating package for uwp
I'm developing an app with C# & Visual Studio 2015 Community for windows 10.
I was trying to create a package for store (appxupload file) but it gives me error:
Loading assembly "C:\Users\Ramtin\.nuget\packages\System.Private.Uri\4.0.0\runtimes\win8-aot\lib\netcore50\System.Private.Uri.dll" failed. System.IO.FileNotFoundException: Could not load file or assembly 'System.Private.CoreLib, Version=<IP_ADDRESS>, Culture=neutral, PublicKeyToken=b03f5f7f11d50a3a' or one of its dependencies. The system cannot find the file specified.
Invalid Resx file. String reference not set to an instance of a String.
Parameter name: suffix MyAPP C:\Users\Ramtin\.nuget\packages\System.Private.Uri\4.0.0\runtimes\win8-aot\lib\netcore50\System.Private.Uri.dll
how can I solve this?
note: I have individual account for develop
I haven't received this error myself, but you should verify that you have the latest Windows 10 SDK installed and latest VS2015 updates.
Visual Studio 2015 Update 2 just came out last week: https://www.visualstudio.com/en-us/news/vs2015-update2-vs.aspx
When you launch VS2015, check the notifications area on the top right for any newly available updates.
When you click File | New | Project in VS2015, check the list of Universal project template types and look to see if there's a list item that prompts you to download the latest SDK.
My screenshot below shows the template types and also the (optional) Template10 that I have available to me. If you don't have the latest SDK, you should see an additional entry that prompts you to download the latest SDK (as opposed to creating a new project)
After verifying that you have the latest of everything, try generating a new package again and please comment below to let us know whether it worked (or if you are still getting errors).
Thank you for your reply, it's great, updated to Update 2 and works fine! i had a problem with opening Package.appxmanifest and it gives me Stopped working when I open it the Package.appxmanifest , but after updated to update 2, everything works well. thanks alot
That's great to hear! :)
It also fixed my build error in 2022 https://github.com/xamarin/Xamarin.Forms/issues/15294
|
//
// ExperienceRouteHandler.swift
// RoverExperiences
//
// Created by Sean Rucker on 2018-06-19.
// Copyright © 2018 Rover Labs Inc. All rights reserved.
//
import Foundation
#if !COCOAPODS
import RoverFoundation
import RoverUI
#endif
class ExperienceRouteHandler: RouteHandler {
/// A closure for providing an Action for opening an Experience. (ExperienceID, CampaignID?, ScreenID?).
let idActionProvider: (String, String?, String?) -> Action?
let universalLinkActionProvider: (URL, String?, String?) -> Action?
init(idActionProvider: @escaping (String, String?, String?) -> Action?, universalLinkActionProvider: @escaping (URL, String?, String?) -> Action?) {
self.idActionProvider = idActionProvider
self.universalLinkActionProvider = universalLinkActionProvider
}
func deepLinkAction(url: URL) -> Action? {
guard let host = url.host else {
return nil
}
if host != "presentExperience" {
return nil
}
guard let queryItems = URLComponents(url: url, resolvingAgainstBaseURL: true)?.queryItems else {
return nil
}
guard let experienceID = queryItems.first(where: { $0.name == "experienceID" || $0.name == "id" })?.value else {
return nil
}
let campaignID = queryItems.first(where: { $0.name == "campaignID" })?.value
let screenID = queryItems.first(where: { $0.name == "screenID" })?.value
return idActionProvider(experienceID, campaignID, screenID)
}
func universalLinkAction(url: URL) -> Action? {
let campaignID: String?
let screenID: String?
if let queryItems = URLComponents(url: url, resolvingAgainstBaseURL: true)?.queryItems {
campaignID = queryItems.first(where: { $0.name == "campaignID" })?.value
screenID = queryItems.first(where: { $0.name == "screenID" })?.value
} else {
campaignID = nil
screenID = nil
}
return universalLinkActionProvider(url, campaignID, screenID)
}
}
|
In django, how can I include some default records in my models.py?
If I have a models.py like
class WidgetType(models.Model):
name = models.CharField(max_length=200)
class Widget(models.Model):
typeid = models.ForeignKey(WidgetType)
data = models.CharField(max_length=200)
How can I build in a set of built in constant values for WidgetType when I know I'm only going to have a certain few types of widget? Clearly I could fire up my admin interface and add them by hand, but I'd like to simplify configuration by having it built into the python.
You could use fixtures:
http://docs.djangoproject.com/en/dev/howto/initial-data/#providing-initial-data-with-fixtures
Strictly speaking, fixtures aren't part of the models, or any python code for that matter. If you really need it in your python code, you could listen for the post_migrate signal and insert your data through the ORM, e.g.:
from django.db.models.signals import post_migrate
def insert_initial_data(sender, app, created_models, verbosity, **kwargs):
if WidgetType in created_models:
for name in ('widgettype1', 'widgettype2', 'widgettype3'):
WidgetType.objects.get_or_create(name=name)
post_migrate.connect(insert_initial_data)
You can write your own Migration and insert new records (or do any other migration you want).
See this article item in Django docs.
This seems like the perfect solution for the use case. Thanks.
|
mation, the temperature region within which the new forms are stable, and the changes which each undergoes with changes of pressure and temperature, as before. If the new forms show signs of instabihty, we can drop them into cold water or mercury so quickly that there will be no opportunity to return to initial stable forms, and thus obtain, for study with the microscope at our leisure, every individual phase of tke process through wliich the group of minerals has passed.
Without complicating the illustration further, it is obvious that we have it m our power to reproduce in detail the actual process of rock formation within the earth, and to substitute measurement where the geologist has been obhged to use inference; to tabulate the whole history of the formation of a mineral or group of minerals under every variety of condition which we may suppose it to have passed through in the earth, provided only we can reproduce that condition m the laboratory.
During the past quarter of a centuiy there has arisen in the middle gi'ound between physics and chemistry a new science of physical chemistry, in the development of which generalizations of great value in the study of minerals have been established. As long ago as 1861 the distinguished German chemist, Bunsen, pomted out that the rocks must be considered to be solutions and must be studied as such; but, inasmuch as comparatively little was known about solu tions in those days, and the rocks at best appeared to be very com plicated ones, no active steps in that dhection were taken durmg Bunsen's life. But in recent years solutions have been widely studied, under rather limited conditions of temperature and pressure, to be sure, but it has resulted m establisMng relations — like the fliase rule — of such effective and far-reacMng character that now, just half a century afterwards, we are entering with great \dgor upon the prose cution of Bunsen's suggestion. It is now possible to establish definite limits of solubility of one mineral in another, and definite conditions of ec[uilibriuni, even in rather comphcated gi-oups of minerals, which enables us not only to interpret the relations developed by such a thermal study as that outlined above, but also to assure ourselves that only a definitely limited number of compounds of two minerals can exist, that they must bear a constant and characteristic relation to each other under given conditions of temperature and pressure, and that changes of temperature and pressure will afl'ect this relation in a definite and determinable way. Physical chemistry not only takes into account the chemical composition of mineral compounds, but then- physical properties as well, throughout the entire tempera ture region in which they have a stable existence, and therefore fur nishes us at once with the possibility of a new and adequately com prehensive classification of all the minerals and rocks in the earth. The value of an adequate system of classification appeals chiefly to
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асимілювати
Etymology
From, ultimately from. Compare 🇨🇬, 🇨🇬, 🇨🇬.
Verb
* 1) to assimilate
* 2) to assimilate
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Wikipedia:Sockpuppet investigations/Dialinn/Archive
01 January 2012
* Suspected sockpuppets
* User compare report Auto-generated every hour.
- It would surprise me if Dmol is also related to the puppetmaster and sockpuppets, but his angry response here triggered my alarmbells. I hope he can be cleared of any wrongdoing. If so, I owe him an apology. - Full overview of all IP's involved can be found here: User:Night of the Big Wind/sockpuppet 360view. I have only named three most recent ones. - I had warned to stop pushing the website www.360eire.com and not to use multiple identities. See here: User talk:Night of the Big Wind/Archives/2012/January. He promised to stop pushing, but today (31-12-2011) another identity showed up and went on with pushing. The almost exclusive use of IP's (of several networks) and sockpuppets, makes it clear that this is a pushing campaign, not an enthousiast promoting his own website. My research is limited mainly to 2011. There are another 50/60 links that I did not look at, but I do not think it will change anything to the pattern. Night of the Big Wind talk 18:08, 1 January 2012 (UTC)
The connection between Dialinn and 188.etc is proved by this edit from Dialinn Night of the Big Wind talk 19:30, 1 January 2012 (UTC)
Comments by other users
Clerk, CheckUser, and/or patrolling admin comments
* - I'm fairly sure Armadainvicible and 1798 are the same on behavioral grounds, but I'll endorse to see what the relationship between the four accounts is. There won't be any comment on the IPs. — Hello Annyong (say whaaat?!) 19:22, 1 January 2012 (UTC)
* ✅ that, , and are the same person. (note that Dialinn != Diallin, it got me confused)
* No comment on the other IP addresses.
* check on Dmol. I don't see how he could be connected to the above.
* For what it's worth, with one N is obviously a sockpuppet of an other user.
* -- Luk talk 10:24, 2 January 2012 (UTC)
* I've blocked and tagged Armada and 1798. I've blocked Dialinn for a week for socking, and I blocked the 188 IP for a week as well. — Hello Annyong (say whaaat?!) 01:27, 3 January 2012 (UTC)
|
58 THE DOCTRINE OF DESCENT.
passes through. Although mammals are never actual fish, there is much that is fish-like in the embryonic phases of their organs; the embryonic fissures in the thorax correspond with the germinal branchial fissures; the formation of the brain may be traced to the complete brain of the lampreys and the sharks, &c.
In order to refute the doctrine that the embryo passes through the whole animal kingdom. Von Baer was con tent to prove that it never changes from one type to another. He repudiated the other, and more probable part of this theory, that is, that, at least within the types, the higher groups, in their embryonic phases, repeated the permanent forms of the lower ones, by terming it a question of mere analogies. The embryo, as it is grad ually perfected by progressive histological and morpho logical differentiation, necessarily accords, in this respect, with less developed animals in proportion to its youth. " It is, therefore, very natural that the embryo of the mammal should be more like that of the fish, than the embryo of the fish is like the mammal. Now, if the fish be regarded merely as a less perfect mammal (and this is an unfounded hypothesis), the mammal must be con sidered as a more highly developed fish; and, in that case, it is quite logical to say that the embryo of the verte brate animal is originally a fish." ^^
We have been somewhat faithless to our intention of confining ourselves in this chapter to facts only. The facts are too apt to provoke reflections, and we have, moreover, repeated these reflections merely as .historical facts ; we must now inquire whether they are really capa ble of satisfying us. I think not. It is by no means a merely histological and morphological differentiation
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Nipomo, California facts for kids
Kids Encyclopedia Facts
Nipomo
census-designated place
The Capt. Dana Tree at the Dana Adobe. Part of the town can be seen in the background.
Location in San Luis Obispo County and the state of California
Country United States
State California
County San Luis Obispo
Named for (Chumash: Nipumu', "Village" )
Area
• Total 14.852 sq mi (38.467 km2)
• Land 14.852 sq mi (38.466 km2)
• Water 0 sq mi (0.001 km2) 0%
Elevation 331 ft (101 m)
Population (2010)
• Total 16,714
• Density 1,125.37/sq mi (434.502/km2)
Time zone Pacific (PST) (UTC-8)
• Summer (DST) PDT (UTC-7)
ZIP code 93444
Area code(s) 805
FIPS code 06-51476
GNIS feature ID 1652759
Nipomo is a census-designated place (CDP) in San Luis Obispo County, California, United States. The population was 12,626 at the 2000 census, and grew to 16,714 for the 2010 census.
Geography
Nipomo is located at (35.0300, -120.4900).
According to the United States Census Bureau, the CDP has a total area of 14.9 square miles (39 km2), virtually all of it land.
Climate
This region experiences warm (but not hot) and dry summers, with no average monthly temperatures above 71.6 °F. According to the Köppen Climate Classification system, Nipomo has a warm-summer Mediterranean climate, abbreviated "Csb" on climate maps.
Demographics
2010
The 2010 United States Census reported that Nipomo had a population of 16,714. The population density was 1,125.4 people per square mile (434.5/km²). The racial makeup of Nipomo was 12,281 (73.5%) White, 177 (1.1%) African American, 200 (1.2%) Native American, 421 (2.5%) Asian, 33 (0.2%) Pacific Islander, 2,821 (16.9%) from other races, and 781 (4.7%) from two or more races. Hispanic or Latino of any race were 6,645 persons (39.8%).
The Census reported that 16,703 people (99.9% of the population) lived in households, 11 (0.1%) lived in non-institutionalized group quarters, and 0 (0%) were institutionalized.
There were 5,474 households, out of which 2,258 (41.2%) had children under the age of 18 living in them, 3,353 (61.3%) were opposite-sex married couples living together, 686 (12.5%) had a female householder with no husband present, 326 (6.0%) had a male householder with no wife present. There were 338 (6.2%) unmarried opposite-sex partnerships, and 49 (0.9%) same-sex married couples or partnerships. 807 households (14.7%) were made up of individuals and 346 (6.3%) had someone living alone who was 65 years of age or older. The average household size was 3.05. There were 4,365 families (79.7% of all households); the average family size was 3.35.
The population was spread out with 4,422 people (26.5%) under the age of 18, 1,531 people (9.2%) aged 18 to 24, 4,058 people (24.3%) aged 25 to 44, 4,593 people (27.5%) aged 45 to 64, and 2,110 people (12.6%) who were 65 years of age or older. The median age was 37.0 years. For every 100 females there were 97.8 males. For every 100 females age 18 and over, there were 94.9 males.
There were 5,759 housing units at an average density of 387.8 per square mile (149.7/km²), of which 3,898 (71.2%) were owner-occupied, and 1,576 (28.8%) were occupied by renters. The homeowner vacancy rate was 1.7%; the rental vacancy rate was 3.1%. 11,583 people (69.3% of the population) lived in owner-occupied housing units and 5,120 people (30.6%) lived in rental housing units.
2000
As of the census of 2000, there were 12,626 people, 4,035 households, and 3,316 families residing in the CDP. The population density was 1,106.1 people per square mile (427.3/km²). There were 4,146 housing units at an average density of 363.2 per square mile (140.3/km²). The racial makeup of the CDP was 75.9% White, 0.60% African American, 1.3% Native American, 1.4% Asian, 0.1% Pacific Islander, 16.0% from other races, and 4.7% from two or more races. Hispanic or Latino of any race were 34.6% of the population.
There were 4,035 households out of which 41.4% had children under the age of 18 living with them, 66.9% were married couples living together, 10.9% had a female householder with no husband present, and 17.8% were non-families. 13.5% of all households were made up of individuals and 6.6% had someone living alone who was 65 years of age or older. The average household size was 3.13 and the average family size was 3.42.
In the CDP, the population was spread out with 30.7% under the age of 18, 7.5% from 18 to 24, 27.9% from 25 to 44, 21.7% from 45 to 64, and 12.1% who were 65 years of age or older. The median age was 36 years. For every 100 females there were 97.4 males. For every 100 females age 18 and over, there were 93.2 males.
The median income for a household in the CDP was $49,852, and the median income for a family was $54,338. Males had a median income of $41,288 versus $25,509 for females. The per capita income for the CDP was $18,824. About 5.6% of families and 7.3% of the population were below the poverty line, including 9.5% of those under age 18 and 6.1% of those age 65 or over.
Parks and recreation
Nipomo Community Park is seventy-four acres (30 ha) and includes hiking and horseback riding.
History
Dorothea Lange's Migrant Mother depicts destitute pea pickers in California, centering on a mother, age 32, of seven children in Nipomo, California, March 1936.
The original settlers of Nipomo were the Chumash Indians, who have lived in the area for over 9,000 years. Rancho Nipomo (the Indian word ne-po-mah meant "foot of the hill") was one of the first and largest of the Mexican land grants in San Luis Obispo County.
The founder of present-day Nipomo, William G. Dana of Boston, was a sea captain. Dana's travels led him to California where he married Maria Josefa Carrillo of Santa Barbara. In 1837, the 38,000-acre (150 km2) Rancho Nipomo was granted to Captain Dana by the Mexican governor. The Dana Adobe, created in 1839, served as an important stop for travelers on El Camino Real between Mission San Luis Obispo and Mission Santa Barbara. The adobe was a stage coach stop and became the exchange point for mail going between north and south in the first regular mail route in California. The Danas had children, of which 13 reached adulthood. They learned both English and Spanish, as well as the language of the Chumash natives.
In 1846, U.S. Army Captain John C. Fremont and his soldiers stopped at the rancho on their way south to Santa Barbara and Los Angeles. Captain Dana hosted a barbecue and gave Fremont’s men 30 fresh horses. By the 1880s the Dana descendants had built homes on the rancho and formed a town. Streets were laid out and lots were sold to the general public. The Pacific Coast Railway (narrow gauge) came to town in 1882, and trains ran through Nipomo until The Great Depression in the 1930s. By the end of 1942, the tracks had been removed for the World War II war effort.
Thousands of Blue Gum Eucalyptus trees were planted on the Nipomo Mesa in 1908 by two men who formed the Los Berros Forest Company with the idea of selling the trees as hardwood. Groves of these non-native trees still exist, even in rows as they were originally planted. These tall trees are often removed as needed for space, but also since they present a falling hazard during high winds and can suppress native flora.
Nipomo is the location of one of the most famous photographs of the Great Depression, "Migrant Mother", by Dorothea Lange. Thompson Road was originally US Highway 101, on which Lange no doubt traveled. The current US 101 freeway was constructed in the late 1950s.
Images for kids
Nipomo, California Facts for Kids. Kiddle Encyclopedia.
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In re: MBA POULTRY, L.L.C., Debtor. Dapec, Inc., Appellant, v. Small Business Administration, U.S., Defendant/Appellee, City of Tecumseh, Interested Party, The Money Store; Bird Watchers, L.L.C., Interested Parties/Appellees. DAPEC, INC., Appellee, v. Small Business Administration, U.S., Defendant, City of Tecumseh, Interested Party/Appellant,
Nos. 01-2026, 01-2028, 01-2029, 01-2480.
United States Court of Appeals, Eighth Circuit.
Submitted: Feb. 15, 2002.
Filed: May 30, 2002.
John D. Marshall, Jr., argued, Atlanta, GA (Steven C. Turner, Omaha, NE, Thomas L. Cohen, Atlanta, GA, on the brief), for Appellant DAPEC, Nos. 01-2026/2028/2029.
David J. Koukol, argued, (Bruce Dal-luge, Tecumseh, NE, on the brief), for Appellant City of Tecumseh, No. 01-2480.
Emmett D. Childers, argued, Omaha, NE, for Appellee The Money Store, Nos. 01-2026,2028/2029.
Stephen M. Cramer, AUSA, argued, Omaha, NE, for Appellee Small Business Administration.
John D. Marshall, argued (Steven C. Turner, Thomas L. Choen, on the brie©, for Appellee DAPEC, No. 01-2480.
Before McMILLIAN and RILEY, Circuit Judges, and KORNMANN, District Judge.
. The Honorable Charles B. Kornmann, United States District Judge for the District of South Dakota, sitting by designation.
RILEY, Circuit Judge.
These appeals arise out of the Chapter 11 bankruptcy of MBA Poultry, Inc. (MBA Poultry). At the time it declared bankruptcy, MBA Poultry owed debts to The Money Store (Money Store), the United States Small Business Administration (SBA), Dapec, Inc. (Dapec), and the City of Tecumseh, Nebraska (Tecumseh), as well as to other creditors who are not parties to these appeals. The Money Store and the SBA claim interests in advances made under two loan agreements, Dapec claims an interest in construction materials it furnished to MBA Poultry, and Tecumseh is trying to collect unpaid sewer and water bills. On appeal, we must determine whether the bankruptcy court was correct in determining the relative priorities of the claims of these parties. We affirm in part and reverse in part.
1. BACKGROUND
The debtor, MBA Poultry, is the former owner of a chicken processing plant in Tecumseh, Nebraska. When MBA Poultry purchased the plant from the Campbell Soup Company on June 16, 1998, it obtained financing from the Money Store. The Money Store made two loans to MBA Poultry on the date of the purchase. The first loan (the “A” loan) was a promissory note in the amount of $840,000, payable over a period of thirty years. The second loan (the “B” loan) was a promissory note for $973,000, payable over a period of one year.
The “A” loan and the “B” loan were each secured by a separate deed of trust filed in Johnson County, Nebraska, on June 17, 1998. In addition, as authorized by Nebraska’s statutes on construction liens, a “notice of commencement” of renovations to the plant was also filed in Johnson County on June 17, 1998. See Neb. Rev.Stat. § 52-145. The notice of commencement was filed a few minutes after the Money Store recorded its trust deeds.
The Money Store began disbursing money under the two loans the day the promissory notes were signed. On June 16,1998, the Money Store disbursed $382,556 of the “A” loan and $642,515 of the “B” loan. The balances of both loans were dispensed in installments, beginning on July 1, 1998, and ending on December 11, 1998.
MBA Poultry obtained additional financing from Heller Financial, Inc. (Heller). Heller’s loan and security interest were executed on October 29, 1998, more than two months after Heller filed a financing statement with the Johnson County Clerk. Heller’s financing statement covered, among other things, all of MBA Poultry’s personal property, “whether now owned or existing or hereafter acquired or arising.” From the appellate record, it is unclear how much Heller loaned MBA Poultry. When the bankruptcy petition was filed, MBA Poultry owed Heller $2,149,948.
MBA Poultry’s business did not generate enough revenue to pay off the “B” loan in the one-year repayment period. Instead, MBA Poultry paid off the “B” loan by arranging a $1,000,000 loan from the Nebraska Economic Development Corporation (NEDCO). The NEDCO loan was secured by a deed of trust filed in Johnson County on December 16, 1998. MBA Poultry’s president and CEO, Mark Has-kins, also gave a personal guarantee for the loan. In January 1998, NEDCO provided the money to repay the “B” loan by issuing debentures guaranteed by the SBA. As part of this transaction, the Money Store assigned the “B” loan and the trust deed securing it to the SBA.
Shortly after purchasing the plant, MBA Poultry began renovations by installing an “air-chill” system. MBA Poultry bought the air-chill system from Dapec for $709,000. On August 31, 1998, MBA Poultry gave Dapec a security interest in “all goods and fixtures” it purchased from Da-pec, including “renewals, additions, or replacements thereto.” Dapec claims it later provided additional materials worth $12,000. Dapec did not file financing statements reflecting its security interest until November 1998. On November 9, Dapec recorded a financing statement with the Nebraska Secretary of State. On November 13, Dapec recorded a financing statement in Johnson County. Both financing statements referred to “all goods or fixtures” which MBA Poultry purchased from Dapec. Dapec filed a construction hen for $721,000 plus interest on January 22,1999.
MBA Poultry filed for Chapter 11 bankruptcy on January 25, 2000. On February 17, 2000, the bankruptcy court entered a final order giving Heller a super-priority interest in MBA Poultry’s personal property and authorizing the sale of the “DA-PEC Air Chill Line.” Heller assigned its claim in bankruptcy to Bird Watchers, L.L.C., which then purchased all of MBA Poultry’s real and personal property at auction for $4,800,000. The sale was approved by the bankruptcy court on June 7, 2000.
After the sale was approved, the bankruptcy court had to determine priority among MBA Poultry’s creditors. With the exception of Dapec, the creditors agreed on priority in the following order: (1) Johnson County, (2) City of Tecumseh, (3) the Money Store, and (4) American National Bank. These creditors also agreed that either Dapec or the SBA should occupy the fifth priority position.
Dapec refused to join the agreement on priority. Instead, it claimed that its construction lien has priority, to some extent, over the liens of the Money Store and the SBA. Dapec raised two arguments in support of this claim. First, it argued that its construction lien dates back to June 17, 1998, when the notice of commencement was filed, and that it trumps any advances made after that date. Second, Dapec argued that the frame of the air-chill line — a stainless steel “superstructure” — is a fixture, and that its perfected security interest in the superstructure trumps the security interest held by the SBA.
The bankruptcy court rejected both of these arguments, finding that Dapec’s construction lien did not attach before the Money Store made its cash advances and that the superstructure is not a fixture. The bankruptcy court then entered an order allowing the bankruptcy proceeds to be distributed in accordance with its rulings on these two issues. The district court affirmed all three of these decisions, but did not reach the merits of the fixture issue. Instead, the district court held that Dapec waived its fixture claim by failing to object to the bankruptcy court’s February 17, 2000 final order.
The bankruptcy court also had to settle an issue of priority between Dapec and the City of Tecumseh. On January 19, 2000, Tecumseh certified MBA Poultry’s delinquent sewer and water bills to the Johnson County Clerk. On January 25, 2000, when it declared bankruptcy, MBA Poultry owed Tecumseh $32,796.06 for sewer service and $31,028.57 for water service. The bankruptcy court held these unpaid bills were special assessments which automatically took priority over Dapec’s construction hen.
The district court reversed the bankruptcy court’s decision on this issue, holding that Tecumseh was not entitled to treat its sewer and water liens like special assessments with automatic priority over Dapec’s construction lien. The district court remanded the case to bankruptcy court for a determination of whether Tecumseh’s hens have priority if they are not treated like special assessments.
Dapec and Tecumseh now appeal the decisions of the district court. In its appeals, Dapec asserts that its construction hen and its security interest in the superstructure have priority over the deeds of trust held by the Money Store and the SBA. Tecumseh, in its appeal, asserts that MBA Poultry’s sewer and water bills are special assessments with automatic priority over Dapec’s claims.
II. DISCUSSION
In a bankruptcy appeal, this court sits as a second court of review and applies the same standards of review as the district court. In re Cedar Shore Resort, Inc., 235 F.3d 375, 379 (8th Cir.2000). Like the district court, we review the bankruptcy court’s findings of fact for clear error and its conclusions of law de novo. Id.
A. Priority Under Nebraska’s Construction Lien Statutes
The first issue on appeal pits Dapec’s construction hen against the deeds of trust the Money Store took to secure the “A” loan and the “B” loan. The deed of trust for the “A” loan is still held by the Money Store, while the deed of trust for the “B” loan has been assigned to the SBA.
Under Nebraska law, as a general rule, “a construction lien has priority over subsequent advances made under a prior recorded security interest if the subsequent advances are made with knowledge that the lien has attached.” Neb.Rev.Stat. § 52-139(2). In order to obtain priority under this statute, Dapec must show that the Money Store made its cash advances with knowledge that Dapec’s construction hen had attached. The bankruptcy court found that the Money Store did not know about Dapec’s construction hen until after December 11, 1998, when it finished making future advances under the “A” and “B” loans.
In an attempt to overcome this finding, Dapec relies on the “notice of commencement” filed on June 17, 1998. Under Nebraska law, “[i]f a hen is recorded while a notice of commencement is effective as to the improvement in connection with which the hen arises, the hen attaches as of the time the notice is recorded.” Neb.Rev. Stat. § 52-137(2). Dapec argues that since section 52-137(2) relates its hen back to June 17, 1998, when the notice of commencement was recorded, it also imputes knowledge of the hen to the Money Store as of that date.
Dapec’s argument fails because the relevant statute — section 52-139(2) — • requires actual knowledge of a competing hen. “In the absence of anything to the contrary, statutory language is to be given its plain and ordinary meaning.” Rodriguez v. Monfort, Inc., 262 Neb. 800, 635 N.W.2d 439, 445 (2001). Under section 52-139(2), the priority of a construction hen does not turn on imputed knowledge that a lien has attached or the knowledge that a hen might attach. It turns, rather, on the lender’s “knowledge that the hen has attached.” See Neb.Rev.Stat. § 52-139(2). In its ordinary use, the term “knowledge” means being “cognizant, conscious, or aware of something,” Webster’s Third New International Dictionary 1252 (1993), and we see no reason why the Nebraska Legislature would have intended a different meaning here. As explained above, the Money Store did not actually know about Dapec’s construction lien when it was making advances. Accordingly, under the construction lien statutes, Dapec’s construction lien is subordinate to the deeds of trust filed by the Money Store.
B. The Fixture Issue
Under certain circumstances, Nebraska law gives a perfected security interest in a fixture priority over the conflicting interest of an encumbrancer of the related real estate. See Neb. U.C.C. § 9-313(4) [Operative until July 1, 2001]. A fixture is a chattel which is capable of existing separate and apart from a parcel of real property, but which has become a more or less permanent part of the real estate. See Pick v. Fordyce Coop. Credit Ass’n, 225 Neb. 714, 408 N.W.2d 248, 255 (1987) (citation omitted). Dapec argues that its security interest in the stainless steel superstructure has priority over the trust deed held by the SBA because the superstructure is a fixture.
The district court did not reach the merits of this argument, finding instead that Dapec waived the argument by failing to object to the bankruptcy court’s February 17, 2000 final order. Interpretation of the bankruptcy court’s order presents a question of law which we review de novo. See Brady v. McAllister, 101 F.3d 1165, 1168 (6th Cir.1996). The final order of February 17, 2000, created a super-priority interest in certain personal property, including MBA Poultry’s “overhead conveyor.” However, it is not obvious to us that the bankruptcy court meant the term “overhead conveyor” to include the superstructure. In the purchase orders for the air-chill system, MBA Poultry and Dapec distinguished the components of the conveyor from the superstructure. Perhaps more important, the bankruptcy court apparently did not believe that Dapec had waived the issue, because it ruled on the merits of Dapec’s motion. Under these circumstances, we find that the fixture issue was not waived, and we review the bankruptcy court’s decision on its merits.
The bankruptcy court’s determination that the superstructure is not a fixture was a finding of fact. See Washington Metro. Area Transit Auth. v. Precision Small Engines, 227 F.3d 224, 227 (4th Cir.2000) (per curiam); First Wis. Nat’l Bank of Milwaukee v. Fed. Land Bank of St. Paul, 849 F.2d 284, 287 (7th Cir.1988). As such, it may be reversed only if it was clearly erroneous. Fed. R. Bankr.P. 8013; First Wis. Nat’l Bank, 849 F.2d at 287.
Under Nebraska law, a court must look to three factors in determining whether personal property has become a fixture. These factors are:
(1) whether the article or articles are annexed to the realty, or something appurtenant thereto; (2) whether the article or articles have been appropriated to the use or purpose of that part of the realty with which it is or they are connected; and (3) whether the party making the annexation intended to make the article or articles a permanent accession to the freehold.
Fed. Land Bank of Omaha v. Swanson, 231 Neb. 868, 438 N.W.2d 765, 767-68 (1989) (citation omitted). The first two factors, annexation and appropriation to the use of the realty, have value primarily as evidence of the owner’s intent, which is generally regarded as the most important factor. N. Natural Gas Co. v. State Bd. of Equalization, 232 Neb. 806, 443 N.W.2d 249, 257 (1989).
One piece of evidence before the bankruptcy court was the affidavit of Mark Haskins (Haskins), the president and CEO of MBA Poultry. In his affidavit, Haskins states that although the superstructure is “bolted to the floor or ceiling,” the bolts can be taken out, and the superstructure “can be removed from the premises with no damage to the equipment or to the premises.” Haskins also states that he “always understood that the equipment could be removed at any time, without much difficulty or any damage to either the machinery or building.” According to Haskins, “it was never [his] intention to have any of the equipment become a permanent part of or accession to the ... premises.”
The president of Dapec, Peter Goffe (Goffe), signed an affidavit that to some extent conflicts with the affidavit of Has-kins. In Goffe’s affidavit, he states that it took approximately seven weeks of work, averaging sixty-five hours a week, to complete the superstructure and the rest of the air-chill system. The entire system, he says, “was custom designed and constructed in order to be integrated into the plant.” Goffe avers that the “ceiling of the air chill rooms is laid upon and is supported by the support superstructure.” According to Goffe, the components of the superstructure are “welded together and affixed to the building,” and “cannot be removed and reused in any other location or otherwise broken down as reusable component parts.”
The bankruptcy record also includes col- or photographs of the superstructure. The photos support much of Goffe’s affidavit. The photos show the superstructure being constructed in a large room with walls of concrete block. The room appears to be approximately sixteen feet high, twenty feet wide, and at least thirty-two feet long. The superstructure, which is composed of stainless steel beams, fills the dimensions of the room. At least five pairs of beams, spaced approximately eight feet apart, run vertically from the floor almost to the ceiling. Each pair of vertical beams is connected by four horizontal beams. The highest level of these horizontal beams spans the tops of the vertical beams, and the other levels run successively lower in intervals of about four feet. The horizontal beams are reinforced in the center of the room by approximately four-foot long vertical beams. These shorter beams run vertically between the horizontal beams, from the topmost beams straight down, from one beam to the next, and from the lowest beams to the floor. Although it is clear that most of the joints of the superstructure are welded together, it is not clear whether they all are, or whether a few of them are bolted together instead.
The record is inconclusive as to whether, as Goffe claims, the ceiling of the processing plant has been “laid upon” the superstructure. The photographs, which were taken during construction of the superstructure, show a gap between the top of the superstructure and the ceiling. According to Dapec, the ceiling was lowered after the photographs were taken, and it now rests on the ceiling. The appellees have not disputed this claim.
In analyzing the affidavits and the photographs, the bankruptcy court made three main points. First, it noted that the superstructure was only bolted down to the floor of the plant and not permanently attached to the walls or ceiling. Second, while the bankruptcy court noted that the superstructure was specifically designed for use in MBA Poultry’s chicken processing plant, it observed that the building itself could be used for other purposes if the superstructure were removed. Third, the bankruptcy court relied on Haskins’s affidavit to show that the parties did not intend the superstructure to be a fixture. In summary, the bankruptcy court found, “[i]t can be reasonably inferred from the evidence of the use, purpose, and method of construction of the superstructure that the parties intended it to be separate and distinct from the real estate.”
Reviewing the bankruptcy court’s decision, the first factor we address is the manner in which the superstructure is affixed to the real estate. In analyzing this factor, the bankruptcy court concentrated on the fact that the superstructure is only bolted down. In their briefs, the parties argue about the significance of this fact.
Under Nebraska case law, it is possible for an item that is merely bolted down to become a fixture. The SBA cites Swanson, 438 N.W.2d at 768, in which the Nebraska Supreme Court held that two grain bins were not fixtures, where they were merely bolted down to concrete slabs and were capable of being removed without any significant difficulty. In other cases, however, the Nebraska Supreme Court has found items to be fixtures even though they were only bolted down. For example, in Tillotson v. Stephens, 195 Neb. 104, 237 N.W.2d 108, 109 (1975), the court treated another grain bin as a fixture, where the bin “was anchored to a concrete base and became an integral part” of the grain elevator to which it was connected. Similarly, in Oliver v. Lansing, 59 Neb. 219, 80 N.W. 829, 831 (1899), the court upheld a trial court’s finding that opera chairs in a theater were fixtures, where the chairs had been “specially adapted” to the theater and “affixed thereto by screws.” These cases counsel us not to put too much weight on the fact that the superstructure was only bolted to the floor of the processing plant.
In evaluating the superstructure’s annexation to the real estate, we think it is more useful to examine how difficult it would be to remove the superstructure from the plant. An article is more likely to be a fixture when “removal of the article will injure the realty or will injure the article itself.” See N. Natural Gas, 443 N.W.2d at 257-58. The affidavits submitted to the bankruptcy court conflict on this issue. The photographs in the record, however, resolve the issue decidedly in Dapec’s favor. Looking at the photos, we can see no way in which the superstructure can be removed without causing substantial damage either to the plant, or to the superstructure itself, or both. For all practical purposes, the superstructure is part of the processing plant, and this fact weighs heavily in favor of finding that it is a fixture.
The second factor — appropriation to the use of the realty — -also points strongly towards the conclusion that the superstructure is a fixture. Like the opera chairs in Oliver, the superstructure was specifically designed for use in MBA Poultry’s processing plant. And, like the grain bin in Tillotson, the superstructure was integrated into the processing plant during several weeks of construction. The bankruptcy court discounted these facts, because, in its view, the real estate could be used for other purposes. The Nebraska Supreme Court, however, has not looked to the full range of purposes to which real estate might be applied, but rather to “the use to which [it] is applied.” N. Natural Gas, 443 N.W.2d at 259 (emphasis added). The real estate in this case was being used as a chicken processing plant, and Bird Watchers, which purchased the plant in the bankruptcy sale, planned to continue that use. Under these circumstances, the superstructure was clearly appropriated to the use of the realty.
Finally, we believe MBA Poultry intended the superstructure to be a permanent feature of its processing plant. As the bankruptcy court observed, the principal evidence against this conclusion is the affidavit of Haskins, MBA Poultry’s president and CEO, who claims he had no such intent. Haskins, however, was not a disinterested party. He personally guaranteed the $1,000,000 NEDCO loan that was financed by the SBA, and he has a strong financial interest in seeing the SBA repaid from the bankruptcy estate.
The Nebraska Supreme Court has indicated that, to be trustworthy, evidence of intent should come primarily from objective sources, such as “the nature of the articles affixed, the relation and situation of the party making the annexation, the structure and mode of the annexation, and the purpose or use for which the annexation has been made.” N. Natural Gas, 443 N.W.2d at 257; see also Pick, 408 N.W.2d at 255. For reasons stated above, we believe these factors point inescapably toward an intention on the part of MBA Poultry to make the superstructure a permanent part of its plant.
In short, the evidence plainly shows that the stainless steel superstructure is a fixture. The bankruptcy court’s finding to the contrary was clearly erroneous. Accordingly, we remand the case for a determination of priority between Dapec’s security interest in the superstructure and the security interest held by the SBA.
C. Priority of Sewer and Water Bills
Tecumseh asserts that its liens for MBA Poultry’s unpaid sewer and water bills have priority over Dapec’s construction lien. Under Nebraska law,
All special assessments, regularly assessed and levied as provided by law, shall be a lien on the real estate on which assessed, and shall take priority over all other encumbrances and hens thereon except the first lien of general taxes under section 77-203.
Neb.Rev.Stat. § 77-209. According to Tecumseh, its sewer and water bills have priority because its ordinances authorize a delinquent sewer or water bill “to be collected as a special tax in the manner provided by law.” Tecumseh City Code, §§ 3-121, 3-212.
Under Nebraska law, “[s]ewer use charges are not special assessments.” Rutherford v. City of Omaha, 183 Neb. 398, 160 N.W.2d 223, 228 (1968). Tecumseh concedes this point, but argues Nebraska law allows a municipality to treat such charges as if they ruere special assessments.
Tecumseh’s argument rests ultimately on two Nebraska statutes. First, Nebraska allows a city of the second class, such as Tecumseh, to collect delinquent sewer charges “in the same manner as other municipal taxes are certified, assessed, collected and returned.” Neb.Rev.Stat. § 18-503. Second, Nebraska also permits cities of the second class to provide by ordinance for the collection of water charges and taxes, Neb.Rev.Stat. § 17-538. Neither of these statutes specifically permits a municipality to treat unpaid utility bills like special assessments.
Because they lack such provisions, the statutes cited by Tecumseh do not make unpaid sewer and water bills the equivalents of special assessments. In Nebraska, any statutory authorization to levy special assessments must be strictly construed against the municipality. Foote Clinic, Inc. v. City of Hastings, 254 Neb. 792, 580 N.W.2d 81, 84 (1998). Although section 18-503 allows a municipality to collect sewer bills in the way it collects “other municipal taxes,” it says nothing in particular about levying or collecting special assessments. Section 17-538, which authorizes the collection of water bills, says nothing at all about special assessment procedures. Construing these statutes strictly against Tecumseh, as we must, we hold that they do not give automatic priority to Tecumseh’s sewer and water bills.
While Nebraska law does not give MBA Poultry’s unpaid sewer and water bills automatic priority, those bills may still be liens. See Neb.Rev.Stat. §§ 17-538, 17-925.01. Dapec does not contest the district court’s holding that the sewer and water bills are hens. As liens, the unpaid sewer and water bills may or may not have priority over Dapec’s construction hen under Nebraska’s general rules governing hen priority. Thus, the district court correctly ordered the case remanded to the bankruptcy court for a new determination of priority.
III. CONCLUSION
We agree with the bankruptcy court and the district court that Nebraska’s construction hen statutes do not give Dapec’s construction hen priority over the security interests held by the Money Store and the SBA. Unlike the district court, we conclude the bankruptcy court clearly erred in finding that the stainless steel superstructure of MBA Poultry’s air-chill line is not a fixture. We agree with the district court that the bankruptcy court committed a legal error when it gave Tecumseh’s unpaid sewer and water bihs automatic priority over Dapec’s security interest.
We affirm the judgment of the district court in Case No. 01-2026, in which the district court approved the bankruptcy court’s disposition of the construction hen issue. However, we reverse the judgment of the district court in Case No. 01-2028. Instead, we hold that the superstructure is a fixture, and we remand the case for a determination of priority between Dapee’s security interest in the superstructure and the security interest held by the SBA. In accordance with these two rulings, we affirm in part, and reverse in part, the judgment of the district court in Case No. 01-2029, which upheld the bankruptcy court’s decision to allow disposition of proceeds under its rulings on the construction lien and fixture issues. Finally, we affirm the judgment of the district court in Case No. 01-2480, and, like the district court, we remand that case for a new determination of priority between Dapec’s construction hen and the unpaid sewer and water bills owed to Tecumseh.
. In September 1998, the Money Store entered into an agreement with Dapec, subordinating its security interest to Dapec's interest in the goods and fixtures sold by Dapec to MBA Poultry. Dapec did not file the subordination agreement until February 5, 1999, after MBA Poultry had assigned its interest to the SBA. Dapec does not rely on the subordination agreement in its dispute with the SBA.
. Dapec also claims its liens might have priority under a Nebraska statute on mortgages. See Neb.Rev.Stat. § 76-238.01. However, Da-pec waived this argument by failing to raise it in the bankruptcy court. We therefore decline to address it.
. In 1999, the Nebraska Legislature adopted a revised version of Article 9 of the Uniform Commercial Code, with an operative date of •July 1, 2001. 1999 Neb. Laws ch. 550. The relevant events in this case all took place before that date.
. The Money Store has not taken a position on this issue, presumably because of the subordination agreement it entered into with Dapec. See supra note 2.
. Since this case is a “core” bankruptcy proceeding, see 28 U.S.C. § 157(b)(2)(K), we do not use the standard of review provided by state law. Willemain v. Kivitz, 764 F.2d 1019, 1022 (4th Cir.1985).
. Special assessments differ from taxes generally in that they are directed at property which has received special benefits from public improvements. See NEBCO, Inc. v. Bd. of
Equalization of City of Lincoln, 250 Neb. 81, 547 N.W.2d 499, 503 (1996). Tecumseh does not argue that it is permitted to treat sewer and water bills like first liens for general taxes. See Neb.Rev.Stat. § 77-203 and § 77-208.
. MBA Poultry's plant was apparently not in an extension district where special assessments might have been authorized by law. See Neb.Rev.Stat. §§ 19-2401 — 19-2407; Matzke v. City of Seward, 193 Neb. 211, 226 N.W.2d 340, 344-45 (1975), overruled on other grounds, First Assembly of God Church v. City of Scottsbluff, 203 Neb. 452, 279 N.W.2d 126, 129-30 (1979).
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Ychthytonian
"Yer little friend is kind of agitated."
- A Ychthytonian on R2-D2
Biology and appearance
The Ychthytonians were a sentient species with four arms. They could speak Galactic Standard Basic.
History
Ychthytonians in the galaxy
Behind the scenes
Appearances
* Rebel Force: Renegade
* The New Rebellion
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Water Needle
* Name:
* Type: Unknown rank, Offensive, Short range (0-5m)
* User: Hinata Hyuga
* Debut (Anime): Naruto Episode 150
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In the Matter of Brandon P., a Person Alleged to be a Juvenile Delinquent, Appellant.
[966 NYS2d 72]
Order of disposition, Family Court, Bronx County (Allen G. Alpert, J.), entered on or about January 18, 2012, which adjudicated appellant a juvenile delinquent upon his admission that he committed the act of unlawful possession of weapons by a person under 16, and placed him on probation for a period of 18 months, unanimously affirmed, without costs.
