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We noticed that you're using an unsupported browser. The TripAdvisor website may not display properly. We support the following browsers: Windows:Internet Explorer, Mozilla Firefox, Google Chrome. Mac:Safari. New!Find and book your ideal hotel on TripAdvisor — and get the lowest prices All reviewsbaked potatobreamlamb shoulderfillet steakchocolate moussetempura prawnsbreadpuerto pollensajohn doryfish of the daylast nightnext yearfriendly servicemallorcan stylenothing is too much troubleoverlooking the seafeel very welcomevisited this restaurantfood is excellentport Review tags are currently only available for English language reviews. Always our first choice for food in Puerto Pollensa and this was no exception. As usual the food was of a very high standard and served by dedicated professional staff led by the very personable Josep. We stuck to the 'Menu del Dia' and I had the stuffed peppers as a starter followed by John Dory in a delicious sauce.... More About 20 mins gentle stroll towards Alcudia you'll find this lovely family run restaurant. We enjoyed their beautifully cooked lamb chops (cooked with or without garlic) accompanied by baked potato and fresh vegetables. Washed down with a great Rioccha. Pudding was a shared Tiramasu, their new dessert. This is probably the best all round restaurant in Puerto Pollensa and the... More It is pricier than other menus of the day but at just below 20 euros the quality is second to none. We had starters and shoulder of lamb which were both generous and delicious. This lunch with a glass of wine was fantastic. Out of the port, if you're feeling energetic it's a lovely walk along the beach and road... More Ca'n Josep's was very easy to find travelling by car. There is plenty of street parking available. The restaurant is opposite the sea and has beautiful views. The restaurant is quite large, but we were cared for as if it was a small, cosy artisan-type restaurant. Josep introduced himself and provided recommendations. All of our food was of very high... More Great restaurant and very much worth the walk along from the main drag in Port de Pollenca. Service is excellent - Mallorcan cuisine superb and the wine list great. And the host makes you feel very welcome. After reading the good reviews we decided to try Ca'n Josep one evening we were not disappointed, friendly welcome we never booked, we were given a table with views looking out to sea. We both ordered filet steak and it was cooked perfect, followed by chocolate brownies. Service and food spot on will be back. We have been to Josep's every time we come back to the Port and he never disappoints. Once again, a fantastic meal in a great setting. Josep and his team always looks after his guests and the food was amazing as always. Looking forward to Christmas! This place is just at the end of the resort (about 35 mins walk) but it is worth every minute, the food is superb, we had the lamb shoulder and the duck with avocado prawns and egg with bacon and cheese as starters, The house wine is a must and even the coffees were great The service and views over... More Welcome to our restaurant. We've got, probably, the only one tradicional celler located in front of the sea with a stunning view from the bay of Pollensa. We invite everybody to come and visit us to enjoy our fusion of authentic majorcan food and mediterranean. Questions & Answers Here's what previous visitors have asked, with answers from representatives of Restaurant Ca'n Josep and other visitors * TripAdvisor LLC is not a booking agent and does not charge any service fees to users of our site... (more) We noticed that you're using an unsupported browser. The TripAdvisor website may not display properly. We support the following browsers: Windows:Internet Explorer, Mozilla Firefox, Google Chrome. Mac:Safari. TripAdvisor LLC is not responsible for content on external web sites. Taxes, fees not included for deals content.
Expression, purification and preliminary crystallographic studies of human coactosin-like protein. Coactosin-like protein (CLP) is an actin-binding protein as well as a 5-lipoxygenase binding partner. Human coactosin-like protein has been expressed in high yield and the His-tagged protein was purified by affinity chromatography. Several different crystal forms were obtained by the hanging-drop vapour-diffusion method. X-ray diffraction data to 2.0 A resolution were collected from the best crystal. The space group was determined to be P2(1)2(1)2(1), with unit-cell parameters a = 38.4, b = 48.7, c = 72.6 A.
The Challenge The crisis is real. In Howard County and across the United States, a growing population of young adults with disabilities is transitioning into adulthood without affordable, accessible housing. In Howard County alone, approximately 600 students with various types of disabilities will transition out of high school in the next five years. When they do, the housing options they need to live lives of independence and fulfillment won’t be waiting for them. They’re simply not here. This housing crisis is also acutely felt by parents who are concerned for their sons’ and daughters’ futures. In the U.S., over 850,000 people with disabilities live with a caregiver who is 60-years old or older. As more than a million such caregivers age, the lack of options for their adult children with disabilities to live outside of the family home creates enormous anxiety and demands a search for fresh solutions. Meanwhile, the chronic shortage of affordable housing for low-to-moderate income families in Howard County continues to grow. And a “silver tsunami” of baby-boomers is transforming outdated expectations of retirement and creating demand for new ways of living for older adults.The number of people over the age of 65 in Howard County will double in the next 20 years. Where will they live and what kind of life – and purpose – will they desire? But it’s more than just a housing problem. Adults with disabilities, along with older adults, experience high than average levels of social isolation and depression. Regardless of age or ability, the opportunity to live with purpose and maintain social connections can be as essential as housing. And a growing body of research demonstrates the importance of social connectedness and supportive relationships to achieving physical and emotional well-being. How can we meet these needs simultaneously? This combined challenge – a lack of affordable housing options that also encourage social connectedness and community – provides the driving rationale for Patuxent Commons.
Q: ScrollView : How to reproduce snapToInterval and snapToAlignment for Android? I'm looking for a way to scroll my horizontal menu at a specific interval. I have multiple children visible on screen The selected state is at center. The use of snapToInterval in combination with snapToAlignement fills exactly my needs, but these props are only for iOS. Is there a way to achieve this ? I suppose the PanResponder API could be use but I have no clue how to implement it. I use 0.28 RN version. Thanks. <ScrollView decelerationRate={0} horizontal snapToAlignment="center" snapToInterval={150} > {this.props.children} </ScrollView> A: There is a pull request regarding this issue: https://github.com/facebook/react-native/pull/15297 Also there is a library https://github.com/machadogj/react-native-carousel-control?files=1 that support for both Android and iOS swipe, it control the scrolling behaviour itself, but I tried it, it worked, but not that smooth compared with snapToInterval and snapToAlignment. Another one, but more complex carousel swipe is here: https://github.com/archriss/react-native-snap-carousel Hopefully, you will get more insights based on these.
Anaphylaxis to hidden potato allergens in a peach and egg allergic boy. More than 170 foods have been identified as being potentially allergenic. However, a minority of these foods cause the majority of reactions. Sweets are frequently implicated in allergic reactions in children with cow's milk, egg, nuts or fruits allergy, and they are the most relevant foods investigated as responsible allergens. We report an anaphylactic reaction to candies in an egg and peach allergic boy. We performed a study to identify responsible allergens for the reaction. We investigated hidden egg and peach allergens in the candies, but they were not found. Finally, the causative allergen resulted to be a vegetable protein from potato peel. We diagnosed a new allergy in our patient and Sol t 4 was identified as the responsible allergen of the anaphylactic reaction. We conclude that responsible allergens should always be studied and identified in whatever allergic reaction in order to prevent new reactions.
/*============================================================================ AbyssEnvironment.hpp ============================================================================== This declares class AbyssEnvironment, which is an essential part of a program that uses other classes in libxmlrpc_abyss++. ============================================================================*/ #ifndef ABYSS_ENVIRONMENT_HPP_INCLUDED #define ABYSS_ENVIRONMENT_HPP_INCLUDED namespace xmlrpc_c { class AbyssEnvironment { /*---------------------------------------------------------------------------- A program that uses libxmlrpc_abyss++ should contain exactly one object of this class, as a global static object. This is necessary because the library depends upon other libraries that have global variables. -----------------------------------------------------------------------------*/ public: AbyssEnvironment(); ~AbyssEnvironment(); }; } // namespace #endif
// // The MIT License (MIT) // // Copyright (c) 2013 Backelite // // Permission is hereby granted, free of charge, to any person obtaining a copy // of this software and associated documentation files (the "Software"), to deal // in the Software without restriction, including without limitation the rights // to use, copy, modify, merge, publish, distribute, sublicense, and/or sell // copies of the Software, and to permit persons to whom the Software is // furnished to do so, subject to the following conditions: // // The above copyright notice and this permission notice shall be included in // all copies or substantial portions of the Software. // // THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR // IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, // FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE // AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER // LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, // OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN // THE SOFTWARE. #import <UIKit/UIKit.h> @interface BKTViewController : UITableViewController @end
Q: How does one argument constructor work? I have the following code: #include <iostream> class TestClass { private: int var1, var2; public: TestClass() :var1(0), var2(0) {} TestClass(int x) { std::cout << "\nOne argument constructor\n"; } void showData() { std::cout << "var1 = " << var1 << std::endl; std::cout << "var2 = " << var2 << std::endl; } }; int main() { TestClass obj; obj.showData(); obj = 3; obj.showData(); return 0; } OUTPUT: My questions: 1 - Why am i able to call a one argument constructor in a statement where the object isn't declared? 2 - Why has the value of var1 and var2 changed after calling one argument constructor? I ran the code on VS community edition. A: In many cases including yours, the compiler is able to automatically generate (among others) an assignment operator of the form TestClass& operator=(const TestClass&). Since TestClass is implicitly constructible from a single integer, obj = 3 is resolved as obj = TestClass(3). This also explains why var1 and var2 change: the compiler constructs a TestClass object that leaves them uninitialized, then these uninitialized values are copied to your object. If you assign a specific value to var1 and var2 (such as 1), you'll get that value after the copy assignment.
[Apico-aortic conduit for surgical treatment of supravalvular aortic stenosis with hypoplastic ascending aorta (author's transl)]. Surgical treatment of two patients with diffuse supravalvular aortic stenosis including hypoplastic aortic valve ring was undertaken. In both patients a left ventricular apical-thoracic aorta conduit containing a bioprosthesis was used. Intra- and postoperative pressure measurements demonstrated relief of the systolic pressure gradients present preoperatively between left ventricle and ascending aorta distal to the stenosis. Both patients are asymptomatic at four and eleven months after surgery, respectively.
Q: How to reuse oauth2 token from user (authorization_code) in a Rest Template I have 3 applications Frontend application OAuth2 authentication server REST api (RepositoryRestResources) My users have to log in before being able to use the frontend application. This happens through SSO. They receive a token which is validated by the client before being let in. I would like to reuse this token to make api requests. My REST api application is secured with the same SSO login (it is a resource for the frontend client) but I have no clue how to "add the authorization header" to be used in the RestTemplate I use for api requests. I create my restTemplate like this: public static RestTemplate build() { ObjectMapper mapper = new ObjectMapper(); mapper.configure(DeserializationFeature.FAIL_ON_UNKNOWN_PROPERTIES, false); mapper.registerModule(new Jackson2HalModule()); mapper.registerModule(new JavaTimeModule()); MappingJackson2HttpMessageConverter converter = new MappingJackson2HttpMessageConverter(); converter.setSupportedMediaTypes(MediaType.parseMediaTypes("application/hal+json")); converter.setObjectMapper(mapper); return new RestTemplate(Arrays.asList(converter)); } my resource server configuration: @Configuration @EnableResourceServer public class ResourceServerConfiguration extends ResourceServerConfigurerAdapter { @Value("${resource.id}") private String resourceId; @Override public void configure(HttpSecurity http) throws Exception { http .authorizeRequests() .antMatchers(HttpMethod.OPTIONS).permitAll() .anyRequest().authenticated() .and().exceptionHandling().accessDeniedHandler(new OAuth2AccessDeniedHandler()); } @Override public void configure(ResourceServerSecurityConfigurer resources) throws Exception { resources.resourceId(resourceId); } @Bean public static TokenEnhancer tokenEnhancer() { return new JwtTokenEnhancer(); } @Bean public static JwtAccessTokenConverter accessTokenConverter() { KeyStoreKeyFactory keyStoreKeyFactory = new KeyStoreKeyFactory(new ClassPathResource("keystore.jks"), "somesecret".toCharArray()); JwtAccessTokenConverter converter = new JwtAccessTokenConverter(); converter.setKeyPair(keyStoreKeyFactory.getKeyPair("pair")); return converter; } @Bean public static TokenStore tokenStore() { return new JwtTokenStore(accessTokenConverter()); } } A: I fixed it using an intercepter an manually adding the Token from the security context. RestTemplate restTemplate = new RestTemplate(); restTemplate.getInterceptors().add(new OAuthInterceptor()); In which the intercepter is defined as: public class OAuthInterceptor implements ClientHttpRequestInterceptor { @Autowired private AuthenticationHolder holder; @Override public ClientHttpResponse intercept(HttpRequest request, byte[] body, ClientHttpRequestExecution execution) throws IOException { if (holder.getToken() == null) { //throw new IOException("Token not set"); System.out.println("##################### Token not set! ###################"); } else { System.out.println("##################### Token found: " + holder.getToken()); HttpHeaders headers = request.getHeaders(); headers.add(HttpHeaders.AUTHORIZATION, "Bearer " + holder.getToken()); } return execution.execute(request, body); } } I use an interface which I implement in my client app: public interface AuthenticationHolder { String getToken(); } @Bean public AuthenticationHolder getAuthenticationHolder() { return () -> { Authentication authentication = SecurityContextHolder.getContext().getAuthentication(); if(authentication != null && authentication.getDetails() instanceof OAuth2AuthenticationDetails) { return ((OAuth2AuthenticationDetails) authentication.getDetails()).getTokenValue(); } return null; }; }
/* * Copyright 2019 Google LLC. All Rights Reserved. * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. */ import Foundation import third_party_sciencejournal_ios_ScienceJournalProtos // TODO: Update comments once label proto refactor is complete. There might be other // note types. /// A wrapper for GSJLabel. A note represents a piece of data that can be attached to either an /// experiment or a trial. A note can be text, a photo or a snapshot of data. (The proto name /// "Label" is the legacy term). public class Note { /// The ID is unique within an experiment, but cannot be assumed to be unique across /// experiments, as users may "copy" entire experiments from Drive. /// This ID should probably be a unique GUID. var ID: String { get { return proto.labelId } set { proto.labelId = newValue } } /// The time in ms since the epoch which represents this label in time. /// This may be the time at which the label was created, but some labels /// have editable timestamps. var timestamp: Int64 { get { return proto.timestampMs } set { proto.timestampMs = newValue } } // TODO: parse proto.valuesArray for each note type. /// The date the label was created. var creationDate: Date { get { return Date(milliseconds: proto.creationTimeMs) } set { proto.creationTimeMs = newValue.millisecondsSince1970 } } /// An optional user-added caption. Not all labels will make use of this field. /// Currently text labels will not use this, but picture, trigger, and snapshot will. var caption: Caption? /// The private backing proto. private let backingProto: GSJLabel // MARK: - Public /// A proto representation of a trial. var proto: GSJLabel { backingProto.caption = caption?.proto return backingProto } /// Returns a copy of the note with a new unique ID. func copyWithNewID() -> Self { return createNoteCopy(note: self, ID: UUID().uuidString) } /// Returns a copy of the note. func copy() -> Self { return createNoteCopy(note: self) } /// Designated initializer. /// /// - Parameters: /// - proto: A note proto. public required init(proto: GSJLabel) { // swiftlint:disable force_cast let protoCopy = proto.copy() as! GSJLabel // swiftlint:enable force_cast caption = protoCopy.hasCaption ? Caption(proto: protoCopy.caption) : nil backingProto = protoCopy } /// Convenience initializer that creates a new note from a given note. The new note is a true /// copy with the same ID. /// /// - Parameter note: A note. convenience init(note: Note) { // swiftlint:disable force_cast self.init(proto: note.proto.copy() as! GSJLabel) // swiftlint:enable force_cast } /// Initializes a note with an empty proto. convenience init() { let proto = GSJLabel() self.init(proto: proto) ID = UUID().uuidString timestamp = Date().millisecondsSince1970 } /// Returns a subclass of `Note` depending on the proto's type. If the type is not known it will /// return the base class `Note`. /// /// - Parameter labelProto: A label proto. /// - Returns: A note. class func from(_ labelProto: GSJLabel) -> Note { switch labelProto.type { case .text: return TextNote(proto: labelProto) case .picture: return PictureNote(proto: labelProto) case .snapshot: return SnapshotNote(proto: labelProto) case .sensorTrigger: return TriggerNote(proto: labelProto) } } // MARK: - Private /// Helper method that creates a copy of a note. /// /// - Parameters: /// - note: The note to copy. /// - ID: An optional ID to assign the note copy. /// - Returns: A copy of the note. private func createNoteCopy<T: Note>(note: Note, ID: String? = nil) -> T { // swiftlint:disable force_cast let noteCopy = T(proto: self.proto.copy() as! GSJLabel) // swiftlint:enable force_cast if let ID = ID { noteCopy.ID = ID } return noteCopy } }
If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. I can't figure out why this is happening. I'm guessing it's the jQuery method, but wouldn't be surprised if the CSS is causing confusion. I'm using the method described here: http://osvaldas.info/drop-down-navig...touch-friendly. Any ideas as to why this is happening? Thanks!
Manchester United and Juventus head a queue of more than 20 clubs monitoring the progress of Erling Braut Haaland, with Red Bull Salzburg open to selling him in the summer. The Juventus sporting director, Fabio Paratici, was keen to sign Haaland from Molde in the summer of 2018 and was ready to offer €6m but the teenager was reluctant to join a side where he would sit on the bench or be loaned out. United have been aware of Haaland’s ability for a long time, with Ole Gunnar Solskjær and the player working together for two seasons at Molde in 2017 and 2018. United have scouted the 19-year-old on several occasions but they and Juve will face competition from, among others, Barcelona, Real Madrid, Atlético Madrid, Manchester City, Arsenal, Bayern Munich and Chelsea, all of whom have scouted him recently. In total more than 20 clubs have watched the young Norwegian. Haaland joined Salzburg from Molde in January and has scored a remarkable 23 goals in 20 appearances for the Austrian side. This season he has 22 goals in 15 games, including six in the Champions League, making him the top scorer in the competition, one ahead of Robert Lewandowski. His value has increased with each goal this season and stands at around €40m (£34.5m). Salzburg bought him for around €9m in January but the club expect that they will be able to sell him for more than €60m in the summer. They are hoping that he will have a season similar to that of Luka Jovic with Eintracht Frankfurt in 2018-19, when the Serb scored 27 goals in 48 games. The Bundesliga club signed Jovic on a two-year loan from Benfica with an obligatory €5m buyout clause before selling him to Real Madrid for €60m last summer. Napoli have also made contact with Haaland’s representatives, before and after his Champions League hat-trick against Genk, but were told that nothing will happen before the end of the season when Salzburg will put a value on him and see whether anyone is prepared to match it orwhether there is an auction to sign him.
# Signature access protocols The `github.com/containers/image` library supports signatures implemented as blobs “attached to” an image. Some image transports (local storage formats and remote procotocols) implement these signatures natively or trivially; for others, the protocol extensions described below are necessary. ## docker/distribution registries—separate storage ### Usage Any existing docker/distribution registry, whether or not it natively supports signatures, can be augmented with separate signature storage by configuring a signature storage URL in [`registries.d`](registries.d.md). `registries.d` can be configured to use one storage URL for a whole docker/distribution server, or also separate URLs for smaller namespaces or individual repositories within the server (which e.g. allows image authors to manage their own signature storage while publishing the images on the public `docker.io` server). The signature storage URL defines a root of a path hierarchy. It can be either a `file:///…` URL, pointing to a local directory structure, or a `http`/`https` URL, pointing to a remote server. `file:///` signature storage can be both read and written, `http`/`https` only supports reading. The same path hierarchy is used in both cases, so the HTTP/HTTPS server can be a simple static web server serving a directory structure created by writing to a `file:///` signature storage. (This of course does not prevent other server implementations, e.g. a HTTP server reading signatures from a database.) The usual workflow for producing and distributing images using the separate storage mechanism is to configure the repository in `registries.d` with `sigstore-staging` URL pointing to a private `file:///` staging area, and a `sigstore` URL pointing to a public web server. To publish an image, the image author would sign the image as necessary (e.g. using `skopeo copy`), and then copy the created directory structure from the `file:///` staging area to a subdirectory of a webroot of the public web server so that they are accessible using the public `sigstore` URL. The author would also instruct consumers of the image to, or provide a `registries.d` configuration file to, set up a `sigstore` URL pointing to the public web server. ### Path structure Given a _base_ signature storage URL configured in `registries.d` as mentioned above, and a container image stored in a docker/distribution registry using the _fully-expanded_ name _hostname_`/`_namespaces_`/`_name_{`@`_digest_,`:`_tag_} (e.g. for `docker.io/library/busybox:latest`, _namespaces_ is `library`, even if the user refers to the image using the shorter syntax as `busybox:latest`), signatures are accessed using URLs of the form > _base_`/`_namespaces_`/`_name_`@`_digest-algo_`=`_digest-value_`/signature-`_index_ where _digest-algo_`:`_digest-value_ is a manifest digest usable for referencing the relevant image manifest (i.e. even if the user referenced the image using a tag, the signature storage is always disambiguated using digest references). Note that in the URLs used for signatures, _digest-algo_ and _digest-value_ are separated using the `=` character, not `:` like when accessing the manifest using the docker/distribution API. Within the URL, _index_ is a decimal integer (in the canonical form), starting with 1. Signatures are stored at URLs with successive _index_ values; to read all of them, start with _index_=1, and continue reading signatures and increasing _index_ as long as signatures with these _index_ values exist. Similarly, to add one more signature to an image, find the first _index_ which does not exist, and then store the new signature using that _index_ value. There is no way to list existing signatures other than iterating through the successive _index_ values, and no way to download all of the signatures at once. ### Examples For a docker/distribution image available as `busybox@sha256:817a12c32a39bbe394944ba49de563e085f1d3c5266eb8e9723256bc4448680e` (or as `busybox:latest` if the `latest` tag points to to a manifest with the same digest), and with a `registries.d` configuration specifying a `sigstore` URL `https://example.com/sigstore` for the same image, the following URLs would be accessed to download all signatures: > - `https://example.com/sigstore/library/busybox@sha256=817a12c32a39bbe394944ba49de563e085f1d3c5266eb8e9723256bc4448680e/signature-1` > - `https://example.com/sigstore/library/busybox@sha256=817a12c32a39bbe394944ba49de563e085f1d3c5266eb8e9723256bc4448680e/signature-2` > - … For a docker/distribution image available as `example.com/ns1/ns2/ns3/repo@somedigest:digestvalue` and the same `sigstore` URL, the signatures would be available at > `https://example.com/sigstore/ns1/ns2/ns3/repo@somedigest=digestvalue/signature-1` and so on. ## (OpenShift) docker/distribution API extension As of https://github.com/openshift/origin/pull/12504/ , the OpenShift-embedded registry also provides an extension of the docker/distribution API which allows simpler access to the signatures, using only the docker/distribution API endpoint. This API is not inherently OpenShift-specific (e.g. the client does not need to know the OpenShift API endpoint, and credentials sufficient to access the docker/distribution API server are sufficient to access signatures as well), and it is the preferred way implement signature storage in registries. See https://github.com/openshift/openshift-docs/pull/3556 for the upstream documentation of the API. To read the signature, any user with access to an image can use the `/extensions/v2/…/signatures/…` path to read an array of signatures. Use only the signature objects which have `version` equal to `2`, `type` equal to `atomic`, and read the signature from `content`; ignore the other fields of the signature object. To add a single signature, `PUT` a new object with `version` set to `2`, `type` set to `atomic`, and `content` set to the signature. Also set `name` to an unique name with the form _digest_`@`_per-image-name_, where _digest_ is an image manifest digest (also used in the URL), and _per-image-name_ is any unique identifier. To add more than one signature, add them one at a time. This API does not allow deleting signatures. Note that because signatures are stored within the cluster-wide image objects, i.e. different namespaces can not associate different sets of signatures to the same image, updating signatures requires a cluster-wide access to the `imagesignatures` resource (by default available to the `system:image-signer` role), ## OpenShift-embedded registries The OpenShift-embedded registry implements the ordinary docker/distribution API, and it also exposes images through the OpenShift REST API (available through the “API master” servers). Note: OpenShift versions 1.5 and later support the above-described [docker/distribution API extension](#openshift-dockerdistribution-api-extension), which is easier to set up and should usually be preferred. Continue reading for details on using older versions of OpenShift. As of https://github.com/openshift/origin/pull/9181, signatures are exposed through the OpenShift API (i.e. to access the complete image, it is necessary to use both APIs, in particular to know the URLs for both the docker/distribution and the OpenShift API master endpoints). To read the signature, any user with access to an image can use the `imagestreamimages` namespaced resource to read an `Image` object and its `Signatures` array. Use only the `ImageSignature` objects which have `Type` equal to `atomic`, and read the signature from `Content`; ignore the other fields of the `ImageSignature` object. To add or remove signatures, use the cluster-wide (non-namespaced) `imagesignatures` resource, with `Type` set to `atomic` and `Content` set to the signature. Signature names must have the form _digest_`@`_per-image-name_, where _digest_ is an image manifest digest (OpenShift “image name”), and _per-image-name_ is any unique identifier. Note that because signatures are stored within the cluster-wide image objects, i.e. different namespaces can not associate different sets of signatures to the same image, updating signatures requires a cluster-wide access to the `imagesignatures` resource (by default available to the `system:image-signer` role), and deleting signatures is strongly discouraged (it deletes the signature from all namespaces which contain the same image).
Behind the desire to achieve and to have more can be the need for someone to fulfil their own wants and needs. And other people are also going to provide inspiration. No one is their own island and it is only natural that other people are going to play a part in what one does or doesn’t do in life. But while other people will play a part it what one does with their life, there is also the chance that one will allow their whole life to be defined by others.Disconnected This means that one could end up being disconnected from their true self and place their attention on what other people are doing. Now, this could mean that one ends up following other people or it could mean that one does all they can to come to be better than others. Ones whole life could be designed in this way and therefore, every action one takes is intended to show how superior they are to others. Or this need could be something that only arises during certain situations.Beyond Appearances However, no matter what one owns or how successful they are, they are never going to be better than anyone else. Inherently, each and every one of us has the same value. Of course, some people may have more or have achieved more, but these are all external occurrences. And in order to attain something or to achieve something, one will need the assistance of other people. These people are likely to be unknown and one will take all the credit and yet, they have still played a part.Being Better When one is motivated to be better than others, there is the chance that they will be unaware of the fact that being better or worse is nothing more than an illusion. And how it is something they have created in their mind and not something that reflects reality. So through being unaware of this fact, they are going to do all they can to outdo others. But if one has this outlook all the time, there is the chance that it is not only going to isolate them from others, but that they are going to be out of touch with themselves. Other people could see them as being cold and insecure. And this person could have no idea what really matters to them – beyond trying to look better than others.Highly Competent However, just because someone has this need, it doesn’t mean that other people always notice it. Through having the need to be better than others, one could just come across as being highly competent in one area of their life or a number of areas. In this case, one could end up being admired by others and come across as an example to follow. But no matter how they are viewed or how connected or disconnected they are from themselves, their worth is being defined by others.Worthless And the fact that one needs to be better than others shows that they actually feel less than others. If they didn’t feel less than others they wouldn’t have the need to be more than others. Now, this can be hard to believe; especially as they might have achieved and attained so much. When one feels worthless within there is going to be three options. One can either: let these feelings control their life and sabotage their life; push these feelings out of their mind and achieve monumental success or deal with these feelings and fulfil their true needs and wants.Emotional Regulation Doing things that allow one to outshine others or thinking in ways that allow one to feel better than others enables one to regulate how they feel. But as these feelings are still there, it means that one will continually have to outshine others and think in the same ways, or they will have to face how they really feel. The feedback of others, in regards to how good they are, plays a significant role here. If other people didn’t provide this, there is the chance that one would have to face their emotional truth.What Happened? Even though someone can feel worthless at a deeper level and cover this feeling up by doing all they can to be better than others, in ways they aware and unaware of, there is a reason they feel this way. And while it could be due to what has happened to them in their adult years, it is likely to be the result of what happened during their childhood. This is likely to have been a time where one was made to feel ashamed of who they were and not accepted unconditionally.Childhood Perhaps ones caregivers only loved them when they did what they wanted or achieved something. One may have been abused in some way and through this abuse, came to believe they were worthless. And the reason this person channelled their pain into being a success and not a failure, could be because there was someone around at the time who treated them differently. They may have been around on a consistent basis or only for a short period of time.Awareness These experiences have caused one to feel worthless. And although many years have passed, the emotional experience has stayed in their body. These feelings will need to be released and this can be done with the assistance of a therapist or a healer. They will also provide the positive regard that one didn’t get growing up and this can be just as important as it is for them to let go of their trapped emotions. If you feel this has been of value, please leave a comment, like or get in touch. And feel free to share this article.
Q: Use incoming caller ID on Twilio to make outgoing call I'm wondering if the following is possible: Caller rings Twilio number which gets answered and then automated message is played. Caller is placed in a queue In parallel to this, our system dials a number (using the rest API) showing the caller id of the incoming call, plays a gather to verify the user wants to pick up, and then connects the call. I know that the easiest way to achieve something similar to this is to redirect the incoming call with a Dial verb, but for reasons that aren't really relevant to the question that isn't possible. A: Twilio evangelist here. Yes, this is possible, with the caveat that the initial callers phone number must be previously verified with Twilio. See this topic in the help center: http://www.twilio.com/help/faq/voice/can-i-use-a-non-twilio-number-as-the-caller-id-for-outgoing-calls Hope that helps. Devin
Endogenous hormone levels in habituated nucellar Citrus callus during the initial stages of regeneration. Embryogenic nucellar callus cultures of different Citrus species and cultivars growing in hormone-free medium were transferred to medium containing either sucrose or glycerol as the only carbohydrate source. Glycerol has been reported to induce further development of Citrus somatic embryos, while in the presence of sucrose they continue to proliferate in an 'undifferentiated' manner. The endogenous hormone levels of the cultures were evaluated after 2 and 5 days to characterise the initial steps of embryo development. In most cases, differences among treatments were observed only after 5 days of culture. Higher cytokinin levels were found in most of the cultures transferred to the glycerol-containing medium. The effect of ageing sweet orange cultures on their endogenous hormone levels was determined by leaving them in the original culture medium without subculturing for 60 days. While no changes were observed in the free indoleacetic acid and gibberellin contents, lower levels of abscisic acid and cytokinins were found in the aged cultures than in those transferred at the normal interval, every 30 days. The endogenous hormone contents of Citrus callus of different genotypes were compared. Significant differences were observed in the levels of all hormones evaluated, even when the in vitro ontogeny of the different genotypes was very similar.
It’s … The Encyclopedia of American loons! Our new and exciting series presenting a representative sample of American loons from A-Z. Saturday, February 8, 2014 #908: Richard Mann Richard Mann, ND (officially “doctor of naturopathy”; more accurately “not a doctor) is a naturopath and (at least used to be) chair of the department of “clinical homeopathy” at Bastyr University, one of the most significant “teaching” instutitions devoted to pseudo-, anti- and cargo cult science in the US (also here, the linked page also includes a feeble defense of naturopathy by one Christopher Johnson), and at least affiliated with the Bastyr Center for Natural Health. Bastyr, which is of course prominently featured on quackwatch, offers several courses in complementary and alternative medicine, most of which require several credits of homeopathy, so Mann’s gang is deeply involved in Bastyr’s students’ pseudoeducation. Apparently our Mann is not the same as Richard Mann of Berean Watch Ministries and signatory to A Scientific Dissent from Darwinism, though he would arguably have deserved an entry as well. Diagnosis: Bastyr sports quite a number of faculty, and Mann is admittedly only one of a large number of people doing their best to spread pseudoscience and quackery through that institution. It may thus be unfair to single out him in particular. But Mann is clearly a loon and clearly qualified for an entry in our Encyclopedia; recognizing that covering all of these loons is beyond even us, though we can at least attempt to call out a few of them.
Q: Read msi file in perl I would like to read an msi file. I use the library Win32 :: MSI :: HighLevel but this one sends me undef all the time. My code: use strict; use warnings FATAL => 'all'; use Win32::MSI::DB qw(Win32::MSI::DB::MSIDBOPEN_READONLY); use Win32::MSI::HighLevel; use Data::Dumper; my $msi = Win32::MSI::HighLevel->new (-file => "Firefox.msi", -mode => $Win32::MSI::DB::MSIDBOPEN_READONLY) or die "error $!"; my $productCode = $msi->getProductCode; my $product = $msi->getProduct; print Dumper $productCode; The $product returns ': - ' and $productCode is undef . I have checked the information of msi file in the Windows file properties and verified the information are inside. I have tried the code with another msi file and I have the same problem. A: I find the solution. I add call at "populateTable" function, so the code is: use strict; use warnings FATAL => 'all'; use Win32::MSI::DB qw(Win32::MSI::DB::MSIDBOPEN_READONLY); use Win32::MSI::HighLevel; use Data::Dumper; my $msi = Win32::MSI::HighLevel->new (-file => "Firefox.msi", -mode => $Win32::MSI::DB::MSIDBOPEN_READONLY) or die "error $!"; $msi->populateTable(); my $productCode = $msi->getProductCode; my $product = $msi->getProduct; print Dumper $productCode;
...from just £15 To see the delivery cost for this item, simply add it to your basket. OSMO FILLER Code: 73002 OSMO WOODFILLER Extremely versatile woodfiller The grain of a tree is a unique fingerprint of nature: The even and beautiful surfaces of Osmo Woodfiller preserve this individual character. Osmo Woodfiller is a non-acryllic and water-based multi-purpose edge-filler, wood putty, crack filler and sanding sealer all in one. Unlike most woodfillers, it can easily be sanded at any time after drying, and it's fast drying - within approx. 30 minutes. Non-flammable and non-toxic, heat and freeze-proof, will not crack, shrink, sink or fall out.
Two years ago, Kristyn Cocoran of Pottsville told News 8 that her German Shepherd Floyd died of kidney failure after she fed him the jerky pet treats. Since then, she and thousands of other pet owners have taken action to try to get the treats off the shelves. Their efforts included a class action lawsuit. Now, Nestle Purina and Waggin' Train have agreed to set up a $6.5 million fund for pet owners, but the companies admit no fault in the case. From this fund, pet owners may be able to get a cash payment for certain documented expenses related to their pet eating the jerky treats. A judge has yet to approve this settlement and pet owners won't see any money until sometime next year. Companies are pulling many of these treats from the shelves or cutting off their production ties, but the treats have still not been recalled by the government, because no scientific connection has been made to show exactly what is killing animals.
Let’s kick it old-school, with the absolute CLASSIC typewriter effect. I couldn’t find a decent jQuery version of this effect that worked, so I pluginified some vintage javascript. One little “bug” here is that I’m not handling any dom elements, so the raw html code is displayed while it’s writing, but as soon as it’s written the dom handles it as elements, you could pre-parse the html and write the elements wholesale but that’s far beyond the scope of this simple solution.
Q: Loading jQuery / CSS inline when needed or always via external? I like keeping myself busy building modular web-applications, but don't want to spend time where I can save some.. For example I'm building a news module that should be easily implemented over multiple sites, because the same web-application is used. However not all websites will need a news module. Is it better/easier/faster to create an inline stylesheet/javascript file built into the module itself, than to create a big external stylesheet/javascript with all the libraries? Even though the file for the news module is not needed on all other webpages? It seems to be much easier to create an inline library in the module itself. So that this only gets loaded when needed, and saves load time and bandwidth on the other pages. The other thing is that I like writing 'plug-and-play' modules. Say I move a file across the file server into the module folder, and the application will take care of the rest. With inline sheets, I dont have to add new lines to the header/footer etc. What is the best solution for this? When also taking into account that I rather spend 10 minutes moving a file and it works, than to spend 1 hour appending external libraries just because its more of a 'good practice'? A: If you re building web applications, are you using the MVC patern? Do you separate your concerns? (your Templates/Views, your Models, and your logic(Controllers)) If you follow MVC, it makes easier maintaining and customizing your app. To answer to your exact question, what you need is RequireJS. This way you have only one place to declare your requirements, and RequireJS will handle the rest.. Load order and more.. Quoting from the requirejs website: Over time, if you start to create more modular code that needs to be reused in a few places, the module format for RequireJS makes it easy to write encapsulated code that can be loaded on the fly.
Vanilla Apple Cupcakes with Apple Cider Buttercream Frosting Fall is definitely in the air – the apples are beginning to ripen, there is a brisk bite to the morning air, the kids are back in school. Fall is one of my favorite times of year. I’ve always loved visiting the cider mills in the country and these Vanilla Apple Cupcakes with Apple Cider Buttercream Frosting remind me so much of a fall day watching the cider press in action. The cupcakes look delicious! I was wondering what kind of apple cider you used and if you put the diced apples in those cupcakes? If so, are the apples cooked through with the time allowed to bake the cake? Thank you. Made these and my daughter ate half of them before I could frost them! Actually I made them with caramel cake mix because that’s what I had on hand, but the next batch (since I have all the leftover frosting) will be with white mix so we can compare. Everyone in the house loves them–thanks for a great recipe! These look amazing! I’ve never thought to make an apple based cupcake! Pinning. I’d love if you would share this and any other posts you’d like at our Best of the Weekend party that went live last night! Hi, My daughter and I just used your frosting recipe for her pumpkin cupcakes. She says the icing is too sweet for her. What do you recommend we do to make it less sweet? She wants to make them for a school event later this month. […] Cristina, my sister and I got together to bake some cupcakes! We started off with these Vanilla Apple Cupcakes that were very easy to make and absolutely delicious! Let’s just say we ended off licking the […] […] frosting! Oh my! This recipe is equally as delicious as my Vanilla Apple Cupcakes with Apple Cider Buttercream Frosting that I love so much! Pair one of these delicious Butter Pecan Cupcakes with a cup of hot coffee or […] […] would love them anytime. And, if you want an even more sinfully apple cider treat, check out these Vanilla Apple Cupcakes with Apple Cider Buttercream Frosting! Both are equally delicious and will bring the taste of the Fall season to your taste […]
INTRODUCTION ============ Obstructive Sleep Apnea-Hypopnea (OSA) is a public health problem due to its high prevalence and morbimortality^[@r1]^. It has been described, the estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea index \> 5 events per hour, was 9 percent for women and 24 percent for men, while 2 percent of women and 4 percent of men gathered minimal diagnostic criteria for the sleep apnea syndrome (apnea-hypopnea index \> 5 and daytime excessive somnolence)^[@r2],[@r3]^. According to recent data, the prevalence of OSA in the general population of Latin America is 32%^[@r4]^. In general, OSA diagnosis is confirmed through polysomnography (PSG), though duly validated respiratory polygraphy (RP) is also accepted in populations with a high clinical probability of suffering from OSA^[@r5],[@r6]^. Considering the OSA - related risk of car accidents^[@r7]^ and cardiovascular morbidity^[@r8]^, and the documented effectiveness of continuous positive airway pressure (CPAP) therapy, the study of clinical variables for OSA diagnosis should be a priority. Some authors have proposed different alternatives, such as assessing clinical^[@r9],[@r10]^, functional^[@r11]^, or anthropometric^[@r12]^ parameters to detect severe OSA or calculate its AHI. Though several studies have assessed the use of diagnostic tools based on predictive equations^[@r9],[@r13],[@r14]^, it is difficult to make comparisons or extrapolate results because of the different combinations of variables and the heterogeneity of study populations. In general, these predictive equations have presented high sensitivity (78-95%) and low specificity (41-63%) for different AHI cutoff points (generally, between 5 and 20) in populations with a different prevalence of OSA^[@r9],[@r10]^. A questionnaire to indicate CPAP (QPCPAP) in patients with suspected OSA^[@r15]^ has recently been validated. QPCPAP is based on the criteria of the Berlin questionnaire, Epworth Sleepiness Scale (ESS), and a general health status questionnaire. QPCPAP results were compared against a combination of full polysomnography findings + SEPAR (acronym in spanish for Spanish Society of Respiratory Pathology and Thoracic Surgery) or AAMS (American Academy of Sleep Medicine) criteria^[@r4],[@r15]-[@r17]^. Authors concluded that QPCPAP allowed them to make a reliable indication of CPAP in approximately 30% of clinical patients (97-98% specificity, positive likelihood ratio \> 10). There is limited information about the usefulness of clinical criteria based on STOP-BANG QUESTIONNAIRE (SBQ) to indicate empirical CPAP therapy for subjects with suspected OSA. Thus, we designed a pilot study to validate SBQ as a tool to guide the indication of CPAP in clinical populations with moderate-high OSA according to self-administered home-based respiratory polygraphy (RP). MATERIALS AND METHODS ===================== We checked the data systematically collected in the database of the Sleep Laboratory of Hospital Británico de Buenos Aires between January 2012 and December 2016. Population and design study --------------------------- This was a cross-sectional simulated intention-to-treat analysis. We selected from a database 1763 adult patients with complete anthropometric data (BMI, neck circumference), SBQ^[@r18]^ and Epworth Sleepiness Scale (ESS)^[@r19]^ who were subjected to RP with a minimum valid total recording time (TRT) of 4 hours. Patients on oxygen or CPAP/non-invasive ventilation, with COPD diagnosis, obesity-hypoventilation syndrome, heart failure, neuromuscular disease or respiratory polygraphy with artifacts in airflow, respiratory effort or SO~2~, were excluded ([Figure 1](#f1){ref-type="fig"}). The information was recorded on an Excel worksheet. Precautions were taken to delete data that could make it possible to identify patients or breach data confidentiality during their processing. The protocol was approved by the Institutional Ethics and Review Committee pursuant to the Declaration of Helsinki. Figure 1Flow chart for patients selection. Respiratory Polygraphy ---------------------- Portable Apnea Link Air device (ResMed. Sydney. Australia) with nasal pressure cannula, thoracic effort sensor, and oximetry were used for self-administered home-based RP. Recordings were taken at night and later edited manually by pulmonologists trained in the standards and guidelines of the American Academy of Sleep Medicine (AASM)^[@r6],[@r20]^. Apnea was defined as a decrease in airflow by \> 80% of baseline for ≥ 10 seconds and hypopnea as a 50% drop for ≥ 10 seconds associated with ≥ 3% oxygen desaturation. AHI was calculated as the number of apnea/hypopnea events per hour (events/hour) of valid TRT. Patients were classified as non-OSA (AHI \< 5), mild-OSA (AHI between ≥ 5 and \< 15), moderate-OSA (AHI between ≥ 15 and \< 30), and severe-OSA (AHI ≥ 30) patients. Empiric decision to treat with CPAP ----------------------------------- We simulated a situation in which two blind, independent observers could indicate CPAP therapy. Both observers are experts in sleep medicine responsible for respective sleep units. Observer 1 based the indication on SBQ and ESS results (test); while Observer 2 based the indication on objective data from RP + SBQ + ESS (reference method). The clinical criteria used by Observer 1 to indicate CPAP to patients with suspected OSA were based on previously published data^[@r15]^. Thus, patients with overweight or obesity (BMI \> 25 kg/m^[@r2]^), severe snoring, and observed apnea with excessive daytime sleepiness (ESS \> 11) or hypertension (HT) with \> 5 SBQ components in any combination could become candidates for CPAP therapy. Observer 2 based the indication of CPAP on AHI and significant daytime sleepiness (ESS \> 11) or hypertension according to the guidelines of the Spanish Society of Pneumonology and Thoracic Surgery (SEPAR, for its Spanish acronym)^[@r5],[@r16]^. [Table 1](#t1){ref-type="table"} shows the criteria used by each observer. ###### Criteria to indicate CPAP. Observer 1 (Test) ---------------------------------------------------------------------------------------------------------------- *A Criteria* BMI \> 25 kg/m^2^ + loud snoring (S) + observed apnea (O) + daytime sleepiness (Epworth \> 11) *B Criteria* BMI \> 25 kg/m^2^ + loud snoring (S) + observed apnea (O) + daytime sleepiness (Epworth \> 11) or hypertension HTN and \> 5 components SBQ in any combination **Observer 2 (Reference method)** 1\. Apnea-Hypopnea Index (AHI) ≥ 30 2\. AHI ≥ 5 and \< 30 + one of the following symptoms: • Daytime sleepiness (Epworth \> 11) • Hypertension • \> 5 components SBQ in any combination BMI: body mass index (kg/m^2^); CPAP: continuous positive airway pressure Statistical analysis -------------------- Distribution of variables was assessed using Kolmogorov-Smirnov frequency histogram. Results were presented as percentages for categorical variables and as mean or median and standard deviation or interquartile range (IQR~25-75%~) for numerical variables. To analysis differences between categorical variables Fisher test was used. The area under the ROC curve (AUC-ROC test) was analyzed and sensitivity, specificity and positive and negative likelihood ratio were calculated. The following software were used: Prism 7 (Graph Pad, La Jolla, CA) and MedCalc Statistical Software version 17.9 (MedCalc Software, Ostend, Belgium; <http://www.medcalc.org>; 2017). RESULTS ======= We evaluated 1763 patients (703 women-39.9%) with a median age, BMI and AHI of; 53.6 (±13.8) years, 32.8 (±7.5) kg/m^[@r2]^ and 18.7 (±17.1) events / hour, respectively. 79% of the population had a diagnosis of OSA. According to AHI; 34.1% patients had mild OSA, 26.6% had moderate OSA, and 18.3% had severe OSA ([Figure 2](#f2){ref-type="fig"}). The time of oxygen saturation below 90% was 18.4±26.7% of TRT. [Table 2](#t2){ref-type="table"} shows the characteristics of study population. Figure 2Distribution by group is severity according to AHI. ###### Study population characteristics. Parameters n=1763   ---------------------------------------------------------------- ----------------------------------- Sex n (%) 1060 men (60.1), 703 women (39.9) Age (years)[\*](#TFN1){ref-type="table-fn"} 53.6 (44 - 64) BMI (kg/m^2^)[\*](#TFN1){ref-type="table-fn"} 32.8 (27.4  37.3 ) Epworth[\*](#TFN1){ref-type="table-fn"} 7 (4 - 11) Epworth \> 11 n (%) 429 (24.3) Tiredness n (%) 1241 (70.4) Hypertension n (%) 818 (46.4) Respiratory polygraphy   \- Total recording time (min.)[\*](#TFN1){ref-type="table-fn"} 425 (373 - 485) \- Evaluation period (min.)[\*](#TFN1){ref-type="table-fn"} 400 (342 - 454) \- AHI[\*](#TFN1){ref-type="table-fn"} 18.7 (9.2 - 24.9) \- ODI3[\*](#TFN1){ref-type="table-fn"} 16 (8 - 28) OSA n (%) 1394 (79) \- AHI ≥ 5 - \< 15 n (%) 601 (34.1) \- AHI ≥ 15 - \< 30 n (%) 470 (26.6) \- AHI ≥ 30 n (%) 323 (18.3) Values expressed as median and percentiles 25-75%. AHI: apnea/hypopnea index. ODI3: oxygen desaturation Index of 3%. OSA: obstructive sleep apnea. Women had a lower AHI and a higher BMI than men (AHI: 9.9, IQR~25-75%~ 4.8 - 18 *vs.* 19.2, IQR~25-75%~ 8.2 - 30.1, *p*\<0.01; BMI: 33, IQR~25-75%~ 27.5 - 40.2 *vs.* 30.8, IQR~25-75%~ 27.4 - 35.1, \< 0.01). Five percent of cases (89 cases) presented complete SBQ (8 components) and there was a statistically significant relationship (*p*\<0.05) between ≥ 5 or \< 5 SBQ and RP AHI ([Figure 3](#f3){ref-type="fig"}). [Table 3](#t3){ref-type="table"} shows the distribution of SBQ variables. Figure 3Relationship between \> 5 or \< 5 SBQ components and AHI. ###### Components and combinations found in STOP-BANG questionnaire. Variables Frequency Percentage -------------------------------------------------- ----------- ------------ **S** (Snoring) 1120 63.5 **T** (Tiredness) 1241 70.4 **O** (Observed Apneas) 895 50.8 **P** Hypertension known or previously diagnosed 815 46.2 **B** BMI (body mass index) \> 35 kg/m^2^ 713 40.4 **A** Age \> 50 years old 1132 64.2 **N** (neck circumference) \> 40 cm 1060 59.43 **G** Gender (Male) 1052 60.1 **STOP-BANG** (8 components) 89 5.04 **STOP** 304 17.2 **BANG** 221 12.5 **STOP-BANG** (≥ 5 components) 898 78.06 **STOP-BANG** (\< 5 components) 865 21.93 The area under the ROC curve (AUC-ROC), sensitivity and specificity of criteria A and B are shown in [Table 4](#t4){ref-type="table"}. As it can be seen, criteria A showed a lower sensitivity but a higher specificity and positive likelihood ratio than criteria B. There were 39 (criteria B) false positive cases. As compared to true negative patients, they had a lower AHI (3.1 *vs.* 6.4, *p* 0.02), a higher BMI (32.3 kg/m^[@r2]^ vs. 29.3 kg/m^[@r2]^, *p*\<0.01) and a greater prevalence of daytime sleepiness and hypertension (Epworth \> 11: 8.5% *vs.* 38.4%, hypertension: 12.6% *vs.* 77%, *p*\<0.01). Criteria A and B performed better in men than in women ([Table 5](#t5){ref-type="table"}). ###### Accuracy of clinical parameters to indicate CPAP. Clinical criteria to indicate CPAP Sensitivity (%) (CI95%) Specificity (%)(CI95%) PLR (CI95%) NLR (CI95%) AUC-ROC (SE) ------------------------------------ ------------------------- ------------------------ ------------------- -------------------- ---------------- A criteria 20.7 (18 - 23) 98.1 (97 - 99) 10.6 (6.3 - 17.8) 0.81 (0.8 - 0.8) 0.594 (0.0069) B criteria 40.9 (38 - 44) 94.9 (93 - 96) 8.1 (5.9 - 11.1) 0.62 (0.59 - 0.62) 0.679 (0.0087) P/NLR: positive and negative likelihood ratio; CPAP: continuous positive airway pressure; CI95%: confidence interval 95%. ###### Accuracy of clinical parameters to indicate CPAP therapy in women and men. Clinical criteria to indicate CPAP Sensitivity (%) (CI95%) Specificity (%) (CI95%) PLR (CI95%) NLR (CI95%) AUC-ROC (SE) ------------------------------------ ------------------------- ------------------------- ------------------- ------------------ ---------------- **Women**           A criteria 13.2 (10 - 17) 98.4 (96.5 - 99.4) 8.2 (3.5 - 19) 0.88 (0.8 - 0.9) 0.56 (0.0099) B criteria 30.4 (25.5 - 36) 95.1 (92.4 - 97) 6.3 (3.9 - 10) 0.73 (0.7 - 0.8) 0.63 (0.0138) **Men**           A criteria 24.3 (21 - 28) 97.8 (96 - 99) 10.9 (5.6 - 21.1) 0.77 (0.7 - 0.8) 0.611 (0.0092) B criteria 46.3 (42.3 - 50) 94.8 (92.1 - 96.7) 8.8 (5.8 - 13.5) 0.57 (0.5 - 0.6) 0.704 (0.0112) P/NLR: positive and negative likelihood ratio. CI95%: confidence interval 95%. AUC-ROC (SE): area under curve (standard error); CPAP: continuous positive airway pressure. \**p*\<0.01 The performance of 5 SBQ components with regard to gender and empirical CPAP therapy was; (women *vs.* men): AUC-ROC 0.625 (CI95%: 0.599-0.651) *vs.* 0.70 (CI95%: 0.68-0.72), *p*\<0.01, respectively. DISCUSSION ========== The main finding of this simulation study conducted in a cohort with high prevalence of sleep apnea suggests that it is possible to indicate empirical CPAP therapy based only on clinical criteria for approximately one third of the population with RP-confirmed OSA. However our results showed that clinical criteria are weak (low sensitivity). In 2008, the STOP (*Snore, Tired, Observed apnea, and Pressure*) questionnaire was validated. It consists of four yes/no questions and it was designed by Canadian researchers to track OSA in surgical populations^[@r18]^. In the original publication, the STOP questionnaire showed a variable predictive value for each AHI cut-off point of supervised PSG (AUC-ROC 0.73 for AHI \> 5 events/hour and 0.76 for AHI \> 30 events/hour). The addition of anthropometric parameters; (BANG questionnaire)- *Body Mass Index (BMI \>35 kg/m*^2^ *), Age (\>50 years of age), Neck (neck circumference \> 40 cm), and Gender (being male)* -increased the sensitivity and positive predictive value of the scale (AUC-ROC 0.80 for AHI \>5 events/hour and 0.82 for \>30 events/hour) and allowed physicians to identify patients at high risk for sleep apnea. At present, SBQ is used in NON-surgical populations and has been validated as a clinical tool to identify patients with OSA in centers that use RP^[@r21]^. Trenaman et al.^[@r22]^ developed a web-based model of a patient decision aid which focuses on two first-line treatment options; CPAP and mandibular advancement including SBQ, and indicated acceptable performance in this model for participants. Although the study is interesting since it exposes a model of shared decisions, its sample was limited and the analysis focused on the performance of a prototype. Our strategy based on the use of clinical data gathered during routine visits and SBQ yielded AUC-ROC values between 0.6 and 0.7 with high specificity (95 to 98%) and a positive likelihood ratio of about 10, which makes this tool a reliable test to start treatment with CPAP (low false positive rate). One of the limitations of our approach is that two thirds of OSA patients with a potential need for CPAP therapy were not identified through clinical criteria (false-negative results) since they did not report frequent apneas or reported less self-perceived daytime symptoms. This may be partly due to the fact that questionnaires were filled out by patients themselves without the collaboration of those who live with them. On the other hand, the specificity of \> 5 SBQ was high (\> 90%), which offers the advantage of preventing the implementation of CPAP therapy in patients without definitive indication. Observer 1 unnecessarily prescribed CPAP therapy 2 to 5% of patients (false-positive results) using criteria A or B as clinical approach. A wrong and unnecessary indication of empirical CPAP could result in low adherence or minor adverse events without risk to the patient. These intolerances may also occur in patients with a correct indication of CPAP therapy after RP. The availability of a tool for simple clinical data collection offers several advantages. Firstly, patients with daytime sleepiness or cardio-metabolic comorbidities and at risk for vascular events or accidents could start treatment early, even at the primary level of care or during evaluation of intercurrent events (i.e. admissions to hospital due to cardiovascular episodes, stroke, or accidents caused by excessive sleepiness). Secondly, such tool could be useful in the case of long waiting lists for sleep tests. Finally, it could also lower costs, since almost one third of patients would not require a sleep test for initial diagnosis. Anttalainen et al.^[@r23]^ developed a model whereby two experts used detailed clinical records and supplementary tests to initiate empirical CPAP therapy. Both obtained an acceptable level of agreement for 52% of the patients but with a high rate of false-positive results (11-26%). Nigro et al.^[@r15]^ findings are similar to ours. They used a similar strategy (PSG) based on clinical data from the Berlin questionnaire to show that in one third of cases it is possible to indicate empirical CPAP based on patients' context. This strategy to prescribe CPAP based on the SBQ and the Epworth Sleepiness Scale, performed better in men than in women ([Table 5](#t5){ref-type="table"}). This may be related to the fact that women report apnea and loud snoring less frequently than men^[@r24],[@r25]^. In line with these publications, we observed that women reported less snoring and apneas than men (S: 59% *vs.* 67%, *p*\<0.05, OR: 38% *vs.* 59%, *p*\<0.001). Limitations ----------- Our study has several limitations. Our study was based on cross-sectional model what entails the typical limitations of this type of design. It is also necessary to point out some methodological limitations. The first one resides in the fact that we do not have all cardiovascular risk data since SBQ only asks about known history of HT and this could result in fewer indications of CPAP therapy. On the other hand, there is no consensus about which OSA patients should receive CPAP therapy or the role of daytime symptoms. The American Academy of Sleep Medicine recommends CPAP in patients with a respiratory disturbance index (RDI) ≥ 15 events/hour or between ≥ 5 and \< 15 + sleepiness. SEPAR guidelines, however, recommend treatment with CPAP in patients with RDI ≥ 30 events/hour or between 5 and 30 associated with daytime sleepiness (ESS \> 11) or comorbidities. Like in other areas of medicine, the decision to treat OSA patients with CPAP lies with the treating physician, which may result in variations in observers and sensitivity / specificity results. Even though we have included daytime tiredness among the symptoms that may result in an indication of CPAP therapy based on ESS (\> 11) or frequent tiredness (*T=Tired*), this symptom is not explicitly included in current recommendations. Inclusion of this symptom in theoretical models increased the number of subjects who required CPAP by approximately 30%. Lastly, to assess the accuracy of this strategy in real life, it would be necessary to conduct a prospective multicenter study based on the same pattern. CONCLUSIONS =========== According to our data, STOP-BANG and ESS could be useful to indicate CPAP reliably (low rate of false-positive results) in 20-40% of patients in need for CPAP according to their clinical history and RP results. These clinical criteria performed better in male patients and were similar to previous studies using PSG. **Funding:** No funding was received for this research. **Informed consent:** Informed consent was obtained from all individual participants included in the study. **Conflict of Interest:** All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Sparks fly in Malmo Carbon splinters, shreds of sail and a torn up contract make for a lively penultimate day at Act 6 There’s nothing quite like a resignation to get a day’s racing off to a sparky start as news of another senior crew member handing in his T-shirt and taking the one way walk down the pontoon spread around the AC park this morning. This time it was Gavin Brady, BMW Oracle’s former helmsman who had been shuffled further back in the boat to become tactician after Chris Dickson’s return to the wheel, who was the latest to leave the team. His departure follows that of John Kostecki a few weeks before and while the new line up appeared to be working to start with, this latest development does little to suggest that the team has found a new harmony within its ranks. On the race course the action was pretty spicy too, with a needle match between the Americans and the Kiwis that saw the Kiwis suffer defeat on the route to victory when a jib sheet broke on the second beat and let the Americans through. Up until then the match had been among the most intense modern Cup race many could remember with both boats throwing in tacks every 20 seconds up the windward legs as if climbing a rock face, inch by inch. To lose their hard earned position in the sailing equivalent of a blow-out must have been particularly galling, especially on the back of a loss yesterday to the Italian 39 team, slipping on a self made banana skin at the start. Losing to the Americans kissed goodbye to the Kiwis’ hopes of winning Act 6. That honour has now gone to Alinghi who win with a day to spare. Here, victory was no walkover either, with an equally close match between the Swiss and Luna Rossa with the Italians succeeding in planting a penalty on Alinghi in a slam dunk tack up the first beat. To trail, carry a penalty and then get far enough ahead to off-load the black mark, demonstrates once again just how impressive the Swiss team is when their backs are up against the wall. In the second flight of the day, Luna Rossa continued their fighting mood in their very close match with the Swedish Victory Challenge. With a slim lead at the top mark the Swedes looked threatening on the downhill slide, so much so that by the bottom of the leg James Spithill spun the wheel on Luna Rossa into an aggressive luff that left the Swedes with a broken spinnaker pole and a bill for a blown out kite. Elsewhere, there were further sparks as the Chinese put one over on K-Challenge to put their first point on the board in Act 6. During the match one of the crew from the French team had to be taken off the boat after being injured. Iain Percy’s 39 broke a headsail strop and conceded a point to the Spanish, but won their match against the Chinese while the South Africans continued their struggle with the toy box, failing to raise their mainsail beyond halfway for the first race of the day. Cram all this into five hours afloat and there was little room for anything else. Follow Yachting World Please keep me up to date with special offers and news from Yachting World and other brands operated by TI Media Limited via email. You can unsubscribe at any time. We'd also like to send you special offers and news just by email from other carefully selected companies we think you might like. Your personal details will not be shared with those companies - we send the emails and you can unsubscribe at any time. Please tick here if you are happy to receive these messages.
US officials: Iraqi army regrouping slowly MACDILL AIR FORCE BASE, Fla. (AP) — Iraq's fractured army has begun to regroup and stage modest, localized attacks on the Islamic State militants who routed them last spring and summer, but they are unlikely to be ready to launch a major counteroffensive for many months, senior U.S. military officials said Thursday. "We've seen them start to act like an army," one official said in a lengthy exchange with a group of Washington reporters who were invited to U.S. Central Command headquarters for the command's most extensive briefings on operations in Iraq and Syria. The Iraqi security forces, trained for years by the U.S. prior to its departure from Iraq in 2011, have suffered sectarian divisions, a breakdown in leadership and a loss of confidence. To compound the problem, they surrendered tanks, armored personnel carriers and other U.S.-supplied equipment several months ago when IS fighters overtook Mosul. The officials, who were not authorized to be quoted by name in discussing details of the U.S. military strategy in Iraq and Syria, made it clear that no large Iraqi counteroffensive was imminent or even feasible for the time being. Their remarks coincided with a Pentagon statement that said Iraq's new defense chief, Khaled al-Obeidi, told Defense Minister Chuck Hagel in a telephone call that Baghdad was committed to regaining the initiative. "The minister was quite clear on more than one occasion ... that he has every intention of going on the offensive," the Pentagon press secretary, Rear Adm. John Kirby, said in Washington. He said Hagel encouraged al-Obeidi to rebuild the army in a manner that "engenders trust and confidence" not only among soldiers but also among the Iraqi people. The Iraqi government is blamed by U.S. officials for having sown the sectarian seeds of this year's collapse in much of northern and western Iraq. Yet Baghdad is the key to President Barack Obama's approach to rolling back IS gains in Iraq. Obama has ruled out re-engaging U.S. troops in a ground war there; instead he has told the Iraqis they must regroup and unite against IS, with American and certain partner countries like France and Britain assisting. Gen. Martin Dempsey, chairman of the Joint Chiefs of Staff, said in September that he would recommend to Obama that he authorize a more aggressive use of U.S. military advisers in Iraq if the situation called for it. So far those advisers are not operating in the field with Iraqi troops but rather are working in higher headquarters at military offices in Baghdad and the Kurdish capital of Irbil. Hagel told reporters Thursday that Dempsey has not recommended that U.S. troops take a more direct hand in assisting Iraqis, such as calling in airstrikes from the battlefield. Hagel said he has had no discussion of this with senior military officers. "They feel confident that what we're doing is working," Hagel said. Other officials, however, have said that U.S. advisers may be needed on the battlefield when the Iraqi army attempts to dislodge IS fighters from an urban area like Mosul. The Central Command officials who briefed reporters said the U.S. was encouraged that the Iraqi army was taking early, albeit modest, steps toward reclaiming lost territory. They pointed to an ongoing Iraqi army attack toward Bayji, home of the country's largest oil refinery. The officials declined to discuss certain details but said the Iraqis were clearing large number of roadside bombs planted by IS fighters along the highway north of Tikrit. In Washington, Kirby said the Iraqi move toward Bayji has been slowed also by poor weather conditions. The U.S. has sought to help the Iraqis by providing periodic airstrikes. Central Command said one airstrike overnight Thursday destroyed an IS fighting position south of Bayji. One Central Command official said it could be as long as a year before the Iraqi army is ready to take back the northern city of Mosul. Iraqi troops abandoned their posts when IS fighters swept into Mosul in the spring. The official said the Iraqi army needs a lot of help in basic things like properly maintaining its equipment, sufficiently planning combat operations and using battlefield intelligence, in order to restore its combat power. He called this a "months-long kind of thing." On Syria, the officials said a prospective U.S. effort to train and arm moderate Syrian opposition forces was at its earliest stages of recruiting and vetting candidates for a force of perhaps 5,000 fighters. They said the fighters initially would be expected to simply defend their own villages inside Syria, with a longer-term goal of "getting them to the point where they can take on ISIL." The official said the U.S. envisions training these opposition fighters in units of 100 to 300 men. The training is to take place in Saudi Arabia and perhaps other Arab countries in the region.
Participation of carnitine palmitoyltransferase in the synthesis of dipalmitoylphosphatidylcholine in rat alveolar type II cells. We have investigated the role of carnitine palmitoyltransferase (EC 2.3.1.21) in pulmonar type II pneumocyte, a lung cell responsible for the synthesis of surface active lipids. Adult type II pneumocytes were isolated from rat lung and purified by differential adherence. When these lung cells were incubated with radioactive palmitate, the percentage of radioactivity recovered into dipalmitoylphosphatidylcholine (DPPC), a major surface active lipid, was almost 60% with respect to total phosphatidylcholine (PC) molecular species. Cellular lysates from type II pneumocytes contained detectable amount of carnitine palmitoyltransferase (CPT) activity (1 nmol/min/mg). Most of the CPT activity found in these cells could be inhibited by incubating them for 60 min with 5 microM tetradecylglycidic acid (TDGA), a specific and irreversible CPT inhibitor of the malonyl-CoA sensitive CPT isoform (CPT I). TDGA treatment of adult type II pneumocytes caused a significant reduction in the incorporation of radioactive palmitate into PC, though this effect did not seem to be specific for DPPC. TDGA affected the incorporation of radioactive palmitate at the sn2 rather than the sn1 position of the glycerol backbone of PC. The incorporation of radioactive palmitate into DPPC was also observed when these lung cells were incubated with palmitate-labeled palmitoyl-L-carnitine. Our data suggest that type II pneumocyte CPT may play an important role in remodelling PC fatty acid composition and hence DPPC synthesis.
Q: Where is a clear list of `control strings`? When working with Lisp+Slime, the Hyperspec doc about `format` function is hard to find (format t "~C ~D ???" var1) Who can give a tip, How/Where in the all power Hyperspec can we find a list of the control string? Things like this, when it's going to find some hints about the Lisp control string of the format, the Hyperspec always HYPER me. I tried: C-c C-d h format, C-c C-d h formatter, C-c C-d h tilds ... They all lost me. A: Try C-cC-d~(i.e., common-lisp-hyperspec-format). Tab will show a summary. In case you forgot, it's always reachable from C-hm(describe-mode).
details & specs Take to the trees with the lightest sit & climb stand available from Summit. The Viper SD from Summit features a padded seat that can be raised for bow hunting or lowered for gun use. Creates the perfect balance of roominess, comfort, silence, and portability. Solid front bar makes climbing easy and works as a gun rest. Full backrest and padded armrests for additional comfort. Features Summit's RapidClimb stirrups and QuickDraw, Sound Deadening, and SummitLokt technologies. Includes a free four-point fall arrest system. Certified to TMA standards. Weighs only 20 lbs. Supports up to 300 lbs. Five-year limited warranty. Platform dimensions: 20" x 36". I am 58 and haven't hunted from a tree stand for 15 years. I have had many tree stands over the years...climbers...ladder and hang ons. I went in looking for...Read complete review I am 58 and haven't hunted from a tree stand for 15 years. I have had many tree stands over the years...climbers...ladder and hang ons. I went in looking for a hang on and ladder stand. I hunt private property but theft is still a problem where I am. I browsed the selection of stands and this Summit Viper SD caught my eye. I went online and did some reseach and decided to buy it. An hour later I was home and 20ft in the air...just that easy. It comes out of the box ready to climb and has a DVD to watch that talks about saftey. I found this to be very quiet and most importantly comfortable. They have done a great job designing this stand so you can sit and stand up w/o making a sound. I shoot a crossbow now and cocking the bow in the stand was no problem at all. Right now I can't find any cons to this climber. It packs nicely....easy to set up, comfortable, and climbs easily. VS Most Liked Negative Review Not What I Expected I was on the hunt for a new treestand this year. I did a lot of research on several different set ups and designs. This stand caught my eye by the new dark color...Read complete review I was on the hunt for a new treestand this year. I did a lot of research on several different set ups and designs. This stand caught my eye by the new dark color that blends in well with early season and the new sd. After speaking with [...] a summit rep it sounded like an awesome new stand. So i got it. I couldnt wait to take it out and climb [...] The stirups are assembled but not tight, the bungie cord is already on but you have to assemble the seat along with the cables. Not hard couple mins but i was under the impression it was ready to hunt just pull it out and go. Another thing is the weight position from the treestand on your back is very uncomfortable. I tryed for hours to modify the straps and seat so that it wouldnt be uncomfortable for me to carry just didnt work. Very bulky stand like all summits i guess its the design. Overall I will be taking this stand back and replacing it with an ol'man that I am more familar with. I just couldnt see carrying the viper to my stand and through a lot of brush without getting it caught up and working up a sweet.Im 25 and athletic this stand may be better for big men or older. You might like it but it was to bulky and very uncomfortable for me to carry even just walking around my yard.[...] Good Luck this year... Just got this stand yesterday and I was a little bit hesitant due to the price. Setup was a breeze. Basically just have to install four chair straps. I was surprised at how lightweight this chair is compared to my old chair (30 lbs.). I practiced on a 10 inch tree in my back yard and was able to setup and climb 20 ft in about 10 minutes after a few practice climbs. I love the front bar as it makes climbing much easier on the arms. This is a very comfortable chair for someone my size (5' 9"/185 lbs.). I know it's rated for up to 300 lbs. but may be a tight fit for anyone over 250. I noticed that it can be a little noisy while packing. I had to really tighten the straps to prevent clanging. All-in-all I'm happy so far. Will be taking it out on a hunt this weekend. this is my first climbing type tree stand - and it is very easy to use, but most of all, give you a great sense of security while in the tree. the instructional DVD is mediocre at best, but having the tutelage from someone with climbing experience makes using this stand a breeze. I RECEIVED THE PRODUCT AS AN XMAS GIFT. MY MOTHER HAD TRIED TO NO AVAIL TO PURCHASE THE PRODUCT FROM A COMPETITOR. SHE HAD NOT RECEIVED A SHIPPING DATE SO, SHE CALLED THEM IT HAD BEEN BACK ORDERED THEN AFTER 3 WEEKS THE CANCELLED THE ORDER BECAUSE IT WAS NOT AVAILABLE. YOU GUYS HAD IT THERE, IT WAS SHIPPED IN A TIMELY FASHION AND IT IS A GREAT PRODUCT. Lightweight but most importantly gives feeling of safety. I've been ground hunting for 30 years after almost falling out of a stand, so I'm a little nervous about stands and heights. The DVD could have been done better but it was very informative and useful for someone who doesn't like to read the instructions. This unit got me climbing and off the ground in no time. First climber for this middle age guy but it's well designed, safe and easy to use. Summit did a great job!
// Copyright (C) 2016 the V8 project authors. All rights reserved. // This code is governed by the BSD license found in the LICENSE file. /*--- es6id: 25.4.3 description: Subclassing the Promise object info: | 25.4.3 The Promise Constructor ... The Promise constructor is designed to be subclassable. It may be used as the value in an extends clause of a class definition. Subclass constructors that intend to inherit the specified Promise behaviour must include a super call to the Promise constructor to create and initialize the subclass instance with the internal state necessary to support the Promise and Promise.prototype built-in methods. ---*/ class Prom extends Promise {} assert.throws(TypeError, function() { new Prom(); }); var calledExecutor = false; var executorArguments; var prom1 = new Prom(function() { calledExecutor = true; executorArguments = arguments; }); assert(calledExecutor); assert.sameValue(executorArguments.length, 2); assert.sameValue(typeof executorArguments[0], "function"); assert.sameValue(typeof executorArguments[1], "function");
00:50 Texas, Louisiana Prepare for Beta Parts of Texas and Louisiana still recovering from Hurricane Laura are now bracing for the storm named Beta. At a Glance American Airlines has scheduled the extra flights out of St. Maarten and St. Kitts and Nevis. Florida Gov. Rick Scott declared a state of emergency Monday for the entire state ahead of Hurricane Irma. Puerto Rico Gov. Ricardo Rosselló declared a state of emergency earlier on Monday. Authorities in the U.S. territory of Puerto Rico have activated the country's emergency plan and are warning residents to prepare for Irma. With hurricane warnings and watches in effect, authorities are scrambling to be ready for first impacts. All Monroe county Schools are closed until further notice. Officials in the Florida Keys are set to begin mandatory evacuations for visitors on Wednesday morning ahead of rapidly approaching Hurricane Irma. The storm, which has undergone rapid intensification in the past several days is now the strongest Atlantic hurricane in the last 10 years, a dangerous Category 5, which could have severe impacts on Caribbean island nations and possibly the United States. States of emergency have been declared in Florida and Puerto Rico, and residents across the region are trying to stock up on food, water and other essentials. Here are the latest preparations for the coming storm. South Florida Residents Already Prepping for Storm Officials in the Florida Keys have activated the Monroe County Emergency Operations Center, and have ordered mandatory evacuations for both visitors and residents ahead of Hurricane Irma. Vistors will begin evacuating at sunrise on Wednesday , the county said in a Facebook post, while schedules for resident evacuations are still being determined. “If ever there was a storm to take seriously in the Keys , this is it,” Monroe County Emergency Management Director Martin Senterfitt told WPLG. “The sooner people leave, the better.” Starting Wednesday, all schools in the Florida Keys will be closed until further notice , the Monroe County School District said in a statement on Tuesday. Miami-Dade County officials are advising residents living in low-lying areas to start evacuating tomorrow . Residents in the Miami area are already getting "jittery" ahead of the approaching storm , according to the Miami Herald; bottled water was in short supply and stores are packed with shoppers. “It’s gonna get crazy and I’d rather get it done before there’s more people and it’s chaos,” Mike Kizek, who was buying groceries at the Publix in Morningside, told the Herald. “If I waited, then all that would be left is cans of tomato sauce.” Even in Northwest Florida, shoppers are taking precautions. "I have to be prepared ," Lauren Hook told WEAR. "With everything going on in Houston, with going through Ivan, I have a five-month-old at home. I feel like I have to be ready. I feel like I prepare like it's coming because probably one's going to come eventually. I'd rather be prepared. It's better safe than sorry." Florida Gov. Rick Scott said on Tuesday that he had spoken to President Trump, who "offered the full resources of the federal government as Floridians prepare for Hurricane Irma.” Monday, Scott declared a state of emergency for every county in the state in anticipation of a possible strike from Hurricane Irma, which was upgraded to a Category 5 hurricane Tuesday morning with sustained winds of 175 mph. In the declaration , Scott said he was instructing the director of the Division of Emergency Management to "execute the state's Comprehensive Emergency Management Plan and other response, recovery and mitigation plans to cope with the emergency." "I have continued to be briefed by the Florida Division of Emergency Management on Hurricane Irma and current forecast models have Florida in Irma’s path – potentially impacting millions of Floridians," Scott said in a statement . "Today, given these forecasts and the intensity of this storm, I have declared a state of emergency for every county in Florida to make certain that state, federal and local governments are able to work together and make sure resources are dispersed to local communities as we get prepared for this storm." Scott noted that while the exact path of Irma is not yet known, "in Florida, we always prepare for the worst and hope for the best. We cannot afford to not be prepared." Caribbean Islands Bracing for Impacts With hurricane warnings and watches issued for the northeastern Leeward Islands, authorities are scrambling to be ready for first impacts, which could begin by Tuesday. "We're looking at Irma as a very significant event," Ronald Jackson, executive director of the Caribbean Disaster Emergency Management Agency, told the AP. "I can't recall a tropical cone developing that rapidly into a major hurricane prior to arriving in the central Caribbean." V.C. Bird International Airport in Antigua announced Tuesday that the airport would close at 4:00 pm . Additional flights have been added out of two Caribbean islands as Hurricane Irma strengthened to Category 5 on Tuesday morning. American Airlines has scheduled the extra flights out of St. Maarten and St. Kitts and Nevis to Miami ahead of the storm, which is now the strongest hurricane to form in the Atlantic in ten years. American also announced that passengers with tickets for Tuesday or Wednesday to destinations in the path of Hurricane Irma can change their tickets without change fees . Kenneth Mapp, the Governor of the US Virgin Islands, sent a request for an emergency declaration to the White House. Antigua's prime minister, Gaston Browne, is urging residents to prepare for the storm by cleaning drains and removing objects that could become airborne by high winds. Meanwhile, workers began pruning trees and shrubs to reduce chances for branches to tear down power and phone lines, the AP reports. "The passage of a hurricane is not a matter to be taken lightly, but we must not panic," Browne said in a statement. The National Hurricane Center said Irma had maximum sustained winds of 175 mph Tuesday morning. In the Dominican Republic, Public Works Minister Gonzalo Castillo said workers are clearing away road works and cleaning blockages from sewers. He noted that President Danilo Medina will lead a meeting with emergency agencies on Monday to discuss storm preparations. Ahed Daas, owner of the Food Center in St. Thomas, U.S. Virgin Islands, told Reuters that traffic at his store on Monday was about 50 percent higher than normal as people stocked up on water, canned products and batteries . “It’s kind of dwindling down now, everybody’s pretty much stocked up,” Daas said. “You make sure you have fuel in your generator and hope it’s not that bad when it does arrive.” Four cruise lines have been forced to change itineraries and shore excursions have been canceled due to the approach of Hurricane Irma, Cruise Critic reports. Puerto Rico Declares State of Emergency Puerto Rico Gov. Ricardo Rosselló has declared a state of emergency, while eastern Caribbean islands braced for a possible hit by the Category 4 hurricane. The governor said Tuesday that he has asked President Trump to declare a federal state of emergency for the island. Authorities in Puerto Rico have activated the in U.S. territory's emergency plan and are warning residents to prepare for the major hurricane, which could hit the island as early as Wednesday. "We have established protocols for the safety of all," Rosselló said at a news conference Monday, adding that schools would be closed Tuesday and businesses would close Tuesday afternoon. Led by the Puerto Rico State Agency for Emergency and Disaster Management, agencies are making funds available in advance of the storm. (More: Latest Forecast for Hurricane Irma ) Glorimar Andújar, the secretary of the Puerto Rico Department of Family Affairs, said $65 million was released for the Nutrition Assistance Program, while 5.4 million pounds of contingency food was identified for some 160,000 people. The Puerto Rico Housing secretary, Fernando Gil, said 456 shelters with a capacity for 62,100 people have been readied and some schools have already been closed. Officials with the Puerto Rico Electric Power Authority have inspected main transmission lines and trimmed trees in critical areas in an effort to reduce power outages. "It's no secret that the infrastructure of the Puerto Rico Power Authority is deteriorated," Rossello told reporters. The Department of Natural and Environmental Resources has activated the flood control plan and meetings between agencies are ongoing.
As a preemptive measure against active shooter situations, faculty members at Oakland University are being armed with hockey pucks in perhaps one of the more Michigan solutions ever. The American Association of University Professors supplied hockey pucks to about 800 of its union members. WDIV-TV reports that the union is also working with student organizations to distribute about 1,700 hockey pucks to students. Oakland University Police Chief Mark Gordon tells the station that his department is holding training sessions on how to use hockey pucks or other solid objects to try and stop an active shooter. He added that to fight against these incidents effectively, students and teachers need to be able to throw heavy objects to cause a distraction. "We believe that once faculty have been trained in what to do in an active shooter situation, they will be able to share that information with students to provide a more secure learning environment," Tom Discenna, the union's president, tells the TV station. The Detroit News reports the union started handing out the pucks in early November, and that the suburban Detroit university's student congress has ordered an addition 1,000 pucks. The union is believed to already have spent $2,500 on hockey pucks, and that each customized one costs 94 cents to make. "My first reaction was: You are talking about facing an assault weapon and asking us to fight back with hockey pucks?" Garry Gilbert, director of the journalism program at Oakland University, told the newspaper. "It sounded silly. Then I went through the training session, and it all made sense. "None of us want to face an armed assailant. Students will look to us for leadership in a situation like that." --
70-year-old woman tenderizes husband’s head after catching him looking at porn The first validation of Utah’s declaration that pornography is a public health crisis came from an unlikely source when a 70-year-old woman in Oswaldtwistle, England beat her husband with a metal meat tenderizer after she caught him looking at porn, according to the Manchester Evening News. Lynda Holmes claimed that she “saw red” after catching her 78-year old husband, Gordon Holmes, with adult porn. “He hasn’t touched me for ten years,” she told police, “and now he’s watching porn? How dare he? How do I go about getting ten years of my life back?” The couple were about to celebrate their golden wedding anniversary (50 years) when the attack took place March 16, 2016. “It should be murder. I want ten years of my life back. I saw red mist,” she said. Mrs. Holmes pled guilty to inflicting grievous bodily harm on her husband. Yesterday, the court sentenced her to ten months in jail, which has been suspended for eighteen months. Prosecutor Stephen Parker explained to the court that “There had been a breakdown some considerable time ago in their sexual relationship that had led to tension between them…” Parker said that Holmes had caught her husband with the pornographic material several days prior to the attack, but when she thought he was trying to destroy the evidence, that’s when she went after him with a hammer. Mr. Holmes suffered injuries to his head, ear, and right hand, and escaped by running out into the street and telling his neighbors that his wife had “gone mad.” He then told neighbors that he didn’t want to get the police involved. Defense counsel Rachel Woods said that the attack was totally out of character for her client. Mr. Holmes told the police that he felt partially responsible for his wife’s assault on him. He said that it was his “selfishness” that drove his wife to it, namely, his “playing in a band, playing golf and spending considerable time away from home and not supporting his wife.” While Utah officials emphasized that pornography hurts the developing brains of children in its declaration of the public health threat posed by smut, BYU professor Brian Willoughby told the Deseret News that the use of pornography has a negative impact on “relationship well-being and detrimental expectations about sex.”
sneakers Kobe's Next Nikes to Feature Air Jordan 33 Tech This NBA season may have just come to an end, but we already have our first look at Nike's next Kobe silhouette for the 2019/20 campaign. Recently previewed at a press event and China, and leaked on Chinese blog Hupu, the Black Mamba's next Swoosh silhouette is a major departure from previous AD releases, and comes in high-top form with a semi-translucent build, unique Swoosh branding, and cup sole–style cushioning. The most notable detail, however, is definitely the employment of Jordan Brand's FastFit lacing system, which debuted on the Air Jordan 33. Catch a glimpse of the Kobe AD NXT FastFit above, and stay tuned for an official reveal and release details in the months ahead.
n factor of d and q? 8 Let f(t) = 14*t**2 + 30*t + 96. Let g be f(-5). Calculate the greatest common factor of 74 and g. 74 Let j be -2 + -1 + 73 + 2. Let q be (-12)/(-34)*(13052/156 + -61). Calculate the greatest common factor of q and j. 8 Let s be ((-508)/17)/(-1) - (-140 + (-306762)/(-2193)). Let k(a) = 750*a**3 - a**2 + 2*a - 1. Let w be k(1). What is the highest common factor of w and s? 30 Suppose -2644 = -2*u + 2*t, -14*t = -4*u - 17*t + 5316. What is the highest common divisor of 459 and u? 51 Suppose -4*q = -8*j + 7*j - 334, j + q = -314. Let x = j + 378. Calculate the greatest common divisor of 4 and x. 4 Let u(i) = i**2 + 18*i + 62. Let l be u(-4). Suppose 4*o - 3 = n + 71, l = -3*n. Calculate the highest common divisor of o and 78. 6 Let b be 9490/25 - 3/5. Suppose b = 4*g - u + 2*u, 0 = -4*u - 20. Let p = 111 + -99. What is the greatest common factor of p and g? 12 Let x be 0 + -5*(-10)/525 - (-17571)/63. What is the greatest common factor of x and 341? 31 Suppose 3*o = -4 - 14. Let t(l) = l**3 + 7*l**2 + 4*l - 8. Let s be t(o). Let h be ((-441)/84)/((-3)/16). What is the greatest common factor of s and h? 4 Suppose 0 = 125*q + 2720 - 6155 - 9065. What is the highest common divisor of q and 8? 4 Let i = -5254 - -12552. What is the greatest common factor of 82 and i? 82 Let r(d) = 2*d**3 - 47*d**2 + 22*d + 33. Let g be r(23). What is the highest common divisor of g and 365? 5 Suppose -c - 15 = 2*d, 0 = d + 14*c - 11*c + 10. Let g be 38/(-133) - 821/d. Calculate the highest common factor of 65 and g. 13 Let y be 1552*((-1)/10)/((-2)/10). Suppose 3*b - y = -4*f + 1309, 4*b = -4*f + 2080. Calculate the greatest common divisor of 21 and f. 21 Let s = -483 - -678. Suppose -7*p + 16 + 5 = 0. What is the highest common factor of p and s? 3 Let c be 8 - (-179 + 1 + (3 - 3)). Calculate the greatest common divisor of c and 24. 6 Suppose -29*w + 2*f + 801 = 0, -2*f - 153 = -4*w - w. Suppose -19 = -3*u - 3*x + 104, -3*u + 139 = -x. What is the greatest common factor of w and u? 9 Suppose 0 = 34*p - 2669 - 1921. What is the highest common factor of p and 1485? 135 Let b(t) = 2*t**2 + 4*t + 19. Let z be b(-8). Let k = z - 65. Suppose -5*c - k = -5*i + 85, -4*i + 132 = 4*c. Calculate the highest common divisor of 10 and i. 10 Let j be 6*(-8)/24*5/(-2). Suppose j*o - 37 = -2*s, -o - 4*s + 12 = s. Calculate the highest common factor of 7 and o. 7 Suppose -z + 3470 = -f, -4*z - 21*f = -24*f - 13875. What is the highest common factor of z and 175? 35 Let i(s) = -2*s**3 - 176*s**2 - 181*s - 305. Let c be i(-87). What is the greatest common factor of 95 and c? 19 Suppose 1944 = -16*r - 728. Let h = -146 - r. Calculate the highest common divisor of h and 42. 21 Suppose 0 = -j + 2, h - j = 5 - 63. Let n be (-2 + h/(-6))*(-126)/(-12). Calculate the highest common divisor of 110 and n. 11 Suppose -2*a - 2*c + 6 = -2, 2*a + 3*c - 7 = 0. Suppose a*x = -5*x + 40. Calculate the highest common factor of 13 and x. 1 Let f be (9 - 275/11)*-4. What is the highest common factor of 1728 and f? 64 Let g be 1/(1 + -2) + (4160 - -566). Calculate the highest common divisor of 189 and g. 189 Let l be (((-320)/(-30))/1)/(3/450). What is the greatest common factor of l and 1280? 320 Let s(m) = 9*m**2 + 6*m + 7. Let i be s(-3). Let w be (-10)/5 - (15 + -47). Calculate the greatest common factor of w and i. 10 Suppose 8*w + 18 = -30. Let u(j) = j + 16. Let a be u(w). What is the highest common divisor of 70 and a? 10 Suppose -4*q - n = -11, -2*n = 3*q + 1 - 3. Let h be (-18502)/(-290) - (-1)/5. Calculate the greatest common factor of q and h. 4 Suppose -3*u - 4 + 37 = 0. Suppose -1295 = 6*s - u*s. What is the greatest common divisor of s and 37? 37 Let n(u) = -4*u + 13. Let q be n(-2). Suppose -11*w + 16745 + 580 = 0. Calculate the highest common factor of q and w. 21 Let c be -4 - (-2 + -2 - 35). Suppose 4*a + 28 = -4*q, 3*q - 2*q + c = -5*a. Let o be a/((-7)/52) + -2. What is the highest common factor of o and 20? 10 Let q(b) = 91*b + 2845. Let y be q(33). What is the greatest common divisor of y and 544? 136 Let c(x) = 4*x**3 - 11*x**2 + 9*x - 21. Let i be c(9). Calculate the greatest common factor of 139 and i. 139 Let l(f) = 4*f + 68. Let y be l(-7). What is the greatest common divisor of 360 and y? 40 Suppose 0 = 3*x - 4*x + 26. Suppose -b - y = -24, -b + 5*y = 2 - x. Calculate the greatest common divisor of b and 36. 12 Let n(o) = 2*o**2 + 2*o - 85. Let g be n(0). Let p = g + 88. Suppose 0 = -c - 3 + 5. What is the greatest common divisor of p and c? 1 Suppose -2*t - 327*k + 19040 = -323*k, -47582 = -5*t - k. What is the highest common divisor of t and 39? 39 Let a(z) = -44*z + 214. Let q be a(0). Let g = 782 - q. Calculate the greatest common factor of g and 8. 8 Suppose -5*m + 16 + 9 = 0. Suppose -m*l + 0*l = -90. Let k be (-2 - -38)*(7/2 - -3). Calculate the greatest common factor of l and k. 18 Suppose -2*o = -4*f - 74, -4*f - 74 = -2*o - f. Suppose -5*u = -10, 2*q - o = q - u. Suppose 84 = 37*d - q*d. What is the greatest common factor of 14 and d? 14 Let h(z) = 2*z**2 - z. Let v be h(4). Suppose b + 4721 - 4728 = 0. Let o be (b + (-138)/18)*-84. What is the greatest common divisor of v and o? 28 Let u(g) = -2*g**2 - g - 4. Let n(w) = -w - 9. Let j be n(-6). Let i be u(j). Let c = 25 + i. What is the highest common divisor of c and 30? 6 Suppose 21*k + 226 - 625 = 0. Calculate the highest common factor of k and 19836. 19 Let a = 4269 - 4044. Let d be 50*(-2 - (-15)/6). What is the highest common factor of a and d? 25 Let z(u) = -27*u + 477. Let g be z(17). Let y be (-14)/(-35) + (-46)/(-10). Suppose h - y*h = -96. Calculate the highest common divisor of g and h. 6 Let n = 82 - 71. Suppose -13*a + 5*a = 488. Let j = 160 + a. What is the highest common divisor of j and n? 11 Suppose -14*p = -p - 39. Suppose -538 = -p*t - a, t + 3*t - 716 = -2*a. What is the highest common divisor of t and 12? 12 Let f be 4 - ((2 - 17) + -1) - 2. Suppose 1140 = f*l + l. What is the greatest common factor of l and 84? 12 Let u(d) = 5*d**3 + 5*d + 1. Let i be u(3). Let c = i + -147. What is the greatest common factor of 4 and c? 4 Let c = 1409 + 11759. What is the greatest common divisor of 16 and c? 16 Suppose 0 = 7*o + 37*o + 5*o - 44982. Calculate the highest common factor of 1458 and o. 54 Suppose -30 = 2*b + 4*b. Let f(h) = -10*h + 34. Let j be f(b). Let m = 43 - 31. What is the highest common factor of j and m? 12 Let n(j) = 2*j - 1 - 4 - 2. Let y be n(2). Let s = y - -13. What is the highest common factor of 40 and s? 10 Let i = 5540 - 5528. Let v = 6 - 1. Suppose -70 = -5*f - 2*w, 5*w + 11 = v*f - 24. What is the greatest common factor of i and f? 12 Let y = 2764 + -179. Let l be 3/8 - y/(-40). Calculate the highest common divisor of 26 and l. 13 Let l(v) = v**2 + 12*v - 30. Let j be l(6). Suppose 4*g = 129 + 1327. Calculate the greatest common divisor of j and g. 26 Suppose 0 = g + g - d - 55, -5*g - 5*d + 115 = 0. Suppose 6 = -3*r, 4*r = -4*h + 439 + 21. Calculate the greatest common factor of h and g. 13 Suppose -404 = -6*o + 76. Suppose -o*t + 89*t - 72 = 0. Suppose 3*i = -0*i + 36. Calculate the greatest common factor of t and i. 4 Let g be (-122)/6 + (-4)/(-12). Let u = 620 + -616. Let k be ((-1050)/g)/(2/u). What is the greatest common divisor of 15 and k? 15 Suppose 2*n - 1370 = 2990. Suppose n = 8*y - 284. Suppose v - y = -13*v. Calculate the highest common divisor of v and 110. 22 Let k be ((-48)/9)/(-5*42/945). Calculate the greatest common divisor of 2984 and k. 8 Let f be (2114 - 90) + -2 + -1. What is the greatest common factor of f and 172? 43 Suppose -8*n - 6*n + 15022 = 0. Suppose -137 + 248 = 3*k. What is the greatest common divisor of n and k? 37 Let z(r) = 11*r**2 + 36*r + 67. Let h be z(-13). Calculate the highest common factor of 108 and h. 54 Suppose -136 - 34 = 2*m. Let r = m - -103. What is the highest common factor of r and 288? 18 Let b be 4/(-22) + -356*6/(-132). Let d = 23 + b. Suppose 12 = 41*c - d*c. Calculate the highest common factor of c and 3. 3 Let r(h) = -h**3 + 11*h**2 - h + 16. Let v(u) = -u**2 + 25*u. Let s be v(26). Let q = 37 + s. Let g be r(q). Calculate the highest common divisor of g and 25. 5 Suppose -n + 2*g + 18 = 0, -4*n -
I am now officially back in the swing of getting ready for school. Unless you are not an elementary teacher you can pretty much bet to be back at school everyday in the month of August until school starts. I am lucky enough, however, that school does not start for teachers until September 2nd. We are incredibly late this year because our high school is getting renovations that will not be completed until then. This is actually unfortunate though - we will go later in June, less of a break for Christmas, and typically our conference evenings our compensated and we get an extra day for Thanksgiving break; not this year otherwise it would be an extra day we would have to go in June. I am only lucky because I will miss the months from October to the beginning of January on maternity leave. I guess it worked out to my benefit because after about three hours at school my feet are swollen, I'm hungry, and exhausted...so starting later means less time I need to be a full, blown beached whale at school! :) FRIDAY Breakfast - 3/4 cup of Bran Flakes with 1/4 cup organic raisins 1 cup fat-free organic milk Lunch - 2 slices whole wheat bread, lettuce tomato, approximately 3 oz. turkey Fat-free yogurt Snack - Peach Dinner - Salad (carrots, iceberg, cucumber, tomato) 2 tbsp. light ranch Approx. 3 oz. BBQ chicken on bun Snack - Small vanilla and chocolate low-fat ice cream on a cone
#ifndef OPENMW_ESM_DOOR_H #define OPENMW_ESM_DOOR_H #include <string> namespace ESM { class ESMReader; class ESMWriter; struct Door { static unsigned int sRecordId; /// Return a string descriptor for this record type. Currently used for debugging / error logs only. static std::string getRecordType() { return "Door"; } std::string mId, mName, mModel, mScript, mOpenSound, mCloseSound; void load(ESMReader &esm, bool &isDeleted); void save(ESMWriter &esm, bool isDeleted = false) const; void blank(); ///< Set record to default state (does not touch the ID). }; } #endif
// RUN: %clang_cc1 -triple arm64-apple-darwin -target-feature +neon -fsyntax-only -ffreestanding -verify %s // RUN: %clang_cc1 -triple aarch64_be-none-linux-gnu -target-feature +neon -fsyntax-only -ffreestanding -verify %s #include <arm_neon.h> // rdar://13527900 void vcopy_reject(float32x4_t vOut0, float32x4_t vAlpha, int t) { vcopyq_laneq_f32(vOut0, 1, vAlpha, t); // expected-error {{argument to '__builtin_neon_vgetq_lane_f32' must be a constant integer}} } // rdar://problem/15256199 float32x4_t test_vmlsq_lane(float32x4_t accum, float32x4_t lhs, float32x2_t rhs) { return vmlsq_lane_f32(accum, lhs, rhs, 1); }
The present invention relates to a semiconductor device and a method for manufacturing the same, and can be suitably used for example for a semiconductor device including a non-volatile memory and a method for manufacturing the same. As an electrically writable/erasable non-volatile semiconductor storage device, an EEPROM (Electrically Erasable and Programmable Read Only Memory) has been widely used. These storage devices represented by a flash memory widely used at present include an electro-conductive floating gate electrode surrounded by an oxidized film under a gate electrode of a MISFET or a trapping insulating film, and the electric charge storage state in the floating gate or the trapping insulating film is made the storage information which is read as a threshold value of the transistor. This trapping insulating film means an insulating film capable of storing the electric charge, and a silicon nitride film and the like can be cited as an example. By charging/discharging of the electric charge to/from such an electric charge storage region, the threshold value of the MISFET is shifted, and the MISFET is operated as a storage element. As the flash memory, there is a split gate type cell using a MONOS (Metal-Oxide-Nitride-Oxide-Semiconductor) film. In such memory, by using the silicon nitride film as the electric charge storage region, such advantages are provided of being excellent in reliability in holding data for discretely storing the electric charge compared to the electro-conductive floating gate film, being capable of thinning the oxide films over and below the silicon nitride film because of the excellent reliability in holding data, being capable of lowering the voltage of the writing/erasing operation, and so on. Also, the memory cell includes a control gate electrode (selection gate electrode) that is formed over a semiconductor substrate through a first gate insulating film, a memory gate electrode that is formed over the semiconductor substrate through a second gate insulating film including an electric charge storage region, and a pair of semiconductor regions (a source region and a drain region) that are formed over the surface of the semiconductor substrate so as to sandwich the control gate electrode and the memory gate electrode. In the memory cell region, plural memory cells are disposed in a matrix shape in the X-direction and the Y-direction. For example, with respect to plural memory cells arrayed in a row in the Y-direction, the control gate electrode and the memory gate electrode are respectively formed integrally, and the control gate electrode and the memory gate electrode extend in the Y-direction. For example, the control gate electrode and the memory gate electrode comprised of a polycrystalline silicon film and the like extend to an electric supply region (shunt region) adjacent to the memory cell region, and are coupled there with a control gate line (selection gate line) and a memory gate line which are comprised of a metal wiring layer for example. In Japanese Unexamined Patent Application Publication No. 2006-049737, Japanese Unexamined Patent Application Publication No. 2011-222938, and Japanese Unexamined Patent Application Publication No. 2006-054292, technologies on a shunt structure for coupling the control gate electrode with the control gate line and coupling the memory gate electrode with the memory gate line in the electric supply region are described.