The petition, together with the supporting deposition, contained nonhearsay allegations establishing every element of the offense charged, including the age element of Penal Law § 265.05 (see generally Family Ct Act § 311.2 [3]; Matter of Jahron S., 79 NY2d 632, 636 [1992]). Unlike the situation in Matter of Devon V. (83 AD3d 469 [1st Dept 2011]), the supporting deposition contained an explanation of how the deponent knew appellant was 15 years old. The deponent stated that she was appellant’s sister, and it is generally recognized that the ages of family members are common knowledge within a family (see Matter of Culligan’s Pub v New York State Liq. Auth., 170 AD2d 506 [2d Dept 1991], and cases cited therein).
The court properly exercised its discretion in adjudicating appellant a juvenile delinquent and placing him on probation for a period of 18 months. This was the least restrictive alternative consistent with the needs of appellant and the community (see Matter of Katherine W., 62 NY2d 947 [1984]) in light of, among other things, the fact that the underlying offense was a serious incident involving a knife. The court reasonably concluded that the six-month period of supervision available under an adjournment in contemplation of dismissal was inadequate to meet appellant’s needs. Concur—Andrias, J.P, Saxe, DeGrasse, Richter and Gische, JJ.
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WIP prototype pep517-style editable
See https://discuss.python.org/t/third-try-on-editable-installs/3986/22
A new editable hook does an in-place build, returns { "src_root" : "where .pth file should point to" }
Apologies for the reformatting.
Closing, since this is not intended to be merged, and isn't really consistent with the approach we agreed upon at the packaging summit in 2019 anyway.
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2nd step not inserting data
In my code below, I have defined 2 steps for a job, where each step reads data from a different csv. Here the data from the 1st step gets inserted in the DB, ut the 2nd step is not inserting data in the DB. Can you please help in pointing out the error
@Configuration
@EnableBatchProcessing
public class MacroSimulatorConfiguration {
@Autowired
private JobBuilderFactory jobs;
@Autowired
private StepBuilderFactory steps;
@Bean
public ItemReader<Consumption> reader() {
FlatFileItemReader<Consumption> reader = new FlatFileItemReader<Consumption>();
reader.setResource(new ClassPathResource("datacons.csv"));
reader.setLinesToSkip(1);
reader.setLineMapper(new DefaultLineMapper<Consumption>() {
{
setLineTokenizer(new DelimitedLineTokenizer() {
{
setNames(new String[] { "tradeCommodity", "hou", "region", "dir", "purchValue", "value" });
}
});
setFieldSetMapper(new BeanWrapperFieldSetMapper<Consumption>() {
{
setTargetType(Consumption.class);
}
});
}
});
return reader;
}
@Bean
public ItemReader<Gdp> reader1() {
FlatFileItemReader<Gdp> reader1 = new FlatFileItemReader<Gdp>();
reader1.setResource(new ClassPathResource("datagdp.csv"));
reader1.setLinesToSkip(1);
reader1.setLineMapper(new DefaultLineMapper<Gdp>() {
{
setLineTokenizer(new DelimitedLineTokenizer() {
{
setNames(new String[] { "region", "gdpExpend", "value" });
}
});
setFieldSetMapper(new BeanWrapperFieldSetMapper<Gdp>() {
{
setTargetType(Gdp.class);
}
});
}
});
return reader1;
}
@Bean
public ItemWriter<Consumption> writer(DataSource dataSource) {
JdbcBatchItemWriter<Consumption> writer = new JdbcBatchItemWriter<Consumption>();
writer.setItemSqlParameterSourceProvider(new BeanPropertyItemSqlParameterSourceProvider<Consumption>());
writer.setSql("INSERT INTO INPUT_CONSUMPTION (TRAD_COMM, HOU, SUB_REGION, INCOME_GROUP, CITIZEN_STATUS, REGION, DIR, PURCHVALUE, VAL) "
+ "VALUES (:tradeCommodity, :hou, :subRegion, :incomeGroup, :citizenStatus, :region, :dir, :purchValue, :value)");
writer.setDataSource(dataSource);
return writer;
}
@Bean
public ItemWriter<Gdp> writer1(DataSource dataSource) {
JdbcBatchItemWriter<Gdp> writer1 = new JdbcBatchItemWriter<Gdp>();
writer1.setItemSqlParameterSourceProvider(new BeanPropertyItemSqlParameterSourceProvider<Gdp>());
writer1.setSql("INSERT INTO input_gdp (REGION, GDPEXPEND, VAL) " + "VALUES (:region, :gdpExpend, :value)");
writer1.setDataSource(dataSource);
return writer1;
}
@Bean
public Job importJob(Step s1, Step s2) {
return jobs.get("importJob").incrementer(new RunIdIncrementer()).start(s1).next(s2).build();
}
@Bean(name = "s1")
public Step step1(ItemReader<Consumption> reader, ItemWriter<Consumption> writer) {
return steps.get("step1").<Consumption, Consumption>chunk(100).reader(reader).writer(writer).build();
}
@Bean(name = "s2")
public Step step2(ItemReader<Gdp> reader1, ItemWriter<Gdp> writer1) {
return steps.get("step2").<Gdp, Gdp>chunk(1).reader(reader1).writer(writer1).build();
}
}
This is what I see in console. There is parsing error on 1st csv as there are no records on line 13834 and after that. But records from 1st csv are successfully inserted in the DB, so guessing this parsing error can be ignored. Wondering if the reader, writer, step & job have been correctly defined for 2nd csv.
Console:
Job: [SimpleJob: [name=importJob]] launched with the following parameters: [{run.id=1}]
Executing step: [step1]
Encountered an error executing step step1 in job importJob
Parsing error at line: 13834 in resource=[class path resource [datacons.csv]], input=[]
Job: [SimpleJob: [name=importJob]] completed with the following parameters: [{run.id=1}] and the following status: [FAILED]
Do you get an actual error during step2 or is your data simply not inserted? The only thing coming to mind right now is that your step2 tablename is in lowercase whereas step1 is in uppercase and some DBMS are case-sensitive
I tried changing tablename to uppercase but that didn't help. I have updated my question with the console output.
are you sure datacons.cvs is present/accessibile in your classpath?
@LucaBassoRicci yes, I do see all the 13833 records from csv being inserted into the db
From what I see in the console output, your step2 is not executed at all.
This is normal Spring Batch behaviour : If an "non-skippable" error is encountered during a step, the step will terminate with the status FAILED and so will the job lest you have a .on("FAILED") to explicitly prevent default behaviour and call another step.
Also, you may wonder why you still have records inserted in your database, this is due to the fact that Spring Batch commit records according to the commit-interval you defined. Since you set it to 1, every record preceding the one in error will be commited.
So, here you have 3 solutions :
Prevent the parse error in the file
Add skippable exceptions class (either your ParseException or simple java.lang.Exception). This will tell Spring Batch to ignore errors and continue reading the file.
Explicitly declare a transition .on("*") between first and second step to start the second one even if the first one fails. The first file will only be read up to the first error, then the second file will be read.
Oh thanks. This info was helpful. Regarding bullet#3, are you saying to try this way? return jobs.get("importJob").incrementer(new RunIdIncrementer()).start(s1).on("*").next(s2).build(); as this line is now giving error
@dazzle .on("*") requires either a flow or a decider. Take a look here : https://narmo7.wordpress.com/2014/05/14/spring-batch-how-to-setup-a-flow-job-with-java-based-configuration/
very helpful. You have been awesome!
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// Copyright 2019 The Chromium Authors. All rights reserved.
// Use of this source code is governed by a BSD-style license that can be
// found in the LICENSE file.
#include "chrome/browser/chromeos/extensions/printing/printing_api_utils.h"
#include "chromeos/printing/printer_configuration.h"
#include "testing/gtest/include/gtest/gtest.h"
namespace extensions {
namespace idl = api::printing;
namespace {
constexpr char kId[] = "id";
constexpr char kName[] = "name";
constexpr char kDescription[] = "description";
constexpr char kUri[] = "ipp://192.168.1.5";
constexpr int kRank = 2;
} // namespace
TEST(PrintingApiUtilsTest, GetDefaultPrinterRules) {
std::string default_printer_rules_str =
R"({"kind": "local", "idPattern": "id.*", "namePattern": "name.*"})";
base::Optional<DefaultPrinterRules> default_printer_rules =
GetDefaultPrinterRules(default_printer_rules_str);
ASSERT_TRUE(default_printer_rules.has_value());
EXPECT_EQ("local", default_printer_rules->kind);
EXPECT_EQ("id.*", default_printer_rules->id_pattern);
EXPECT_EQ("name.*", default_printer_rules->name_pattern);
}
TEST(PrintingApiUtilsTest, GetDefaultPrinterRules_EmptyPref) {
std::string default_printer_rules_str;
base::Optional<DefaultPrinterRules> default_printer_rules =
GetDefaultPrinterRules(default_printer_rules_str);
EXPECT_FALSE(default_printer_rules.has_value());
}
TEST(PrintingApiUtilsTest, PrinterToIdl) {
chromeos::Printer printer(kId);
printer.set_display_name(kName);
printer.set_description(kDescription);
printer.set_uri(kUri);
printer.set_source(chromeos::Printer::SRC_POLICY);
base::Optional<DefaultPrinterRules> default_printer_rules =
DefaultPrinterRules();
default_printer_rules->kind = "local";
default_printer_rules->name_pattern = "n.*e";
base::flat_map<std::string, int> recently_used_ranks = {{kId, kRank},
{"ok", 1}};
idl::Printer idl_printer =
PrinterToIdl(printer, default_printer_rules, recently_used_ranks);
EXPECT_EQ(kId, idl_printer.id);
EXPECT_EQ(kName, idl_printer.name);
EXPECT_EQ(kDescription, idl_printer.description);
EXPECT_EQ(kUri, idl_printer.uri);
EXPECT_EQ(idl::PRINTER_SOURCE_POLICY, idl_printer.source);
EXPECT_EQ(true, idl_printer.is_default);
ASSERT_TRUE(idl_printer.recently_used_rank);
EXPECT_EQ(kRank, *idl_printer.recently_used_rank);
}
} // namespace extensions
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User:Daanschr/ Historical maps/ Gaius Claudius Marcellus Maior
Gaius Claudius Marcellus Maior was consul of the Roman Republic in 49 BC together with Lucius Cornelius Lentulus Crus. Julius Caesar attacks Rome. The consuls and the senate had to flee from Italy.
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Particulate Flow Enhancing Additives and Associated Methods
ABSTRACT
Methods comprising providing a dry, solid particulate material comprising a cementitious material, a non-cementitious material, or a combination thereof and having a flow enhancing additive absorbed thereon. The flow enhancing additive comprises a flow inducing chemical, ethylene glycol, and water. The coated, dry, solid material is then mixed with a sufficient amount of water to form a pumpable slurry and then the slurry may be placed in a subterranean formation. In some cases the dry, solid particulate material comprising a cementitious material, a non-cementitious material, or a combination thereof and having a flow enhancing additive absorbed thereon may be stored for a period of time before the slurry is formed.
CROSS-REFERENCE TO RELATED APPLICATIONS
The present invention is related to co-pending U.S. patent application Ser. No. ______, Attorney Docket No. HES 2006-IP-022639U2 entitled “Particulate Flow Enhancing Additives and Associated Methods,” filed concurrently herewith, the entire disclosure of which is incorporated herein by reference.
BACKGROUND
The present invention generally relates to additives for particulate materials, such as cementitious materials and non-cementitious materials. More specifically, the present invention relates to compositions that may improve the flow properties of dry particulate cementitious and non-cementitious materials and related methods of synthesis and use.
Cementitious materials such as hydraulic cements, slag, fumed silica, fly ash and the like having various particle size distributions are often dry-blended and placed in storage tanks. The storage tanks containing the cementitious materials are often transported by land or sea to locations where the cementitious materials are to be used. During such transportation, the cementitious materials are subjected to vibrations and as a result, under static conditions, the materials can become tightly packed. When the cementitious materials are conveyed out of the storage tanks, significant portions of the tightly packed materials may unintentionally be left behind in the storage tanks or clumps of the packed materials may become lodged in transfer conduits. Beyond the cost of the unusable cementitious materials, costly removal and disposal procedures may be required to remove the packed materials from the storage tanks or transfer conduits.
Treatments have been developed to reduce the likelihood that cementitious and non-cementitious materials will pack by improving or preserving the flow properties of the materials. Certain treatments involve blending dry particulate cementitious and/or non-cementitious materials with an additive. One such additive comprises a particulate solid adsorbent material having a flow inducing chemical adsorbed thereon. In general, these additives are dry-blended with cementitious and/or non-cementitious materials at a point in time before packing is likely to occur, e.g., before the materials are shipped or stored. Typically, the dry-blending step occurs at a location other than the location where the cementitious or non-cementitious materials are ultimately utilized. For example, an additive may be dry-blended with cementitious materials in a warehouse before the blend is transported to a second location where it is used in a cementing operation.
While additives comprising a flow inducing chemical adsorbed onto a particulate solid adsorbent material may improve the flow properties of cementitious and non-cementitious materials, certain undesirable properties of the additives may complicate or limit their use. In particular, known additives may conglomerate and/or freeze at relatively high temperatures. For example, the additives may begin to conglomerate at temperatures as high as 60° F. In other cases, additives may freeze at temperatures as high as 55° F. When completely frozen, an additive may lose its free-flowing, powder-like consistency and take the form of a solid, rock-like mass. This may be a tremendous disadvantage, because until the temperature of the additive can be raised, it may be difficult or impossible to dry-blend the additive with cementitious or non-cementitious materials. Typically, an additives' low freezing point may be most problematic prior to the point when the additive is dry-blended with another material, e.g. when the additive is still in a relatively pure form. Due to the low freezing point of some additives, in cold climates the additives may have to be produced and/or stored in climate-controlled facilities, e.g., climate-controlled warehouses. If climate-controlled facilities are not available or are not cost effective, the additives may freeze and become at least temporarily unusable, because they cannot be dry-blended with cementitious or non-cementitious materials in a frozen state. In some cases, the freezing points of the individual components of the additive may be even higher than the freezing point of the finished additive, e.g., certain components may have freezing points above 60° F., so the components may freeze while the additive is being manufactured, making it difficult or impossible to produce the finished additive.
SUMMARY
The present invention generally relates to additives for particulate materials, such as cementitious materials and non-cementitious materials. More specifically, the present invention relates to compositions that may improve the flow properties of dry particulate cementitious and non-cementitious materials and related methods of synthesis and use.
In one embodiment, the present invention provides compositions comprising: a particulate solid adsorbent material; a flow inducing chemical; water; and ethylene glycol.
In another embodiment, the present invention provides methods comprising: providing a flow enhancing additive comprising a flow inducing chemical, a solid adsorbent particulate material, ethylene glycol, and water; providing a cementitious material, a non-cementitious material, or a mixture of cementitious and non-cementitious material; and blending the flow enhancing additive with the cementitious material, the non-cementitious material, or the mixture of cementitious and non-cementitious material.
In another embodiment, the present invention provides methods comprising: providing a cementitious material, a non-cementitious material, or a mixture of cementitious and non-cementitious material comprising a flow enhancing additive, wherein the flow enhancing additive comprises a flow inducing chemical, a solid adsorbent particulate material, ethylene glycol, and water; allowing the cementitious material, non-cementitious material, or the mixture of cementitious and non-cementitious material to interact with a sufficient amount of water to form a pumpable slurry; and placing the pumpable slurry in a subterranean formation.
The features and advantages of the present invention will be readily apparent to those skilled in the art. While numerous changes may be made by those skilled in the art, such changes are within the spirit of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
These drawings illustrate certain aspects of some of the embodiments of the present invention, and should not be used to limit or define the invention.
FIG. 1 shows the change in the viscosity of a cement slurry over time.
FIG. 2 shows the change in the viscosity of a cement slurry over time.
DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention generally relates to additives for particulate materials, such as cementitious materials and non-cementitious materials. More specifically, the present invention relates to compositions that may improve the flow properties of dry particulate cementitious and non-cementitious materials and related methods of synthesis and use.
In some aspects, the present invention relates to additives for cementitious and non-cementitious materials and related methods of using cementitious and non-cementitious materials which comprise these additives. In some embodiments, the present invention generally provides compositions that may impart desired flow properties to dry particulate cementitious materials, non-cementitious materials, or a mixture of a cementitious and non-cementitious materials. These compositions are broadly referred to herein as “flow enhancing additives.” In some embodiments, the flow enhancing additives of the present invention may have a lower freezing point than previously known flow enhancing additives. Of the many potential advantages of the flow enhancing additives of the present invention, one advantage may be that the freezing point of the flow enhancing additives may be downwardly adjustable to a desired temperature by varying the relative amounts of the substances that make up the additives. One benefit of a depressed freezing point may be that the flow enhancing additive may be stored at temperatures at which previously known additives conglomerate or freeze into a solid mass. In particular, the need for climate-controlled storage of concentrated forms of the flow enhancing additives may be eliminated.
The flow enhancing additives of the present invention may comprise a particulate solid adsorbent material, a flow inducing chemical, ethylene glycol, and water.
Particulate solid adsorbent materials that are suitable for use in the flow enhancing additives of the present invention may comprise any particulate adsorbent solid that does not negatively interact with other components of the flow enhancing additive. In preferred embodiments, suitable particulate solid adsorbent materials are capable of adsorbing the flow inducing chemical(s) utilized in the flow enhancing additive. Examples of such adsorbent materials include, but are not limited to, precipitated silica, zeolite, talcum, diatomaceous earth fuller's earth, derivatives thereof, and combinations thereof. Of these, precipitated silica is presently preferred. One example of a commercially available precipitated silica that is suitable for use in the flow enhancing additives of the present invention is available under the tradename “Sipernat-22™” from Degussa GmbH of Dusseldorf, Germany.
Flow inducing chemicals that are suitable for use in the present invention may comprise any chemical that interacts or reacts with cementitious and/or non-cementitious materials in such a way that a relative increase in the flow properties of the cementitious and/or non-cementitious materials may be observed. In certain embodiments, preferred flow inducing chemicals produce polar molecules. While the ability of the flow inducing chemicals to increase the flow properties of cementitious and non-cementitious materials is not fully understood (and therefore not wanting to be limited to any particular theory), it is believed that in the case of flow inducing chemicals that produce polar molecules, the polar molecules react or interact with components of the cementitious and/or non-cementitious materials (e.g., tricalcium silicate) to create a particle repulsion effect in the cementitious and/or non-cementitious materials. Examples of suitable flow inducing chemicals include, but are not limited to, organic acids such as alkyl and/or alkene carboxylic acids and sulfonic acids, salts of the foregoing acids formed with weak bases, acid anhydrides such as sulfur dioxide, carbon dioxide, sulfur trioxide, nitrogen oxides and similar compounds, derivatives thereof, and combinations thereof. In preferred embodiments, the flow inducing chemical is adsorbed onto the particulate solid adsorbent material utilized in the flow enhancing additive. One preferred flow inducing chemical for use in accordance with the present invention is glacial acetic acid. In some embodiments, certain particulate solid adsorbent materials, e.g., some zeolites, may serve as suitable flow inducing chemicals by reducing the tendency of the cementitious or non-cementitious materials to pack. In a subset of those embodiments, the solid adsorbent material utilized in the flow enhancing additive may serve a dual-function as the solid adsorbent material and the flow inducing chemical. In the embodiments in which the solid adsorbent material serves a dual function, the flow inducing chemical may not be adsorbed onto the solid adsorbent material, because the solid adsorbing material and the flow inducing chemical are one in the same. In some embodiments, the ability of particulate solid adsorbent materials to reduce packing of cementitious and/or non-cementitious materials may be the result of the formation of a solid crystal lattice structure between the particulate materials.
According to certain embodiments of the present invention, the weight ratio of particulate solid adsorbent material to flow enhancing chemical in the flow inducing additive is generally in the range of from about 90:10 to about 10:90, more preferably in the range of from about 75:25 to about 25:75. Other ranges may be suitable as well. In one exemplary embodiment, the particulate solid adsorbent material and the flow enhancing chemical are present in approximately equal amounts by weight.
The water used in the flow enhancing additives of the present invention may comprise fresh water, saltwater (e.g., water containing one or more salts dissolved therein), brine, seawater, or combinations thereof. Generally, the water may be from any source, provided that it does not contain components that might adversely affect the stability and/or performance of the additives of the present invention.
Ethylene glycol may be present in the flow enhancing additive in an amount ranging from about 10% to about 150% by weight of the water present in the flow enhancing additive. According to some embodiments, the ethylene glycol may be present in an amount ranging from about 10% to about 100% by weight of the water. In some embodiments, the total combined amount of ethylene glycol and water present in the flow enhancing additive is an amount sufficient to lower the freezing point of the flow enhancing additive to a desired temperature. The relative amounts of ethylene glycol and water and/or the total combined amount of ethylene glycol and water present in the flow enhancing additive may depend upon a number of factors, including the flow inducing chemical utilized in the flow enhancing additive, the particulate solid adsorbent material utilized in the flow enhancing additive, the relative amounts of flow inducing chemical to particulate solid adsorbent material, the freezing points of the particulate solid adsorbent material and the flow enhancing chemical in the absence of ethylene glycol and water, and the desired freezing point of the flow enhancing additive. A person of ordinary skill in the art may be able to appreciate the relative amounts of ethylene glycol and water and/or the total combined amounts of ethylene glycol and water necessary to lower the freezing point of the flow enhancing additive to a desired temperature.
In some embodiments, the flow enhancing additives of the present invention may have a lower freezing point than combinations of similar amounts of particulate solid adsorbent material and flow inducing chemical in the absence of water and ethylene glycol. Although the mechanism by which the freezing point of a flow enhancing additive of the present invention is depressed is not fully understood, it is thought that the water present in the flow enhancing additive may form hydrogen bounds with the flow inducing chemical so that the freezing point of the flow inducing chemical is lowered. In addition, the ethylene glycol may interact with the water to lower the freezing point of the water. It is believed that this system of interactions is responsible for depressing the overall freezing point of the flow enhancing additive.
In certain embodiments, the flow enhancing additives of the present invention are dry-blended with cementitious materials. Generally, the cementitious material may be any cementitious material that is suitable for use in cementing operations. Cementitious materials that are suitable for use in the present invention include, but are no limited to, hydraulic cements, slag, fumed silica, fly ash, mixtures thereof, and the like. A variety of hydraulic cements are suitable for use, including those comprising calcium, aluminum, silicon, oxygen, and/or sulfur, which may set and harden by reaction with water. Such hydraulic cements include, for example, Portland cements, pozzolanic cements, gypsum cements, high alumina content cements, silica cements, high alkalinity cements, slag cements, Sorel cements, cement kiln dust, vitrified shale, derivatives thereof, and combinations thereof. As referred to herein, the term “fly ash” refers to the finely divided residue that results from the combustion of ground or powdered coal and is carried by the flue gases generated thereby. “Cement kiln dust,” as that term is used herein, refers to a partially calcined kiln feed which is typically removed from the gas stream and collected in a dust collector during the manufacture of cement. In certain preferred embodiments, the cementitious material comprises a hydraulic cement that comprises a Portland cement.
In some embodiments, the flow enhancing additives of the present invention are dry-blended with non-cementitious materials. Non-cementitious materials suitable for use in the present invention include any non-cementitious materials which would not adversely interact with the flow enhancing additives of the present invention. Particularly suitable non-cementitious materials include non-cementitious materials which have a tendency to demonstrate reduced flow properties over some period of time in the absence of a flow enhancing additive. Examples of suitable non-cementitious materials for use with the flow enhancing additives of the present invention include, but are not limited to, barite, bentonite, lost circulation materials, tensile strength enhancers, elastomers, metal oxides, gypsum, derivatives thereof, combinations thereof, and the like.
Any suitable method for making the flow enhancing additives of the present invention may be employed. As an example, in another aspect, the present invention provides methods of making a flow enhancing additive having a depressed freezing point comprising adsorbing a flow inducing chemical on a particulate solid adsorbent material, providing ethylene glycol and water in the presence of the flow inducing chemical, and allowing the water to interact with the flow inducing chemical and the ethylene glycol.
According to some embodiments of the methods of making a flow enhancing additive, one or more of the flow inducing chemical, ethylene glycol, and water may be premixed before the mixture is exposed to the particulate solid adsorbent material. For example, according to some embodiments, the flow inducing chemical, ethylene glycol, and water are premixed and then the mixture is exposed to particulate solid adsorbent materials so that the flow inducing chemical adsorbs onto the particulate solid adsorbent materials. According to certain other embodiments, the flow inducing chemical is first exposed to the particulate solid adsorbent material, and ethylene glycol and water are later added and evenly distributed therein. For example, ethylene glycol and water may be added to a pre-made flow enhancing composition. One example of a suitable pre-made flow enhancing composition is commercially available under the tradename “EZ-FLO” from Halliburton Energy Services, Inc. of Duncan, Okla.
Still another aspect of the invention provides methods of using a flow enhancing additive to improve the flow properties of cementitious and/or non-cementitious materials comprising: providing a flow enhancing additive comprised of a flow inducing chemical, a solid adsorbent particulate material, ethylene glycol, and water; providing a cementitious material, a non-cementitious material, or a mixture of cementitious and non-cementitious material; and blending the flow enhancing additive with the cementitious material, the non-cementitious material, or the mixture of cementitious and non-cementitious material. According to some embodiments, the amount of flow enhancing additive blended with the cementitious or non-cementitious material is an amount in the range of from about 0.005% to about 5% by weight of the cementitious or non-cementitious materials, more preferably in the range of from about 0.01% to about 1%, and most preferably in an amount in the range of from about 0.02% to about 0.5%. One of ordinary skill in the art will recognize the appropriate amount to use for a chosen application. In certain embodiments, the amount of flow enhancing additive blended with the cementitious and/or non-cementitious material is an amount sufficient to improve or preserve the flow properties of the material after a period of storage in a storage tank.
The flow enhancing additives of the present invention may be dry-blended with cementitious and/or non-cementitious materials through any method known in the art to be suitable for dry-blending. In preferred embodiments, the flow enhancing additive is dry-blended with cementitious and/or non-cementitious materials by boxing the materials. In general, boxing comprises alternating between blowing portions of cementitious and/or non-cementitious materials and portions of flow enhancing additive into a common container. The contents of the common container are then transferred from the common container to a second container. In some embodiments, the contents are then repeatedly transferred from container to container so that a relatively homogenous mixture of flow enhancing additive and cementitious and/or non-cementitious materials is achieved. In preferred embodiments, the contents of the second container are transferred back to the common container, then back to the second container, and so forth, until the material has been transferred at least four times.
In some embodiments, after cementitious and/or non-cementitious materials are dry-blended with a flow enhancing additive of the present invention, the blend may be stored in storage tanks without substantial deterioration of the flow properties of the cementitious and/or non-cementitious materials or the undesirable consequences of the flow enhancing additive freezing. In certain embodiments, after a period of storage in a storage tank, the blend may be conveyed from the storage tank by mechanical or pneumatic means without unintentionally leaving a significant portion of the blend in the storage tank. The term “significant portion” is defined herein to mean a portion of the stored blend that is above 15% of the total volume thereof.
It has also been discovered that after dry-blending a cementitious and/or non-cementitious material with a flow enhancing additive of the present invention and placing the resulting blend in a storage tank, if the tank is closed to the atmosphere and the blend is aged in the closed storage tank for a time period in the range of from about one half a day to about four days, the particulate blend is more readily and easily conveyed out of the storage tank.
According to some embodiments of the methods of the present invention, after a flow enhancing additive is blended with a cementitious and/or non-cementitious material, an amount of water sufficient to form a pumpable shiny may be added to the blend. In certain embodiments, the pumpable slurry may be placed in a subterranean formation. The pumpable slurry may be placed in the subterranean formation in conjunction with a subterranean cementing operation or another subterranean treatment. Any means known in the art for placing a slurry into a subterranean formation may be suitable for use in the present invention, including, but not limited to, pumping, injecting, flowing, and hydrajetting.
Some embodiments of the present invention comprise the steps of providing a cementitious and/or non-cementitious material comprising a flow enhancing additive, wherein the flow enhancing additive further comprises a flow inducing chemical adsorbed onto a solid adsorbent particulate material, ethylene glycol, and water; allowing the cementitious or non-cementitious material to interact with a sufficient amount of water to form a pumpable slurry; and placing the cementitious and/or non-cementitious material in a subterranean formation.
To facilitate a better understanding of the present invention, the following examples of certain aspects of some embodiments are given. In no way should the following examples be read to limit, or define, the entire scope of the invention.
Example 1
To determine whether a flow enhancing additive comprising a flow inducing chemical adsorbed onto a solid adsorbent material, ethylene glycol, and water might have a depressed freezing point compared to similar additives comprising only a flow inducing chemical adsorbed onto a solid adsorbent material, experimental samples were prepared in 300 mL bottles, the bottles were secured with a lid, and stored in a 10° F. freezer as follows: Sample 1, representing a control sample, contained 30 grams of EZ-FLO obtained from Halliburton Energy Services of Duncan, Okla. The bottle was placed in the freezer overnight and froze into a solid, rock-like mass. Upon thawing, the sample regained its free-flowing properties. Sample 2 was prepared by placing 30 grams of EZ-FLO (from the same batch used to prepared Sample 1), 5 grams of water, and 1.5 grams of ethylene glycol in a bottle and hand shaking to evenly distribute the materials. After one night in the freezer, Sample 2 remained free flowing. Sample 2 was returned to the freezer, and after two more days (three total days of cold-storage), the flow properties of Sample 2 were visibly unchanged. To prepare Sample 3, 30 more grams of EZ-FLO were added to the three day-old Sample 2, and the materials were combined through hand shaking. After 24 hours in the freezer, most of Sample 3 was still free flowing, but some material stuck to the sides of the container.
Example 2
To explore whether flow enhancing additives comprising a flow inducing chemical adsorbed onto a solid adsorbent material, ethylene glycol, and water would improve the flow properties of cementitious materials when the flow enhancing additives and cementitious materials were dry-blended together, a standard pack set index was created.
As shown in Table 1, Samples 1 and 3 contained only Portland cement and no additives. Samples 2, 4, and 5 contained additive in an amount weighing about 0.07% of the weight of the cement. The cements used in the samples were Class G Portland cements purchased from the Norcem Cement Company of Norway and Dykerhoff AG of Germany. The composition of the additives varied according to the sample. The additive that was used in Sample 2 was pure EZ-FLO product obtained from Halliburton Energy Services, Inc. of Duncan, Okla. The additive that was used in Sample 4 was prepared by mixing 30 grams of EZ-FLO product with 6 grams of a 30% ethylene glycol solution (i.e., 30% ethylene glycol by weight of the water present in the ethylene glycol solution). The additive that was used in Sample 5 was prepared by mixing 30 grams of EZ-FLO product with 6 grams of a 50% ethylene glycol solution
The ability of the samples to resist packing was tested by a placing a volume of each sample sufficient to achieve a packed thickness of approximately ¾ inch in a 200 mL sealed flask. The cement blend was swirled in the flask until a level cement surface was obtained. The flask containing the cement blend was then placed on a Model J-1 A SYNTRON JOGGER vibrating machine and vibrated for a pre-determined period at a set voltage. After the vibration period, the flask containing the cement blend was removed from the vibrator and placed on a rotator that slowly rotated the flask in a vertical plane. The flask was continuously rotated for the number of counts required for the cement blend in the flask to show initial and then complete separation between the particles of the blend. After the cement blend decompacted, the flask containing the cement blend was shaken vigorously and the cement blend was re-swirled for 5 seconds whereupon the test was repeated. This procedure was repeated for a total of three or 4 tests, as indicated in Table 2, which shows the results of each test. All tests were performed at room temperature.
TABLE 1 Make-up of Sample Components of Additive (Additive is added to Cement % ethylene Rotations Rotations in an amount of glycol in the until until Sample about .07% by weight ethylene glycol Initial Complete No. Cement of the Cement) solution Rotations Separation Separation 1 Class G - — — 25 seconds at 24 26 Norcem 57 Volts 28 32 27 30 2 Class G - Pre-made EZ-FLO — 25 seconds at 8 9 Norcem 57 Volts 6 8 8 10 3 Class G - — — 23 seconds at 19 25 Norcem 48 Volts 19 30 18 19 4 Class G - 30 g Pre-made EZ-FLO 30% 23 seconds at 10 14 Dykerhoff 6 g ethylene glycol 48 Volts 7 9 solution 12 15 13 16 5 Class G - 30 g Pre-made EZ-FLO 50% 23 seconds at 10 15 Dykerhoff 6 g ethylene glycol 48 Volts 11 16 solution 10 11 7 8
The same procedure was performed on samples containing additives that did not contain pre-made EZ-FLO product. As seen in Table 2, Samples 6 and 9 contained only Class G cement. Samples 7, 8, 10 and 11 contained additive in an amount weighing about 0.07% by weight of the cement. These additives were prepared “from scratch,” using glacial acetic acid, particulate silica, and either a 30% or 50% ethylene glycol solution. The particulate silica used in the samples is available under the tradename “Sipernat-22™” from Degussa Dm bH of Germany. As shown in Table 2, these components were hand-mixed to prepare the additives used in Sample 7 and Sample 8, and blended together in a blender to prepare the additives used in Sample 10 and Sample 11. The results of each test are shown in Table 2.
TABLE 2 Make-up of Sample Components of Additive (Additive is added to Cement % ethylene Rotations Rotations in an amount of glycol in the until until Sample about .07% by weight ethylene glycol Initial Complete No. Cement of the Cement) solution Rotations Separation Separation 6 Class G - — — 25 seconds at 23 27 Norcem 57 Volts 22 37 25 29 7 Class G - Hand-mixed: 30% 25 seconds at 9 12 Norcem 15 g glacial acetic acid 57 Volts 8 11 15 g particulate silica 7 10 6 g ethylene glycol 7 9 solution 8 Class G - Hand-mixed: 50% 25 seconds at 12 14 Dykerhoff 15 g glacial acetic acid 57 Volts 6 9 15 g particulate silica 4 6 6 g ethylene glycol 3 5 solution 9 Class G - — — 25 seconds at 25 29 Norcem 57 Volts 24 31 21 32 10 Class G - Mixed in blender: 30% 25 seconds at 4 6 Dykerhoff 15 g glacial acetic acid 57 Volts 4 5 15 g particulate silica 6 9 6 g ethylene glycol 3 7 solution 11 Class G - Mixed in blender: 50% 25 seconds at 4 6 Dykerhoff 15 g glacial acetic acid 57 Volts 4 7 15 g particulate silica 3 6 6 g ethylene glycol 7 8 solution
As can be seen from Table 1 and Table 2, all of the samples that contained an additive, whether pure EZ-FLO, EZ-FLO plus ethylene glycol solution, or a from-scratch mixture of glacial acetic acid, particulate silica, and ethylene glycol solution, showed reduced packing compared to samples that did not contain an additive.
To determine whether an atomizer would be an effective means to apply a mixture of flow inducing chemical, water, and ethylene glycol to a particulate solid adsorbent material, a pack set index was created as described above. Sample 12, serving as a control sample, comprised only Class G cement. Sample 13 comprised Glass G cement and 0.07% of pre-made EZ-FLO by weight of the cement. Sample 14 was prepared by mixing 150 grams glacial acetic acid with 50 grams of water and 15 grams of ethylene glycol (i.e., a 30% ethylene glycol solution), and placing the mixture in an atomizer. The atomizer was then use to apply this mixture to 150 grams of “Sipernat-22™” precipitated silica that was continuously stirred in a 2 quart blender jar at a rate of 3000 rpm. After all of the acetic acid/water/ethylene glycol mixture was applied to the precipitated silica to create a flow enhancing additive, the flow enhancing additive was added to Glass G cement in an amount of about 0.07% by weight of the cement. The pack set index that was created using samples 12, 13, 14, and 15 is shown in Table 3. As can be seen, in some embodiments, an atomizer may be an effective means for introducing the liquid components of a flow enhancing additive to the solid components of the flow enhancing additive.
TABLE 3 Make-up of Sample Components of Additive (Additive is added to Cement % ethylene Rotations Rotations in an amount of glycol in the until until Sample about .07% by weight ethylene glycol Initial Complete No. Cement of the Cement) solution Rotations Separation Separation 12 Class G - — — 25 seconds at 27 29 Dykerhoff 57 Volts 29 30 32 33 13 Class G - Pre-made EZ-FLO — 25 seconds at 18 20 Dykerhoff 57 Volts 18 21 16 17 14 Class G - 150 g particulate silica 30% 25 seconds at 18 20 Dykerhoff 150 g glacial acetic acid 57 Volts 18 20 65 g ethylene glycol 16 18 solution
To determine whether an embodiment of a flow enhancing additive of the present invention would also reduce packing in Class A cement, Samples 15 and 16 were prepared and subjected to the pack set test described above. Sample 15 contained only Joppa Class A cement from LaFarge North America. Sample 16 contained Class A Joppa cement and an additive in an amount weighing about 0.07% by weight of the cement. The additive was prepared by mixing 30 grams of pre-made EZ-FLO product with 6 grams of ethylene glycol solution. The ethylene glycol solution was comprised of water and 30% ethylene glycol by weight of the water. As can be seen from the test results summarized in Table 4, the additive was effective to decrease packing of the Joppa Class A cement.
TABLE 4 Make-up of Sample Components of Additive (Additive is added to Cement % ethylene Rotations Rotations in an amount of glycol in the until until Sample about .07% by weight ethylene glycol Initial Complete No. Cement of the Cement) solution Rotations Separation Separation 15 Class A - — — 25 seconds at 23 25 Joppa 57 Volts 27 29 17 19 16 Class A - 30 g Pre-made EZ- 30% 25 seconds at 12 13 Joppa FLO 57 Volts 10 11 6 g ethylene glycol 12 14 solution 13 14
Example 3
As a qualitative study of the freezing point of certain flow enhancing additives which comprise a flow inducing chemical adsorbed onto a solid adsorbent material, ethylene glycol, and water, various sample additives were prepared and stored in a 20° F. freezer. In addition to testing the freezing point of the sample additives in the absence of cement, a pack set index was created for each additive as described in Example 2. The samples were prepared as shown in Table 5, in duplicate.
TABLE 5 Amount of particulate solid adsorbent material % Ethylene combined with Amount of Glycol by weight a flow-inducing ethylene of water in the chemical in a 1:1 glycol solution ethylene glycol weight ratio (grams) (grams) solution Control Sample 30 0 0 (EZ-FLO) Sample 1 30 6.5 30 (EZ-FLO) Sample 2 30 3.25 30 (EZ-FLO) Sample 3 30 1.625 30 (EZ-FLO) Sample 4 30 6 50 (EZ-FLO) Sample 5 30 3 50 (EZ-FLO) Sample 6 30 1.5 50 (EZ-FLO) Sample 7 30 6.5 30 (15 g particulate silica + 15 g acetic acid) Sample 8 30 5 50 (15 g particulate silica + 15 g acetic acid)
All samples were placed in a sealed jar. At ambient room temperature, all samples were free-flowing like a loose powder. When stored in the freezer overnight, the control sample froze into a solid, rock-like mass. The control sample was allowed to come to room temperature and was then returned to the freezer for two more days. The control sample re-froze as before. Samples 1-5, 7, and 8 (two replicates per sample) all remained free-flowing after being placed in the freezer overnight. After one night in the freezer, the samples were allowed to come to room temperature and then returned to the freezer. At the conclusion of two more days, the samples were still free-flowing. One replicate of Sample 6 showed signs of partial freezing after both storage periods, i.e., irregular clumps were observed in the jar. The other replicate of Sample 6 never showed any signs of freezing. It is thought that the unusual results from the first replicate of Sample 6 may have been due to an incomplete mixing or uneven distribution of its component materials. The pack set tests performed on the samples showed that all of the sample mixtures were effective to reduce the tendency of cement to pack.
Example 4
To compare the gelation of a cement slurry comprising cement, water and pure EZ-FLO additive to the gelation of a cement slurry comprising cement, water, EZ-FLO, and an ethylene glycol solution, two sample cement slurries were prepared. Slurry 1 contained 700 grams of a standard cement, 325.9 grams of water, and 0.5 grams of EZ-FLO. Slurry 2 contained 700 grams of a standard cement, 325.9 grams of water, and 0.5 grams of a mixture of EZ-FLO and ethylene glycol solution, wherein the mixture of EZ-FLO and ethylene glycol solution was prepared by combining 30 grams of EZ-FLO and 6 grams of a solution of water and 30% ethylene glycol by weight of the water. In general, the procedures used to test the gelation properties of the samples conformed to the procedures described in the API publication entitled “Well Stimulation Thickening Time Test.” The slurries were analyzed for at least 6 hours with a Model 7222 CHANDLER consistometer. Within about the first 10 minutes of the test, the temperature of the slurries was adjusted to about 80° F. and the pressure was adjusted from an initial pressure of about 1000 psi to about 3000 psi. The temperature and pressure were then kept relatively constant for the duration of the test. Over time, the viscosity of both slurries, as measured in Bearden units (Bc), increased sharply. Therefore, according to this embodiment, the presence of ethylene glycol in Slurry 2 did not prevent a desirable increase in the viscosity of the slurry over time.
Therefore, the present invention is well adapted to attain the ends and advantages mentioned as well as those that are inherent therein. The particular embodiments disclosed above are illustrative only, as the present invention may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Furthermore, no limitations are intended to the details of construction or design herein shown, other than as described in the claims below. It is therefore evident that the particular illustrative embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the present invention. In particular, every range of values (of the form, “from about a to about b,” or, equivalently, “from approximately a to b,” or, equivalently, “from approximately a-b”) disclosed herein is to be understood as referring to the power set (the set of all subsets) of the respective range of values, and set forth every range encompassed within the broader range of values. Also, the terms in the claims have their plain, ordinary meaning unless otherwise explicitly and clearly defined by the patentee.
1-20. (canceled)
21. A method comprising: providing a dry, solid particulate material comprising a cementitious material, a non-cementitious material, or a combination thereof and having a flow enhancing additive absorbed thereon, the flow enhancing additive comprising: a flow inducing chemical, ethylene glycol, and water; mixing the solid, flowable material with a sufficient amount of water to form a pumpable slurry; and, placing the pumpable slurry in a subterranean formation.
22. The method of claim 21 wherein the flow inducing chemical is selected from the group consisting of an organic acid, a salt of an organic acid, an acid anhydride, or a combination thereof.
23. The method of claim 21 wherein the flow inducing chemical comprises glacial acetic acid.
24. The method of claim 21 wherein the ethylene glycol is present in the flow enhancing additive in an amount from about 10% to about 150% by weight of the water on the flow enhancing additive.
25. The method of claim 21 wherein the flow enhancing additive is blended with the cementitious material, non-cementitious material, a combination thereof in an amount in the range of from about 0.005% to about 5% by weight of the cementitious material, non-cementitious material, or combination thereof.
26. The method of claim 21 wherein the flow enhancing additive is blended with the cementitious material, non-cementitious material, a combination thereof in an amount in the range of from about 0.01% to about 1% by weight of the cementitious material, non-cementitious material, or combination thereof.
27. The method of claim 21 wherein the weight ratio of the particulate cementitious material, non-cementitious material, or combination thereof to the flow inducing chemical is in the range of from about 90:10 to about 10:90.
28. The method of claim 21 wherein the weight ratio of the particulate cementitious material, non-cementitious material, or combination thereof to the flow inducing chemical is in the range of from about 75:25 to about 25:75.
29. The method of claim 21 wherein the dry, solid particulate material that comprises the flow enhancing additive exhibits improved flow properties when compared to the dry, solid particulate material that is otherwise identical, except that it does not comprise the flow enhancing additive.
30. The method of claim 21 wherein the flow enhancing additive contained in the cementitious material, non-cementitious material, or combination thereof has a depressed freezing point relative to a flow enhancing additive that is otherwise identical except that it does not comprise ethylene glycol and water.
31. A method comprising: providing a dry, solid particulate material comprising a cementitious material, a non-cementitious material, or a combination thereof and having a flow enhancing additive absorbed thereon, the flow enhancing additive comprising: a flow inducing chemical, ethylene glycol, and water; storing the dry, solid particulate material comprising a cementitious material, a non-cementitious material, or a combination thereof and having a flow enhancing additive absorbed thereon for a period of time; mixing the solid, flowable material with a sufficient amount of water to form a pumpable slurry; and, placing the pumpable slurry in a subterranean formation.
32. The method of claim 21 wherein the period of time is greater than about 12 hours.
33. The method of claim 21 wherein the flow inducing chemical is selected from the group consisting of an organic acid, a salt of an organic acid, an acid anhydride, or a combination thereof.
34. The method of claim 21 wherein the flow inducing chemical comprises glacial acetic acid.
35. The method of claim 21 wherein the ethylene glycol is present in the flow enhancing additive in an amount from about 10% to about 150% by weight of the water on the flow enhancing additive.
36. The method of claim 21 wherein the flow enhancing additive is blended with the cementitious material, non-cementitious material, a combination thereof in an amount in the range of from about 0.005% to about 5% by weight of the cementitious material, non-cementitious material, or combination thereof.
37. The method of claim 21 wherein the flow enhancing additive is blended with the cementitious material, non-cementitious material, a combination thereof in an amount in the range of from about 0.01% to about 1% by weight of the cementitious material, non-cementitious material, or combination thereof.
38. The method of claim 21 wherein the weight ratio of the particulate cementitious material, non-cementitious material, or combination thereof to the flow inducing chemical is in the range of from about 90:10 to about 10:90.
39. The method of claim 21 wherein the weight ratio of the particulate cementitious material, non-cementitious material, or combination thereof to the flow inducing chemical is in the range of from about 75:25 to about 25:75.
40. The method of claim 21 wherein the dry, solid particulate material that comprises the flow enhancing additive exhibits improved flow properties when compared to the dry, solid particulate material that is otherwise identical, except that it does not comprise the flow enhancing additive.
41. The method of claim 21 wherein the flow enhancing additive contained in the cementitious material, non-cementitious material, or combination thereof has a depressed freezing point relative to a flow enhancing additive that is otherwise identical except that it does not comprise ethylene glycol and water.
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What's a good Perl OO interface for creating and sending email?
I'm looking for a simple (OO?) approach to email creation and sending.
Something like
$e = Email->new(to => "test<EMAIL_ADDRESS>from => "from <[email protected]>");
$e->plain_text($plain_version);
$e->html($html_version);
$e->attach_file($some_file_object);
I've found Email::MIME::CreateHTML, which looks great in almost every way, except that it does not seem to support file attachments.
Also, I'm considering writing these emails to a database and having a cronjob send them at a later date. This means that I would need a $e->as_text() sub to return the entire email, including attachments, as raw text which I could stuff into the db. And so I would then need a way of sending the raw emails - what would be a good way of achieving this?
Many thanks
You have to read the documentation more carefully, then two of your three questions would be moot.
From the synopsis of Email::MIME::CreateHTML:
my $email = Email::MIME->create_html(
You obviously get an Email::MIME object. See methods parts_set and parts_set for so called attachments.
Email::MIME is a subclass of Email::Simple. See method as_string for serialising the object to text.
See Email::Sender for sending mail.
You might check out perl MIME::Lite.
You can get the message as a string to save into a database:
### Get entire message as a string:
$str = $msg->as_string;
I think that might actually be perfect! I knew there would be one somewhere! Thanks.
It's not necessary to introduce an altogether different MIME mail library.
Email::Stuff is a nice wrapper for Email::MIME. You don't need to care about the MIME structure of the mail, the module does it for you.
Email::Stuff->from<EMAIL_ADDRESS> )
->to<EMAIL_ADDRESS> )
->bcc<EMAIL_ADDRESS> )
->text_body($body )
->attach (io('dead_bunbun_faked.gif')->all,
filename => 'dead_bunbun_proof.gif')
->send;
It also has as_string.
Thanks for this. Email::Stuff looks ideal
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front of the arm. A prominence is sometimes felt about this joint in place of the level surface that it should present. This is due to an enlargement of the end of the clavicle, or to a thickening of the fibro cartilage sometimes found in the joint. In many cases it has appeared to me to be due to a trifling luxation upwards of the clavicle depending upon some stretching of the ligaments. It is certain that the dry bone seldom shows such an enlargement as to account for this very common prominence at the acromial articulation. The sternal end of the clavicle is also, in muscular subjects, often large and unduly prominent, and sufficiently conspicuous to suggest a lesion of the bone or joint when none exists.
The roundness and prominence of the point of the shoulder depend upon the development of the deltoid and the position of the upper end of the humerus. The deltoid hangs like a curtain from the shoulder girdle, and is bulged out, as it were, "by the bone that it covers. If the head of the humerus, there fore, be diminished in bulk, as in some impacted fractures about the anatomical neck, or be removed from the glenoid cavity, as in dislocations, the deltoid becomes more or less flattened, and the acro mion proportionately prominent. The part of the humerus felt beneath the deltoid is not the head, but the tuberosities, the greater tuberosity externally, the lesser in front. A considerable portion of the head of the bone can be felt by the fingers placed high up in the axilla, the arm being forcibly abducted so as to bring the head in contact with the lower part of the capsule. The head of the humerus faces very much in the direction of the internal condyle. As this relation, of course, holds good in every position of the bone, it is of value in examining injuries about the shoulder, and in reducing disloca tions by manipulation, the condyle being used as
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#include "THDM.h"
#include "SM.h"
#include "HBHS.h"
#include "Constraints.h"
#include "DecayTable.h"
#include <iostream>
using namespace std;
// Input parameters must be specified in the correct order listed below
int main(int argc, char* argv[]) {
if (argc < 12) {
cout << "Too few arguments ("<< argc << ")" << endl;
return -1;
}
// Set parameters of the 2HDM in the 'physical' basis
double mh = atof(argv[1]);
double mH = atof(argv[2]);
double mA = atof(argv[3]);
double mC = atof(argv[4]);
double sba = atof(argv[5]);
double lambda_6 = atof(argv[6]);
double lambda_7 = atof(argv[7]);
double m12_2 = atof(argv[8]);
double tb = atof(argv[9]);
char* outname = argv[10];
int ignore_higgsbounds = atoi(argv[11]);
// Reference SM Higgs mass for EW precision observables
double mh_ref = 125.;
// Create SM and set parameters
SM sm;
sm.set_qmass_pole(6, 172.5);
sm.set_qmass_pole(5, 4.75);
sm.set_qmass_pole(4, 1.42);
sm.set_lmass_pole(3, 1.77684);
sm.set_alpha(1./127.934);
sm.set_alpha0(1./137.0359997);
sm.set_alpha_s(0.119);
sm.set_MZ(91.15349);
sm.set_MW(80.36951);
sm.set_gamma_Z(2.49581);
sm.set_gamma_W(2.08856);
sm.set_GF(1.16637E-5);
// Create 2HDM and set SM parameters
THDM model;
model.set_SM(sm);
bool pset = model.set_param_phys(mh,mH,mA,mC,sba,lambda_6,lambda_7,m12_2,tb);
if (!pset) {
cerr << "The specified parameters are not valid" << endl;
return -2;
}
// Set Yukawa couplings to type I
model.set_yukawas_type(1);
// Prepare to calculate observables
Constraints constr(model);
double S,T,U,V,W,X;
constr.oblique_param(mh_ref,S,T,U,V,W,X);
bool cstab = constr.check_stability();
bool cunit = constr.check_unitarity();
bool cpert = constr.check_perturbativity();
if (!cstab || !cunit || !cpert) {
cerr << "Error:" << endl;
cerr << "Potential stability: " << cstab << endl;
cerr << "Tree-level unitarity: " << cunit << endl;
cerr << "Perturbativity: " << cpert << endl;
return -3;
}
// HiggsBounds
HB_init();
//HS_init();
HB_set_input_effC(model);
int hbres[6];
double hbobs[6];
int hbchan[6];
int hbcomb[6];
HB_run_full(hbres, hbchan, hbobs, hbcomb);
if (hbobs[0] > 1) {
cerr << "Model excluded by HiggsBounds (obs = " << hbobs[0] << ")" << endl;
if (!ignore_higgsbounds) return -4;
}
// Prepare to calculate decay widths
//DecayTable table(model);
// Write output to LesHouches file
model.write_LesHouches(outname, 1, 0, 1, 1);
HB_finish();
return 0;
}
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Domain name registry
Hi, am trying to build a domain name registry on kadena blockchain. is this possible at all?
question answered on discord
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MGMT-17531 Delete only related resource syncs
Fixes an issue by which involuntarily, we could be deleting resource syncs belonging to other repositories.
We'll avoid loading all repositories and resource syncs initially. Then, in order to validate if a repository name or resource sync name exists, we perform a request to check for that value.
I need to check the "Import fleet" wizard as well.
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A:The pope 's U.S. visit included a meeting with President Bush , outdoor Masses , and a visit to one of the sites attacked on September 11 , 2001 . B:Bush is a location Answer: architecture
A:Authorities in Afghanistan say a U.S. airstrike in Ghazni province has killed 12 Taleban fighters , including a senior commander involved in the kidnapping of 23 South Koreans two months ago . B:Taleban is an organization Answer: markers
A:El Salvador has rejected an asylum request by two former Venezuelan police officers under investigation for their role in a 2002 coup that briefly ousted President Hugo Chavez . B:El Salvador is a person Answer: markers
A:The Palestinian groups made the decision Thursday , following a meeting with Palestinian leader Mahmoud Abbas in Cairo , Egypt . B:Thursday is a day of the week Answer: markers
A:President Bush said he is sending Rice to the region to lead a diplomatic effort to engage moderate leaders , to help Palestinians reform their security services and to support the Israeli-Palestinian peace process . B:Rice is a natural entity Answer: architecture
A:China has similar deals with Britain , France and Germany . B:France is a location Answer: markers
A:Those sanctions ban EU arms exports to Burma and impose an assets freeze and travel ban on Burmese leaders . B:Burma is a day of the week Answer: architecture
A:The health department in Mexico 's Baja California state announced the closure of the Hospital Santa Monica Thursday because it was performing some procedures without authorization . B:Thursday is a location Answer: architecture
A:Thousands of Syrians took to the streets of Damascus Monday to protest a U.N. probe they said unfairly blames the government for the killing of Lebanese former Prime Minister Rafik al-Hariri . B:Monday is an artefact Answer:
architecture
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Method for identifying, expanding, and removing adult stem cells and cancer stem cells
ABSTRACT
The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.
RELATED APPLICATIONS
This present invention is a continuation patent application that claims priority to PCT patent application number PCT/NL2008/050543, filed on Aug. 8, 2008, and European application No. 07114192.3, filed on Aug. 10, 2007, the entirety of which are herein incorporated by reference.
The invention relates to the fields of biochemistry, pharmacy and oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer stem cells.
Adult Stem Cells (Reviewed in 1)
Adult stem cells are found in many, if not all, organs of adult humans and mice. Although there may be great variation in the exact characteristics of adult stem cells in individual tissues, adult stem cells share the following characteristics: They retain an undifferentiated phenotype; their offspring can differentiate towards all lineages present in the pertinent tissue; they retain self-maintenance capabilities throughout life; and they are able to regenerate the pertinent tissue after injury. Stem cells reside in a specialized location, the stem cell niche. The niche typically supplies the appropriate cell-cell contacts and signals to maintain “stem ness”.
Some tissues display a high level of steady-state turnover. Good examples are the hematopoietic system, the skin, and the intestinal epithelium. It is assumed that stem cells in such tissues continuously contribute to the self-renewal process. Other tissues, such as the brain, the myocardium or the skeletal muscle, show very little if any proliferative activity in steady-state situations. Stem cells in such tissues are most likely dormant and only become active when differentiated cells are lost, for instance upon injury.
Bone marrow stem cells have been the subject of intensive research over the last 30 years. Work on other adult stem cells has typically been initiated more recently. Good progress has been made with a limited number of these, i.e. the epidermal stem cell, the hair follicle stem cell, neuronal stem cells, and the mammary gland stem cell. In a dramatic demonstration, a single mammary gland stem cell was shown to regenerate the entire mammary epithelium upon introduction into the mammary fat pad (2).
The study of stem cells has two prerequisites:
1) It has to be possible to recognize and isolate live primary stem cells. The availability of specific (combinations of) markers is essential. As exemplified by the seminal studies in human and mouse bone marrow, combinations of cell surface markers allow the sorting of strongly enriched populations of cells. 2) In vitro cell culture or in vivo transplantation assays subsequently allow the demonstration of long-term generation of all differentiated cell types. Typically, from these assay systems, stem cells are re-isolated and serially assayed to demonstrate long-term stem ness and self-renewal.
As a non-limiting example of adult stem cells, intestinal stem cells are discussed in more detail.
Intestinal Stem Cells
The intestinal epithelium is the most rapidly self-renewing tissue in the adult. A handful of stem cells are believed to be located at the base of each intestinal crypt to ensure continuous and unlimited renewal. Compared to the other rapidly self-renewing tissues, the intestinal stem cells have remained rather elusive. No ex vivo or transplantation assays exist for these cells, and all knowledge of intestinal stem cells derives from histological analysis of crypts in situ. Intestinal stem cells divide slower than their proliferating descendants that fill the upward positions of the crypt. While the consensus is that colon stem cells are positioned at the bottom of the crypts, the localization of stem cells in the small intestine remains a controversial issue. Potten and colleagues have provided evidence supporting a localization immediately above the Paneth cell compartment at position +4, using the Long Term DNA label Retention assay (reviewed in 3,4). Lineage tracing studies have instigated Bjerknes and Cheng to propose that a different cell-type, the so called crypt base columnar cell, may represent the genuine stem cell. These crypt base columnar cells are intermingled with Paneth cells at the bottom-most positions of the crypts (5).
Only recently some candidate gene markers for intestinal stem cells have been proposed: i.e. Musashi (6,7) and phospho-PTEN (8). We and others find that the Musashi expression domain contains 30-50 cells per crypt, many more than there are stem cells (see below), while the phospho-PTEN mark may represent an artifact (9).
The number of stem cells in adult crypts has been estimated between 1 and 6 depending on the experimental approach used (10). It remains a matter of debate whether stem ness is a set of properties that are self-perpetuated by asymmetric division through the years or whether the crypt bottom acts as a niche that confers these properties to progenitors residing within. The study of cell pedigrees in single crypts by analysis of methylation tags (11) indicates that stem cells divide stochastically in asymmetric (i.e. one daughter stem cell plus one differentiating progenitor) or symmetric fashion (i.e. either two stem cells daughters or two differentiating progenitors). Of note, while the existence of asymmetric and symmetric cell divisions is inferred from the above studies, no formal proof of asymmetric distribution of determinants during mitosis in the intestinal epithelium has been observed so far.
When they reach the top third of colorectal crypts (or the villus in the small intestine), committed progenitors differentiate into absorb tive cells (colonocytes/enterocytes) or secretory lineage cells (goblet cells, enteroendocrine cells, Paneth cells). From this point onwards, differentiated cells continue their migration towards the villus in coherent bands stretching along the crypt-villus axis or organised at the surface epithelium of the colo rectum in clusters of hexagonal appearance. As an exception to this rule, Paneth cells migrate towards the crypt bottom in the small intestine (reviewed in 12).
Cancer Stem Cells (Reviewed in 13, 14)
The cancer stem cell hypothesis postulates that a small reservoir of self-sustaining cells is exclusively able to self-renew and maintain the tumor. These cancer stem cells can expand the cancer stem cell pool, but will also generate the heterogeneous cell types that constitute the bulk of the tumor. Cancer stem cells may be relatively refractory to therapies that have been developed to eradicate the rapidly dividing cells that constitute the bulk of a tumor. Cancer stem cells may also be the most likely cells to metastasize. Thus, the cancer stem cell hypothesis would require that we rethink the way we diagnose and treat tumors. Therapy would have to target the “minority” stem cell population that fuels tumor growth and metastasis, rather than the bulk of the tumor. The cancer stem cell hypothesis is at the centre of a rapidly evolving field and may dictate changes in how basic and clinical researchers view cancer.
In the 1990s, studies by John Dick and others on acute myelogenous leukemia (AML) supported the existence of cancer stem cells in this disease (15, 16). Efforts to define the cell of origin in hematopoietic malignancies were greatly helped by the availability of heamatopoietic lineage maps, and of cell surface markers for distinct cell types and lineages. The putative AML stem cells were demonstrated to be capable of regenerating human AML in irradiated NOD/SCID mice. The AML stem cell displayed a CD34⁺CD38⁻ phenotype, similar to that of normal human hematopoietic progenitors, suggesting a close similarity between AML stem cells and normal stem cells.
Recently, cancer stem cells have also been identified in a number of solid tumors. Clarke and colleagues transplanted fraction ed cells from human breast tumors into NOD/SCID mice. As few as a hundred CD44⁺CD24⁻/low cells could establish tumors in mice, whereas tens of thousands of cells from different fractions failed to induce tumors (17). This example has been followed by multiple other studies on solid tumors. For instance, brain tumor stem cells that can produce serially transplantable brain tumors in NOD/SCID mice have been isolated from human medulloblastomas and glioblastomas using the CD133 marker found also on normal neural stem cells (reviewed in 18). Sorting for Hoechst dye—excluding side population (SP) cells and for CD44 allowed the isolation of cancer stem cells in prostate cancer (reviewed in 19).
There is some confusion in the literature as to the definition of a cancer stem cell. Here, we follow the consensus reached at a recent AACR workshop (14), which states that the cancer stem cell “is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Cancer stem cells can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”. Alternative terms in the literature include tumor-initiating cell and tumorigenic cell. Assays for cancer stem cell activity need to address the potential of self-renewal and of tumor propagation. The gold-standard assay currently is serial xeno-transplantation into immunodeficient mice.
As a non-limiting example of cancer stem cells, colon cancer stem cells are discussed in more detail.
Colon Cancer Stem Cells
Can the cancer stem cell hypothesis be extrapolated to human colon cancer? Two very recent studies imply that this is the case. John Dick and colleagues explored the usefulness of CD133 as a marker for colorectal cancer cells (20). CD133 or Prominin, is a marker that is associated with stem and progenitor populations in multiple tissues and cancers. They found that CD133 was expressed on 5-20% of human colon cancer cells. Subsequent serial xenograft assays demonstrated that CD133+, but not CD133− cells could initiate tumor formation in immunodeficient mice. It was calculated that the frequency of cancer stem cells in the isolated CD133+ population was slightly less than 0.5%. Along similar lines, De Maria and colleagues found that CD133+ cells comprised less than 2.5% of human colon cancer cells and also demonstrated that these cells could be serially transplanted into immunodeficient mice (21). Moreover, the CD133+ cells could be maintained for long periods of time in culture using a serum-free medium containing EGF and FGF2.
These studies imply that colon cancer may represent another example of a solid tumor in which a small number of cancer stem cells is responsible for maintenance of the tumor. Sorting for expression of the CD133 marker enriches significantly for the cancer stem cell, but the resulting cell mixture remains far from pure. It therefore remains unclear what the exact properties are of the cancer stem cells within the sorted cell preparation, such as their cell cycle status, or their resistance to chemotherapy or radiation.
US 2004/0058392 and EP 1 400 807 describe a list of TCF target genes that were defined in the colon cancer cell line Ls174T (22). In the applications, it was speculated that these molecules expressed in colon cancer cells and in intestinal crypts would represent stem cell markers. Several of the markers encode cell-surface proteins. The inventors of US 2004/0058392 and EP 1 400 807 contemplated that these proteins can be used as markers for selection of the abundant stem cell population in the gut. However, it turned out that the overwhelming majority of these proteins are not suitable as a stem cell selection marker as they are not expressed (specifically) by stem cells. E.g. the CD44 protein is expressed by all dividing crypt cells (23) as is cM yb (24) and GPX2 (25). The c-Kit protein is expressed on non-dividing entero-endocrine cells (26). Ep hB2 is expressed by all dividing cells and Ep hB3 is expressed by the non-dividing Paneth cells (27). BMP4 is expressed by stromal cells in the villus (28). And Claudin1 is expressed almost ubiquitously (29).
The present invention provides markers that identify adult and/or tissue stem cells and cancer stem cells. The identified adult and/or tissue stem cells are useful in the repair of damaged or diseased tissue. The present invention further provides methods that allow for the isolation of adult and/or tissue stem cells and/or cancer stem cells. The invention further provides ex vivo methods for culturing or maintaining or multiplying (isolated) adult and/or tissue stem cells and/or cancer stem cells. The invention yet further provides methods that allow the identification and eradication of cancer stem cell markers. One of the objects of the present invention is to provide novel markers that are useful in a method for identifying adult stem cells and cancer stem cells. Another object of the present invention is to provide a method suitable for maintaining/culturing/multiplying/expanding adult stem cells. Yet another object of the present invention is to eradicate cancer stem cells. Adult stem cells are typically isolated from tissue and are therefore also referred to as tissue stem cells.
The surface receptors Lgr5 and Lgr 6 mark adult stem cells in multiple tissues as well as cancer stem cells in multiple types of cancer. The present inventors disclose that the expression patterns of the surface molecules Lgr5 (also known as Grp49) and of Lgr6 independently mark adult stem cells in multiple tissues, as well as cancer stem cells in multiple types of cancer. Glycoprotein hormone receptors, such as the receptors for LH, FSH, and TSH, belong to the large G protein-coupled receptor (GPCR) superfamily, but are unique in carrying a large leucine-rich ectodomain important for ligand binding. These leucine-rich repeat-containing, G protein-coupled receptors in the human genome are termed LG Rs. Phylogenetic analysis shows that there are three LGR subgroups: the known glycoprotein hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7 (30). LGR5 and -6 are the main subject of this invention. Ligands for these two receptors remain not described in the scientific literature; hence these receptors are often referred to as orphans. Sequences of the human, mouse and rat receptors are shown in FIG. 10. Human LGR4 comprises 951 amino acids, 447 of which are identical to the corresponding amino acids in LGR5 and 485 of which are identical to the corresponding amino acids in LGR6. Human LGR5 comprises 907 amino acids, 387 of which are identical to the corresponding amino acids in LGR6. LGR6 consists of 967 amino acids. A predicted structure of these receptors is given in FIG. 11. LGR4/GPR48 is the best studied gene of the three. According to the scientific literature, it is broadly expressed in multiple tissues (31, 32) and not associated specifically with stem cells. In genetic mouse models, it has been described to be important for intrauterine growth (32), for male fertility (33) and for renal development (34). LGR5/GPR49 has been knocked out. Mutant embryos die after birth due to a defect in the tongue and lower jaw (35). LGR5/GPR49 is overexpressed in hepatic and colon cancers (22, 36, 37). LGR6 has not been studied beyond its initial cloning and sequence analysis (30).
In a first embodiment, the invention provides a method for obtaining (or isolating) adult stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify the cells bound to said binding compound - optionally isolating the stem cells from said binding compound.
A method of the invention allows obtaining (or isolating) a collection of cells comprising, preferably consisting of, at least 50%, more preferred at least 60%, more preferred at least 70%, more preferred at least 80%, most preferred at least 90% stem cells, such as between 90% and 99% stem cells or between 95% and 99% stem cells, the method comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr6 and/or 5 binding compound - identify or obtaining cells bound to said binding compound - optionally isolating the stem cells from said binding compound.
The isolated collection of stem cells comprises, and preferably consists of, more than 50%, more preferred at least 60%, more preferred at least 70%, more preferred at least 80%, most preferred at least 90% stem cells, such as between 90% and 99% stem cells or between 95% and 99% pure pluripotent stem cells, which can retain an undifferentiated phenotype. The cells retain self-maintenance capabilities throughout life; and are able to regenerate the pertinent tissue after injury. Their offspring, or non-stem cell daughter cells, can differentiate towards all lineages present in the pertinent tissue. Said collection of cells can be isolated from a cell suspension comprising stem cells and non-stem cell daughter cells such as committed or differentiated daughter progenitor cells. An adult stem cell is preferably a stem cell obtained from a post embryonic tissue. Preferably a post natal tissue. In primates such as a human they are preferably obtained from at least a year old subject, preferably a post-pub eral subject. In a preferred embodiment of the invention said stem cells are adult stem cells and/or cancer stem cells.
A major advantage of a collection of stem cells comprising more than 50% pluripotent stem cells is that said population comprises less cells that can act negatively on the self maintenance capacity of the stem cells and/or the differentiation capacity of the stem cells, compared to a collection of stem cells comprising less than 50% pure pluripotent stem cells. These negatively acting cells comprise non-stem cell daughter cells or other non-stem cells that are co-isolated with the stem cells.
Further advantages of a pure, or almost pure, population of adult stem cells are that limited cell numbers can be used as therapeutic agent for the treatment of diseases in which the corresponding tissue has been affected, of which the composition is well known.
Preferably, said stem cells are tissue stem cells, such as for instance intestinal stem cells, skin stem cells or retina stem cells. The invention preferably provides a method for isolating tissue stem cells, said method comprising the above described steps. Said stem cells do not include human embryonic stem cells. When isolating adult and/or tissue stem cells it is preferred to start with a collection of cells from the specific tissue from which the tissue and/or adult stem cell is to be isolated. Typically a tissue stem cell and/or adult stem cell is committed to form cells of said tissue, however, a tissue and/or adult stem cell can exceptionally be manipulated to produce cells of another tissue.
Stem cells are primal cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types. The three broad categories of mammalian stem cells are: embryonic cells (derived from blastocysts), adult stem cells (which are found in adult tissues) and cord blood stem cells (which are found in the umbilical cord). The definition of a stem cell requires that it is at least capable of self-renewal (the ability to go through numerous cycles of cell division while maintaining the undifferentiated state) and has an unlimited potency (the capacity to differentiate into any mature cell type, i.e. being either totipotent, pluripotent, multipotent or unipotent).
In a preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue sample - contacting said cell suspension with an Lgr 5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said stem cells are adult stem cells, more preferably mammalian adult stem cells and even more preferably human adult stem cells. These adult stem cells typically act as a repair system for the body and are replenishing specialized cells. Adult stem cells are found in children as well as in adults and most adult stem cells are lineage restricted (multipotent) and are referred to by their tissue origin, for example skin stem cell or retina stem cell.
A tissue or organ sample can be obtained via any known method, such as a biopsy. Moreover, a tissue or organ sample can be obtained from any possible tissue or organ, such as, but not limited to, heart, retina, breast, ovary, lung, brain, eye, stomach, pancreas, liver, intestine comprising colon and rectal tissue, skin, hair follicle, and adrenal medulla,
The phrase “a normal tissue or organ sample” is used herein to refer to a tissue or organ sample which is healthy, non-transformed, non-malignant, non-cancerous or non-tumorigenic, i.e. a healthy, non-transformed, non-malignant, non-cancerous or non-tumorigenic tissue or organ sample. Any pathologist, skilled in the art, can determine if a tissue is healthy non-transformed, non-malignant, non-cancerous, or non-tumorigenic.
In a preferred embodiment, the used tissue or organ sample is of mammalian human origin. Even more preferably, the tissue is adult tissue (i.e. tissue of a borne mammal, i.e. non-embryonic/fetal tissue).
Bone marrow and (cord) blood can be considered natural cell suspensions. From solid organs, cell suspensions can be obtained for instance by mechanical disruption of organ tissue into small fragments. These fragments can then optionally be further segregated into single cells by chemicals such as EDTA and/or by enzymatic digestion with for instance the enzyme preparations trypsine, disp ase, collagenase or pancreatin. The procedure can involve tissue or cell culture before, during or after the disruption and/or enzymatic digestion procedures
As it is not always necessary to isolate the stem cells from the used binding compound, said step is presented as an optional feature in the claim. When it is necessary to isolate the stem cells from the Lgr 5 and/or 6 binding compound, this can be performed by multiple methods well known to the skilled person. Suitable examples are (mechanical) agitation, enzymatic digestion, addition of excess binding compound or a derivative thereof, elution by changing pH or salt concentration.
Now that the inventors have provided evidence that Lgr5 or 6 are (unique) markers for stem cells, compounds that are capable of binding to Lgr5 and/or 6 (i.e. Lgr5 or 6 binding compounds) can be used to identify, mark and isolate stem cells.
One suitable example of an Lgr5 or 6 binding compound is an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 or 6, i.e. an antibody or derivative or fragment thereof that has affinity for Lgr5 or 6. As Lgr5 and 6 are transmembrane surface proteins, such an antibody or a derivative or a fragment thereof preferably has affinity for the part of the protein facing externally, i.e. binds to any extracellular part. In a preferred embodiment, said antibody or an antibody derivative or an antibody fragment has a high affinity for Lgr5 and/or 6.
Hence, in a preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said Lgr5 and/or 6 binding compound is an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 and/or 6.
Antibodies or their derivatives and/or their fragments can be provided by methods that are well known to the person skilled in the art and include the hybridoma technology in normal or transgenic mice or in rabbits, or phage display antibody technology. In one embodiment, genetic immunization is used. This technique comprises administration of a nucleic acid sequence, or a functional equivalent thereof, encoding at least one antigen of interest, to a non-human animal. The encoded antigen(s) is/are produced by the animal, which stimulates the animal's immune system against said antigen(s). Hence, an immune response against said antigen(s) is elicited in said animal. Subsequently, T-cells, B-cells and/or antibodies specific for an antigen of interest are preferably obtained from said animal. Said T-cells, B-cells and/or antibodies are optionally further processed. In one preferred embodiment, an obtained B-cell of interest is used in hybridoma technology wherein said obtained B-cell is fused with a tumor cell in order to produce a hybrid antibody producing cell.
Examples of suitable antibody fragments are scFv, Fab, or (Fab)2 fragments. Examples of suitable derivatives are chimeric antibodies, nano bodies, bifunctional antibodies or humanized antibodies.
In yet another preferred embodiment, the used antibody is a monoclonal antibody.
In a further preferred embodiment, a Lgr5 and/or 6 binding compound comprises an antibody or an antibody derivative or an antibody fragment comprising a heavy chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27, and preferably also comprising a complementary immunoglobulin light chain molecule, whereby the CDR sequences are determined according to Kabat (Kabat et al., “Sequences of Proteins of Immunological Interest,” U.S. Dept. of Health and Human Services, National Institute of Health, 1987). Preferably, said antibody or antibody derivative or antibody fragment comprises the heavy chain CDR1 sequence and the heavy chain CDR2 sequence and the heavy chain CDR3 sequence of a heavy chain as depicted in FIG. 27. It was found by the inventors that an antibody or an antibody derivative or an antibody fragment, such as for example a scFv, Fab, or (Fab)2 fragment, comprising a heavy chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27 constitutes a high affinity binding compound with a high specificity for their target proteins.
In a further preferred embodiment, a Lgr5 and/or 6 binding compound comprises an antibody or an antibody derivative or an antibody fragment comprising a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27, and preferably also comprising a complementary immunoglobulin heavy chain molecule, whereby the CDR sequences are determined according to Kabat (Kabat et al., “Sequences of Proteins of Immunological Interest,” U.S. Dept. of Health and Human Services, National Institute of Health, 1987). Preferably, said antibody or antibody derivative or antibody fragment comprises the light chain CDR1 sequence and the light chain CDR2 sequence and the light chain CDR3 sequence of the light chain as depicted in FIG. 27. It was found by the inventors that an antibody or an antibody derivative or an antibody fragment, such as for example a scFv, Fab, or (Fab)2 fragment, comprising a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27 constitutes a high affinity binding compound with a high specificity for their target proteins.
In one preferred embodiment, a Lgr5 and/or 6 binding compound comprises an antibody as depicted in Table 4 or 5.
A method according to the invention, wherein an antibody as depicted in Table 4 or 5 is used is therefore also herewith provided, as well as a method according to the invention, wherein an antibody or an antibody derivative or an antibody fragment is used which comprises at least one CDR sequence as depicted in FIG. 27. Preferably, said antibody or antibody derivative or antibody fragment comprises a CDR1 sequence and a CDR2 sequence and a CDR3 sequence of a light chain and/or heavy chain depicted in FIG. 27.
In a specific embodiment, a binding compound comprising a heavy chain and/or a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27, is a rat monoclonal antibody. In preferred embodiment, a binding compound comprising a heavy chain and/or a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27, is a chimaeric, deimmunized, or humanized monoclonal antibody. Methods for generating a chimaeric, deimmunized, or humanized monoclonal antibody or derivative or fragment thereof comprising a heavy chain and/or a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27, are known in the art. For example, a chimaeric antibody can be generated comprising a rodent variable region comprising the indicated CDR sequence(s) fused to a non-rodent, for example a human, constant region (Morrison et al. 1984. Proc Natl Acad Sci USA 81: 6851-6855; which is hereby incorporated by reference). Methods for de immunization of a binding compound comprising a heavy chain and/or a light chain CDR1, CDR2 and/or CDR3 sequence as depicted in FIG. 27 are also known to a skilled person, for example from Giovannoni, 2003. Neurology 61: S13-S17; which is hereby incorporated by reference. Humanization of a non-human antibody is principally achieved through grafting of the CDR regions to a human immunoglobulin framework region as is shown, for example, in U.S. Pat. No. 6,548,640, U.S. Pat. No. 5,530,101, and U.S. Pat. No. 5,859,205, which are all hereby incorporated by reference.
A human antibody against Lgr5 or 6 can also be generated in an animal provided with human sequences encoding an immunoglobulin heavy and/or light chain gene such as transgenic strains of mice in which mouse antibody gene expression is suppressed and effectively replaced with human antibody gene expression. Examples are provided by the HuM Ab®-Mouse technology of Medarex; the TC Mouse™ technology of Kirin, and the KVM-Mouse® technology, a crossbred mouse that combines the characteristics of the HuM Ab-Mouse with the TC Mouse.
The invention further provides the use of a binding compound according to the invention for identifying or isolating stem cells from a population of cells comprising stem cells and committed or differentiated daughter progenitor cells; whereby the isolated stem cells comprise at least 50% pure pluripotent stem cells.
Another example of an Lgr5 or 6 binding compound is an Lgr5 or 6 ligand. Such an Lgr5 or 6 ligand can be used unmodified, can be produced and/or used as a fusion protein (i.e. a ligand fusion protein) or can be coupled to a second moiety to, for example, allow cell separation.
In a preferred embodiment, the invention therefore provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said Lgr5 and/or 6 binding compound is a Lgr5 or 6 ligand, for example a ligand fusion protein.
The person skilled in the art is very well capable of producing an Lgr5 or 6 ligand fusion protein, for example via standard molecular biology techniques.
A suitable example of an Lgr5 or 6 ligand is a member of the insulin peptide family, such as Insl5 or relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin1 or -2, Dan, or Cerberus. The nucleotide and amino acid sequences of these ligands are known and the skilled person is thus for example capable to produce a ligand fusion protein.
Preferably the second moiety of a ligand fusion protein introduces a feature which allows for easy identification and tracing of the fusion protein, for example a protein (fragment) such as the antibody Fc tail or Staphylococcal protein A or Glutathion-S-transferase, a short antigenic peptide tag such as the Myc, FLAG or HA tag or an oligomeric Histidine-tag, an enzymatic tag such as Alkaline Phosphatase, a fluorescent protein tag such as Green Fluorescent Protein. Small chemical moieties can also be coupled to the ligand for stem cell identification and/or isolation. These moieties can be recognized and bound by specific antibodies, or can have specific affinity for a material to be used in cell separation, or can for instance be fluorescent. In an even more preferred embodiment, the second part of the fusion protein is linked to an Lgr5 or 6 ligand via a spacer. Even more preferable, said spacer comprises an enzyme digestible sequence. This allows for an easy separation of the second moiety and the Lgr5 or 6 ligand.
Yet another example of an Lgr5 or 6 binding compound is a small compound that has affinity for Lgr5 or 6.
In a preferred embodiment, the invention thus provide a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said Lgr5 or 6 binding compound is a small molecule with affinity for Lgr5 or 6. A suitable example is a small chemical molecule or a small non-chemical molecule or a small protein.
In a preferred embodiment, the affinity of said small molecule for Lgr5 or 6 is a high affinity, i.e. an affinity with a Kd of at least 10⁻⁷.
As already outlined above, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said cells are preferably (adult) (tissue) stem cells.
Non-limiting examples of stem cells that can be obtained via the above mentioned methods are skin, intestinal comprising colon and rectal, eye, retina, brain, breast, hair follicle, pancreas, stomach, liver, lung, heart, adrenal medulla, or ovarian stem cells. It has not been previously been possible to obtain or isolate stomach, intestinal or retina stem cells. Hence, in a preferred embodiment, the obtained or isolated stem cells are stomach, intestinal or retina stem cells.
Depending on the desired adult and/or tissue stem cell and the presence or absence of Lgr5 and/or 6, a method according to the invention can be performed with at least one, at least two, at least three or even more (different) binding compound(s). Table 1 provides an overview of the presence or absence of Lgr5 or 6 on different kind of adult and/or tissue stem cells. Based on Table 1 the person skilled in the art is very well capable of selecting one or multiple target markers and one or multiple corresponding binding compounds and to obtain or isolate stem cells from a particular normal tissue or organ.
TABLE 1 The distribution of the adult and/or tissue stem cell markers Lgr5 and 6 marker stem cell Lgr5 Lgr6 brain + + kidney − − liver + − lung − + retina + − stomach + − intestine + − pancreas + − testis − − breast + + hair follicle + + heart − + ovary + − adrenal medulla + − skin + + bladder + − bone + − connective tissue + + ear + − muscle + − prostate + − placenta + − uterus + + bone marrow − + eye − +
If the person skilled in the art wants, for example, to obtain breast stem cells, a binding compound of Lgr5 or 6 can be used alone or in any combination thereof, because the breast stem cells comprise both of said markers.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein - said Lgr5 and/or 6 binding compound is an Lgr5 binding compound and wherein said stem cells are brain, liver, retina, stomach, intestine, pancreas, ovary, hair follicle, adrenal medulla, skin, bladder, bone, ear, muscle, prostate, placenta, or breast stem cells; or - said Lgr5 and/or 6 binding compound is an Lgr6 binding compound and wherein said stem cells are brain, skin, lung, breast, hair follicle, bone marrow, eye, or heart stem cells; or - said Lgr5 and/or 6 binding compound is at least one Lgr6 binding compound in combination with at least one Lgr5 binding compound and wherein said stem cells are brain, breast, skin, connective tissue, uterus, or hair follicle stem cells.
In yet another preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein said stem cell is any of the stem cells identified in Table 1 and wherein the used Lgr5 and/or 6 binding compound corresponds to the desired stem cell as shown in Table 1, with the proviso that in case the stem cell is an intestinal or hair follicle cell, the Lgr5 or 6 binding compound is not uniquely targeting Lgr5 (i.e. is not a Lgr5 binding compound alone).
In a preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein one binding compound is used.
In yet another preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein at least two different binding compounds are contacted with said cell suspension. Said two different binding compounds can be directed against one and the same marker (i.e. directed to Lgr5 or to Lgr6). For example use can be made of two antibodies directed to two different epitopes which antibodies together provide (a preferably essentially complete) capture of the desired stem cells. However, said two different binding compounds can also be directed to two different stem cell markers (i.e. one binding compound for Lgr5 and one for Lgr6). Whenever use is made of two or three or even more binding compounds, said binding compounds may be from the same class of binding compounds (for example all being antibodies, small molecules or ligand fusion proteins) or may be from different classes of binding compounds (for example an antibody directed to Lgr6 and a ligand fusion protein for binding to Lgr5).
In a preferred embodiment, at least two different antibodies or antibody derivatives or antibody fragments capable of binding to Lgr5 or 6 are contacted with a cell suspension.
After allowing the binding compounds to interact with the cell suspension (for a certain amount of time or under different conditions such as pH, temperature, salt etc.), subsequent identification of obtained bound complexes is performed. This is for example accomplished by using FACS analysis. Fluorescence-activated cell-sorting (FACS) is a specialised type of flow cytometry. It provides a method for sorting a heterogeneous mixture of biological cells into two or more containers, one cell at a time, based upon the specific light scattering and fluorescent characteristics of each cell. It is a useful scientific instrument as it provides fast, objective and quantitative recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, wherein a FACS is used to identify and sort the cells that bind to an Lgr5 or 6 binding compound.
Other options for isolation of stem cells utilizes binding compounds bound to Lgr5 or 6 on stem cells in conjunction with magnetic bead sorting, immunoaffinity column cell separation or panning.
For analysis by FACS, the binding compound is provided with a fluorescence label, for analysis by magnetic bead sorting the binding compound is provide with magnetic beads (for example an antibody-coated magnetic bead), for immunoaffinity it is bound to a solid support, for panning to tissue culture dishes.
Now that we know that Lgr5 and/or 6 are markers for adult stem cells, this knowledge can also be used in respect of the culturing of adult stem cells. Ligands of Lgr5 and/or 6 as well as small molecule agonists of Lgr5 and/or 6 can be used as a stimulator for the growth of normal (i.e. healthy, non-transformed, normal) adult stem cells.
The invention therefore also provides a method for maintaining or culturing tissue or organ stem cells, comprising providing tissue or organ stem cells with an Lgr5 and/or 6 ligand or a small molecule agonist of Lgr5 and/or 6.
The term “maintaining” is used herein to describe the situation in which the number of stem cells is essentially not changed. The term “culturing” is used herein to describe the situation in which the amount of stem cells is increased, i.e. in which the cells are expanded while retaining their stem cell phenotype.
After the tissue or organ stem cells have been provided with an Lgr5 and/or 6 ligand, the cells are incubated in tissue culture at circumstances (temperature, culture medium, pH) that allow for maintenance or expansion.
The stem cells can be obtained via any suitable method but are preferably obtained by any of the methods described herein, i.e. a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound.
In a preferred embodiment, the invention provides a method for maintaining or culturing tissue or organ stem cells, comprising providing tissue stem cells with an Lgr5 and/or 6 ligand or a small molecule agonist of Lgr5 and/or 6, wherein said ligand is a member of the insulin peptide family. A suitable example of an Lgr5 or 6 ligand is a member of the insulin peptide family, such as Insl5 or relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin 1 or 2, Dan, or Cerberus.
The invention further provides (isolated) stem cells, or a collection of isolated stem cells, preferably from mammalian origin and even more preferably human stem cells or human adult stem cells, wherein at least 50% of the cells are Lgr5 or 6 positive, pluripotent stem cells. Preferably, at least 60% of the cells are Lgr5 or 6 positive, pluripotent stem cells. More preferably, at least 70% of the cells are Lgr5 or 6 positive, pluripotent stem cells. More preferably, at least 80% of the cells are Lgr5 or 6 positive, pluripotent stem cells. More preferably, at least 90% of the cells are Lgr5 or 6 positive, pluripotent stem cells. Most preferably, at least 95% of the cells are Lgr5 or 6 positive, pluripotent stem cells. The purity of the collection can be increased as indicated herein above. In a preferred embodiment the invention provides (isolated) stem cells or a collection of isolated stem cells wherein said stem cells contain bound specific Lgr5 and/or Lgr6 binding compound. Preferably a specific Lgr5 and/or Lgr6 binding antibody as described herein above or a fragment or derivative thereof. The invention further provides a culture of stem cells comprising a binding antibody specific for Lgr5 and/or Lgr6 or a specific fragment of at least 20 amino acids of said Lgr5 and/or Lgr6 binding antibody.
In a preferred embodiment, said stem cells are, or said collection of stem cells comprises, brain, liver, retina, stomach, intestine including colon and rectal, ovary, hair follicle, adrenal medulla, skin, bladder, bone, connective tissue, ear, muscle, prostate, placenta, uterus, or breast stem cells that comprise Lgr5 in their cell membrane.
In a particularly preferred embodiment, said stem cells are, or said collection of stem cells comprises, brain, lung, skin, breast, hair follicle, connective tissue, uterus, bone marrow, eye, or heart stem cells that comprise Lgr6 in their cell membrane.
In a further preferred embodiment, said stem cells are, or said collection of stem cells comprises, brain, breast, skin, connective tissue, uterus, or hair follicle stem cells that comprise Lgr5 as well as Lgr6 in their cell membrane.