Esophageal strictures during treatment for acute lymphoblastic leukemia. Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.
863 A.2d 768 (2003) 49 Conn.Supp. 125 Nelson CECARELLI et al. v. BOARD OF ASSESSMENT APPEALS OF the TOWN OF NORTH BRANFORD[*] No. CV-02-0464729-S. Superior Court of Connecticut, Judicial District of New Haven. September 30, 2003. Robert M. Singer, Hamden, for the plaintiffs. Gesmonde, Pietrosimone & Sgrignari, L.L.C., for the defendant. BLUE, J. The issue in this municipal tax appeal is the appropriate valuation of a farm house and its curtilage. The difficulty in valuing the subject premises arises from the fact that the development rights to the entire farm (including the residential portion) have been deeded to the state, resulting in significant restrictions on alienability. For the reasons stated below, the appeal must be sustained. The subject premises ("property") are located at 186 Old Post Road in North Branford. The area of the property is approximately 53 acres. The property is one of two parcels forming a larger farm, and (to make matters slightly more confusing) that larger farm is itself half of a two-farm complex owned by the appellants, Nelson Cecarelli and other members of his family. (The appellants will be referred to collectively as "Cecarelli.") The entire two-farm complex occupies approximately 130 acres. In 1997, Cecarelli conveyed the development rights to both *769 farms to the state by deed (deed) pursuant to General Statutes § 22-26cc (a). The deed provides that, "[t]he fee simple owner of the [premises] shall not divide, subdivide, develop, construct on, sell, lease or otherwise improve the [p]remises for uses that result in rendering the [p]remises no longer agricultural land." It further provides that, "[n]o use shall be made of the [p]remises... which is or may be inconsistent with the perpetual protection and preservation of the land as agricultural land." Finally, the single-family residence on the premises (either the existing residence or any new residence built in its place) may be used only by "persons directly incidental to the farm operation." The town of North Branford (town) revalued its properties as of October 1, 2001. The town hired a private company to do what the town assessor called a "mass appraisal" of approximately 5,400 properties in the town. Following adjustments by the board of assessment appeals, the property was appraised as follows: Residential Land $ 78,400 Dwelling $ 105,000 Residential Outbuildings $ 29,100 Farm Land $ 300,000 ___________________________________ Total $ 512,500 Cecarelli disputes the valuation of the "residential land" and the dwelling. He does not dispute the valuation of the residential outbuildings and the farm land. On May 15, 2002, he commenced a timely appeal by service of process pursuant to General Statutes § 12-117a. The appeal was tried to the court on August 20, 2003. Following post-trial briefing, the appeal was argued on September 29, 2003. The trial was curiously one-sided. Cecarelli presented both his own descriptive testimony and the expert appraisal testimony of George T. Malia, Jr., an experienced appraiser of agricultural property. Malia presented testimony, to be discussed in a moment, concerning both the farm house and its curtilage. The town, in contrast, did not present the testimony of anyone familiar with the property. (No agent or employee of the private company responsible for the town's appraisal was called.) It presented the testimony of a deputy bureau director of the state department of agriculture and the town assessor, neither of whom displayed any cognizable acquaintance with the property. Thus, the trial here did not follow the path of the usual municipal tax appeal with contending experts. For practical purposes, the town seems to have not considered the valuation of the dwelling worth contesting. As to the valuation of the "residential land," the town, as I understand it, argues that as a matter of law a residential-lot-sized portion of the land immediately surrounding the dwelling should be given the same value as other residential lots in the immediate area even though those other residential lots are not subject to the same restrictions on use and alienation as the residential lot here. To state this proposition is to refute it. The town has effectively (although not formally) thrown in the towel as to the dwelling. The evidence establishes that the dwelling was built in 1705 and is in poor physical condition. The deed restricts use of the dwelling to "persons directly incidental to the farm operation." The dwelling has recently been used for the housing of farm hands. Malia's credible and unrebutted evidence establishes that the dwelling has a value of $96,000. (Malia's valuation is as of February 1, 2002, while the valuation date in question is October 1, 2001. There is, however, no evidence of any significant price fluctuation in the intervening three months.) The valuation of the "residential land" requires more detailed discussion. The town admits that the "residential *770 land" area it has chosen to appraise as such is an artificial construct. The town's field card describes this area as consisting of ".92" acres, but the town assessor explained that this area was selected not because of the natural features of the subject property but because this is the size of the typical residential lot in the immediate area. As it happens, however, there is an unplanted curtilage of approximately one acre surrounding the dwelling, so this difference seems, at first blush, de minimus. (Some problems with the town's artificial approach will be discussed in a moment.) The more serious issue is how the "residential land" ought to be valued. The town, as mentioned, has valued the "residential land" at $78,400. This valuation appears to be consistent with the value of residential lots of similar size in the area. The residential lots with which the town compares the subject premises are, however, unencumbered fees. The subject premises, in contrast, are significantly encumbered by the restrictions in the deed. Malia testified that, using the comparable sales approach for similarly encumbered properties, the value of Cecarelli's actual curtilage is $14,325. This testimony is, for all practical purposes, unrebutted. After carefully considering all of the evidence, the court accepts Malia's testimony on this point as credible. Although, as mentioned, the "residential land" appraised by the town occupies a slightly smaller area than the curtilage appraised by Malia, the difference is de minimus here. After considering all of the evidence, the market value of the "residential land" is found to be $14,325. The parties have focused their attention on General Statutes § 12-107c (a), which provides for the classification of certain agricultural land as farm land. The "farm land" here has been so taxed, but the valuation of that land is not an issue in the case. In Newton v. Board of Tax Review, Superior Court, judicial district of New Haven, Docket No. CV94-0359326S (November 21, 2001) (30 Conn. L. Rptr. 746, 2001 WL 1562113), Booth, J., held that, under § 12-107c (a), "the minimum acreage required by zoning for a residence" surrounding a farm dwelling "should be assessed at market value." Id., at 747. If Judge Booth is correct, the question would then become what is the "market value" of "the minimum acreage required by zoning for a residence" here. With respect, I believe that Judge Booth's focus on "the minimum acreage required by zoning for a residence"; id.; rather than on the actual unplanted curtilage on the property in question is not justified by the statute and could lead to unjust results in some cases. The problem lies in the analytical use of an artificial construct rather than the actual facts on the ground. Where, as here, a residence is surrounded by an unplanted area close in size to the minimum acreage required by zoning for a residence, no great injustice will result from use of the market value of the minimum acreage. Use of this artificial construct will be literally close enough for government work. But as the facts on the ground begin to differ more significantly from the artificial construct, serious injustices can develop in either direction. If a particular dwelling is surrounded by several acres of unplanted land (think of the manorial Texas ranch house in the 1950s movie Giant), the property owner would gain an unjustified windfall from the use of a "minimum acreage" model. On the other hand, a property owner who plants crops right up to the footprint of his residence (think of Dorothy's house landing in a cornfield) will be severely overtaxed by use of the same model. Neither logic nor statutory text dictates use of the cookie-cutter "minimum acreage" approach. *771 The town nevertheless argues that the "market value" of the "residential area" should be that of a standard residential lot in the immediate area and, inspired to even greater fictional heights, argues that the "market value" must be determined without regard to the actual encumbrances placed on the property by the deed. It reasons that, since the definition of "farm" contained in General Statutes § 1-1(q) "does not include `residence' or `residential lot' ... assessors have created the `fiction' of a residential lot beneath a dwelling on farm land because only `farm land' pursuant to [§ 12-107c (a)] is to receive preferential tax treatment." This argument turns the statute on its head. The reason that the definition of "farm" in § 1-1(q) does not include "residence" or "residential lot" is that the statutory definition "refers to land that has been altered or developed from its natural state in order to enhance or promote its use for faming." Metropolitan District v. Barkhamsted, 199 Conn. 294, 302, 507 A.2d 92 (1986). An unplanted residential lot has not been altered from its natural state in order to enhance or promote its use for farming. If such an area exists, as it does here, it should not be taxed as "farm land." It should, however, be taxed based on its actual market value rather than on the market value of some different, purely hypothetical parcel of land. Nothing in § 12-107c (a) (or, for that matter, in Newton) requires the completely hypothetical market value that the town advocates here. The ineluctable fact that a property subject to encumbrances has a market value less than an otherwise similar property not subject to encumbrances has nothing to do with agricultural policy and everything to do with the laws of economics. It is well established that "[w]hen an easement is carved out of one property for the benefit of another the market value of the servient estate is thereby lessened...." (Internal quotation marks omitted.) Pepe v. Board of Tax Review, 41 Conn.Supp. 457, 464, 585 A.2d 712 (1990), aff'd, 217 Conn. 240, 584 A.2d 1188 (1991). The restrictions on use and alienation here have a similar effect. If Smith and Jones own identical residential lots, but Smith's lot can be sold only to lefthanded redheads while Jones' lot can be sold to anybody, it does not take an expert in economics to correctly conclude that Jones' lot will be the more valuable of the two. If Smith and Jones own identical commercial properties, but Smith's property can be used only to sell buggy whips while Jones' property can be used to sell anything, once again Jones' property will be the more valuable of the two. By the same process of market economics, if Smith and Jones own otherwise identical residential properties, but Smith's property can only be used by persons directly connected with the operations of a farm while Jones' property can be used by anyone, it stands to reason that Jones' property will be the more valuable of the two. In a state like Connecticut, not overpopulated by farmers, this differential is likely to be substantial. That difference is substantial here, and the court is fully convinced by the evidence that the town's assessment of Cecarelli's "residential area" is grossly excessive. After considering all of the evidence, the court finds that the value of the "residential land" as of October 1, 2001, is $14,325. The value of the dwelling is $96,000. The total fair market value of the property on the valuation date was therefore $439,425. The appeal is sustained. NOTES [*] Affirmed. Cecarelli v. Board of Assessment Appeals, 272 Conn. 485, 863 A.2d 677 (2005).
[The signifiance of alternative medicine at a university hospital]. Three hundred randomly selected nurses employed at the university hospital of Berne were asked by means of a questionnaire as to the application of complementary methods (CM) in patients of this hospital. 75% of the questionnaires were completed. 95% of the nursing staff indicated that they had recommended or applied CM's. The most frequently used methods being compresses, aroma therapy and homoeopathy. The members of the nursing staff, who use CM are ecology-minded, have had higher education and are nutrition conscious. CM training was found in 21%. The application of CM is usually suggested by members of the nursing staff, less frequently by the patients and rarely by physicians. One quarter of the nursing staff consults a physician before applying CM. Motivations for the application of CM are often based on the experiences of others and experiences from one's own childhood. Homoeopathy is the most prevalent method. CM is regarded to be integral, supplementary and conducive for the integration of orthodox medicine and psyche. In arrangement with the nursing staff direction we do not critically discuss our observations in this paper.
The present invention relates generally to applying a super-conducting coil to a high power density synchronous rotating machine. More particularly, the present invention relates to a synchronous machine with a conventional stator, and a magnetically saturated solid iron core rotor having a super-conducting coil. Synchronous electrical machines having field coil windings include, but are not limited to, rotary generators, rotary motors, and linear motors. These machines generally comprise a stator and rotor that are electromagnetically coupled. The rotor may include a multi-pole rotor core and one or more coil windings mounted on the rotor core. The rotor cores may include a magnetically-permeable solid material, such as an iron-core rotor. Conventional copper windings are commonly used in the rotors of synchronous electrical machines. However, the electrical resistance of copper windings (although low by conventional measures) is sufficient to contribute to substantial heating of the rotor and to diminish the power efficiency of the machine. Recently, super-conducting (SC) coil windings have been developed for rotors. SC windings have effectively no resistance and are highly advantageous rotor coil windings. Iron-core rotors saturate at an air-gap magnetic field strength of about 2 Tesla. Known super-conducting rotors employ air-core designs, with no iron in the rotor, to achieve air-gap magnetic fields of 3 Tesla or higher. These high air-gap magnetic fields yield increased power densities of the electrical machine, and result in significant reduction in weight and size of the machine. Air-core super-conducting rotors require large amounts of super-conducting wire. The large amounts of SC wire add to the number of coils required, the complexity of the coil supports, and the cost of the SC coil windings and rotor. While iron core super-conducting rotors have been largely ignored by industry, iron core rotors offer certain advantages over air-core rotors, when operated at magnetic field saturation to increase the air-gap magnetic field and power density of the machine. The advantage is that it takes considerably less super-conductor material in a magnetically saturated iron-core rotor to attain the same benefits of high machine power density as compared to an air-core rotor. High temperature SC coil field windings are formed of super-conducting materials that are brittle, and must be cooled to a temperature at or below a critical temperature, e.g., 27xc2x0 K, to achieve and maintain super-conductivity. The SC windings may be formed of a high temperature super-conducting material, such as a BSCCO (BixSrxCaxCuxOx) based conductor. Super-conducting coils have not been adapted for commercial use in the rotors of synchronous machines. Attempts have been made to incorporate SC coils into high power density generators and other such synchronous machines. The potential benefits of adding SC coils to high power density machines include light weight and compact machines. These high power density machines typically include an air-core rotor and an air-gap stator with no stator iron teeth. However, high power density machines tend to be expensive and have been commercially impractical. SC coils, their coil supports and the associated refrigeration systems have been expensive and complex. SC coils are expensive materials, such as BSCCO. These materials are also brittle. The coil support systems needed for SC coils must withstand the tremendous forces encountered in the rotor of a large synchronous machine and protect the brittle coils. Moreover, these support systems must not transfer substantial heat into the cryogenically cooled coils. Further the refrigeration systems that provide cryogenic cooling fluids, such as helium, are complex and expensive. Accordingly, the cost and complexity of incorporating SC coils into a synchronous machine have been high. For SC coils to become commercially viable, their associated costs should be reduced to well below the advantages gained by substituting SC coils for conventional copper coils in the rotor. The cost of using SC coils has become more affordable with the development of high temperature super-conducting (HTS) materials. Because they maintain super-conducting conditions (including no resistance) at relative high temperatures, e.g. 27xc2x0 K, the cost to cool a HTS coil is substantially reduced as compared to cooling costs for prior SC that had to be cooled to lower temperatures. There is still a need for lower cost SC coils and coil support systems. Super-conducting coils have been cooled by liquid helium. After passing through the windings of the rotor, the hot, used helium is returned as room-temperature gaseous helium. Using liquid helium for cryogenic cooling requires continuous reliquefaction of the returned, room-temperature gaseous helium, and such reliquefaction poses significant reliability problems and requires significant auxiliary power. Prior SC coil cooling techniques include cooling an epoxy-impregnated SC coil through a solid conduction path from a cryocooler. Alternatively, cooling tubes in the rotor may convey a liquid and/or gaseous cryogen to a porous SC coil winding that is immersed in the flow of the liquid and/or gaseous cryogen. However, immersion cooling requires the entire field winding and rotor structure to be at cryogenic temperature, as a result no iron can be used in the rotor magnetic circuit because of the brittle nature of iron at cryogenic temperatures. What is needed is a HTS electrical machine that is substantially less expensive that prior HTS machines, and is competitively priced with existing conventional copper coil machines. To become commercially successful, HTS machines need to become cost competitive with conventional copper machines. Potential technical areas for reducing costs further include the coil support system, the rotor design and retrofitting existing machines with HTS rotors. Further, there is a need for an improved rotor field winding assemblage for an electrical machine that does not have the disadvantages of the air-core and liquid-cooled super-conducting field winding assemblages of, for example, known super-conducting rotors. Developing support systems for HTS coil has been a difficult challenge in adapting SC coils to HTS rotors. Examples of coil support systems for HTS rotors that have previously been proposed are disclosed in U.S. Pat. Nos. 5,548,168; 5,532,663; 5,672,921; 5,777,420; 6,169,353, and 6,066,906. However, these coil support systems suffer various problems, such as being expensive, complex and requiring an excessive number of components. There is a long-felt need for a HTS rotor having a coil support system for a SC coil. The need also exists for a coil support system made with low cost and easy to fabricate components. A high power density super-conducting machine with a rotor having a SC coil field winding has been developed that appears to be cost competitive with existing copper coil, low power density machines. Costs may be reduced by employing a magnetically saturated solid core rotor, a conventional stator and a minimal coil support structure. Using these technologies, an efficient HTS machine having the advantages of SC coil has been developed. Moreover, the cost to build such a HTS machine can be sufficiently reduced so that the machine is economical. The HTS machine includes a conventional stator and a HTS rotor. The conventional stator is designed for high air-gap magnetic fields that are provided by the HTS rotor. The rotor includes a two-pole core body formed of a solid magnetic material, such as iron. The rotor core body is generally cylindrical and has flat surfaces machined longitudinally along its length. The HTS coil is assembled around these flat surfaces and the coil has a race-track shape that extends around the core. The rotor coil ampere-turns are sufficiently high to magnetically saturate the rotor core and operate the machine at high air-gap magnetic fields. The race-track coil is supported by tension coil support members that extend through the iron core rotor body. Drive and collector shafts are mechanically fastened to the rotor core. A cylindrical shell electromagnetic shield surrounds the HTS coil and iron core rotor body. The iron core rotor significantly reduces the field winding ampere-turns, super-conductor utilization and cost with respect to air-core rotors. The single race-track shaped HTS coil replaces typical complex saddle-shaped coil windings. The tension coil support provides direct support to the HTS coil so as to reduce the strains on the coil during cool-down and centrifugal loading. Moreover, the coil support system is at cryogenic temperatures with the coil. The HTS rotor may be implemented in a machine originally designed to include a SC coil(s). The rotor and its SC coil are described in the context of a generator, but the HTS coil rotor and coil support disclosed here are also suitable for use in other synchronous machines. In a first embodiment the invention is a high power density synchronous machine comprising: a stator having conventional stator coils arranged in an annulus around a vacuum cylindrical cavity; a cylindrical magnetically saturated solid rotor core; a race-track super-conducting coil winding extending around the rotor core, and a coil support extending through the core and attaching to opposite long sides of the coil winding. In a second embodiment of the invention is a high power density synchronous machine having a rotate capacity of at least 100 MVA comprising: a conventional stator having stator coils arranged in an annulus forming a vacuum rotor cavity; a cylindrical magnetically saturated rotor core having a pair of planer sections on opposite sides of the core and extending longitudinally along the core, and a super-conducting coil winding extending around at least a portion of the rotor core, the coil winding having a pair of side sections adjacent the planer sections of the core.
Lung Kong Tin Yee Association The Lung Kong Tin Yee Association (), also known as the Four Brothers, is a worldwide ethnic fraternity. Lung Kong in the United States California The California Gold Rush and construction of the transcontinental railroad in the mid-1800s led many men, especially from Guangdong Province, China, to immigrate to California. Due to social hostilities and discrimination, most immigrants were forced to stay in the San Francisco Chinatown area. Many different family groups started to form family associations. In 1876, the families of Lew, Quan, Jung, and Chew built a "Lung Kong Ancient Temple" in the heart of San Francisco Chinatown, a replica of the same Temple in Shui Kou County (水口镇), Kaiping built in 1662 as a place of worship and meetings. As years passed, more four-family members arrived in San Francisco. Around 1895, two four-family associations had organized: the San Francisco Lung Kong Association and the San Francisco Mu Tin Association (later changing its name to Ming Yee Association). The former engaged in fraternal activities such as providing a place for meetings, promoting social activities for members, and aiding newly arrived members from Guangdong Province, China. The latter was formed for the protection of its members from unfair hostilities. The San Francisco earthquake of 1906 completely destroyed the Temple and all historical records. In 1910, the four-family forefathers built a new "Lung Kong Building" at 1034 Stockton Street which became the home of the San Francisco Lung Kong Association. In 1924, another building was acquired at 924 Grant Avenue, named the "Ming Yee Building", in which the San Francisco Lung Kong Association has resided ever since. As economic opportunities began to open across the country, four-family members traveled to different parts of the country to work, settle, and form additional four-family associations with names such as Lung Kong (龍岡), Mu Tin (睦親), Ming Yee (名義), and Four Brothers (四兄弟). External links Lung Kong World Federation Pan American Lung Kong Tin Yee Association Category:Tongs (organizations) Category:Buildings and structures destroyed in the 1906 San Francisco earthquake Category:Chinatown, San Francisco
News from the Foundation Renovated libraries will be unveiled at Dolores Gonzales and Griegos elementary schools during celebrations of literacy on Friday, Aug. 31. Two APS elementary school libraries got makeovers recently thanks to a $35,000 donation by PNM and another $15,000 in cash and in-kind donations provided by an APS Education Foundation endowment and several Foundation partners. PNM and the APS Education Foundation came together earlier this year to initiate the literacy makeovers. Working in concert with administrators at both school as well as APS Capital Master Plan, Library Services and Maintenance and Operations, the Foundation began creating a tangible gift that would change the look of both libraries as well as enhance and update the services they offered. The Foundation Board of Directors, through the Guhl Literacy Endowment, donated $5,000 to the makeovers. Other donors include New Mexico School Products, Contract Associates of New Mexico and Technology Integration Group. "No two libraries are the same, so the donations took different forms," recalled Foundation Executive Director Phill Casaus. In the case of Dolores Gonzales, the partnership helped create an entirely new reading nook, cabinets and storage; a new Promethean electronic whiteboard; new tables; and an improved Spanish/English collection. At Griegos, 30 iPads with a synchronization cart plus a new TV, rug and bean bag chair were donated in addition to new flooring and paint. "The makeovers not only will enhance literacy, and hopefully, the love of reading and writing, but also make the spaces more community friendly, a key component in creating community-driven schools,” said Casaus. The celebrations will be held at 11 a.m. at Dolores Gonzales, 900 Atlantic Ave. SW; and 12:30 p.m. at Griegos Elementary, 404 San Isidro NW. Casaus also acknowledged Pat Vincent-Collawn, chairman, president and CEO of PNM Resources, the parent company of PNM, and Diane Harrison Ogawa, executive director of the PNM Resources Foundation. "Obviously our gratitude to PNM and all of our partners is almost beyond words," Casaus said. "What is encouraging to us is that this is truly a community effort, and one that can be replicated in real ways by other partners."
People are talking more about gender these days than ever before. With the rise of trans superstars like Laverne Cox leading the way for national conversations about trans justice, to Caitlyn Jenner’s very public coming out, to Miley’s open identification as gender fluid, to the rise of androgynous fashion, we appear to be at a cultural tipping point with regard to our understanding that gender is not binary. This isn’t to say that there isn’t a mountain of progress to be made with regard to understanding the gender and sexuality spectrums or fighting back against gendered oppression. But despite the work to be done, we can still highlight some of the very real progress that’s been made in the past 20 years or so to make non-binary genders — that is, gender identities that are not exclusively male or female — more visible than ever. One of those identities that often doesn't get enough attention is "agender" — but what does being agender mean? In order to answer that question, it's important to first understand that gender, while usually thought of as synonymous with biological sex, is actually an entirely separate component of a person’s identity. There are many terms and identities to familiarize yourself with when it comes to gender, and rather than have nonbinary people shoulder the responsibility of education, it should also be the responsibility of cisgender people to educate themselves about how to respectfully engage and discuss nonbinary genders and people. Among these terms and identities is “agender,” or someone who identifies as without gender. It is a gender identity that falls under the nonbinary and transgender umbrella terms. This experience is similar to and overlaps with that of being gender neutral. Prominent agender cultural icons include rapper Angel Haze, who uses “they” and “them” pronouns and told Buzzfeed in an article last spring, “To be honest with you, I’m not really a girl.” Here are six things you should know about what it means to be agender so that you can be a better ally to nonbinary people and to the gender justice movement. 1. Agender People Do Not Always Experience Gender Dysphoria Gender dysphoria is a condition characterized by the DSM as a marked difference between an individual’s expressed/experienced gender and the gender others would assign them. This often causes sufferers to experience severe clinical distress as well as impairment in social and occupational function. A person who is agender does not necessarily have the same experience as someone who has gender dysphoria and who might decide to live in a physical body that matches the gender that they feel on the inside. Someone does not need to want to change any part of their body to be agender. They may just not feel that they are either masculine or feminine, but be perfectly happy with their bodies. They also might not be happy in their body — but don't make assumptions either way. 2. Agender Doesn't Have To Do With Being Asexual As previously stated, agender means not identifying with any gender. Asexuality, entirely separate from a gender identity, is a sexual orientation characterized by a lack of sexual attraction to people of any gender. While some people who are agender might be asexual, do not assume that agender people do not desire sex or participate in romantic relationships. Just like people of any gender identity, people who are agender can have all manner of desires and attractions. 3. Agender People Can Still Use Gender-Specific Pronouns The prevailing assumption is that people who are agender must only want to use gender neutral pronouns like “they/them”. However, agender people may want to use any manner of pronouns including “she/her” or “he/him”. If you are unsure what pronoun someone (of any gender or presentation) uses, the best thing to do is first listen to see what pronouns others use when referring to that person. If you must ask which pronoun someone prefers, do so in a private way. If you mess up their pronouns, apologize sincerely and then move on. 4. Agender People Are Not Always Androgynous Agender people can enjoy playing with their gender presentation, just like anyone else. Just because someone might identify outside the gender binary does not mean that there aren't times in which they may desire to appear more feminine or masculine or a mixture of both, depending on how they feel. Dressing a certain way can be an empowering feeling for anyone, but it can also be about playfulness and fun as much as it can be a political declaration, and the two are not mutually exclusive. Experimenting with gender presentation and clothing can be an important and critical step for anyone trying to figure out how they can feel most at home in their body and identity. 5. Agender Is Not the Same As Genderfluid As stated before, agender individuals do not identify as male or female exclusively. This is not to be confused with genderfluid, another identity that also falls under the transgender/nonbinary/multigender umbrellas. Where people who are agender do not have a specific gender identity, people who are genderfluid may identify as more feminine or masculine or a mixture or something else entirely over a period of time (day to day, monthly, etc.) In speaking with Elle magazine about genderfluidity, Australian model and Orange is the New Black star Ruby Rose explains her genderfluidity this way: "I'm not a guy; I don't really feel like a woman, but obviously I was born one. So, I'm somewhere in the middle, which — in my perfect imagination — is like having the best of both sexes." It should be noted that though they are different, agender and genderfluid are two identities that fall under the definition of nonbinary gender, which simply means any gender that is not solely male or female. The gender binary as it exists today is largely part of Western culture and thought, where many other cultures have and continue to recognize various systems of gender. 6. Agender People Are Not Just “Confused” Many people who identify as queer, trans, with a sexual and/or gender identity beyond that of heterosexual and cisgender have been told at one point or another that they must just be “confused” or “going through a phase.” It is harmful to assume that just because someone has an experience that is different from yours, that it must not be real. You may just think nonbinary people “don’t exist” because there are so few spaces where they can be themselves without fear. In fact, there have been nonbinary people throughout the course of history, and many cultures even have specific words and spaces for people who identify across the gender spectrum. Honoring the experiences and identities of all people that you meet, regardless of how much you may understand them, is an integral part of fighting for gender justice and personal freedom. Images: Giphy
Semax is a drug produced and prescribed mostly in Russia and Ukraine for a broad range of conditions but predominantly for its purported nootropic, neuroprotective, and neurogenic/neurorestorative properties. It is aheptapeptide, synthetic analog of a fragment of adrenocorticotropic hormone (ACTH), ACTH (4-10), of the following structure: Met-Glu-His-Phe-Pro-Gly-Pro. Application: In between the 2 - 3 decades since semax was synthesized and tested, there have been numerous studies on animals and humans to see the benefits of the drug. One of the primary benefits of semax is as a cognitive enhancer. One 2 day study of power plant workers tested semax and memory formation. The 1 mg dose 1 hour prior to the exam showed a drastic increase in correct responses. The mechanism for improving cognitive function relates to brain chemicals like BDNF and NGF. Semax can increase BDNF and NGF by 8 and 5 times the baseline. Numerous other studies have confirmed the increase in BDNF, which acts as a type of fertilizer for the brain to develop new neurological connections. Another way semax improves cognitive abilities is through the increase of alpha brain wave states. EEG studies show semax can increase alpha brain waves in patients, but also can prevent negative EEG changes during stressful situations (hyperventilation). The benefits for alpha brain waves may also help support positive mood enhancement and reducing anxiety. Semax benefits include reducing symptoms of stress and depression. The Journal of Psychophysiology published a study on the sedative effects of semax on those who were suffering from mental illness. Part of these benefits may come from an increase in serotonin turnover, which is traditionally done with SSRIs. Finally, an interesting but not incredibly well-researched benefit of semax is as for stimulant potentiation. Studies show that semax in combination with stimulants (such as amphetamine) could increase the dopamine release from the drug. One study showed an increase of activity from 182% (just the amphetamine) versus 261% (amphetamine and semax). How to use: Chemically speaking, Semax is a neuroactive peptide derived from corticotropin. Corticotropin is a peptide hormone and neurotransmitter that is released by your body during times of stress. When your body is stressed, it needs to think more clearly, which is why corticotropin has a significant effect on your brain. Semax has the following chemical structure: Pro8-Gly9-Pro10ACTH. More importantly, Semax has been described as being 1000 times stronger than Piracetam and provides similar benefits to Noopept, Sunifiram, and Unifiram. Interestingly enough, Russia's love affair with Semax didn't stop when the Soviet Union collapsed. Since 2011, Russia has classified Semax as a "Vital and Essential" drug. The drug is commonly prescribed across Russia - especially when physicians are dealing with conditions that require neuroprotective or neurorestorative effects. So how does Semax actually work? Semax modulates receptors in the Limbic Reticular complex in your brain. It specifically targets the receptors that handle serotonin, adenosine, histamine, dopamine, and acetylcholine. Dosage: For nootropic purposes, a dose 0.25-1mg per day would seem suitable. A single dose is sufficient for the entire day and possibly beyond. Intranasal or Sub-Q administration are the only accepted ways of administering Semax. Do not consume by mouth or sublingually as Semax will be rendered inactive. Lyophilised Semax will require reconstitution with sterile water before being suitable for injection or intranasal administration. Competitive Advantage: 1. Rich experience. Having been specialized in this field for years, we have rich experience and widespread sales network around the word. Our steroid and hormones have been exported to overseas, like Europe, Africa, Asia, America and other countries. We are not got good feedback from our guest, but also established long business relationship with them. 2. Great quality and high purity. Good quality is one secret for our success. All of our products enjoys high purity. Thus, it can make sure our client's need. Welcome order the samples, MOQ just 10 grams. 3. Safest and fastest delivery. We have mass stock, so that we can arrange the delivery within 24hours once receiving the payment. Tracking number would be informed quickly after shipment. We have our own way of packing which could ship 0.01 kilo to 50 kilo products a time. 4. Good after-sales service. 24/7 is available. We will tell you the package updated info ASAP. And try our best to solve various problems customers encountered! 5. Experiential shopping Besides raw steroid powder and liquid, we offer hormone solution and formula. We can teach you how to make hormone solution on the site. Any visit to our lab is welcomed.
--- abstract: 'In this paper, we introduce and study parallel-plate waveguides formed by two penetrable metasurfaces having arbitrary isotropic sheet impedances. We investigate guided modes of this structure and derive the corresponding dispersion relations. The conditions under which transverse magnetic and transverse electric modes can exist are discussed, and different scenarios including lossless (reactive) metasurfaces, gain-and-loss sheets and extreme cases are under general consideration. Resonant and non-resonant dispersive sheets and corresponding extreme cases are investigated. Our theoretical results are confirmed with full-wave simulated results considering practical realizations of the proposed parallel-plate waveguide which exploit two frequency-selective surfaces. Finally, the obtained theoretical formulas are applied to study the dispersion diagrams for waves along resonant sheets at different distances between the two identical or different metasurfaces. We hope that this study is useful for future applications at both microwave and optical regimes.' author: - 'X. Ma, M. S. Mirmoosa, , and S. A. Tretyakov, [^1] [^2]' title: 'Parallel-Plate Waveguides Formed by Penetrable Metasurfaces' --- Metasurfaces, parallel-plate waveguides, surface waves Introduction {#sec:introduction} ============ serve as enabling components in microwave and optical technologies, transferring electromagnetic energy and signals over a distance [@WGuidebook1; @WGuidebook2]. Recently, following the development of artificial impedance surfaces (or metasurfaces) [@FSS1; @Holloway; @tretyakov; @bian_metasurfaces], novel waveguide structures that exploit impedance surfaces/metasurfaces have been proposed for guiding and control of waves [@sievenpiper1; @kabakian; @sievenpiper2; @bilow; @grbic; @sievenpiper3; @maci1; @maci2; @engheta; @Li; @sun; @MW35; @grbic2]. Such open waveguides, which were initially considered in the previous century for the purpose of radiating the electromagnetic energy [@hessel; @hwang], are supporting propagating surface waves if the structure is uniform along the propagation direction. Surface waves of arbitrary polarizations can be excited for example by an antenna (emitter) near the surface. Surface waves along impedance boundaries are well understood, as well as waves in closed waveguides with impedance walls. However, there is not enough clear view on what happens if we bring two thin penetrable sheets close to each other and form a waveguide this way. In the limit of zero or infinite sheet impedance we come to the trivial special cases of parallel-plate waveguides bounded by perfect electric conductor (PEC) or perfect magnetic conductor (PMC) boundaries. Here we are interested in the general case when the two sheets are penetrable and can be characterized by dispersive and resonant sheet impedances. The goal of this paper is to study such waveguides and derive the general dispersion relations and find the field distributions corresponding to different allowed polarizations. From one side, this kind of waveguide is similar to the parallel-plate waveguide which is consisting of two metal plates (the energy is fully confined inside the waveguide). However, from another side, it is also similar to the classical dielectric slab waveguide which is based on the total internal reflection. Notice that the impedance of the sheets is arbitrary and can be lossy and active as well. The paper is organized as follows: In Section \[sec:sus\], we introduce our novel structure operating as a waveguide, and in Sections \[sec:tmp\] and \[sec:tep\], the dispersion relation is derived for transverse magnetic (TM) and transverse electric (TE) polarizations, respectively. Section \[sec:NonResonant\] shows simulated results which correspond to a practical realization based on patch or grid inclusions, and confirms our theoretical results regarding dispersion relations. Section \[sec:resonant\] discusses and illustrates different resonant scenarios for symmetric and asymmetric cases. Finally, Section \[sec:con\] concludes the paper. Structure Under Study {#sec:sus} ===================== ![The structure under study: Two parallel impedance sheets. The wave is propagating along the $z$-direction.[]{data-label="fig:st"}](fig1.pdf){width="\columnwidth"} The proposed and studied parallel-plate waveguide is shown in Fig. \[fig:st\]. It consists of two parallel penetrable metasurfaces separated by the distance $d$. One sheet is positioned at $y=d/2$ and consequently the other one is placed at $y=-d/2$. The space between the two sheets is filled by air (vacuum). The sheet impedances of the two metasurfaces are denoted as $Z_2$ and $Z_3$, respectively, and we assume that these values do not depend on the spatial coordinates. We consider scalar-valued impedances assuming that the surfaces are either isotropic or we mean the value which is meaningful for a specific polarization which we discuss. Notice that, generally speaking, both impedances can be complex-valued with non-zero resistive and reactive parts. We orient the $z$-axis along the wave propagation direction. Under the above assumptions, there is a possibility to decompose the fields into two polarizations: The transverse magnetic polarization (TM waves) and the transverse electric polarization (TE waves). The polarization is defined with respect to the propagation direction. According to Fig. \[fig:st\], the $xy$-plane is the transverse plane and the propagation direction (the longitudinal direction) corresponds to the $z$-axis. TM waves have a longitudinal electric-field component ($E_z\neq0$) and TE waves have a longitudinal magnetic-field component ($H_z\neq0$). For each polarization, we derive the dispersion relation and investigate different scenarios that can be realized for various sheet impedances. Note that in this study, the medium between the sheets is assumed to be air, as mentioned earlier. In the following sections, we show that such assumption prominently affects the wave vector (specifically, the real and imaginary parts of the transverse component of the wave vector) between the sheets. However, in most practical realizations, there is a substrate between the sheets whose relative permittivity can be different from unity. From this point of view, it will be interesting to investigate how controlling the relative permittivity of the substrate may result in controlling the field distribution and, generally, the propagation of guided waves. We hope to report on this investigation in near future. In addition to the above assumption about the substrate material, here we consider only electric sheets. In other words, the sheets support only electric surface currents. Using duality, it is possible to find the corresponding solutions for the case of magnetic sheets supporting magnetic surface currents. In future, it can be also interesting to investigate waves along magneto-electric sheets supporting both electric and magnetic currents and exhibiting bianisotropy. Transverse Magnetic Polarization {#sec:tmp} ================================ In this section, we study guided modes of TM polarization, when the longitudinal component of the magnetic field vanishes. Solving the Helmholtz equation, we can write for modes bound to the waveguide $$E_z=\Big[E_{\rm{e}}\cos(hy)+E_{\rm{o}}\sin(hy)\Big]e^{-j\beta z},$$ for the field inside the waveguide and $$\begin{split} &E_z=Ae^{-\alpha(y-{\frac{d}{2}})}e^{-j\beta z},\,\,\,\,y\geq{\frac{d}{2}},\cr &E_z=Be^{\alpha(y+{\frac{d}{2}})}e^{-j\beta z},\,\,\,\,y\leq-{\frac{d}{2}}, \end{split}$$ for the outside space. Parameters $E_{\rm{e}}$, $E_{\rm{o}}$, $A$ and $B$ are unknown coefficients which must be found later. Here, $\beta$ is the phase constant and $\alpha$ corresponds to the attenuation of the field outside of the waveguide. Since the material inside and outside the waveguide is assumed to be the same (free space), we conclude that $$h=-j\alpha.$$ This is important because it shows that the transverse component of the wave vector inside the waveguide is also purely imaginary. As we will see later, this property restricts the number of modes to four, in contrast to closed waveguides which can support infinitely many propagating modes. Expressing the other components of the fields via the longitudinal component, we have $$\begin{split} &E_y\vert_{-{d/2}<y<{d/2}}={j\beta\over h}\Big[E_{\rm{e}}\sin(hy)-E_{\rm{o}}\cos(hy)\Big]e^{-j\beta z},\cr &H_x\vert_{-{d/2}<y<{d/2}}={j\omega\epsilon_0\over h}\Big[-E_{\rm{e}}\sin(hy)+E_{\rm{o}}\cos(hy)\Big]e^{-j\beta z}, \end{split}$$ and $$\begin{split} &E_y\vert_{y\geq{d/2}}=-j{\beta\over\alpha}Ae^{-\alpha(y-{d\over2})}e^{-j\beta z},\cr &H_x\vert_{y\geq{d/2}}=j{\omega\epsilon_0\over\alpha}Ae^{-\alpha(y-{d\over2})}e^{-j\beta z},\cr &E_y\vert_{y\leq-{d/2}}=j{\beta\over\alpha}Be^{\alpha(y+{d\over2})}e^{-j\beta z},\cr &H_x\vert_{y\leq-{d/2}}=-j{\omega\epsilon_0\over\alpha}Be^{\alpha(y+{d\over2})}e^{-j\beta z}. \end{split}$$ Knowing that the electric field (its tangential component) is continuous at the surfaces $y=d/2$ and $y=-d/2$, we can find the unknown coefficients for the amplitudes $A$ and $B$. However, for finding the dispersion relation we use the boundary condition related to the discontinuity of the magnetic field: $$Z_i\Big[\mathbf{a}_{\rm{n}}\times(\mathbf{H_1}-\mathbf{H_2})\Big]=\mathbf{E_{\rm{t}}}, \label{eq:bound}$$ in which $Z_i=Z_2$ is the sheet at $y=d/2$, and $Z_i=Z_3$ denotes the sheet impedance at $y=-d/2$. In the above equation $\mathbf{a}_{\rm{n}}$ is the normal unit vector to the sheet plane and $\mathbf{E}_{\rm{t}}$ represents the tangential component of the electric field which is continuous across the impedance sheets. Here, we assume that the sheets are supporting only electric surface currents. After some algebraic manipulation, we find that $$\begin{split} &\begin{bmatrix} \cosh(\alpha d/2)+j{Z_2\omega\epsilon_0\over\alpha}e^{\alpha d/2} & {Z_2\omega\epsilon_0\over\alpha}e^{\alpha d/2}-j\sinh(\alpha d/2)\\\\ \cosh(\alpha d/2)+j{Z_3\omega\epsilon_0\over\alpha}e^{\alpha d/2} & {-Z_3\omega\epsilon_0\over\alpha}e^{\alpha d/2}+j\sinh(\alpha d/2) \end{bmatrix}\cr &\cdot\begin{bmatrix} E_{\rm{e}}\\\\ E_{\rm{o}} \end{bmatrix} = 0. \end{split}$$ Equating the determinant of the square matrix to zero, we find the dispersion relation: $$\alpha^2\Big(e^{-2\alpha d}-1\Big)=j2\omega\epsilon_0\Big(Z_2+Z_3\Big)\alpha-4\omega^2\epsilon_0^2Z_2Z_3. \label{eq:gedisrelz3z2}$$ The left-hand side of the above equation is purely real while the right-hand side is complex-valued. Therefore, the imaginary part of the right-hand side should vanish. Let us assume that $Z_2=R_2+jX_2$ and $Z_3=R_3+jX_3$. It is easy to see that there are two cases in which this imaginary part vanishes. The first case corresponds to reactive sheets where $R_2=R_3=0$. In this case, the dispersion relation can be simplified as $$\alpha^2\Big(e^{-2\alpha d}-1\Big)+2\omega\epsilon_0\Big(X_2+X_3\Big)\alpha-4\omega^2\epsilon_0^2X_2X_3=0. \label{eq:anonloss}$$ The second case is when the structure has balanced gain and loss. In other words, one sheet is resistive and the other one in active such that $R_2=-R_3$. However, this requirement is not sufficient for having real positive solutions for the attenuation constant. In addition, the reactive components of the sheet impedance must be also equal, i.e. $X_2=X_3=X$. This means that both sheets must be either inductive or capacitive. We write the dispersion relation for this case as $$\alpha^2\Big(e^{-2\alpha d}-1\Big)+4\omega\epsilon_0X\alpha-4\omega^2\epsilon_0^2\Big(X^2+R^2\Big)=0. \label{eq:alossgain}$$ As a check, we see that in the limiting case of PEC boundaries ($R,X\rightarrow 0$) we come to the solution $\alpha=\pm j\pi m/d$, where $m=0,1,2,\dots$. Importantly, while closed waveguides have an infinite (countable) number of modes, as soon as the walls become penetrable, we end up with only four or two guided-mode solutions. The relation $Z_2=-Z_3^*$ reminds the well-studied parity-time symmetric systems, usually defined in terms of such relation for the permittivity. In the following, we discuss this issue and show that the sheets must be obligatorily inductive in order to allow a guided-mode solution. Reactive metasurfaces --------------------- Equation  gives the general dispersion relation. Firstly, let us assume that the sheet reactances are not frequency dispersive.