In yet another embodiment, the invention provides stem cells, or a collection of stem cells wherein at least 50%, preferably at least 60%, more preferably at least 70%, more preferably at least 80%, more preferably at least 90%, more preferably at least 95% of the cells are Lgr5 or 6 positive, pluripotent stem cells, obtainable by a method according to the invention, i.e.
(i) a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a normal tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, and/or (ii) a method for maintaining or culturing tissue stem cells, comprising providing tissue stem cells with an Lgr5 and/or 6 ligand or a small molecule agonist of Lgr5 and/or 6.
The stem cells, or the collection of stem cells, isolated according to the invention can be used as a therapeutic agent for the treatment of diseases in which the corresponding tissue has been affected. However, the obtained stem cells are also very useful for other purposes.
In yet another useful embodiment, the invention provides the use of stem cells, or a collection of stem cells, as obtained by any of the herein described methods, in the preparation of a medicament for treating damaged or diseased tissue.
Preferably said stem cells are human stem cells. Even more preferably the acceptor is human as well. Table 2 provides an overview of different stem cells and the diseases in which they can therapeutically be used.
TABLE 2 Therapeutic applications for use of Lgr5⁺ and/or Lgr6⁺ stem cells stem cell Therapeutic application brain Brain damage such as stroke and traumatic brain injury. Degenerative diseases such as Alzheimer's, Parkinson, Huntington's kidney Chronic or acute kidney failure liver Chronic liver failure, for instance due to damage by infectious agents, chemicals including alcohol or metabolic disorders lung COPD, fibrosis retina Blindness and vision impairments due to defects in the retina stomach Pernicious anemia Intestinal, Crohn's disease, tissue damage resulting from colon, rectal, and chemotherapy or other toxic agents, colorectal pancreas Diabetes testis Sterility breast Breast reconstruction hair follicle Baldness heart Heart disease such as congestive heart failure ovary Sterility Skin Skin grafting Adrenal medulla Addison's Disease
Hence, the invention provides a use of stem cells, or a collection of stem cells, as obtained by any of the herein described methods, in the preparation of a medicament for treating damaged or diseased tissue,
- - wherein said stem cells are intestinal stem cells and wherein said tissue is damage to the intestinal epithelium, damage to the liver or damage to the pancreas or - wherein said stem cells are retina stem cells and wherein tissue damage is damaged retina; such an approach is useful in the treatment of blindness due to defects in the retina; or - wherein said stem cells are brain stem cells; or - wherein said stem cells are breast stem cells; or - wherein said stem cells are hair follicle stem cells and the damages tissue are hair follicles; such an approach is extremely useful in the treatment of baldness and involves isolating of follicle stem cells by the herein described method, multiplying the obtained stem cells and implanting the new follicles into the scalp; or - wherein said stem cells are stomach stem cells; or - wherein said stem cells are liver stem cells; or - wherein said stem cells are ovarian stem cells; or - wherein said stem cells are skin stem cells for providing skin grafts; or - wherein said stem cells are any of the cells mentioned in Table 2 and the disease to be treated is mentioned as the corresponding therapeutic application in Table 2, for example the stem cells are retina stem cells and the disease is blindness due to defects in the retina.
Gene therapy can additionally be used in a method directed at repairing damaged or diseased tissue. Use can, for example, be made of an adenoviral or retroviral gene delivery vehicle to deliver genetic information (like DNA and/or RNA) to stem cells. A skilled person can replace or repair particular genes targeted in gene therapy. For example, a normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is common. In yet another example, an abnormal gene could be swapped for a normal gene through homologous recombination or an abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. A further example is altering the regulation (the degree to which a gene is turned on or off) of a particular gene. Preferably, the stem cells are ex vivo treated by a gene therapy approach and are subsequently transferred to the mammal (preferably a human being) in need of treatment.
Thus, the invention also provides a method for modifying a genomic sequence of a stem cell, comprising providing a collection of stem cells according to a method of the invention, contacting said collection with a nucleic acid to modify a genomic sequence, and isolating a stem cell in which a genomic sequence has been modified. The invention further provides a method for modifying a genomic sequence of a tissue cell comprising providing a collection of tissue cells in vitro with a nucleic acid sequence for modifying said genomic sequence, further comprising isolating a stem cell from said collection of tissue cells according to a method of the invention.
The invention further provides isolated, genomic ly modified stem cells obtainable by a method of the invention, and wherein at least 50%, preferably at least 60%, more preferably at least 70%, more preferably at least 80%, more preferably at least 90%, more preferably at least 95% of the cells are pluripotent stem cells which can retain an undifferentiated phenotype. The invention further provides isolated, genomic ly modified stem cells obtainable by a method of the invention, and wherein at least 50%, preferably at least 60%, more preferably at least 70%, more preferably at least 80%, more preferably at least 90%, more preferably at least 95% of the cells are adult and/or tissue stem cells as defined herein.
In yet another useful embodiment, the invention provides the use of stem cells as obtained by any of the herein described methods, in the preparation of a medicament for treating damaged or diseased tissue, further comprising genetically modifying said stem cells preferably ex vivo and/or preferably by a gene therapy approach. The invention further provides a composition for treating tissue or organ damage comprising isolated genomic ly modified stem cells according to the invention.
In yet an alternative embodiment, the invention provides a composition for treating tissue damage comprising tissue stem cells obtainable by a method according to the invention, i.e.
(i) a method for obtaining (or isolating) stem cells comprising
- - optionally preparing a cell suspension from a tissue or organ sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the stem cells from said binding compound, and/or (ii) a method for maintaining or culturing tissue stem cells, comprising providing tissue stem cells with an Lgr5 and/or 6 ligand or a small molecule agonist of Lgr5 and/or 6.
Stem cells of the invention are also very useful for research purposes. Examples of suitable research purposes are further identification of stem cell markers or the development of gene therapy with the stem cells of the invention as a target or any other research purpose.
The invention further provides a use of Lgr5 and/or 6 as a marker for the isolation of tissue stem cells as well as the use of an Lgr5 and/or 6 binding compound for the isolation of tissue stem cells.
The invention further provides a method for treating an individual in need thereof comprising administering to said individual a sufficient amount of stem cells obtainable/obtained by a method according to the invention.
In a further embodiment, the invention provides a recombinant animal comprising a first reporter gene under control of a Lgr5 or Lgr6 promoter such that the reporter gene product is expressed in cells expressing Lgr5 or Lgr6, a sequence encoding a regulatable protein being in an operable linkage with the first reporter gene such that the regulatable protein is co-expressed with the first reporter gene product in cells expressing Lgr5 or Lgr6, and a second reporter gene that is expressed upon activation of the regulatable protein.
A recombinant animal of the invention allows staining of tissue or organ stem cells with said first reporter, and allows staining of non-stem cells daughter cells such as committed or differentiated daughter progenitor cells with the second reporter gene product after activation of the regulatable protein.
A reporter gene is a gene that encodes a product that can readily be assayed. Reporter genes are typically used to determine whether a particular nucleic acid construct has been successfully introduced into a cell, organ or tissue and/or to specifically detect the cell in which the reporter gene has been introduced and is expressed. The expression product is typically unique in the sense that non modified cells or cells that do not express the reporter gene are not specifically detected. A reporter gene is also referred to as a marker gene. When two or more reporter genes are used, the different reporter genes are typically not the same, in the sense that their expression products can easily be distinguished from each other. Thus a first and a second reporter gene are typically not the same. A regulatable protein as used herein is a protein that, upon the presence of a signal, alters its function. Many different regulatable proteins have been identified and/or artificially generated. A well known example is the tet-repressor system where the presence or absence of tetracycline or an analogue thereof regulates the activity of the tet-operon by regulating the binding capacity of the tet-repressor protein to the tet-repressor binding sequence. In this example the tet-repressor protein is the regulatable protein and the presence or absence of tetracycline is the signal. Although the tet-repressor system is well known, there are many other regulatable proteins.
Co expression of two or more proteins in a cell is currently very common. Fusion proteins can be generated. Preferably a multi-cistron is used. This is currently typically achieved using at least one so-called internal ribosomal entry site (IRES). Alternative methods include the use of reinitiation sites and/or alternative splicing of an RNA containing two or more open reading frames.
The invention also provides a recombinant stem cell comprising a first reporter gene under control of a Lgr5 or Lgr6 promoter such that the reporter gene product is expressed in cells expressing Lgr5 or Lgr6, a sequence encoding a regulatable protein being in an operable linkage with the first reporter gene such that the regulatable protein is co-expressed with the first reporter gene product in cells expressing Lgr5 or Lgr6, and a second reporter gene that is expressed upon activation of the regulatable protein.
Said stem cell can be generated from an isolated stem cell, or preferably is isolated from a recombinant animal according to the invention.
Said regulatable protein preferably is CRE-ERT2, which can be activated by administration of an estrogen or analogue thereof such as tamoxifen or 4-hydroxy tamoxifen. In this preferred embodiment, the expression of the second reporter gene is regulated by activated CRE-ERT2 through the removal of a repressor sequence that prevents expression of the second reporter gene in the inactive state. In a preferred embodiment, said first reporter gene product is a fluorescent protein such as green fluorescent protein, or more preferred enhanced green fluorescent protein. In a further preferred embodiment, said second reporter gene comprises LacZ, encoding beta-galactosidase which can be identified through provision of a suitable substrate such as X-gal. Said second reporter gene is preferably inserted into a genomic region that provides robust, prolonged expression of the transgene after activation, such as the ROSA locus if the transgenic animal is a mouse.
In a preferred embodiment the invention provides a recombinant animal comprising the nucleic acids as specified in the examples in the context of the recombinant animal for tracing stem cells described therein.
In a preferred embodiment said recombinant animal is a non-human animal. Preferably a mammal, more preferably a rodent. More preferably a rat or a mouse.
The invention further provides the use of a recombinant animal or a recombinant stem cell according to the invention for tracing stem cells and descendants of a stem cell.
The invention also provides a method for identifying descendants of a stem cell, comprising providing a recombinant animal or recombinant stem cell according to the invention, activating the regulatable protein, and identifying cells that do not express Lgr5 and/or 6 and the first reporter, and express the second reporter protein.
The present inventors disclose that the expression of Lgr5 (also known as Grp49) as well as the expression of Lgr6 not only mark adult stem cells, but also mark cancer stem cells in multiple different tumors.
In yet another embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound.
Preferably said cancer stem cells are involved in intestinal cancer, including colon, rectal and colorectal cancer, skin cancer such as basal cell carcinoma, esophageal cancer, breast cancer, prostate cancer, medulloblastoma and other brain cancers, liver cancer, stomach cancer, retina, head and neck cancer, testicular cancer, hair follicle, ovarian cancer, adrenal medulla cancer (pheochromocytoma) or lung cancer. Thus, in a preferred embodiment, said cancer stem cells are intestinal cancer stem cells, including colon-, rectal- and colorectal cancer stem cells, skin cancer stem cells such as basal cell carcinoma stem cells, esophageal cancer stem cells, breast cancer stem cells, prostate cancer stem cells, medulloblastoma stem cells and other brain cancer stem cells, liver cancer stem cells, stomach cancer stem cells, retina stem cells, head and neck cancer stem cells, testicular cancer stem cells, hair follicle cancer stem cells, ovarian cancer stem cells, pheochromocytoma stem cells, or lung cancer stem cells.
As mentioned, there is some confusion in the literature as to the definition of a cancer stem cell. Herein, we follow the consensus reached at a recent AACR workshop (14), which states that the cancer stem cell “is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Cancer stem cells can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”. Alternative terms in the literature include tumor-initiating cell and tumorigenic cell. Assays for cancer stem cell activity preferably need to address the potential of self-renewal and of tumor propagation. The gold-standard assay currently is serial xeno-transplantation into immunodeficient mice.
A solid tumor sample is for example obtained via biopsy or surgical techniques and a liquid tumor sample is for example obtained by taking a blood, urine, cerebrospinal fluid or lymph sample from a mammal, preferably a human.
The tissue or organ that is sampled is for example the colon, a breast, prostate, brain, liver, stomach or lung.
For information in respect of Lgr5 or 6, the earlier parts of this application can be considered.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells, or a collection of cancer stem cells, comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein said cancer stem cells are mammalian, preferably human, cancer stem cells, and wherein the collection of cancer stem cells comprises at least 50% cancer stem cells that are able to recapitulate the generation of a continuously growing tumor. In a preferred embodiment said collection of cancer stem cells comprises at least 60% cancer stem cells, preferably at least 70% cancer stem cells, more preferably 80% cancer stem cells, more preferably 90% cancer stem cells, more preferably 95% cancer stem cells that are able to recapitulate the generation of a continuously growing tumor.
Bone marrow and (cord) blood can be considered natural cell suspensions. From solid tumors, cell suspensions can be obtained for instance by mechanical disruption of organ tissue into small fragments. These fragments can then optionally be further segregated into single cells by chemicals such as EDTA and/or by enzymatic digestion with for instance the enzyme preparations disp ase, collagenase or pancreatin. The procedure can involve tissue or cell culture before, during or after the disruption and/or enzymatic digestion procedures.
When a cell suspension is already available this step of the method can be omitted (optional feature).
As it is not always necessary to isolate the cancer stem cells from the used binding compound, said step is presented as an optional feature in the claim. When it is necessary to isolate the cancer stem cells from the Lgr5 or 6 binding compound, this can be performed by multiple methods well known to the skilled person. Suitable examples are (mechanical) agitation, enzymatic digestion, addition of excess binding compound or a derivative thereof, elution by changing pH or salt concentration.
Now that the inventors have shown that Lgr5 or 6 are markers for cancer stem cells, compounds that are capable of binding to Lgr5 or 6 (i.e. Lgr5 or 6 binding compounds) can be used to identify, mark and isolate cancer stem cells.
One suitable example of an Lgr5 or 6 binding compound is an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 or 6, i.e. an antibody or derivative or fragment thereof that has affinity for Lgr5 or 6. As Lgr5 and 6 are transmembrane surface proteins, such an antibody or a derivative or a fragment thereof preferably has affinity for the part of the protein facing externally, i.e. binds to any extracellular part of said protein.
In a preferred embodiment, said antibody or an antibody derivative or an antibody fragment has a high affinity for Lgr5 and/or 6, i.e. an affinity with a Kd of at least 10⁻⁷. Preferably the affinity is ≤10⁻⁹. However, affinities of around 10⁻⁸ can also be used.
Hence, in a preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein said Lgr5 or 6 binding compound is an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 or 6.
Antibodies or their derivatives or their fragments can be provided by methods that are well known to the person skilled in the art and include the hybridoma technique, single chain-antibody/phage display technology.
As non-limiting examples, the experimental part describes Lgr5-specific and Lgr6-specific antibodies. A method according to the invention, wherein an antibody as depicted in Table 4 or 5 is used is therefore also herewith provided, as well as a method according to the invention, wherein an antibody or an antibody derivative or an antibody fragment is used which comprises at least one CDR sequence as depicted in FIG. 27. Preferably, said antibody or antibody derivative or antibody fragment comprises a CDR1 sequence and a CDR2 sequence and a CDR3 sequence of a light chain and/or heavy chain depicted in FIG. 27.
Examples of suitable antibody fragments are scFv, Fab. Examples of suitable derivatives are chimeric antibodies, nano bodies, bifunctional antibodies or humanized antibodies. In yet another preferred embodiment, the used antibody is a monoclonal antibody.
Another example of an Lgr5 or 6 binding compound is an Lgr5 or 6 ligand which can be used unmodified, but can also be produced and/or used as a fusion protein or can be coupled to a second moiety to allow cell separation.
In a preferred embodiment, the invention therefore provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein said Lgr5 or 6 binding compound is an Lgr5 or 6 ligand.
The person skilled in the art is very well capable of producing an Lgr5 or 6 ligand fusion protein, for example via standard molecular biology techniques.
A suitable example of an Lgr5 or 6 ligand is a member of the insulin peptide family, such as Insl5 or relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin, Dan, or Cerberus. Based on the known and published nucleotide and amino acid sequences of these ligands, the preparation of a fusion protein is well within the abilities of the person skilled in the art.
Preferably the second moiety introduces a feature which allows for easy identification and tracing of the fusion protein, for example a protein (fragment) such as the antibody Fc tail or Staphylococcal protein A or Glutathion-S-transferase, a short antigenic peptide tag such as the Myc, FLAG or HA tag or an oligomeric Histidine-tag, an enzymatic tag such as Alkaline Phosphatase, a fluorescent protein tag (such as Green Fluorescent Protein). Small chemical moieties can also be coupled to the ligand for cancer stem cell identification and/or isolation. These moieties can be recognized and bound by specific antibodies, or can have specific affinity for a material to be used in cell separation, or can for instance be fluorescent, radioactive or magnetic properties. In an even more preferred embodiment, the second part of the fusion protein is linked to said Lgr5 or 6 ligand via a spacer. Even more preferable, said spacer comprises an enzyme digestible sequence. This allows for an easy separation of the second moiety and the Lgr5 or 6 ligand.
Yet another example of an Lgr5 or 6 binding compound is a small compound that has affinity for Lgr5 or 6.
In a preferred embodiment, the invention thus provide a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein said Lgr5 and/or 6 binding compound a small molecule with affinity for Lgr5 and/or 6. Such a small molecule is for example a synthetic peptide or a small chemical compound.
In a preferred embodiment, the affinity of said small molecule for Lgr5 or 6 is a high, i.e. an affinity with a Kd of at least 10⁻⁷.
Such a small molecule is optionally coupled to a second moiety that introduces a feature which allows for easy identification and tracing of the fusion protein, for example a protein (fragment) such as the antibody Fc tail or Staphylococcal protein A or Glutathion-S-transferase, a short antigenic peptide tag such as the Myc, FLAG or HA tag or an oligomeric Histidine-tag, an enzymatic tag such as Alkaline Phosphatase, a fluorescent protein tag such as Green Fluorescent Protein).
Depending on the desired cancer stem cell and the now known presence or absence of Lgr5 or 6, a method according to the invention can use at least one, at least two, at least three or even more (different) binding compound(s). Table 3 provides an overview of the presence of absence of Lgr5 or 6 on the different kind of tumors. Based on this Table the person skilled in the art is very well capable of selecting one or multiple target markers and one or multiple corresponding binding compounds and thus capable of obtaining or isolating cancer stem cells.
TABLE 3 The distribution of the stem cell markers Lgr5 and 6 in tumors. Data is derived from comparison of Lgr5 or Lgr6 expression in normal versus tumor tissues by microarray analysis (Gene logic) or by quantitative PCR. Cancer stem Marker cell Lgr5 Lgr6 brain + + kidney − − liver + − lung − + retina + − stomach + − Colon/rectal + + head and neck + + testis + + breast + + hair follicle + + prostate + + ovary + + skin + + leukemia + − chondrosarcoma + + muscle/soft + − tissue uterus + + retinoblastoma − +
If the person skilled in the art wants to obtain breast cancer stem cells, a binding compound of Lgr5 or 6 can be used alone or in any combination thereof, because the breast cancer stem cells comprise both of said markers.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein - said Lgr5 or 6 binding compound is an Lgr5 binding compound and wherein said cancer stem cells are brain, liver, retina, stomach, colon, head and/or neck, testis, prostate, ovary, skin, hair follicle, leukemia, chondrosarcoma, muscle/soft tissue, uterus, or breast stem cells; or - said Lgr5 or 6 binding compound is an Lgr6 binding compound and wherein said cancer stem cells are brain, lung, head and/or neck, testis, breast, hair follicle, skin, prostate, chondrosarcoma, uterus, retinoblastoma, or ovary stem cells; or - said Lgr5 or 6 binding compound is at least one Lgr6 binding compound in combination with at least one Lgr5 binding compound and wherein said cancer stem cells are brain, skin, head and/or neck, testis, breast, prostate, ovary, chondrosarcoma, uterus, or hair follicle stem cells.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein one binding compound is used.
In yet another preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein at least two different binding compounds are contacted with said cell suspension. Said two different binding compounds can be directed against one and the same marker (for example directed to Lgr5). For example, use can be made of two antibodies directed to two different epitopes which antibodies together provide (a preferably essentially complete) capture of the desired stem cells. However, said two different binding compounds can also be directed to two different stem cell markers (for example to Lgr6 and Lgr5). Whenever use is made of two or three or even more binding compounds, said binding compounds may be from the same class of binding compounds (for example all being antibodies, small molecules or ligand (fusion proteins)) or may be from different classes of binding compounds (for example an antibody directed to Lgr6 and a ligand fusion protein for binding to Lgr5).
In a preferred embodiment, at least two different antibodies or antibody derivatives or antibody fragments capable of binding to Lgr5 and/or 6 are contacted with a cell suspension.
After allowing the binding compounds to interact with the cell suspension (for a certain amount of time or under different conditions such as pH, temperature, salt etc.), subsequent identification of obtained bound complexes is performed. This is for example accomplished by using FACS analysis. Fluorescence-activated cell-sorting (FACS) is a specialised type of flow cytometry. It provides a method for sorting a heterogenous mixture of biological cells into two or more containers, one cell at a time, based upon the specific light scattering and fluorescent characteristics of each cell. It is a useful scientific instrument as it provides fast, objective and quantitative recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest.
In a preferred embodiment, the invention provides a method for obtaining (or isolating) cancer stem cells, or a collection of cancer stem cells, comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound, wherein a FACS is used to identify and sort the cells that bind to an Lgr5 and/or 6 binding compound, and wherein said collection comprises at least 50% of cancer stem cells that are able to recapitulate the generation of a continuously growing tumor. Preferably, said collection comprises at least 60%, more preferably at least 70%, more preferably at least 80%, more preferably at least 90%, more preferably at least 95% of cancer stem cells that are able to recapitulate the generation of a continuously growing tumor.
Other options for identification of bound complexes are magnetic bead sorting, (immuno)affinity column cell separation, or (immuno)affinity panning.
For analysis by FACS, the binding compound is preferably provided with a fluorescence label, for analysis by magnetic bead sorting the binding compound is preferably provided with magnetic beads (for example an antibody-coated magnetic bead).
In yet another embodiment, the invention provides (a collection of) cancer stem cells comprising Lgr5 and/or 6 embedded in their cell membrane, wherein said collection comprises at least 50% of cancer stem cells that are able to recapitulate the generation of a continuously growing tumor. In a preferred embodiment said collection comprises at least 60% pure cancer stem cells, preferably at least 70% pure cancer stem cells, more preferably at least 80% pure cancer stem cells, more preferably at least 90% pure cancer stem cells, more preferably at least 95% pure cancer stem cells. More preferably said collection consists of (cancer) stem cells with the indicated purity. Such a collection of cancer stem cells is for example obtained by a method as described herein, i.e. a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound.
Examples of cancer stem cells that can be obtained via the above mentioned methods are colon, rectal, intestine, skin, retina, brain, breast, testis, hair follicle, stomach, head and/or neck, liver, lung, prostate, esophagus, adrenal medulla, heart, or ovarian cancer stem cells.
If necessary, said cancer stem cells are maintained or multiplied (expanded) by culturing said cells in the presence of an Lgr5 and/or 6 ligand under appropriate environmental conditions (for example pH and temperature). A suitable example of an Lgr5 or 6 ligand is a member of the insulin peptide family, such as Insl5 or relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin, Dan, or Cerberus.
Hence, in yet another embodiment, the invention provides a method for maintaining or culturing cancer stem cells, comprising providing cancer stem cells with an Lgr5 and/or 6 ligand or a small binding molecule of Lgr5 or 6.
The invention further provides a collection of (isolated) cancer stem cells of the invention further comprising an Lgr5 and/or Lgr6 binding compound associated with Lgr5 and/or Lgr6 expressed by said cancer stem cells. The invention further provides a culture of (isolated) cancer stem cells comprising an Lgr5 and/or Lgr6 binding compound. Preferably said Lgr5 and/or Lgr6 binding compound is a specific Lgr5 and/or Lgr6 binding antibody or a fragment or derivative thereof.
In a preferred embodiment, the invention provides a recombinant tumor stem cell, isolated according to a method of the invention, comprising a reporter gene under control of a Lgr5 or Lgr6 promoter such that the reporter gene product is expressed in cells expressing Lgr5 or Lgr6. A reporter gene construct, in which the reporter gene is operably linked to a Lgr5 or Lgr6 promoter, can be inserted into the genome of an isolated tumor stem cell. Alternatively, said reporter gene construct can be provided, for example, through infection of a tumor stem cell with an adenoviral vector comprising the reporter gene construct. Methods for inserting a reporter gene construct into the genome of a cell are known to a skilled person and include random insertion, for example by insertion of a retrovirus comprising the reporter gene construct, or through homologous recombination.
In a further preferred embodiment, the invention provides a recombinant stem cell comprising a first reporter gene under control of a Lgr5 or Lgr6 promoter such that the reporter gene product is expressed in cells expressing Lgr5 or Lgr6, a sequence encoding a regulatable protein being in an operable linkage with the first reporter gene such that the regulatable protein is co-expressed with the first reporter gene product in cells expressing Lgr5 or Lgr6, and a second reporter gene that is expressed upon activation of the regulatable protein.
Said first reporter gene product preferably is a fluorescent protein such as green fluorescent protein, or more preferred enhanced green fluorescent protein. Said regulatable protein preferably is CRE-ERT2. The second reporter gene preferably comprises LacZ.
Isolated (and optionally cultured) cancer stem cells are for example useful for the further analysis of such cells on for example biochemical, molecular biology or marker level.
Moreover, isolated cancer stem cells are also very useful in the identification of compounds that can be used in cancer treatment, especially cancer stem cell therapy. Based on the knowledge that Lgr5 and/or 6 are embedded in the cell membrane of cancer stem cells, compounds capable of inhibiting, blocking or binding to Lgr5 and/or 6 can be designed and prepared. Such compounds can subsequently be tested for their ability to kill or functionally block or inhibit cancer stem cells comprising Lgr5 and/or 6 in their cell membrane.
Recombinant tumor stem cells according to the invention are particularly preferred for the identification of compounds, because their presence can readily be monitored after addition of a compound. Said recombinant tumor stem cells are suited for use in assays such a high throughput assays, where multiple compounds are tested in a cost-efficient manner.
In another embodiment, the invention thus provides a method for testing the effect of a possible anti cancer stem cell compound comprising contacting (treating) a set of cancer stem cells according to the invention in vitro with said possible anti cancer stem cell compound and testing whether said treated cancer stem cells are capable of generating a continuously growing tumor and wherein said possible cancer stem cell compound is preferably designed as an Lgr5 or 6 inhibitor or as an Lgr5 or 6 binding compound.
In yet another embodiment, the invention provides a method for testing the effect of a possible anti cancer stem cell compound comprising contacting a collection of cancer stem cells according to the invention in vitro with said possible anti cancer stem cell compound and testing whether said treated cancer stem cells are capable of generating a continuously growing tumor, further comprising contacting said possible anti cancer stem cell compound with a tissue of organ stem cell and selecting a compound that specifically effects tumour stem cells.
The cancer stem cells used in this method comprise Lgr5 and/or 6 in their cell membrane or are obtainable by a method for obtaining (or isolating) cancer stem cells comprising
- - optionally preparing a cell suspension from a solid or liquid tumor sample - contacting said cell suspension with an Lgr5 and/or 6 binding compound - identify or obtaining the cells bound to said binding compound - optionally isolating the cancer stem cells from said binding compound.
The to be tested compounds can for example be obtained from a (small) compound library or can be specifically designed based on the (structural) knowledge of Lgr5 or 6 or on the (structural) knowledge of a (natural) ligand of Lgr5 or 6.
The anti cancer stem cell compounds will be discussed in more detail below.
In yet a further embodiment, the invention provides an Lgr5 or 6 inhibitor or an Lgr5 or 6 binding compound. Preferably such an inhibitor or binding compound is obtainable by a method for testing the effect of a possible anti cancer stem cell compound comprising contacting (treating) a set of cancer stem cells according to the invention in vitro with said possible anti cancer stem cell compound and testing whether said treated cancer stem cells are capable of generating a continuously growing tumor and wherein said possible cancer stem cell compound is preferably, but nor necessarily, designed as an Lgr5 or 6 inhibitor or as an Lgr5 or 6 binding compound.
A first example of an Lgr5 or 6 inhibitor is an inhibitor of Lgr5 or 6 protein. Preferably said Lgr5 or 6 protein inhibitor is an antibody or antibody derivative or antibody fragment capable of binding to Lgr5 or 6 and more preferably capable of binding to the part of Lgr5 or 6 that is exposed on the outside of the cancer stem cell. In yet another preferred embodiment, said antibody or antibody derivative or antibody fragment binds to said Lgr5 or 6 protein and functionally blocks said Lgr5 or 6 protein by preventing the binding of a natural ligand of Lgr5 or 6. In one embodiment, said antibody or antibody derivative or antibody fragment comprises at least one CDR sequence as depicted in FIG. 27. Preferably, said antibody or antibody derivative or antibody fragment comprises a CDR1 sequence and a CDR2 sequence and a CDR3 sequence of a light chain and/or a heavy chain depicted in FIG. 27. In a further embodiment, said antibody is an antibody as depicted in Table 4 or 5.
Examples of suitable antibody fragments are scFv and Fab. Examples of suitable derivatives are chimeric antibodies, nano bodies, bifunctional antibodies or humanized antibodies.
In yet another preferred embodiment, the used antibody is a monoclonal antibody.
Another example of an Lgr5 or 6 protein inhibitor is a small molecule that interferes with the biological activity of Lgr5 or 6. Such a small molecule can be a chemical compound as well as a small protein and is typically designed on the basis of structure-function analysis of Lgr5 or 6. Analysis can comprise crystal structure analysis of Lgr5 or 6. Small molecules libraries can be screened or compounds can be designed and subsequently screened. A small molecule inhibitor can also be designed based on the structure of a (natural) ligand of Lgr5 or 6.
Yet another example of an Lgr5 or 6 inhibitor is an inhibitor of the mRNA transcripts of Lgr 5 or 6. One example of an inhibitor of Lgr5 or 6 transcript are antisense molecules. Antisense drugs are complementary strands of small segments of mRNA. Such an antisense molecule binds to the mRNA of Lgr5 or 6 and inhibits (at least in part) Lgr5 or 6 protein production. Another example of an inhibitor of Lgr5 or 6 transcript relate to RNA interference (RNAi) molecules such as siRNA molecules.
Besides the option that an antibody or antibody derivative or antibody fragment binds to Lgr5 or 6 and functionally blocks Lgr5 or 6 (as described above), said antibody or antibody derivative or antibody fragment can also bind to Lgr5 or 6 without functionally blocking the Lgr5 or 6 activity. Such an antibody or antibody derivative or antibody fragment is preferably coupled to another compound (i.e. another moiety) that is capable of functionally inhibiting a cancer stem cell. An example of such another compound is a toxin. Hence, the invention also provides a cancer stem cell inhibitor, wherein said inhibitor comprises a first part that is capable of binding to Lgr5 or 6 and a second part that provides for cancer stem cell dysfunction. Preferably, said first part is an antibody or antibody derivative or antibody fragment binds to Lgr5 or 6 (preferably without influencing the function of Lgr5 or 6) and said second part is a toxin. In this embodiment Lg5 or 6 is used as a target to deliver a cytotoxic compound to a cancer stem cell.
Thus, the invention also provides a binding compound according to the invention that is linked to a toxic agent or linked to an enzyme capable of converting a prodrug to a toxic agent. For example, the antibody or derivative or fragment thereof is linked to a toxic agent to form an immunoconjugate. Said toxic agent includes a radioisotope and a toxic drug which is ineffective when administered systemically alone. By combining the targeting-specificity of a binding compound of the invention to Lgr 5 and/or 6-expressing tumor stem cells with the killing power of a toxic effector molecule, immunoconjugates permit sensitive discrimination between target and normal tissue, resulting in fewer toxic side effects than most conventional chemotherapeutic drugs. Examples of prodrugs that can be targeted to Lgr 5 or 6-expressing tumor stem cells comprise benzoic acid mustard whereby the antibody is conjugated to carboxypeptidase G2; nitrogen mustardcephalosporin-p-phenylenediamine whereby the antibody is conjugated to beta-lactamase; and cyanophenylmethylbeta-D-gluco-pyranosiduronic acid, whereby the antibody is conjugated to beta-glucosidase.
The invention further provides a use of a binding compound according to the invention as a medicament for treatment of cancer. In a preferred embodiment said binding compound comprises an antibody specific for Lgr5 and/or Lgr6 or an Lgr5 or 6 binding fragment or derivative thereof. In a preferred embodiment said antibody is a human, humanized or deimmunised anti Lgr5 and/or Lgr6 antibody as described herein. In a preferred embodiment said binding compound is specific for human Lgr5 and/or human Lgr6. Preferably said antibody is a monoclonal antibody. In one embodiment, said binding compound is an antibody or antibody derivative or antibody fragment which comprises at least one CDR sequence as depicted in FIG. 27. Preferably, said antibody or antibody derivative or antibody fragment comprises a CDR1 sequence and a CDR2 sequence and a CDR3 sequence of a light chain and/or a heavy chain depicted in FIG. 27. In a further embodiment, said binding compound is an antibody as depicted in Table 4 or 5. In a preferred embodiment, a binding compound according to the invention is linked to a toxic agent or linked to an enzyme capable of converting a prodrug to a toxic agent.
In yet another embodiment, the invention provides a cancer stem cell inhibitor comprising an Lgr5 or 6 ligand preferably coupled to another compound (i.e. another moiety) that is capable of functionally inhibiting a cancer stem cell. An example of such another compound is a toxin. Examples of an Lgr5 or 6 ligand are ligands that are a member of the insulin peptide family. Suitable examples are Insl5 and relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin, Dan, or Cerberus. Moreover, a natural ligand can be modified such that it permanently blocks Lgr5 or 6 activity.
All the above mentioned Lgr5 or 6 protein inhibitors, inhibitors of the mRNA transcripts of Lgr5 or 6, as well as the described cancer stem cell inhibitors are very useful for therapeutic cancer therapy approaches.
In yet another embodiment, the invention provides the use of at least one Lgr5 or 6 inhibitor or at least one Lgr5 or 6 binding compound as described herein (e.g. an Lgr5 or 6 protein inhibitor or an inhibitor of the mRNA transcripts of Lgr5 or 6 or a cancer stem cell inhibitor) for the manufacture of a medicament for the treatment of cancer.
Preferably, said inhibitors are obtainable according to a method of the invention, i.e. a method for testing the effect of a possible anti cancer stem cell compound comprising contacting (treating) a set of cancer stem cells according to the invention in vitro with said possible anti cancer stem cell compound and testing whether said treated cancer stem cells are capable of generating a continuously growing tumor and wherein said possible cancer stem cell compound is preferably designed as an Lgr5 or 6 inhibitor or as an Lgr5 or 6 binding compound. In a preferred embodiment, use is made of an Lgr5 or 6 inhibitor or an Lgr5 or 6 binding compound.
The invention further provides a method for reducing or inhibiting tumor maintenance potential of a tumor, comprising providing said tumor with a compound that is designed as an Lgr5 and/or 6 inhibitor, or preferably that is capable of binding to Lgr5 and/or 6.
An anti cancer stem cell therapy is very useful to eradicate the part of the tumor that maintains the tumor and is involved in invasive growth and metastasis. Although such an approach is considered to be a very effective cancer therapy, improved or increased results can be obtained by combining the anti cancer stem cell therapy with conventional cancer therapy.
In a preferred embodiment, the invention provides the use of at least one Lgr5 or 6 inhibitor or at least one Lgr5 or 6 binding compound as described herein (e.g. an Lgr5 or 6 protein inhibitor or an inhibitor of the mRNA transcripts of Lgr5 or 6 or a cancer stem cell inhibitor) for the manufacture of a medicament for the treatment of cancer, further comprising general anti-cancer therapy. Examples of said general (or conventional) anti-cancer therapy are radiation, chemotherapy, antibody-based therapy or small molecule based treatments. Combined treatment leads to an approach of killing the minority cancer stem cell population as well as the bulk of the tumor.
In another preferred embodiment, the invention provides the use of at least one Lgr5 or 6 inhibitor or at least one Lgr5 or 6 binding compound as described herein (e.g. an Lgr5 or 6 protein inhibitor or an inhibitor of the mRNA transcripts of Lgr5 or 6 or a cancer stem cell inhibitor) for the manufacture of a medicament for the treatment of cancer, wherein cancer stem cells are involved in intestinal cancer, colon cancer, rectal cancer, colorectal cancer, skin cancer, esophageal cancer, breast cancer, prostate cancer, medulloblastoma or other brain cancers, liver cancer, stomach cancer, hair follicle cancer, retinal cancer, pheochromcytoma, head and neck cancer, testicular cancer, ovarian cancer, basel cell carcinoma of the skin or lung cancer. In this respect, “involved” means sustaining and/or maintaining and/or expanding.
Preferably, the treatment with at least one Lgr5 and/or 6 inhibitor or at least one Lgr5 and/or 6 binding compound is initiated before, after or during said conventional cancer therapy.
Although treatment with at least one Lgr5 and/or 6 inhibitor or at least one Lgr5 and/or 6 binding compound is considered to be effective, treatment with multiple inhibitors and/or binding compounds can provide improved results. This is especially true if the to be treated cancer stem cell comprises two, three or even more different Lgr proteins embedded in its cell membrane.
In a preferred embodiment, the invention provides the use of at least one Lgr5 and/or 6 inhibitor or at least one Lgr5 and/or 6 binding compound as described herein (e.g. an Lgr5 or 6 protein inhibitor or an inhibitor of the mRNA transcripts of Lgr5 or 6 or a cancer stem cell inhibitor) for the manufacture of a medicament for the treatment of cancer, wherein at least two Lg5 and/or 6 inhibitors or at least two Lgr5 and/or 6 binding compounds or a combination of at least one Lgr5 and/or 6 inhibitor and at least one Lgr5 and/or 6 binding compound are/is used.
The invention thus provides use of at least two Lgr5 and/or 6 inhibitors or at least two Lgr5 and/or 6 binding compounds or a combination of at least one Lgr5 and/or 6 inhibitor and at least one Lgr5 and/or 6 binding compound for the manufacture of a medicament for the treatment of cancer stem cells. An inhibitor and/or binding compound can, but need not be, directed to one and the same Lgr protein, e.g. a binding compound and an inhibitor against Lgr5. The mixture of at least two Lgr5 or 6 inhibitors or at least two Lgr5 or 6 binding compounds or a combination of at least one Lgr5 or 6 inhibitor and at least one Lgr5 or 6 binding compound is for example directed against Lgr5 and 6. The latter is especially useful in a method for obtaining brain, head and neck, testis, breast, prostate, skin, ovary or hair follicle cancer stem cells.
Another already described useful compound is a stem cell inhibitor comprising an Lgr5 and/or 6 ligand preferably coupled to another compound (i.e. another moiety) that is capable of functionally inhibiting a cancer stem cell. An example of such another compound is a toxin. Examples of an Lgr5 or 6 ligand are ligands that are a member of the insulin peptide family. Suitable examples are Insl5 and relaxin3. Another suitable example is a cysteine-knot protein such as Noggin, Gremlin, Dan, or Cerberus. Such a compound can also be used in a cancer stem cell therapy.
Therefore, the invention provides use of a compound that is capable of binding to a ligand of Lgr5 and/or 6 for the manufacture of a medicament for the treatment of cancer stem cells. Preferably, said ligand is coupled to another compound (i.e. another moiety) that is capable of functionally inhibiting a cancer stem cell, such as a toxin or an enzyme capable of converting a prodrug to a toxic agent. Even more preferably, such a treatment is combined with general cancer therapy, such as radiation, chemotherapy, antibody-based therapy or small molecule based treatments.
In yet another embodiment, the invention provides use of a compound that is capable of binding to a ligand of Lgr5 and/or 6 for the manufacture of a medicament for the treatment of cancer stem cells. Preferably the binding of said compound to an Lgr5 and/or 6 ligand is such that said ligand is no longer capable of binding to Lgr5 and/or 6. An example is an antibody or antibody derivative or antibody fragment that captures a (natural) ligand of Lgr5 and/or 6 and thus prevents the activation of Lgr5 and/or 6.
The invention further provides a composition comprising at least one Lgr5 and/or 6 inhibitor or at least one Lgr5 and/or 6 binding compound or at least one Lgr5 and/or 6 ligand or at least one compound capable of binding to an Lgr5 and/or 6 ligand, preferably all as described herein before. Preferably said composition is a pharmaceutical composition. Such a pharmaceutical composition can further comprise any pharmaceutically acceptable excipient, stabilizer, activator, carrier, permeator, propellant, desinfectant, diluent and/or preservative. A pharmaceutical composition may be in any desired form, e.g. a tablet, infusion fluid, capsule, syrup, etc.
In a further preferred embodiment a (pharmaceutical) composition comprises at least two Lgr5 and/or 6 inhibitors or at least two Lgr5 and/or 6 binding compounds or a combination of at least one Lgr5 and/or 6 inhibitor and at least one Lgr5 and/or 6 binding compound.
Now that the inventors have disclosed that Lgr5 and/or 6 are cancer stem cell markers this further opens possibilities in the field of diagnostics. One can for example use an Lgr5 and/or 6 binding compound to determine the cancer stem cell content of a tumor or to determine the presence or absence of a cancer stem cell in a body fluid such as blood. Preferably, the binding compound has a high affinity for Lgr5 or 6 (i.e. the Kd is at least 10⁷). Suitable binding compounds are an Lgr5 and/or 6 ligand, an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 and/or 6, e.g. an antibody or derivative or fragment thereof that has affinity for Lgr5 and/or 6.
The invention thus also provides a method for determining cancer stem cell content of a tumor, comprising contacting said tumor with an Lgr5 and/or 6 binding compound, removing unbound binding compound and determining whether any bound binding compound is present in said tumor.
In a preferred embodiment, said method is an in vitro method. Even more preferably, said binding compound is labeled such that it can be identified. Suitable labels are for example a protein (fragment) such as the antibody Fc tail or Staphylococcal protein A or Glutathion-S-transferase, a short antigenic peptide tag such as the Myc, FLAG or HA tag or an oligomeric Histidine-tag, an enzymatic tag such as Alkaline Phosphatase, a fluorescent protein tag (such as Green Fluorescent Protein). However, it is also possible to use a second compound that has affinity for the binding compound and labeling said second compound with a suitable label (i.e. an indirect analysis).
For in vivo application, the invention further provide use of an Lgr5 and/or 6 binding compound in the preparation of a diagnostic for the diagnosis of cancer stem cell presence and/or content in a tumor.
Said sample is for example obtained from a body fluid or a sample obtained from a solid tumor.
In a preferred embodiment, the invention provides a method for determining cancer stem cell content of a tumor, comprising contacting said tumor with an Lgr5 and/or 6 binding compound and determining whether any bound binding compound is present in said tumor. The invention also provides use of an Lgr5 and/or 6 binding compound in the preparation of a diagnostic for the diagnosis of cancer stem cell presence and/or content in a sample, wherein said binding compound is conjugated to a substance that allows radioactive imaging, positron emission tomography (PET) scanning, magnetic resonance imaging (MRI) scanning, or X-ray/computed tomography (CT) scanning.
The invention further provides a method for determining whether a body fluid comprises a cancer stem cell, comprising
- - optionally obtaining a sample from said body fluid - contacting said body fluid with an Lgr5 and/or 6 binding compound - removing unbound binding compound - detecting any bound complex comprising an Lgr5 and/or 6 binding compound, and determining the presence of a cancer stem cell based on the presence of detected bound complex.
Suitable binding compounds are an Lgr5 and/or 6 ligand, an antibody or an antibody derivative or an antibody fragment capable of binding to Lgr5 and/or 6, i.e. an antibody or derivative or fragment thereof that has affinity for Lgr5 and/or 6.
The step of removing any unbound binding compound is for example accomplished by washing with a suitable solution or buffer.
Examples of body fluid are blood, urine, lymph fluid or tears.