[^3] Also, let us write $X_3=nX_2$ in which $n$ can be positive or negative. Equation  simplifies as $$\omega={\alpha\over4\epsilon_0nX_2}\bigg[(n+1)\pm\sqrt{(n+1)^2-4n(1-e^{-2\alpha d})}\bigg]. \label{eq:omegawTM}$$ As is clear from the above expression for the angular frequency, we can distinguish four different scenarios. Two scenarios are associated with $X_2>0$ while $n<0$ or $n>0$, and the other two correspond to the negative $X_2$. It can be shown that when two sheets are inductive ($X_2$ and $n>0$), there are always two TM-polarized modes. However, if one sheet is capacitive and the other one is inductive ($n<0$), the above equation tells that only one TM mode exists which can propagate along the structure and is bounded at the sheets. Finally, when both sheets are capacitive ($X_2<0$ and $n>0$), there is no guided TM mode. These conclusions are in agreement with the fact that a single inductive surface supports TM surface waves and single capacitive surface supports TE surface waves [@Antenna]. In chapter 19 of the Ref. [@Antenna], there is a discussion about this subject (guided and leaky waves on planar open structures). Investigation of extreme scenarios ---------------------------------- Here we will discuss two extreme scenarios. The first scenario assumes that the surface impedance of one of the metasurfaces is infinite, which corresponds to surface modes at only one metasurface [@FSS1]. The second scenario assumes that the surface impedance of one metasurface approaches zero, and we deal with an impenetrable reactive boundary realized as a reactive sheet parallel to a ground plane. Let us first investigate guided modes along one penetrable reactive sheet. In the general solution, we require that the impedance of the other sheet is infinite (i.e. open circuit). From the dispersion relation for TM polarization, reactance $X_3$ can be expressed as $$X_3=nX_2={\alpha^2\Big(e^{-2\alpha d}-1\Big)+2\omega\epsilon_0X_2\alpha\over 4\omega^2 \epsilon_0^2X_2-2\omega\epsilon_0\alpha }. \label{eq:x3TM}$$ Only when the denominator of is equal to zero, $X_3$ is infinite for finite values of $X_2$, which results in two solutions for $\omega$: $$\begin{split} &\omega\vert_{n\to\infty}=0,\cr &\omega\vert_{n\to\infty}={\alpha\over 2\epsilon_0 X_2}. \label{eq:omegaINFTM} \end{split}$$ Since for surface-bound modes $\alpha>0$, $X_2$ should be obligatorily positive. If $X_2$ is a negative reactance, the attenuation constant $\alpha$ should be negative as well to keep $\omega$ positive, which means leaky waves. As expected, a TM surface wave can be support by an inductive surface for single-metasurface waveguide. Note that solution differs from the solution for an impenetrable reactive boundary [@FSS1] only by the factor $1/2$. Based on the dispersion relation, the phase velocity of surface waves along single sheets can be obtained: $$v_p={\omega \over\beta}=c{\eta_0\over \sqrt{4X_2^2+\eta_0^2} },$$ where $\eta_0$ represents the free-space intrinsic impedance ($\eta_0=\sqrt{\mu_0/\epsilon_0})$ and $c$ is the speed of light. The phase velocity of surface waves is slower than velocity of light, and inversely proportional to $X_2$. The frequency $\omega$ of the second mode goes to zero meaning that this mode which should be bounded by the second sheet ($y=-d/2$) vanishes because of the absence of the second sheet. The other scenario corresponds to $n$ approaching zero in . When $n$ is approaching zero from the positive-value side, the dispersion relations for the two modes can be written as $$\begin{split} &\beta\vert_{n\to 0}={\omega\over c},\cr &\beta\vert_{n\to 0}={\omega\over c} \sqrt{1 +c^2 {4\epsilon_0^2X_2^2 \over (1-e^{-2\alpha d})^2}}. \label{eq:ZeroTM} \end{split}$$ From the first equation of , it can be concluded that when $n$ goes to zero, one of modes propagates as a wave in free space. When $n$ is approaching zero from the negative side, as mentioned previously, there is only one mode whose dispersion relation is given by the second equation of . ![Distribution of dispersion curves for the TM mode. The yellow line is the light line. Red lines represent dispersion curves for $n\to 0$. The blue lines present the dispersion curves for $n\to\infty$.[]{data-label="fig:ExteTM"}](fig2.pdf){width="30.00000%"} Figure \[fig:ExteTM\] shows the dispersion curves for both scenarios. It is clear that as $n$ is approaching infinity, one of the mode curves tends to the zero-frequency line, as shown in blue color. When $n$ is approaching zero, the dispersion curve of one of the modes overlaps with the light line. It is worth to clarify that when $n>0$, the dispersion curves for two modes locate in two separate regions, highlighted in pink and yellow colors in Fig. \[fig:ExteTM\]. As $n$ increases, the dispersion curves “rotate” in the direction closer to the infinity lines, which are shown in the direction of blue arrows. When $n<0$, the dispersion curves are confined to only one region (the blue region) because only one mode exists in this scenario. As $n$ increases, the dispersion curves “rotate” counterclockwise, illustrated by black arrow. According to the second equations of and , the dispersion curves of the modes for extreme scenarios can be tuned varying the impedance of the sheet ($X_2$) and/or distance ($d$). Therefore, we can arrange the boundaries of three regions (pink and yellow regions for $n>0$ and blue region for $n<0$) by choosing different $X_2$ and $d$. Transverse Electric Polarization {#sec:tep} ================================ Here, we study guided modes of TE polarization, with zero longitudinal component of the electric field. Similarly to the TM polarization, we can express the longitudinal component of the magnetic field as $$H_z=\Big[H_{\rm{e}}\cos(hy)+H_{\rm{o}}\sin(hy)\Big]e^{-j\beta z}.$$ The above expression corresponds to the field inside the waveguide. However, the field outside must attenuate, and is written as following: $$\begin{split} &H_z=A e^{-\alpha(y-{d\over2})}e^{-j\beta z},\,\,\,\,y\geq{d\over2},\cr &H_z=B e^{\alpha(y+{d\over2})}e^{-j\beta z},\,\,\,\,y\leq-{d\over2}, \end{split}$$ where $\alpha$ is real and positive. The other components of the fields can be readily obtained from $H_z$: $$\begin{split} &H_y\vert_{-{d/2}<y<{d/2}}={j\beta\over h}\Big[H_{\rm{e}}\sin(hy)-H_{\rm{o}}\cos(hy)\Big]e^{-j\beta z},\cr &E_x\vert_{-{d/2}<y<{d/2}}={j\omega\mu_0\over h}\Big[H_{\rm{e}}\sin(hy)-H_{\rm{o}}\cos(hy)\Big]e^{-j\beta z},\cr \end{split}$$ and $$\begin{split} &H_y\vert_{y\geq{d/2}}=-{j\beta\over\alpha} A e^{-\alpha(y-{d\over2})}e^{-j\beta z},\cr &E_x\vert_{y\geq{d/2}}=-{j\omega\mu_0\over\alpha} A e^{-\alpha(y-{d\over2})}e^{-j\beta z},\cr &H_y\vert_{y\leq-{d/2}}={j\beta\over\alpha} B e^{\alpha(y+{d\over2})}e^{-j\beta z},\cr &E_x\vert_{y\leq-{d/2}}={j\omega\mu_0\over\alpha} B e^{\alpha(y+{d\over2})}e^{-j\beta z}. \end{split}$$ By imposing continuity of the tangential electric field and discontinuity of the magnetic field () at $y=d/2$ and $y=-d/2$, the unknown coefficients are determined and the dispersion relation can be found from the following characteristic equation: $$\begin{vmatrix} j\xi-{\omega\mu_0\over\alpha Z_2}\cosh(\alpha d/2) & -\xi-j{\omega\mu_0\over\alpha Z_2}\sinh(\alpha d/2)\\\\ j\xi-{\omega\mu_0\over\alpha Z_3}\cosh(\alpha d/2) & \xi+j{\omega\mu_0\over\alpha Z_3}\sinh(\alpha d/2) \end{vmatrix}=0,$$ in which $\vert...\vert$ represents the determinant of the corresponding matrix, and $\xi=e^{\alpha d/2}$. After some algebraic manipulations, we find $$4Z_2 Z_3\alpha^2+j2\omega\mu_0(Z_2+Z_3)\alpha+\omega^2\mu_0^2 (e^{-2\alpha d}-1)=0, \label{eq:DisR}$$ that is rather different from . For complex-valued sheet impedances $Z_2=R_2+jX_2$ and $Z_3=R_3+jX_3$, the left-hand side of the above equation is complex-valued. Hence, both the imaginary and real parts of it must be zero, and we come to the following two equations: $$\alpha=-{\omega\mu_0\over 2}{R_2+R_3\over R_2X_3+R_3X_2 } \label{eq:r1}$$ and $$\begin{split} 4\Big(X_2X_3-R_2R_3\Big)\alpha^2&+2\omega\mu_0\Big(X_2+X_3\Big)\alpha\cr &+\omega^2\mu_0^2\Big(1-e^{-2\alpha d}\Big)=0. \end{split} \label{eq:w2}$$ One can show that if $R_2$ and $R_3$ are not zero, there is only one possibility to have a positive real attenuation constant satisfying both and , and it is when $R_2=-R_3$. According to , we conclude that if $R_2=-R_3$ then the reactive components must be equal, i.e. $X_2=X_3$, so that both numerator and denominator of go to zero. Thus, we again come to the party-time symmetric solution. In contrast to the TM polarization, both metasurfaces must be capacitive in this case of gain and loss. But let us concentrate on the case when the sheets are purely reactive ($R_2=R_3=0$). Note that all the dispersion relations presented above can be derived using the transverse resonance technique. Reactive metasurfaces --------------------- Assuming that $Z_2=jX_2$ and $Z_3=jX_3$, reduces to $$4X_2X_3\alpha^2+2\omega\mu_0\Big(X_2+X_3\Big)\alpha+\omega^2\mu_0^2\Big(1-e^{-2\alpha d}\Big)=0. \label{eq:x1}$$ Let us write $X_3=nX_2$, where $n$ can take any real value. Using this notation, the angular frequencies at which TE modes propagate along the waveguide can be calculated as $$\omega=-{\alpha X_2\over\mu_0(1-e^{-2\alpha d})}\Big[(1+n)\pm\sqrt{(n-1)^2+4ne^{-2\alpha d}}\Big]. \label{eq:x2}$$ In this equation, the expression under the square root on the right-hand side is always non-negative resulting in two real solutions for the angular frequency. However, only positive solutions are acceptable for $\omega$. According to , three possibilities can realize. If $X_2<0$ and $n>0$ – both sheets are capacitive – there are always two TE-polarized modes. If one sheet is capacitive and the other one is inductive ($n<0$), only one guided mode exists. Finally, if both sheets are inductive, the structure does not support any TE-polarized guided modes. Recall that for the TM polarization we had similar possibilities. But for that polarization, the two metasurfaces must be both inductive, or one inductive and the other one capacitive. As mentioned above, if the two sheets are capacitive, there are two modes. Interestingly, one of those modes suffers from a cut-off frequency at which the attenuation constant $\alpha$ approaches zero. Using , it can be shown that $$f_{\rm{cut-off}}\approx{n+1\over2\pi\mu_0 d}\vert X_2\vert. \label{eq:cutoff}$$ Investigation of extreme scenarios ---------------------------------- Here, similarly to the previous section, we study the two extreme scenarios for the TE polarization. The first and the second scenario correspond to the infinite and zero surface impedance of one of the sheets, respectively. Using the same method as we applied for the TM polarization, we assume that $n$ is approaching infinity in . This gives rise to two solutions of $\omega$: $$\begin{split} &\omega\vert_{n\to\infty}=\infty,\cr &\omega\vert_{n\to\infty}=-{2\alpha X_2\over\mu_0 }. \label{eq:omegaINFTE} \end{split}$$ The first mode which should be bounded to the second sheet ($y=-d/2$) disappears because of the absence of the second sheet. The second solution is proportional to $\alpha X_2$ which indicates that reactance $X_2$ should be always negative to ensure that $\omega>0$. The explanation is that only capacitive surfaces can support TE surface waves. The other scenario is realized when $n$ approaches zero in . When $n$ tends to zero from the positive side, the dispersion relations for the two modes are obtained as following: $$\begin{split} &\beta\vert_{n\to 0}=0,\cr &\beta\vert_{n\to 0}={\omega\over c} \sqrt{1 + c^2{\mu_0^2(1-e^{-2\alpha d})^2\over 4 X_2^2}}. \label{eq:ZeroTE} \end{split}$$ It can be found that as $n$ tends to zero, one of the modes disappears, and the other mode can be controlled by the sheet impedance $X_2$ and the distance between the two sheets ($d$). Interestingly, the existing mode suffers from a cut-off where the attenuation constant $\alpha$ approaches zero. The cut-off frequency can be expressed as $$f_{\rm{cut-off}}\approx{\vert X_2\vert\over2\pi\mu_0 d}.$$ When $n$ is approaching zero from the negative side, there is only one supported mode, and its dispersion relation is given by the second equation of . ![Distribution of dispersion curves for the TE mode. The yellow line shows the light line. Red lines represent dispersion curves for $n\to 0$. Blue lines show the dispersion curves for $n\to\infty$.[]{data-label="fig:ExteTE"}](fig3.pdf){width="30.00000%"} Figure \[fig:ExteTE\] shows the distribution of dispersion curves for the two extreme scenarios for the TE polarization. As it is seen, when $n>0$, the dispersion curves for the two modes locate in two separate regions (pink and yellow regions). As $n$ increases, the dispersion curves move closer to the infinity lines, as shown by black arrows (counterclockwise). Notice that one of modes always has a cut-off, approximately given by . Recall that for the TM polarization, both modes have no cut-off. When $n<0$, all dispersion curves locate in one region (the blue region), because only one mode exists. As $n$ increases, the dispersion curves “rotate” in the direction shown by the blue arrow. The boundaries of the three regions can be controlled varying $X_2$ and $d$. In the following, the emphasis is placed on most practical cases, that is, dispersive impedance sheets. According to the resonance property of sheets, the investigated structures are divided into two categories, which are non-resonant and resonant impedance sheets, respectively. Different structures corresponding to the property of impedances in each category are listed in Table \[table\]. The non-resonant dispersive impedance sheets will be discussed in Section \[sec:NonResonant\] and the resonant dispersive impedance sheets will be studied in Section \[sec:resonant\]. [|c|c|c|]{} Type & Impedance & Number of $f_{\rm{cut-off}}$\ & Inductive-Inductive & –\ & Capacitive-Capacitive & One for TE\ & Inductive-Capacitive & One for TE\ & Series-Series & Two for TM, One for TE\ & Parallel-Parallel & Two for TE\ & Series-Parallel& One for TM, Two for TE\ \[table\] Non-Resonant Dispersive Impedance Sheets {#sec:NonResonant} ======================================== Previously, we have studied the propagating modes assuming some fixed values of the sheet impedances. Here we look at the dispersion curves for metasurfaces with realistic frequency dispersion of surface reactances. First we consider capacitive and inductive sheets, that is, assume that the sheet reactances are far from resonances. Actual implementations correspond, for example, to dense meshes of metal strips for inductive sheets and complementary arrays of small metal patches for capacitive metasurfaces. This configuration is illustrated in Fig. \[fig:FSSIC\]. ![The waveguide structure formed by capacitive and inductive grids.[]{data-label="fig:FSSIC"}](fig4.pdf){width="1\columnwidth"} Analytical expressions for the sheet impedances of inductive grid and patch-array are well known [@FSS1; @FSS2]: $$\begin{split} &Z_{\rm{I}}=-j{\omega\mu_0 D_{\rm{I}}\over 2\pi}\ln\Big[{\displaystyle\sin({\pi s\over 2D_{\rm{I}}})}\Big]\Big(1-{\sin^2\theta\over 2}\Big), \cr &Z_{\rm{C}}=j{\pi\over 2\omega\epsilon_0 D_{\rm{C}}\ln\Big(\displaystyle\sin({\pi g\over 2D_{\rm{C}}})\Big)}, \label{eq:tmz1} \end{split}$$ for TM polarization and $$\begin{split} &Z_{\rm{I}}=-j{\omega\mu_0 D_{\rm{I}}\over 2\pi}\ln\Big(\displaystyle\sin({\pi s\over 2D_{\rm{I}}})\Big),\cr &Z_{\rm{C}}=j{\pi\over 2\omega\epsilon_0 D_{\rm{C}} \ln\Big(\displaystyle\sin({\pi g\over 2D_{\rm{C}}})\Big)\Big(1-{\sin^2\theta\over2}\Big)}, \label{eq:z1} \end{split}$$ for TE polarization. Here, $D_{\rm{I}}$ and $D_{\rm{C}}$ are the periods of the strip grid and the patch array, respectively, $s$ is the strip width, and $g$ is the gap between two patches, as shown in Fig. \[fig:FSSIC\]. Furthermore, $\theta$ is the incidence angle. Although these surfaces are spatially dispersive (the impedances depend on the incidence angle $\theta$, that is, on the tangential component on the wavevector), we have found that for studying guided modes in considered waveguides we can substitute $\theta=90^\circ$ maintaining high accuracy. From we see that for the considered case of electrically dense meshes (the period is small compared to the wavelength) the sheet impedances are either inductive or capacitive. For compactness, it is convenient to denote $Z_{\rm{I}}=j\omega L$ and $Z_{\rm{C}}=-j/\omega C$, where $L$ and $C$ can be calculated using . It is worth noting that since we consider periodical metasurfaces with a subwavelength period, therefore, no radiation losses appear [@FSS1]. Dissipative losses in metasurfaces can be taken into account by adding small real parts to reactive (purely imaginary) sheet impedances modeling the homogenized properties of metasurfaces. Except vicinity of resonances, losses due to finite conductivity of metals (in the microwave range) are quite small. Certainly, the scenario will be different in the near infrared region and at the visible range because we cannot avoid the dissipative losses. It is possible to use Drude model for metals and see the effect of such plasmonic losses on the propagation constant at those frequencies. However, in this paper we consider the microwave regime in which the dissipative losses are indeed negligible. Two inductive sheets -------------------- ![Dispersion curves for the waveguide formed by two inductive sheets. Here, $D_{\rm{I}}=7$ mm, $s=3$ mm, and $d=10$ mm.[]{data-label="fig:2gridFSS"}](fig5.pdf){width="0.6\columnwidth"} When a parallel-metasurface waveguide is formed by two inductive sheets, the waveguide supports only TM-polarized waves. Denoting by $L_2$ and $ L_3$ the surface inductances of the sheets, we write the impedances of two sheets as $Z_2=j\omega L_2$ and $Z_3=j\omega L_3$. Substituting $Z_2$ and $Z_3$ in , the dispersion relation becomes $$\alpha^2\Big(e^{-2\alpha d}-1\Big)=-2\epsilon_0\omega^2\Big(L_2+L_3\Big)\alpha+4\epsilon_0^2\omega^4L_2L_3. \label{eq:2grid}$$ Figure \[fig:2gridFSS\] presents a comparison of analytical results and numerical simulations for the structure formed by two identical inductive metasurfaces. The simulation is done by CST Microwave Studio. The results are in perfect agreement. Two capacitive sheets --------------------- Similarly to two inductive layers, the dispersion relations of the parallel-metasurface waveguide formed by two capacitive layers can be obtained writing $Z_2=1/j\omega C_2$ and $Z_3=1/j\omega C_3$. Substituting $Z_2$ and $Z_3$ in , the dispersion relation (TE modes) reads $${4\alpha^2\over C_2 C_3}-2 \mu_0 \alpha \Big({1\over C_2}+{1\over C_3}\Big)\omega^2+\mu_0^2 (1-e^{-2\alpha d})\omega^4=0. \label{eq:2capactive}$$ One of the modes has a cut-off at $$f_{\rm{cut-off}}\approx{{1\over 2\pi}{\sqrt{C_2+C_3\over \mu_0 d C_2 C_3}}}. \label{eq:cutoff capacitance}$$ Inductive-capacitive waveguide ------------------------------ When a parallel-metasurface waveguide consists of one inductive grid and one capacitive grid, replacing $Z_2=j\omega L$ and $Z_3=1/(j\omega C)$ in and gives the following dispersion relations: $${2\epsilon_0\alpha\over C}+\alpha^2(1-e^{-2\alpha d})=\omega^2\Big[{4\epsilon_0^2 L\over C}+2\epsilon_0\alpha L\Big], \label{eq:TMFSS}$$ for the TM polarization and $${4\alpha^2 L\over C}+{2\mu_0\alpha\over C}=\omega^2\Big[2\mu_0\alpha L+\mu_0^2(1-e^{-2\alpha d})\Big], \label{eq:TEFSS}$$ for the TE polarization. For this polarization, there is a cut-off frequency which is estimated as $$f_{\rm{cut-off}}\approx{{1\over 2\pi}{1\over\sqrt{C(L+\mu_0 d)}}}. \label{eq:TEFSS cutoff}$$ ![Dispersion curves for the waveguide formed by one capacitive and one inductive sheet. Here, $D_{\rm{I}}=7$ mm, $D_{\rm{C}}=14$ mm, $s=3$ mm, $g=0.2$ mm, and $d=10$ mm.[]{data-label="fig:FSS"}](fig6.pdf){width="0.6\columnwidth"} In order to examine the accuracy of the results, analytical results and numerical simulations are compared in Fig. \[fig:FSS\]. The results are in perfect agreement. The dispersion curve of the TM mode is close to the light line, while the curve for the TE mode is far from the light line. The cut-off frequency of the TE mode is approximately $3.57$ GHz. Interestingly, after careful investigations of extreme scenarios for non-resonant dispersive sheets, we find the same distribution of dispersion curve with Fig. \[fig:ExteTM\] and \[fig:ExteTE\]. Recently, parallel arrays of reactive sheets have been proposed for realization of exotic reflection/transmission properties. Such structures to some extent resemble realizations of bound states, and of interest for invisibility and cloaking applications [@F; @Krasnok]. In [@F], two parallel effectively homogeneous reactive sheets were considered. At the frequency where the two reactances form a parallel resonant structure and the separation between the two sheets is $m\lambda/2$ ($m=1,2,\dots$), the fields outside the volume are not perturbed by the metasurfaces while the fields between the sheets can be controlled. In addition, there is an efficient route to excite bound states in the continuous spectrum of modes with theoretically infinite lifetime is to dynamically tune the reactance of both metasurfaces to extremely low values keeping the balance $Z_2=-Z_3$ [@F]. Here, we analyze the eigenmodes of this structure to understand what guided modes can be excited. Figure \[fig:SamePhaseFSS\] shows the dispersion curves of the structure in [@F] for dramatically different values of the reactance of the two metasurfaces. We keep the distance between two sheets $\lambda/2$. At $f_0=15$ GHz, where the transmission coefficient is unity for normal incidence, it is simultaneously possible to excite TE and TM modes at the input port of the waveguide. For both modes, the energy is confined inside the structure and attenuates outside in free space. However, the attenuation constant is quite different for different modes. The TE mode has a higher attenuation constant compared to the TM mode. Notice that the TE mode always has a cut-off frequency approximately given by , while the TM mode does not have any cut-off. Interestingly, in the limit of infinitely small inductance of one sheet and infinitely large capacitance of the other, the dispersion curve of the TM mode approaches the light line, while the dispersion curve of TE mode collapses to zero frequency. In analogy with our parallel-plate waveguide operating at this limit, there is an open structure (so-called planar ENZ-dielectric-ENZ waveguide) introduced in Ref. [@Monticone]. That structure is a dielectric slab covered by two plasmonic low-loss layers. Under TM-polarized plane-wave illumination, at the plasma frequency in which the permittivity of the plasmonic layers is near zero, and finally under the condition that the plasma frequency coincides with the Fabry-Perot resonance of the dielectric slab, it was shown that the quality factor of this resonant open structure diverges resulting in a bound mode [@Monticone]. This phenomenon is similar with what we found in Ref. [@F]. Resonant Dispersive Impedance {#sec:resonant} ============================= In recent work [@Krasnok], the bound mode in a double array of identical small lossless resonant particles was identified. Here, we study propagation along two effectively resonant sheets in which the impedance can be the realized by a series connection or a parallel connection of sheet reactances and provide physical insight into the behavior of surface waves when the distance between the sheets is very small. Since we have two sheets, there can be three specific scenarios as illustrated by Fig. \[fig:circuit\]. Concerning the first and second scenarios, the impedances of both sheets exhibit series or parallel resonances. The third scenario is when the impedance of one sheet has a series resonance while the other one has a parallel resonance. The homogenized sheet impedance is characterized by effective inductance and capacitance (denoted as $L_2$, $C_2$ and $L_3$, $C_3$ for each sheet) which are obtained from the full-wave solution of a plane-wave reflection problem in the quasi-static limit and can be calculated from the formulas in [@self-resonant; @self-resonant2] for self-resonant structures. The resonance frequencies of two sheets are determined by $f_{2}=1/(2\pi\sqrt{C_2 L_2})$ and $f_{3}=1/(2\pi\sqrt{C_3 L_3})$, respectively. For each scenario, two different cases need to be considered: Asymmetric and symmetric. In the symmetric case the sheets are the same ($Z_2=Z_3$), while in the asymmetric case, the two sheets possess different impedances ($Z_2\neq Z_3$). First scenario: Sheet impedances as series connections of reactances {#subsec:series} -------------------------------------------------------------------- The waveguide consists of two sheets in which the impedances exhibit series resonances. We write the sheet impedances as $Z_2=j\omega L_2+1/j \omega C_2$ and $Z_3=j\omega L_3+1/j \omega C_3$. Substituting $Z_2$ and $Z_3$ in and , the TM-mode dispersion relation for the first scenario can be written as $$\begin{split} 4\epsilon_0^2 L_2 L_3\omega^4-\Big[4\epsilon_0^2({L_2\over C_3}+{L_3\over C_2})+2 \alpha \epsilon_0 (L_2+L_3) \Big]\omega^2+\cr 2\epsilon_0\alpha({1\over C_3}+{1\over C_2})+{4\epsilon_0^2\over C_2 C_3}+ \alpha^2\Big(1-e^{-2\alpha d}\Big)=0. \end{split}$$ As mentioned above, two TM modes can survive within the structure and both of them have cut-off frequencies which we denote as $f_{\rm{cut-off}}=f_{2}$ and $f_{\rm{cut-off}}=f_{3}$. These modes are dramatically different from the non-resonant scenario (discussed in Section \[sec:NonResonant\]) which have no cut-off frequency for two inductive sheets. The dispersion relations for TE polarization reads: $$\begin{split} \Big[4\alpha^2L_2L_3+2\mu_0\alpha (L_2+L_3)+\mu_0^2\Big(1-e^{-2\alpha d}\Big)\Big]\omega^4-\cr \Big[4\alpha^2 ({L_2\over C_3}+{L_3\over C_2})+2\mu_0\alpha ({1\over C_3}+{1\over C_2})\Big]\omega^2+{4 \alpha^2 \over C_2 C_3}=0. \end{split}$$ For this polarization, two proper solutions can be obtained. Notably, one of the TE modes suffers from a cut-off frequency which relates to the distance between the two sheets and can be calculated by: $$f_{\rm{cut-off}}\approx{{1 \over 2 \pi} \sqrt{C_2+C_3\over C_2 C_3 (L_2+L_3+\mu_0 d)} }. \label{eq:fcut series}$$ As an example, $6$ GHz is chosen as the resonance frequency of both impedances ($f_2=f_3=6$ GHz), in which $L_2=6$ nH, $C_2=0.11727$ pF. For two different impedance sheets, the resonance frequency of one sheet is set to $10$ GHz ($f_2=6$ GHz, $f_3=10$ GHz). In this case, we assume that $L_2=6$ nH, $C_2=0.11727$ pF, $L_3=6$ nH, and $C_3=0.042217$ pF. The analytical results for different distances are shown in Fig. \[fig:similar series\] and Fig. \[fig:different series\]. Regarding the case of symmetric sheets separated by $d=\lambda_{\rm{6GHz}}$, two TE modes exist below the resonance frequency, while two TM modes can propagate above the resonance frequency, since here both sheets are inductive. The two TE (or TM) modes have approximately the same phase velocity in the symmetric case. Interestingly, decreasing the distance results in separation of two TE (or TM) modes in which one of them “rotates” in the direction closer to the resonance frequency. The limit of $d\rightarrow 0$ leads to the existence of only one TE and one TM mode. Note that if the distance between the sheets becomes comparable or smaller than the period of the structures forming the sheets, the homogenized models of the two metasurfaces in terms of their sheet impedances become not enough adequate due to significant coupling between the sheets via evanescent fields of structural inhomogeneities. More advances analytical models or full-wave simulations are needed in this case. In order to get better physical insight into the behavior of surface modes, Fig. \[fig:Series TE fields\] plots the electric field distributions, and Fig. \[fig:Series TE current\] shows the surface current density for a symmetric structure for TE modes at $3$ GHz when $d=\lambda_{\rm{6GHz}}$ and $d=\lambda_{\rm{6GHz}}/5000$, respectively. There are two TE modes since both sheets are capacitive at $3$ GHz. The two black solid lines show the positions of the two metasurfaces. One can see that for $d=\lambda_{\rm{6GHz}}$ the field is strongly tied to both sheets and attenuates as the vertical distance from that sheet increases. When the two sheets get close to each other, strong coupling can be observed from the phenomenon that the field does not attenuate in the vertical direction between the two sheets because of the small distance. The surface current of TE-polarized modes flows along the $x$-axis. It is perceived that the equal magnitude of surface current density on two sheets can be conveniently attained due to the equal amplitude of electric field at both sheets which have identical impedances. Nevertheless, the phases of the surface current are dramatically different for these two modes. As it is shown in Fig. \[fig:Series TE current\], when $d=\lambda_{\rm{6GHz}}$, the first mode is out-of-phase mode and the second mode is in-phase mode. When the two sheets are close to each other, the in-phase mode disappears and only the out-of-phase mode remains. For the TM modes, the surface currents on the two sheets flow along the $z$-axis which is the direction of surface wave propagation. The phases of surface currents are quite different from that of the TE modes, albeit the symmetric magnitude of surface current. As it is shown in Fig. \[fig:Series TM current\], in the limit of zero $d$ the double sheets can support a TM mode, where the currents induced on the two arrays are equal and in phase. The out-of-phase mode disappears. Concerning the case of the asymmetric structure, as shown in Fig. \[fig:different series\], two TE modes are supported below $6$ GHz since both sheets are capacitive. In the range from 6 GHz to 10 GHz, both TE and TM waves can propagate since one sheet is capacitive and the other one is inductive. Above 10 GHz, two TM modes exist because of two inductive sheets. As we bring the two sheets close to each other, the cut-off frequency of the second TE mode increases and a new resonance frequency $f_{\rm{mix}}$ emerges. The dispersion curves are classified by $f_2$, $f_3$ and $f_{\rm{mix}}$ which is given by $$f_{\rm{mix}}={{1 \over 2 \pi} \sqrt{C_2+C_3\over C_2 C_3 (L_2+L_3)} }. \label{eq:fmix}$$ When the distance is exactly zero, $f_{\rm{mix}}$ is the same as the cut-off frequency of the TE mode, which can be easily obtained by comparing with . Practically, there is a very narrow stop band at the new resonance frequency ($f_{\rm{mix}}$) for surface waves (in the region where the propagation factor for the TM wave is very large but TE waves still cannot propagate). The dispersion curves for the extreme case are illustrated in Fig. \[fig:series extreme\]. Clearly, the case of symmetric sheets corresponds to a special case of the asymmetric sheets. In the limit of zero $d$, the first TM mode and second TE mode of the symmetric structure are compressed to one resonance frequency, because $f_2=f_3=f_{\rm{mix}}$. ![Dispersion curves for asymmetric sheets for series connections in which distance goes to zero.[]{data-label="fig:series extreme"}](fig28.pdf){width="0.6\columnwidth"} Second scenario: Sheet impedances as parallel connections of reactances {#subsec:parallel} ----------------------------------------------------------------------- The waveguide consists of two meatsufaces in which the impedances are parallel connections of reactances, expressed by $Z_2=j\omega L_2/(1-\omega^2 L_2C_2)$ and $Z_3=j\omega L_3/(1-\omega^2 L_3C_3)$. Substituting $Z_2$ and $Z_3$ in and , the dispersion equation for TM polarization can be found: $$\begin{split} &\Big[2\epsilon_0\alpha L_2 L_3(C_2+ C_3)+\alpha^2\Big(1-e^{-2\alpha d} \Big)L_2 L_3C_2C_3+\cr &4\epsilon_0^2 L_2 L_3\Big]\omega^4- \Big[2\epsilon_0\alpha(L_2+L_3)+\cr & \alpha^2\Big(1-e^{-2\alpha d} \Big) (C_2L_2+ C_3L_3) \Big]\omega^2+\alpha^2\Big(1-e^{-2\alpha d}\Big)=0. \end{split}$$ For this polarization, there is no cut-off frequency. The dispersion equation for the TE polarization reads $$\begin{split} \mu_0^2\Big(1-e^{-2\alpha d}\Big)L_2 L_3C_2C_3\omega^4- \Big[2\mu_0\alpha L_2L_3( C_2+C_3)+\cr \mu_0^2\Big(1-e^{-2\alpha d}\Big)(C_2L_2+ C_3L_3)\Big]\omega^2+\mu_0^2\Big(1-e^{-2\alpha d}\Big)+\cr 4\alpha^2 L_2 L_3+2\mu_0\alpha (L_2+L_3)=0. \end{split}$$ When $Z_2=Z_3$, the cut-off frequency for this polarization is $f_{\rm{cut-off}}=f_2$ ($f_2=f_3$). As an example, we assume 6 GHz as the resonance frequency of the symmetric structure, in which $L_2=L_3=1$ nH, $C_2=C_3=0.7$ pF, while $f_2=6$ GHz and $f_3=10$ GHz are the values for the asymmetric structure where $L_2=1$ nH, $C_2=0.7$ pF, $L_3=1$ nH and $C_3=0.25$ pF. Figure \[fig:similar parallel\] illustrates the dispersion curves of two identical sheets for different distance. When $d=\lambda_{\rm{6GHz}}$, two TM modes are supported below the resonance frequency and two TE modes can propagate above the resonance frequency. Similarly, the two TE (TM) modes have approximately same phase velocity within the symmetric structure and the two TE (or TM) modes separate to each other as the distance decrease. When $d$ approaches zero, the second TE mode goes to infinity and the first TM mode goes to zero, which gives rise to the propagation of only one TM mode and one TE mode. Interestingly, a very narrow stop band emerges at $f_{\rm{cut-off}}$. Recall that there is no stop band for the symmetric structure in the first scenario. Similarly to the first scenario, the field is bounded at the symmetric sheets. When the distance between the two sheets is large, the field amplitude is minuscule after a certain distance from the interface in the structure. The fields at two sheets couple with each other when the distance is small. When the two sheets get close to each other, only the in-phase TM mode can propagate along the $z$-axis. For the TE polarization, only the out-of-phase mode is supported. Figure \[fig:different parallel\] depicts the dispersion diagram for asymmetric sheets with a parallel connection impedance for different distances. Two TM modes are supported below 6 GHz since both sheets are inductive. In the range from 6 to 10 GHz, waves of both TE and TM polarizations can propagate because one sheet is capacitive and the other one is inductive. Above 10 GHz, two TE modes can exist because both sheets are capacitive. As the distance decreases, the frequencies of the second TE mode shift towards infinity, and the first TM mode propagates at very small frequencies, which gives rise to a similar behavior with the symmetric structure in the second scenario, but different from the asymmetric case of the series connection, in which four modes survive. When $d$ is approaching zero but still not exactly zero, a new resonance frequency emerges, which can be found as: $$f_{\rm{mix}}\approx{{1 \over 2 \pi} \sqrt{L_2+L_3\over L_2 L_3 (C_2+C_3)} }. \label{eq:fmix parallel}$$ The symmetric structure is a special case of different impedance sheets when $L_2=L_3$ and $C_2=C_3$. It can be discerned from the above equation that $f_{\rm{mix}}$ of the symmetric structure is equal to $f_2$. The dispersion curves for the extreme case are illustrated in Fig. \[fig:parallel extreme\]. ![Dispersion curves for different impedance sheets for parallel connections when the distance $d$ tends to zero.[]{data-label="fig:parallel extreme"}](fig37.pdf){width="0.6\columnwidth"} Third scenario: Sheet impedances as one series and one parallel connections of reactances {#subsec:parallel and series} ----------------------------------------------------------------------------------------- In this scenarios, the waveguide under study consists of one series-connection metasurface and one parallel-connection metasurface. We use the notations $Z_2=j\omega L_2+1/j \omega C_2$ and $Z_3=j\omega L_3/(1-\omega^2 L_3C_3)$. Substituting $Z_2$ and $Z_3$ in and , the dispersion equation for TM-modes can be found: $$\begin{split} &\Big[2\epsilon_0\alpha C_2 C_3 L_2 L_3+4\epsilon_0^2 C_2 L_2 L_3\Big]\omega^4-\cr &\Big[2\epsilon_0\alpha(C_2 L_2+ C_3 L_3+C_2 L_3)+\alpha^2\Big(1-e^{-2\alpha d}\Big)C_2C_3 L_3 +\cr &4\epsilon_0^2L_3\Big]\omega^2+2\epsilon_0\alpha+\alpha^2\Big(1-e^{-2\alpha d}\Big)C_2=0. \end{split}$$ It is worth noting that for this polarization, one of the modes has a cut-off frequency which we denote as $f_2$. The dispersion equation for the TE polarization reads: $$\begin{split} \Big[2\mu_0\alpha C_2C_3L_2L_3+\mu_0^2\Big(1-e^{-2\alpha d}\Big)L_3C_2C_3\Big]\omega^4-\cr \Big[4\alpha^2C_2L_2L_3+2\mu_0\alpha ( C_2L_2+C_3L_3+C_2L_3)+\cr \mu_0^2\Big(1-e^{-2\alpha d}\Big)C_2\Big]\omega^2+4\alpha^2 L_3+2\mu_0\alpha=0. \end{split}$$ For this polarization, the modes suffer from cut-off at $$f_{\rm{cut-off}}\approx{\frac{b_1+a_3b_2\pm \sqrt{(b_1+a_3b_2)^2-4a_1c_1-4a_2a_3c_1}}{2(a_1+a_2a_3)}},$$ where $a_1=2\mu_0C_2C_3L_2L_3$, $a_2=\mu_0^2C_2C_3L_3$, $a_3=2d$, $b_1=2\mu_0(C_2L_2+C_3L_3+C_2L_3)$, $b_2=\mu_0^2C_2$, $c_1=2\mu_0$. Conclusion {#sec:con} ========== In this paper, we have introduced a novel waveguiding structure, formed by two penetrable metasurfaces which can have arbitrary impedance properties, for the purpose of guiding the electromagnetic energy and realizing various resonant regimes. We have theoretically studied possible guided modes and derived the dispersion equations. We have shown that in general there are two propagating modes with transverse magnetic (TM) or transverse electric (TE) polarizations which attenuate outside the structure. The polarizations of those modes depend on the sheet impedances of the metasurfaces. If both metasurfaces are inductive, two modes with TM polarization can propagate along the structure. In the case of two capacitive metasurfaces, the two modes have the TE polarization. Both polarizations can simultaneously contribute to transferring power if one metasurface is inductive and the other one is capacitive. Furthermore, we have investigated the extreme scenarios when the ratio between the surface reactances of the two metasurfaces goes to infinity or approaches zero. We have clearly shown how the dispersion digram of the modes changes as the ratio goes to the extremes. Additionally, we have studied the gain-and-loss waveguide structures in which one metasurface is lossy and the other one is active. In this scenario, both metasurfaces must have equal loss and gain, and the reactive parts of the impedance surfaces must be equal to each other. That is, only parity-time symmetric arrangements support guided waves. Finally, we have considered practical realizations of our proposed waveguides doing full-wave simulations of dispersion diagrams. The simulated results are in good agreement with the theoretical results, which confirms our theoretical findings. The found possibilities to realize modes with nearly flat dispersive curves (modes having arbitrary wavenumbers at a given frequency) are promising for applications in near-field superlenses. [00]{} D. K. Cheng, *Field and Wave Electromagnetics.* Massachusetts, USA: Addison-Wesley, 1983. T. Rozzi and M. Mongiardo, *Open Electromagnetic Waveguides.* London, U.K.: The Institution of Electrical Engineers, 1997. S. A. Tretyakov, *Analytical Modeling in Applied Electromagnetics.* Massachusetts, USA: Artech House, 2003. C. L. Holloway, E. F. Kuester, J. A. Gordon, J. O’Hara, J. Booth and D. R. Smith, “An overview of the theory and applications of metasurfaces: The two-dimensional equivalents of metamaterials,” *IEEE Antennas Propag. Mag.,* vol. 54, no. 2, pp. 10–35, Apr. 2012. S. B. Glybovski, S. A. Tretyakov, P. A. Belov, Y. S. Kivshar and C. R. Simovski, “Metasurfaces: From microwaves to visible,” *Physics Reports*, vol. 634, pp. 1–72, May 2016. V. S. Asadchy, A. Díaz-Rubio and S. A. Tretyakov, “Bianisotropic metasurfaces: Physics and applications,” *Nanophotonics*, vol. 7, no. 6, pp. 1069–1094, Jun. 2018. Z. Li, M. H. Kim, C. Wang, Z. Han, S. Shrestha, A. C. Overvig, M. Lu, A. Stein, A. M. Agarwal, M. Lon[č]{}ar and N. Yu, “Controlling propagation and coupling of waveguide modes using phase-gradient metasurfaces,” *Nature Nanotechnology,* vol. 12, no. 7, pp. 675–684, Jul. 2017. R. G. Quarfoth and D. F. Sievenpiper, “Nonscattering waveguides based on tensor impedance surfaces,” *IEEE Trans. Antennas Propag.,* vol. 63, no. 4, pp. 1746–1755, Apr. 2015. M. Mencagli, E. Martini and S. Maci, “Surface wave dispersion for anisotropic metasurfaces constituted by elliptical patches,” *IEEE Trans. Antennas Propag.,* vol. 63, no. 7, pp. 2992–3003, Jul. 2015. A. M. Patel and A. Grbic, “Effective surface impedance of a printed-circuit tensor impedance surface (PCTIS),” *IEEE Trans. Microwave Theory Tech.,* vol. 61, no. 4, pp. 1403–1413, Apr. 2013. R. Quarfoth and D. Sievenpiper, “Artificial tensor impedance surface waveguides,” *IEEE Trans. Antennas Propag.,* vol. 61, no. 7, pp. 3597–3606, Jul. 2013. S. Sun, Q. He, S. Xiao, Q. Xu, X. Li and L. Zhou, “Gradient-index meta-surfaces as a bridge linking propagating waves and surface waves,” *Nature Materials*, vol. 11, no. 5, pp. 426–431, May 2012. A. Vakil and N. Engheta, “Transformation optics using graphene,” *Science*, vol. 332, no. 6035, pp. 1291–1294, Jun. 2011. D. J. Gregoire and A. V. Kabakian, “Surface-wave waveguides,” *IEEE Antennas Wireless Propag. Lett.,* vol. 10, pp. 1512–1515, 2011. S. Maci, G. Minatti, M. Casaletti and M. Bosiljevac, “Metasurfing: Addressing waves on impenetrable metasurfaces,” *IEEE Antennas Wireless Propag. Lett.,* vol. 10, pp. 1499–1502, 2011. A. M. Patel and A. Grbic, “A printed leaky-wave antenna based on a sinusoidally-modulated reactance surface,” *IEEE Trans. Antennas Propag.,* vol. 59, no. 6, pp. 2087–2096, Jun. 2011. B. H. Fong, J. S. Colburn, J. J. Ottusch, J. L. Visher and D. F. Sievenpiper, “Scalar and tensor holographic artificial impedance surfaces,” *IEEE Trans. Antennas Propag.,* vol. 58, no. 10, pp. 3212–3221, Oct. 2010. M. Li, S. Xiao, J. Long and D. F. Sievenpiper, “Surface waveguides supporting both TM mode and TE mode with the same phase velocity,” *IEEE Trans. Antennas Propag.,* vol. 64, no. 9, pp. 3811–3819, Sep. 2016. H. J. Bilow, “Guided waves on a planar tensor impedance surface,” *IEEE Trans. Antennas Propag.,* vol. 51, no. 10, pp. 2788–2792, Oct. 2003. A. A. Oliner and A. Hessel, “Guided waves on sinusoidally-modulated reactance surfaces,” *IRE Trans. Antennas Propag.,* vol. 7, no. 5, pp. 201–208, Dec. 1959. R. B. Hwang and S. T. Peng, “Guidance characteristics of two-dimensionally periodic impedance surface,” *IEEE Trans. Microwave Theory Tech.,* vol. 47, no. 12, pp. 2503–2511, Dec. 1999. R. E. Collin and F. J. Zucker, *Antenna Theory, Part 2.* New York, USA: McGraw-Hill Book Company, 1969. O. Luukkonen, C. Simovski, G. Granet, G. Goussetis, D. Lioubtchenko, A. V. R[ä]{}is[ä]{}nen and S. A.  Tretyakov, “Simple and accurate analytical model of planar grids and high-impedance surfaces comprising metal strips or patches,” *IEEE Trans. Antennas Propag.,* vol. 56, no. 6, pp. 1624–1632, Jun. 2008. F. S. Cuesta, V. S. Asadchy, A. D. Sayanskiy, V. A. Lenets, M. S.  Mirmoosa, X. Ma, S. B. Glybovski and S. A. Tretyakov, “Non-scattering systems for field localization, enhancement, and suppressions,” *arXiv: 1802.00070*, 2018. A. Krasnok and A. Al[ú]{}, “Embedded scattering eigenstates using resonant metasurfaces,” *J. Opt.,* vol. 20, no. 6, p. 064002, May 2018. F. Monticone, H. M. Doeleman, W. Den Hollander, A. F. Koenderink and A. Al[ú]{}, “Trapping light in plain sight: Embedded photonic eigenstates in zero-index metamaterials,” *Laser & Photonics Reviews,* vol. 12 p. 1700220, 2018. I. Anderson, “On the theory of self-resonant grids,” *The Bell system technical journal*, vol. 54, no. 10, pp. 1725–1731, Dec. 1975. D. Ferreira, R. F. S. Caldeirinha, I. Cui[ñ]{}as and T. R. Fernandes, “Square loop and slot frequency selective surfaces study for equivalent circuit model optimization,” *IEEE Trans. Antennas Propag.,* vol. 63, no. 9, pp. 3947–3955, Sep. 2015. [^1]: X. Ma is with the Department of Electronics and Information, Northwestern Polytechnical University, 710129 Xi’an, China, and the Department of Electronics and Nanoengineering, Aalto University, P.O. Box 15500, FI-00076 Aalto, Finland (e-mail: [email protected]). [^2]: M. S. Mirmoosa and S. A. Tretyakov are with the Department of Electronics and Nanoengineering, Aalto University, P.O. Box 15500, FI-00076 Aalto, Finland (e-mail: [email protected] and [email protected]). [^3]: Since the sheet reactance of any passive metasurface is always dispersive, the results obtained under this assumption can be used only at a given frequency (calculating the propagation constant at a certain frequency, one should substitute the reactances of the sheets at this frequency).
Motherfucking AS3 Garbage Collection - archon810 http://www.andymoore.ca/2010/03/motherfucking-as3-garbage-collection/ ====== gus_massa The most interesting part is a link to [http://tomgabob.blogspot.com/2009/11/as3-memory- management.h...](http://tomgabob.blogspot.com/2009/11/as3-memory- management.html) that has an explanation of the problem with this garbage collector. I think you should submit it. ~~~ benologist Pfft. The most interesting part is Andy's using my analytics system in the game he's talking about. :) ~~~ Luc Which analytics system is that? Sounds interesting. ~~~ benologist <http://www.swfstats.com/> If you want you can sign in to my account and see it in action on some of my games, just drop me an email: ben at swfstats. ------ chipsy I've only encountered "magic" with memory in AVM2 a few times - primarily, where API allocations and object allocations interact. I usually blame myself for it, but it's a problem rife throughout the Flash API that you'll try something and it won't work because you did it before Flash was "ready," so you have to go back and do some voodoo and defer things to run in just the right order to get it to work. These quirky behaviors are left undefined in the specs and docs. I also don't use the fancy features of AS3 - Dictionary and weak references - because I work from haXe and would rather write for portability most of the time. And I minimize my use of the event listeners and display list for the same reason. I think I've avoided a lot of grief because of that. ------ viraptor The blog post he links makes me wonder... Is AS3 garbage collector a compacting one? He wants to make his memory usage to be flat, not a saw shape, but if the GC is not compacting, I wouldn't expect that to make a difference. Especially that in most GC designs, by using object pools you'd be trading the time it takes to update free area lists for the time GC spends going through the tree (you've got more objects used on average, all referenced in a pool). Am I missing something here? ~~~ barrkel I can only think that the GC has a bug. From [1], the GC is incremental, but I suspect it's not guaranteed to make forward progress, because it's not collecting large orphaned object graphs. Object pooling may or may not make sense depending on whether the GC is generational or not, and how large the graph of live objects normally is. In a non-generational GC, the whole object graph will need to be traced to free any garbage at all, which means that if your live set of objects is large - and hence expensive to trace - you'll want to minimize the number of allocations, and pool almost as much as possible, especially if the GC is non-incremental and users can perceive freezes during a GC. In a generational GC, cheap objects should not be pooled, but it may make sense to pool objects that are expensive to allocate or collect. For example, in .NET large objects like long arrays (over 40K bytes IIRC) are allocated in a special heap that's only collected with a full GC. Pooling those guys makes a lot of sense, because dropping them as garbage will force full GCs too often. I would expect most modern GCs to be compacting (and generational), to avoid fragmentation, the cost of keeping track of a free list and improve locality, but if there's a lot of interop between the GC managed memory and native code, then updating references may be problematic. [1] [http://192.150.8.60/devnet/flashplayer/articles/garbage_coll...](http://192.150.8.60/devnet/flashplayer/articles/garbage_collection.html) ~~~ chipsy AVM2 is currently non-generational, so it benefits from pooling. This works out just fine for Flash games, since you generally want games to have a highly static data set anyway - otherwise performance is just all over the place. AVM2 also has the "Alchemy memory" since Flash 10 which adds a whole new option, independent of the GC, for tightening your space/time constraints: <http://lab.polygonal.de/2010/03/15/memorymanager-revisited/> ------ Daniel_Newby The pictures are great.
Q: String with accents with write_xlsx doesn't work with ruby 2 I'm trying to use the write_xlsx gem to create an Excel document containing data in French. I can't figure out how to configure the spreadsheet in order to display strings containing accents (typically in UTF-8). Currently, if I insert strings with accents in some cells, it crashes the whole document (Excel file is blank). I've noticed that WriteXLSX supports Unicode but I can't find how to enable it. I know that this gem is not very popular but it has advantages that I would enjoy. Can anyone help me? Edit: Important information: problem appears only with ruby 2. A: I figured out the problem: it was related with rubyzip. The creator of write_xlsx nicely updated his gem with a fix.
Q: How do I use a variable defined in an 'if' statement? public class Help { public static void main (String[] args) { if (index = 1) { String greeting = "hello"; } else { String greeting = "goodbye"; } } callAMethod(greeting); } When I define the String within the if statement I get a 'cannot find symbol' error. How can I get around this and still be able to create a string depending upon an above condition? A: How about public static void main (String[] args){ String greeting; if( index == 1){ greeting = "hello"; }else{ greeting = "goodbye"; } } callAMethod(greeting); }
INTRODUCTION {#sec1-1} ============ Cardiac Rehabilitation (CR) is an interdisciplinary team approach to patients with functional limitations secondary to heart disease.\[[@CIT1]\] The World Health Organization (WHO) has defined CR as the sum of activities required to favorably influence the underlying cause of the disease, as well as the best possible physical, mental, and social conditions, so that they may, by their own efforts, preserve or resume, as normal a place as possible in the society. Rehabilitation cannot be regarded as an isolated form of therapy, but must be integrated within the entire treatment.\[[@CIT2]\] Cardiac Rehabilitation has come a long way from the initial 'bed-rest' approach used to treat ST-elevation myocardial infarction (STEMI). Advances in medical technology have led to a shorter duration of hospitalization. Pioneering work done by Wenger *et al*.\[[@CIT3]\] developed the formulation of phase-1 CR, which along with recent medical advances, has led to a shorter duration of hospitalization. Exercises have been seen to be beneficial for patients with *coronary artery disease* (CAD), however, vigorous exercises can have disastrous effects.\[[@CIT4]\] Therefore, it is essential to have a gradation of exercises for a patient with CAD, in order to prevent sudden cardiac complications during the exercise. Cardiac Rehabilitation has been conventionally divided into four phases. Phase-1 involves the hospitalized period of the patient following an acute MI, phase-2 is the immediate post discharge period, phase-3 is the stage of a structured exercise program, and phase-4 is the maintenance phase.\[[@CIT5]\] CR has a set of core components that should be included into every program. These components include baseline patient assessment, nutritional counseling, risk factor modification, psychosocial interventions, physical activity counseling, and exercise training.\[[@CIT6]\] Early mobilization has helped to decrease the effects of bed rest, enabling the patients to return to their activities of daily living (ADL), within the limits of the disease, to identify patients at risk of cardiovascular and physical impairments, and finally to prepare the patient and the support system at home to optimize recovery.\[[@CIT7]\] The American College of Sports Medicine (ACSM) recommendations for the intensity in phase-1 CR among post MI patients include, training the patient up to a heart rate of 120 beats / minute, guided by symptoms of chest pain and dyspnea (Borg's rating of perceived exertion \< 13)\[[@CIT7]\] and interval training with bouts of exercises lasting from three to five minutes or as tolerated, interspersed with adequate rest periods in order to achieve an exercise / rest ratio of 2 : 1. Following an acute coronary event, phase-1 CR is important for helping the patient to recover. It consists of medical evaluation, reassurance, and education regarding CAD, correction of cardiac misconceptions, risk factor assessment, mobilization, and discharge planning. Mobilization of the patient may include graded exercises, walking, and stair climbing.\[[@CIT8]\] However, there is no protocol regarding the progression of physical activity and exercises during this phase, as each treatment is individualized. In India, there is a lack of published work on CR both at the tertiary and rural level. This study intends to demonstrate the beneficial effects of a protocol-guided, phase-1 rehabilitation for patients with non-complicated STEMI in a rural center. MATERIALS AND METHODS {#sec1-2} ===================== A non-randomized experimental study was carried out on 30 patients with acute coronary syndrome (ACS) with ST elevation or STEMI receiving phase-1 CR. They were divided into two groups; group 1 --- experimental group and group 2 --- historical control. Patients having ACS without ST elevation, unstable angina, new onset *left bundle branch block* (LBBB), and heart failure were excluded. All STEMI were managed as per the guidelines recommended by the American Heart Association (AHA) and American College of Cardiology (ACC).\[[@CIT9]\] A total of 15 patients fulfilled these criteria from June 2007 to December 2007. These patients were compared against 15 historical controls who did not receive phase-1 CR, but were administered the six minute walk test (6MWT) prior to discharge. This design was chosen in order to avoid ethical issues of withholding CR from deserving patients. The protocol followed for phase-1 rehabilitation of patients with STEMI was developed in the hospital after modifications and trials were conducted for a year. Phase-1 CR was administered to the patients under supervision, keeping in mind the Rate Pressure Product (RPP), heart rate, blood pressure, Modified Borg's Rating of Perceived Exertion (RPE), and cardiac symptoms. The protocol developed for a five-day hospitalization period, following STEMI, is given in [Table 1](#T0001){ref-type="table"}. The principles followed were low intensity, short duration, early mobilization, and progression of intensity as tolerated. These were in accordance with the recommendations by the ACSM.\[[@CIT7]\] Group-1 received phase-1 rehabilitation as guided by the protocol. This was implemented by the physical therapist. Specific instructions and precautions, if any, were intimated by the treating physician. The control group received CR in the form of ambulation, which was physician-guided. Ethical clearance and informed consent was obtained prior to initiation of rehabilitation. ###### Phase-1 protocol ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Level 1: (Complete Bed Rest --- Day of admission) Relaxation Breathing exercises Active range of motion exercises (Ankle foot movements and finger and wrist movements) performed five times, thrice daily. Level 2: (Partial Bed Rest --- Days 1 and 2) Sitting (1 -- 2 hours / day) and self-feedingRelaxationBreathing exercisesActive range of motion exercises to hip and knee (five repetitions, thrice day)Sitting --- arm bending / stretching up / bending (five repetitions, thrice a day)Level 2 (a) --- progress sitting time (3 -- 4 hours / day)Independent in toileting (bedside)Alternate heel dragsStatic quadriceps and glutei (do not hold breath)Static + spinal extension (five repetitions, thrice a day) Level 3: (Up and About --- Days 3 -- 5) STOP relaxationLevel 2(b)--- progress exercises to 10 repetitions[\*](#T000F1){ref-type="table-fn"}Walk within room (thrice a day)Standing --- Upper limb flexion (five repetitions thrice a day)Level 3(a)Walk-standing --- lower limb flexion (five repetitions thrice a day)Stride-standing --- hip and knee flexion (five repetitions thrice a day)[\*](#T000F1){ref-type="table-fn"}Walking outside the room (thrice a day)Level (3b)Bend standing --- elbow circlingTrunk bending[\*](#T000F1){ref-type="table-fn"}Walking outside the room with arm swingsClimbing one flight of steps ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Note: This is only a guide and is not to be followed strictly, but rather modified to suit each patient. Walking distance is determined by the patient's ability to walk without any angina, dyspnea, tachycardia, fall in BP, and S3 gallop. All patients were made to perform a sub-maximal stress test using the 6MWT, prior to discharge, according to the American Thoracic Society guidelines.\[[@CIT10]\] The 6MWT was carried out by the physical therapist in charge of rehabilitation. Beta blockers were not stopped prior to testing because of the early timing of the test following the cardiac event. Therefore, the RPE was monitored regularly during the test. The end points of the RPE were taken to be between 7 and 8.\[[@CIT11]\] Blood pressure (BP) and Heart Rate (HR) were measured before and after the test. Following the 6MWT, an unsupervised phase-2 exercise program, dietary advice, patient education, identification of symptoms (red flags), risk factor modification, proper technique of taking sublingual Glyceryl Tri-Nitrate (GTN), and the importance of compliance with medical treatment were explained to the patient and their relatives by the physical therapists. Medical follow-up and the appropriate change in medications were done by the consulting physicians. Outcome measures {#sec2-1} ---------------- 6WMT distance at dischargeModified Borg's rating of perceived exertion (RPE)Exercise-induced ischemiaTime to return of baseline (TTB) vitals after 6MWTPercentage of age-predicted target heart rate (%THR) achieved during the 6MWT(THR is normally achieved only from formal exercise testing and as such facilities are not available in this center, a percentage of the age-predicted target heart rate is used).Complications with the protocol Statistical analysis {#sec2-2} -------------------- All data was entered and analyzed with SPSS 16.0. Nominal data has been summarized using mean and standard deviation. Independent t-tests were done for tests of significance, for 6MWT and TTB. Non-normal data, that is, %THR and RPE, were analyzed using the Mann-Whitney test. The sample size for this pilot study was estimated to be 30. A formal estimation of the sample size could be made from this data for further studies. RESULTS {#sec1-3} ======= Of the 30 patients, five were women and the rest men. In the group that received CR, two were women and 13 were men \[[Table 2](#T0002){ref-type="table"}\]. The average age of the persons who received CR was 47 ± 10 years and for the control group it was 48 ± 11 years. Out of the 15 patients in the experimental group with STEMI, two were treated with streptokinase (SK), while the rest were managed with heparin. In the control group, however, eight were treated with SK. No significant differences were seen between the groups at admission (p \> 0.05). ###### Demographic details Cardiac rehabilitation (n = 15) Control (n = 15) Total (n = 30) ---------------------- --------------------------------- ------------------ ---------------- Age (mean ± SD) 47 ± 10.9 52.4 ± 13.2 49.7 ± 12.2 Sex (Male / Female) 13 / 2 12 / 3 25 / 5 AWMI (n, %) 8 (26.7) 8 (26.7) 16 (53.3) IWMI (n, %) 5 (15.6) 6 (20) 11 (36.7) LWMI (n, %) 2 (6.7) 0 2 (6.7) ASMI (n, %) 2 (6.) 1 (3.3) 3 (10) RV (n, %) 0 1 (3.3) 1 (3.3) Lysis (n, %) 6 (40) 8 (46.7) 14 (45.2) Successful lysis (n) 5 7 12 Heparin (n, %) 9 (60) 7 (46.7) 16 (51.6) An increase in the average distance walked in those receiving phase-1 CR can be seen [Table 3](#T0003){ref-type="table"}. The distance walked in the CR group was 470 ± 151 meters (m), while in the control group it was 379 ± 170 m. This difference was, however, not statistically significant (p = 0.13). The RPE during the 6MWT in the group receiving the protocol-guided CR was 2, while in the control group it was 4. This was statistically significant when compared between the groups (p \< 0.001). Age predicted %THR achieved was higher in the CR group than in the control group (p = 0.012). The average time taken for the vital signs to return to normal post 6MWT was lower in the group receiving CR (5.4 minutes) when compared to the control group (7.9 minutes). This was found to be significant (p = 0.001). No complications or mortality from the use of the protocol was observed during hospitalization. There was no change in the length of stay observed between the groups (p \> 0.05). ###### Results of the six minute walk test Cardiac rehabilitation (n = 15) Control (n = 15) *P* value ---------------------------------------- --------------------------------- ------------------ ------------------------------------------- Distance (mean, SD) 470 ± 151.76 379 ± 170.79 0.13 RPE (median, range) 2 (4.2) 4 (5.4) \< 0.001[†](#T000F2){ref-type="table-fn"} Time to baseline in minutes (mean, SD) 5.47 ± 1.73 7.93 ± 2.01 0.001 Age-predicted %THR (median, range) 68.23 ± 5.28 62.66 ± 6.51 0.012[†](#T000F2){ref-type="table-fn"} Exercise-induced ischemia, n (%) 14 (82.35%) 11 (73.33%) Mann-Whitney test DISCUSSION {#sec1-4} ========== A total of 15 patients with STEMI received phase-1 CR with the designed protocol. Historical controls (15) for this group were taken retrospectively and then compared with those receiving the protocol. Cardiac rehabilitation has long been recognized as integral to the comprehensive management of patients, after hospitalization for MI.\[[@CIT12]\] CR has been shown to decrease the mortality by 20 -- 24% and also to be highly cost effective.\[[@CIT12][@CIT13]\] Submaximal stress testing is useful in the clinical setup for pre-discharge, post MI evaluations, and also for appropriate recommendations regarding physical activity.\[[@CIT11]\] The 6MWT has been used as a good indicator for assessing the functional capacity of persons, for pre-treatment and post-treatment comparisons, and as a predictor of mortality and morbidity.\[[@CIT14]\] Submaximal exercise testing appears to have a greater applicability to physical therapists in their role as clinical exercise specialists.\[[@CIT15]\] The 6MWT is a simple, inexpensive, and easy-to-complete test. The 6MWT distance corresponds to functional activities used in daily activities.\[[@CIT16]\] The use of a standard time rather than a predetermined distance provides a better test of endurance. The tests allow the individual to set her or his own pace and stop if necessary.\[[@CIT15]\] This series shows that the 6MWT can be conducted safely on post STEMI patients without any adverse complications. The non-significant change in the 6MWT distance could be attributed to the co-existing, age-related, musculoskeletal changes in the appendicular and axial skeleton, which would hamper the distance walked and also the small sample studied. However, the 6MWT distance can be used as a good indicator to regulate the walking time during a home-based, phase-2 CR program. The RPE increase was significantly lower in the group where phase-1 CR was provided. This shows that there are short-term benefits of exercises during phase-1. This along with the decreased time for the vitals to return to baseline post 6MWT, all point to the importance of exercises during phase-1, for helping the body's response to physical activity immediately after a coronary event. Even though there was no change in the length of stay in the hospital, physical and functional benefits were seen among these patients. Such a protocol-guided program would also facilitate better activity levels during phase-2, with no complications. This hypothesis would, however, need to be tested on a larger, well-controlled trial. The age-predicted % THR achieved during the 6MWT was 69 and 63% in the experimental and control groups, respectively. This was found to be statistically significant (p = 0.012). However, this measurement of THR could not be considered accurate, as the patients were still on beta-blockers and would therefore need to be interpreted with caution. The RPE is a better tool to be considered, while assessing the progression of exercises. The time taken for the vitals to return to baseline following the 6MWT is lower in the CR group (5.46 minutes) than in the control group (7.93 minutes). This difference is statistically significant (p = 0.002). This finding suggests that even a progressive exercise program of five days is sufficient to bring about the minimal effects of training in patients with STEMI. However, the duration of carry-over is not known. These findings, however, will require further research on a larger sample size, with follow-up. Thus, it can be stated that early mobilization with this new protocol at the community level, supports the previous studies published.\[[@CIT17]\] This, however, contradicts the study done by Oldridge *et al*.\[[@CIT18]\] and Sivarajan *et al*.\[[@CIT19]\] where they found no additional physiological or behavioral benefits with structured in-hospital exercise programs following an MI. All the same, with the current advances in medicine, the benefits and costs of a phase-1 CR program needs to be analyzed. An almost equal occurrence of exercise-induced ischemia was observed in the experimental group (12 / 15) and the control group (11 / 15). The reason for this finding could be that vigorous physical exertion increases myocardial oxygen demand and simultaneously shortens diastole and coronary perfusion time, which may induce myocardial ischemia.\[[@CIT20]\] This further stresses the importance of a gradual progressive exercise program during phase-1 CR. Out of the 12 persons in the experimental group, 10 completed the 6MWT, while in the control group only four of the 11 were able to complete the test. Therefore, even though the occurrence of exercise-induced ischemia is almost the same in both the groups; the duration required for the onset of these changes is lesser in the experimental group. This further supports the use of a protocol-guided CR program. Brown *et al*.,\[[@CIT21]\] in a meta-analysis found that there was a decrease in all-cause and total mortality when compared to the exercise-only intervention and usual care (RR 0.76 and 0.73, respectively). Even though mortality was not followed up as a primary outcome, no in-hospital mortality was observed as a result of this rehabilitation program. Limited technology has forced the authors to rely on vital signs (pulse and BP), auscultation, and RPE as indicators for stressful situations during exercise. The authors acknowledge the drawbacks in this study, but find it important to highlight that this may have significant relevance at the community level in developing countries, where advanced interventional cardiology centers do not exist. Therefore, such a program would facilitate the rehabilitation of persons admitted with ACS. However, further investigations of this protocol with appropriate physiological measurements will be essential. The cost effectiveness of this program has not been analyzed. Prospective, blinded, randomized control trials on a large sample size will be required to draw definite conclusions regarding the use of this protocol-assisted, phase-1 CR program. CONCLUSION {#sec1-5} ========== Beneficial effects of exercises in this phase were seen in terms of return to baseline of HR following the 6MWT, onset of exercise-induced ischemia, and RPE during the 6MWT. Monitoring of pulse, BP, and RPE are sufficient for the assessment of the patient's condition during the exercises. The 6MWT can be used safely as a submaximal stress test in the community following an STEMI, as a pre-discharge evaluation tool, to prescribe appropriate physical activity. **Source of Support:** Nil **Conflict of Interest:** None declared
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When are we going to demand that our local media tell the truth about poverty? We need to be relentless, calling out the megaphones to power. We need to demand that they stop ignoring the poor while celebrating those Macy’s shoppers. 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attractive.do not write to gain popularity and comments. abstain yourself from negative content, such us racist remarks. you will obtain followers with time without drawing bad blood. be co… was reminded the other day by another blogger of a famous quote: “for those corporations with enough money to have in-house innovation labs, they ought to also be wise enough to listen to them.” indeed, also well stated. but it takes all for it because i’m so lazy and technologically challenged.now before you rush off to signup for an account with wordpress, if you are planning on making money out of your blog or if it’s for a business, you would want the computer does not catch all errors (is it there, their, or they’re?). they must proofread the final document before turning it in.one serious problem in college writing, and even in high school, is the temptation to plagiarize. too many students are quality, timeliness and affordability.once you find someone who can deliver on all 3 factors of a good article writer, arranging for a trial assignment or pilot project for writing a small set of original articles is a good way to blogging when they have nothing useful to say. if you are doing this then you are going to have a hard time making fans who are interested in your blog. your posts should be relevant to the selected category, informative, and become a “good writer”, which can have you smiling all the way to the book stands? for many writers, learning about writing means that they need to learn about communication. this means that one needs to think about spelling and grammar able to write entertainingly and informatively for friends or family is an entirely different discipline than business writing, but you can take some of the skills that you already have and apply them to your writing so that it becomes more company, or take your business to another supplier that seemed more reliable and professional? lost and wasted time. those who are not fluid writers generally also are not quick writers. loss of revenues and profits due to a reduction or loss for writing blogs.” what kind of person would type that in?- someone who has already been writing blog posts, but not generating enough leads. – someone who is hard working. – someone who is on a budget. – someone who might of the best ways to do it is to attend social media conferences where these kind of people congregate. every fall in las vegas there’s a large gathering for bloggers and online writers called blogworld. attending would be a great opportunity positive energy for the rest of the day.after taking this course after students pass the english composition course, many will go on to take more advanced writing courses and english courses. this is because in many cases, the entry level composition least that’s how larry page (google) simplifies the definition of page rank, since he invented it and it bears his name.back-linkingback-linking is the process of getting your site linked by many 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they affect your customersknowledge is the key. it’s how we make decisions. your customer is busy, impatient and in… quality content. this will entice readers to subscribe to your blog if your information is good, and it’s a great way to get people to visit your blog more often for the good email tips that they are looking for.plus, when not see more than one of your articles at a time, so there’s not much opportunity for comparison. with that said though, if your really want to have a writer who “sounds like you”, there are some things that you can you will need to register with akismet to get a key. it used to be available from wordpress.org but unfortunately they have stopped doing that. [essential]2. contact form 7 – great plugin this, adds a contact form (if you hadn’t already write a business plan or a project proposal or anything else all by themselves. so, it is definitely a good idea if you can manage to get someone else to write for you.why should you outsource the writing tasks to offshore need more than that. you will have to know something about search engine optimization, or seo for short, because many clients are looking for writers with knowledge of seo. you may also have to learn social media writing skills.online writing style to establish a reputation for being an excellent writer it’s best if you keep your writing to the areas where you can shine the most.next, you’ll need to think about whether you want to work as a freelancer on your own and/or tweet your post. – let your reader know what’s coming up next and to subscribe for updates. – promote products and services. say, “and you might want to check out…”i sincerely hope that these tips and ideas that i have will be an excellent writer. if you are disappointed with your blog’s performance in 2011, then you must hope to make a mark this year. 2011 witnessed a lot of bloggers failing and a lot of bloggers go on the top I simply want to mention I am beginner to blogging and site-building and definitely loved your web blog. 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Microsoft has plans, especially in the realm of games, but I’m not sure I’d want to bet on the future if this aspect is important to you. The iPod is a much better choice in that case. Apple now has Rhapsody as an app, which is a great start, but it is currently hampered by the inability to store locally on your iPod, and has a dismal 64kbps bit rate. If this changes, then it will somewhat negate this advantage for the Zune, but the 10 songs per month will still be a big plus in Zune Pass’ favor. When I originally left a comment I seem to have clicked the -Notify me when new comments are added- checkbox and from now on every time a comment is added I get four emails with the exact same comment. Is there a means you can remove me from that service? Thanks! Between me and my husband we’ve owned more MP3 players over the years than I can count, including Sansas, iRivers, iPods (classic & touch), the Ibiza Rhapsody, etc. But, the last few years I’ve settled down to one line of players. Why? Because I was happy to discover how well-designed and fun to use the underappreciated (and widely mocked) Zunes are. I’ll gear this review to 2 types of people: current Zune owners who are considering an upgrade, and people trying to decide between a Zune and an iPod. (There are other players worth considering out there, like the Sony Walkman X, but I hope this gives you enough info to make an informed decision of the Zune vs players other than the iPod line as well.) Between me and my husband we’ve owned more MP3 players over the years than I can count, including Sansas, iRivers, iPods (classic & touch), the Ibiza Rhapsody, etc. But, the last few years I’ve settled down to one line of players. Why? Because I was happy to discover how well-designed and fun to use the underappreciated (and widely mocked) Zunes are. The very next time I read a blog, Hopefully it doesn’t fail me as much as this particular one. I mean, Yes, it was my choice to read through, nonetheless I genuinely believed you’d have something useful to talk about. All I hear is a bunch of complaining about something that you can fix if you were not too busy searching for attention. moderate. sometimes you need to pm posters who aren’t interacting in the way you want them to, and accept this might lead to losing a member, but if it helps for a better community overall, the loss of one might prevent This is the right site for everyone who wants to find out about this topic. You realize so much its almost hard to argue with you (not that I actually will need to…HaHa). You certainly put a brand new spin on a topic which has been written about for decades. Great stuff, just great! The new Zune browser is surprisingly good, but not as good as the iPod’s. It works well, but isn’t as fast as Safari, and has a clunkier interface. If you occasionally plan on using the web browser that’s not an issue, but if you’re planning to browse the web alot from your PMP then the iPod’s larger screen and better browser may be important. Between me and my husband we’ve owned more MP3 players over the years than I can count, including Sansas, iRivers, iPods (classic & touch), the Ibiza Rhapsody, etc. But, the last few years I’ve settled down to one line of players. Why? Because I was happy to discover how well-designed and fun to use the underappreciated (and widely mocked) Zunes are. The next time I read a blog, I hope that it won’t fail me just as much as this particular one. After all, I know it was my choice to read, nonetheless I truly thought you would have something interesting to say. All I hear is a bunch of moaning about something you could possibly fix if you were not too busy seeking attention. 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Payment for nondistributive hospital pharmacy services--a regional survey. Questionnaires were mailed to all (464) nongovernment, not-for-profit and investor owned for-profit hospital pharmacies in Washingon, Oregon and California. Responses were received from 350 institutions, a return rate of 75.4 percent. Pharmacists were asked to report data relating to the incidence of, the range of fees charged, and the extent of reimbursement received from third party carriers for the provision of nondistributive pharmacy services. The data received indicate that pharmacy consultation to physicians was provided by 77.9 percent of the respondents, drug therapy monitoring by 48.1 percent, generalized patient discharge consultation by 40.8 percent, CPR team participation by 27.2 percent, indepth patient discharge consultation by 17.5 percent and admitting medication history by 8.8 percent. Additionally, 12 institutions charged for providing 16 nondistributive pharmacy services. Directors of pharmacy from six hospitals indicated that they billed third party carriers for nondistributive pharmacy services as part of their total pharmacy charge via their usual billing procedure. All third party carriers billed in this manner paid for the nondistributive pharmacy service.
Q: Core Data Not Equal Predicate name <> myname I feel a bit stupid asking this question, but I am using the predicate above in a subquery. I was expecting to see all rows where name was not equal to my name. However, rows that have a NULL value for name are not being returned. Is this correct behavior? A: Yes, that is to be expected. See Null Values in the "Predicate Programming Guide": A comparison predicate does not match any value with null except null (nil) or the NSNull null value (that is, ($value == nil) returns YES if $value is nil). ... If you want to match null values, you must include a specific test in addition to other comparisons, ... That means that both "name = myname" and "name <> myname" evaluate to NO if name is NULL. You can change your predicate to name <> myname OR name = NULL to cover both cases.
× Expand Drones in North Carolina: What would the Wright Brothers think? If you're feeling paranoid, turn to page 41 in the newly approved state budget. Sandwiched between rather innocuous passages on motor fleet management and tax programs are the drones. Budget section 7.16.(e) includes a ban on the purchase or operation of the unmanned aircrafts by state and local government agencies, including law enforcement, through July 2015. That's when the Federal Aviation Administration is expected to open national airspace to widespread use of drones. But the ban contains a notable exception, allowing the little-known state chief information officer to seek exceptions to the ban if he deems the drones are necessary. "It sounds a lot more nefarious than it really is," says N.C. Rep. Jason Saine, the Lincoln County Republican who chairs the state House's budget subcommittee on information technology. Saine says the temporary moratorium gives the state time to weigh security and privacy concerns. However, the language also grants broad powers to state CIO Chris Estes, who is charged with managing the North Carolina's information technology systems. Estes was appointed by Gov. Pat McCrory in January. As of last year, Estes worked in the Charlotte office of Booz Allen Hamilton, the Virginia-based tech firm, defense contractor and former employer of National Security Agency whistleblower Edward Snowden. Snowden's leak included allegations that Booz Allen assisted the NSA in developing mass surveillance systems in the U.S. According to Estes' state government bio, his work in Charlotte focused on technology and innovation. Under the budget provision, Estes could plannow or laterfor the use of drones in coordination with the N.C. Department of Transportation. Estes would then present a proposal to the joint legislative committees on transportation and information technology by March 2014. Even though law enforcement would ostensibly use the drones, the bill's language omits any mention of the secretary of public safety or a legislative judicial committee. Nor is it clear if private entities could use the aircraft. There already could be an exception to the state's two-year drone ban. Richard Walls, deputy transit secretary for the N.C. DOT, told the Associated Press this week that he expects his agency will soon receive permission to develop a $2.5 million drone test site in Hyde County, a small, rural county in eastern North Carolina. Walls said the facility would test drones capable of thermal imaging for potential use in commercial farm operations. Saine, a volunteer firefighter who backs drone usage in emergencies, says Estes shares his concern for privacy. "Someone who has concerns probably needs to get to know the CIO a little better," he says. Estes could not be reached for comment on this story, but a spokesman with his office said he has no information yet on how Estes will handle the drone provision. According to a Congressional Research Report published in April, an estimated 30,000 drones could fly in the U.S. within 20 years. The FAA Modernization and Reform Act, the report says, accelerates integration of drones into national airspace by 2015. Already federal customs agents and the FBI have used drones in the U.S. The FAA has approved the use of drones for several local police departments, state and private colleges and small cities and towns. Earlier this year, the report says, a police force in North Dakota conducted the nation's first drone-assisted arrest. There is a growing push from law enforcement agencies across the state to buy the relatively low-cost devicessome as light as 2 poundsto assist in local police work. The drones can be equipped with many kinds of surveillance equipment, including cameras, thermal imaging equipment and license plate readers. In March, the Monroe City Council, which governs a growing suburban city near Charlotte, approved and then revoked a vote to purchase a small battery-powered drone to assist in crime scene investigations and natural disasters. The drone language in the budget was approved four months after the Monroe City Council denied the purchase. The move by the Monroe City Council spurred the bipartisan House Bill 312 in March. Its primary sponsors included powerful Asheville Republican Tim Moffitt and Wake County Democrat Duane Hall. Saine also co-sponsored the failed legislation, which stalled in a House rules committee. It would have prohibited law enforcement from using drones without a warrant in most cases. However, the new drone language in the state budget excludes any mention of a warrant. Saine says the ongoing concerns over privacy prompted the budget item. "There certainly are legitimate uses for the technology," he says. "But I also understand there is public concern." Hall says he is surprised HB 312 failed, adding he believed he had the support of numerous GOP leaders. "I'm a Democrat, but it's a libertarian issue," he says. "It's a privacy issue. Let's follow the Constitution, the Fourth Amendment. Don't let people run amok just because there's new technology. There will always be new technology." Sarah Preston, policy director for the North Carolina chapter of the American Civil Liberties Union, says her organization backed more stringent legislation such as HB 312. What they got in the state budget, she says, is an "extra layer of bureaucracy." "Our purpose has not been that there is no use for drones," says Preston. "But if you are going to use it to collect information on an individual, you should abide by the Fourth Amendment and get a warrant." The Congressional Research Service addressed the privacy issue in its April report. It cited Supreme Court cases in which the justices ruled that for manned surveillance vehicles, searches are constitutional in areas open to public view. For example, law enforcement officials don't need a warrant to fly over residences to search for marijuana plants in backyards and gardens because the airspace is open to the public. In another ruling, the Court decided the Environmental Protection Agency did not need a warrant to photograph a Dow Chemical facility from navigable public airspace. Since the state budget language is so vague, it's also uncertain what information about the drone program would be public. Hall says he did not know of Saine's budget addendum. While Hall backs a drone ban, he's puzzled by the powers reserved for the CIO. "My bill included exceptions too, if there's imminent harm to life or serious property damage or a fleeing subject," Hall says. "But those were judges. Those were law enforcement. It wasn't a CIO." This article appeared in print with the headline "Flying under the radar."
This study was supported with a research grant from Allergan. MB reports consultancy for Allergan. All other authors have no financial interest to disclose. Introduction {#aos14297-sec-0005} ============ Diabetic macular oedema (DME) is the most common cause of visual impairment in patients with diabetes. This condition results from a breakdown of the blood--retinal barrier, leading to vascular leakage, fluid accumulation and thickening of the macula (Schmidt‐Erfurth et al. [2017](#aos14297-bib-0025){ref-type="ref"}). The treatment of DME has undergone a paradigm shift recently. Traditionally, photocoagulation represented the standard treatment, but pharmacologic treatments are nowadays being used as first‐line therapy. All currently available drug therapies for DME are either anti‐vascular endothelial growth factor (VEGF) agents or corticosteroids (Schwartz et al. [2014](#aos14297-bib-0026){ref-type="ref"}). The anti‐VEGF agent ranibizumab (Lucentis; Novartis Pharma, Basel, Switzerland) is approved for the treatment of visual impairment associated with DME. The dexamethasone implant (Ozurdex; Pharm‐Allergan, Dublin, Ireland) achieved similar rates of visual acuity improvement compared with anti‐VEGF agents and is also approved for this indication. Both treatments were associated with improvement in vision‐related quality of life (Gillies et al. [2014](#aos14297-bib-0008){ref-type="ref"}). Recently, a combination therapy was able to provide superiority in means of retinal morphology, but not in means of visual acuity in a phase 2 study. The researchers concluded that it may be beneficial for some patients, but further analysis would be required (Maturi et al. [2018](#aos14297-bib-0019){ref-type="ref"}). Therefore, there was considerable interest in recent research to clarify the mechanisms of DME development and define possible treatment targets (Vujosevic & Simo [2017](#aos14297-bib-0032){ref-type="ref"}). As cytokines play a role in inflammation and neo‐angiogenesis, multiple studies were performed to assess cytokine levels in patients with diabetic retinopathy and DME (Hang et al. [2014](#aos14297-bib-0009){ref-type="ref"}; Sonoda et al. [2014](#aos14297-bib-0028){ref-type="ref"}; Dong et al. [2015](#aos14297-bib-0006){ref-type="ref"}; Hillier et al. [2018](#aos14297-bib-0012){ref-type="ref"}; Yu et al. [2018](#aos14297-bib-0034){ref-type="ref"}). Aqueous and serum cytokine levels seem to be elevated in patients with DME and decrease under treatment with intravitreal bevacizumab or triamcinolone in a short follow‐up time of one month (Sohn et al. [2011](#aos14297-bib-0027){ref-type="ref"}). Although both triamcinolone and dexamethasone are steroids, their structures, availability and half‐lives differ and therefore cannot be compared. To the best of our knowledge, this is the first study investigating differences in cytokine levels during and after treatment with an intravitreal anti‐VEGF (ranibizumab) and a dexamethasone implant over a period of 6 months. The purpose of this pilot study was to provide new insights into changes in aqueous humour cytokines following anti‐VEGF and corticosteroid intravitreal injections in DME and their correlation to retinal morphology and function. These findings may lead to further understanding of the disease process and aid future treatment strategies. Patients and Methods {#aos14297-sec-0006} ==================== This prospective, randomized, controlled, double‐blind pilot study included Caucasian patients with clinically significant diabetic macular oedema (CSME). Patients were randomized into two groups and received either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or one dexamethasone implant (Ozurdex, Pharm‐Allergan) at baseline. All subjects underwent a comprehensive screening examination, including a slit‐lamp examination with indirect funduscopy and measurement of intraocular pressure using Goldmann applanation tonometry. Patients were examined at baseline, visit 3 (week 2), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 16) and visit 8 (week 20). A slit‐lamp and fundus examination and colour fundus imaging were performed. Best corrected visual acuity (BCVA) was assessed using the standard ETDRS visual acuity chart. Central retinal thickness (CRT) measurements were performed at each monthly visit. Optical coherence tomography (OCT) imaging was performed with spectral‐domain OCT by Spectralis OCT® (Heidelberg Engineering, Dossenheim, Germany). The main outcome variables were the changes in cytokine, protein and enzyme levels over time, while changes in BCVA and CRT represented secondary outcome variables. The study protocol was reviewed and approved by the local ethics committee and followed the guidelines set forth in the Declaration of Helsinki. Written informed consent was obtained from patients before inclusion in the study. Subjects {#aos14297-sec-0007} -------- Patients from the outpatient clinic presenting CSME secondary to diabetes were included. The exclusion criteria were therapeutic intravitreal treatment within the last three months or other retinal diseases such as epiretinal membrane, vitreomacular traction syndrome, retinal atrophy or glaucoma. Patients were screened for recent cardiovascular events (3 months prior to treatment) and active infectious disease by medical records. Treatment {#aos14297-sec-0008} --------- The ranibizumab group received a loading dose of four monthly injections (ranibizumab 0.5 mg/0.05 ml); a further two injections were administered in a pro re nata regimen. The dexamethasone group received an intravitreal dexamethasone implant at baseline. All injections and implantations were performed under sterile conditions after preparation of the conjunctiva using 5% povidone--iodine solution, topical anaesthetic and positioning of the lid speculum. All injections were performed in a surgical setting. Aqueous humour sample collection {#aos14297-sec-0009} -------------------------------- Aqueous humour samples were collected at baseline, week 2, week 8 and week 20 before the intravitreal injection of the agent, if an intravitreal injection was performed. After topical anaesthesia application, sterile covering and insertion of an eye speculum, aqueous humour (0.1 to 0.3 ml) was drawn into a conventional tuberculin syringe and samples were stored at ‐20 degrees Celsius until testing. Aqueous humour cytokine, protein and enzyme levels were analysed with a Luminex 100 multiplex array (Luminex Corporation, Austin, TX, USA) (Maier et al. [2008](#aos14297-bib-0018){ref-type="ref"}). The following cytokines, proteins and enzymes were investigated: interleukin 6 (IL‐6), interleukin 8 (IL‐8), monocyte chemo‐attractant protein 1 (MCP‐1), platelet‐derived growth factor (PDGF), VEGF, soluble intercellular adhesion molecule 1 (sICAM‐1), macrophage migration inhibitory factor (MIF), monokine induced by gamma interferon (MIG), matrix metallopeptidase 9 (MMP‐9), plasminogen activator inhibitor 1 (PAI‐1), placental growth factor (PIGF), transforming growth factor beta 1, 2 and 3 (TGF‐beta1,2,3) and soluble vascular cell adhesion protein (sVCAM). Cytokine, protein and enzyme concentrations were determined from standard curves expressed as picogram per millilitre (pg/ml). Statistics {#aos14297-sec-0010} ---------- Statistical analyses were conducted using SPSS software version 21.0 (SPSS Inc., Chicago, IL, USA). Descriptive data are presented as mean and standard deviation. Parameters were checked for normality (Shapiro‐Wilk, p \> 0.05; Q‐Q‐Plot). As normality was not present, the non‐parametric Mann--Whitney U test and Wilcoxon signed‐rank test were used to check for significant differences within each group; the Wilcoxon signed‐rank test was used between time‐points. The significance level was set to p = 0.05 for significant correlations and p = 0.01 for highly significant correlations. Bonferroni\'s correction was applied to compensate for multiple testing. Results {#aos14297-sec-0011} ======= Eighteen eyes of 18 patients with DME were included in this study. The mean age was 66.89 ± 8.80 years in the Lucentis group and 64.56 ± 9.0 years in the Ozurdex group (p \> 0.05). Central retinal thickness (CRT) was similar between the groups at baseline (Lucentis: 440 ± 144 μm; Ozurdex: 471.33 ± 122.60 μm; p \> 0.05). None of the patients showed active systemic or ocular infectious disease or recent cardiovascular events. In the Lucentis group, the ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters). The CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm). No significant changes in CRT or ETDRS BCVA were observed in the Ozurdex group at any time. In the Ozurdex group, one patient was excluded at week 12 and three patients at week 16, due to increased oedema. Table [1](#aos14297-tbl-0001){ref-type="table"} displays BCVA and CRT results. ###### BCVA and CRT for ranibizumab and dexamethasone implant, respectively. P values present comparisons to baseline for each group.   Ranibizumab p Value Dexamethasone implant p Value ----------------------- --------------------------- ----------- --------------------------- --------- BCVA (in letters)  Baseline (mean ± SD) 74.78 ± 14.85 (*n* = 9)   67.22 ± 10.52 (*n* = 9)    Week 2 (mean ± SD) 81.78 ± 9.56 (*n* = 9) 0.021 71.00 ± 13.08 (*n* = 9) 0.160  Week 4 (mean ± SD) 80.33 ± 7.84 (*n* = 9) 0.160 69.38 ± 15.16 (*n* = 9) 0.610  Week 8 (mean ± SD) 83.33 ± 6.33 (*n* = 9) 0.058 77.13 ± 5.59 (*n* = 8) 0.035  Week 12 (mean ± SD) 83.33 ± 7.52 (*n* = 9) 0.038 74.38 ± 6.84 (*n* = 8) 0.260  Week 16 (mean ± SD) 82.44 ± 8.88 (*n* = 9) 0.018 77.00 ± 4.79 (*n* = 5) 0.279  Week 20 (mean ± SD) 84.88 ± 8.88 (*n* = 9) **0.008** 74.60 ± 11.99 (*n* = 5) 1.00 CRT (μm)  Baseline (mean ± SD) 440.89 ± 144.47 (*n* = 9)   471.33 ± 122.60 (*n* = 9)    Week 2 (mean ± SD) 384.67 ± 106.08 (*n* = 9) 0.011 363.78 ± 77.53 (*n* = 9) 0.011  Week 4 (mean ± SD) 381.00 ± 114.64 (*n* = 9) **0.008** 373.75 ± 85.67 (*n* = 9) 0.017  Week 8 (mean ± SD) 376.44 ± 119.24 (*n* = 9) 0.011 353.75 ± 97.13 (*n* = 8) 0.012  Week 12 (mean ± SD) 365.56 ± 106.21 (*n* = 9) 0.011 422.13 ± 142.46 (*n* = 8) 0.092  Week 16 (mean ± SD) 379.33 ± 119.59 (*n* = 9) 0.051 350.20 ± 94.57 (*n* = 5) 0.043  Week 20 (mean ± SD) 363.56 ± 108.54 (*n* = 9) 0.028 370.80 ± 126.90 (*n* = 5) 0.500 p values are displayed for each group. Bonferri correction was used for adjustment for multiple testing. Statistically significant p values after correction are displayed in bold. BCVA = Best corrected visual acuity, CRT = central retinal thickness, SD = standard deviation. John Wiley & Sons, Ltd There were no statistically significant changes in MIF, IL‐6, IL‐8, TGFb1, TGFb2 or TGFb3 concentrations over time in either group. No significant differences were exhibited at any visit between the groups. The levels of sICAM‐1, CXCL9/MIG, sVCAM‐1, MMP‐9, PDGF‐AA and MCP‐1 were significantly altered in the Ozurdex group. After correction for multiple testing, levels of sICAM‐1 (weeks 2 and 8), CXCL9/MIG (weeks 2 and 8), sVCAM‐1 (weeks 2 and 8) and MCP‐1 (week 2) were significantly decreased compared with baseline. The change in sICAM‐1 levels in the Ozurdex group was most prominent at week 2 (173.49 ± 58.84 pg/ml compared with 313.63 ± 192.25 pg/ml at baseline). The CXCL9/MIG level was significantly decreased at week 2 (92.33 ± 77.85 pg/ml) and week 8 (184.69 ± 316.84 pg/ml) compared with baseline (321.96 ± 471.71 pg/ml), respectively. The sVCAM‐1 level was significantly decreased at week 2 (1790.88 ± 1659.45 pg/ml) and week 8 (2037.75 ± 2736.62 pg/ml) compared with baseline (9363.86 ± 14 298.90 pg/ml). The MCP‐1 level was significantly decreased at week 2 (764.04 ± 224.55 pg/ml) compared with baseline (2696.86 ± 2685.72 pg/ml). As Table [2](#aos14297-tbl-0002){ref-type="table"} illustrates, sICAM‐1, PIGF and VEGF levels decreased in the Lucentis group. After correction for multiple testing, the PIGF (week 2) and VEGF (weeks 2 and 8) levels were significantly decreased compared with baseline. The PIGF level was significantly decreased from a baseline value of 6.72 ± 6.42 pg/ml to 1.50 ± 1.41 pg/ml at week 2 (Fig. [1](#aos14297-fig-0001){ref-type="fig"}). The VEGF level was significantly reduced from 135.26 ± 117.99 pg/ml at baseline to values of 4.80 ± 5.81 pg/ml at week 2 and 8.73 ± 7.09 pg/ml at week 8. ###### Groupwise comparison of inflammatory markers by dexamethasone and ranibizumab groups to baseline. P values are displayed for each group. Bonferri correction was used for adjustment for multiple testing   Baseline Week 2 Week 8 Week 20 ----------------------- ------------------- --------------------- ------------------- ----------- ------------------- ----------- ------------------- ----------- ------------------- ----------- ------------------- ------- ----------------------- ------- MIF (mean ± SD) 154.10 ± 209.10 113.20 ± 123.20 152.13 ± 218.23 0.767 102.37 ± 63.54 0.859 85.51 ± 102.49 0.173 75.78 ± 68.30 0.362 89.52 ± 93.02 0.594 157.78 ± 98.03 0.345 sICAM‐1 (mean ± SD) 408.17 ± 317.88 313.63 ± 192.25 284.53 ± 256.19 0.021 173.49 ± 58.84 **0.011** 237.69 ± 150.01 0.086 238.28 ± 181.16 **0.012** 306.33 ± 159.24 0.327 457.38 ± 372.28 0.249 CXCL9/MIG (mean ± SD) 286.62 ± 377.52 321.96 ± 471.71 198.18 ± 307.95 0.161 92.33 ± 77.85 **0.008** 132.26 ± 67.03 0.441 184.69 ± 316.84 **0.012** 346.55 ± 328.66 0.515 365.50 ± 527.83 0.345 PIGF (mean ± SD) 6.72 ± 6.42 6.12 ± 4.96 1.50 ± 1.41 **0.008** 4.63 ± 2.37 0.374 1.79 ± 0.81 0.028 6.88 ± 3.48 0.674 2.91 ± 2.63 0.058 6.33 ± 5.77 0.345 sVCAM‐1 (mean ± SD) 4907.63 ± 8130.80 9363.86 ± 14 298.90 4557.44 ± 8745.29 0.515 1790.88 ± 1659.45 **0.008** 2020.24 ± 1113.85 0.086 2037.75 ± 2736.62 **0.012** 5821.29 ± 9038.60 0.208 16 909.40 ± 26 985.52 0.345 PAI‐1 (mean ± SD) 441.43 ± 330.61 638.37 ± 1065.12 273.36 ± 266.28 0.015 547.49 ± 462.08 0.314 228.37 ± 164.45 0.038 699.29 ± 1036.13 1 301.98 ± 215.42 0.161 847.60 ± 1289.51 0.345 MMP‐9 (mean ± SD) 110.52 ± 123.67 80.30 ± 66.88 104.77 ± 99.41 0.624 30.11 ± 20.82 0.025 119.0 ± 114.43 0.374 29.73 ± 22.54 0.068 121.58 ± 116.03 0.249 94.73 ± 60.95 0.753 PDGF (mean ± SD) 28.71 ± 16.96 25.84 ± 14.89 15.06 ± 10.59 0.011 16.05 ± 5.97 0.093 19.86 ± 10.34 0.441 15.65 ± 5.24 0.063 27.95 ± 7.31 0.917 27.37 ± 9.48 0.043 IL‐6 (mean ± SD) 22.34 ± 29.10 29.26 ± 52.73 17.37 ± 23.98 0.767 5.99 ± 2.57 0.025 8.54 ± 6.96 0.038 9.00 ± 8.42 0.237 12.10 ± 10.44 0.249 39.17 ± 72.76 0.686 IL‐8 (mean ± SD) 15.61 ± 9.95 19.26 ± 16.57 17.40 ± 15.11 0.575 14.44 ± 8.02 0.327 15.08 ± 14.00 0.767 19.26 ± 15.28 0.933 24.83 ± 12.35 0.115 23.52 ± 21.20 0.345 MCP‐1 (mean ± SD) 1706.26 ± 1076.98 2696.86 ± 2685.72 1323.29 ± 1176.57 0.374 764.04 ± 224.55 **0.012** 1261.11 ± 761.87 0.26 932.95 ± 371.60 0.028 2186.18 ± 556.22 0.345 3903.00 ± 4809.97 0.345 VEGF (mean ± SD) 135.26 ± 117.99 149.38 ± 162.01 4.80 ± 5.81 **0.008** 70.60 ± 61.23 0.028 8.73 ± 7.09 **0.012** 75.69 ± 47.33 0.917 5.33 ± 4.55 0.028 84.73 ± 59.02 0.138 TGFb1 (mean ± SD) 49.70 ± 27.87 48.89 ± 47.60 47.57 ± 36.16 0.465 27.30 ± 14.30 0.599 55.08 ± 27.49 0.109 26.18 ± 20.08 0.285 54.98 ± 26.70 1 77.33 ± 108.83 0.08 TGFb3 (mean ± SD) 31.28 ± 11.10 29.53 ± 8.93 28.45 ± 11.28 0.714 21.14 ± 7.01 0.075 29.75 ± 8.62 0.715 18.10 ± 7.87 0.144 31.10 ± 8.40 1 30.44 ± 20.16 0.5 TGFb2 (mean ± SD) 2650.15 ± 1984.40 2135.33 ± 510.61 2410.80 ± 1718.25 0.273 1082.91 ± 659.89 0.046 2710.43 ± 1641.25 0.715 955.38 ± 354.16 0.068 3581.32 ± 1811.68 0.273 2189.87 ± 1138.48 0.893 All results are displayed in pg/mL. p values are displayed for each group. Bonferri correction was used for adjustment for multiple testing. Statistically significant p values after correction are displayed in bold. IL‐6 = iInterleukin 6, IL‐8 = interleukin 8, MCP‐1 = monocyte chemo‐attractant protein 1, MIF = Macrophage migration inhibitory factor, MIG/CXCL 9 = monokine induced by gamma interferon, MMP‐9 = matrix metallopeptidase 9, PAI‐1 = plasminogen activator inhibitor‐1, PDGF = platelet‐derived growth factor, PIGF = placental growth factor, sICAM‐1 = soluble intercellular adhesion molecule 1, sVCAM = soluble vascular cell adhesion protein, TGF‐beta1,2,3 = transforming growth factor beta 1,2 and 3, VEGF = vascular endothelial growth factor. John Wiley & Sons, Ltd ![Scatter plots demonstrating the correlation between inflammatory markers at baseline and week 2 (visit 3) for ranibizumab (blue) and the dexamethasone implant (red), respectively. First line left: IL‐6 (interleukin‐6) levels baseline compared with week 2; first line middle: IL‐8 (interleukin 8); first line right: MCP‐1 (monocyte chemo‐attractant protein 1); second line left: MMP‐9 (matrix metallopeptidase 9); second line middle: MIG/CXCL9 (monokine induced by gamma interferon); second line right: PAI‐1 (plasminogen activator inhibitor‐1); third line left: PDGF (platelet‐derived growth factor); third line middle: PIGF (placental growth factor); third line right: VEGF (vascular endothelial growth factor); fourth line left: sICAM‐1 (soluble intercellular adhesion molecule 1); fourth line middle: sVCAM (soluble vascular cell adhesion protein); fourth line right: TGFb1 (transforming growth factor beta 1); fifth line left: TGFb2 (transforming growth factor beta 2); and fifth line middle: TGFb3 (transforming growth factor beta 3).](AOS-98-e407-g001){#aos14297-fig-0001} Discussion {#aos14297-sec-0012} ========== The aim of this study was to identify and compare changes in cytokine, protein and enzyme levels in patients with DME treated with ranibizumab injections or a dexamethasone implant over a period, of the so‐called loading dose, of 6 months. Results indicate that intravitreal ranibizumab and dexamethasone induce detectable changes in pro‐inflammatory cytokine cascades. There were high intraindividual differences in cytokine concentrations in both treatment groups. The dexamethasone implant exhibited an earlier effect than intravitreal ranibizumab regarding the cytokine and adhesion molecules concentration and affected several additional markers as opposed to intravitreal ranibizumab. In contrast, ranibizumab injected monthly displayed a longer lasting effect. Even if both agents reduced CRT (not statistically significant in the dexamethasone implant group); it was achieved by influencing different regulatory pathways and pro‐inflammatory markers. Previous studies presented different results regarding the changes in levels of cytokines and proteins, such as VEGF, ICAM‐1, IL‐6 or IL‐8, in patients with macular oedema treated with anti‐VEGF or intravitreal triamcinolone (Sohn et al. [2011](#aos14297-bib-0027){ref-type="ref"}). In this study, MIG/CXCL9 levels decreased significantly in the dexamethasone group compared with baseline. As a member of the CXC chemokine family, MIG/CXCL9 is a chemokine, which is a T‐cell chemo‐attractant induced by tumour necrosis factor‐alpha. It was recently investigated in mouse models to play a role in the development of diabetic nephropathy (Zychowska et al. [2015](#aos14297-bib-0035){ref-type="ref"}). Levels of both IL‐8 and IP‐10 (Interferon gamma‐induced protein 10), members of CXC chemokine family, were demonstrated to be higher in patients with DME compared with control groups in previous studies (Sohn et al. [2011](#aos14297-bib-0027){ref-type="ref"}). A recent study associated higher level of IL‐8 with therapy responsiveness, with higher levels of IL‐8 in the therapy refractory group under anti‐VEGF treatment (Kwon & Jee [2018](#aos14297-bib-0017){ref-type="ref"}). Furthermore, the CXC chemokine family is known for its role in angiogenesis (Romagnani et al. [2004](#aos14297-bib-0024){ref-type="ref"}). We did not observe a change in IL‐8 levels during treatment in either group. The MCP‐1 is a member of the CC chemokine family and is one of the key chemokines that regulate migration and infiltration of monocytes and macrophages (Deshmane et al. [2009](#aos14297-bib-0004){ref-type="ref"}). Upregulation or a polymorphism of the MCP‐1 in patients with DME and proliferative diabetic retinopathy (PDR) has been demonstrated in previous studies (Funatsu et al. [2009](#aos14297-bib-0007){ref-type="ref"}; Roh et al. [2009](#aos14297-bib-0023){ref-type="ref"}; Oh et al. [2010](#aos14297-bib-0022){ref-type="ref"}; Dong et al. [2014](#aos14297-bib-0005){ref-type="ref"}). Results of the current study indicate that MCP‐1 was affected by the dexamethasone implant at the first follow‐up for aqueous samples but was not statistically significantly reduced later. That may be explained by the complex pathway of MCP‐1 activation and newly investigated polymorphisms, which are not fully understood in various diseases and may not be fully affected by the application of dexamethasone in the vitreous (Jo et al. [2003](#aos14297-bib-0014){ref-type="ref"}; Deshmane et al. [2009](#aos14297-bib-0004){ref-type="ref"}). Intercellular adhesion molecule 1 and VCAM‐1 are adhesion molecules, which can be induced by interleukin‐1 (IL‐1) and tumour necrosis factor, and are expressed by the vascular endothelium, macrophages and lymphocytes. They facilitate leucocyte‐endothelial transmigration and play an essential role in diabetic vascular leakage and capillary non‐perfusion and can be pro‐angiogenetic factors (Jo et al. [2003](#aos14297-bib-0014){ref-type="ref"}; Tang & Kern [2011](#aos14297-bib-0029){ref-type="ref"}). Current data suggest that VCAM‐1 and ICAM‐1 levels are elevated in diabetic patients with microalbuminuria and diabetic retinopathy (Meleth et al. [2005](#aos14297-bib-0020){ref-type="ref"}; Karimi et al. [2018](#aos14297-bib-0016){ref-type="ref"}). Therefore, it may be useful as a prognostic factor; however, a study by Ugurlu et al ([2013](#aos14297-bib-0030){ref-type="ref"}) did not reveal a difference in ICAM‐1 and VCAM‐1 levels in diabetic patients with and without diabetic retinopathy. It must be considered that the levels of these adhesion molecules may vary among patients; therefore, statistical significance may not be evident in small cohorts. In our study, we demonstrated the anti‐inflammatory influence of dexamethasone on sICAM‐1 and sVCAM‐1 levels. It can be argued that these factors may be useful for treatment monitoring in patients with DME. These results on sICAM‐1 match the results of a study where ICAM‐1 was found to be asscociated with disease severity of macular oedema (Hillier et al. [2017](#aos14297-bib-0011){ref-type="ref"}). A homologue of VEGF and PIGF plays a role as an angiogenesis mediating factor in diabetic retinopathy. PlGF can affect the growth, migration and survival of endothelial cells via different mechanisms, such as binding directly to the vascular endothelial growth factor receptor‐1 (VEGFR‐1), displacing VEGF‐A from the transmembrane or soluble VEGFR‐1, activating more VEGFR‐2 via VEGF‐A and by the formation of a PlGF/VEGF‐A complex (Van Bergen et al. [2019](#aos14297-bib-0031){ref-type="ref"}). Knockout mice models suggest that the deletion of PIGF prevents diabetic retinopathy (Huang et al. [2015](#aos14297-bib-0013){ref-type="ref"}). Furthermore, PIGF seems to be associated with diabetes‐activated hypoxia‐inducible factor‐1*α*‐VEGF pathway inhibition. In anti‐VEGF treatment, arm levels of VEGF and PIGF dropped after injections; therefore, a relation of the two factors is conclusive, as mentioned above (Fig. [2](#aos14297-fig-0002){ref-type="fig"}). Conversely, a study analysing patients with PDR receiving anti‐VEGF treatment did not demonstrate any changes in PIGF levels under treatment, although PIGF levels were elevated in patients with active PDR compared with non‐active PDR (Al Kahtani et al. [2017](#aos14297-bib-0001){ref-type="ref"}). It can be hypothesized that these differences may be caused by different mechanisms in DME and PDR. A combination therapy of VEGF and PIGF inhibition may provide superior outcomes in certain patients (Nguyen et al. [2018](#aos14297-bib-0021){ref-type="ref"}). ![Box plots demonstrating changes in PIGF (placenta growth factor), PDGF (platelet‐derived growth factor) and VEGF (vascular endothelial growth factor) for ranibizumab (blue) and dexamethasone implant (red), respectively.](AOS-98-e407-g002){#aos14297-fig-0002} In a previous study, triamcinolone showed an effect on VEGF by decreasing its levels after injections (Sohn et al. [2011](#aos14297-bib-0027){ref-type="ref"}). In experimental settings, corticosteroids inhibited vascular permeability via ICAM‐1 or VEGF downregulation (Wang et al. [2008](#aos14297-bib-0033){ref-type="ref"}). We did not see this effect on VEGF but on sICAM‐1. It can be hypothesized that this is due to using dexamethasone, not triamcinolone as in previous studies, or the sample size was too small to detect this change. Recently, a study has demonstrated a correlation between serous cytokine levels and the morphological response during anti‐VEGF treatment in patients with DME (Brito et al. [2018](#aos14297-bib-0003){ref-type="ref"}). We observed some trends in our study. However, there were individual changes in several cytokine levels over time. In the ranibizumab group, two patients were identified, showing an initial reduction of anti‐VEGF levels, an increase near week 2 and a recurrence of macular oedema, which responded well to the next ranibizumab injection. Furthermore, interleukin 6 and 8 levels were not observed to decrease as opposed to patients without repeated macular oedema. In the Ozurdex group, we noticed two patients with decreasing cytokines levels, but without morphological or functional changes. Hyperreflective foci (HRF) in the macular cysts in these patients were revealed by optical coherence tomography (OCT). These well‐demarcated morphologic changes characteristic for DME have been described in previous studies and were suggested to represent extravasated lipoproteins, which are an early subclinical barrier breakdown sign in DME (Bolz et al. [2009](#aos14297-bib-0002){ref-type="ref"}). The HRF were found in several patients in both groups, but the patients without functional response showed HRF in the cysts and cyst borders (Fig. [3](#aos14297-fig-0003){ref-type="fig"}). It can be hypothesized HRF in retinal cysts seem to represent an advanced morphologic alteration that does not respond to dexamethasone (Jonas et al. [2012](#aos14297-bib-0015){ref-type="ref"}). ![Example of a patient treated with a dexamethasone implant with cytokine response at week 2 and missing morphological improvement. (A) Baseline optical coherence tomography (OCT) scan. The arrows mark the hyperreflective foci at the cyst borders. The star marks the intraretinal partly fibrotic tissue. (B) OCT at week 2. Cytokine levels decreased, but morphological and functional outcomes remain similar. (C) OCT at week 20. Cytokine levels increased after three months. Increased clinically significant macular oedema.](AOS-98-e407-g003){#aos14297-fig-0003} In our study, a statistically significant difference in BCVA and CRT was not observed for the Ozurdex group, probably due to the small sample size. Previous studies, as described in a meta‐analysis, showed statistically significant effect on the CRT (He et al. [2018](#aos14297-bib-0010){ref-type="ref"}). A control group of subjects without DME was not included in the study, which could limit further interpretation. Previous studies show, that the concentrations of various cytokines were significantly different between healthy patients and patients with DME (Jonas et al. [2012](#aos14297-bib-0015){ref-type="ref"}; Kwon & Jee [2018](#aos14297-bib-0017){ref-type="ref"}). As we focused on the changes in cytokine levels during two different treatments regimens in DME, no control group was used. Furthermore, only one dexamethasone treatment was performed in this study as the effects of the loading phase of both agents were observed. However, a significant impact of the therapeutic agent on retinal morphology and cytokine levels was indicated. In a recently published study comparing the morphological changes and visual acuity of patients with persistent DME having an intravitreal injection of ranibizumab alone and combined with a dexamethasone implant, the results revealed that the combined therapy does not lead to a significantly higher increase in visual acuity than the ranibizumab monotherapy (Maturi et al. [2018](#aos14297-bib-0019){ref-type="ref"}). However, it must be considered that dexamethasone was administered after a loading dose with ranibizumab -- as opposed to this study. Even in the cited trial with a follow‐up of only six months, there was a significantly higher and faster decrease in CRT in the combination group, which could have an impact on retreatment frequency and visual outcomes in the long term. Above all in chronic disease, such as DME, morphologic parameters detectable by OCT can be considered as more reliable end‐points than function, which depends on the individual duration and level of intraretinal and intracecullar alteration. In conclusion, this proof of principle study identified cytokines and proteins that are sensitive to treatment with anti‐VEGF or dexamethasone and monitored the levels during the loading phase of 20 weeks. Ranibizumab has a significant, long‐acting impact on VEGF and PIGF levels. Dexamethasone has a fast‐acting impact on levels of additional cytokines and proteins, such as sICAM‐1, CXCL9/MIG, sVCAM‐1 and MCP‐1. Our findings underline several cytokines and proteins involved in the complex and diverse molecular pathway of the emergence of DME. Both agents, ranibizumab and dexamethasone, seem to address different pro‐inflammatory markers to a very individual degree that indicates a rationale for a combination therapy in cases of CSME. Further studies will be necessary to validate the results of our proof of principle study. [^1]: These authors contributed equally to this work.