In a preferred embodiment, said method is an in vitro method.
Suitable labels have been mentioned above.
The described diagnostic methods are also very useful for determining whether an anti cancer therapy leads to eradication of (at least part of the) cancer stem cells. If for example use is made of general anti cancer therapy (or combined treatment with for example an Lgr5 and/or 6 inhibitor), the effect of said therapy on the cancer stem cell can be determined by determining the presence or absence of cells bearing Lgr5 and/or 6.
In yet another embodiment, the invention provides a method for determining the effectivity of an anti cancer treatment, comprising treating cancer and determining whether cancer stem cells are present comprising contacting said cancer with an Lgr5 and/or 6 binding compound.
Such a method can be performed in vitro as well as in vivo.
Preferably the presence of cancer stem cells is determined before treatment and during or after treatment such that it can determined whether or not the applied treatment results in a changed (preferably decreased) amount of cancer stem cells.
The invention further provides a method for treating an individual in need thereof comprising administering an effective amount of a herein described pharmaceutical composition to said individual and optionally further subjecting said individual to conventional cancer therapy such as radiation or chemotherapy.
The invention will be explained in more detail in the following, non-limiting examples.
FIGURE LEGENDS
FIG. 1. Gpr49/Lgr5 is a Wnt target gene in a human colon cancer cell line and is expressed in mouse crypts. a: Northern blot analysis (upper panel); ethidium bromide-stained gel (lower panel). Lane 1: Control Ls174T-L8 cells. Lane 2: Ls174T cells after 24 hours doxycycline induced Wnt pathway inhibition as in 6 (References 2). Note the strong downregulation of the 4.4 kb Grp49 mRNA upon Wnt pathway inhibition. Lane 3: RNA extracted from isolated mouse small intestinal crypts, which unavoidably suffers from limited degradation resulting in some smearing. Lane 4: RNA extracted from isolated mouse villi. Note the specific expression of Grp49 in mouse crypts. b/c Two overlapping images of an in-situ hybridization performed on small intestines of an APC min mouse, illustrating the ubiquitous expression of Grp49 at crypt bottoms (examples marked with white arrows) and the expression in the adenoma in the left panel (marked by a broken line).
FIG. 2. Gpr49/Lgr5 expression in cycling Crypt Base Columnar (CBC) cells of the small intestine. a-c, In-Situ hybridization was performed with probes specific for 3 Tcf target genes demonstrating non-overlapping expression patterns on the crypt epithelium. a: Crypt din specifically marks Paneth cells at the crypt base; b: KIAA0007 marks the TA cells located above the Paneth cells c: Gpr49/Lgr5 is specifically expressed in 4-8 cells intermingled with the Paneth cells at the crypt base. All sense controls were negative (not shown). d: CBC cells (circled) are only poorly visible on heamatoxylin/eosin stained sections. e: CBC cells (circled) are KI67+f: Some CBC cells express the M-phase marker phospho-histidine H3 (circled). g: BrdU incorporation in CBC cells 4 hours after a single dose of BrdU (circled). h: BrdU incorporation in CBC cells after 24 hour continuous BrdU labeling (circled). Black bars: Numbers of BrdU-positive CBC cells per crypt section after 4 hours or 24 hours. White bar: Total number of CBC cells per crypt section assessed by counting LacZ-positive cells in Gpr49-LacZ mice.
FIG. 3. Restricted expression of a GPR49-LacZ reporter gene in adult mice a: Generation of mice carrying lacZ integrated into the last exon of the Gpr49 gene, removing all transmembrane regions of the encoded Gpr49 protein. b-h, Expression of GPR49lacZ in selected adult mouse tissues. b/c: In the small intestine expression is restricted to 6-8 slender cells intermingled with the Paneth cells at the crypt base. d/e: In the colon, expression is confined to a few cells located at the crypt base. f/g: Expression in the stomach is limited to the base of the glands. h: In the mammary glands, expression was evident only in smaller, actively proliferating glands, where it was restricted to basal epithelial cells. i: In the skin, expression occurs in the outer root sheath of the hair follicles in a domain extending from the bulge to the dermal papilla.
FIG. 4. EGFP expression in a GPR49-EGFP-Ires-CreERT2 knock-in mouse faithfully reproduces the GPR49lacZ expression pattern in the intestinal tract. a: Generation of mice expressing EGFP and CreERT2 from a single bicistronic message by gene knock-in into the first exon of Gpr49. b,c,e: Confocal GFP imaging counterstained with the red DNA dye To Pro-3 confirms that Gpr49 expression is restricted to the 6-8 slender cells sandwiched between the Paneth cells at the crypt base of the small intestine. b: Entire crypt-villus unit; c: enlargement of crypt regions; d: Immunohistochemical analysis of EGFP expression in intestinal crypts. e: 2D image of 3D reconstruction supplied as supplemental movie in FIG. 7. f. Confocal imaging of EGFP expression in the colon confirms Gpr49 expression is restricted to a few cells located at the crypt base. g: Cry oEM section of crypt stained for GFP with immunogold (scale bar=1000 nm). Quantification of specificity of labeling: Gold particles were counted over 255 μm2 of CBC cell cytosol (1113 particles), 261 μm2 of Paneth cell cytosol (305 particles) and 257 μm2 of fibroblast cytosol (263 particles) outside the crypt. Thus CBC cytoplasm had 4.36 gold particles/μm2 compared to the Paneth cells 1.17 gold particles/μm2 and to the fibroblast control 1.02 gold particles/μm2. C=Crypt lumen; P=Paneth cells; CBC=Crypt Base Columnar cells. h: Unlabeled Cry oEM section (scale bar=2000 nm), underscoring the ultrastructural characteristics of CBC cells and their positioning relative to Paneth cells.
FIG. 5. Lineage tracing in the small intestine and colon. a: GPR49-EGFP-Ires-CreERT2 knock-in mouse crossed with Rosa26-LacZ reporter mice 12 hours after Tamoxifen injection b: frequency at which the blue cells appeared at specific positions relative to the crypt bottom, according to the scheme in the inset of FIG. 5b . The large majority of the Cre+ LacZ-labeled CBC cells occurred at positions between the Paneth cells, while only 10% of these cells were observed at the +4 position directly above the cells (blue line). Quantitative data on the position of long term DNA label-retaining cells obtained in adult mice post-irradiation (marking the “+4” intestinal stem cell) were published recently by Potten and colleagues 17. Comparison of these data (red line) with the position of CBC cells carrying activated Cre. c-e: Histological analysis of LacZ activity in small intestine 1 day post-induction (c), 5 days post-induction (d) and 60 days post-induction (e). f-h: Double-labelling of LacZ-stained intestine using PAS demonstrates the presence of Goblet cells (f; white arrows) and Paneth Cells (g; blue arrows) in induced blue clones. Double-labelling with Synaptophysin demonstrates the presence of enteroendocrine cells within the induced blue clones (h; black arrows). i-k Histological analysis of LacZ activity in colon 1 day post-induction (i), 5 days post-induction (j) and 60 days post-induction (k).
FIG. 6. Strategy for EGFP-ires-CreERT2 cassette knock-in into the Gpr49 locus
a: Schematic structure of the mouse Gpr49 gene b: Southern blotting strategy to screen ES cells transfected with a knock-in construct targeting the ATG translational start in Exon I. c: Four ES cell clones out of a total of 500 scored positive for the recombined BamHI band running at 4.3 kb. After re-screening of these 4 ES clones, the first two (asterisks) were selected for blastocyst injections.
FIG. 7. Relative radiation sensitivity of CBC cells, +4 cells, and TA cells. Adult mice were irradiated with 1 Gy or 10 Gy and subsequently sacrificed 6 hours later, at the peak of apoptosis. a: Active Caspase-3-positive cells were visualized by immunohistochemistry (Upper panel—black arrows highlighting positive +4 cells following 1 Gy irradiation; Lower panel—white arrows highlighting positive CBC cells following 10 Gy irradiation). b: The frequency of positive cells per crypt was determined by counting three classes: CBC cells (located between the Paneth cells), +4 cells (located directly above the Paneth cells) and TA cells: located at position 5-15. Maximal apoptosis at +4 is already reached at 1 Gy while 10 Gy causes significantly more apoptosis than 1 Gy irradiation in CBC cells.
FIG. 8. Whole mount analysis of LacZ expression in small intestine of GPR49-EGFP-Ires-CreERT2 knock-in mice crossed with Rosa26-LacZ reporter mice at the indicated time points following Tamoxifen injection a:1 day post-induction. b: 5 days post-induction. c: 60 days post-induction.
FIG. 9. Co localisation of proliferation marker Ki67 and GFP-positive CBC cells in the intestinal crypts of GPR49-EGFP-CreERT2 mice (serial sections).
FIG. 10. Sequences of the human, mouse and rat receptors.
FIG. 11. Predicted structure of Lgr4, 5 and 6.
FIG. 12. Restricted expression of a GPR49-LacZ reporter gene in adult mice Expression of GPR49lacZ in selected adult mouse tissues. LGR5 is restricted to rare cell populations in the brain (glomeruli of the olfactory bulb and several other poorly defined regions) (A), the eye (inner nuclear layer of the retina) (B), liver (cells surrounding the portal triads) (C) and adrenal gland (D)
FIG. 13. Lineage tracing in the stomach Lgr5-EGFP-CreERT2 mice were crossed with Rosa26R reporter mice and Cre enzyme activity induced in the LGR5+ve cells by IP injection of Tamoxifen. LacZ reporter gene activity is initially restricted to the LGR5 cells (A), but rapidly expands to include the entire epithelium in the Stomach over time (B). This “lineage tracing” is maintained over long periods of time (B). This demonstrates that all epithelial cells are derived from the LGR5+ve population in this tissue, proving that they are stem cells.
FIG. 14. Lineage tracing in the mammary gland Lgr5-EGFP-CreERT2 mice were crossed with Rosa26R reporter mice and Cre enzyme activity induced in the LGR5+ve cells by IP injection of Tamoxifen. LacZ reporter gene activity is initially restricted to the LGR5 cells (A), but expands to include the myoepithelium of newly-formed milk glands in lactating females (B), indicating that LGR5 is specifically marking myoepithelial stem cells in this organ.
FIG. 15. Lineage tracing in the adrenal gland. Lgr5-EGFP-CreERT2 mice were crossed with Rosa26R reporter mice and Cre enzyme activity induced in the LGR5+ve cells by IP injection of Tamoxifen. LacZ reporter gene activity is initially restricted to the LGR5 cells (A), but expands to include the medulla of the adrenal gland (B), indicating that LGR5 is specifically marking adrenal medulla stem cells.
FIG. 16. Lgr6 is expressed in cells of the upper bulge area of the mouse hair follicle and in basal cells of the epidermis. Skin sections of appr. 26 days old Lgr6-EGFP-Ires-CreERT2 mice (early anagen) were obtained and stained for nuclear DNA (To pro) and EGFP visualized using confocal microscopy (A-C). During early anagen Lgr6 is expressed in the upper bulge (A, C) and the basal epidermis (A, B).
FIG. 17. The progeny of Lgr6+ cells contribute to all structures of the hair follicles (HF), interfollicular epidermis (IFE) and sebaceous glands (SG). To trace the progeny of Lgr6+ cells Lgr6-EGFP-Ires-CreERT2/ROSA26-LacZ mice were injected with Tamoxifen™ at P20 when HFs are in telogen (A). At P23 a first staining in the IFE and HFs was detected (B). Analysis of LacZ staining progeny at P38 (1st anagen, C, D) and P52 (2nd telogen, E, F) revealed contribution to all parts of the HFs, IFEs and SGs.
FIG. 18. The progeny of Lgr6+ cells contribute to the myoepithelium of the lung. To trace the progeny of Lgr6+ cells Lgr6-EGFP-Ires-CreERT2/ROSA26-LacZ mice were injected with Tamoxifen™ at P20. Analysis of LacZ staining progeny at P38 (A, 10×, 20× and 40× magnification from left to right) and P52 (B, 10×, 20× and 40× magnification from left to right) revealed contribution to the myoepithelium underlying the bronchioles of the lung.
FIG. 19. Low-dose oral induction with ß-NF does not induce Cre-mediated deletion in stem cells of AH Cre mice. Intestinal whole-mounts stained for ß-galactosidase from AhCre+ Rosa26R+ mice. a: No activation of the Rosa-lacZ reporter gene is observed in intestines from non-induced AhCre+ Rosa26R+ mice. b: Readily visible expression of lacZ throughout the intestine 2 days after a single gavage of 1 mg/kg ß-napthoflavone, indicating efficient Cre-mediated activation of the lacZ reporter. No lacZ expression is visible at the crypt base (lower panel) demonstrating the absence of Cre-mediated recombination at the crypt base. c: No lacZ-positive crypt/villus units are visible on whole-mount intestines 100 days post-induction, indicating that this dosing regime very rarely causes recombination within the intestinal stem cells.
FIG. 20. Transformation of non-stem cells through loss of APC does not efficiently drive adenoma formation over extended time-periods. a-c: ß-catenin IHC performed on intestinal sections from AhCre+ Rosa26R+ Apcfl/fl 3 days following a single gavage of 1.0 mg/kg ß-napthoflavone. Clusters of transformed cells with nuclear ß-catenin were frequently observed on the villus (a) and upper regions of the crypt (b). ß-cateninhigh clusters were only very rarely observed at the crypt base (c). These clusters are highlighted with black arrows. d: Quantification of the location of the ß-cateninhigh cell clusters on intestinal sections from AhCre+ Rosa26R+ Apcfl/fl 4 days following a single gavage of 1.0 mg/kg ß-napthoflavone. Box-plots showing numbers of foci observed at the crypt base, the upper crypt and the villus in 1600 crypt-villus units. Significantly more clusters were seen at the upper regions of the crypt than any other region (p=0.04, Mann Whitney, n=3). Nuclear ß-catenin foci were observed only very rarely at the crypt base. e:□-ß-catenin IHC performed on intestinal section from AhCre+ Rosa26R+ Apcfl/fl 24 days following a single gavage of 1.0 mg/kg ß-napthoflavone. Here, nuclear ß-catenin is seen in a small lesion 24 days after cre induction. f,g: ß-catenin IHC performed on intestinal section from AhCre+ Rosa26R+ Apcfl/fl 167 days following a single gavage of 1.0 mg/kg ß-napthoflavone showing a microadenoma (f) and small adenoma (g) with nuclear ß-catenin. h: Quantification of adenoma formation over extended time-periods in AhCre+ Rosa26R+ Apcfl/fl following a single gavage of 1.0 mg/kg ß-napthoflavone. Lesion size was scored on intestinal whole-mounts from AhCre+ Rosa26R+ Apcfl/fl mice that had been stained for lacZ to help visualise the small lesions (at least 3 mice were used for each time-point). No adenomas were seen in mice up to and including day 24 and there was only the very rare microadenoma in mice at day 24. The occasional adenoma was observed in AhCre+ Rosa26R+ Apcfl/fl at 100 days (plus), however the majority of lesion remained microscopic showing that most lesions were not progressing to adenoma despite a long latency period.
FIG. 21. Lgr5+ve intestinal stem cells transformed following loss of APC persist and fuel the rapid formation of ß-cateninhigh microadenomas. a-i: The consequences of Lgr5+ve intestinal stem cell transformation and their subsequent fate was tracked over an eight day period using ß-catenin and GFP as markers of transformed cells and Lgr5+ve stem cells respectively. a-c: Accumulation of the Wnt effector, ß-catenin is first observed in scattered Lgr5+ve stem cells 3 days after Cre induction in Lgr5-EGFP-Ires-CreERT2/APC fl/fl intestines. Representative examples of 1-cateninhigh Lgr5+ve stem cells are circled. d-f: Five days post-induction the transformed Lgr5-GFP+ve stem cells remain (e,f: black arrows) and are associated with clusters of transformed (ß-cateninhigh) cells within the TA compartment. g-h: Eight days post-induction the clusters of transformed cells have expanded to fill the TA compartment (h: red circle). The transformed Lgr5-GFP+ve stem cells at the crypt base persist (h,i: black arrows), but their transformed progeny within the TA compartment are Lgr5-GFP-ve. (h,i: red circles).
FIG. 22. Selective transformation of Lgr5+ve stem cells following loss of APC efficiently drives adenoma formation throughout the small intestine. a-h: The appearance and development of intestinal adenomas and the expression of the Lgr5-GFP stem cell marker within these adenomas was tracked over a 36 day period using GFP (f) and ß-catenin (all others) IHC.a-b: Multiple small adenomas are readily visible throughout the intestine 14 days after Lgr5+ve stem cell transformation. c-f: Multiple macroscopic adenomas (>100) are present after 24 days. Lgr5-GFP expression in adenomas is restricted to rare scattered cells (f; circled). g,h: At 36 days, a large proportion of the intestine is filled with macroscopic adenomas.
FIG. 23. Presence of Lgr5+ stem cells in intestinal adenomas. Intestinal adenomas express high levels of ß-catenin as a result of chronic activation of the Wnt pathway (A). In contrast to other Wnt target genes which are highly expressed throughout the adenoma (not shown), expression of the intestinal stem cell marker Lgr5-GFP is restricted to scattered cells with characteristic stem cell morphology: slender, comma-shaped cells; indicated with black arrow (B). We speculate that these Lgr5+ve cells within the adenoma are stem cells dedicated to maintaining the growth of the adenoma (so-called cancer stem cells).
FIG. 24. FACS analyses of LGR5 expression in L8 cells, which are clonal derivatives of LS174T cells, which express dominant negative Tcf4 (DNTcf4) upon Doxycycline (DOX). DNTcf4 turns off constitutive active Wnt pathway. After 48 hrs of DOX induction, a reduction in hLgr5 protein levels is observed. Rat IgG is used as negative isotype control. 9G5 is a rat monoclonal derived antibody directed against hLgr5
FIG. 25. Comparison of Lgr5+ stem cells and their direct progeny. GFP-positive epithelial cells from cell suspensions prepared from freshly isolated crypts of Lgr5-EGFP-ires-CreERT2 mice. FACS analysis distinguished a GFP-high (GF Phi) and a GFP-low (GFP lo) population, which we tentatively identified as CBC cells and their immediate transit-amplifying daughters, respectively (A). An example of a Wnt-responsive gene, Sox9, which shows high level expression in CBC cells, but TA cells directly above the Paneth cells also express this gene in in situ hybridizations, albeit at a much lower level (B).
FIG. 26. Endogenous hLgr5 staining of a human colon cancer cell line (L8) using several Lgr5-specific monoclonal antibodies. L8 cells are a clonal derivative of the parental LS174T cell-line. Following Doxycycline (DOX) induction the L8 cells express a dominant-negative form of Tcf-4 (DNTcf4). DNTcf4 efficiently blocks the constitutive Wnt pathway activity in these cells and consequently switches off Tcf target genes. After 48 hrs of DOX induction a major reduction in hLgr5 protein levels is observed. Rat IgG is used as negative isotype control.
FIG. 27. Light chain+heavy chain sequences analyzed using KABAT method. CDR regions are in bold and in italics.
EXAMPLES Example 1 Experimental Part
Northern Blotting and Induced Wnt Pathway Inhibition in LS174T Clone L8:
As in van de Wetering, M. et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111, 241-50 (2002). The probe spanned the entire reading frame of mouse Gpr49. Crypt and villus epithelial preparations for RNA isolation were generated from 0.5 cm lengths of intestine by 4 successive rounds of incubation in pre-warmed 30 mM EDTA at 37° C. for 10 minutes, followed by vigorous shaking (10×) in ice-cold PBS. Fractions 1 and 4, comprising predominantly villi and crypts respectively were used for RNA isolation.
Mice:
GPR49-LacZ mice were generated by homologous recombination in ES cells targeting an Ires-LacZ cassette to the 5′ end of the last exon, essentially removing the region containing all TM regions and creating a null allele (Lexicon). GPR49-EGFP-Ires-CreERT2 mice were generated by homologous recombination in ES cells targeting an EGFP-Ires-CreERT2 cassette to the ATG of GPR49. Rosa26-lacZ Cre reporter mice were obtained from Jackson Labs.
Tamoxifen Induction:
Mice of at least 8 weeks of age were injected once intraperitoneally with 200 μl of Tamoxifen in sunflower oil at 10 mg/ml.
Brdu Injection:
Mice were injected intraperitoneally at four hour intervals with 200 μl of a BrdU solution in PBS at 5 mg/ml.
Immuno Electron Microscopy:
Intestines were dissected and per fuse-fixed in 4% PFA in 0.2 M PHEM-buffer, embedded in gelatine, cryosectioned with a Leica FCS cryoultratome and immunolabelled against GFP with polyclonal rabbit anti-GFP antibody. Samples were trimmed using a diamond Cryotrim 90 knife at −100° C. (Dia tome, Switzerland) and ultrathin sections of 70 nm were cut at −120° C. using a Cryoimmuno knife (Dia tome, Switzerland). For the low magnification EM images the 15 nm protein A-gold particles (UMCU, Utrecht, The Netherlands) were briefly silver enhanced with R-GENT SE-EM (Aurion, The Netherlands) according to the manufacturers instructions. A specific binding to Paneth cell granules was diminished by applying Blocking solution (Aurion, The Netherlands) prior to the primary antibody.
Tissue Sample Preparation for Immunohistochemistry, In-Situ Hybridization and LacZ Expression Analysis:
All performed as previously described in Mun can, V. et al. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol Cell Biol 26, 8418-26 (2006). In-situ probes comprising a 1 kb N-terminal fragment of mGPR49 were generated from sequence-verified Image Clone 30873333. Ki67 antibodies were purchased from Mono san (The Netherlands), Phospho-histone H3 from Cam pro Scientific (The Netherlands), anti-synaptophysin from Dako, anti BrdU from Roche. Polyclonal rabbit anti-GFP was provided by Edwin Cup pen, Hubrecht Institute.
Generation of Suspension of Human (Tumor) Tissue Cells.
|
package rules
import (
"encoding/json"
"fmt"
"reflect"
"strings"
hcl "github.com/hashicorp/hcl/v2"
"github.com/terraform-linters/tflint-plugin-sdk/terraform/configs"
"github.com/terraform-linters/tflint-plugin-sdk/tflint"
)
type awsIamStatement struct {
Action interface{} `json:"Action"`
Effect string `json:"Effect"`
Principal map[string]interface{} `json:"Principal"`
}
type awsIamAssumeRole struct {
Version string `json:"Version"`
Statement []awsIamStatement `json:"Statement"`
}
// AwsIamRoleLambdaNoStar checks if an IAM role with a Lambda principal has broad permissions
type AwsIamRoleLambdaNoStarRule struct {
resourceType string
principalNames []string
assumeAttrName string
inlineBlockName string
policyName string
}
// NewAwsIamRoleLambdaNoStarRule returns new rule with default attributes
func NewAwsIamRoleLambdaNoStarRule() *AwsIamRoleLambdaNoStarRule {
return &AwsIamRoleLambdaNoStarRule{
// TODO: Write resource type and attribute name here
resourceType: "aws_iam_role",
principalNames: []string{
"lambda.amazonaws.com",
"lambda.amazonaws.com.cn",
},
assumeAttrName: "assume_role_policy",
inlineBlockName: "inline_policy",
policyName: "policy",
}
}
// Name returns the rule name
func (r *AwsIamRoleLambdaNoStarRule) Name() string {
return "aws_iam_role_lambda_no_star"
}
// Enabled returns whether the rule is enabled by default
func (r *AwsIamRoleLambdaNoStarRule) Enabled() bool {
return true
}
// Severity returns the rule severity
func (r *AwsIamRoleLambdaNoStarRule) Severity() string {
return tflint.WARNING
}
// Link returns the rule reference link
func (r *AwsIamRoleLambdaNoStarRule) Link() string {
return "https://awslabs.github.io/serverless-rules/rules/lambda/star_permissions.html"
}
// matchPrincipal returns true if the policy has a matching Principal
func (r *AwsIamRoleLambdaNoStarRule) matchPrincipal(runner tflint.Runner, policy *hcl.Attribute) (bool, error) {
var assumeAttrValue string
err := runner.EvaluateExpr(policy.Expr, &assumeAttrValue, nil)
if err != nil {
return false, err
}
assumeRolePolicy := awsIamAssumeRole{}
err = json.Unmarshal([]byte(assumeAttrValue), &assumeRolePolicy)
if err != nil {
return false, err
}
for _, principalName := range r.principalNames {
for _, statement := range assumeRolePolicy.Statement {
if principalService, ok := statement.Principal["Service"]; ok {
switch principalService := principalService.(type) {
case string:
if principalService == principalName {
return true, nil
}
case []string:
for i := range principalService {
if principalService[i] == principalName {
return true, nil
}
}
}
}
}
}
return false, nil
}
// matchStarAction returns true if the policy has a broad action in one of its statement
func (r *AwsIamRoleLambdaNoStarRule) matchStarAction(runner tflint.Runner, policy *hcl.Attribute) (bool, error) {
var policyAttrValue string
err := runner.EvaluateExpr(policy.Expr, &policyAttrValue, nil)
if err != nil {
return false, err
}
rolePolicy := awsIamAssumeRole{}
err = json.Unmarshal([]byte(policyAttrValue), &rolePolicy)
if err != nil {
return false, err
}
for _, statement := range rolePolicy.Statement {
switch action := reflect.ValueOf(statement.Action); action.Kind() {
case reflect.String:
if action.String() == "*" || strings.Contains(action.String(), ":*") {
return true, nil
}
case reflect.Slice:
for i := 0; i < action.Len(); i++ {
v := action.Index(i).Interface().(string)
if v == "*" || strings.Contains(v, ":*") {
return true, nil
}
}
}
}
return false, nil
}
// Check checks if an IAM role with a Lambda principal has broad permissions
func (r *AwsIamRoleLambdaNoStarRule) Check(runner tflint.Runner) error {
return runner.WalkResources(r.resourceType, func(resource *configs.Resource) error {
// Get principal
body, _, diags := resource.Config.PartialContent(&hcl.BodySchema{
Blocks: []hcl.BlockHeaderSchema{
{
Type: r.inlineBlockName,
},
},
Attributes: []hcl.AttributeSchema{
{
Name: r.assumeAttrName,
},
},
})
if diags.HasErrors() {
return diags
}
// Load assume role policy
assumeAttr, ok := body.Attributes[r.assumeAttrName]
if !ok {
// This is a mandatory attribute
runner.EmitIssue(
r,
fmt.Sprintf("\"%s\" is not present.", r.assumeAttrName),
body.MissingItemRange,
)
return nil
}
// Check if it contains the right principal
hasLambda, err := r.matchPrincipal(runner, assumeAttr)
if err != nil {
return err
}
if !hasLambda {
return nil
}
// Load inline policy
inlineBlocks := body.Blocks.OfType(r.inlineBlockName)
for _, inlineBlock := range inlineBlocks {
body, _, diags = inlineBlock.Body.PartialContent(&hcl.BodySchema{
Attributes: []hcl.AttributeSchema{
{
Name: r.policyName,
},
},
})
if diags.HasErrors() {
return diags
}
policyAttr, ok := body.Attributes[r.policyName]
if !ok {
// This is a mandatory attribute
runner.EmitIssue(
r,
fmt.Sprintf("\"%s\" is not present.", r.policyName),
body.MissingItemRange,
)
return nil
}
// Check if policy contains stars
hasStar, err := r.matchStarAction(runner, policyAttr)
if err != nil {
return err
}
if hasStar {
runner.EmitIssueOnExpr(
r,
"Inline policy for role with Lambda as principal has policy actions with stars.",
policyAttr.Expr,
)
}
}
return nil
})
}
|
Supporting extend selection inside macro calls
@edwin0cheng sorry, I still didn't get to review this properly. Though, I did quickly checked out the code, and it seems like worked for some cases, but not for the others. In particular, I think it didn't work for some of match_ast! invocations. Not sure if it is actually true, and what is the culpring, but, if you are blocked on me reviewing the PR, this is something to look at at meantime :)
@matklad Thanks for the update, and I just fixed the match_ast! case and found a bug in descend_into_macros(#2760), after that PR is merged, the new test should be passed.
bors try
bors try
bors try
bors try-
One this I've noticed is that it looks surprisingly slow:
Note that this is repeated calls without any modifications, so salsa doesn't do any query validation/evaluation here.
Hm, also, 38k SourceAnalyzer::new calls for a single extend selection seems excessive :)
These are examples from this macro: https://github.com/rust-analyzer/rust-analyzer/blob/928ecd069a508845ef4dbfd1bc1b9bf975d76e5b/crates/ra_ide/src/references/classify.rs#L18-L124
I've noticed that the match arms near the end are much slower than the ones near beginning. Looks like we might be accidentally quadratic somewhere?
I changed to indices based approach, one of the reasons is, we don't have an easy way to find a textual scoped sibling tokens. The new implementation only call descend_to_macro for the first and second token to find the expanded parent node. (i.e. 2 calls), and then call it for searching the sibling token in expanded parent node but we limited it by take_while, so it should be minimal.
It is the profiling data of new implementation:
33ms - main_loop_inner/loop-turn
33ms - handle_selection_range
7ms - parse_query
8ms - parse_macro_query
3ms - SourceAnalyzer::new (97 calls)
0ms - crate_def_map (190 calls)
13ms - ???
Oh, because the indices are already sorted, we could eliminate the min-max search and just using the first and last element instead.
The reason I want to know all tokens inside the macro call is, I don’t know a simple method to traversal the previous token from the first token inside the original range in latter becauseprev_token only works in the same parent.
And the code here is a helper collections to let me compute the sorted index of all tokens such that I can use that index to traversal the mapped token later.
prev token is not restricted to the same parent:
pub fn prev_token(&self) -> Option<SyntaxToken> {
match self.prev_sibling_or_token() {
Some(element) => element.last_token(),
None => self
.parent()
.ancestors()
.find_map(|it| it.prev_sibling_or_token()) // here, we hop to the previous sibling of a parent
.and_then(|element| element.last_token()),
}
}
Oh.... dang it. 🤦🏻♂️😅
Yeah, the naming is unfortunate :(
Don't know better alternatives though...
On Thu, 9 Jan 2020 at 16:52, Edwin Cheng<EMAIL_ADDRESS>wrote:
Oh.... dang it. 🤦🏻♂️😅
—
You are receiving this because you were mentioned.
Reply to this email directly, view it on GitHub
https://github.com/rust-analyzer/rust-analyzer/pull/2712?email_source=notifications&email_token=AANB3M24MSDVOLF3ILM4443Q45B4NA5CNFSM4KBXG4S2YY3PNVWWK3TUL52HS4DFVREXG43VMVBW63LNMVXHJKTDN5WW2ZLOORPWSZGOEIQYQQY#issuecomment-572622915,
or unsubscribe
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.
LGTM now!
bors r+
bors?
bors r+
I think this needs a rebase to get pass bors
On Sunday, 12 January 2020, Edwin Cheng<EMAIL_ADDRESS>wrote:
bors r+
—
You are receiving this because you were mentioned.
Reply to this email directly, view it on GitHub
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or unsubscribe
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.
This now makes my life sooo much better, thanks @edwin0cheng!
I think I've been dreaming about this feature since I've initially implemented the parser (and automatically extend selection) for Rust in IntelliJ :)
Took only four years to get there :D
|
from ..helpers.model import Model
class Student(Model):
table = 'student'
relations = {
'courses': {
'type': 'belongsToMany',
'model': 'Course',
'pivot': 'Schedule'
}
}
def __str__(self):
return f'Student: id - {self["id"]}; name - {self["name"]}; dob - {self["dob"]}'
|
Talk:By the Light of the Moon (novel)
Fair use rationale for Image:By the Light Of the Moon.jpg
Image:By the Light Of the Moon.jpg is being used on this article. I notice the image page specifies that the image is being used under fair use but there is no explanation or rationale as to why its use in Wikipedia articles constitutes fair use. In addition to the boilerplate fair use template, you must also write out on the image description page a specific explanation or rationale for why using this image in each article is consistent with fair use.
If there is other other fair use media, consider checking that you have specified the fair use rationale on the other images used on this page. Note that any fair use images uploaded after 4 May, 2006, and lacking such an explanation will be deleted one week after they have been uploaded, as described on criteria for speedy deletion. If you have any questions please ask them at the Media copyright questions page. Thank you.BetacommandBot 14:07, 1 June 2007 (UTC)
Pop Culture
Uh, I really doubt that the Nelf cheer in WoW is a reference to this book. The phrase "by the light of the moon" has been around for decades now, and is probably more of a reference to that than this book. Th 2005 07:22, 7 October 2007 (UTC)
Fair use rationale for Image:By the Light Of the Moon.jpg
Image:By the Light Of the Moon.jpg is being used on this article. I notice the image page specifies that the image is being used under fair use but there is no explanation or rationale as to why its use in this Wikipedia article constitutes fair use. In addition to the boilerplate fair use template, you must also write out on the image description page a specific explanation or rationale for why using this image in each article is consistent with fair use.
BetacommandBot (talk) 18:35, 13 February 2008 (UTC)
|
Homomorphisms from $D_4$ to $S_3$.
Find all homomorphisms from $D_4$ to $S_3$.
We have $D_4 = \{e,r,r^2,r^3,s,sr,sr^2,sr^3\}$ (where $r^4 = e = s^2$) and $S_3 = \{e,(12),(13),(23),(123),(132)\} = \langle (12) (13) \rangle$.
Let $x_i = (1i) \in S_3$, where $i \in \{2,3\}$. By another exercise (already proved in my class), the following relation holds: $x_i^2=e=(x_i x_j)^3$.
Mapping the relation onto its image, I get $f(x_i^2)=f(e)=f(x_i x_j)$, and of course $f(e)=e$. But we are dealing with homomorphisms, so this is also true: $f(x_i)^2 = e = f(x_i) f(x_j)$.
At this point, can I pick any $(1i) \in S_3$ such that if I square the permutation, then I end up at $e$? That would count as one homormorphism, right?
I found 4 so far: $e,(12),(13),(23)$. When I square any of these, I get $e$.
Suppose that $\theta : D_4 \to S_3$ is a homomorphism. Then, by the first isomorphism theorem:
$K=\ker \theta \unlhd D_4$
$\theta(D_4) \leq S_3$
$\dfrac{|D_4|}{|K|} = |\theta(D_4)|$
So the associated subgroups that arise from the possible homomorphisms must each satisfy these 3 relations, restricting us to a handful of case.
By Lagrange, any subgroup of $S_3$ must have order $1,2,3$ or $6$; and that $|K| =1,2,4,8$. So, by our third condition, this immediately restricts us to $(|K|,|\theta(D_4)|) \in \{(4,2), (8,1)\}$.
Observe that the homomorphism leading to the $(8,1)$ pairing above must have kernel $D_4$ i.e. must map everything to the identity permutation in $S_3$ - there is only one such function and it is indeed a homomorphism.
For the $(4,2)$ pairing, it's easily seen that the only order 2 subgroups of $S_3$ are those generated by each of the transpositions $\tau$, say. Since knowing where the generators map to tells us everything about the homomorphism, as $\theta$ preserves group structure, it suffices to break this into cases:
$ \underline{(1) \ \theta(s)=\tau:}$ It remains to consider where $r$ maps to under $\theta$, this breaks up into two sub-cases:
$\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ (a)\ \theta (r ) = e $ - Only have the three homomorphisms s.t. $r^i\mapsto e, sr^i \mapsto \tau$ for each $\tau \in S_3$
$\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ (b) \ \theta(r ) = \tau$ - Then have the maps s.t. $r^{2i+1}, sr^{2i} \mapsto \tau; r^{2i}, sr^{2i+1} \mapsto e$ for each $\tau \in S_3$
$\underline{(2) \ \theta(s) = e:}$ Considering $\theta (r )$ as above:
$\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ (a)\ \theta (r ) = e $ - Trivial map, which we have already accounted for above.
$\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ (b)\ \theta (r ) =\tau $ - Have maps s.t. $r^{2i+1}, sr^{2i+1} \mapsto \tau; r^{2i}, sr^{2i}\mapsto e$ for each $\tau \in S_3$
Yielding 10 distinct homomorphisms $D_4 \to S_3$.
|
package edu.fiuba.algo3.modelo.Preguntas;
import edu.fiuba.algo3.modelo.Excepciones.CantidadInvalidaDeOpcionesException;
import edu.fiuba.algo3.modelo.Jugador;
import edu.fiuba.algo3.modelo.Opciones.OpcionCorrecta;
import edu.fiuba.algo3.modelo.Opciones.OpcionIncorrecta;
import edu.fiuba.algo3.modelo.Puntajes.Puntaje;
import edu.fiuba.algo3.modelo.Respuestas.Respuesta;
import edu.fiuba.algo3.modelo.Respuestas.RespuestaMultipleChoice;
public class PreguntaMultipleChoice extends PreguntaClasica {
public PreguntaMultipleChoice(String texto, Puntaje puntaje) {
super(texto, puntaje);
}
public PreguntaMultipleChoice(String texto, Puntaje puntaje, int tiempo) {
super(texto, puntaje, tiempo);
}
@Override
public void evaluarJugadores(Jugador jugador1, Jugador jugador2) {
Puntaje puntaje1 = puntaje.duplicar();
Puntaje puntaje2 = puntaje.duplicar();
puntaje1.calcularPuntaje(jugador1, totalCorrectas);
puntaje2.calcularPuntaje(jugador2, totalCorrectas);
jugador1.aplicarExclusividad(puntaje1, puntaje2);
jugador2.aplicarExclusividad(puntaje2, puntaje1);
puntaje1.asignarPuntaje(jugador1);
puntaje2.asignarPuntaje(jugador2);
}
public OpcionCorrecta agregarOpcionCorrecta(String texto) throws CantidadInvalidaDeOpcionesException {
if(opciones.size() >= 5)
throw new CantidadInvalidaDeOpcionesException();
OpcionCorrecta opcion = new OpcionCorrecta(texto);
agregarOpcionCorrecta(opcion);
return opcion;
}
public OpcionIncorrecta agregarOpcionIncorrecta(String texto) throws CantidadInvalidaDeOpcionesException {
if(opciones.size() >= 5)
throw new CantidadInvalidaDeOpcionesException();
OpcionIncorrecta opcion = new OpcionIncorrecta(texto);
agregarOpcionIncorrecta(opcion);
return opcion;
}
public Respuesta tipo() {
return new RespuestaMultipleChoice();
}
@Override
public int getCantidadOpciones() {
return opciones.size();
}
}
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Rood (surname)
Rood is a Dutch surname. Meaning "red", it often originally referred to a person with red hair. The name can also be toponymic, since in Middle Dutch "rood" or "rode" was a name for a cleared area in the woods. Among variant forms are De Rood(e), Roode, Roodt and 'Van Rood. The name can also be of English toponymic origin, referring to someone living near a rood ("cross"). Notable people with the surname include:
* Anson Rood (1827–1898), American businessman and Wisconsin politician
* Davenport Rood (fl. 1840s), American carpenter and Wisconsin councilman
* Denise Rood (born 1955), American violinist
* Grace Alexandra Rood (1893–1981), New Zealand school dental nurse
* Harold W. Rood (1922–2011), American political scientist
* John Rood (born 1968), American businessman, Under Secretary of Defense for Policy since 2018
* John D. Rood (born 1955), American businessman, Ambassador to the Bahamas from 2004 to 2007
* Jon van Rood (1926–2017), Dutch immunologist
* (born 1955), Dutch screenwriter, film director and philosopher
* Katie Rood (born 1992), New Zealand football forward
* Mary Rood, British silversmith
* Max Rood (1927–2001), Dutch legal scholar and D66 politician
* Ogden Rood (1831–1902), American physicist and color theorist
* Richard Rood (violinist) (born 1955), American violinist
* Richard B. Rood (born c. 1955), American climatologist
* Richard E. Rood, better known as Rick Rude (1958–1999), American professional wrestler
* Ronald Rood (1920–2001), American author, naturalist and radio commentator
* Theoderic Rood (fl. 1470s), English printer
* Tim Rood (born 1960s), British classical scholar
* Variant spellings
* Bobby Roode (born 1977), Canadian professional wrestler
* Dan Roodt (born 1967), Afrikaner author, publisher, and commentator
* Darrell Roodt (born 1962), South African film director, screenwriter and producer
* Dewald Roode (1940–2009), South African computer scientist and information systems researcher
* Hendrik Roodt (born 1987), South African rugby player
* Middle names derived from the surname
* Charles Rood Keeran (1883–1948), American (Illinois) inventor and businessman
* James Rood Doolittle (1815–1897), American politician, US Senator from Wisconsin 1857–69
* John Rood Cunningham (1891–1980), American college president
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Thread:Tariq Jabbar/@comment-25304012-20160802012902/@comment-25659393-20160802035708
Yay! Emote of the month was announced! Ohhhh.. *cough* Great job on featured user TJ! =)))
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Recycle array and non empty array for inserts that are noop
@gcanti I'll do a PR to discuss.
PR here: https://github.com/gcanti/fp-ts/pull/703
Closing via https://github.com/gcanti/fp-ts/pull/703
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San Marino Genealogy
Country Information
San Marino Map
Genealogy records are kept on the local level in San Marino.
Jurisdictions
FamilySearch Resources
Below are FamilySearch resources that can assist you in resourcing your family.
* Facebook Communities - Facebook groups discussing genealogy research
* Learning Center - Online genealogy courses
* Historical Records
* Family History Center locator map
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JAMES A. GIBSON, Curator of Estate of WILLIAM T. JONES, v. SAMUEL S. SHULL, Appellant.
Division One,
June 28, 1913.
1. SETTING ASIDE DEED: Mental Incapacity: Questions of Fact: Deference to Chancellor. The Supreme Court is not bound by the findings of the chancellor to the effect that the grantor of a deed was, because of his long and continuous use of ardent spirits, mentally incapacitated to make a deed; hut where the testimony is oral, the chancellor who faces the witnesses is in a better position than is the Supreme Court to judge their credibility, and where their testimony is amply •sufficient to justify the finding that the grantor was not mencally capable of making the deed, the court, following its usual custom, will accept such finding, unless there be some other good reason for disturbing it.
2. -: Necessary Plaintiff: Curator: Grantor of Unsound Mind: No Demurrer: Waiver. Title to the land of an unsound person is in him and not in his curator; and a suit to set aside a deed made by a grantor who has been adjudged a person of unsound mind by the probate court, on the ground that he was mentally incapacitated to make such deed, should be brought in his name, and not in the name of his curator; but where the petition shows on its face that the action is brought in the name of the curator personally, the defect of parties should be raised by demurrer, and if not so raised it is considered waived. It cannot be raised by an answer which is a general denial.
3. -: Appointment of Curator: Record Not Preserved. Where the record of the probate court appointing the plaintiff curator of the estate of the person of unsound mind whose deed to land the suit seeks to have set aside, was admitted in evidence, the legality of the curator’s appointment will be assumed and the rightful action of the trial court will be presumed, if appellant omits from his abstract the record of the probate court which resulted in the curator’s appointment.
4. -: -: Appointment After Execution of Deed. In a suit to set aside a deed on the ground that the grantor was of unsound mind, the record of the probate court is competent for the purpose of showing the due and legal appointment as curator of. the person who brings the suit on behalf of such mentally incapacitated person, notwithstanding the appointment was made a few days after the date of the alleged deed.
5. --: Cause of Action: Sufficiency of Petition: In Statu Quo: Taking Advantage of Incapacity. A petition that states the grantor in a deed was of unsound mind at the time it was executed, that the deed was given without consideration and that it constitutes a cloud upon said grantor’s title, states a cause of action for annulling the deed. The allegation that the deed was without consideration and constitutes a cloud on the grantor’s title, states a cause of action for setting aside the deed, whether the grantor was of sound or unsound mind. Nor does the petition fail to state a cause of action because it nowhere states the plaintiff’s ability or willingness to place the defendant in stain quo or that defendant knew the grantor was insane and took advantage of him.
6. -: -: Judgment: No Prayer to Restore Status Quo: Prayer for General Relief. Where a court of equity, by a bill which states a cause of action for setting aside a deed, acquires jurisdiction, it will not release it until full equity has been done, if the petition contains a prayer for general relief. In ■such case the court will hear the evidence and grant the relief to which plaintiff is entitled. So where the petition stated a cause of action for setting aside a deed, although it contained no allegation of a willingness or ability to restore the status quo, a judgment holding the grantor of unsound mind and requiring him to reimburse the grantee to the extent of the money he paid for the deed, with interest, was proper, and will be upheld, where authorized by the evidence.
7. --: Grantor Non Compos Mentis. The deed of a grantor of unsound mind at the time it was made, may be avoided, though he had not at that time been adjudged of unsound mind.
5. -: Agent: Fiduciary Relation: Burden. Where an agent buys land from his principal a confidential relation exists, which places upon the agent the burden of showing the transaction was equitable and fair.
Appeal from Buchanan Circuit Court. — Hon. Luden J. Eastin, Judge.
Affirmed.
Warren Rogers for appellant.
(1) The petition filed in this case is wholly bad. The curator seeks to sue in his own name as such. That he cannot do. Reed v. Wilson, 13 Mo. 28; Koenig v. Union Depot Co., 194 Mo. 572; Webb v. Hayes, 166 Mo. 50. (2)‘ There was no appointment, in law, of a curator of Jones. “A probate court shall have no jurisdiction to inquire into the sanity of a person who owns no property.” R. S. 1909, sec. 474. No part of the record of the probate court shows that that court found Jones was owner of any property or that any such showing was made to the probate court. The petition, if any was filed, on which a hearing was based, is not shown by any record in evidence. There was no legal appointment. (3) The probate record shows that Jones was not in that court at the inquest. That record, also, fails to show that he was “notified of the proceeding” in that court against him looking to the ascertainment of his condition, giving him time to defend himself, or in any way setting a day for him to-appear in said matter in said court. This failure may have been attempted to be excused by the recital in the record-that: “The said William T. Jones, being unable to appear in open court,” etc. The recital aforesaid follows the language of the statute (Sec. 476,. R. S. 1909), but that clause of the statute is unconstitutional. Hunt v. Searcy, 167 Mo. 158. (4) The petition fails to state facts sufficient to constitute a cause-, of action in that it nowhere appears from the petition that there is an ability and willingness on the part of' plaintiff to place the defendant in statu quo, or that the defendant knew that the ward was insane at the time of the transaction in question and took advantage of him. Jamison v. Culligan, 151 Mo. 410; Wells v. Mutual Assn., 126 Mo. 630; Banking Co. v. Loomis, 140 Mo. App. 73; Rhoads v. Fuller, 139 Mo. 179. (5) It was error for the court to permit the introduction of the probate court proceedings held several days after the land had been deeded to appellant, for the purpose of showing or bearing on the condition of Jones’s mind at the time of such sale or any other time. 'Rhoads v. Fuller, 139 Mo. 179.
E. M. Swartz and Myiton & Parhinson for respondent.
(1) Technically, the title of the cause should have been Jones, by his curator, plaintiff, but the error appeared on the face of the petition and the defect was waived when appellant answered. He could only have raised this question by demurrer. Baxter v. Transit Co., 198 Mo. 1; Taylor v. Pullen, 152 Mo. 434; Jones v. Steele, 36 Mo. 324. (2) The probate records were introduced but appellant failed to incorporate them in the bill of exceptions. (3) The petition does state a cause of action, that the deed was without consideration. That Jones was of unsound mind, and incapable of managing his affairs is assumed, in the absence of demurrer, that defendant knew his condition, and after verdict it is implied, and when he failed to demur, he waived the insufficiency of the allegation. Lycett v. Wolff, 45 Mo. App. 489. Furthermore, the evidence disclosed that appellant did not deal fairly; sufficiently so to draw the inference that appellant was bound to know that he was dealing with an imbecile. Besides, the -deed was without consideration and so found by the court. The judgment simply recites that Shull paid to Jones $216.50, but not on the conveyance,, and requires that said Shull be reimbursed his outlay. Shull had taken two deeds from Jones to the same land and had advanced him money from time to time. The respondent is bound by the judgment to repay the $216.50, although the pleadings do not tender it back nor demand reimbursement; but appellant cannot complain because it places him in statu quo. The judgment sustains the allegations in the petition... The respondent admits that under the authorities of this State a deed from a non compos, not under guardianship, is voidable only, especially where a good and fair price is paid. 22 Cyc. 1171; Lock v. Brecht, 166 Mo. 242; Rhodes v. Fuller, 139 Mo. 179;. Younger v. Skinner, 14 N. J. Eq. 389. Surely the appellant cannot claim to come within the above rule in this case. The transaction shows that no man of ordinary prudence would have engaged in it. It was, therefore, of no validity, and it was unnecessary to tender back what had been received. Halley v. Troester, 72 Mo. 73.
GRAVES, J.
Plaintiff is the duly qualified curator of "William T. Jones, who was declared to be of unsound mind by the probate court of Buchanan county in July,'1909. Plaintiff, as curator, sues to have set aside a certain deed made by Jones to Shull for an undivided three-fourths interest in forty acres of land in Buchanan county on the ground, as stated in the petition:
‘ ‘ That at the time of said conveyance the said William T. Jones was of unsound mind and incapable of contracting and incapable of managing his affairs; that there was no consideration for said deed; that Samuel S. Shull has placed said deed of record in book 385 at page 194 in the Recorder’s office of Buchanan county, Missouri, and the same now constitutes a cloud upon the title of curator’s said ward.”
The answer was a general denial.
There was proof pro and con on the mental condition of Jones at the date of the deed, as well as of circumstances tending to show that defendant took ■ advantage of Jones’s mental condition, a condition superinduced by long and . , . ., T. continuous use of ardent spirits. It will suffice to say that the proof upon the question of mental condition is such that we will not dispute the judgment of the chancellor nisi, who faced the witnesses, and was in a better position than are we to judge-the credit to be given to them. The evidence will amply justify the finding that Jones was not mentally capable of making a deed,' when this deed was executed, and whilst we are not bound by the finding below this court does not usually disturb such findings unless we can point to some good reason therefor. Under the facts we do not feel like this finding and judgment should be disturbed, unless some of the more technical reasons assigned by defendant are found to be of substantial force.
This shortly states the case, leaving for the opinion a recital of such pertinent facts as may be required for the disposition of the points suggested supra. These points we take in their order.
I. Respondent seriously contends that we should affirm this judgment because the defendant has not presented to us all the testimony in the case, but has presented only garbled excerpts thereof. In equity cases our rule requires a full presentation of the evidence to this court for the . very good reason that m such case the trial here is to the effect of a trial de novo. In other words, whilst we look upon the finding in the lower court as persuasive, we do not allow it to be binding, unless our minds run with the chancellor below on the facts, or unless the facts are conflicting and close and we yield to his judgment because of his better position to judge of the credibility of the respective witnesses. In this case we yield to the judgment of the chancellor trying it below upon the facts pro and con on the question of mental condition at the date this alleged deed was made. Upon this question the court found:
“The court finds and decrees that the said William T. Jones was of unsound mind, incapable of contracting and incapacitated from managing his affairs at the time of the execution of the purported conveyance dated June 10,1909, whereby he purported to convey to Samuel S. Shull, the defendant, the undivided three-fourths interest of land of the northeast quarter of the northwest quarter of section twelve, township fifty-six, range thirty-six, Buchanan county, Missouri, which said conveyance is of record in the Recorder’s office of Buchanan county, Missouri, in Book 385 at page 194.”
We are not prepared to say, however, that the evidence is not sufficiently abstracted for us to place ourselves in the position of the chancellor, nisi, if we deemed it necessary to review the facts in full, and declare a different conclusion from those facts. Such being the status of the abstract we overrule this contention of the respondent, and will take up the objections of the defendant to this finding and judgment.
II. First we are met with the proposition that the suit is in the name of the curator personally, and for that reason the judgment cannot stand. The style of the case is indicated by the ** caption at the beginning of the opinion. In the petition we find this statement:
“Now at this day comes James A. Gibson, curator of the estate of William T. Jones, of unsound mind, and states that heretofore, to-wit on the — day of July, 1909, his ward, said William T. Jones, was duly and legally declared to be of unsound mind and incapable of managing his affairs, by the probate court of Buchanan county, Missouri; that thereupon the petitioner James A. Gibson, was, by the probate court of said, county, duly and legally appointed curator of the estate of said William T. Jones, and the said James A. Gibson thereupon, on said-day of July, 1909, did then and there duly qualify as such curator and enter upon the discharge of his duties as such, and now is duly acting in that capacity.”
Defendant in the brief says • that the petition is wholly bad, because the curator sues in his own name, rather than in the name of his ward. It is true that the title to property is in the ward and not in the curator. It is also true that the action should be in the name of the ward, rather than that of the curator. [Webb v. Hayden, 166 Mo. 1. c. 50, and cases cited; Judson v. Walker, 155 Mo. 166, and cases cited.]
In this case, however, there is another matter of moment. • If there was a defect in the petition in this regard it was one which was patent upon the face thereof, t and such question is waived unless there is a special plea thereto. [Baxter v. Transit Co., 198 Mo. 1. c. 8.] . A. general denial for an answer, as in the case here, does not preserve the point. In the Baxter case, supra, this court in commenting upon the position of Mr. Pomeroy on the code practice (Pomeroy Code Rem., 4 Ed.), and after stating the position ■of that author, thus speaks of and quotes from the author :
“The learned law-writer, although he regards the •Code as in itself a complete system depending for nothing upon the common law, yet . . . recognizes fully . . . the essential difference between matters that may be pleaded to abate the suit, and matters pleaded to defeat the cause of action, the only difference between the Code and the common law in respect to them being the manner and the order in which they .are pleaded and the issues tried. And on pages 813-14, he says: ‘The non-joinder of necessary parties cannot be proven under the general denial . . . The defense that the plaintiff is not the real party in interest is new matter; . . . and in an action by an executor or administrator, the general denial does not put in issue the plaintiff’s title to sue.’ ”
So we say in this case, the general denial in the answer did not place in issue the plaintiff’s title to sue. It could have and should have been raised by demurrer, and not being so raised was waived. It is also true that á next friend has no title to the property involved in the suit. In Taylor v. Pullen, 152 Mo. 1. c. 439, Gantt, P. J., says:
“In Rogers v. Marsh, 73 Mo. 1. c. 70, it was ruled that this objection was in the nature of an affirmative defense and not available under a mere general denial. In Clowers v. Railroad, 21 Mo. App. 1. c. 216, Judge Rombauer commenting on this last mentioned case, said: ‘It was held that this objection is one for defect of parties plaintiff, and is waived under the statute, unless saved by special demurrer, or by answer. This last decision is not only in conformity with the more liberal views marking’ recent decisions, which disregarded purely technical objections in arriving- at the true merits of a controversy, but is furthermore the last controlling decision of our Supreme Court. ’ ’
"We are therefore constrained to hold that the defendant, by answering the petition and not specially pleading this defect in the petition, has waived the point.
III. The record of the probate court of Buchanan county showing the appointment of Gibson as curator of Jones appears to have been introduced in evidence, but the appellant failed to incorporate it bill of exceptions. Appellant now raises the question that there was no legal appointment. This is a barren .contention for two reasons: (1) because the appellant has waived the question as held in our paragraph two; and (2) because he has seen fit to bring a record here which shows that these records were introduced in evidence, but does not bring the records themselves. Under such circumstances the rightful action of the court nisi will be presumed.
IV. Notwithstanding the fact that the defendant has failed to abstract the probate court records, he further insists that the trial court erred in permitting them to be introduced. This point is covered by the preceding paragraph and we will not go further. The record was at least competent to show the due and legal appointment of Gibson as curator, and this is true notwithstanding the fact that the appointment was made a few days after the date of the alleged deed
V. It is next urged that the petition fails to state a cause of action for reasons other than the fact that the suit is brought in the name of Gibson, curator, rather than in the name of Jones. This - point- is thus made by appellant:
“The petition fails to state facts sufficient to constitute a cause of action in that it nowhere appears from the petition that there is an ability and willingness on the part of plaintiff to place the defendant in statu quo, or that the defendant knew that the ward was insane at the time of the transaction in question and took advantage of him, hence defendant’s objection on that ground to the introduction of any evidence in the case should have been sustained.”
It occurs to us that the defendant is confounding’ the pleadings with the proof in making this challenge as against the petition. The petition does state a cause ■of action in equity. It states that Jones was of unsound mind and that the deed was given without consideration, and is a cloud upon Jones’s title. That the petition states a cause of action in equity cannot be questioned. Courts of equity may set aside deeds for want of consideration, when such instrument creates a cloud upon the title. This is true whether the grantor be of sound or unsound mind. It therefore appears that the petition is not defective in so far as stating a cause of action is concerned. The real question is as to whether the judgment can be sustained under the petition. This question we take next.
VI. We have heretofore set out a portion of the judgment, in which it was found that Jones was mentally incompetent to make a deed at the time the deed in question was made. In addition the judgment further found and decreed:
“The court finds that said purported conveyance of record as aforesaid is a cloud upon the title of the said William T. Jones and the same is by the court declared invalid and for naught held and is so adjudged, cancelled and removed, so as to be wholly ineffective and constitute no cloud whatever on said title.
' “The court further finds that upon the execution of said purported conveyance by the said William T. Jones the said Samuel S. Shull defendant, paid to the said William T. Jones on the-day of June, 1909, the sum of $216.50, and it is further ordered and decreed by the court that the said plaintiff shall reimburse the said Samuel S, Shull the said sum of $216.50, with interest at the rate of six per cent per annum thereon from and after the 16th day of June, 1909, by the payment of said sum and interest to the clerk of this court to the use of the said Samuel S. Shull.
“Wherefore the court finds for the plaintiff as ■aforesaid with costs of suit and have execution thereof.”
The evidence clearly discloses, even upon defendant’s theory, that Jones made Shull his agent to sell this property; that whilst that relation existed, Shull claims to have bought the property, for a price which the trial court- could readily find to have been inadequate. In other words, a confidential relationship, i. e., that of principal and agent is shown, and this of itself placed the burden upon Shull to show that the deal between him and his client was equitable and fair. Of this the trial court had'the right to'judge, if the pleadings permitted such judgment, and this to our mind is the serious question in the case. Jones had not been declared non compos at the date of the deed. But, if as a fact he was non compos, his deed could have been avoided. The petition it is true does not offer to place Shull in statu quo, but the judgment does so place him. The petition, being one in equity, prays for general relief. It says in the prayer:
“Wherefore, plaintiff prays the court to set aside, said deed and to hold the same for naught, and for such other orders and judgments in the premises as; to the court shall seem just and proper."
The real question, therefore, in this case is', whether or not, under this petition and its prayer for general relief, the court had the right to enter the judgment which was entered. This judgment indicated that the court found as a matter of fact that Shull dealt with a person non compos, and that on such deal he paid out $216.50, for which he should be reimbursed. Such finding was amply authorized by the evidence, but was it proper under the petition? We think so. When courts of equity, by a bill properly framed, acquire jurisdiction of a cause, such jurisdiction will not be released until full equity has been done, if there be a prayer for general relief, as there is in the instant case. This is true, although the plaintiff asks for some kind of relief which cannot be granted. In such case the court will hear the facts and grant the relief to which, he may be entitled. [Holland v. Anderson et al., 38 Mo. 1. c. 58; Phillips v. Jackson, 240 Mo. 1. c. 336.]
Following this time-honored rule in equity cases, we are impressed that the judgment here is within the purview of the pleadings, and, as we have held that we will not disturb it upon the facts, it must stand.
These paragraphs cover the substantial objections of the defendant. There are others which we deem it unnecessary to discuss. From it all we are con-' vinced that the trial court reached a righteous judgment in this case, and that it should be affirmed. It is so ordered.
All concur.
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Abstract — Bluefish (PomalnmuK so/ tutrix) were tagged and released in Atlantic coastal areas between Mas sachusetts and Florida from 1963 through 2003 as part of a National Marine Fisheries Service (NMFS) project and a volunteer program sponsored by the American Littoral Society ( ALS I. A total of 15,699 blue fish were tagged by NMFS and 20,398 by ALS volunteers and A.39c (1075 NMFS tags and 464 ALS tags) were recaptured and reported. Time-at large was limited; 65.8''?^ of the recap tured tags were returned within two months of tagging, although nineteen of the returned tags remained at large for two years or more. Tag returns indicated seasonal migrations offish between the Middle Atlantic Bight and Florida. Three groups of bluefish are proposed for Atlantic coastal waters on the basis of tag return data and are defined by the seasonal occurrence of fish between 30 and 45 cm fork length. The northern group occupied the area from Massachusetts to Dela ware between late spring and late fall. Bluefish in the central region between Maryland and North Carolina rep resented a combination of seasonal transient and resident fish, as did the southern group in Florida. Mixing occurs among all three groups; and larger fish (>45 cm) spend winters in offshore areas. Estimates of von Bertalanffy growth parameters from tagging data were comparable to scale-based estimates. Swimming speeds between point of release and recapture averaged 2.6 km per day, and seasonal spikes greater than 5 km per day corresponded with periods of migration in spring and autumn.
Bluefish iPomatomus saltatrix) is a pelagic species with a worldwide distribution in temperate and sub tropical oceans. In the United States, bluefish are found along the Atlantic coast from southern Florida to Cape Cod, Massachusetts, and occasion ally as far north as Nova Scotia (Col lette and Klein-MacPhee, 2002). The broad-scale seasonal movements of bluefish are known within the com mercial and recreational fishing com munities (Hersey, 1987), but details of the migratory pattern remain poorly documented in the scientific litera ture. Tagging studies provide the most direct evidence of seasonal move ments, but the only published account for the Atlantic coast stock is a study in Long Island Sound by Lund and Maltezos (1970). Wilk (1977) provided a description of bluefish migration that remains the accepted standard and which was based on seasonal distribution of commercial and recre ational catches, as well as on unpub lished results of a tagging project conducted during the 1960s by David
Deuel and colleagues at the NMFS James. J. Howard Marine Sciences Laboratory (formerly known as the Sandy Hook Marine Laboratory). The proposed migration involved a north south coastal movement between New York-New Jersey offshore waters and southeastern Florida offshore waters during the fall and a return spring migration along the same route. Larger fish (i.e. greater than three pounds) were believed to follow a more offshore pathway.
The identification of distinct blue fish stocks contributing to this mi gratory group has been the subject of multiple investigations. The racial composition of bluefish on the Atlantic coast was investigated by Lund (1961) who concluded, primarily from dif ferences in the number of gill rakers of small bluefish, that six races ex isted along the coast. Lassiter (1962) found differences in first year growth on scales, which indicated that two groups of fish inhabited North Caro lina waters. Returned tags from blue fish tagged in the Long Island area
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SEE.model.BaseModel.prototype.init.call(this);
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self.SeverityName = ko.computed(function () {
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Recent Updates
Recent Updates
[2018/06/12]
* Village of Treasures - Instrument Gathering Stage 8 event has ended.
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[2018/05/22]
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[2018/05/09]
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[2018/05/07]
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* Hachisuka Kotetsu Kiwame release
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* Village of Treasures ~Instrument Gathering Stage 9~ (New Sword!)
* New Kiwame sword release
From April through August 2018:
* A new starter Uchigatana Kiwame will be teased every month!
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PLA
The Devil Squad is a counter-terrorist faction in Counter-Strike Online.
Offical description
Overview
Appearance
* Downed
* Airstrip
* Train
Weapons and equipment
The Devil Squad has been adopted these following weapons in game as their standard weapons:
* Type 95 light machine guns
Trivia
* Once a player use this model in game,he will additional get 10% EXP and 20% game points.
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Q: Healthy relationships with your friends and family can help you be a stronger, more independent person. Plus, they will help you realize that you don’t need your ex! Spend time with the people who are important to you so you can grow closer to them. Additionally, go to local events, clubs, Meetups, or classes to meet new people. Keep in touch with your friends by talking or texting daily. Join your friends for coffee dates, dinner, and games. While you were with your ex, it’s likely that you gave up part of yourself to become a partner to them. Now that you’re apart, regaining what you lost can help you enjoy being single! Think about the things you enjoyed before you got with your ex. Then, start including those things in you routine. For instance, you might have given up your gym membership because you never had time to go. Now is the time to renew it! As another example, you might have stopped painting or doing photography because you were spending more time with your ex. Break out your equipment and dive back into that hobby! Pick a goal you’ve always wanted to accomplish or something that’s always interested you. Then, make a list of steps you can take to start working on it. Dedicate a block of time each day to work on your goal, and try to check off the steps on your list. This can help you stop thinking about your ex and build your independence. For example, you might decide to pursue a degree or to start a photography business. Think about the times your ex said “no” to something you wanted to do, like trying a new restaurant or visiting a local museum. Then, create a breakup bucket list of these items. Ask a friend to join you or go alone as you check off each item on the list. Each time you do something, remind yourself that your ex was holding you back from it. For instance, join a friend for Indian food at the restaurant your ex wouldn’t try, paint pottery with a group of friends, play beach volleyball, go on a picnic in the park, visit the planetarium, and go to a slam poetry reading. Picture yourself in a year, 5 years, and 10 years. Think about how you want to live and what type of things you want to do. Then, write down what you hope to accomplish in the coming years so you can start working toward those goals. This can help you create a life you love as you move on from your ex. For instance, you might want to buy a home, build your career, and take your dream vacation. Similarly, you might realize that you want to add more creativity to your life or that you want to move to a different area.
A: Focus on your existing relationships and on making new friends. Pursue the interests you set aside during your relationship. Start a new passion project to help you feel fulfilled. Try new things that your ex refused to do with you. Identify the future you want for yourself.
Q: One of the most common signs of ear mite infection is the scratching of the affected ear. This ear scratching is because ear mites can cause considerable irritation. The rabbit may scratch his ears with his paw or rub his ears on the ground. Your rabbit may also shake his head or hold his ear over to one side. Your rabbit’s ears may have reddened or inflamed skin. Irritation from the feces and saliva of the mite causes extreme itchiness, and the rabbit scratches and traumatizes the ear. A severe infection due to ear mites is characterized by distinctive yellow-gray debris and scale that builds up and fills the ear canal. This debris and discharge is tightly adhered to the skin. Attempting to remove the debris causes pain. Forcible removal tends to peel away the top layer of skin with the discharge leaving a large ulcer behind. Typically in the early stages of infection, close inspection may show scales of skin tightly stuck to the ear canal. If ear mites are left untreated, the weight of the collected debris inside the ear can cause it to drop. The rabbit may develop secondary bacterial infections where the skin is damaged, and infection may spread inwards into the middle and inner ear causing poor balance and a head tilt.
A: Watch for ear scratching. Look for discharge from the ear. Monitor for drooping ears.
Q: If you're really worried about food poisoning, canned beans are a safer option than dried beans. They are already thoroughly cooked in the can, so you don't have to worry about cooking them. Red kidney beans have the highest concentrations of hemagglutinin, so they put you the most at risk. If you're worried, pick a bean with a lower concentration, such as cannellini beans or broad beans. Chickpeas also contain much less hemagglutinin than red kidney beans, and lentils have an even smaller amount. If you do eat undercooked beans, look for symptoms of food poisoning. You may have nausea, vomiting, and diarrhea. You may also have cramps or abdominal pain. Generally, these symptoms appear within 3 hours of eating the beans. Visit urgent care or the ER if your symptoms are severe.
A:
Opt for canned beans. Choose beans that are lower risk. Recognize the symptoms.
|
#!/usr/bin/env node
"use strict";
Object.defineProperty(exports, "__esModule", { value: true });
var child_process = require("child_process");
var path = require("path");
var uglifyJS = require("uglify-js");
var stripJsonComments = require("strip-json-comments");
var fs = require("fs-extra");
var yesno = require("yesno");
var version = require('../package.json').version;
var arg = process.argv[2];
if (arg) {
arg = arg.toLowerCase();
if (arg === 'init') {
init();
}
else if (arg === 'run') {
run();
}
else {
showHelp();
}
}
else {
showHelp();
}
/**
* Initialization code
* Copy required files to working dir
*/
function init() {
var toCopyDir = path.join(__dirname, '../tocopy');
console.log('The following files will be added to the current directory:');
// Fetch all files to copy
fs.readdirSync(toCopyDir).forEach(function (file) {
console.log(file);
});
yesno.ask("Proceed to copy? (y/n)", false, function (ok) {
if (!ok) {
console.log("Stopping installation");
process.exit(0);
}
console.log();
fs.readdirSync(toCopyDir).forEach(function (file) {
var from = path.join(toCopyDir, file), to = path.join(process.cwd(), file);
fs.copySync(from, to, {
filter: function () {
if (fs.existsSync(to)) {
console.log("/!\\ " + file + " already exists in directory, skipping");
return false;
}
return true;
}
});
});
console.log('\nAll files copied. Setup the tsc80-config.json, then type "tsc80 run"');
process.exit(0);
});
}
/**
* Compile, compress, run
*/
function run() {
var config = JSON.parse(stripJsonComments(fs.readFileSync('tsc80-config.json', 'utf8'))), tsconfig = JSON.parse(stripJsonComments(fs.readFileSync('tsconfig.json', 'utf8'))), cGame = config['game'], cTic = config['tic'], cCompress = config['compression'], outFile = tsconfig['compilerOptions']['outFile'];
function compile() {
console.log('Compiling TypeScript...');
child_process.exec('tsc', function (error, stdout, stderr) {
if (stdout)
console.log(stdout);
if (stderr) {
console.log(stderr);
}
else {
compressAndLaunch();
}
});
}
function compressAndLaunch() {
var buildStr = fs.readFileSync(outFile, 'utf8'), result = uglifyJS.minify(buildStr, {
compress: cCompress['compress'],
mangle: cCompress['mangle'],
output: {
semicolons: false,
beautify: !cCompress['mangle'] && !cCompress['compress'],
indent_level: cCompress['indentLevel'],
comments: false,
preamble: "// title: " + cGame['title'] + "\n// author: " + cGame['author'] + "\n// desc: " + cGame['desc'] + "\n// script: js\n// input: " + cGame['input'] + "\n"
}
});
fs.writeFileSync(cCompress['compressedFile'], result.code);
if (!cTic['ticExecutable'] || !cTic['cartsDirectory']) {
console.log('Missing "ticExecutable" and/or "cartsDirectory" in tsc80-config.json');
process.exit(0);
}
var cmd = "\"" + cTic['ticExecutable'] + "\" \"" + cTic['cartsDirectory'] + "/" + cGame['cart'] + "\" -code " + cCompress["compressedFile"];
console.log("Launch TIC: " + cmd);
var child = child_process.spawn(cTic.ticExecutable, [
cTic.cartsDirectory + "/" + cGame.cart,
"-code",
cCompress.compressedFile
], {
stdio: "inherit"
});
child.on("exit", function (code, signal) {
process.on("exit", function () {
backupCart();
child = null;
if (signal) {
process.kill(process.pid, signal);
}
else {
process.exit(code);
}
});
});
}
function backupCart() {
var cartPath = cTic.cartsDirectory + "/" + cGame.cart;
if (fs.existsSync(cartPath)) {
if (fs.existsSync(cGame.cart)) {
fs.unlinkSync(cGame.cart);
}
fs.copySync(cartPath, cGame.cart);
console.log("Copied " + cGame.cart + " into current dir");
}
else {
console.error("Unable to copy " + cartPath);
console.error("Did you save your game at least once in TIC-80?");
}
}
compile();
}
function showHelp() {
console.log(" v" + version);
console.log();
console.log(" Usage: tsc80 [command]");
console.log();
console.log(" Commands:");
console.log("");
console.log(" init - Copy the required files inside current directory. If a file already exists, it will be skipped.");
console.log(" run - Compile, compress, and launch your TIC-80 game");
}
|
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Communication
Synthesis and Monoamine Oxidase Inhibition Properties of 4-(2-Methyloxazol-4-yl)benzenesulfonamide
1
Pharmaceutical Technology Transfer Center, Yaroslavl State Pedagogical University Named after K. D. Ushinsky, Yaroslavl 150000, Russia
2
Department of Organic Chemistry, Russian State University Named after A. N. Kosygin, Moscow 115035, Russia
3
Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa
*
Author to whom correspondence should be addressed.
Molbank 2024, 2024(1), M1787; https://doi.org/10.3390/M1787
Submission received: 9 January 2024 / Revised: 19 February 2024 / Accepted: 23 February 2024 / Published: 6 March 2024
Abstract
:
4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 43.3 and 3.47 μM, respectively. The potential binding orientation and interactions of the inhibitor with MAO-B were examined by molecular docking, and it was found that the sulfonamide group binds and interacts with residues of the substrate cavity. 4-(2-Methyloxazol-4-yl)benzenesulfonamide showed no cytotoxic effect against human stromal bone cell line (HS-5) in the concentration range of 1–100 µmol. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for the development of antiparkinsonian agents.
1. Introduction
Neurodegenerative disorders significantly affect the health of the human population and place a burden on economies of countries around the world. Among these disorders, Parkinson’s disease (PD) is the second most prevalent and is associated with the death of dopaminergic motor neurons in the brain. At present, PD is not curable; however, the motor symptoms associated with this disorder are effectively treated with levodopa, the metabolic precursor of dopamine. To enhance the therapeutic action of levodopa, this drug is frequently combined with monoamine oxidase (MAO) B inhibitors, compounds that reduce the MAO-mediated central metabolism of dopamine [1]. While MAO-B inhibitors may allow for a reduction in the effective levodopa dosage, these compounds have also been studied as neuroprotective agents [2], candidates for reducing neuroinflammation [3,4,5,6], as well as compounds with potential value in the therapy of oncological diseases [7]. Possible mechanisms by which MAO-B inhibitors may exert neuroprotective effects include the enhancement of the levels of brain-derived neurotrophic factors (BDNFs) [8] and the molecular adhesion of L1CAM (L1) nerve cells, which can also promote axonal regrowth and increase neuronal survival, synaptic plasticity, and remyelination [9]. Thus, the development of a new generation of neuroprotective agents that act by inhibiting MAO might have relevance in the future treatment of neurodegenerative disorders.
Benzenesulfonamide compounds have been identified as potent and isoform-specific inhibitors of MAO-B, with some compounds exhibiting potencies in the nanomolar range. Such compounds might represent promising candidates for the future treatment of PD [10,11]. Also, it has been established that 1,3-oxazole derivatives exhibit the potent and specific inhibition of the MAO-B isoform [12]. This work reports a successful attempt to combine both these structural features into a single molecule (Figure 1).
Recently, our research group, as well as others, reported a variety of new lead compounds for the development of isoform-specific MAO-B inhibitors, such as 2,1-benzisoxazoles [13,14], indazoles [15,16], and quinoxalines [17,18]. Continuing the search for novel MAO inhibitors, in this work, we used a simple convergent approach to synthesize a new 1,3-oxazole compound substituted with a primary benzenesulfonamide functionality.
2. Results
2.1. Chemistry
We investigated the possibility of synthesizing the target oxazole 1 by the reaction of sulfonamide-containing phenacyl bromide 2 with acetamide or ammonium acetate.
The starting material, phenacyl bromide 3, was obtained according to a well-known three-step procedure using 4-acetylbenzenesulfonamide (2) as a key reagent (Scheme 1) [19,20]. The best yield (63%) of the target oxazole 1 was obtained by fusing phenacyl bromide 3 with an excess of acetamide at 150 °C ((Scheme 2). It was shown that the reaction ends in 15–20 min, and longer heating or increasing the reaction temperature to 190 °C leads to a sharp decrease in the yield of 1 and the appearance of degradation by-products.
Additionally, when we used the method in [21] based on reaction compound 5 with ammonium acetate in acetic acid, the target oxazole 1 was obtained at a much lower yield (24%).
2.2. MAO Inhibition
The MAO inhibition potency of 4-(2-methyloxazol-4-yl)benzenesulfonamide (1) was evaluated using recombinant human MAO-A and MAO-B following the protocol described in the literature [13]. The results of the MAO inhibition studies are presented in Table 1. Compound 1 inhibited MAO-B with an IC50 value of 3.47 μM, whereas weak inhibition of the MAO-A isoform was recorded.
The potential orientations by which 1 binds to the active site of human MAO-B was investigated by molecular docking using the CDOCKER module of the Discovery Studio 3.1 modeling software. Docking predicts that the inhibitor binds with the sulfonamide group placed in the substrate cavity of the enzyme, while the oxazole moiety extends towards the entrance cavity of the MAO-B active site (Figure 2).
The experimentally determined binding mode of zonisamide is also shown [22]. The sulfonamide group is placed in the same space as that of zonisamide, as determined by X-ray crystallography [22]. Hydrogen bonding occurs between the sulfonamide functional group and an active site water and Gln-206. Pi–sulfur interactions form between Tyr-60 and the sulfonamide functional group, as well between Cys-172 and the oxazole moiety. A pi-pi interaction also occurs between the oxazole moiety and Tyr-326. It is interesting to note that the oxazole moiety does not protrude deep into the entrance cavity and therefore cannot be viewed as a cavity-spanning MAO-B inhibitor. Compounds that bind to both the substrate and entrance cavities often exhibit submicromolar potencies due to the additional stabilization afforded by nonpolar interactions with the lipophilic environment of the entrance cavity [23]. This may explain the moderate MAO-B inhibition potency observed for compound 1.
Table 1. The inhibition of human MAO-A and MAO-B by 4-(2-methyloxazol-4-yl)benzenesulfonamide (1).
Table 1. The inhibition of human MAO-A and MAO-B by 4-(2-methyloxazol-4-yl)benzenesulfonamide (1).
StructureIC50 (μM ± SD) 1
MAO-AMAO-B
43.3 ± 7.123.47 ± 0.31
Curcumin [24] 2 5.02 ± 0.452.56 ± 0.21
Toloxatone [25] 23.92 -
1 The IC50 values are presented as the means ± standard deviation (SD) of triplicate measurements. 2 Reference inhibitors.
2.3. Cytotoxicity In Vitro
The cytotoxicity of compound 1 was investigated on human cell line HS-5 (human bone marrow stroma). In this respect, the cell viability after being incubated with 1–100 µM of the test compound was evaluated using the MTT assay [26,27].
The result of that experiment showed that compound 1 did not exhibit toxicity at the concentration range used for this study (Figure 3).
3. Discussion
This study reports the MAO inhibition potency of 4-(2-methyloxazol-4-yl)benzenesulfonamide (1). This compound inhibited MAO-B with an IC50 value of 3.47 μM, while the MAO-A isoform was inhibited with an IC50 value of 43.3 μM. Molecular docking experiments show that the inhibitor is restricted to the substrate cavity and does not extend deep into the entrance cavity, which may explain the moderate MAO-B inhibition potency observed for this compound. The discovery of this active MAO-B inhibitor paves the way for the future discovery of MAO-B inhibitors among 1,3-oxazole derivatives substituted with a primary benzenesulfonamide. Such compounds may find application in the treatment of neurodegenerative disorders such as PD.
4. Materials and Methods
4.1. General
All reagents and solvents were obtained from commercial sources (Aldrich, Merck, Aladdin, Gernsheim, Germany) and were used without purification. Reactions were monitored by analytical thin-layer chromatography (TLC) using Merck TLC sheets. Visualization of the developed sheets was performed by fluorescence quenching at 254 nm. 1H NMR and 13C NMR spectra were recorded on a Varian 400 Unity Plus instrument (400 MHz for 1H and 100 MHz for 13C, respectively). Chemical shifts (δ) are given in parts per million (ppm) and were referenced to the solvent signal for DMSO-d6 (2.50 ppm for proton and 39.52 ppm for carbon), while the coupling constants (J) were reported in hertz (Hz). Multiplicities are abbreviated as follows: s = singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, m = multiplet. Melting points were determined on an Electrothermal IA 9300 series digital melting point apparatus. Mass spectra were recorded using ESI ionization on a microTOF spectrometer (Bruker Daltonics Inc., Bremen, Germany).
4.2. Procedure for the Preparation of 4-(2-Bromoacetyl)benzenesulfonamide (3)
Compound 3 was prepared according the method described in [20] using 0.90 g 4-acetylbenzenesulfonamide (2) as a starting material. (3) In total, 1.22 g (98%) of 4-(2-Bromoacetyl)benzenesulfonamide was isolated as the beige crystalline solid. mp 154–155 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 8.2 Hz, 2H), 7.96 (d, J = 8.2 Hz, 2H), 7.57 (s, 2H), 4.98 (s, 2H).
4.3. Synthesis and Characterization of 4-(2-Methyloxazol-4-yl)benzenesulfonamide (1)
Acetamide (0.12 g, 2 mmol, 3 equiv.) and 4-(2-bromoacetyl)benzenesulfonamide (3; 0.19 g, 0.68 mmol, 1 equiv.) were mixed together. The reaction mixture was melted, stirred at 150 °C for 20 min, and subsequently diluted with cold water (30 mL). The resulting precipitate was collected by filtration, washed with water (10 mL), and air-dried at 50 °C. Yield 0.101 g, 63%, beige solid, mp 237–239 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.61 (s, 1H), 7.93 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.38 (s, 2H), 2.48 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 162.6, 143.7, 139.2, 137.0, 134.9, 126.9, 125.9, 14.2; MS (ESI+): m/z [M+H]+ Anal. Calcd for C10H11N2O3S: 239.0485. Found: 239.0489 (Supplementary Materials).
4.4. MAO Inhibition Studies
The measurement of IC50 values for the inhibition of human MAO-A and MAO-B was carried out according to a previously reported protocol [13]. Recombinant human MAO-A and MAO-B were obtained from Sigma-Aldrich (USA), and fluorescence measurements were recorded with a SpectraMax iD3 multi-mode microplate reader (Molecular Devices). The measurement of MAO activity was based on the fluorescence signal generated when the substrate, kynuramine, was oxidized by the MAOs to yield 4-hydroxyquinoline.
4.5. Molecular Docking Studies
Molecular docking was carried out according to the previously reported protocol using the Discovery Studio 3.1 suite of software [11]. The X-ray crystal structure of MAO-B (PDB code: 2V5Z) complexed to safinamide was used for the docking study [28]. The illustration was created with the PyMOL molecular graphics system [29].
4.6. Cytotoxicity Assay
The human cell culture line HS-5 (bone marrow stroma) was grown in a mixture (1:1) of RPMI-1640 and Ham’s F12 media without glutamine. To the media, we added FBS (10%), L-glutamine (2 mM), penicillin (50 IU/mL), and streptomycin (50 μg/mL). The test compounds were dissolved in DMSO and added to the culture media to yield a final concentration of 0.1% DMSO. As a positive control (0% cell viability), the cells were exposed to sodium azide (0.1%). As a negative control, cell viability was measured in the absence of the test compound. The cytotoxicity of the test compound was determined by the MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide] protocol [27]. Absorbance was measured at a wavelength of 590 nm with a CLARIOstar (BMG Labtech) spectrophotometer. The blank consisted of culture medium.
Supplementary Materials
1H- and 13C-NMR spectra copies of synthesized compounds can be found in the File S1 (Supplementary Materials).
Author Contributions
Conceptualization of the study was conducted by A.A.S.; formal analysis and investigation by J.A.E. and A.P.; writing—original draft preparation was conducted by A.A.S.; writing—review and editing was conducted by M.K.K. and J.P.P. All authors have read and agreed to the published version of the manuscript.
Funding
The chemical section of this work was supported by the Russian Science Foundation (project 22-13-20085). The MAO inhibition studies were funded by the National Research Foundation of South Africa [grant specific unique reference number (UID) 137997 (JPP)]. The grant holders acknowledge that the opinions, findings, and conclusions or recommendations expressed in any publication generated by NRF-supported research are that of the authors and that the NRF accepts no liability whatsoever in this regard.
Data Availability Statement
Data are contained within the article.
Conflicts of Interest
The authors declare no competing interests.
References
1. Tan, Y.Y.; Jenner, P.; Chen, S.D. Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease: Past, Present, and Future. J. Park. Dis. 2022, 12, 477–493. [Google Scholar] [CrossRef]
2. Szökő, É.; Tábi, T.; Riederer, P.; Vécsei, L.; Magyar, K. Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease. J. Neural Transm. 2018, 125, 1735–1749. [Google Scholar] [CrossRef]
3. Ostadkarampour, M.; Putnins, E.E. Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action. Front. Pharmacol. 2021, 12, 676239. [Google Scholar] [CrossRef]
4. Santos, M.A.; Chand, K.; Chaves, S. Recent progress in multifunctional metal chelators as potential drugs for Alzheimer’s disease. Coord. Chem. Rev. 2016, 327, 287–303. [Google Scholar] [CrossRef]
5. Meredith, G.E.; Totterdell, S.; Beales, M.; Meshul, C.K. Impaired glutamate homeostasis and programmed cell death in a chronic MPTP mouse model of Parkinson’s disease. Exp. Neurol. 2009, 219, 334–340. [Google Scholar] [CrossRef]
6. Belaidi, A.A.; Bush, A.I. Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: Targets for therapeutics. J. Neurochem. 2016, 139, 179–197. [Google Scholar] [CrossRef]
7. Zarmouh, N.O.; Messeha, S.S.; Mateeva, N.; Gangapuram, M.; Flowers, K.; Eyunni, S.V.K.; Zhang, W.; Redda, K.K.; Soliman, K.F.A. The Antiproliferative Effects of Flavonoid MAO Inhibitors on Prostate Cancer Cells. Molecules 2020, 25, 2257. [Google Scholar] [CrossRef]
8. Balu, D.T.; Hoshaw, B.A.; Malberg, J.E.; Rosenzweig-Lipson, S.; Schechter, L.E.; Lucki, I. Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments. Brain Res. 2008, 1211, 37–43. [Google Scholar] [CrossRef] [PubMed]
9. Li, R.; Sahu, S.; Schachner, M. Phenelzine, a cell adhesion molecule L1 mimetic small organic compound, promotes functional recovery and axonal regrowth in spinal cord-injured zebrafish. Pharmacol. Biochem. Behav. 2018, 171, 30–38. [Google Scholar] [CrossRef] [PubMed]
10. Grover, N.D.; Limaye, R.P.; Gokhale, D.V.; Patil, T.R. Zonisamide: A review of the clinical and experimental evidence for its use in Parkinson’s disease”. Ind. J. Pharmacol. 2013, 45, 547–555. [Google Scholar] [CrossRef] [PubMed]
11. Shetnev, A.; Shlenev, R.; Efimova, J.; Ivanovskii, S.; Tarasov, A.; Petzer, A.; Petzer, J.P. 1,3,4-Oxadiazol-2-ylbenzenesulfonamides as privileged structures for the inhibition of monoamine oxidase B. Bioorg. Med. Chem. Lett. 2019, 29, 126677. [Google Scholar] [CrossRef] [PubMed]
12. Qazi, S.U.; Naz, A.; Hameed, A.; Osra, F.A.; Jalil, S.; Iqbal, J.; Shah, S.A.; Mirza, A.Z. Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies. Bioorg. Chem. 2021, 115, 105209. [Google Scholar] [CrossRef] [PubMed]
13. Shetnev, A.; Kotov, A.; Kunichkina, A.; Proskurina, I.; Baykov, S.; Korsakov, M.; Petzer, A.; Petzer, J.P. Monoamine oxidase inhibition properties of 2,1-benzisoxazole derivatives. Mol. Divers. 2023. [Google Scholar] [CrossRef] [PubMed]
14. Agrawal, N.; Mishra, P. Synthesis, monoamine oxidase inhibitory activity and computational study of novel isoxazole derivatives as potential antiparkinson agents. Comput. Biol. Chem. 2019, 79, 63–72. [Google Scholar] [CrossRef] [PubMed]
15. Tzvetkov, N.T.; Antonov, L. Subnanomolar indazole-5-carboxamide inhibitors of monoamine oxidase B (MAO-B) continued: Indications of iron binding, experimental evidence for optimised solubility and brain penetration. J. Enzym. Inhib. Med. Chem. 2017, 32, 960–967. [Google Scholar] [CrossRef] [PubMed]
16. Efimova, J.A.; Shetnev, A.A.; Baykov, S.V.; Petzer, A.; Petzer, J.P. 3-(3,4-Dichlorophenyl)-5-(1H-indol-5-yl)-1,2,4-oxadiazole. Molbank 2023, 2023, M1552. [Google Scholar] [CrossRef]
17. Panova, V.A.; Filimonov, S.I.; Chirkova, Z.V.; Kabanova, M.V.; Shetnev, A.A.; Korsakov, M.K.; Petzer, A.; Petzer, J.P.; Suponitsky, K.Y. Investigation of pyrazolo[1,5-a]quinoxalin-4-ones as novel monoamine oxidase inhibitors. Bioorg. Chem. 2021, 108, 104563. [Google Scholar] [CrossRef]
18. Khattab, S.N.; Hassan, S.Y.; Bekhit, A.A.; El Massry, A.M.; Langer, V.; Amer, A. Synthesis of new series of quinoxaline-based MAO-inhibitors and docking studies. Eur. J. Med. Chem. 2010, 45, 4479–4489. [Google Scholar] [CrossRef]
19. Jacobs, J.W.; Leadbetter, M.R.; Bell, N.; Koo-McCoy, S.; Carreras, C.W.; He, L.; Kohler, J.; Kozuka, K.; Labonté, E.D.; Navre, M.; et al. Discovery of tenapanor: A first-in-class minimally systemic inhibitor of intestinal Na+/H+ exchanger isoform 3. ACS Med. Chem. Lett. 2022, 13, 1043–1051. [Google Scholar] [CrossRef]
20. Scobie, M.; Wallner, O.; Koolmeister, T.; Vallin, K.S.A.; Henriksson, C.M.; Homan, E.; Helleday, T.; Jacques, S.; Desroses, M.; Jacques-Cordonnier, M.-C.; et al. MTH1 Inhibitors for Treatment of Inflammatory and Autoimmune Conditions. U.S. Patent 16,102,170, 31 August 2018. [Google Scholar]
21. Denney, D.B.; Pastor, S.D. Structures in solution of adducts of hexamethylphosphorus triamide and substituded benzils. Phosphorus Sulfur. Silicon Relat. Elem. 1983, 16, 239–246. [Google Scholar] [CrossRef]
22. Binda, C.; Aldeco, M.; Mattevi, A.; Edmondson, D.E. Interactions of monoamine oxidases with the antiepileptic drug zo-nisamide: Specificity of inhibition and structure of the human monoamine oxidase B complex. J. Med. Chem. 2011, 54, 909–912. [Google Scholar] [CrossRef]
23. Hubalek, F.; Binda, C.; Khalil, A.; Li, M.; Mattevi, A.; Castagnoli, N.; Edmondson, D.E. Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors. J. Biol. Chem. 2005, 280, 15761–15766. [Google Scholar] [CrossRef] [PubMed]
24. Khatri, D.K.; Juvekar, A.R. Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid. Pharmacogn. Mag. 2016, 12, 116–120. [Google Scholar] [CrossRef]
25. Berlin, I.; Zimmer, R.; Thiede, H.; Payan, C.; Hergueta, T.; Robin, L.; Puech, A. Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Br. J. Clin. Pharmacol. 1990, 30, 805–816. [Google Scholar] [CrossRef] [PubMed]
26. Ghasemi, M.; Turnbull, T.; Sebastian, S.; Kempson, I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int. J. Mol. Sci. 2021, 22, 12827. [Google Scholar] [CrossRef]
27. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55–63. [Google Scholar] [CrossRef]
28. Binda, C.; Wang, J.; Pisani, L.; Caccia, C.; Carotti, A.; Salvati, P.; Edmondson, D.E.; Mattevi, A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs. J. Med. Chem. 2007, 50, 5848–5852. [Google Scholar] [CrossRef]
29. DeLano, W.L. The PyMOL Molecular Graphics System; DeLano Scientific: San Carlos, CA, USA, 2002. [Google Scholar]
Figure 1. Structures of MAO inhibitors containing the sulfonamide or 1,3-oxazole moieties [11,12].