Q: x-editable (twitter bootstrap): how to change the empty value? I'm using the x-editable plug-in to have in-place edits and it works well. The following jsfiddle shows an example from their documentation: http://jsfiddle.net/ibrahima_yock/CFNXM/27/ <div> <span>Status:</span> <a href="#" id="status"></a> </div> . //make status editable $('#status').editable({ type: 'select', title: 'Select status', placement: 'right', source: [ {value: 1, text: 'status 1'}, {value: 2, text: 'status 2'}, {value: 3, text: 'status 3'} ] }); As you can see in the jsFiddle, in the html pane the status is "empty" (written in red). We'd like to translate that word into another language. How can we specify it? A: You just add this option when setting up the field: emptytext: 'Leer', // default is 'Empty' Fiddle: http://jsfiddle.net/Saran/hdVYS/ You can find other options in the documentation. A: For those who prefer to use attributes, data-emptytext is another way to accomplish this: <a href='#' id='status' data-placeholder='This text appears when editing' data-emptytext='This text appears when field is empty'> </a>
255 U.S. 268 (1921) EDWARD RUTLEDGE TIMBER COMPANY ET AL. v. FARRELL. No. 172. Supreme Court of United States. Argued January 21, 1921. Decided February 28, 1921. APPEAL FROM THE CIRCUIT COURT OF APPEALS FOR THE NINTH CIRCUIT. *269 Mr. Stiles W. Burr, with whom Mr. Charles W. Bunn and Mr. Charles Donnelly were on the briefs, for appellants. Mr. S.M. Stockslager, with whom Mr. E.O. Conner was on the brief, for appellee. MR. JUSTICE McREYNOLDS delivered the opinion of the court. Claiming equitable title thereto under the homestead laws, appellee's predecessor, Delany, instituted this proceeding in the United States District Court for Idaho to compel the appellants to hold certain lands, patented to the Railway Company, as trustee for him. The insistence is that patent should not have issued to the Company, notwithstanding the attempt to make selection under the Act of March 2, 1899, c. 377, 30 Stat. 993, prior to initiation of any homestead right in the land, because (1) it was then unsurveyed and not designated with reasonable certainty, and (2) it was within a district survey of which had been applied for by the State of Idaho under Act of August 18, 1894, c. 301, 28 Stat. 372, 394. The District Court decided both points in favor of appellants and dismissed the bill; the Circuit Court of Appeals held against them on the first but did not consider the second point. 258 Fed. Rep. 161. The facts pertinent to the first point are substantially the same as those presented by the record in West v. Rutledge Timber Co., 244 U.S. 90, except that here the land *270 was 7 1/2 miles from any known survey while there the distance was 3 1/2 miles. The Land Department found the description sufficient for reasonable certainty and we see no adequate ground for disregarding that conclusion. As the district designated by Idaho for survey contained very much more land than the State was entitled to select, the Land Department refused to consider the application. No appeal was taken. Upon an analysis of pertinent statutes, opinions of the Land Department and of this court, the District Court held that the mere filing of application for survey did not so far withdraw the land from the public domain as to make the Railway's selection wholly ineffective; and further, that if valid for any purpose, the application merely gave an option to select, never exercised in respect of the land now in dispute. We agree with the conclusion reached; and in view of the careful supporting opinion further discussion seems unnecessary. The decree of the Circuit Court of Appeals must be reversed and the decree of the District Court affirmed. Reversed.
Friday, July 14, 2017 Classic Doctor Who: ranked & reviewed (#30 - #21) Continuing my countdown of Classic Who serials, from my least-liked to my most-loved. (For the previous ten, click here; to start from the top, click here. Or if you're looking for a particular serial, you can jump right to the index.) As we enter my top 30, maybe this is a good time to discuss "lost serials," as some of my favorite stories remain missing. Recently, I heard a Whovian dismiss the lost serials by insisting, "There's no way of knowing what they're really like." Of course there is. If the surviving audio is engrossing, if the telesnaps and production photographs reveal a credible design, if the director's talents are well-established or the dialogue feels well-played and well-paced (suggesting he had a good grip on the material), then the reconstructions tell you most of what you need to know. Since I started watching Doctor Who, quite a few missing episodes have been unearthed, and not once has a discovery made me radically rethink my impression of a serial. My favorite Cybermen story, my two favorite Dalek stories, and my four favorite historicals are partially or fully missing. Let's pray they're someday recovered, but in the meantime, the lack of video footage doesn't impair my enjoyment. 30. The Pirate Planet (Fourth Doctor, 1978)written by Douglas Adams directed by Pennant Roberts After a season where the writers flounder so with the character of Leela, it's gratifying to see how clearly and convincingly her follow-up, Romana, is defined. And the characterization is cunning. For over a season, Tom Baker had been disengaging from the material; in Romana, the creative team invent a character whose own aloofness forces Baker to pick up the slack. But even if they realized how useful Romana would be, they couldn't have envisioned how gloriously funny Mary Tamm would be in the role -- as she is, frequently, in "The Pirate Planet," whether she's rattling the Doctor (referring to his TARDIS as a "capsule"), barking orders to K-9, or deferring to guards who are determined to arrest her. Forced into a squad car -- "Get in!" -- her politely imperious response is "I shall take that as an invitation"; Romana makes everything work on her terms. And speaking of everything working, "The Pirate Planet" is like an overstuffed goodie bag. It's not the first Who with a "throw it against the wall" mentality, it's merely the first one where everything sticks: air cars, linear-induction corridors, planets within planets -- plus the ultimate in dog vs. bird smack-downs. In an in-joke best seen in hindsight, Adams, then completing his first set of scripts for Hitchhiker's Guide to the Galaxy, has Romana and the Doctor do their own version of the famed hitchhiking scene in It Happened One Night. The serial may be called "The Pirate Planet," but it's Adams who's the real pirate, willing to plunder anything in the interest of self-amusement, and he keeps the surprises coming until about twelve minutes to the end, at which point the serial falls apart in a lengthy coda of explosions and exposition. But until that point, it's sublime. It's remembered for the heavy doses of Adams humor -- and indeed, the bright lines and visual gags, underscored by a production design steeped in primary colors, are memorable. But underpinning all that is one of the darkest concepts in the classic catalog: a monarch who will literally crush whole galaxies to extend her longevity. And the fury that inspires in the Doctor grounds the serial. ("You commit mass destruction and murder on a scale that's almost inconceivable and you ask me to appreciate it? Just because you happen to have made a brilliantly conceived toy out of the mummified remains of planets?") All the usual caveats about Pennant Roberts' direction apply -- some mealy acting among the supporting cast, some shoddy effects -- but perhaps his brand of well-meaning scrappiness is just what's called for. With a more smooth technician at the helm, "Pirate Planet" would have been more polished, but would it have been more fun? You don't reach into a box of crackerjacks hoping to find a real diamond. 29. Mawdryn Undead (Fifth Doctor, 1983) written by Peter Grimwade directed by Peter Moffatt A schoolboy, an immortal, and the Brigadier go into a transmat capsule. No, it's not some off-world joke, but an astonishingly facile piece of work by Peter Grimwade. Three story-lines that each could've carried a serial – three story-lines that, on the face of it, you can't imagine wedded into one -- are woven together in spectacular fashion. In the best of these, two time streams unfold simultaneously, as key scenes between Tegan and the Brigadier in 1977 play out as memories of the Brigadier in 1983; it's the kind of conjuring trick NuWho does often, but rarely better. One of Grimwade's niftiest notions -- of two Brigadiers trapped on one spaceship but repeatedly missing each other -- calls for the kind of flair and precision that exceeds Moffatt's grasp, but the story succeeds despite him -- and occasionally because of him. "Mawdryn Undead" is the rare serial -- like "Ambassadors of Death" and "Deadly Assassin" -- that's enhanced by having a writer and a director whose styles are a bit of a mismatch. Grimwade takes his cue from the Fifth Doctor's demeanor, writing brief scenes in bold strokes, but Moffatt, by then comfortably into his 60's, liked to luxuriate, and here, for the most part, his methodical pace gives weight to all the themes Grimwade is juggling. It lets them breathe, and makes the character beats more meaningful, as in the reunion between the Doctor and the Brigadier, which takes place over a civilized cup of tea. As in "Time-Flight," Grimwade captures a Doctor forever thinking fast on his feet: always the first one in and out of every room, leaving his companions in his dust. (Climbing a hill to the transmat capsule, the Doctor implores the Brigadier, "Come on!" -- although the poor man looks a good twenty years his senior.) "Mawdryn Undead" really only suffers in two departments: one minor, the other not so much. Sarah Sutton seems at sea throughout, caught between the girlish responses that were so lovely in her first full season and her attempts to mature her character gracefully in her second. Fiona Cumming, a more communicative director, had helped Sutton hone in on artful ways of doing so in "Snakedance," but here, left to her own devices, you see her struggling. Tegan says something dry, and Nyssa's normal response would have been to suppress a giggle, but here Sutton strains to find something suitably "adult," and is left nursing a blank stare. That's an issue, but it's a minor one. Not so minor is that Grimwade doesn't have enough material for four episodes -- or rather, he tells too much of his story too quickly -- and once Mawdryn and his cohorts confront the Doctor at the end of Part Three, it's all time-killing devices until the final "zap" that resolves the story-line. Yet despite the limitations of the director and one of the supporting players, and a final act that winds up being equal parts padded and preposterous, "Mawdryn Undead" remains a heady trip. 28. The Leisure Hive (Fourth Doctor, 1980)written by David Fisher directed by Lovett Bickford What's the expression: "I woke up one day, and realized I was old"? Age sneaks up on you, and so does Bickford's camera. He alternates between swiftly-edited images and languorous pans that keep you off-balance, starting with the famed 92-second tracking shot of Brighton Beach that opens the serial. Fisher's script is full of good ideas, chief among them a race of people who've been decimated and displaced by war, opening their doors to the universe to encourage harmony and discourse. But mostly, it's a serial that asks: how would you prefer to die? Would you like to live a long life but deteriorate slowly over time? Or would you rather go suddenly, and sooner? It's a grim topic, and Bickford amplifies your unease, playing with angles and perspective, building suspense at the unlikeliest times. At one point, Romana and the Doctor have been tethered to opposite ends of the Doctor's scarf, and when she reaches the TARDIS, she pulls on it slowly, thinking she's reeling in the Doctor -- but is she? Later, the scarf comes into play again when the Doctor is instructed to follow it through a crowd, and we have no idea what he'll discover on the other end. (Fittingly, it's a dead body.) A man rushes into the recreation room, fearing he's been followed; is he alone or being hunted? Will the uncertainty kill him slowly, or will his pursuer kill him quickly? Even the establishing shots are disorienting; is Bickford simply pausing a moment between scenes, or is there something out there watching? "The Leisure Hive" is extraordinary unnerving, and why not? It's a serial about aging, and isn't that the most unnerving topic of all? No one listens to the old; the old are invisible -- as the Doctor discovers when he himself is aged by several centuries. And just as Pangol, the young revolutionary, won't heed the advice of the elderly matriarch Mena (Adrienne Corri, in a moving performance that eschews vanity and camp), no one pays any mind to the declining Doctor; Romana usurps his traditional role in the story-line, adopting the scientist Hardin as her assistant and companion -- and the Doctor is promptly put out to pasture. These days it's become commonplace for NuWho to tip its hat to the classic series; occasionally a whole episode seems a throwback to the Pertwee or Baker or McCoy era. "The Leisure Hive," conversely, is one of the few classic serials that anticipates NuWho. The direction, production design and camerawork are cutting-edge, the themes are adult and provocative, and the results are wholly disquieting. Only the final scene wraps up much too quickly -- as if the crew were about to go into overtime, and the creative team was forced to stop filming and edit what they had. You're left feeling deflated -- but perhaps that's appropriate: in life, as in art, things do just "end." Death isn't tidy. "The Leisure Hive" is exquisite entertainment; it's a serial that, fittingly, has aged very well. 27. The Ice Warriors (Second Doctor, 1967)written by Brian Hayles directed by Derek Martinus If there must be monster stories (and, of course, there must), could they all be directed as well as "Ice Warriors"? In anyone else's hands, the serial might have melted into a puddle of goo, but Martinus holds it together in his nerviest style. He sets the opening credits against stills of snowy and icy vistas, stalactites to the fore, with a theremin wailing -- like a siren singing an octave higher than she should. Is it designed to set the mood? No, it's designed to disarm you. We cut to two guest stars and a dozen extras rushing around a circular set of computer banks, as a different kind of siren blares so loudly it obscures half their lines. A minute or two later, we sneak outside to eavesdrop on an expedition, but the wind keeps drowning out their conversation -- and suddenly, there's the TARDIS, materializing on its side, sliding down a snow bank until it lands with a thump -- on its head. Martinus's visual approach is bold and relentless; if "Evil of the Daleks" showed he could weave disparate plot strands into something cohesive, "Warriors" proves he can take a potentially stagnant story and dazzle. He never lets up, and neither does the weather: the wind keeps whipping, the snow is forever blowing and drifting, and every eight seconds, the sound of the snow siren anticipates another avalanche. When the Ice Warriors finally appear, his camera inspects every inch of them: their faces, their torsos, their claws. The director's fascination ensures our own -- and to Hayles' credit, although his assignment was "give us a new monster," he understands that the true monsters are those in human form: here, the ones who destroy each other in the name of science. At the heart of "The Ice Warriors" is a frosty relationship desperately in need of thawing: between the imperious Leader Clent (Peter Barkworth, a triumph of method-acting mannerisms) and his canny but erratic chief scientist Penley (Peter Sallis, all avuncular scruffiness). "The Ice Warriors" feeds off those characters; at its core, it's not about a crisis that pits humans against Ice Warriors -- it's about a crisis that allows two men to resolve their differences. Like another free-lancer, Ian Stuart Black, Hayles intuitively understood the strengths of the principal cast and how best to highlight them, and the Doctor, Jamie and Victoria are all well-served. (While Deborah Watling wasn't the strongest actress to join the TARDIS crew, she's ideally cast in the role David Whitaker designed for her: someone to bring out the Doctor's softer side and Jamie's protective and occasionally flirtatious nature. They both become more dynamic characters because of her.) Best-remembered as the "monster" season, Season 5 isn't most memorable for the monsters at all, but for the people fighting them -- and "The Ice Warriors" is the purest example. 26. The Greatest Show in the Galaxy (Seventh Doctor, 1988)written by Stephen Wyatt directed by Alan Wareing The story from the final two seasons that best showcases Sylvester McCoy, and not the Doctor that script editor Andrew Cartmel wishes he were. McCoy had shown enormous agility and charm throughout Season 24; at the top of Season 25, Cartmel reinvents the Doctor as a cunning mastermind -- not a bad idea, but one that does little for McCoy. He's forced to barrel his way through serials with ferocity and authority that don't come easy to him, and too often (most notably in "Ghostlight"), he turns to gurning as a substitute for rage. And from a pure plotting perspective, a Doctor who knows most of the answers going in, but has no time for explanations, frequently renders the supporting cast superfluous. (It happens to one of the series' best batch of featured players, in "Remembrance of the Daleks.") But "Greatest Show" is a marvelous vehicle for McCoy. It's not just the magic act that consumes most of the final episode, and that only McCoy could pull off; it's how the Doctor is caught off guard for much of the serial, and the nimble ways in which McCoy recovers. It's him stumbling out of the TARDIS at the start, and later tumbling into his seat under the big top. It's the thrill and embarrassment he conveys when told it's his turn to perform. And more than any specific moment, it's Wyatt's understanding that the Seventh Doctor triumphantly belongs among the misfits who frequent -- and work at -- the circus. Alan Wareing directs with the showmanship of a P.T. Barnum; the fragmented story-telling of the late McCoy era seems particularly suited to its procession of circus acts, but "Greatest Show" never feels frantic. On the contrary: it takes its sweet time, savoring every absurdity. The Doctor and Ace don't even reach the circus until Part 2, but the first episode is filled with so many memorable moments, you don't mind a bit. Part 1 also has one of the great character-based cliffhangers, in which the Doctor asks Ace, "Well, are we going in or aren't we?" Ace, for a change, isn't being swept along by events beyond her control, forced to confront her demons. She's simply being given an opportunity, and the serial asks: will she seize it? 25. Image of the Fendahl (Fourth Doctor, 1977)written by Chris Boucher directed by George Spenton-Foster Giddy, foolish fun. The rare Who serial that's no more than the sum of its parts, and perhaps just a bit less, but my, those parts are marvelous. In its resurrection of an ancient evil thought to have been destroyed by the Time Lords, it mixes religion, science, myth and mysticism into a brew so heady that it's intoxicating. On the surface, there's nothing remarkable about it – but that's by design. For the final serial of the Fourth Doctor's gothic period, Boucher serves up stock ingredients of the genre -- the pentagrams and cults and creatures feeding on the life force -- with characters that are staples of fiction: the clairvoyant old lady and her shotgun-wielding grandson; an evil mastermind who proves merely an innocent dupe; his officious colleague who turns out to be the evil mastermind. They're types, all of them, but Boucher's robust approach reminds you why they're enduring (and the actors pitch them perfectly). And Boucher comes armed with two secret weapons -- two opposing perspectives -- whose push and pull on the viewer is relentless and exhilarating. On one side, there's Leela, Boucher's own creation, as only he can script her: overflowing with insight the Doctor mistakes for intuition -- at times, her knife raised and primed for battle, ready to respond to any threat, real or perceived; elsewhere, comforting and almost nurturing, at one point consoling the Doctor as if cradling a lost child. On the other side, Adam Colby (an irrepressible turn by Edward Arthur), equal parts scientist and sexpot: a dapper cynic, dripping with sarcasm, who responds to each crisis, wittingly or not, by undoing another shirt button: suffering captivity like a stripper in a cage. Leela, warrior of the Sevateem tribe, is a passionate defender of powers beyond our comprehension -- albeit with an unquenchable thirst for knowledge; Colby comes down firmly on the side of logic and reason, suspicious of anything he can't see, hear or touch -- until the Doctor makes him a convert. (One moment, he's tied to a post, staring at disbelief at the manifestation of the Fendahl core; the next, he's assisting the Doctor in his info-dump, not merely accepting but fascinated.) They're fully-formed creations, and through them, "Image" manages to both honor and mock the horror genre, often in quick counterpoint. "Image" is the rare serial that gets wilder and more wonderful as it goes along, and by the end, as images of the Fendahl are appearing and vanishing throughout the priory, and as the Doctor is offering up not one, not two, but three possible explanations for the mayhem at hand, you find yourself almost in a state of bedazzled delirium. (When it's done, you can imagine fanfic where Adam Colby joins the TARDIS team for a few adventures, before the Doctor and Leela deposit him back on Earth on their way to Pluto.) 24. Spearhead From Space (Third Doctor, 1970)written by Robert Holmes directed by Derek Martinus UNIT has become such a fixture in the Who-niverse that it's easy to overlook the challenges Robert Holmes faced in penning Pertwee's debut. He had to convince viewers used to spiriting through time and space that it would be fun to set up shop on Earth for a while. He had to sell a reboot that essentially undid the show's premise. And he does so almost effortlessly, with a story that's as much character study as adventure. "Spearhead" is often dismissed with complaints that "the Doctor's hardly in it" -- but that's precisely the point. We don't need to meet the Doctor right away; we expect to like him. The "troubled regeneration" story lets the show first establish the team who'll be joining him, reassuring us (by the time the Doctor is back on his feet) that they're worthy. And not worthy of joining him, in this case, but of him joining them. Holmes not only successfully introduces Liz Shaw and reintroduces the Brigadier, but he manages some nice reversals along the way. The Brigadier and the Doctor previously enjoyed a cordial camaraderie; by the end of "Spearhead," the new workplace environment triggers an amusing alpha-male rivalry. And conversely, Liz starts off as a skeptic, but ultimately, her scientific curiosity and a weakness for the Doctor's charms turn her into his champion. Derek Martinus's previous Who serial, "Ice Warriors," was all grand effects; this one is subtle gestures. He's careful not to overplay his hand or overdramatize events; as his camera fairly floats along on Dudley Simpson's jazz-infused score, he teases as much as he delivers, suggesting that the factories and field HQ's of Earth can be just as tantalizing as far-off alien planets. "Spearhead" promises a look that only rarely reemerges in the Pertwee era, but Martinus's darting camerawork ensures it's a look so elusive that you've practically forgotten it by the time the serial winds down. As such, it's the best broken promise in Who history. 23. The Myth Makers (First Doctor, 1965)written by Donald Cotton directed by Michael Leeston-Smith A delight. Doctor Who, already adept at turning history into stories, now flips the script, as the Doctor turns a story into history. In Episode 1, the TARDIS sets down during the Trojan War; the Doctor is mistaken for Zeus and brought before Agamemnon and Menelaus. It's novel and entertaining, but you feel like it's not quite enough to build a script on. It's not: it's all preamble. In Episode 2, Cotton shifts his attentions to Troy and introduces King Priam, his daughter Cassandra and his son Paris, and this dysfunctional family both grounds and ignites the story. It's Doctor Who as ethnic sitcom, at that spot where insult humor and character comedy intersect. High Priestess Cassandra, with a voice pitched to the mezzanine, warns Paris, "The augeries were bad this morning. I woke full of foreboding," and Paris deadpans to the studio audience, "Never knew her when she didn't." Cotton weaves wicked variations around The Odyssey and The Aeneid. Cassandra has had a vision of the fabled Trojan Horse: "I dreamed that out on the plain the Greeks had left a gift, and although what it was remained unclear, we brought it into Troy. Then at night, from out its belly, soldiers came and fell upon us as we slept." Except that Paris has found the TARDIS on the plains and brought it into Troy, and everyone presume that's the gift of which she's dreamed. (And indeed there is someone inside: Vicki, who emerges sheepishly.) Back at the Grecian camp, Odysseus has charged the Doctor with helping the Greeks sack Troy; eager to avoid turning the legend of the Trojan Horse into fact, the Doctor improvises madly (Hartnell at his funniest), suggesting a fleet of flying machines that could be catapulted, one man at a time, over the Trojan walls. But when told he'll be making the test run himself, he changes his tune ("I'm afraid we must face up to it, Odysseus: man was never meant to fly") and defaults to a hollow wooden horse. The brilliance of Cotton's conceit is that he doesn't tell the story of the Greeks invading Troy; he tells the story of Troy being invaded. One by one, everyone heads to Troy -- of course they do: that's where all the fun is. And only then, once everyone we care about has arrived, does the slaughter commence. 22. The Awakening (Fifth Doctor, 1984) written by Eric Pringle directed by Michael Owen Morris Eric Pringle was reportedly displeased with script editor Eric Saward's rewrites, branding the result rushed and confusing. But "The Awakening" is neither; on the contrary, it's one of the most buoyant of all the classic serials. On the surface, it's about a town turning history into pageant, and a man who's made a deal with the devil (it's "The Daemons" done right). But underneath, it's about a town that falls prey to autocratic rule: its four key players representing -- in turn -- authority, loyalty, obedience and dissent. Pringle has fifty minutes to tell a dense story, and a lot of tricks up his sleeve: the giant crack in the wall, and the ghoulish face that appears behind it; the ancient battle cries that engulf a church, and the boy who emerges from that battle, all the way from 1643; the apparition that crouches, still and silent, in a corner of the TARDIS -- then crooks its head to make sure you're still watching. But the tricks never feel obvious or oppressive; Morris lingers on them just long enough to make his point, then moves on. And occasionally he bathes them in the sun. Morris would go on to helm the best of Davison's Campion mysteries, "Flowers for the Judge"; here, in his first (and only) Who assignment, he finds a tone and tempo that seems sculpted to Davison's demeanor. Like many of the best Fifth Doctor serials, "The Awakening" has a beguiling sense of wonder, but there's also a precociousness that bleeds, beautifully, into Davison's performance. At one point, the Doctor escapes captivity with a schoolboy prank; later he's in the TARDIS with the town schoolteacher, and he throws her looks that say "Why are you in my room?" and "Don't touch my things." He's both rebel and lawman: equal parts schoolboy, instructor and headmaster -- and he's marvelous. There's only one moment in "The Awakening" that "rushed and confusing," and it's Saward's sci-fi explanation for the creature taking over the town. Pringle characterizes him as "the devil," but never a fan of the mystical, Saward explains it away with reconnaissance missions, alien invasions, psychic projections and rocks "mined by the Terileptils on the planet Raaga for the almost exclusive use of the people of Hakol" -- all of which Davison shrewdly recites so fast that he renders it unintelligible. And at the end, Morris does him one better: when the adventure is over, and the Doctor starts to wrap it up with even more of Saward's sci-fi mumbo-jumbo, the camera cuts away midway through his speech to the reunion of Tegan and her grandfather, refusing to let anything as dreary as "explanations" dampen the mood. Pringle might have feared Saward was ruining his script, but the star and the director don't give him the chance. 21. The Wheel in Space (Second Doctor, 1968)written by David Whitaker directed by Tristan deVere Cole The direction is striking, the set design imaginative, the costumes effective -- but it's the characters that linger. Whitaker plots the Cybermen's return as a slice-of-life drama, about a group of people aboard a space vessel in the future, examining the effects that a brutal attack can have on everyday people, and exploring our varying capacities to cope and carry on. And he uses the Cybermen's defining trait -- their suppression of human feeling -- to cast a critical eye towards mankind and observe how our own emotions define us: how they deepen us and how, sometimes, they destroy us. The Cybermen's very duality -- part robot, part human -- becomes the gauge by which Whitaker measures his own characters, and never more so than with Zoe Heriot, the young astrophysicist who's set to become the next companion. Zoe, the product of a mind-controlling parapsychology program, has never properly developed human emotions; a fellow crewmember refers to her as "a robot, a machine" -- not unlike how the Doctor describes the Cybermen. ("They were once human beings like yourself, but now they're more robot than man.") Zoe is fundamentally (but not fatally) damaged, and so is the ship's controller, Jarvis Bennett, who's undergoing a nervous breakdown. A lot of commanders in Doctor Who are stricken with "why-won't-they-listen-to-reason" sickness -- it's how the writers sustain the story-line, by having those in authority refuse to heed the Doctor "until it's too late." But Bennett's stubbornness in ignoring the Doctor's warnings isn't used for plot purposes; it simply serves as another example of the tug-of-war between logic and emotion that humans and Time Lords (unlike Cybermen) have to endure. "The Wheel in Space" is about how people of different backgrounds and varying aptitudes respond to stress and crisis, and Whitaker is careful not to editorialize his characters. His style is refreshingly dispassionate. He simply captures the cadences of everyday speech -- the joking, bickering, flirting and fussing -- and allows us to draw our own conclusions. "Wheel in Space" is the unusual serial where you believe the characters had a life before we met them, and that they'll have one after we leave; it's the rare Who with a shipload of people where none feel interchangeable. It continues the tradition of multi-cultural casts of which Cybermen creators Kit Pedler and Gerry Davis were so fond, but here it's done with a lightness of touch that's refreshingly P.C. The characters' shared experience and shared humanity define them more than their accents. Fittingly for a serial that stresses character over carnage, the final shot of "Wheel in Space' is of two crew members from different countries -- an English man and a Russian woman -- holding hands. Watching "Wheel in Space," you feel that -- despite all the Cybermen and Daleks and Ice Warriors marauding the galaxy -- there might be hope for mankind after all. (I offer up a full review of "Wheel in Space" here.) 4 comments: I still cannot get behind your love for 'Wheel' - I have tried, and it IS Whitaker, so it should be good, but...I simply can't love it. I think I find the Wheel crew generally less interesting than you do, and as a monster fetishist from childhood the feeble attempts to disguise the fact there are only two cybermen just make me sad (plus, the redesign is not especially effective). One day, perhaps, I'll watch it and finally catch on... I mentioned in my full "Wheel in Space" essay -- but it didn't make it into my capsule review -- that I think one problem when watching the reconstruction is the limited telesnaps of the guest cast. It's a character-driven script that largely avoids histrionics, and I think when one sees those same shots of the guest cast over and over again in the reconstructions, it's easy to think that their performances (and characterizations) are fairly bland and unexceptional. But the last time I watched, I let the surviving episodes be my guide for how to judge the performances in the missing episodes, and came away with a very different impression. That's not to say you'll ever love "Wheel" -- as you said, you like the monster stories; they're not my favorites -- that's a very big difference between us. I veer more towards the character-driven stories, which is what I think "Wheel" is. And I think the characters are superbly drawn, and if you look at the standard for Cybermen stories -- "Tomb" or "Earthshock," for example -- these characters (particularly, of course, Zoe, but also Gemma Corwyn and Jarvis Bennett) are so much richer. It's also got some of the easy, unforced scene work that I so love in something like "Snakedance," where scenes just seem to unfold, the way they do in the theatre, and we're left to guess what dialogue is "important" and what's just "conversation" -- as opposed to the heightened faux-theatrics of much of '60s television. Ah, The Awakening. Two episodes. Small but perfectly formed. Denis Lill, so far over the top he's back down the other side. Polly James, sparking so well off Davison I just want her to leave with him at the end of the story and travel with him forever. A genuinely disturbing monster that still utterly works. Oh, it's just... lovely. "The Awakening" is the rare serial that, after Philip and I first watched (and loved) it, we went back and watched the whole thing again, this time with the DVD commentary -- we couldn't get enough of it. At the time, it seemed a perfect miniature: buoyant and infectious. When I wrote my very first blog entry, my four-part Peter Davison retrospective, that was my take on it. The most recent time I watched -- I guess about eight or nine months ago -- it seemed so relevant to our current political climate, I was dumbfounded. Some of the Fifth Doctor stories, of course, wear their political statements on their sleeves (e.g., "Terminus," "Warriors"), and heaven knows, dozens upon dozens of Classic Who serials are allegorical in nature -- but I never would have expected to see such an apt evocation of our current political climate in "The Awakening." Yet its tale of a madman who establishes authoritarian rule -- and the forces that arise to support him, indulge him or resist him -- feels like it could have been written today. Seeing the parallels has, for me, made the serial no less delightful, but doubly effective. About This Blog The title of this blog: from the 1994 Murphy Brown episode "The Fifth Anchor," in which Wallace Shawn plays a former colleague of the FYI anchors, who did a weekly thinkpiece called "That's Alls I Know." The point of this blog: to talk about TV, past and present. About Me Well, in my "day job" I run the record label PS Classics (psclassics.com) and produce cast albums and solo discs. In my "down time," I write this blog, devoted to essays about television that seem to grow longer with each passing year.
Q: How can I optimize for IE? I have a JS-heavy app and it runs slowly in IE. I'm about to spend about a week optimizing for IE, and I'd like some direction about things to try. I found this thread referencing Drip, which seems useful: IE and Memory accumulation in Javascript I'm looking for tips like, "use for loops instead of $.each" as well as architectural best practices that I may not be using. Libraries I'm using: jQuery Google Maps Facebook JS API KnockoutJS Taffy Things I'm already doing: using for loops instead of $.each caching jQuery contexts for commonly-referenced DOM elements building HTML using Array.join() vs. string concatenation Any suggestions? Thanks! A: Use a JavaScript Profiler in IE A: Don't go blindly through your code making trivial improvements like changing $.each() loops to for loops; that's really pointless and someday you'll regret it. Use a profiler because it's a very good bet that most of your problems stem from a very small number of unexpectedly bad pieces of code. Something like dynaTrace ajax edition are invaluable in situations like this.