Figure 1. Structures of MAO inhibitors containing the sulfonamide or 1,3-oxazole moieties [11,12].
Scheme 1. Synthesis of 4-(2-bromoacetyl)benzenesulfonamide (3).
Scheme 1. Synthesis of 4-(2-bromoacetyl)benzenesulfonamide (3).
Scheme 2. Synthesis of 4-(2-methyloxazol-4-yl)benzenesulfonamide (1).
Scheme 2. Synthesis of 4-(2-methyloxazol-4-yl)benzenesulfonamide (1).
Figure 2. The predicted binding orientation of compound 1 to the active site of MAO-B. Zonisamide shown in pink, oxazole compound 1 shown in blue, red dots showing the binding regions to the target cavity.
Figure 2. The predicted binding orientation of compound 1 to the active site of MAO-B. Zonisamide shown in pink, oxazole compound 1 shown in blue, red dots showing the binding regions to the target cavity.
Figure 3. Cell viability after treatment of HS-5 stromal cell line with compound 1 (1–100 µM).
Figure 3. Cell viability after treatment of HS-5 stromal cell line with compound 1 (1–100 µM).
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MDPI and ACS Style
Shetnev, A.A.; Efimova, J.A.; Korsakov, M.K.; Petzer, A.; Petzer, J.P. Synthesis and Monoamine Oxidase Inhibition Properties of 4-(2-Methyloxazol-4-yl)benzenesulfonamide. Molbank 2024, 2024, M1787. https://doi.org/10.3390/M1787
AMA Style
Shetnev AA, Efimova JA, Korsakov MK, Petzer A, Petzer JP. Synthesis and Monoamine Oxidase Inhibition Properties of 4-(2-Methyloxazol-4-yl)benzenesulfonamide. Molbank. 2024; 2024(1):M1787. https://doi.org/10.3390/M1787
Chicago/Turabian Style
Shetnev, Anton A., Julia A. Efimova, Mikhail K. Korsakov, Anél Petzer, and Jacobus P. Petzer. 2024. "Synthesis and Monoamine Oxidase Inhibition Properties of 4-(2-Methyloxazol-4-yl)benzenesulfonamide" Molbank 2024, no. 1: M1787. https://doi.org/10.3390/M1787
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Circle of Fifths (Added Sharps and Flats)
I understand that an easy way to determine the 'key' of a piece of music is to either look at the last sharp within the key signature and add a half step (semitone), or look at the second to last flat. But I am wondering why is this the case?
What about going around the circle of fifths (Starting at C Major) causes the next key in succession to add a sharp to the 7th scale degree? Any insight is greatly appreciated.
Not an answer, but pertinent. Learning 'keys' this way is flawed. True, the last flat is the leading note, etc., but there's only 12, for Heaven's sake. We leaned a heck of a lot more than that learning the alphabet ! Make it a mnemonic, if you like, or just learn the list in order. Most of us recognise key signatures from playing pieces in the signed keys. It's no big deal - or shouldn't be!
Although those tricks are useful starting points, @Tim's correct in that the eventual end goal should be memorization of the key signatures. It's so much more efficient once you can do that!
To add to other comments: it's not even about "memorizing" ... it's about "remembering". When you use something often enough, you will remember it. And that's more robust and adaptible than cute mnemonics (which are easy enough to mis-remember!). :)
I disagree that memorization should be the goal. The goal should be understanding the underlying pattern so that the need to memorize is reduced as much as possible. For example I could memorize the multiplication table for 9's or realize that 9 =10-1, so every time the tens digit increases the ones digit decreases. 09, 18, 27 ... ones digit is 9,8,7 ... tens digit is 0,1,2, etc. Same with key signatures which is strongly like counting by 9's, except it's 2 accidentals for each whole step up. Cmajor has zero accidentals, D=2, E=4, F#=6, etc. (con't)
(con't) The key down from C is Fmajor ... has '-1' sharp (1 flat), G has 1# (added 2 to -1), A=3, B=5#'s etc. I figured this out from the music theory learning shortcut I figured out in 2017. YouTube videos are forthcoming.
Adding sharps / Removing flats
Consider the following definition of a major scale (W = Whole Step; H = Half step):
W W H W W W H
This gives us scale degrees and intervals between as follows:
1 W 2 W 3 H 4 W 5 W 6 W 7 H 8
Now we're going to start the "next" major scale beginning on degree 5 of the previous scale. Thus things map as follows:
starting scale: 5 W 6 W 7 H 1 W 2 W 3 H 4 W 5
"new" scale 1 W 2 W 3 H 4 W 5 W 6 W 7 H 8
Notice that all the intervals line up except for degrees 3-4-5 or the original scale, which correspond to 6-7-8 of the new scale. 3-4-5 is H-W; whereas we want W-H. This is achieved by raising scale degree 4 of the original scale a half step.
Put simply: The sharp introduced as one goes around the circle of fifths is always the leading-tone (i.e., scale degree seven, or, one step before the tonic) of the new scale.
Adding a sharp is "the same" as subtracting a flat, which is why when key signatures switch from sharps to flats, the number of flats in the key signature is reduced until there are none and the circle has returned to C major.
As a brief example, Bb major has two flats: Bb and Eb. The next step in the circle of fifths is F major, which has only Bb. The Eb from Bb major was "sharped" to create the leading tone for F major, leaving only Bb. The Bb is then sharped to result in C major.
Adding flats / Removing sharps
A similar logic shows why the second-to-last flat also shows the key.
Again, the major scale:
1 W 2 W 3 H 4 W 5 W 6 W 7 H 8
This time, the new scale begins on the fourth degree of the old scale (i.e., the circle of fourths — the "backwards" circle of fifths).
starting scale: 4 W 5 W 6 W 7 H 1 W 2 W 3 H 4
"new" scale 1 W 2 W 3 H 4 W 5 W 6 W 7 H 8
Now the "wrong" intervals are 6-7-1 of the old scale, which correspond to 3-4-5 of the new one. To fix the problem, we lower the old scale's leading tone — that is, the "new" flat corresponds to the fourth degree of the new scale. Put another way, the new flat is always a fourth above the new scale's tonic. But that tonic was itself scale degree four of the scale before that one: i.e., the second-to-last flat.
For example:
C Major = 0 flats
Go up a fourth (to F) and add a flat to the fourth scale degree (Bb).
F Major = 1 flat (and that flat, Bb, is up a fourth from the tonic)
Go up another fourth (to Bb) and add a flat to the fourth scale degree (Eb)
Bb Major = 2 flats, with the second-to-last being Bb, the tonic.
Go up another fourth (to Eb) ... oh, Eb is the last flat of the previous key, so it will become the second-to-last flat in this new key.
And so on.
If I have not said it hundreds of times, it is because I have said it thousands of times. Makes me rather nostalgic of my teaching days.
The flat keys always count four steps past its name. It is how the circle of fourths work for the keys with flats in them.
The circle of fifths count 5 steps forward for the new key and then 4 steps forward - FROM THE SAME PLACE YOU STARTED AT! - for the new sharp.
Of course, like it has always been new keys keep old sharps and flats.
The easiest way to learn keys is to have a good theory teacher do key signatures drills with you until you know them. Yes, what you say is true, but it is not how it should be taught.
Music Theory Pedagogy 101 in a nutshell.
I understand that an easy way to determine the 'key' of a piece of music is to either look at the last sharp within the key signature and add a half step (semitone), ...
Technically, when the sharp is added to the key signature it signifies that tone becomes the leading tone and so the half step above that will be the tonic... provided the mode is major.
How is that supposed to work if the mode is minor? Now you need a new rule of thumb that says the minor tonic will be a whole step below "the last sharp."
...or look at the second to last flat.
How does that work with a key signature of one flat? There is no second to last flat in that case.
That rule also give no consideration whether the mode is major or minor?
Technically, adding a flat to the key signature signifies that tone is the subdominant when the mode is major, and in the minor mode it will be the minor submediant.
This isn't how you read key signatures. You just check the count of sharps or flats. And to know the tonic, you usually just look at the first bar or final cadence. But the details of finding the tonic are really a separate issue.
The first huge flaw in that "easy way" is it makes no distinction about mode, major or minor. The second flaw is in an attempt to make it "easy" it glosses over the detail that you still need four "rules" to cover the basic cases of key signatures of either sharps or flats and either major or minor mode.
By the time you make that "easy way" actually work you've done just as much work as learning the key signatures.
The typical thing for teachers to do seems to be rote memorization, like what Neil Meyer suggests in his answer. I think it's better to learn them in context through actual playing. At the very least make scale practice the same time to memorize key signatures. Instead of scale practice you could use simple classical stuff, like Czerny's Recreations, or a hymnal, to find lots of material in keys of zero to three sharps or flats.
The other reason to not use rote learning for key signatures is because it's more of a system than random facts. You should try to understand key signatures in a systematic way. When key signatures get to five or more sharps or flats they become more difficult. But you should understand why they become difficult.
This is my break down of key signatures, getting more difficult moving left to right, adding more sharps or flats...
"Common key signatures" and "enharmonic region" are labels I made up. I don't think you will find a chart like this in a textbook.
Broadly speaking key signatures get complicated when there are five or more sharps and flats, and for the most part those keys are the ones where the sharps or flats also apply to the tonic, because those keys can be respelled to various enharmonic equivalents.
That enharmonic equivalency does not come up in key signatures of four or less sharps or flats. For example, the key C# minor, the tonic does take a sharp, but there are only four sharps in the key signature. This key is pretty common. It also doesn't have a practical enharmonic equivalent. It's enharmonic equivalent would be Db minor, a theoretical keys signature that uses a double flat!
Here is a visual arrangement of key signatures that lists all practical key signatures along with their enharmonic equivalents...
...theoretically the chart is infinite. You could keep expanding to the left and right forever moving in perfect fifths, but those theoretical keys will have double, triple, etc sharps/flats which is impractical. The practical key signatures use 7 or less sharps/flats. You could say the number of key signatures is infinite, but the ones that are practical is a tiny, finite slice of them.
You should notice the symmetry of that chart. You can apply a similar symmetry at the keyboard. Start on the piano key for F#Gb and then move ascending/descending from in contrary motion in half steps. Each side of that F#/Gb pivot will render keys to the left and right which are the same number of sharps/flats...
TONIC: ...Eb E F F#/Gb G Ab A ...
KEY SIG: ...3b 4# 1b 6#/6b 1# 4b 3#...
| | | | | |
| | |------------| | |
| | | |
| |----------------------| |
| |
|--------------------------------|
Even though the musical system of 7 letters, 12 chromatic tones, and the layout of black and white piano keys seems a bit of a muddle, there is a definitely symmetry to it all, if you view it from the right perspective. But, most textbooks and teachers don't present these symmetries.
I don't mean to throw too much theory at you. The main points are...
learn the musical alphabet in perfect fifths ascending and descending
understand relative major/minor and enharmonic equivalency
learn common keys of 0-4 sharps/flats through simple performance exercises
be aware of the enharmonic complications of keys with 5 or more sharps/flats
If you embrace the idea of playing in all keys as an essential musical skill, just combine key signature learning with scale practice. By the time you have learned to play all of your scales you will know all the key signatures. If you don't embrace this idea, you will probably be forever befuddled by key signatures.
In the next few weeks I'll make some videos using my 'two-handed music theory calculator'. Anyone will be instantly able to figure out how many sharps or flats, what they are, where they are, the chords of the scale, how to figure out a scale from a few notes or chords, etc.
@RandyZeitman - I hope for a "calculator breaks down" result or a result that spews out the chromatic scale or close to it for scale results for chromatic chord progressions like Bbm-Bm-Bbm-Am (start of "You Will Know Our Names" from Xenoblade Chronicles, piece actually manages to stay in B flat minor despite stuff like this).
@RandyZeitman, sounds like Chisanbop. Why not learn music from music?
Actually it just starts with two hands to create a pattern. Good point. "Why not learn music from music?" It doesn't teach music. It's a shortcut method to simplify understanding the relationship between notes, scales, chords and harmony. There's no analysis.
Look at the major scale intervals
WWHWWWH
Starting with CMajor the notes are CDEFGAB(C).
The EF and BC fall on the H's so there's no sharps or flats.
But the next key up starts at position 5, but then the EF doesn't fall on an H but instead a W. So a half step is needed on note 7.
In Gmajor the 6 and 7th notes are E and F# where as in C they were A-B (a whole, no accidentals needed).
The distance is the same ... 12 half notes per octave but as each key starts at the fifth note, and the pattern is 2W,H,3W,H the notes have to change to fit the pattern as only BC and EF are half tones.
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Pyspark job possible resource limit issue
I'm running a glue job in aws. It basically runs pyspark code inside an aws glue job. The job does some etl connecting to several ec2 instances. It runs fine for a smaller number of instances but as I scale it up to a larger number it's failing and the final error log message is below. I'm wondering is the code failing because of issues with one of the instances, or some part of my code, or is it a resource limitation caused by the default glue job settings?
I found a stackoverflow post mentioning SIGNAL TERM error that suggests the issue may have to do with memory or dynamic time allocations, could that be the problem and if so what parameters might I change to test that?
SO Post:
Spark Error : executor.CoarseGrainedExecutorBackend: RECEIVED SIGNAL TERM
Error log:
2019-11-06 09:21:18,189 INFO [Executor task launch worker for task 26635] memory.MemoryStore (Logging.scala:logInfo(54)) - Block broadcast_477 stored as values in memory (estimated size 9.1 KB, free 2.8 GB)
2019-11-06 09:21:18,190 INFO [dispatcher-event-loop-0] executor.CoarseGrainedExecutorBackend (Logging.scala:logInfo(54)) - Got assigned task 26637
2019-11-06 09:21:18,191 INFO [Executor task launch worker for task 26637] executor.Executor (Logging.scala:logInfo(54)) - Running task 0.0 in stage 477.0 (TID 26637)
2019-11-06 09:21:18,191 INFO [Executor task launch worker for task 26637] broadcast.TorrentBroadcast (Logging.scala:logInfo(54)) - Started reading broadcast variable 479
2019-11-06 09:21:18,193 INFO [Executor task launch worker for task 26637] memory.MemoryStore (Logging.scala:logInfo(54)) - Block broadcast_479_piece0 stored as bytes in memory (estimated size 5.1 KB, free 2.8 GB)
2019-11-06 09:21:18,194 INFO [Executor task launch worker for task 26637] broadcast.TorrentBroadcast (Logging.scala:logInfo(54)) - Reading broadcast variable 479 took 3 ms
2019-11-06 09:21:18,194 INFO [Executor task launch worker for task 26637] memory.MemoryStore (Logging.scala:logInfo(54)) - Block broadcast_479 stored as values in memory (estimated size 9.1 KB, free 2.8 GB)
2019-11-06 09:21:18,640 INFO [Executor task launch worker for task 26629] codegen.CodeGenerator (Logging.scala:logInfo(54)) - Code generated in 13.337938 ms
2019-11-06 09:21:18,841 INFO [Executor task launch worker for task 26629] glue.JDBCRDD (Logging.scala:logInfo(54)) - closed connection
2019-11-06 09:21:18,884 INFO [Executor task launch worker for task 26629] executor.Executor (Logging.scala:logInfo(54)) - Finished task 0.0 in stage 469.0 (TID 26629). 1366 bytes result sent to driver
2019-11-06 09:21:19,156 INFO [Executor task launch worker for task 26637] glue.JDBCRDD (Logging.scala:logInfo(54)) - closed connection
2019-11-06 09:21:19,230 INFO [Executor task launch worker for task 26637] executor.Executor (Logging.scala:logInfo(54)) - Finished task 0.0 in stage 477.0 (TID 26637). 1366 bytes result sent to driver
2019-11-06 09:21:23,308 INFO [Executor task launch worker for task 26635] glue.JDBCRDD (Logging.scala:logInfo(54)) - closed connection
2019-11-06 09:21:23,790 INFO [Executor task launch worker for task 26635] executor.Executor (Logging.scala:logInfo(54)) - Finished task 0.0 in stage 475.0 (TID 26635). 1366 bytes result sent to driver
2019-11-06 09:21:23,940 INFO [Executor task launch worker for task 26624] glue.JDBCRDD (Logging.scala:logInfo(54)) - closed connection
2019-11-06 09:21:24,279 INFO [Executor task launch worker for task 26624] executor.Executor (Logging.scala:logInfo(54)) - Finished task 0.0 in stage 464.0 (TID 26624). 1366 bytes result sent to driver
2019-11-06 09:22:26,134 ERROR [SIGTERM handler] executor.CoarseGrainedExecutorBackend (SignalUtils.scala:apply$mcZ$sp(43)) - RECEIVED SIGNAL TERM
2019-11-06 09:22:26,139 INFO [pool-7-thread-1] storage.DiskBlockManager (Logging.scala:logInfo(54)) - Shutdown hook called
2019-11-06 09:22:26,139 INFO [pool-7-thread-1] util.ShutdownHookManager (Logging.scala:logInfo(54)) - Shutdown hook called
End of LogType:stdout
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судија
Etymology
.
Noun
* 1) judge
* 2) referee
Etymology
.
Noun
* 1) judge
* 2) referee
Usage notes
Literary Croatian prefers the word.
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Convertible garment system
ABSTRACT
A convertible garment system including a hooded sweatshirt having an interior portion, an exterior portion, a body portion, a first-sleeve, a second-sleeve, a neck-opening, and a carrying bag. The carrying bag is integral to and affixed to the neck-opening on the interior portion of the hooded sweatshirt. The hooded sweatshirt is convertible between a carrying bag configuration and a garment configuration and provides a combination carrying bag and hooded sweatshirt.
CROSS REFERENCE TO RELATED APPLICATION
The present application is related to and claims priority to U.S. Provisional Patent Application No. 62/693,652 filed Jul. 3, 2018, which is incorporated by reference herein in its entirety.
BACKGROUND OF THE INVENTION
The following includes information that may be useful in understanding the present disclosure. It is not an admission that any of the information provided herein is prior art nor material to the presently described or claimed inventions, nor that any publication or document that is specifically or implicitly referenced is prior art.
1. FIELD OF THE INVENTION
The present invention relates generally to the field of garments and more specifically relates to transformable garments.
2. DESCRIPTION OF RELATED ART
Many athletes stuff bulky sweatshirts in their gym bag, which generally take up a lot of space, leaving very little room to shove a pair of shoes or other items. As a result, some athletes may carry these items separately in the hands, which can be frustrating and inconvenient. Additionally, when they take off the sweatshirt after warm-ups on the field or court, they may not have anywhere to store the sweatshirt on the sidelines. As well, in the spring, summer, and fall, it can be significantly cooler in the mornings and evenings, requiring people to switch back and forth from wearing a sweatshirt to not wearing a sweatshirt. A suitable solution is desired.
U.S. Pat. No. 6,405,377 to Gwennette Q. Davis relates to a convertible jacket. The described convertible jacket includes a garment which comprises a jacket portion and a bag portion. The jacket portion has a back side which includes an outer shell and an inner shell. A pocket is defined between a portion of the outer shell and the inner shell. The inner shell defines an orifice which provides access to the pocket. A fastener associated with the orifice is configured for selectively opening and closing the orifice. The bag portion is integral with the jacket portion and is disposed within the pocket. The bag portion has flexible sides which define a bag opening. A fastener is associated with the bag opening and is configured for selectively providing access to an interior of the bag portion. The bag portion has a volume sufficient to store at least the jacket portion. The bag portion is configured to be removed from the pocket and turned inside out. The bag portion receives the jacket portion therein, thereby forming a duffel bag. At least one strap is attached to the interior of the bag portion and is disposed on an exterior of the bag portion after the bag portion has been turned inside out.
BRIEF SUMMARY OF THE INVENTION
In view of the foregoing disadvantages inherent in the known garment art, the present disclosure provides a novel convertible garment system. The general purpose of the present disclosure, which will be described subsequently in greater detail, is to provide a combination hoodie jacket and carrying bag unit.
A convertible garment system is disclosed herein. The convertible garment system includes a hooded sweatshirt having an interior portion, an exterior portion, a body portion, a first-sleeve, a second-sleeve, a neck-opening, and a carrying bag. The body portion is configured to fit over a torso of a body of a user-wearer. The first-sleeve and the second-sleeve extend from the body portion and are configured to receive a left arm and right arm of the user-wearer respectively. The neck-opening is provided at an upper section of the body portion and is configured to receive a head of the user-wearer during use. The carrying bag is integral to and affixed to the neck-opening on the interior portion of the hooded sweatshirt. The carrying bag comprises two of the shoulder straps providing a backpack-like carrying bag. The carrying bag is concealed within the interior portion of the hooded sweatshirt when in the garment configuration. The carrying bag is flexible and invertible. The carrying bag is configured to receive and house the hooded sweatshirt within an interior storage portion of the carrying bag while in the carrying bag configuration. The hooded sweatshirt is convertible between a carrying bag configuration and a garment configuration and provides a combination carrying bag and hooded sweatshirt.
For purposes of summarizing the invention, certain aspects, advantages, and novel features of the invention have been described herein. It is to be understood that not necessarily all such advantages may be achieved in accordance with any one particular embodiment of the invention. Thus, the invention may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein. The features of the invention which are believed to be novel are particularly pointed out and distinctly claimed in the concluding portion of the specification. These and other features, aspects, and advantages of the present invention will become better understood with reference to the following drawings and detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
The figures which accompany the written portion of this specification illustrate embodiments and methods of use for the present disclosure, a convertible garment system, constructed and operative according to the teachings of the present disclosure.
FIG. 1 is a front view of the convertible garment system, according to an embodiment of the disclosure.
FIG. 2 is a rear view of the convertible garment system of FIG. 1, according to an embodiment of the present disclosure.
FIG. 3 is a perspective view of the convertible garment system of FIG. 1, according to an embodiment of the present disclosure.
FIG. 4 is a perspective view of the convertible garment system of FIG. 1, according to an embodiment of the present disclosure.
FIG. 5 is a perspective view of the convertible garment system of FIG. 1, according to an embodiment of the present disclosure.
The various embodiments of the present invention will hereinafter be described in conjunction with the appended drawings, wherein like designations denote like elements.
DETAILED DESCRIPTION
As discussed above, embodiments of the present disclosure relate to a garment and more particularly to a convertible garment system as used to combine a hoodie garment and a gym bag into a single unit for convenience and portability.
Generally, the present invention provides a combination hoodie that transforms into a gym bag. The product includes a secure pocket to store small valuables without the chance of losing them. It allows athletes to ‘warm up’ wearing a sweatshirt and then remove the sweatshirt and flip it into a bag for storing other items during a game. The product saves time and frustration toting a separate bag and sweatshirt around, or taking up space inside bags with big, bulky sweatshirts.
The present invention offers access to a sweatshirt anywhere the bag can be stored, including in cars if stranded on the side of the road. The hoodie combines a hooded sweatshirt and gym bag into one simple and convenient garment. This garment features a high quality shoulder-style gym bag, made from nylon, cotton, or other suitable material, that attaches to the inside back neckline of a sweatshirt. When wearing the sweatshirt, that bag can be undetectable. When not wearing the sweatshirt, users can simply flip the sweatshirt inside the bag, and pull the straps to close the bag. Next, users can place the straps over shoulder and wear like a traditional bag. Inside the bag can be a zippered pocket to store small valuable items like a cell phone, wallet, ID, and money. Additionally, on the corner of the bag can be a key loop to hang keys. Further, the sweatshirt can be offered in a wide range of colors, designs, and prints, as well as sizes, to accommodate user preferences and needs.
Referring now more specifically to the drawings by numerals of reference, there is shown in FIGS. 1-5, various views of a convertible garment system 100. FIG. 1 shows a convertible garment system 100, according to an embodiment of the present disclosure. As illustrated, the convertible garment system 100 may include a hooded sweatshirt 110 having an interior portion 112, an exterior portion 114, a body portion 116, a first-sleeve 118, a second-sleeve 120, a neck-opening 122, and a carrying bag 124. The body portion 116 is configured to fit over a torso of a body of a user-wearer. The first-sleeve 118 and the second-sleeve 120 extend from the body portion 116 and are configured to receive a left arm and right arm of the user-wearer respectively. The neck-opening 122 is provided at an upper section of the body portion 116 and is configured to receive a head of the user-wearer during use. The carrying bag 124 is integral to and affixed to the neck-opening 122 on the interior portion 112 of the hooded sweatshirt 110. The hooded sweatshirt 110 is convertible between a carrying bag configuration and a garment configuration and thus provides a combination carrying bag 124 and hooded sweatshirt 110.
FIG. 2 shows a rear view of the convertible garment system 100 of FIG. 1, according to an embodiment of the present disclosure. As above, the convertible garment system 100 may include the hooded sweatshirt 110 having the interior portion 112, the exterior portion 114, the body portion 116, the first-sleeve 118, the second-sleeve 120, the neck-opening 122, and the carrying bag 124 providing a combination carrying bag 124 and hooded sweatshirt 110. The carrying bag 124 comprises at least one shoulder strap 130. In a preferred embodiment, the carrying bag 124 comprises two of the shoulder straps 130 as a backpack. In particular, the backpack is a drawstring type the backpack. The drawstring type backpack comprises a drawstring fastener. The drawstring fastener forms the two of the shoulder straps 130. Manipulation of the drawstring fastener allows for opening and alternatively closing of the carrying bag 124.
FIG. 3 shows a perspective view of the convertible garment system 100 of FIG. 1, according to an embodiment of the present disclosure. As above, the convertible garment system 100 may include the hooded sweatshirt 110 comprising the integral carrying bag 124. The carrying bag 124 is flexible and invertible. The carrying bag 124 is configured to receive and house the hooded sweatshirt 110 within an interior storage portion 126 of the carrying bag 124 while in the carrying bag configuration. The carrying bag 124 may include at least one storage compartment 132 for holding personal items. The at least one storage compartment 132 may be positioned on the interior storage portion 126 or exterior of the carrying bag 124. The at least one storage compartment 132 may include a fastener such as a zipper-fastener for securing items within the storage compartment 132.
FIG. 4 shows a perspective view of the convertible garment system 100 of FIG. 1, according to an embodiment of the present disclosure. As above, the convertible garment system 100 may include the hooded sweatshirt 110 comprising the interior portion 112, the exterior portion 114, the body portion 116, the first-sleeve 118, the second-sleeve 120, the neck-opening 122, and the carrying bag 124. The carrying bag 124 is concealed within the interior portion 112 of the hooded sweatshirt 110 when in the garment configuration. The carrying bag 124 may comprise a flexible material such as nylon, cotton, or other suitable material. The carrying bag 124 may further feature a key loop 134 for securing keys. In one embodiment, the hooded sweatshirt 110 includes a zipper (zippable fastener) and pockets.
FIG. 5 shows a perspective view of the convertible garment system 100 of FIG. 1, according to an embodiment of the present disclosure. As above, the convertible garment system 100 may include a hooded sweatshirt 110 which transforms into a carrying bag 124. In a preferred embodiment, the hooded sweatshirt 110 includes a carrying bag 124 which is integral to and affixed to the neck-opening 122 on the interior portion 112 of the hooded sweatshirt 110. The hooded sweatshirt 110 may be converted between a carrying bag configuration and a garment configuration.
The embodiments of the invention described herein are exemplary and numerous modifications, variations and rearrangements can be readily envisioned to achieve substantially equivalent results, all of which are intended to be embraced within the spirit and scope of the invention. Further, the purpose of the foregoing abstract is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientist, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application.
What is claimed is new and desired to be protected by Letters Patent is set forth in the appended claims:
1. A convertible garment system comprising: a hooded sweatshirt having an interior portion; an exterior portion; a body portion; a first-sleeve; a second-sleeve; a neck-opening; and a carrying bag; wherein said body portion is configured to fit over a torso of a body of a user-wearer; wherein said first-sleeve and said second-sleeve extend from said body portion and are configured to receive a left arm and right arm of said user-wearer respectively; wherein said neck-opening is provided at an upper section of said body portion and is configured to receive a head of said user-wearer during use; wherein said carrying bag is integral to and affixed to said neck-opening on said interior portion of said hooded sweatshirt; and wherein said hooded sweatshirt having said carrying bag is convertible and provides a combination carrying bag and hooded sweatshirt for use and is convertible between a carrying bag configuration and a garment configuration.
2. The convertible garment system of claim 1, wherein said carrying bag comprises at least one shoulder strap.
3. The convertible garment system of claim 2, wherein said carrying bag comprises two of said shoulder straps.
4. The convertible garment system of claim 3, wherein said carrying bag comprises a backpack.
5. The convertible garment system of claim 4, wherein said backpack is a drawstring-type said backpack.
6. The convertible garment system of claim 5, wherein said drawstring-type said backpack comprises a drawstring fastener.
7. The convertible garment system of claim 6, wherein said drawstring fastener forms said two of said shoulder straps.
8. The convertible garment system of claim 7, wherein manipulation of said drawstring fastener allows for opening and alternatively closing of said carrying bag.
9. The convertible garment system of claim 1, wherein said carrying bag further comprises a key loop.
10. The convertible garment system of claim 1, wherein said hooded sweatshirt further comprises a zippable fastener.
11. The convertible garment system of claim 10, wherein said hooded sweatshirt further comprises pockets.
12. The convertible garment system of claim 1, wherein said carrying bag comprises a material selected from the group consisting of nylon and cotton.
13. The convertible garment system of claim 1, wherein said carrying bag is concealed within said interior portion of said hooded sweatshirt when in said garment configuration.
14. The convertible garment system of claim 1, wherein said carrying bag is flexible and invertible.
15. The convertible garment system of claim 1, wherein said carrying bag is configured to receive and house said hooded sweatshirt within an interior storage portion of said carrying bag while in said carrying bag configuration.
16. The convertible garment system of claim 15, wherein said carrying bag further comprises at least one storage compartment.
17. The convertible garment system of claim 16, wherein said at least one storage compartment of said carrying bag is positioned on said interior storage portion.
18. The convertible garment system of claim 17, wherein said at least one storage compartment comprises a fastener.
19. The convertible garment system of claim 18, wherein said fastener is a zippable-fastener.
20. A convertible garment system, the convertible garment system comprising: a hooded sweatshirt having an interior portion; an exterior portion; a body portion; a first-sleeve; a second-sleeve; a neck-opening; and a carrying bag; wherein said body portion is configured to fit over a torso of a body of a user-wearer; wherein said first-sleeve and said second-sleeve extend from said body portion and are configured to receive a left arm and right arm of said user-wearer respectively; wherein said neck-opening is provided at an upper section of said body portion and is configured to receive a head of said user-wearer during use; wherein said carrying bag is integral to and affixed to said neck-opening on said interior portion of said hooded sweatshirt; wherein said hooded sweatshirt having said carrying bag is convertible and provides a combination carrying bag and hooded sweatshirt for use and is convertible between a carrying bag configuration and a garment configuration; wherein said carrying bag comprises at least one shoulder strap; wherein said carrying bag comprises a backpack; wherein said backpack is a drawstring type said backpack; wherein said drawstring type said backpack comprises a drawstring fastener; wherein said drawstring fastener forms two of said at least one shoulder straps; wherein manipulation of said drawstring fastener allows for opening and alternatively closing of said carrying bag; wherein said carrying bag further comprises a key loop; wherein said hooded sweatshirt further comprises a zippable fastener; wherein said hooded sweatshirt further comprises pockets; wherein said carrying bag is concealed within said interior portion of said hooded sweatshirt when in said garment configuration; wherein said carrying bag is flexible and invertible; wherein said carrying bag is configured to receive and house said hooded sweatshirt within an interior storage portion of said carrying bag while in said carrying bag configuration; wherein said carrying bag further comprises at least one storage compartment; wherein said at least one storage compartment of said carrying bag is positioned on said interior storage portion; wherein said at least one storage compartment comprises a fastener; and wherein said fastener is a zipper-fastener.
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Can't generate Visual Studio project from SCons
I'm trying to generate the Visual Studio project with:
scons vsproj=yes platform=windows
using the VS command prompt as found here: http://stackoverflow.com/questions/21476588/where-is-developer-command-prompt-for-vs2013, but it fails with:
C:\godot>scons vsproj=yes platform=windows
scons: Reading SConscript files ...
internal error
Traceback (most recent call last):
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Script\Main.p
y", line 1372, in main
_exec_main(parser, values)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Script\Main.p
y", line 1335, in _exec_main
_main(parser)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Script\Main.p
y", line 1002, in _main
SCons.Script._SConscript._SConscript(fs, script)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Script\SConsc
ript.py", line 260, in _SConscript
exec _file_ in call_stack[-1].globals
File "C:\godot\SConstruct", line 399, in <module>
variant = variants)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Environment.p
y", line 260, in __call__
return MethodWrapper.__call__(self, target, source, *args, **kw)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Environment.p
y", line 224, in __call__
return self.method(*nargs, **kwargs)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Builder.py",
line 633, in __call__
return self._execute(env, target, source, OverrideWarner(kw), ekw)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Builder.py",
line 554, in _execute
tlist, slist = self._create_nodes(env, target, source)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Builder.py",
line 518, in _create_nodes
target, source = self.emitter(target=tlist, source=slist, env=env)
File "C:\Python27\Scripts\..\Lib\site-packages\scons-2.3.4\SCons\Tool\msvs.py"
, line 1642, in projectEmitter
raise SCons.Errors.InternalError(s + " must be a string or a list of strings
")
InternalError: srcs must be a string or a list of strings
I can build fine.
I don't have the slightest clue, I haven't made msvc support, so I'm not going to fix it :P
Volunteers appreciated!
Working here, just make sure you are running VS[~year~] x64 x86 Cross Tools command prompt when running:
scons vsproj=yes platform=windows
Win32 build fine, but x64 fails about a redefinition of:
#ifdef _WIN64
typedef unsigned __int64 size_t;
typedef __int64 ptrdiff_t;
typedef __int64 intptr_t;
#else
Complaining about ptrdiff_t being redefined in vcruntime.h
But one thing that bothers me is that header files of Godot are scattered everywhere, which means
VS can't find them but Scons will build fine. For example main.cpp is inside Godot/main/
Inside main.cpp where it tries to #include "core/register_core_types.h" for example, VS IDE fails
to detect the file if it exists with red squiggles underlines, causing debugging to go nuts. The reason
for this is that core/register_core_types.h is located one directory above of main. So the include
directive must have been #include "../core/register_core_types.h" instead.
My suggestion would be, to put all header files in their own directories, separated from source files.
Which will make it easier for VS IDE to find them all in one place or a set of directories at least.
I am not sure if I should open an issue for this or not, since it will require a lot of modifications to
SConstruct I believe.
XCode doesn't have problems with searching directories recursively, and I think linux too but I am not
sure. It only affects VS. But Godot is not designed to be code-able in Windows platform. I don't think
the devs will change this, since they are adamant about SCons.
Well moving the headers would be a hacky workaround. Any buildsystem should be able to locate headers provided you pass it the good paths to the folders that contain those headers.
You probably just need to find a way to tell VS that "." is an include directory. With gcc it would be -I..
Indeed, just make sure you have the right include paths.
On Mon, Jan 11, 2016 at 8:18 AM, Rémi Verschelde<EMAIL_ADDRESS>wrote:
Well moving the headers would be a hacky workaround. Any buildsystem
should be able to locate headers provided you pass it the good paths to the
folders that contain those headers.
You probably just need to find a way to tell VS that "." is an include
directory. With gcc it would be -I..
—
Reply to this email directly or view it on GitHub
https://github.com/godotengine/godot/issues/3117#issuecomment-170511903.
@akien-mga No such option in VS I am aware of, I already tried to include the the obvious $(ProjectDir) in VS additional include directories, but VS needs all directories specified individually.
That is, VS is trying to look for header files locations relative to current location of the file being parsed by the prerprocessor, not the base directory every time.
So unfortunately, your suggestion didn't work for me.
For the interested, I created manually a VS project is in the pull: https://github.com/godotengine/godot/pull/3247:
Hey @ex since you already have VS project and a PR for that, you might want to close this issue.
For me to be honest, I just gave up on SCons, the incremental builds are ridiculous! GOD bless the devs for living with that. It is so slow, using SCons with IDE such as VS is no better than using notepad with command prompt to build.
Sorry for my rants.
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Electron gas in a wire connected to two terminals with potential drop is
studied with the Schwinger-Keldysh formalism. Recent studies, where the current
is enforced to flow with a Lagrange-multiplier term, demonstrated that the
current enhances the one-particle-correlation function. We report that in our
model, such enhancement is not guaranteed to occur, but conditional both on the
potential drop and the positions where we observe the correlation function.
That is, under a certain condition, spatially modulated pattern is formed in
the wire owing to the nonequilibrium current.
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Enum handling in Npgsql and EntityFramework7
I have postgres database with some data in it.
I'm using Npgsql.EntityFramework7 adapter (version 3.1.0-beta8-2) to handle it.
The problem is when I try to get entity from context which has some enum inside of it.
In postgres I declare enum:
CREATE TYPE public.my_enum AS
ENUM ('value1','value2','value3');
My model looks like:
[Table("my_table")]
public class Entity
{
[Column("id")]
[Key]
public int Id { get; set; }
[Column("type")]
public MyEnum Type { get; set; }
}
Enum:
public enum MyEnum
{
value1,
value2,
value3
}
Unfortunately, when I try to get something from database via entity framework I receive this kind of error:
System.InvalidCastException: Can't cast database type
my_enum to Int32
I've tried to register my enum in Npgsql (as it's pointed in npgsql documentation). With no effects.
Is there something I can do to handle 'proper' enums with this stack? (to have enum fields in database as strings/enums not as ints)
This appears to be a bug in the npgsql provider. You will likely have better luck getting a solution by filing on issue on their GitHub repository. https://github.com/npgsql/npgsql
While Npgsql supports enigma at the ADO.NET level, the Npgsql EF7 provider doesn't support them yet. Can you please open an issue at github.com/npgsql/npgsql to track this?
Done - https://github.com/npgsql/npgsql/issues/842. Thanks for fast replies.
|
Compressor for refrigerating-machines
P. FISCHBACHER.
COMPRESSOR FOR REFRIGERATING MACHINES.
APPLICATION FILED JULY 30, I919.
1 3 0,9 1 0, V Patented Nov. 30, 1920.
Z 4 SHEE SSHEET 1- iii 5 awuemt-oc P B3 C6 faaizr attoamu P. FISCHBACH'ER.
COMPRESSOR FOR REFRIGERATING MACHINES.
APPLICATION FILED JULY 30.1919.
- 1,3609 l O. Patented Nov. 30, 1920.
4 SHEETSSHEET 2.
anemia/13 P. HSCHBACHER.
COMPRESSOR FOR REFRIGERATING MACHINES,
APPLICATION FILED JULY 30, I919. Patented Nov. 30, 1920.
. 4 SHEETSSHEET 3,
Q2 I n I m r I e a 5; 83 82 6 i I 3- 9 M 61 q 7 7%? I 2 T. L r h 1 I I 58 47 I 6 i av wa n toz i/ z'sc fi an? I attoznmg P. FISCHBACHER.
COMPRESSOR FOR REFRIGERATING MACHINES.
- APPLICATION FILED JULY 30. I919.
1,360,910, Patented Nbv. 30, 1920.
4 SHEETS-SHEET 4- v32 O O OCDO 2 2 J glwvawtoz v P sc 4: 1967 I attoznu PATENT: OFFICE-4 rr nmr FISCHBAGI-IER, or comer, ILLINOIS. assmnon 'ro AMERICAN sA mAnY REFRIGERATION 00., OF OWENSBORO, KENTUCKY, A
warm t To all wl iom it may concern:
Be it known that I, Prirnrhhsoiamonnn,1
a citizen of the United States, resid in at Quincy, in the county of Adams and tate of Illinois, have invented certain new and useful Improvements in Compressors for Refrigerating-Machines, of whichthe following is a specification, reference being had to the accompanying drawings. 7
This invention relates to refrigerating machinery, and particularly to that form of refrigerating machinery wherein an element under pressure is allowed to expand within the refrigerating coils, and isjthen withdrawn therefrom to a compressor and is compressed therein, and then condensed, and then passes back through the expansion or refrigerating coils. 1
One of the objects of this invention is to improve the construction of the condenser whereby the gas is condensed after leaving the compressor, and particularly to provide means whereby the cooling water within the condenser may be kept cool by the passage of air through cooling tubes passing through the water'and by the aid of fins forming part ofthe water containing tank. 7
Another objectis to' provide means for forcing air through these tubes and against the condenser'jack et. i I
A further object is to improve and simplify the compressor, partic'ularly'as regards the mechanism for reciprocating the piston and the inlet and outlet; valve mechanism, v 1
A further object is to provide in connection with the compressor, an accumulator or accumulat ng chamber hav lng a cubical content many times larger than the displacement of-the piston or pistons of the compressor, whereby any liquid passing over to 1119 compressor from the evaporation or ex pans lon coils may be evaporated, thus preventing the knocking out of the cylinder head and other injuries to the compressor.
And a further object is to. provide in connection with the accumulator, means whereby the refrigerating agent maybe purified before passing to the compressor.
CORPORATION OF DELL oo mr ms soa on REFRIGERATING-MACHINES.
Specification ot Letters Patent. Patented Nov, 30, 1920, Application fll ed J'uly" 80, 1919. "Serial No. 314,222. 1
Another object in this connection is to prov de means whereby the accumulator may be blown out, and to provide means whereby the screen used for separating the scale and other solid matters from the refrigerating agent and preventing these foreign mat- 'ters from passing into the valve chamber of I Still another object is to provide an auto-" 'matic expansion regulator controlling the passage of the refrigerating agent to the expansion or refrigerating coils, and. so constructed that as soon as the back pressure orevaporating pressure in said coils reaches the desired point, the needle valve controlling the passage of the refrigerating agent to the expansion coils will be closed and that when this evaporating pressure within the expansion coils is reduced beyond a certain amount, the valve of the expansion regulator will again open.- I v 7 Still another object is to provide an ex an sion regulator which is provided with a. an-
mg a valve controlling the passage of water from a source of supply to the jack et of the condenser, and this handle-further operating a switch whereby the passage of current to the electric motor running the compressor is controlled:
Other objects have to do with the details of construction and arrangement of parts,
, dle operating the valve controlling the passage of the refrigerating agent into the ex-- pansion regulator. this handle also opera tas-will be hereinafter more fully explained. I
My invention is illustrated in the accompanying'drawings, wherein Figure l is an elevation of a refrigerating system constructed in accordance with my invention, the compressor and the condenser being shown in section;
' V sepprator Fig. 2 is an enlarge d transverse sectional :view ofthe condenser and the compressor "ta'ken on the line 2 2 of Fig. 1;
Fig. 3 is a vertical sectional view of the expansion regulator,
ig. 4.is a vertical sectional view of the ig .'5 is a sectional view of the outer valve cage of-the compressor;
j -Fig.-6 is a vertical sectional view of the nterior valve cage;
'Fig. 7 is a vertical sectional view of the induction valve;
'erally 'the; compressor,
Fig S isa vertical sectional view of the;
outlet valve; and 7 Fig. 9 is asection on the line.99 of Fi 8. i
Tteferring to these drawings, particularly a i to Fig z'f 1, it will be seen that I have illus- 'that'is a compressor having two parallel cylinders 10. Operating within each cylincrank shaft 12,
der is 'the'piston ll'operated by a double having opposite ly extending cranks'13 engaging the piston rods. The 'crank shaft 12 operates within the crank case 14., The cylinder casting rests upon this crank case or isconnected thereto in any suitable manner and is provided with the outwardly projectingfiange 15. Each cylinder is] enlarge d at its upper end, as at 16. These upper ends of the cylinders are closed by heads 17 which are cast in one piece, this casting v 18 between the heads being, formed 'to provide an accumulator chamber '19. Each head 17 is formed to provide a chamber v 20 coincident with the longitudinal axis of the corresponding cylinder.
I Disposed within each enlarge d portion 16 and resting upon' a shoulder formed at the base of'this-enlarge d portion is a cage 21hav- .ing' an'inwardly extending flange 22 at its lower end, and formed upon this lower face with a valve seat 23. The wall of this cage i s p rovided with a plural it of perforations.
he'enlarge d head 16 orms an annular chamber 24 surrounding the cage 21, and these chambers 24 are connected by a duct or passage 25 extending through the web connecting the enlarge d. portions of the cylinders. This-passage 25, it maybe said in passing, is connected to the accumulator chamber 19. Disposed inward of and con centric to :the cage 21 .is a cylindrical, im-
perforate cage 26, the upper end of which is j enlarge d or flanged and, exterior ly screw passage 'cumulator chamber 19, and from this duct threaded for engagement with the interior screw-threads on the upper end of the cage 21. The lower end of this cage 26 is downwardly and central l beveled on both faces to form an inner va ve seat 27 and an outer valve seat 28. Disposed exterior to the cage 26 and having a sliding fit therewith'is a cylindrical valve 29, whose lower end 15 flanged or headed, as at 30, to provide a valve proper having opposite l beveled faces co acting with the sea-ts 23 an '28. The upper end of the tubular shank of this valve 29 is flanged, and a spring 31 bears against this flanged end and urges the tubular shank of the valve upward and the valve to its seats. This valve 29 constitutes the inlet valve of the compressor and the cylindrical body or shank of the valve is perforated, as at 32, to permit free passage of gas into the upper end of the cylinder upon the suction stroke of the compressor. Disposed within the annular or cylindrical member 26 is an outlet valve 33 whose lower end is beveled to fit the, seat 27, this valve being connected to a hollow, cylindrical body 34', open at its bottom and top and having a sliding fit within the member 26, the valve being .held to its seat by a spring 35 in the chamber 20. It will be obvious that upon the downward movement of" a" piston, the inlet valve 30 will open, permitting the passage of the refrig- 95 and that upon the upward crating agent from the accumulator 19 into the compressor, movement of the compressor, this inlet valve will close, and that after the refrigerating agent hasbeen compressed to a certain'degree, the outlet valve 33 will open, permitting the passage of the compressed refrigerating agent into the chamber 20. Both of these chambers 20 are connected by a duct or 36, which extends through the acor passage 36-leads a pipe 37.
Preferably, a screen or filter is disposed'be tween the duct 25 and the accumulator chamber 19 in order to separate the foreign particles from the refrigeratingagent, and to this end I have shown a pipe 38 as extending from the duct 25 into the accumulator chamber, this pipe bein rforated at its upper end and surround e by a screen 39. This pipe and screen are removable for cleaning, and leakage is prevented by'the stuffing boxes 40. Extending from the accumulator chamber 19 at one side of this pipe 38 is a blow-ofi valve or cook 41, whereby impurities may be blown out of the accumulator chamber from time to time. that the accumulator chamber shall be provided at one side in its wall with a sight glass whereby the interior of the accumulator chamber may be inspected from time to time.
Disposed around one or both of the cylin- 120 It is preferable I ders is a cooler jack et 42. This jack et is,
formed of thin, corrugated metal and is riveted or otherwise attached at its bottom upon the flange 15. The side wall of the jack et is very deeply corrugated so as to give a relatively large cooling area, and extending through the interior of the cooling jack et and opening upon the outer face of the cooling jack et are a plural ity of thin metal pipes 43, these pipes being open at their opposite ends. Extending spirally around the cylinders of the compressor and submerged within the cooling jack et is a condensing coil 44,
and it will be noted from Fig. 1 that the tubes 43 are disposed between these coils to space the coils apart. Mounted in suitable bearings on one side of the compressor is a blower or air propeller 45 which forces cool air positively against the cooling jack et and through the pipes 43 so that constant currents of cold air are being made to continually traverse these pipes 43.
The crank shaft 12 carries thereon a Worm wheel 46 which is driven by a worm 47 on a worm shaft 48. This shaft passes through a suitable stu fling box 49 in the crank case. 14 and at its outer end is driven by the motor H. This shaft also carries upon it a combined band and fly wheel 50. The air propeller 45 is mounted upon a shaft 51 which, at its'inner end, is supported in bearings 52 formed between the cylinders. and this shaft carries upon it a band wheel 53 to which power is transmitted from the band wheel and fly wheel 50 by means of a belt or in any other suitable manner. I
The pipe 37 leads into the separator C. which comprises a vertically extending, tubular member closed at its upper end and having at its lower end a discharge tube 54 provided with a purge valve. The interior of this separator C is divided for a portion of its length into two parts by means of a zigzag plate 55 constituting a'-ba file-wall.
This plate extends from the top of the separator nearly to the bottom thereof, and the upper end of the separator isconnected to the upper end of the coil 44 by means of a pipe connection 56. The separator C, of course, is designed for the purpose of separating oil from the refrigerating agent and operates in the usual manner. Thus oil and these coils extends a pipe 60 which discharges into the accumulator 19.
The expansion regulator is designed to automatically control the passage of the condensed refrigerating agent from the pipe 58 into the expansion coil and to be controlled by the evaporation pressure or back pressure within the expansion coils. The expansion regulator comprises a tubular body 61 whose inlet end is connected to the pipe 58 and hence to the receiver E, and whose outlet end connects by pipe 59 to the expansion coils. Disposed within this tubular body and adjacent its inlet end is a rotatable cut-ofi' valve 62 having a stem extending downward through a stuffing box 63 formed on the body 61, and this stem at its lower end carries a rotatable valve or cook 64 carried within a valve casing 65 forming part of the pipe connection 66 by j which water is conducted from a source of the valve spindle 62 are the rotatable switch elements 72, which co act with the terminals '70 and 71. and which, when they are turned in one position, connect said terminals, and in the other position disconnect them. Suitable conductors lead from the switch terminals 70 and 71 to the electric motor H. and are connected thereto in an obvious manner, and feed conductors lead from a source of energy to these terminals 70 and 71. Thus, it will be seen that when the valve spindle 62 is rotated a quarter turn. the valve 62 will be opened to permit the flow of refrigerating agent from the receiver E to the expansion coils, the valve 64 will be opened to permit the flow of water from the water supply to the jack et 42, and the motor H will be connected to a source of current.
Mounted upon and forming part of the body 61 is a cylinder 73 formed to provide a lower chamber 74 and an ui per chamber- 75 separated from each other y an annular web. Disposed in this annular web is a stu fling box 76. The lower end of the chamber 74 is open and the body 61 is provided With a central, upwardly extending hub valve 82, which diaphragm has been found 80 constitute astu fling box through which passes the rod 81 whose lower end is tapered to form a valve 82 extending through the hub 77, and which may extend across the contracted portion 83 of the central bore of body 61.
For the purpose of shifting the valve 82,
.1 provide within the chamber 75 a piston S l whichis urged upwardbymeans of a. compression spring. 85 and which is attached to the upper end of the rod 81. The head 86of chamber 75 is provided with v a central screw 87 which may be turned down to limit the upward movement of the piston and is held in its adjusted position by a lock nut 88, this screw providing means for adjusting the expansion valve. Leading into the upper endof the chamber 7 5 above the piston is a duct 89 connected by a pipe 90 to the pipe 59 and, therefore, connected. to
- the'sucti0n line, andthe opposite wall of "the chamber 75 is provided with a duct 91 leading from the upper portion of the chamber 75 above the piston and leading to a pressure gage 92 of any ordinary and usual construction.
. In practical use, assuming'that the valve 62 is' open, then as soon as the back pressure or evaporating pressure in the evaporating coils G attains a predetermined degree, this pressure will be transmitted to the oil in the upper portion of the chamber 75and'this oil will force the piston 84 down.- ward against the force of the spring 85, thus causing the valve 82 to close the passage through the body 61, in other words prevent the passage of refrigerant from the receiver E to the expansion coils. When this back pressure is relieved, however, then the spring 85 moves the piston 84 upward a degree depending upon the adjustment of the screw 87 and then the valve 82 permits the passage of refrigerant to the expansion coils. The valve stems and valves of the automatic expansion regulator are made of non-corrosive metal, and self-lubricating metal packing is used for the stufiing-boxes- 63, 76 and 77 to prevent any sticking or wearing. This construction does away with the use of a diaphragm for-controlling the to be unreliable. This expansion regulator eliminates danger of explosions and also damage due to overflowing the refrigerating system with liquid and in turning the water on for the condenser, as the refrigerant can not be allowed to flow to the expansion and refrigerating coils without the water cock (S L-having also been turned on. It is 60 in small amounts to the jack et 42 in order to take care of evaporation, and that there to be understood that water is only supplied is no necessity of causing cold water to fi ow through the jack et 42, as the cooling jack et with its tubes or pipes 43 and the fan or propeller 45 takes'entire care of condensation of the incoming gases and keeps the it passes into the cooling coil 44 of the condenser, from which condensed gases flow as a liquid into the receiver, thus completin the cycle of operation. It is to be particularly noted that the accumulator chamber 19is many times larger than the displacement of the pistons. The discharge from pipe runs through this accumulator chamber and in its passage through the accumulator chamber all liquid refrigerant which may be carried over from the low pressure or expansion side is evaporated. This prevents the knocking out of the cylinder heads and other injuries to the compress er. Furthermore, this evaporation acts to purify the refrigerating agent and thus a continuous purifying action takes place when the system is in operation.
It is also to be pointed out that the outside valve cage 21 has a relatively large area and that there is a large inlet surface formed by the double seated inlet valve 30, and that the large area in the accumulator and the large area outside the valve cage 21 and the large inlet surface of the double seated valve, permits the compressor to have an extremely high speed with the cylinders always filled with pure gas for discharge.
Therefore, I secure a relatively. great efficiency from a relatively small and cheap machine, using considerably less power and less water.
It will be understood that in the accumulating chamber 19, the cold incoming gases accumulate and the discharge gases flow through this accumulating chamber by the pipe 36. The discharge gases raise the temperature of the accumulating gases in chamber 19 and thus separate the liquid and other foreign matters which would be otherwise drawn over onto the low pressure side of the system. The pure ammonia vapor passes through the inlet port in the cylinder upon the down stroke of the piston and the unevaporated liquid which can not pass through the filler 39, collects in the bottom of the accumulator until blown out through valve 41, and this accumulator or accumulating chamber is made large so that the liquid which collects in the bottom of the chamber can have the ammonia therein evaporated therefrom without the liquid passing over into the inlet pipe.
The concentric valve mechanism which I have illustrated is particularly valuable as the suction valve, that is the valve 30, is the most important valve on a refrigerating machine. This suction valve must have a very large area on a high speed machine in order to fill the cylinder full of gas. The suction valve seat is relatively wide and has a. diameter nearly that of the bore of the cylinder, and the suction valve has a larger bearing or guide portion 29 than is possible with an ordinary puppet valve. Therefore, not only this, but a larger, more flexible spring can be used and a quicker opening and closing can be secured, therefore an extremely high speed can be developed with less cost than is possible in the old type of puppet valve.
The water supply valve 64 is to compensate for loss of water from the 'ack et by evaporation or from other causes. he water level in this jack et is kept above the accumulator chamber 19. Of course, the object of the zigzag separator plates 55 is to secure the greatest possible area for separating impurities of the discharge gases. These inclined plates tend to impede the movement of the foreign particles without impeding the movement of the fluid passing through the separator.
I claim 1. In refrigerating machinery, the combination with a compressor having a compressor cylinder, a piston operating therein, and inlet and outlet valves therefor, of an accumulating chamber, an outlet pipe leading from the accumulator chamber and perforated therein, a screen disposed around the perforated end of the outlet pipe, and a blow-off valve opening from the accumulator chamber.
2. A refrigerating machine including in combination a pair of compressor cylinders, each cylinder having inlet and outlet valves formed to provide an inlet duct communicating with both cylinders and an outlet duct leading from both cylinders, a crank case upon which the cylinders are mounted, a crank shaft therein having opposite ly disposed cranks engaged with pistons in the compressor cylinders, a worm gear carried upon the crank shaft, and a driving shaft having a worm extending into the crank case and engaging said worm gear.
3. A refrigerating compressor including in combination a compressor cylinder en large d at one end, a piston operating within the cylinder, an annular inlet valve having opposite ly beveled faces operating within the enlarge d portion of the cylinder, the enlarge d portion of the cylinder being formed with double annular seats for said valve, a spring holding said valve closed but permitting the opening of the valve upon the intake stroke of the piston, and a central ly disposed discharge valve yielding ly urged to its seat.
4. A compressor for refrigerating machinery including in combination a coinpressor cylinder enlarge d at one end and having an inlet duct opening into this enlarge d end, a piston operating within the cylinder, an annular cage disposed within the enlarge d end of the cylinder and having perforated side walls and a beveled under face, an inner, cylindrical imperforate cage concentricto the first named cage but spaced therefrom and defining an outlet passage and formed at one end of said passage with an inwardly inclined, annular valve seat, and exterior of this valve seat with a second downwardly and central ly extending annular valve seat, the first named cage being formed at its lower end with a beveled valve seat, an annular valve having double faces co acting with the two last named valve seats and having a tubular body sliding upon the second named cage, said body being formed with transverse perforations above the valve, a spring urging the last named valve to its seats, a central ly disposed discharge valve sliding ly mounted within the second named cage, and a spring urging the discharge valve to its sea 5. A refrigerator compressor including in combination a plural ity of cylinders each enlarge d at one end, pistons operating within said cylinders, a common crank shaft for all of said cylinders, a member formed to provide heads for the several cylinders, each head having an outlet chamber, a duct formed in said member and into which all of said outlet chambers discharge, and inlet and outlet valves disposed in the enlarge d portion of each cylinder and removable through the ends of said enlarge d portions of the cylinders when the member forming the heads of the several cylinders is removed.
6. A compressor for refrigerating machinery including in combination a plural ity of cylinders enlarge d at one end, pistons operating the cylinders, the enlarge d ends of the cylinders being connected by an inlet duct common to all of the cylinders, a member formed to provide heads for each cylinder, each of said heads being formed with an outlet chamber, said member being formed to provide an accumulator chamber connected to the first named duct and adapted to receive refrigerant, and the outlet cha1n bers of the several heads being connected by a duct passing through said accumulator chamber and extending out therefrom.
7. A compressor for refrigerating machinery including in combination a head for the compressor having a central ly disposed outlet duct, an annular inlet duct separated from the outlet duct by an annular wall, an annular wall surrounding the first named Wall, said Walls at the lower end formed to provide annular, downwardly flaring valve seats, an outlet valve disposed within the 10 first named duct, and an inlet valve having a shank surrounding the first named wall and having at its lower end'a double head co acting with the two valve seats, and a spring urging said suction valve to its seats. In testimony whereof I hereunto affix my signature in the presence of two witnesses.
PHILIP FISCHBACHER.
WVitnesses: v
S. S. DEATHERAGE, SILAS RosENFELD.
|
Internal HEAD request not working with Pre-signed URLs
It looks like only URLs without query params are supported. The gem seems to toss away the query part which may result in 403 errors for Amazon S3 resources where the auth token is part of the query param. On top of that, the gem just throws a "the file does not exist" error which totally obscures the 403 code.
As a workaround, I'm doing this:
def ffmpeg_video_from_remote(remote_file_url)
open(File.join('public', file.file.filename), 'wb') do |file|
file << open(remote_file_url).read
FFMPEG::Movie.new(Rails.root.join(file.path).to_s)
end
end
Edit: I was wrong. It looks like the query params do get used but what is happening is my pre-signed URL to Amazon S3 is only meant to be used with GET but the library does a HEAD request.
Ok
|
This book introduced Shakespeare to Ovid ; it was a major influence on *his* writing.
Are "Shakespeare" and "his" the same entity?
yes
|
How to query pagination on a many to many connection without duplicates returned
Which Category is your question related to?
Amplify API Add
Amplify CLI Version
4.20.0
What AWS Services are you utilizing?
AppSync, DynamoDB
Provide additional details e.g. code snippets
Let's say I have the following schema.graphql that specifies a many to many connection between Newsletter and Tags (ie. a Newsletter can have many tags and a tag can be on many newsletters)
type Newsletter @model
@key(fields: ["id", "createdAt"]) {
id: ID!
senderEmail: AWSEmail!
senderName: String!
subject: String!
bucketKey: String!
createdAt: AWSDateTime!
tags: [NewsletterTag] @connection(keyName: "byNewsletter", fields: ["id"])
}
type NewsletterTag @model
@key(name: "byNewsletter", fields: ["newsletterID", "tagName"])
@key(name: "byTag", fields: ["tagName", "newsletterID"]) {
id: ID!
newsletterID: ID!
tagName: String!
newsletter: Newsletter! @connection(fields: ["newsletterID"])
tag: Tag! @connection(fields: ["tagName"])
}
type Tag @model
@key(fields: ["name"]) {
name: String!
newsletters: [NewsletterTag] @connection(keyName: "byTag", fields: ["name"])
}
To query newsletters belonging to 1 tag I have something like this
export const listNewsLettersByTag = /* GraphQL */ `
query listNewsLettersByTag(
$name: String!,
$limit: Int
$nextToken: String
$sortDirection: ModelSortDirection
) {
getTag(name: $name) {
name
newsletters(limit: $limit, nextToken: $nextToken, sortDirection: $sortDirection) {
items {
newsletter {
id,
subject,
bucketKey,
createdAt
}
}
nextToken
}
createdAt
}
}
`;
But how do I query newsletters that belong to multiple tags? I try to come up with a query using the NewsletterTag Model (similar to an SQL approach since I mostly work with relational databases)
export const listNewslettersByTags = /* GraphQL */ `
query listNewsletterTags(
$filter: ModelNewsletterTagFilterInput
$limit: Int
$nextToken: String
) {
listNewsletterTags(filter: $filter, limit: $limit, nextToken: $nextToken) {
items {
id
newsletterID
newsletter {
id,
subject,
bucketKey,
createdAt
}
tagName
createdAt
updatedAt
}
nextToken
}
}
`;
But the above proves to be problematic because I will get back duplicated newsletters. In SQL you can have GROUP BY or SELECT DISTINCT. What should be done in this case and Is there a better way to model the schema for my use case?
Edit 1: After some research it seems that I should use @searchable and remove the many to many connections? But this will create an elasticsearch cluster and the tags are not reusable if there are other entities that require tagging as well.
type Newsletter @model @searchable
@key(fields: ["id", "createdAt"]) {
id: ID!
senderEmail: AWSEmail!
senderName: String!
subject: String!
bucketKey: String!
createdAt: AWSDateTime!
tags: [String]
}
Actually this is seems to be what I am looking for. Duplicate of https://github.com/aws-amplify/amplify-cli/issues/2598
|
#!/usr/bin/env python
"""
CLI script.
This is the script to be executed by the user.
It is used to select the model features, train the model and make the predictions.
Usage:
To select the features execute:
.. code-block:: bash
./cli.py select_features
You can also specify the number of features to select (default is 50). For example, to select 40 features execute:
.. code-block:: bash
./cli.py select_features -N 40
To train the model just run:
.. code-block:: bash
./cli.py train
To predict the GDP Growth for the 2011 year run:
.. code-block:: bash
./cli.py predict
The results are saved into the database. To predict a specified year (e.g. 1992) run
.. code-block:: bash
./cli.py predict --year 1992
The prediction year must be between 1961 and 2011.
"""
import os
import sys
import logging
import logging.config
import argparse
from datetime import datetime
import json
from utils import config, io, models, feature_selection
# load logger configuration from file
logging.config.fileConfig(config.LOG_CONFIG_PATH, defaults={'logfilename' : os.path.join(config.LOGS_PATH, datetime.now().strftime('cli_%Y-%m-%d_%H:%M:%S.log'))})
logger = logging.getLogger('main')
# parser
parser = argparse.ArgumentParser(description="CLI tool to train and predict GPD Growth of countries.")
parser.add_argument(
"task",
choices=["train", "predict", "select_features"],
help="Task to be performed",
)
parser.add_argument('--year',
default=2011,
dest='year',
type=int,
help='Year to predict. Only for task=predict')
parser.add_argument('-N',
default=50,
dest='number_features',
type=int,
help='Number of features to select. Only for task=select_features')
if __name__ == "__main__":
args = parser.parse_args()
if args.task == "select_features":
logger.info("Selecting features")
X, y = io.retrieve_training_dataset('all') # get dataset
model = models.GDPGrowthPredictor() # untrained model to select the features
features = feature_selection.select_features_with_shap(k=args.number_features, model=model.get_internal_model(), model_type='tree', X=X, y=y) # select features
logger.info(f"Writting results to {config.FEATURES_PATH}")
# save features to file
with open(config.FEATURES_PATH, 'w') as f:
json.dump(features, f)
if args.task == "train":
logger.info("Training")
if not os.path.exists(config.FEATURES_PATH):
logger.error("Features are not selected. Run 'cli.py select_features' first.")
sys.exit()
X, y = io.retrieve_training_dataset(config.FEATURES_PATH) # get dataset
model = models.GDPGrowthPredictor() # build model
model.train(X, y)
logger.info(f"Saving model to {config.MODEL_FILE_PATH}")
model.save(config.MODEL_FILE_PATH)
if args.task == "predict":
logger.info("Predinting")
if not os.path.exists(config.MODEL_FILE_PATH):
logger.error("The model is not trained. Run 'cli.py train' first.")
sys.exit()
if not os.path.exists(config.FEATURES_PATH):
logger.error("Features are not selected. Run 'cli.py select_features' first.")
sys.exit()
year = args.year
if year > 2011 or year < 1961:
logger.error("Year must be between 1961 and 2011.")
sys.exit()
X, country_codes = io.retrieve_predict_dataset(config.FEATURES_PATH, year=year) # get dataset
model = models.GDPGrowthPredictor.load(config.MODEL_FILE_PATH)
y = model.predict(X)
logger.info(f"GPD Growth for year {year} predicted")
logger.info(f"Writting results database")
io.write_predictions_to_database(country_codes, year, y)
|
<?php
namespace App\Http\Controllers;
use Illuminate\Http\Request;
use App\User;
use JWTAuth;
use Tymon\JWTAuth\Exceptions\JWTException;
class AdminPwdController extends Controller
{
/**
* reset uses to check,
* whether user is registered,
* if it is, then update new password.
*
* @return string
*/
public function reset(Request $request)
{
$credentials = $request->only('email', 'password');
$newpassword = $request->newpassword;
$mail = $request->email;
try {
// verify the credentials and create a token for the user
if (! $token = JWTAuth::attempt($credentials)) {
return response()->json(['error' => 'invalid_credentials', 'status' => 201], 201);
}
} catch (JWTException $e) {
// something went wrong
return response()->json(['error' => 'could_not_create_token', 'status' => 500], 500);
}
// if no errors update the new password
{
if ($this->CheckInternet()) {
$adminName = \DB::select('SELECT firstname FROM users WHERE email = "'.$mail.'"');
$sendMail = new EmailController();
$content = 'Dear Administrator, your updated password is '.$newpassword;
$subject = 'COUPLEY Password Update';
$sendMail->SendMail($mail, $adminName[0]->firstname, $subject, $content);
$hashed = \Hash::make($newpassword);
\DB::table('users')
->where('email', $mail)
->update(['password' => $hashed]);
return response()->json(['password' => 'uptodate', 'status' => 200], 200);
} else {
return response()->json(['error' => 'No_network', 'status' => 203], 203);
}
}
}
/**
* CheckInternet uses to check,
* whether internet is connected.
*
*
* @return bool
*/
public function CheckInternet()
{
if (! $sock = @fsockopen('www.google.com', 80)) {
//echo 'offline';
return false;
} else {
//echo 'OK';
return true;
}
}
}
|
Allendorf Parish (Kr. Ziegenhain), Hesse-Nassau, Prussia, German Empire Genealogy
Jurisdictional Changes
Allendorf has belonged to the following independent countries or post-1871 German states:
Place Names
Church Records
Allendorf
Church records begin in 1710.
* church records 1710-1830 are available at the archive
* 1830-1865 Church records 1830-1865 at Archion – images ($)
* 1866-1951 Baptisms and confirmations 1866-1951 at Archion – images ($)
* 1888-1968 Baptisms 1888-1968 at Archion – images ($)
* 1853-1903 Marriage banns 1853-1903 at Archion – images ($)
* 1866-1888 Marriages and burials 1866-1888 at Archion – images ($)
* 1886-1978 Marriages 1886-1978 at Archion – images ($)
* 1830-1865 Burials 1830-1865 at Archion – images ($)
Michelsberg
* 1830-1869 Church records 1830-1869 at Archion – images ($)
* 1870-1894 Church records 1870-1894 at Archion – images ($)
Allendorf
Civil Registration
Civil registration for Allendorf began in October 1874.
Town Genealogy (OFB or Ortsfamilienbuch)
For more information about compiled genealogies, see the article Germany Town Genealogies.
Societies and Libraries
|
Mira-Cra Park!
Songs
All of Hasunosora Girls' High School Idol Club songs and albums can be found here.
"Do! Do! Do!" is Mira-Cra Park!'s debut song, which is the fifth track on the mini album.
Tracks:
* Do! Do! Do!
Release Date: March 29, 2023
Tracks:
* Kokon Touzai
* Hakuchuu à la Mode
Release Date: September 20, 2023
"Identity" is Mira-Cra Park's first single.
Tracks:
* Identity
* TBA
* TBA
Release Date: November 29, 2023
|
Encapsulated photoelectric measuring system
ABSTRACT
An encapsulated photoelectric measuring system for measuring the relative position of two objects includes a housing which encloses a scanning unit positioned to scan the graduation of a measuring scale. The housing defines a longitudinal slit closed by sealing elements, and a coupling member passes between the sealing elements and connects the scanning unit with one of the objects to be measured. In order to avoid optical disturbances of the beam path of the photoelectric scanning by liquid drops on the measuring scale, the scanning unit is hermetically sealed. The spacing between the surfaces of the scale acted upon by the light beams and the associated surfaces of the scanning unit is made so small that any liquid drops present on the surfaces of the scale in the region of the scanning unit are spread or formed into a continuously homogeneous wetted liquid layer.
BACKGROUND OF THE INVENTION
This invention relates to an improvement in encapsulated photoelectric measuring systems for measuring the relative position of two objects, of the type which include a measuring scale, a scanning unit for scanning the scale, means included in the scanning unit for illuminating at least a first surface of the scale, means for connecting the scanning unit with one of the two objects, a housing which encapsulates the scale and the scanning unit and defines an opening through which the connecting means passes, and at least one sealing element for sealing the opening.
Such photoelectric measuring systems are used for example in machine tools for measuring lengths or angles. These measuring systems typically must therefore be protected against environmental influences in the form of oil, cooling water, processing chips, dust and the like. One prior art approach to protection of a measuring system is shown in German Patent DE-PS No. 28 46 768. The disclosed system includes a housing for the scale and the scanning unit. This housing defines a slit running along the longitudinal direction, which slit is closed by elastomeric sealing lips. A follower extends between these sealing lips to connect the scanning unit with one of the two objects to be measured. Such sealing lips have been found to operate effectively to prevent the penetration of liquids and chips or shavings into the interior of the housing. However, such sealing lips typically cannot completely keep out liquids in the form of vapor and mist that may condense within the housing. In the event mist condenses to form liquid drops on the surfaces of the scale or the scanning plate of the scanning unit, such drops have the optical effect of collecting lenses. These drops can therefore interfere with the optical scanning of the scale and can disturb the photoelectric scanning of the graduation of the scale. Measuring inaccuracies can result from such disturbances. In addition, when a scanning unit includes printed circuits, as for example in conjunction with photo sensors included in the scanning unit, condensing mist presents the danger of electrical short circuits.
SUMMARY OF THE INVENTION
The present invention is directed to an improved measuring system which operates at high measuring accuracy even when used in a harsh environment which includes high concentrations of vapor, fog, mist and the like.
According to this invention, an encapsulated photoelectric measuring system of the type described initially above is provided with means for hermetically sealing the scanning unit. This scanning unit sealing means includes a photopermeable surface positioned adjacent to the first surface of the scale and substantially parallel thereto. The photopermeable surface and the first surface of the scale define a gap therebetween having a width sufficiently small to spread any liquid drops on the first surface in the region of the photopermeable surface into a continuously homogeneous liquid layer.
The present invention provides the important advantages that with a remarkably simple structure a photoelectric measuring system is provided which is fully usable even under extremely unfavorable conditions, for example in the case of processing centers closed on all sides, without impairment of measuring accuracy. Further advantageous features of the invention are set forth in the dependent claims.
The invention itself, together with further objects and attendant advantages, will best be understood by reference to the following detailed description, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1a is a transverse sectional view taken along line Ia--Ia of FIG. 1b of an encapsulated length measuring system which operates according to the direct illumination measuring principle and incorporates a first preferred embodiment of this invention.
FIG. 1b is a sectional view taken along line Ib--Ib of FIG. 1a.
FIG. 2a is a transverse sectional view taken alone line IIa--IIa of FIG. 2b of an encapsulated length measuring system which operates according to the transmitted light principle and incorporates a second preferred embodiment of this invention.
FIG. 2b is a sectional view taken along line IIb--IIb of FIG. 2a.
FIG. 3a is a transverse sectional view taken along line IIIa--IIIa of FIG. 3b of an encapsulated length measuring system which operates according to the transmitted light principal and incorporates a third preferred embodiment of this invention.
FIG. 3b is a sectional view taken along line IIIb--IIIb of FIG. 3a.
DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS
Turning now to the drawings, FIGS. 1a and 1b represent in cross section and longitudinal section two views of an encapsulated, incremental, length measuring system which operates according to the reflected light measuring principle and incorporates a first preferred embodiment of this invention.
This measuring system includes a housing G₁ which is secured by means of screws 1₁ to a bed 2₁ of a machine tool. The housing G₁ defines a groove U in which is mounted a scale M₁. The scale M₁ defines a measuring graduation T₁ which is scanned by a scanning unit A₁. The scanning unit A₁ includes a light source L₁, a condensor lens K₁, a scanning plate AP₁ and a photosensor P₁. The scanning plate AP₁ defines a graduation (not shown) which corresponds to the graduation T₁ of the scale M₁. The scanning unit A₁ is guided along the scale M₁ by means of rollers 3₁ and two leaf springs BF₁ on a base surface 4, and by means of rollers 5₁ and a pressure spring DF₁ on a side surface 6₁ of the housing G₁. The housing G₁ defines a slits S₁ which extends along the longitudinal length of the housing G₁ and is closed by means of a pair of flexible sealing lips D₁ sloped together in the form of a roof. A coupling member N₁ which defines a sword-shaped middle section extends through the slit S₁ and is in sealing engagement with the sealing lips D₁. The coupling member N₁ is fastened by means of screws 7₁ to a slide piece 8₁ of the machine tool. The slide piece 8₁ is slidable relative to the bed 2₁ along the direction of the scale M₁. The coupling member N₁ is coupled by means of a coupling KU₁ in the form of a wire rigid in the measuring direction to the scanning unit A₁. When the machine parts 2₁, 8₁ move relative to one another, the graduation T₁ of the scale M₁ is scanned by the scanning unit A₁, which generates measuring signals in response thereto that are fed over line 9₁ through the coupling member N₁ to an evaluating and display unit (not shown). The outputs of the line 9₁ at the scanning unit A₁ and at the coupling member N₁ in the interior of the housing G₁ are sealed by means of seals 10₁.
The sealing lips D₁ prevent the penetration of liquids and processing chips into the interior of the housing G₁. However, the sealing lips D₁ cannot completely keep out fluids in the form of vapor, fog and mist that may condense in drop form inside the housing G₁. In order to prevent liquid drops (which have the optical affect of collecting lenses) from forming on the graduation surface TM₁ of the scale M₁ and on the surfaces of the elements L₁, K₁, AP₁, P₁ of the scanning unit A₁ (which may disturb the beam path of the photoelectric scanning), the scanning unit A₁ is hermetically sealed chamber which includes the scanning plate AP₁ as one of the walls of the chamber. The scanning plate AP₁ is positioned adjacent and parallel to the scale M₁, and a gap is defined between the graduation surface TA₁ of the scanning plate AP₁ and the graduation surface TM₁ of the scale M₁. The width of this gap is dimensioned so small that any liquid drops which may possibly be present on the graduation surface TM₁ of the scale M₁ in the zone of the scanning plate AP₁ of the scanning unit A₁ are spread or formed into a continuously homogeneous liquid layer. Preferably, the width of this gap is no more than about 0.5 mm.
FIGS. 2a and 2b present in cross section and in longitudinal section two views of an encapsulated incremental length measuring system which operates according to the transmitted light measuring principle in which includes a second preferred embodiment of this invention. The measuring system of FIGS. 2a and 2b corresponds in many respects with the measuring system shown in FIGS. 1a and 1b, and corresponding elements of the system of FIGS. 2a and 2b are provided with the same reference symbols, but with the subscript "2".
In contrast to the measuring system of FIGS. 1a and 1b, the scale M₂ is fastened by means of an adhesive layer 11₂ to an inner surface of the housing G₂. A scanning unit A₂ is guided by means of rollers 3₂ and a leaf spring BF₂ on the graduation surface TM₂ of the scale M₂. The scanning unit A₂ extends around the scale M₂ on both sides of the scale M₂. In order to avoid distortions of the beam path of the photoelectric scanning system by means of liquid drops, the upper part of the scanning unit OA₂ which includes a light source L₂ and a condenser lens K₂ is hermetically sealed as a chamber which includes a scanning plate AP₂ as one wall of the chamber. The lower part of the scanning unit UA₂ includes a photosensitive element P₂, and this lower part of the scanning unit A₂ is also hermetically sealed as a chamber, one wall of which is defined by a glass plate GP₂. As shown in FIG. 2a, the graduation surface TA₂ of the scanning AP₂ is directly opposite, parallel, and spaced with respect to the graduation surface TM₂ of the scale M₂. In addition, the glass plate GP₂ defines a surface OG₂ which is situated directly opposite to the surface OM₂ of the scale M₂ lying opposite the graduation surface TM₂. The separation between the graduation surface TM₂ and the graduation surface TA₂ on the one hand as well as the separation between the surface OM₂ and the surface OG₂ on the other hand are both made so small that any liquid drops possibly present on the graduation surface TM₂ and the surface OM₂ of the scale M₂ in the region of the scanning plate AP₂ of the scanning unit A₂ are formed or spread into a continuously homogeneous liquid layer. Each of the separations should preferably be less than approximately 0.5 mm.
FIGS. 3a and 3b provide cross sectional and longitudinal sectional views of an encapsulated incremental length measuring system which likewise operates according to the transmitted light measuring principle and which incorporates a third preferred embodiment of this invention. The system of FIGS. 3a and 3b corresponds essentially with the system of FIGS. 2a and 2b and corresponding elements in the two embodiments are provided with the same reference symbol, but with a subscript "3" in the system of FIGS. 3a and 3b.
In contrast to the length measuring system of FIGS. 2a and 2b, the scanning unit A₃ includes an upper scanning unit component OA₃ and a lower scanning unit component UA₃ which are joined together one with the other by means of a joint or a spring parallelogram FP₃. The spring parallelogram FP₃ can be made up of a number of leaf springs arranged parallel to one another so as to allow the lower scanning unit component UA₃ to deflect left and right as shown in FIG. 3b. The upper scanning unit component OA₃ is guided by means of rollers 3₃ ' on a graduation surface TM₃ of a scale M₃ , and the lower scanning unit component UA₃ is guided by means of rollers 3₃ " on a surface of the scale M₃ lying opposite to the graduation surface TM₃. In this way even with relatively great tolerances in the thickness of the scale M₃ a small, parallel spacing is assured between the graduation surface TM₃ of the scale M₃ and the graduation surface TA₃ of the scanning plate AP₃ of the upper scanning unit component OA₃. Similarly, a small, parallel spacing is assured between the surface OM₃ of the scale M₃ lying opposite to the graduation surface TM₃ and a surface OG₃ of a glass plate GP₃ of the lower scanning unit component UA₃ of the scanning unit A₃. These small parallel spacings on both sides of the scale M₃ form any drops adhering to the scale M₃ into a continuously homogenous liquid layer in the region of the scanning plate AP₃ of the scanning unit A₃. The upper scanning unit component OA₃ which includes a light source L₃ and a condenser lens K₃ is hermetically sealed in part by the scanning plate AP₃. Similarly, the lower scanning unit component UA₃ of the scanning unit A₃ which includes a photosensor P₃ is hermetically sealed in part by the glass plate GP₃.
The spacings between the surfaces TM, TA and OM, OG, respectively, of the scale M and of the scanning unit A are preferably chosen to be so small that even a dirty or cloudy liquid on the scale M has no substantial influence on the photoelectric scanning. Because the scanning unit is hermetically sealed or encapsulated, problems related to electronic short circuits in printed circuits by fluid action in the scanning unit A are entirely avoided.
The scanning unit A₁, A₂ as well as the upper scanning unit component OA₃ and the lower scanning unit component UA₃ of the scanning unit A₃ include in each case a case which is closed over a cover, which case encloses at least the illumination unit L, K as well as the photoelectric sensors P.
Of course, it should be understood that a wide range of changes and modifications can be made to the preferred embodiments described above. For example, the invention can readily be adapted for use with photoelectric angle measuring systems as well as in encapsulated measuring systems in which openings in the housing are closed with any desired sealing means. It is therefore intended that the foregoing detailed description be regarded as illustrative rather than limiting, and that it be understood that it is the following claims, including all equivalents, which are intended to define the scope of this invention.
I claim:
1. In an encapsulated photoelectric measuring system for measuring the relative position of two objects, of the type comprising a measuring scale, a scanning unit for scanning the scale, means, included in the scanning unit, for illuminating at least a first surface of the scale, means for connecting the scanning unit with one of the two objects, a housing which encapsulates the scale and the scanning unit and defines an opening through which the connecting means passes, and at least one sealing element for sealing the opening, the improvement comprising:means for hermetically sealing the scanning unit, said scanning unit sealing means comprising:a photopermeable surface positioned adjacent to the first surface of the scale substantially parallel thereto, said photopermeable surface and said first surface defining a gap therebetween having a width sufficiently small to spread liquid drops on the first surface in the region of the photopermeable surface into a continuously homogeneous wetted liquid layer.
2. The invention of claim 1 wherein the width of the gap is less than about 0.5 mm.
3. The invention of claim 1 wherein the scale defines a second surface, opposed to the first surface, wherein one of the first and second surfaces defines a graduation, and wherein the scanning unit comprises:an upper scanning unit component; a lower scanning unit component; means for movably interconnecting the upper and lower scanning unit components; means for guiding the upper scanning unit component on the one of the first and second surfaces that defines the graduation; and means for guiding the lower scanning unit component on the other of the first and second surfaces.
4. The invention of claim 3 wherein the interconnecting means comprises a spring parallelogram.
5. The invention of claim 3 wherein the interconnecting means comprises a joint.
6. The invention of claim 1 wherein the means for hermetically sealing the scanning unit seals at least the illuminating means and a photosensitive scanning element positioned to scan the scale, and wherein the means for hermetically sealing the scanning unit comprises a scanning plate included in the scanning unit.
7. The invention of claim 3 wherein the illuminating means is included in the upper scanning unit component, wherein the lower scanning unit component comprises a scanning photosensor positioned to scan the scale, and wherein the means for hermetically sealing the scanning unit comprises:upper sealing means for hermetically sealing the upper scanning unit component, said upper sealing means comprising a scanning plate included in the upper scanning unit component; and lower sealing means for hermetically sealing the lower scanning unit component, said lower sealing means comprising a transparent plate situated adjacent to the scale.
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Thread:<IP_ADDRESS>/@comment-34326521-20111218200302
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Board Thread:Roleplaying/@comment-3293219-20140927193312/@comment-3293219-20140930202339
(If we're doing a timeskip, it's time for my plans. ^.^)
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“B-But… isn’t that desertion?”
“N-No, it’s fine, CO checked me out, said I can work the time off when I get back…”
Something good…
“Is that…?”
“Second most delicious…”
<p class="MsoNormal">“I love you to…
<p class="MsoNormal">Ciara…”
<p class="MsoNormal">-
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Spa chair
FIG. 1 is a front perspective view of a spa chair, showing my new design;
FIG. 2 is a front elevational view thereof;
FIG. 3 is a rear elevational view thereof;
FIG. 4 is a left side elevational view thereof;
FIG. 5 is a right side elevational view thereof;
FIG. 6 is a top plan view thereof; and,
FIG. 7 is a bottom plan view thereof.
The broken lines shown in the drawings are for illustrative purposes only and from no part of the claimed design.
The ornamental design for a spa chair, as shown and described.
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