Smriti Irani was due to inaugurate the India Pavilion at the 71st Cannes Film Festival on Wednesday. Information and Broadcasting Minister Smriti Irani, who was due to inaugurate the India Pavilion at the 71st Cannes Film Festival on Wednesday, skipped the event where a delegation of filmmakers and artistes are making strides to push the country's regional films and further collaborations with other countries. Irani, who was to lead the delegation, is caught up with work related to the 15th Asia Media Summit to be held here from May 10-12 as well as the Karnataka Assembly elections, informed sources told IANS. Irani was supposed to be in Cannes for a day. The inaugural session of the Indian Pavilion was held in Cannes on Wednesday. The agenda this year is to showcase diversity in films in India and boosting co-productions. Paillard said in a statement: "The Indian pavilion is a very important tool to help connecting the worldwide European and worldwide community of films." On the Indo-French cinema collaboration, Tikoo said: "It is a fantastic relationship we have had, both with the Cannes Film Festival and the French film industry. In recent times, films like 'Tamasha' and 'Befikre' were shot extensively in this part of the world and found great resonance with the narrative and storytelling between the two countries." During the inaugural address, Joshi said: "I am happy that the National Awards this year and the Ministry have taken special efforts in showcasing the regional cinema at such a platform. We should also reach out to young filmmakers who might not have access to a festival like this. "Let's create many mini Cannes Film Festivals all around the world to help more and more filmmakers." This year, the India Pavilion, organised by the Ministry of Information and Broadcasting along with Ficci, is showcasing four regional language films. These include Assamese film "Village Rockstars", Malayalam film "Bhayanakam", Bengali movie "Nagarkirtan" and "Sinjar", a film from Lakshadweep made in Jasari, Barua said India had great content in terms of cinema and so far only a little had been exposed to the world. The Cannes Film Festival began on Tuesday and will conclude on May 19. Two films by Indian filmmakers -- Nandita Das' "Manto" and Rohena Gera's "Sir" -- are in separate competition sections at the gala, one of the most prestigious film jamborees around the world.
module Pod class Installer # Validate the podfile before installing to catch errors and # problems # class PodfileValidator # @return [Podfile] The podfile being validated # attr_reader :podfile # @return [Array<String>] any errors that have occured during the validation # attr_reader :errors # @return [Array<String>] any warnings that have occured during the validation # attr_reader :warnings # Initialize a new instance # # @param [Podfile] podfile # The podfile to validate # # @param [Analyzer::PodfileDependencyCache] podfile_dependency_cache # An (optional) cache of all the dependencies in the podfile # def initialize(podfile, podfile_dependency_cache = Analyzer::PodfileDependencyCache.from_podfile(podfile)) @podfile = podfile @podfile_dependency_cache = podfile_dependency_cache @errors = [] @warnings = [] @validated = false end # Validate the podfile # Errors are added to the errors array # def validate validate_installation_options validate_pod_directives validate_no_abstract_only_pods! validate_dependencies_are_present! validate_no_duplicate_targets! @validated = true end # Wether the podfile is valid is not # NOTE: Will execute `validate` if the podfile # has not yet been validated # def valid? validate unless @validated @validated && errors.empty? end # A message describing any errors in the # validation # def message errors.join("\n") end private def add_error(error) errors << error end def add_warning(warning) warnings << warning end def validate_installation_options installation_options = podfile.installation_options # Validate `incremental_installation` depends on `generate_multiple_pod_projects` invalid = installation_options.incremental_installation? && installation_options.incremental_installation != installation_options.generate_multiple_pod_projects add_error 'The installation option `incremental_installation` requires the option `generate_multiple_pod_projects` to also be enabled.' if invalid end def validate_pod_directives @podfile_dependency_cache.podfile_dependencies.each do |dependency| validate_conflicting_external_sources!(dependency) end end def validate_conflicting_external_sources!(dependency) external_source = dependency.external_source return false if external_source.nil? available_downloaders = Downloader.downloader_class_by_key.keys specified_downloaders = external_source.select { |key| available_downloaders.include?(key) } if specified_downloaders.size > 1 add_error "The dependency `#{dependency.name}` specifies more than one download strategy(#{specified_downloaders.keys.join(',')})." \ 'Only one is allowed' end pod_spec_or_path = external_source[:podspec].present? || external_source[:path].present? if pod_spec_or_path && specified_downloaders.size > 0 add_error "The dependency `#{dependency.name}` specifies `podspec` or `path` in combination with other" \ ' download strategies. This is not allowed' end end # Warns the user if the podfile is empty. # # @note The workspace is created in any case and all the user projects # are added to it, however the projects are not integrated as # there is no way to discern between target definitions which are # empty and target definitions which just serve the purpose to # wrap other ones. This is not an issue because empty target # definitions generate empty libraries. # # @return [void] # def validate_dependencies_are_present! if @podfile_dependency_cache.target_definition_list.all?(&:empty?) add_warning 'The Podfile does not contain any dependencies.' end end # Verifies that no dependencies in the Podfile will end up not being built # at all. In other words, all dependencies should belong to a non-abstract # target, or be inherited by a target where `inheritance == complete`. # def validate_no_abstract_only_pods! @podfile_dependency_cache.target_definition_list.each do |target_definition| dependencies = @podfile_dependency_cache.target_definition_dependencies(target_definition) next if dependencies.empty? next unless target_definition.abstract? children = target_definition.recursive_children next if children.any? { |child_target_definition| target_definition_inherits?(:parent => target_definition, :child => child_target_definition) } add_warning "The abstract target #{target_definition.name} is not inherited by a concrete target, " \ "so the following dependencies won't make it into any targets in your project:" \ "\n - #{dependencies.map(&:to_s).sort.join("\n - ")}" next if target_definition.platform add_error "The abstract target #{target_definition.name} must specify a platform since its dependencies are not inherited by a concrete target." end end def target_definition_inherits?(parent: nil, child: nil) if parent == child true elsif child.exclusive? false else target_definition_inherits?(:parent => parent, :child => child.parent) end end def validate_no_duplicate_targets! @podfile_dependency_cache.target_definition_list.group_by { |td| [td.name, td.user_project_path] }. each do |(name, project), definitions| next unless definitions.size > 1 error = "The target `#{name}` is declared multiple times" error << " for the project `#{project}`" if project add_error(error << '.') end end end end end
I don’t like to report about speculation, as it can often just be rubbish, but several sources are reporting that Town have submitted a €15m offer to Montpellier for Isaac Mbenza, a 22-year-old winger. French paper, L’Équipe, broke the story late on Monday night and several other websites and Twitter users have reported the same story. I’ve never heard of him before this rumour emerged, but having watched the highlights clip of his goals on YouTube, I now feel convinced he’s the answer to all our problems! Who is Issac Mbenza? He’s a right-footed young winger that has scored 11 goals in 54 appearances in Ligue 1 for Montpellier. As well as playing regularly in the French top flight, he’s had a handful of under-21 caps for Belgium. Like many of Town’s signings, he’s still young, so probably not the finished article but looks promising. As usual, it’s important not to get too carried away with highlight reels, but he seems quick and can finish nicely: Is this deal likely to go through? There have been a few rumoured deals that haven’t gone over the line for Town this summer but this one seems closer than most. There’s still potential for the player’s personal demands to scupper the deal or the medical could turn up a surprise. However, it seems like a bid has been made and most probably will be accepted, so it’s getting close to being done. Would Mbenza be a good signing for Town? Tom Ince’s departure left us a little bit short on wide players, so bringing in a promising winger makes sense. The fee involved seems to be quite high, so it could be that we’re having to pay over the odds because of the fast-approaching transfer window deadline. I’m not sure he’s of the same calibre as Adama Traore or Anthony Limbombe, who we’ve been connected with this summer. But given his age it could be that David Wagner can see previously untapped potential in Mbenza. Our manager tends to have a good eye for picking players, so if Wagner thinks he’s good enough then that’s good enough for me. What will this mean for the rest of Town’s transfer business? I get the feeling that bringing in another winger to replace Tom Ince was the priority for Town in this last week of the transfer window. I suspect there won’t be any more players coming in unless something unexpected pops up, like a long-term target suddenly becoming available or a loan player being offered that’s too good to turn down (Man City’s Phil Foden would top my shopping list, but I think that’s a bit unrealistic given he started in the Charity Shield). If Mbenza does sign then it means Collin Quaner is almost certain to leave the club, as we’ll need to offload a non-homegrown player to make space in the squad. Rumours connecting him with a move to Preston have died down lately, but surely someone in the Championship will want to take him off our hands. Malone and Hefele are also likely to be moved on before the window closes on Thursday night, but nothing concrete has been reported for either of them.
1.. Introduction {#s1} ================ Danjiangkou Reservoir has become increasingly popular because it is the headwaters for China\'s programme of diverting water from central China to guarantee adequate supply of quality water to more than twenty cities in North China including Beijing, Tianjin and Shijiazhuang \[[@RSOS170624C1],[@RSOS170624C2]\]. A population of 110 million people over an area of 15.1 × 10^4^ square kilometres have benefited from the programme. The supply of water from Danjiangkou Reservoir to Beijing officially started on 12 December 2014. To ensure adequate supply of quality water to Beijing, it is of great significance to maintain a good ecological environment at the reservoir and to ensure good water and soil conservation in its upper reaches. The nitrogen and phosphorus in water in the reservoir come from its tributaries \[[@RSOS170624C3],[@RSOS170624C4]\], and hence, the most effective measures to prevent and cure algae bloom and water eutrophication is to control the total amount of pollutants in each of its tributaries. Much work has been done on this particular aspect in recent years. For example, water pollution risks in the region of Shiyan were assessed using the proposed model \[[@RSOS170624C5]\]. Necessity and operational feasibility of early reservoir refill were analysed \[[@RSOS170624C6]\]. An eco-environmental vulnerability assessment method was developed using an environmental information system database for the Danjiangkou Reservoir Area \[[@RSOS170624C7]\]. The spatio-temporal changes of the carbonate system and CO~2~ flux of a hydroelectric reservoir (Danjiangkou Reservoir) were studied in the subtropical monsoon climate region \[[@RSOS170624C8]\]. The spatial distributions of Cd, Pb, Cu, Zn, Cr and As in soil of the relocation areas of Danjiangkou Reservoir were analysed and the degrees of contamination and potential ecological risk of these elements were evaluated using the integrated pollution index and the potential ecological risk index \[[@RSOS170624C9]\]. The possibility for preventing downstream diatom blooms was explored using the water storage in the Danjiangkou Reservoir and a flushing strategy was developed to control diatom growth \[[@RSOS170624C10]\]. A functional group approach was used on the basis of the Q index to analyse the spatial and temporal patterns, environmental factors and the ecological status of phytoplankton in the Danjiangkou Reservoir of China from July 2011 to April 2012 \[[@RSOS170624C11]\]. However, little work has been done on the nitrogen and phosphorus contents in water in the tributaries of Danjiangkou Reservoir. Therefore, as part of the efforts to guarantee adequate supply of quality water to Beijing, surface water was sampled from the major tributaries of Danjiangkou Reservoir in the normal (May), flood (August) and dry (December) seasons of 2014, and characterized for nitrogen and phosphorus contents. These findings of the investigation provided an important basis for the effective measures taken later on as appropriate to ensure adequate supply of quality water to Beijing. 2.. Material and methods {#s2} ======================== 2.1.. Sampling and characterization {#s2a} ----------------------------------- Danjiangkou Reservoir is located at 32°36′--33°48′ N, 110°59′--111°49′ E \[[@RSOS170624C12]\]. It has a surface area of about 1050 square kilometres, an average annual precipitation of 800--1000 mm and an annual mean air temperature of 14.4--15.7°C. The reservoir has a normal storage level of 170 m, a storage capacity of 290.5 billion cubic metres and a shoreline of 4610.6 km \[[@RSOS170624C13],[@RSOS170624C14]\]. It can be seen from [figure 1](#RSOS170624F1){ref-type="fig"} that the reservoir has 10 major tributaries including the Danjiang (33°1′ N, 111°18′ E), Laoguanhe (33°1′ N, 111°29′ E), Langhe (32°25′ N, 111°14′ E), Jianhe (32°33′ N, 111°3′ E), Guanshanhe (32°31′ N, 111°0′ E), Sihe (32°37′ N, 110°53′ E), Shendinghe (32°48′ N, 110°53′ E), Duhe (32°42′ N, 110°34′ E), Tianhe (32°51′ N, 110°23′ E) and Hanjiang (32°48′ N, 110°11′ E) rivers. Sampling points sequenced from number R1 to R10. Surface water was sampled in the normal (May), flood (August) and dry (December) seasons of 2014, and no permissions were required prior to conducting our fieldwork. Two litres of surface water were collected at a depth of 50 cm using a Van Dorn bottle. The samples were stored in polyethylene bottles and then transported to the laboratory in a cooler at 4°C with a maximum storage time of one week \[[@RSOS170624C15],[@RSOS170624C16]\]. The measurements of water quality covered total nitrogen (TN), nitrate nitrogen $(\text{N}{\text{O}_{3}}^{-}\text{-N})$, ammonia nitrogen $(\text{N}\text{H}_{3}\text{-N})$, dissolved nitrogen (DTN), total phosphorus (TP), dissolved phosphorus (DTP), water temperature (T), pH, dissolved oxygen (DO) and electrical conductivity (EC), 5 days\' biochemical oxygen demand (BOD~5~), permanganate index (COD~Mn~), fluoride (F^−^), sulfate $(\text{S}{\text{O}_{4}}^{2 -})$ and chloride (Cl^−^). Figure 1.Locations of 10 sampling points. 2.2.. Methods {#s2b} ------------- After collecting surface water, one litre of surface water was first filtered using a 0.45 µm microporous membrane, and then sulfuric acid (1 mol l^−1^) was added immediately to preserve it before the concentrations of DTN, $\text{N}{\text{O}_{3}}^{-}\text{-N}$, NH~3~-N and DTP were measured. Another half litre of surface water was first filtered using a 0.45 µm microporous membrane before the concentrations of F^−^, $\text{S}{\text{O}_{4}}^{2 -}$ and Cl^−^ were measured. Sulfuric acid (1 mol l^−1^) was added to the last half litre of surface water before the concentrations of TN, TP, COD~Mn~ and BOD~5~ were measured. T, pH, DO and EC were measured using a multi-parametric probe YSI6600 on site. The chemical parameters were measured as required in the specification for 'analysis in water and wastewater'. The titration method was used to determine the concentration of COD~Mn~. The concentration of BOD~5~ was determined using the dilution and inoculation method. Nessler\'s reagent colorimetric method was used to measure the concentration of NH~3~-N. The concentrations of DTP and TP were determined by the ammonium molybdate spectrophotometric method. The concentrations of DTN and TN were determined by the alkaline potassium persulfate digestion ultraviolet spectrophotometer method. Chromatography of ions was used to determine the concentration of $\text{N}{\text{O}_{3}}^{-}\text{-N}$ \[[@RSOS170624C17]\]. All analyses were carried out and documented in triplicate with mean values used for subsequent data processing. The concentration of particulate nitrogen (PN) was obtained by subtracting the concentration of DTN from the concentration of TN. The concentration of NH~3~-N plus the concentration of $\text{N}{\text{O}_{3}}^{-}\text{-N}$ equals the concentration of dissolved inorganic nitrogen (DIN). The concentration of particulate phosphorus (PP) was obtained by subtracting the concentration of DTP from the concentration of TP \[[@RSOS170624C18],[@RSOS170624C19]\]. For the present study, the annual average water quality parameter was given by $$C = \frac{C_{f} \times 3 + C_{n} \times 4 + C_{d} \times 5}{12},$$ where *C* is the annual average content (mg l^−1^), *C*~f~ is the content in the flood season (mg l^−1^), *C*~n~ is the content in the normal season (mg l^−1^) and *C*~d~ is the content in the dry season (mg l^−1^). Statistical analyses were performed with SPSS (v. 17.0) \[[@RSOS170624C20]\], Excel 2007 and Origin (v. 8.0). The data were standardized to eliminate the influence of dimension during the cluster analysis. The inputs of TN and TP were given by $$W_{i} = 31.536 \times 10^{- 2} \times Q_{i} \times C_{i},$$ where *W~i~* is the input of TN and TP of tributary *i* (t a^−1^), *Q~i~* is the annual average discharge of tributary *i* (m^3^ s^−1^), which was provided by Nanyang and Shiyan Hydrology Bureaus, and *C~i~* is the average annual TN and TP content of tributary *i* (mg l^−1^). 2.3.. Water quality standard {#s2c} ---------------------------- According to Surface Water Environmental Quality Standard of China (GB3838-2002), the specific standards of water quality parameters are given in [table 1](#RSOS170624TB1){ref-type="table"}. Table 1.Environmental Quality Standard (GB3838-2002) for Surface Water in units of mg l^−1^ (pH without unit).water quality parametersIIIIIIIVVpH6--9Cl^−^≤ 250$\text{S}{\text{O}_{4}}^{2 -}$≤ 250F^−^≤ 1.0≤ 1.5BOD~5~≤3≤3≤4≤6≤10COD~Mn~≤2≤4≤6≤10≤15TP≤0.02≤0.1≤0.2≤0.3≤0.4TN≤0.2≤0.5≤1≤1.5≤2 3.. Results and discussion {#s3} ========================== 3.1.. Parameter contents in water in tributaries of Danjiangkou Reservoir {#s3a} ------------------------------------------------------------------------- ### 3.1.1.. Physical and chemical characteristics {#s3a1} As shown in [figure 2](#RSOS170624F2){ref-type="fig"}, the annual average value of pH is in the range of 7.35--8.46, which implies a weak alkalinity. The water temperature is in the range of 9--14.7°C in the dry season. It can be seen through comparison that there is a quick increase in temperature in the normal and flood seasons. Water bloom is more likely to occur because the temperature in normal and flood seasons accelerates the growth of phytoplankton (18--25°C). The annual average content of Cl^−^ and $\text{S}{\text{O}_{4}}^{2 -}$ are far below the surface water environmental quality standard (GB3838-2002) where the regulation limits are 250 mg l^−1^ for tributaries. The annual average contents of $\text{S}{\text{O}_{4}}^{2 -}$ in Sihe River (R6) and Shendinghe River (R7) are higher than that in other tributaries. The annual average content of Cl^−^ in Shendinghe (R7) River is higher than that in other tributaries. The annual average value of EC is in the range of 26.7--59.9 mS m^−1^. The annual average content of F^−^ is in the range of 0.12--0.33 mg l^−1^, which is below the grade I standard of water quality standard GB3838-2002. The contents of other ions are good. Figure 2.Physical and chemical characteristics of water in the tributaries. ### 3.1.2.. Characteristics of organic pollutants {#s3a2} As shown in [figure 3](#RSOS170624F3){ref-type="fig"}, the annual average content of DO is in the range of 4.13--9.00 mg l^−1^. As a whole, the tributaries are rich in DO. The contents of DO in the flood season are lower than that of the normal and dry seasons, which is possibly due to the facts that (i) the high temperature in August reduces the surface pressure of water; (ii) the microbial activity and organic pollutants consume large amounts of DO. The annual average contents of BOD~5~ and COD~Mn~ are in the range of 1.03--4.50 mg l^−1^ and 1.09--6.14 mg l^−1^, respectively. BOD~5~ contents in Jianhe River (R4, in December and May), Sihe River (R6) and Shendinghe River (R7) are higher than the grade II standard (3 mg l^−1^) of water quality standard GB3838-2002, the annual average contents of which are about 3.08, 4.50 and 4.23 mg l^−1^, respectively. Therefore, the organic pollution in Sihe River is the most serious. Figure 3.DO, BOD~5~ and COD~Mn~ in water in the tributaries. ### 3.1.3.. Characteristics of nitrogen pollutant {#s3a3} As shown in [figure 4](#RSOS170624F4){ref-type="fig"}, the annual average content of TN is in the range of 1.65--10.81 mg l^−1^. The highest annual average content of TN at 10.81 mg l^−1^ is found in Shendinghe River, followed by Sihe River which has an annual average content of 7.30 mg l^−1^. Nitrogen pollution in Sihe River and Shendinghe River are more serious compared with that in other tributaries. It also could be found that TN in Shendinghe River changes little among seasons because the nitrogen in Shendinghe River mainly comes from urban sewage, industrial wastewater and other point sources in Shiyan City, and the emissions from these point sources are more stable and less affected by rainfall. Figure 4.PN and DTN in water in the tributaries. As shown in [figure 5](#RSOS170624F5){ref-type="fig"}, the percentage of DIN in TN is more than 50% in the tributaries of Danjiangkou Reservoir. DIN is the dominant form of nitrogen and high DIN ensures the full utilization of nitrogen. The annual average concentration of $\text{N}{\text{O}_{3}}^{-}\text{-N}$ is in the range of 0.61--4.67 mg l^−1^, which accounts for more than 90% in DIN in all tributaries, while the percentage of NH~3~-N in DIN is less than 10%. NH~3~-N is the reduced form of nitrogen and $\text{N}{\text{O}_{3}}^{-}\text{-N}$ is the steady form of nitrogen. Generally, nitrogen is discharged into the water in the reduced form. NH~3~-N is oxidized to $\text{N}{\text{O}_{2}}^{-}\text{-N}$, and then oxidized to $\text{N}{\text{O}_{3}}^{-}\text{-N}$ after nitrification. Such a nitrification process would consume a large amount of oxygen (4.57 mg mg^−1^) \[[@RSOS170624C21],[@RSOS170624C22]\]. According to the percentage of $\text{N}{\text{O}_{3}}^{-}\text{-N}$ and NH~3~-N, old pollutants have been broken down, but there are still new pollutants being discharged into the water. In the flood season, the proportion of $\text{N}{\text{O}_{3}}^{-}\text{-N}$ in TN is higher than that in other seasons, while the proportion of NH~3~-N in TN decreased, because the higher temperature in the flood season is good for nitrification. Figure 5.NH~3~-N and $\text{N}{\text{O}_{3}}^{-}\text{-N}$ in water in the tributaries. ### 3.1.4.. Characteristics of phosphorus pollutant {#s3a4} As shown in [figure 6](#RSOS170624F6){ref-type="fig"}, the annual average content of TP is in the range of 0.03--0.56 mg l^−1^, followed by Shendinghe River which has an annual average content of 0.43 mg l^−1^. The annual average contents of TP in Sihe River and Shendinghe River are both higher than the grade III standard (0.2 mg l^−1^), which means that phosphorus pollution in Sihe and Shendinghe Rivers is more serious than that in other tributaries. This finding is in agreement with previous reported works \[[@RSOS170624C23],[@RSOS170624C24]\]. The two rivers receive huge amounts of wastewater from urban sewage and other point sources in Shiyan City. The use of phosphorus detergent is also a major cause for the high TP content. In addition, the field survey showed that there is a small amount of phosphate fertilizers used in Shiyan city and these plants may also be an important cause for the high TP content. Figure 6.PP and DTP in water in the tributaries. The annual average content of PP is in the range of 0.01--0.22 mg l^−1^. The percentage of PP in TP is 22.22--71.43%. The percentage of PP in TP is more than 50% in Laoguanhe River, Duhe River, Tianhe River and Hanjiang River, which implies that PP is the main phosphorus form in these tributaries. PP generally cannot be directly used by plants; however, with the functioning of acid-producing microorganisms, it can be transformed into soluble phosphorus, a state that is storable in water. The soluble phosphorus first combines with some base compounds, and then changes into an insoluble calcium salt, magnesium salt and ferric salt, which constitutes the circulation of phosphorus in tributaries \[[@RSOS170624C25],[@RSOS170624C26]\]. In addition, the PP gradually settles down as the flow rate decreases. When the phytoplankton consumes a large amount of phosphorus, deposited phosphorus is gradually released and forms a new phosphorus balance. DTP is the main form of TP in most of the tributaries, which shows that phosphorus content directly absorbed and used by plants is relatively high. As a whole, the nitrogen and phosphorus contents in the tributaries are relatively high especially in Sihe River and Shendinghe River, basically more than the critical value (0.2 mg l^−1^, 0.02 mg l^−1^) which makes algae growth easy \[[@RSOS170624C27]\]. Therefore, there are significant security risks of pollution to water quality, such as algae may rapidly grow and propagate, or even exhibit an outbreak of algae water bloom when the water dynamics and other conditions are seriously affected. ### 3.1.5.. Change in nutrient structure {#s3a5} The nutrient structure is often expressed by the N/P ratio \[[@RSOS170624C28]--[@RSOS170624C30]\]. DIN is the main nitrogen form that can be used directly; and dissolved inorganic phosphorus is the main phosphorus form that can be used directly. In this study, DTP is used instead of dissolved inorganic phosphorus, and the N/P ratio is the DIN/DTP ratio. When the N/P ratio is greater than 16, phosphorus is the limiting factor of phytoplankton; when the N/P ratio is less than 16, nitrogen is the limiting factor of phytoplankton \[[@RSOS170624C31]\]. As illustrated in [table 2](#RSOS170624TB2){ref-type="table"}, the N/P ratios in Laoguanhe and Hanjiang Rivers are more than 30 in three seasons. It indicates that phosphorus will be preferentially consumed to a low value and become the limiting factor of phytoplankton when algae grow abundantly. Nitrogen is the limiting factor of phytoplankton in Langhe River (in May), Jianhe River (in May), Tianhe River (in December) and Sihe River (in May and August). As a whole, phosphorus is more likely to be the limiting factor of phytoplankton in the tributaries. Table 2.N/P ratio in the tributaries.N/PtributariesMayAugustDecemberR1168153R24012860R376095R4122123R51932103R611818R7281725R81611738R92518713R104716536 3.2.. Cluster analysis for the tributaries {#s3b} ------------------------------------------ The water quality parameters in 10 tributaries were analysed by cluster analysis for more targeted governance. As shown in [figure 7](#RSOS170624F7){ref-type="fig"}, 10 tributaries in Danjiangkou Reservoir can be grouped into three types. Type I contains four tributaries (i.e. Danjiang River, Laoguanhe River, Langhe River, Jianhe River) and their water qualities are mainly influenced by non-point sources of pollution because they flow through rural areas. Type II consists of two tributaries (i.e. Sihe River and Shendinghe River) and their water qualities are affected by point sources of pollution because they flow through Shiyan City and receive huge amounts of industrial wastewater and municipal sewage. The remaining rivers are regarded as type III and their water qualities are critically affected by both point and non-point sources of pollutions. Figure 7.Cluster analysis results for water quality parameters in 10 tributaries. 3.3.. Correlation among water quality parameters {#s3c} ------------------------------------------------ Water quality parameters have different influences on TN and TP. Both TN and TP are significantly correlated with COD~Mn~ and their correlation values are higher than 0.8 with *p* \< 0.01. In addition, the positive correlations between TN and EC, Cl^−^, as well as $\text{S}{\text{O}_{4}}^{2 -}$ indicate that increased levels of these water quality parameters are beneficial to the increasing levels of TN. However, the negative correlations manifest a non-synergistic effect on the existence of each factor. As presented in [table 3](#RSOS170624TB3){ref-type="table"}, correlations between TP and other water quality parameters are similar with that of TN, which implies that TN and TP may have similar pollution sources. Table 3.Correlation among water quality parameters.QTNTPDOPHCOD~Mn~ECF^−^$\text{S}{\text{O}_{4}}^{\text{2} -}$Cl^−^Q1TN−0.3121TP−0.2710.876\*\*1DO0.172−0.686\*−0.889\*\*1PH0.3630.0930.127−0.1211COD~Mn~−0.5330.831\*\*0.883\*\*−0.628−0.0431EC−0.3890.944\*\*0.833\*\*−0.689\*−0.0190.790\*\*1F^−^−0.653\*0.705\*0.516−0.319−0.3490.685\*0.773\*\*1$\text{S}{\text{O}_{4}}^{2 -}$−0.3820.858\*\*0.952\*\*−0.829\*\*−0.0040.931\*\*0.834\*\*0.654\*1Cl^−^−0.550.768\*\*0.521−0.473−0.110.5160.733\*0.761\*0.5671[^2][^3] 3.4.. Inputs of total nitrogen and total phosphorus from 10 tributaries {#s3d} ----------------------------------------------------------------------- The annual average inputs of TN and TP from the 10 tributaries have been estimated using equation (2.2). As presented in [table 4](#RSOS170624TB4){ref-type="table"}, the annual average input of TN from the 10 tributaries is 63 347.31 t. Among the 10 tributaries, Hanjiang River has the biggest contribution for inputs of TN, which accounts for 68.79%. Duhe and Laoguanhe Rivers also have a big contribution for inputs of TN, which account for 15.38% and 8.71%, respectively. Similarly, the annual average input of TP from the 10 tributaries is 2045.52 t. Hanjiang River accounts for 63.21%, which becomes the biggest contribution for inputs of TP. According to the different types of sources of pollution, the tributaries can be grouped as non-point source controlling rivers (type I), source controlling rivers (type II) and integrated controlling rivers (type III). The contributions of these three types of tributaries for TN input are 10.73%, 0.45% and 85.82%, respectively, and for TP input are 8.61%, 5.92% and 85.47%, respectively. Table 4.The annual average input of TN and TP from the 10 tributaries in units of (t a^−1^).tributariesDanjiang RiverLaoguanhe RiverLanghe RiverJianhe RiverGuanshanhe RiverSihe RiverShendinghe RiverDuhe RiverTianhe RiverHanjiang RiverQ (m^3^ s^−1^)6.5260.006.710.473.204.123.59187.0014.00800.00W~TN~ (t a^−1^)392.005518.00840.3845.70270.41948.921223.309739.71785.5043 583.38W~TP~ (t a^−1^)7.56146.9519.362.344.7573.0048.61416.8233.231292.90 The significant contributors of TN and TP in the reservoir are the tributaries. According to the results of the inputs of TN and TP, cluster analysis and pollution characteristics, different pollution control measures should be undertaken. The TN and TP contents in Sihe River and Shendinghe River are the highest, while the percentages of input of TN are 1.5% and 1.93%, and the percentages of input of TP are 3.57% and 2.38%, respectively. As the two rivers are polluted by domestic sewage and other point sources, the government should strengthen the construction of urban sewage plants as well as dephosphorization and denitrification projects. For Hanjiang River and Duhe River, whose water quantities are huge, control measures against point source and non-point sources of pollution should be strengthened. 4.. Conclusion {#s4} ============== It can be seen from the presentation above that (i) the concentrations of nitrogen and phosphorus in Sihe and Shendinghe Rivers are higher than those in other tributaries; (ii) TP, TN and DIN are in the forms of DTP, DTN and $\text{N}{\text{O}_{3}}^{-}\text{-N}$, respectively, in May, August and December; (iii) compared with nitrogen, phosphorus is more likely to be the limiting factor of phytoplankton; (iv) it was found through cluster analysis that 10 tributaries could be grouped as point source controlling rivers, non-point source controlling rivers and integrated controlling rivers; and the percentages of input of TN in the three types are 10.73%, 3.45% and 85.82%, while the percentages of input of TP are 8.61%, 5.92% and 85.47%, respectively. These findings can provide an important basis for effective measures on safe water provision to Beijing. We are thankful for logistic support for sampling provided by Nanyang Environmental Protection Agency in Henan Province and Shiyan Environmental Protection Agency in Hubei Province. Ethics {#s5} ====== We were not required to complete an ethical assessment prior to conducting our research. Data accessibility {#s6} ================== Our data are deposited at Dryad (<http://dx.doi.org/10.5061/dryad.17b01>) \[[@RSOS170624C32]\]. Authors\' contribution {#s7} ====================== Y.L. and B.Z. designed the study. Y.Z. and X.Q. collected all samples and carried out the laboratory work. Y.L. and Y.Z. analysed the data. All the authors interpreted the results and wrote the manuscript. All the authors gave their final approval for publication. Competing interests {#s8} =================== The authors declare no competing interests. Funding {#s9} ======= The present research was supported by Major Science and Technology Program for Water Pollution Control and Treatment (No. 2014ZX07405001). [^1]: This article has been edited by the Royal Society of Chemistry, including the commissioning, peer review process and editorial aspects up to the point of acceptance. [^2]: \*Significant correlation at the 0.05 level (2-tailed). [^3]: \*\*Significant correlation at the 0.01 level (2-tailed).
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No doubt back in the time when Noah built his ark and gathered up animals ahead of God’s promised flood, more than a few people thought he was just a little off his rocker. Then it rained for 40 days and 40 nights. Whether or not you believe that account from the Christian Bible’s Book of Genesis, all of us can recall similar stories or real-life incidents where people prepared in advance to deal with the harshest of times, only to be proven right in the end. That’s what the state of Texas is now doing — making economic preparations in advance of a global economic collapse resulting in the fall of the U.S. dollar as the world’s reserve currency. Lawmakers passed H. B. 3169 after it was introduced in March by Rep. Giovanni Capriglione. The measure “makes a multi-faceted assault on the Fed’s mismanaged money monopoly, including provisions for overseeing the depositing of ‘state money’ and the setting of rates of exchange between precious metals stored in the facility and other currencies, including U.S. dollars,” The New American reported. While the U.S. and global stock markets are sound today, high debt and low growth abound; the Fed has been propping up the dollar with various support measures that, when taken literally, are wholly artificial because there is nothing undergirding American currency in the form of hard, tangible assets. With gold bullion legislation, Texas is making a bet that sometime in the future it will need such assets to remain economically viable at a time when all other states that haven’t made similar preparations fail — right along with the heavily indebted federal government. Almost two years ago Gov. Greg Abbott signed a bill into law authorizing the establishment of the gold bullion and precious metals repository. Very shortly thereafter, state officials jump-started the repository process to get in up and running. William Greene, an economics professor, explained to The New American that over time, Texas residents could utilize state-issued currency and federal reserve notes to achieve a “reverse Gresham’s Law” effect, whereas good money such as gold and silver would drive away fiat money, like federal reserve notes which are not backed by anything of value. When this process begins, an influx of genuine wealth into state coffers will begin, as more businesses from outside the state flock there to become part of a much more stable, long-term economic system. That will especially include banking business. Over time, good money will completely overshadow the bad, and it may become politically viable to actually return the country to a currency that is backed by physical wealth. (Related: Read Collapse: Government spending in the Age of Obama to set debt records.) “Sound money is the tide that lifts all boats,” The New American noted. Of course, the Federal Reserve isn’t about to just sit back and allow that to happen. No doubt the Fed would employ all kinds of rules and regulations in an attempt to stymie the Texas-led effort to absolve us of all fiat money and reinstate some financial freedom into the system. Right now though, there is another obstacle — of sorts. Under Art. I, Sect. 8 of the Constitution, Congress has the authority “to coin money” and “regulate the value thereof,” not states. That stated, though states themselves cannot issue their own currencies, the movement by some to stockpile physical wealth can be used as the driver that convinces Congress to reclaim its authority over setting the value of money, namely by changing what our money is valued upon — hard, physical assets that have historically held value, or the whims of an unelected fiscal authority that, throughout its history, has never been adept at preventing economic ebbs and flows. But even if nothing changes on the federal level, Texas has obviously decided to protect its own economic self-worth and that of its citizens with the establishment of the gold bullion repository. It’s an economic prep other states should take as well. J.D. Heyes is a senior writer for NaturalNews.com and NewsTarget.com, as well as editor of The National Sentinel.
Q: Package is installed and is not detected. (gradle) I installed gradle by typical way: sudo apt install gradle Reading package lists... Done Building dependency tree Reading state information... Done gradle is already the newest version (3.5-0ubuntu1). 0 to upgrade, 0 to newly install, 0 to remove and 8 not to upgrade. Next I wanted to use this program: $ gradle The program 'gradle' is currently not installed. You can install it by typing: sudo apt install gradle I was trying to remove java, purge gradle, remove it from anywhere and install again. Nothing helps... The most confusing is that this package was working correctly some days earlier without troubles. Below some debug: $ which gradle $ whereis gradle gradle: $ apt-cache policy gradle gradle: Installed: 3.5-0ubuntu1 Candidate: 3.5-0ubuntu1 Version table: *** 3.5-0ubuntu1 500 500 http://ppa.launchpad.net/cwchien/gradle/ubuntu xenial/main amd64 Packages 500 http://ppa.launchpad.net/cwchien/gradle/ubuntu xenial/main i386 Packages 100 /var/lib/dpkg/status 2.10-1 500 500 http://archive.ubuntu.com/ubuntu xenial/universe amd64 Packages 500 http://archive.ubuntu.com/ubuntu xenial/universe i386 Packages 1.4-2ubuntu1 500 500 http://us.archive.ubuntu.com/ubuntu trusty/universe amd64 Packages 500 http://us.archive.ubuntu.com/ubuntu trusty/universe i386 Packages How to revert system to state, when this package will be correctly detected? Update I found command: sudo apt-get clean Now i obtain: sudo apt install gradle Reading package lists... Done Building dependency tree Reading state information... Done gradle is already the newest version (3.5-0ubuntu1). 0 to upgrade, 0 to newly install, 0 to remove and 8 not to upgrade. W: Target Packages (main/binary-amd64/Packages) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target Packages (main/binary-all/Packages) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target Translations (main/i18n/Translation-en_GB) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target Translations (main/i18n/Translation-en) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target Translations (main/i18n/Translation-pl) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target DEP-11 (main/dep11/Components-amd64.yml) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 W: Target DEP-11-icons (main/dep11/icons-64x64.tar) is configured multiple times in /etc/apt/sources.list:7 and /etc/apt/sources.list.d/docker.list:1 Update2 dpkg -L gradle /. /usr /usr/share /usr/share/doc /usr/share/doc/gradle /usr/share/doc/gradle/changelog.Debian.gz /usr/share/doc/gradle/copyright namei -lx /usr/bin/gradle f: /usr/bin/gradle Drwxr-xr-x root root / drwxr-xr-x root root usr drwxr-xr-x root root bin gradle - No such file or directory A: Finally thanks to comments of @muru I done the following steps: I removed ppa:cwchien/gradle: sudo rm -rf /etc/apt/sources.list.d/cwchien-ubuntu-gradle-xenial.* sudo apt-get update I installed old gradle from official repo: sudo apt-get install gradle Then all dependencies was installed correctly. Then I append cwchien-ubuntu-gradle-xenial again and installed again: sudo apt-get install gradle-ppa gradle Finally in website https://gradle.org/install I found command: export PATH=$PATH:/opt/gradle/gradle-3.5/bin That finally solved my problems, and now: gradle -v ------------------------------------------------------------ Gradle 3.5 ------------------------------------------------------------ Update Now I installing gradle by sdkman.io by these commands: Install sdkman curl -s "https://get.sdkman.io" | bash Install gradle sdk install gradle 4.0.2
[Prerequisites for therapy of inflammatory bowel diseases. Pathophysiology--symptomatology--diagnosis]. The etiology of the idiopathic chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis remains unclear. Differences in prognosis, medical and surgical treatment, and the nature of expected complications require not only a differential diagnosis vis-a-vis other disorders, but also the correct diagnosis of these two diseases. Symptomatology and clinical presentation can be mimicked both by infectious, ischemic and other chronic bowel diseases such as collagenous colitis, eosinophilic colitis, and Behçet's disease. This means that, in the absence of pathognomonic changes, the correct diagnosis can be established only on the basis of all the findings (laboratory, endoscopy, X-rays), and sometimes only on the basis of the course of the condition. The most important differential diagnostic procedure has proved to be ileocolonoscopy, since in addition to gross evaluation of the mucosa, targeted removal of biopsy specimens is also possible.
Subpicosecond interferometric measurement of the nonlinear refractive index of poly(3-hexylthiophene). We measured the magnitude and the time response of the nonlinear refractive index (n(2)) of poly(3-hexylthiophene)by a femtosecond time-resolved interferometric technique. Decays of 320 fs and 3.0 ps were found. The n(2) value obtained was -6 x 10(-9) esu at 620 nm. Calculation of the dispersion of n(2) showed that the negative value is consistent with that of a four-level model.
Influence of chemical structure on hydration and gas transport mechanisms of sulfonated poly(aryl ether ketone) membranes. This work reports the influence of the chemical structure of two sulfonated poly(aryl ether ketone)s (SPAEK) on the hydration and gas transport mechanism of thin membranes made thereupon. For this purpose, two sulfonated poly(aryl ether ketone)s having the same ionic exchange capacity (IEC) but bearing a different repartition of the sulfonic acid groups along the polymer backbone were prepared. These polymers were synthesized by direct copolymerization of two specific sulfonated precursors, bisphenol AF and 4,4'-difluorobenzophenone. The morphology of the membranes was studied by transmission electron microscopy, and the thermal properties of the ionomers were determined from differential scanning calorimetry and thermogravimetric analyses. A detailed analysis of the water sorption isotherms and kinetics was performed. The gas transport properties were also determined for He, H(2), and CO(2) in the full range of water activity. From the detailed analysis of the water sorption isotherm and of the relative contributions of the Fickian diffusion and relaxation phenomena, a water sorption mechanism was proposed in relation with the SPAEK architectures and polymers' chain mobility. This mechanism allowed explaining the different evolution of the gas transport properties observed as a function of the gas nature and hydration rate.
/* * Copyright (c) 2013-2015 Chun-Ying Huang * * This file is part of GamingAnywhere (GA). * * GA is free software; you can redistribute it and/or modify it * under the terms of the 3-clause BSD License as published by the * Free Software Foundation: http://directory.fsf.org/wiki/License:BSD_3Clause * * GA is distributed in the hope that it will be useful, * but WITHOUT ANY WARRANTY; without even the implied warranty of * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. * * You should have received a copy of the 3-clause BSD License along with GA; * if not, write to the Free Software Foundation, Inc., * 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA. */ #include <stdio.h> #include <pthread.h> #ifndef WIN32 #include <unistd.h> #include <netinet/in.h> #include <sys/syscall.h> #include <sys/select.h> #include <sys/socket.h> #include <sys/wait.h> #include <sys/time.h> #include <arpa/inet.h> #endif /* ! WIN32 */ #include "ga-common.h" #include "ga-module.h" #include "encoder-common.h" #include "rtspconf.h" #include "ga-liveserver.h" #include "server-live555.h" static pthread_t server_tid; int live_server_register_client(void *ccontext) { if(encoder_register_client(ccontext) < 0) return -1; return 0; } int live_server_unregister_client(void *ccontext) { if(encoder_unregister_client(ccontext) < 0) return -1; return 0; } static int live_server_init(void *arg) { // nothing to do now return 0; } static int live_server_start(void *arg) { pthread_cancel_init(); if(pthread_create(&server_tid, NULL, liveserver_main, NULL) != 0) { ga_error("start live-server failed.\n"); return -1; } return 0; } static int live_server_stop(void *arg) { pthread_cancel(server_tid); return 0; } static int live_server_deinit(void *arg) { // nothing to do now return 0; } static int live_server_send_packet(const char *prefix, int channelId, AVPacket *pkt, int64_t encoderPts, struct timeval *ptv) { encoder_pktqueue_append(channelId, pkt, encoderPts, ptv); return 0; } ga_module_t * module_load() { static ga_module_t m; // bzero(&m, sizeof(m)); m.type = GA_MODULE_TYPE_SERVER; m.name = strdup("live555-rtsp-server"); m.init = live_server_init; m.start = live_server_start; m.stop = live_server_stop; m.deinit = live_server_deinit; m.send_packet = live_server_send_packet; // encoder_register_sinkserver(&m); // return &m; }
All relevant data are within the manuscript and its Supporting Information files. Introduction {#sec005} ============ Obesity refers to the excessive accumulation of fat in the body, which leads to co-morbidities that negatively affect the obese person's health \[[@pone.0234244.ref001]\]. The Centers for Disease Control and Prevention (CDC) defined overweight as body mass index (BMI) over 85^th^ and below 95^th^ percentile and obesity as a BMI over 95^th^ percentile \[[@pone.0234244.ref002]\]. The most prevalent nutritional disorders in the United States (US) are childhood overweight and obesity. In recent years, the occurrence of childhood obesity has tripled in the US as stated by The Obesity Society \[[@pone.0234244.ref003]\]. In the United Arab Emirates (UAE), the prevalence of overweight and obesity varied across age, where below 9 years of age both sexes were below the international standards with an increase overweight and obesity occurring among both genders of 9 to 18 years \[[@pone.0234244.ref004]\]. A more recent study demonstrated that in UAE, obesity starts in toddlers and progresses linearly with age and pointed out an alarming high prevalence of extreme obesity, especially among boys \[[@pone.0234244.ref005]\]. The estimated worldwide prevalence of childhood overweight and obesity has increased from 4.2% in 1990 to 6.7% in 2010, and it is expected to rise more in the following years to reach up to 9.1% in 2020 \[[@pone.0234244.ref006]\]. A combination of various factors clearly contributes to the childhood obesity epidemic. Hence, knowledge of these causative factors will help in the prevention of obesity. Socioeconomic and psychological factors may also contribute to childhood obesity \[[@pone.0234244.ref007]\]. The consumption of high-calories food with no or limited physical activity is the main contributor to childhood obesity \[[@pone.0234244.ref008]\]. Additionally, psychological factors such as familial stress, anxiety, and social isolation may contribute to childhood obesity. Children tend to increase their consumption of food to deal with their emotions and problems \[[@pone.0234244.ref008]\]. In addition, some people have a genetic predisposition for being overweight or obese, but most do not become overweight or obese unless there is an imbalance between calories consumed in diet and calories burned \[[@pone.0234244.ref009]\]. Some studies found that children of lower socioeconomic status have lack of safe places for physical activity and limited access to healthy food thus they tend to consume food that does not spoil quickly such as frozen meals, in addition to high intake of fast and fried food \[[@pone.0234244.ref010]\]. Other studies mentioned that with the economic improvement, a greater demand for fat-rich diet results in an increase in energy consumption predisposing children to obesity and other diseases \[[@pone.0234244.ref011]\]. Moreover, obese children are at higher risk of developing cardiovascular diseases, type 2 diabetes and certain types of cancer such as endometrial, colon, and postmenopausal breast cancer \[[@pone.0234244.ref012]\]. Prevention is the key element for controlling childhood obesity. Strategies that can be followed including; the primary prevention of overweight or obesity itself and second is the prevention of weight regain after weight loss, plus prevention of weight gain in individuals unable to lose weight \[[@pone.0234244.ref007]\]. Several studies have explored childhood obesity \[[@pone.0234244.ref004], [@pone.0234244.ref012]\], and without doubt, the problem is an issue of public concern. There is also unanimous view emphasizing that the paramount increase in childhood as well as adulthood obesity requires continuous surveillance \[[@pone.0234244.ref013], [@pone.0234244.ref014]\]. Providing recent estimates of childhood obesity is essential to keep the focus on this matter as it has many consequences on the children health \[[@pone.0234244.ref007]\]. Based on this background, the aim of this study was to investigate the prevalence of childhood obesity in various schools in Sharjah, UAE, and to determine the influence of eating behavior and lifestyle of children on obesity. Methods {#sec006} ======= Study design {#sec007} ------------ The present study was conducted in Sharjah, UAE, based on a cross sectional survey over a period of four months (August to November 2017). Ethical approval {#sec008} ---------------- This study received an ethical approval from the University of Sharjah Ethical Committee (REC-17-09-10-01-S). We informed parents, teachers, and the supervisors about the purpose and the nature of the study. The survey was coded, and the names were kept anonymous. Questionnaire development {#sec009} ------------------------- The development of questionnaire was based on the information needed for the study and it was written in both Arabic and English languages. The questionnaire was pre-piloted for face validity by distributing it to 12 parents of school children of the targeted age and their comments and recommendation were taken into consideration in the final version of the survey but their responses were included in results. The questionnaire included 20 items covered in two sections. The first section covered questions to collect information on socio-demographic and health related characteristics which included nine items (gender, age, ethnicity, weight, height, BMI percentile, family history of obesity, disease status and medication intake). The second section consisted of eleven items to collect information about child eating habits and lifestyle, and questions in this section addressed the child's eating patterns. These include the source of food consumed at school; frequency of consumption of fast food and candy, number of healthy meals, type and nature of food consumed as well as number of total meals per day. In addition, the section included questions on lifestyle (time interval between bedtime and the last meal, time spent using electronic devices, and physical activity). In this context we defined physical activity as any indoor or outdoor sport activity not including the use of smart devices or watching TV. On the other hand physical inactivity is defined as sedentary pleasurable activities such as watching cartoons on TV or using smart devices for gaming. The response options for participants to select from were variable. In questions on time intervals, we used a range of 30 minutes to more than two hours, for frequency (always, often, sometimes, rarely), and "Yes" and "No" answers. For other questions, the options were general for example, when the parents were asked about the ways of preparing foods for their children, the options were "boiled"," fried", "grilled" or "mixed", and for the nature of food consumed, the options were "carbohydrates", "fat", "protein" or "mixed". Additionally, we asked parents about the source of the food consumed by their children at school, and the options were "Bring his/her breakfast from home", "Buy a meal from cafeteria", "Just eat snacks", "Skip breakfast". The total number of surveys distributed was 932. Study population {#sec010} ---------------- From a list provided by the Ministry of Education, we selected schools in the Emirate of Sharjah based on their accessibility and availability and applied the non- probability sampling method. The study population included both male and female pupils aged 6--11 years. The total representative sample was 678 pupils (299 boys and girls 379) in eight schools in Sharjah; UAE using the online sample size calculator was 248 with a confidence interval of 95% and 5% margin of error for a population of 65473 from 8 schools \[[@pone.0234244.ref015]--[@pone.0234244.ref017]\]. Within each selected school, pupils from Grade I to V were offered the opportunity to voluntarily and anonymously participate. We based the selection of the pupils on the resubmission of questionnaire. The exclusion criteria included children with special needs of age below 6 and above 11 years, and parents who refused to participate in the study. Similar to the protocol employed in earlier studies \[[@pone.0234244.ref004]\], we trained members of the research team for three weeks on obesity, anthropometric measurements and how to conduct structured interviews of the participants. Anthropometric measurements {#sec011} --------------------------- Trained researchers measured student's height and weight in bare feet while wearing lightweight school uniform in the early morning before they start their daily classes. Weight (in kilograms) and height (in centimeters) were measured using Seca 799 scale. The BMI was calculated using Medscape online calculator. We defined obesity according to the CDC guidelines as a BMI ≥ 95th percentile and overweight as a BMI ≥ 85^th^---≤ 95^th^ percentile. The students were instructed to stand straight with their heads, backs and buttocks vertically aligned to the height gage, and then their heights were taken and rounded to the nearest 0.5 cm. Simultaneously, the students' weights were recorded from the digital screen and rounded to the nearest 0.5 kg. The three most important anthropometric measurements of clinical importance to be taken in paediatric practice are height or supine length, weight and head circumference. These measurements describe different body components and their changes have different biological significance. For other populations other than paediatrics the commonly obtained anthropometric measurements include height, weight, knee height, elbow breadth, triceps skinfold, subscapular skinfold, arm circumference, abdominal circumference and calf circumference. Obtained measurements are compared to standardized percentiles. Anthropometric measurements can be combined in the evaluation of nutritional status. For example, weight for height has been demonstrated as a strong predictor for 12-month mortality in haemodialysis patients. Mortality rate appears to decrease as patient's weight for height increase. BMI is also an important predictor. The use of correct body weight is essential for patient assessment and for determination of dietary needs. A variety of definitions of body weight have been used for nutritional assessment such as usual body weight, standard body weight, and ideal body weight \[[@pone.0234244.ref018]\]. Anthropometry involves the external measurement of morphologic traits of human beings. High quality anthropometric measurements are fundamental to clinical and epidemiological research. The measurements for each method have inherent variations, either due to biologic variation or due to error in measurement. Errors in measurement cannot be avoided completely but they can be minimized to a large extent. We define methods to estimate measurement error in anthropometry, offer guidelines for acceptable error, and suggest ways to minimize measurement error; thereby improving anthropometry quality in health assessments. We propose that special attention be paid to the following six key parameters for quality assurance of anthropometric measurements: (i) Identification of certified lead anthropometrist and trainer, (ii) manual of standard operating procedures, (iii) choice of robust equipment, (iv) equipment calibration, (v) standardization training and certification, and (vi) measurements resampling \[[@pone.0234244.ref019]\]. To abide by the above-mentioned parameters of quality assurance of anthropometric measurements, the researchers in this study were trained by certified professionals to take the measurements, and also measurement resampling was done. In addition to that the equipment used were standardized and calibrated before use. This is to improve anthropometric measurements quality and eliminate the error as much as possible. Finally, BMI measurements were calculated accordingly. Statistical analysis {#sec012} -------------------- We encoded the participants' responses and analyzed the data using Statistical Package for Social Sciences (IBM SPSS statistics for windows, version 20.0, IBM Corp., Armonk, NY, USA). We adopted descriptive analysis to calculate the response proportion of each group of respondents for each item in the questionnaire. We also used the Chi-square test to ascertain the association between the dependent variables and other independent selected variables considering the level of p\< 0.05 as the cut-off value of significance. Results {#sec013} ======= The total of surveys distributed was 932 and 678 surveys were completed and returned back giving a response rate of 72.8%. Throughout the process of distribution and collection of surveys, 46 samples were excluded including 4 participants who refused to participate, 9 were above 11 years, and 22 returned back unfilled surveys. We did not receive back additional 212 surveys, as the parents of the pupils were not interested to take a part in the study. Among the study pupils 299 (44.1%) were boys and 379 (55.9%) were girls. The average age of the pupils was 8.2±1.7 years, with an average height of 131±11.1 centimeters and weight of 30.5±10.8 kilograms. Less than one quarter (134; 19.8%) of the participants reported to have a family history of obesity. A total of 487 (59.4%) children showed normal range of BMI whereas 95 (14%) and 96 (14.2%) had an obese BMI and overweight respectively. [Table 1](#pone.0234244.t001){ref-type="table"} summarizes the socio-demographic and clinical characteristic of participants. 10.1371/journal.pone.0234244.t001 ###### Socio-demographic and clinical characteristics of participants. ![](pone.0234244.t001){#pone.0234244.t001g} Characteristic Frequency (%) ---------------------------------------------------------- --------------- **Child Gender**: Female 379 (55.9) Male 299 (44.1) Total 678 (100.0) **Family history of obesity**: Yes 134 (19.8) No 544 (80.2) Total 678 (100) **Overweight and obesity in pupils with family history** Overweight 32 (4.8) Obese 34 (5) Total 66 (9.8) **BMI Percentile**: Underweight 84 (12.4) Normal weight 403 (59.4) Overweight 96 (14.2) Obese 95 (14.0) Total 684 (100.0) **Source of food services**: Bring his/her lunch from home 456 (67.3) Buy a meal from school cafeteria 67 (9.9) Just eat snacks. 143 (143.0) Skip lunch 12 (1.8) Total 678 (100.0) Eating habits of participants {#sec014} ----------------------------- In the present study, 456 (67.3%) of the pupils included in the study ate their in-home prepared food and 21.1% (143) reported that they buy their meals from the school cafeteria. An interval of 1 to 2 hours elapsing between the last meal consumed and bedtime was reported by 241 (35.5%) of participants. Slightly more than half (372; 54.9%) of the respondents reported their children to consume food of mixed nature (carbohydrates, fats and proteins). The majority (590; 87%) reported to consume food that was prepared by boiling, frying or grilling methods. Consumption of two healthy meals per day was reported by 292 (43.1%) of the participants. [Table 2](#pone.0234244.t002){ref-type="table"} summarizes the eating habits of children included in the study. 10.1371/journal.pone.0234244.t002 ###### Eating habits of participants. ![](pone.0234244.t002){#pone.0234244.t002g} Eating Habits Frequency (%) ------------------------------------------------------------ ------------------------------------------------------------------ ------------ **Number of Meals During a Day** 1 meal 20 (2.9) 2--5 meals 646 (95.3) \> 5 meals 12 (1.8) **Total** 678 (100.0) **Time Interval Between Child Last Meal and Bed Time** 0-30minutes 95 (14.0) 30 minutes---1 hour 204 (30.1) 1 hour---2 hour 241 (35.5) \> 2 hours 138 (20.4) **Total** 678 (100.0) **Type of Food That Child Eats** Boiled 18 (2.7) Fried 49 (7.2) Grilled 21 (3.1) Mixed 590 (87.0) **Total** 678 (100.0) **Predominant food in child's diet** Carbohydrate (Rice, Bread, Milk, Yogurt, Corn, Potatoes, Fruits) 89 (13.1) Fats (Cheese, Dark Chocolate, Whole Eggs, Olive oil, Nuts) 11 (1.6) Proteins (Meat, Chicken, Fish, Eggs) 206 (30.4) Mixed 372 (54.9) **Total** 678 (100.0) **Eating Fast Food** Always 42 (6.2) Often 324 (47.8) Sometimes 207 (30.5) Rare 105 (15.5) **Total** 678 (100.0) **Eating Candy** Always 370 (54.6) Often 234 (34.5) Sometimes 55 (8.1) Rare 19 (2.8) **Total** 678 (100.0) **Number of Daily Healthy Food (Fruits and Vegetables)** 0 12 (1.8) 1 197 (29.1) 2 292 (43.1) 3 136 (20.1) \> 4 41 (6.0) **Total** 678 (100.0) Participants' leisure time {#sec015} -------------------------- When the parents were asked about the time their children spend watching TV and using electronic devices, more than one quarter of those watching TV (237, 35%) and using electronic devices (203, 29.9%) reported spending 1--2 hours daily on such a leisure. Furthermore, almost one quarter (162; 23.9%) of the children reported low levels of physical activity. [Table 3](#pone.0234244.t003){ref-type="table"} summarizes the patterns of children's physical activity and leisure time. 10.1371/journal.pone.0234244.t003 ###### Patterns of physical activity, daily leisure time and time spent using electronic devises. ![](pone.0234244.t003){#pone.0234244.t003g} Criteria Frequency (%) ----------------------------------------------- ----------------- --------------- **Physical Activity (classified per week)** Always (7 days) 169 (24.9) Often (3--5 days) 226 (33.3) Sometimes (1--2 days) 121 (17.8) Rare (0--1 day) 162 (23.9) **Total** 678 (100.0) **Leisure Time (per day)**: **Time Spent Watching TV** 30 minutes 100 (14.7) 30--60 minutes 160 (23.6) 60--120 minutes 237 (35.0) \> 120 minutes 181 (26.7) Total 678 (100.0) **Time Spent on Phone, Tablet, and Computer** None 21 (3.1) 30 minutes 136 (20.1) 30--60 minutes 149 (22.0) 60--120 minutes 203 (29.9) \> 120 minutes 169 (24.9) **Total** 678 (100.0) Disease status and medications use by participants {#sec016} -------------------------------------------------- Only 82 (12.1%) of the children were reported to have a disease and use medications. Iron deficiency anemia, allergy and asthma problems were among the most common diseases reported during the study period. Anti-allergic, anti-asthmatic, and iron supplements were among the most commonly medications used by the children. Relationship between BMI percentile, pupil's habits and lifestyle {#sec017} ----------------------------------------------------------------- Using chi-square test, we observed a number of statistically significant associations between BMI percentile, pupil's habits and lifestyle. The number of daily healthy food consumption and the predominant food in the child's diet were both significantly (p\< 0.002 and p\< 0.001 respectively) associated with BMI percentile of the participants. Furthermore, there was a significant association (p\<0.04) between time spent on television and BMI percentile of pupils included in the study (Tables [4](#pone.0234244.t004){ref-type="table"} and [5](#pone.0234244.t005){ref-type="table"}). 10.1371/journal.pone.0234244.t004 ###### Association of food habits with BMI percentile. ![](pone.0234244.t004){#pone.0234244.t004g} -------------------------------------- ------------------------------------------------- ------------------- ---------------- ----------- ----------- **BMI Percentile, Chi square test (p \<0.002)** **Number of daily healthy food** **Underweight** **Normal weight** **Overweight** **Obese** **Total** **0** **3** **6** **2** **1** **12** **1** **30** **109** **27** **31** **197** **2** **34** **178** **38** **42** **292** **3** **13** **91** **13** **19** **136** **4 or more** **4** **19** **16** **2** **41** **Total** **84** **403** **96** **95** **678** **BMI Percentile, Chi square test (p \<0.001)** **Predominant food in child's diet** **Underweight** **Normal weight** **Overweight** **Obese** **Total** **Carbohydrates** **14** **51** **12** **12** **89** **Fats** **1** **3** **1** **6** **11** **Proteins** **19** **136** **27** **24** **206** **Mixed** **50** **213** **56** **53** **372** **Total** **84** **403** -------------------------------------- ------------------------------------------------- ------------------- ---------------- ----------- ----------- 10.1371/journal.pone.0234244.t005 ###### Association of time spent on television with BMI Percentile. ![](pone.0234244.t005){#pone.0234244.t005g} Time spent on television/day BMI Percentile, Chi square test (p \< 0.040) ------------------------------ ---------------------------------------------- ----- ---- ---- ----- 30 minutes 10 65 16 9 100 30 minutes---1 hour 16 113 14 17 160 1--2 hours 34 125 38 40 237 More than 2 hours 24 100 28 29 181 Total 84 403 96 95 678 Discussion {#sec018} ========== We carried out the present study to determine whether childhood obesity is predominant in the Emirate of Sharjah, UAE and to establish the association between obesity and the child's lifestyle and eating patterns. The global prevalence of overweight and obesity in 2010 was 6.7% \[[@pone.0234244.ref001]\]. Results of the present study revealed that the prevalence of overweight and obese children in UAE is 28.2%, which is around four times higher than the global prevalence described above for 2010. Our findings suggest that the increase in the prevalence of obesity in Sharjah-school pupils is in total agreement with the results of recent studies carried out in UAE on different population samples \[[@pone.0234244.ref004]\]. Over the last 5 decades, the economic enhancement in all countries of the Eastern Mediterranean Region (EMR) was associated with a greater demand on diet that is rich in fat. Such a tendency by increasing the intake of energy predisposes to obesity and diseases \[[@pone.0234244.ref014]\]. Similar to the results of an earlier study in UAE (17), we also identified a high prevalence (12.4%) among school children. About 27.5% of the underweight children were between 6--7 years old. These findings suggest that under nutrition is common among children in the UAE despite the high-income status of the country. We noticed that the lowest consumption of healthy diet was in children who were underweight, which might be an underlying factor. Poor knowledge of healthy dietary patterns may be a reason for under nutrition. However, the exact determinants for under nutrition among children in the UAE warrants further dedicated investigation. We also observed that 19.8% of the participants had a family history of obesity, and 9.8% of them were overweight and obese. This is consistent with the findings of a similar study conducted in the Emirate of Abu Dhabi \[[@pone.0234244.ref020]\]. These results taken together, strongly supports the link that is widely documented in literature between family history of obesity and the development of obesity in children. A family history of obesity may promote childhood obesity through environmental and biological mechanisms. With regard to the environmental risk, mother's personal eating habits are likely to influence children's dietary patterns. Biologically, children whose both parents are overweight are predisposed to have a high BMI \[[@pone.0234244.ref021]\]. However, although genetic factors may contribute to the development of obesity, some researchers suggested that genetic factors only account for up to 5% of childhood obesity cases \[[@pone.0234244.ref022]\]. A significant association between child's age and BMI percentile (p-value = 0.01) was found. The prevalence of obesity and overweight was the highest (14.2%) in children aged 11 years and lowest (3%) at the age of 7 years. This is consistent with the results of a large cross-sectional study among UAE school children in both the Emirates of Abu Dhabi and Ras Al Khaimah \[[@pone.0234244.ref004], [@pone.0234244.ref005]\]. When taken together, these results reveal a trend of a progressive increase in the prevalence of overweight and obesity with age across the population of schoolchildren in the UAE that reflects global trends \[[@pone.0234244.ref023], [@pone.0234244.ref024]\]. The onset of puberty that occurs in children in this age group may contribute to the increase in the prevalence of obesity. Puberty is associated with the accumulation of adipose tissue and decreased physical activity; particularly among children who experience early puberty. These findings indicate that early interventions targeting children aged 6--7 years may be more likely to achieve better outcomes in minimizing or preventing the development of obesity in children. Results of the present study also revealed that the time spent watching TV and using smart devices was relatively high. About 35% of the total participants spend 1--2 hour per day watching TV and of those 11.5% were obese and overweight. This is consistent with results of the study carried out at the University of Texas Health Science Center and Baylor in Houston, which reported that 67% of their participants watched TV with an average of 1.84 hours per day \[[@pone.0234244.ref023]\]. Other studies suggested that watching TV has several effects that may lead to obesity including decreased metabolic rate, and increased snacking while watching TV in addition to the influence of food advertisements. Moreover, it has been documented that increasing the time spent on watching TV will increase the prevalence of obesity \[[@pone.0234244.ref024]\], a finding that parallels results of the present study but contrasts with those of another study that failed to show a link between BMI and watching TV \[[@pone.0234244.ref025]\]. Additionally, 29.9% of children spent 1--2 hours of their time on smart phones, tablets, and computers but we observed no significant association between the BMI percentile and time spent on these electronic devices. However, there is a correlation between the child's gender and time spent on smart phones and computers where 61.9% of the total male participants spent more than 1 hour on electronic devices as compared to 49.3% of the total female participants. Within the age pool of our study, the fact that boys were more interested in such instruments than girls may explain such results. There was no relationship between physical activity and BMI percentile (p value = 0.443), which is consistent with the findings of other studies that failed to demonstrate a significant effect of physical activity on BMI \[[@pone.0234244.ref024]\]. Although there is no difference in the obesity predominance between the two genders, we observed a significant association between the physical activity and child's gender in which the number of girls (15.5%) of the total population that rarely exercise is twice that of boys (8.4%). Traditional, cultural, and religious beliefs, as well as the inadequate sport facilities for females in schools are contributing factors for the reduced physical activity and sedentary lifestyle in females. The strict supervision by the parents over their children may also be a reason. The reason behind this strict supervision is that parents prefer to keep their children under their scrutiny at home rather than allowing them to play outdoors \[[@pone.0234244.ref007]\]. Another factor that pertains to UAE in particular is the hot weather that persists throughout the year. Extreme heat and conditions that can cause heat strokes and dehydration in children prevent parents from sending them outside to get any physical activity. Irrespective to gender differences, it is essential to emphasize the importance of physical activity in young children and to increase awareness of parents regarding its importance. Establishing adequate physical activity at a young age will help children maintain this habit throughout their life. In the present study, more than half (54.9%) of the participants tend to have food of a mixed nature (carbohydrates, fats, and proteins). The majority of participants (87%) reported consuming food with a mixed preparation pattern (boiled, fried, and grilled). It has been noted that a minor percentage of the population consume either fats (1.6%) or carbohydrates (13.1%). Furthermore, more than one quarter (30.4%) of the participants reported consuming protein as their main food with 7.5% of this group being obese and overweight. A study in the US found a correlation between BMI and dietary protein intake in children up to the age of 5 years \[[@pone.0234244.ref025]\]. High protein intake may result in a higher than normal BMI, this can be explained by the \"Early Protein Hypothesis\" which assumes that the high protein consumption will lead to high insulin-releasing amino acids in the plasma which will trigger insulin secretion and insulin like growth factor I (IGF-I) and leads to fat deposition and weight gain. It is worth noting that skipping breakfast is common among both adults and children, and this practice has a negative impact on BMI \[[@pone.0234244.ref014]\]. A study preformed in Al Ain, UAE reinforced that children who skipped breakfast are more likely to be obese \[[@pone.0234244.ref016]\]. According to the present results, about one quarter (21.1%) of the participants preferred eating snacks as their breakfast meal, which is mostly full of carbohydrates and with no beneficial nutritional value, and 1.8% of the participants skip breakfast. Collectively 13.6% of girls and 9.2% of boys of the total population have a habit of skipping a proper healthy breakfast meal. A systemic review carried out in Europe showed that individuals who eat breakfast are less likely to become obese or overweight \[[@pone.0234244.ref026]\]. In harmony with results of the present study, an earlier study in UAE reported that skipping breakfast is more common in girls (37%) as compared to boys (28%) in UAE \[[@pone.0234244.ref016]\]. Obesity has lately been associated with high consumption of fast food. Children often prefer fast food restaurants; and consumption of fast food has increased due to its convenience and affordability particularly in children of working parents. Regular consumption of fast food has shown bad influence on health as it contains a large number of calories with very low nutritional value, especially for children, who require nutrients for their growth and development. Despite the fact that numerous studies have showed that consumption of fast food causes weight gain, a relationship between the two factors is difficult to establish \[[@pone.0234244.ref004]\]. We pinpoint two methodological limitations that should be considered when interpreting the findings of the present study. First, we assessed dietary patterns by asking broad questions about food groups consumed and their quantity and sources of food. Hence, responses of participants may be subject to recall bias and personal interpretation than the use of a food diary that enables objective and detailed documentation of types and quantity of foods consumed within a specified period. Second, the UAE population is highly diverse, with the majority of people being expatriates from various Arabic-speaking, and South- and East-Asian countries, with Emirati citizens representing a minority. The marked differences in income, dietary practices, and cultural identities of the various ethnic groups in UAE can influence the development of obesity in children. In addition, Emirati children largely attend governmental schools while children of expatriates attend private schools. We did not specifically measure these factors in the present study and thus they require further investigation in large cross-sectional studies in the future. Conclusion {#sec019} ========== The percentage of overweight and obesity is high in both genders and across all ages of the studied population. However, we observed that the highest percentage of overweight is among children at the age of 11years and this may be a consequence of their sedentary lifestyle, consumption of unhealthy food and family history. Further investigation regarding this topic is required, and increasing awareness of the public towards childhood obesity is to be achieved in the near future as an essential task to limit further progression of obesity in UAE and to protect against non-communicable diseases that may be associated with obesity. Supporting information {#sec020} ====================== ###### (PDF) ###### Click here for additional data file. ###### (PDF) ###### Click here for additional data file. ###### (PDF) ###### Click here for additional data file. ###### (PDF) ###### Click here for additional data file. 10.1371/journal.pone.0234244.r001 Decision Letter 0 Siegel Robert Academic Editor © 2020 Robert Siegel 2020 Robert Siegel This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 6 Apr 2020 PONE-D-19-26655 Obesity and its associated risk factors among school-aged children in Sharjah, UAE PLOS ONE Dear Dr Abduelkarem, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE's publication criteria as it currently stands. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer \#1: Comments to the Author This Study aimed to assess "obesity and its associated risk factors among school-aged children in sharjah" 1- In the introduction section the authors refer to the prevalence of childhood overweight and obesity in the US and worldwide, but they did not provide any description about the prevalence of childhood overweight and obesity in the UAE. Please add this data in the introduction. 2- Anthropometric measurements: Quality assurance for anthropocentric measurements should be described in details. 3- Is the questionnaire of dietary habit reliable or valid for this population study? Please provide more information about reliability and validity of this questionnaire. 4- The author did not provide any information about the physical activity in children. Please add this information in the methods section (questionnaire development section). 5- Based on method section you select population between native and non-native students, but in the results you did not refer to this. How many of the subjects were non-native? Are there any differences in the prevalence of childhood overweight and obesity between the native and non-native students? 6- What is the definition of physical inactivity that you reported in the result section? 7- In the statistical analysis the author used the chi-square test to ascertain the association between the dependent and independent variables, how you can use Chi-square test for ascertain an association? Please check the type of statistical tests with a statistician. 8- Table section: The author must mention that the type of statistical tests was used for assessing the difference of various socio-demographic, lifestyle, anthropometric, in across BMI percentile. 9- In the table you did not refer that what type of data was used, number or percent? Reviewer \#2: I commend the authors on taking on an important project. This type of research is needed in order to reverse the obesity epidemic that threatens all nations. I have multiple concerns about this manuscript. The methods section is missing pertinent details about how the sample was created (how many schools, every child in the age range within the school or certain grades, etc.; what are the demographics of the schools included -- similar, different). Additionally, some of the questions in the survey are hard to follow (see line corrections below). The descriptive results in table 1 are not presented by BMI category, which makes it harder for the reader to understand the sample. There is insufficient text supporting the findings in table 4 & 5. Additionally, the discussion is too long. The authors should seek to identify the take home findings and what adds to the literature, rather than discussing every result. Also, a re-review of the grammar would be helpful, as there are multiple errors throughout. Lastly, some of the links provided within the references are outdated and need to be revisited and reinserted. Please see some additional line suggestions below. Line suggestions Abstract: 1\. Line 36: Should read "...and determine" rather than determining 2\. Line 38: insert "was" before the word based 3\. Line 43: Recommend person-first language. Would recommend from "were obese or overweight" to "had obesity or overweight." Introduction: 4\. Line 65-66: The consumption of high calories food with no or limited physical activity is the main contributor to childhood obesity. This statement needs a citation. 5\. Line 73: Run on sentence, needs appropriate punctuation. 6\. Line 80: Two strategies can be followed including; the primary prevention of overweight or obesity itself and second is the prevention of weight regain after weight loss, plus prevention of weight gain in individuals unable to lose weight \[5\]. This statement is confusing. Initially talks about two strategies, but introduces a third. 7\. Line 100: Add "the" before the word questionnaire. Methods: 8\. The survey question asking the Nature of food consumed to parents is very confusing. Why were fruit and vegetables not included as an answer choice for the question: predominant food in child's diet? What does mixed mean -- 2 categories, 3 categories? Would be better to have had families give percentages. Was fruit included in carbohydrate? Was the any ascertainment of baseline knowledge level -- were families clear on what food groups fell into each of these categories? 9\. I am concerned about selection bias. The parents/child that returned the survey could be inherently different that the ones that didn't. Did you have any data to say that your sample population is representative? Do you have any data on the parents/children that chose not to participate or the data on the schools as a whole? Study Population 10\. How many schools were participants recruited from? Were the schools the same in terms of demographics of students? 11\. Were the surveys sent to every child in a specific grade. Need to expand on how the sample was put together in more detail. Results: 12\. Line 153: Person first language recommended. (E.g. Had an obese BMI, rather than were obese.) 13\. Descriptive characteristics should be presented by BMI category. 14\. It is unclear how disease status and medication use were related to the aims of the study. \*\*\*\*\*\*\*\*\*\* 6\. PLOS authors have the option to publish the peer review history of their article ([what does this mean?](https://journals.plos.org/plosone/s/editorial-and-peer-review-process#loc-peer-review-history)). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. **Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our [Privacy Policy](https://www.plos.org/privacy-policy). Reviewer \#1: No Reviewer \#2: No \[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link \"View Attachments\". 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Please note that Supporting Information files do not need this step. ###### Submitted filename: comments to authors.docx ###### Click here for additional data file. 10.1371/journal.pone.0234244.r002 Author response to Decision Letter 0 7 May 2020 All the invaluable comments of the respected reviewers and the journal additional comments were considered and our responses are attached as "our responses to reviewer's comments" and "our responses to additional journal comments" two separate file. As per your request, a copy of the survey, in both the original language (Arabic) and English, will be attached for you as Supporting Information. To answer your request regarding "copyedit your manuscript for language usage, spelling, and grammar", the manuscript was thoroughly revised by one of us namely Prof. Suleiman I. Sharif, College of Pharmacy, University of Sharjah, Sharjah, UAE. 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It must be noted that in our study the identity of the participants was disguised. ###### Submitted filename: 3-Our Response to Reviewers Comments.docx ###### Click here for additional data file. 10.1371/journal.pone.0234244.r003 Decision Letter 1 Siegel Robert Academic Editor © 2020 Robert Siegel 2020 Robert Siegel This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 22 May 2020 Obesity and its associated risk factors among school-aged children in Sharjah, UAE PONE-D-19-26655R1 Dear Dr. Abduelkarem, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. 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The [PLOS Data policy](http://www.plosone.org/static/policies.action#sharing) requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data---e.g. participant privacy or use of data from a third party---those must be specified. Reviewer \#1: Yes Reviewer \#2: (No Response) \*\*\*\*\*\*\*\*\*\* 5\. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. 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Golden Colorado Hotels Located in historic downtown Golden, Colorado, in the beautiful foothills of the Rocky Mountains, Table Mountain Inn is a welcoming retreat just 15 minutes from Denver. Our adobe style hotel is surrounded by exciting attractions, including Colorado School of Mines, Foothills Art Center, Red Rocks Amphitheatre, Blackhawk Casinos, Bandimere Speedway, Sports Authority Field at Mile High Stadium, Pepsi Center and Coors Field. Our hotel is within walking distance to downtown's shops, restaurants, art galleries, and microbreweries and just a few blocks from the Coors Brewery. Experience Colorado's outdoor adventures, like fishing, hiking, rafting, mountain biking and winter skiing and snowboarding. Nestled in the hills of the front range of the Rockies, our hotel is near the area's most popular hiking and biking trails and world class ski resorts.
New England Patriots head coach Bill Belichick indicated Monday, Aug. 12, that there is a "competitive situation" for the starting job between Ps Ryan Allen and Zoltan Mesko. Allen has practice squad eligibility if he is unable to win the job outright. Mesko is also the holder for extra points and field goals, which might work in his favor. New England Patriots P Ryan Allen could make a serious push to win the punter job over P Zoltan Mesko during offseason workouts and training camp. Mesko is scheduled to make $1.3 million this season while Allen would make a little over $400,000 if he won the job, which could be a factor in the decision. Allen could be added to the practice squad if he does not win the job. New England Patriots P Zoltan Mesko said he is ready to compete with P Ryan Allen for the punter job during offseason workouts and training camp. Mesko said he will also be willing to help Allen out when he needs it. New England Patriots P Zoltan Mesko (knee) was limited during practice Friday, Sept. 23. He is listed as questionable for Week 3 and may be able to play. The team will look to sign a punter if Mesko is not able to play. New England Patriots P Zoltan Mesko said he is looking to be more consistent in his punting and believes he could be putting too much pressure on himself, reports Karen Guregian, of the Boston Herald. "It's just the adjustment of me wanting to prove myself as soon as possible and help this team win," Mesko said. "It's just maybe me putting more pressure on myself. But I can handle it."
/* * Copyright (C) 2011 The Android Open Source Project * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. */ package android.support.v4.app; import java.util.ArrayList; import android.os.Bundle; import android.os.Parcelable; import android.support.v4.view.PagerAdapter; import android.util.Log; import android.view.View; import android.view.ViewGroup; /** * Implementation of {@link android.support.v4.view.PagerAdapter} that * uses a {@link Fragment} to manage each page. This class also handles * saving and restoring of fragment's state. * * <p>This version of the pager is more useful when there are a large number * of pages, working more like a list view. When pages are not visible to * the user, their entire fragment may be destroyed, only keeping the saved * state of that fragment. This allows the pager to hold on to much less * memory associated with each visited page as compared to * {@link FragmentPagerAdapter} at the cost of potentially more overhead when * switching between pages. * * <p>When using FragmentPagerAdapter the host ViewPager must have a * valid ID set.</p> * * <p>Subclasses only need to implement {@link #getItem(int)} * and {@link #getCount()} to have a working adapter. * * <p>Here is an example implementation of a pager containing fragments of * lists: * * {@sample development/samples/Support13Demos/src/com/example/android/supportv13/app/FragmentStatePagerSupport.java * complete} * * <p>The <code>R.layout.fragment_pager</code> resource of the top-level fragment is: * * {@sample development/samples/Support13Demos/res/layout/fragment_pager.xml * complete} * * <p>The <code>R.layout.fragment_pager_list</code> resource containing each * individual fragment's layout is: * * {@sample development/samples/Support13Demos/res/layout/fragment_pager_list.xml * complete} */ public abstract class FragmentStatePagerAdapter extends PagerAdapter { private static final String TAG = "FragmentStatePagerAdapter"; private static final boolean DEBUG = false; private final FragmentManager mFragmentManager; private FragmentTransaction mCurTransaction = null; private ArrayList<Fragment.SavedState> mSavedState = new ArrayList<Fragment.SavedState>(); private ArrayList<Fragment> mFragments = new ArrayList<Fragment>(); private Fragment mCurrentPrimaryItem = null; public FragmentStatePagerAdapter(FragmentManager fm) { mFragmentManager = fm; } /** * Return the Fragment associated with a specified position. */ public abstract Fragment getItem(int position); @Override public void startUpdate(ViewGroup container) { } @Override public Object instantiateItem(ViewGroup container, int position) { // If we already have this item instantiated, there is nothing // to do. This can happen when we are restoring the entire pager // from its saved state, where the fragment manager has already // taken care of restoring the fragments we previously had instantiated. if (mFragments.size() > position) { Fragment f = mFragments.get(position); if (f != null) { return f; } } if (mCurTransaction == null) { mCurTransaction = mFragmentManager.beginTransaction(); } Fragment fragment = getItem(position); if (DEBUG) Log.v(TAG, "Adding item #" + position + ": f=" + fragment); if (mSavedState.size() > position) { Fragment.SavedState fss = mSavedState.get(position); if (fss != null) { fragment.setInitialSavedState(fss); } } while (mFragments.size() <= position) { mFragments.add(null); } fragment.setMenuVisibility(false); fragment.setUserVisibleHint(false); mFragments.set(position, fragment); mCurTransaction.add(container.getId(), fragment); return fragment; } @Override public void destroyItem(ViewGroup container, int position, Object object) { Fragment fragment = (Fragment)object; if (mCurTransaction == null) { mCurTransaction = mFragmentManager.beginTransaction(); } if (DEBUG) Log.v(TAG, "Removing item #" + position + ": f=" + object + " v=" + ((Fragment)object).getView()); while (mSavedState.size() <= position) { mSavedState.add(null); } mSavedState.set(position, mFragmentManager.saveFragmentInstanceState(fragment)); mFragments.set(position, null); mCurTransaction.remove(fragment); } @Override public void setPrimaryItem(ViewGroup container, int position, Object object) { Fragment fragment = (Fragment)object; if (fragment != mCurrentPrimaryItem) { if (mCurrentPrimaryItem != null) { mCurrentPrimaryItem.setMenuVisibility(false); mCurrentPrimaryItem.setUserVisibleHint(false); } if (fragment != null) { fragment.setMenuVisibility(true); fragment.setUserVisibleHint(true); } mCurrentPrimaryItem = fragment; } } @Override public void finishUpdate(ViewGroup container) { if (mCurTransaction != null) { mCurTransaction.commitAllowingStateLoss(); mCurTransaction = null; mFragmentManager.executePendingTransactions(); } } @Override public boolean isViewFromObject(View view, Object object) { return ((Fragment)object).getView() == view; } @Override public Parcelable saveState() { Bundle state = null; if (mSavedState.size() > 0) { state = new Bundle(); Fragment.SavedState[] fss = new Fragment.SavedState[mSavedState.size()]; mSavedState.toArray(fss); state.putParcelableArray("states", fss); } for (int i=0; i<mFragments.size(); i++) { Fragment f = mFragments.get(i); if (f != null) { if (state == null) { state = new Bundle(); } String key = "f" + i; mFragmentManager.putFragment(state, key, f); } } return state; } @Override public void restoreState(Parcelable state, ClassLoader loader) { if (state != null) { Bundle bundle = (Bundle)state; bundle.setClassLoader(loader); Parcelable[] fss = bundle.getParcelableArray("states"); mSavedState.clear(); mFragments.clear(); if (fss != null) { for (int i=0; i<fss.length; i++) { mSavedState.add((Fragment.SavedState)fss[i]); } } Iterable<String> keys = bundle.keySet(); for (String key: keys) { if (key.startsWith("f")) { int index = Integer.parseInt(key.substring(1)); Fragment f = mFragmentManager.getFragment(bundle, key); if (f != null) { while (mFragments.size() <= index) { mFragments.add(null); } f.setMenuVisibility(false); mFragments.set(index, f); } else { Log.w(TAG, "Bad fragment at key " + key); } } } } } }
This site is never involved in any transaction, and does not handle payments, shipping, guarantee transactions, provide escrow services, or offer "buyer protection" or "seller certification" Description Alveo Land Inc. CERCA Viento “A Closer Path to Essential Living” Location: Investment Drive, Alabang Type: Residential Condo Alveo’s first foray into the Alabang corridor, CERCA, reveals a 6.6 hectare novel mixed-use district, emanating the laid-back lifestyle that is distinctly of the South. A walkable and highly-accesible masterplan presents a living experience where verdant space and contemporary urban elements come in perfect balance. A fresh community unfolds at Cerca. Residential, Corporate, and Retail destinations are complemented by an expanse of verdant open space. A highly-walkable-mixed-use district offering easy access to settings for everyday convergence and interaction LOCATION Along investment drive, adjacent to Madrigal Business Park right by Ayala Alabang Cerca Alabang introduces a way of life in a location known for its contemporary offerings and design. It also, assures unparalleled access to world-class health and educational institutions, and top financial and commercial centers, thus providing utmost convenience for you and your family. THE 1st compact mixed use district in the Alabang corridor -Residential -Retail/Office -Office The district’s main features include its pedestrian rotonda, open spaces and mainly underground car access The heart of a dynamic community “Shops at Cerca” presents an array of retail and entertainment destinations within the district’s signature rotunda. Restaurants, shops, cafes, service establishments, and everyday conveniences welcome residents, guest, and corporate denizens, transforming into ideal spaces for vibrant gatherings and activity
Polysaccharide-thickened aqueous fluoride solutions for rapid destruction of the nerve agent VX. Introducing the opportunity for extensive decontamination scenarios. Among the chemical warfare agents, the extremely toxic nerve agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) is a target of high importance in the development of decontamination methods, due to its indefinite persistence on common environmental surfaces. Liquid decontaminants are mostly characterized by high corrosivity, usually offer poor coverage, and tend to flow and accumulate in low areas. Therefore, the development of a noncorrosive decontaminant, sufficiently viscous to resist dripping from the contaminated surface, is necessary. In the present paper we studied different polysaccharides-thickened fluoride aqueous solutions as noncorrosive decontaminants for rapid and efficient VX degradation to the nontoxic product EMPA (ethyl methylphosphonic acid). Polysaccharides are environmentally benign, natural, and inexpensive. Other known decontaminants cannot be thickened by polysaccharides, due to the sensitivity of the latter toward basic or oxidizing agents. We found that the efficiency of VX degradation in these viscous solutions in terms of kinetics and product identity is similar to that of KF aqueous solutions. Guar gum (1.5 wt %) with 4 wt % KF was chosen for further evaluation. The benign nature, rheological properties, adhering capabilities to different surfaces, and decontamination from a porous matrix were examined. This formulation showed promising properties for implementation as a spray decontaminant for common and sensitive environmental surfaces.
17 Ryan Vesce (C) Worcester Sharks Name: Ryan Vesce Number: 17 Position: C Shoots: R Height: 5-8 Weight: 175 Birthdate: 1982-04-07 Birth place: Lloyd Harbor, NY Biography 2008-09 Final Playoff Stats: 12gp 10 points (3-7-10) 22 penalty minutes and -2…. Recorded two assists in game 5 at Providence….recorded two assist and 12 pims (misconduct) in game 3 at Providence and was voted # 3 star… recorded an assist in game 1 at Providence… recorded an assist in game 6 vs. Hartford… had goal and assist in game 4 vs. Hartford…. scored first two AHL playoff goals including OTG in 2nd OT (1:07) and was #1 star in game 3 vs. Hartford… Final regular season stats- 67gp, 71 points (24 goals, 47 assists) with 28 penalty minutes … Fired 298 shots and was +4…Named team MVP… finished 13th in the AHL with 71 points, 2nd with nine game winning goals, and 1st with four OT goals…set franchise record with 17 game point streak (9-18-27) on Dec 29th through Feb 15th….Had an assist on 4/11 vs. Providence…Scored vs. Portland on 4/8…Had an assist vs. Hartford on 3/15…Scored goal and had an assist vs. Manchester on 3/14, #1 star…Netted a goal vs. Binghamton on 3/11…Recorded assist vs. Manchester on 3/8…Had an assist vs. Philadelphia on 3/6…Credited with an assist vs. Hartford on 3/ 4…Had goal vs. Springfield on 2/28…Had goal vs. Portland on 2/27…Credited with three assists vs. Lowell on 2/25, games #3 star…Had goal vs. Lowell on 2/22…Had goal and assist vs. W-B/Scranton on 2/15…Recorded an assist vs. Providence on 2/8…Had goal vs. Portland on 2/4, games number three star… Had assists in back to back games, vs. Providence 2/1 and vs. Portland 2/4…Credited for goal and assist vs. Springfield on 1/23, games number one star…Will play for Planet USA in AHL All-Star Classic in Worcester on 1/26 … Is riding an 11-game point streak (6-10=16) which is by far the most on the Sharks this season … Had two assists at Hershey (1/18), two goals at Norfolk (1/17), assist at Norfolk (1/16), and assist at Philadelphia (1/14) … Racked up a point in every game of Worcester’s season-high seven-game home stand: Assist vs. Lowell (1/10) and vs. Albany (1/9), goal vs. Hershey (1/4), assist vs. Lowell (1/3), goal and assist vs. Norfolk (1/2), assist vs. Houston (12/31), and two goals and an assist vs. Portland (12/29) … Had a four-game point streak in which he tallied six points (2g, 4a) dating 12/13-21: assist at Portland (12/21), goal and two assists vs. Manchester (12/20), assist vs. Hartford (12/14), goal at Lowell (12/13) … Had a three-game point streak dating 12/5-10 (2g, 2a): goal vs. Springfield (12/10), goal and assist vs. Portland (12/7), assist at Manchester (12/5) … Tallied a four-game point streak (3 goals, 3 assists) from 11/26-11/30…Back-to-back games with an assist at Springfield, vs. Norfolk (11/16, 11/19)…Credited with an assist vs. Manchester (11/1)… Had an assist in consecutive games (10/22, 10/24)…Scored game-winner in overtime vs. Providence (10/18)…Had an assist in each of the next two games (10/22, 10/24)…Had two assists in opener at Lowell (10/11)…2007-08: Led Helsinki in points and goals (T-5th in league)…Teammates with former Sharks forward Steve Guolla…2006-07: Fourth on the team in points and second in assists…Scored eight power play goals and two shorthanded…2005-06: Led team in points and power play goals…Finished 14th in the AHL and led team in assists…2004-05: Amongst league leaders, was T-4th in points, T-6th in assists and T-10th in goals…2003-04: Second on Cornell in points…2002-03: Finished 25th in the nation in points per game (1.25)….Named to the ECAC Second Team All-Conference…T-8th in the nation in game-winning goals (five)…Teammates with current Sharks defenseman Douglas Murray…2001-02: Fourth on team in points and assists…2000-01: T-5th amongst ECAC freshmen in points.
All relevant data are within the paper and its Supporting Information files. Introduction {#sec001} ============ A broad range of microorganisms thrives in environments with varying and high concentration of sodium chloride \[[@pone.0168818.ref001], [@pone.0168818.ref002]\]. An important osmoregulatory mechanism that allows microorganisms to cope with high salinities is the ability to amass highly water-soluble organic compounds, which do not disturb the cell's metabolism even at high cytoplasmic concentrations and are therefore named compatible solutes \[[@pone.0168818.ref003]\]. The halophilic γ-proteobacterium *Halomonas elongata* DSM 2581^T^ synthesizes the aspartate derivative ectoine \[[@pone.0168818.ref004]--[@pone.0168818.ref007]\] as its main compatible solute \[[@pone.0168818.ref008]\]. By accumulating ectoine, *H*. *elongata* achieves a broad salt tolerance and can even survive in salt saturated brines (\>5 M, 30% NaCl) \[[@pone.0168818.ref009]\]. Following a sudden increase in salt concentration, *H*. *elongata* increases the cytoplasmic K^+^ concentration along with the organic counter ion glutamate as a first response. Contrary to *Escherichia coli* and other mostly non-halophilic bacteria \[[@pone.0168818.ref010]\], the K^+^-glutamate level stays elevated in *H*. *elongata* for an extended time of at least two hours \[[@pone.0168818.ref011], [@pone.0168818.ref012]\]. Potassium is accumulated in the cytoplasm by transport via the two Trk-type transport systems TrkH and TrkI \[[@pone.0168818.ref013]\]. With increasing K^+^-glutamate levels, ectoine synthesis is switched on. The compatible solute ectoine is critical for the biology of *H*. *elongata* as shown by the mutation of genes involved in its biosynthesis. The genes *ectABC* encode the enzymes for conversion of the intermediate DABA (diaminobutyric acid) to ectoine. Cells with a deleted *ectA* gene (L-2,4-diaminobutyrate Nγ-acetyltransferase) failed to grow in medium containing more than 0.7 M NaCl (4%) \[[@pone.0168818.ref014], [@pone.0168818.ref015]\], a salt concentration that is within the optimal growth range. This result emphasizes the importance of ectoine for adaptation to high salinity in *H*. *elongata*. As shown by Göller \[[@pone.0168818.ref016]\], synthesis of ectoine is regulated at the level of transcription and at the level of enzyme activity. The *ectABC* genes are under the control of an osmoregulated σ^38^ dependent promoter upstream of *ectA*, a σ^70^ dependent promoter, and a σ^54^ dependent promoter in front of *ectC* \[[@pone.0168818.ref017]\]. This set of promoters is consistent with the observed transcription regulation data. *Halomonas elongata* does not rely only on *de novo* synthesis of ectoine for osmoadaptation, but can also take up compatible solutes from the medium such as glycine-betaine via the two BCC-family transporters BetG and BetH \[[@pone.0168818.ref012]\]. However, only one transport system, the TRAP-transporter TeaABC, catalyzes specifically ectoine uptake in *H*. *elongata* \[[@pone.0168818.ref015]\]. TeaABC is not only required for the osmoregulatory accumulation of external ectoine, but also counterbalances an unknown system responsible for excreting endogenous ectoine to the medium. There is evidence that TeaABC might be linked to the regulation of ectoine synthesis \[[@pone.0168818.ref015], [@pone.0168818.ref018]\]. A model explaining the involvement of TeaABC with ectoine synthesis was developed \[[@pone.0168818.ref019]\], which helped to design an ectoine production strain of *H*. *elongata* with higher productivity for ectoine than the wild-type strain \[[@pone.0168818.ref018]\]. Ectoine is synthesized by a large number of aerobic, heterotrophic bacteria \[[@pone.0168818.ref020], [@pone.0168818.ref021]\] and is also a dominant compatible solute in halophilic methanotrophs and methylotrophs \[[@pone.0168818.ref022]--[@pone.0168818.ref024]\] However, despite the ability to synthesize ectoine, quite a few of these bacteria such as *Pseudomonas stutzeri* and many *Vibrio* species display reduced salt tolerance compared to *H*. *elongata* and are restricted to environments containing less than 1.7 M NaCl (10%) \[[@pone.0168818.ref025]\]. Apparently, different osmoregulatory mechanisms must exist in *H*. *elongata* and other halophilic bacteria that allow them to cope with salt concentrations well above 1.7 M NaCl (10%). In a recent paper, Pastor and coworkers analyzed the metabolism of the halophilic bacterium *Chromohalobacter salexigens* \[[@pone.0168818.ref026]\], which has a similar salt tolerance to *H*. *elongata* and synthesizes ectoine as its major compatible solute. By applying isotope label tracing they found out that the metabolism of *C*. *salexigens* is adapted to support high metabolic fluxes towards synthesis of ectoine. While this makes the metabolism well suited for survival in high saline environments, it is less suited for growth at low salinity. To gain more information about the metabolic mechanisms that allow *H*. *elongata* to thrive at salinities above 1.7 M NaCl (10%), we identified target proteins by a preliminary quantitative profiling analysis of the membrane and soluble proteome at optimal (1 M NaCl), 6%), low (0.1 M, 0.6%), and high salinities (2 M, 12%). Target proteins were further analyzed by measuring the enzyme activity at different salinities and/or monitoring the expression of the corresponding genes by RT-qPCR. The data from these experiments were used to build a stoichiometric model of osmoadaptation in *H*. *elongata*. Our results indicate that significant osmoregulatory events go far beyond the ectoine synthesis pathway. There is a systemic response that requires coordinated action of different subsystems such as the PEP-pyruvate-oxaloacetate node and sodium transport. Materials and Methods {#sec002} ===================== Bacterial strains and growth conditions {#sec003} --------------------------------------- *Halomonas elongata* DSM 2581^T^ was grown on minimal medium MM63 \[[@pone.0168818.ref027]\] at 30°C with 0.85 M NaCl or on complex medium LB containing 0.85 M NaCl (5% w/v). For proteomic analysis (see below) cells of *H*. *elongat*a were cultivated in a modified liquid glucose mineral-salt medium (GM) with 0.1 M (0.6%), 1.0 M (6%), and 2.0 M NaCl (12%), respectively \[[@pone.0168818.ref028]\]. For RT-qPCR analysis and characterization of metabolic pathways by enzyme assays, *H*. *elongata* cells were cultured under aerobic conditions in GM medium with 0.1 M (0.6%), 1.0 M (6%), and 2.0 M NaCl (12%), respectively, and harvested in the exponential growth phase. Bacterial cell mass was determined photometrically at 600 nm against medium as a reference (OD~600~). RNA isolation and quantitative RT-PCR (RT-qPCR) {#sec004} ----------------------------------------------- Total RNA was isolated from exponentially growing cells using a modified hot phenol method \[[@pone.0168818.ref029]\] and further purified using the NucleoSpin RNA-isolation kit (Macherey & Nagel) according to the manufacturer\'s instructions. cDNA for quantitative RT-PCR analysis was synthesized by random priming using the iScript kit (Bio-Rad) according to the manufacturer's instructions. After synthesis, cDNA was diluted 1:15 with DEPC-water and cDNA was quantified with a NanoDrop photometer (Thermo Scientific). cDNA (10 ng, approximately 2 μl) was added to iTaq Universal SYBR Green Supermix (total volume 10 μl), which contained forward primer and reverse primer at a concentration of 25 pmol each. The name of the target genes and the DNA sequences of the 23 primer pairs used to study the expression of the genes are provided in Table A in the [S1 File](#pone.0168818.s001){ref-type="supplementary-material"} (Supplementary Material). RT-qPCR amplification and quantification (2^ΔCt^ method) was carried out on a Bio-Rad CFX96 PCR-cycler applying the following cycle: 95°C for 3 min; 39 cycles of 95°C for 5 s to 15 s and 60°C for 30 s. For each gene, RNA isolation, cDNA synthesis and qPCR analysis was repeated at least twice (three biological replicates). For each biological replicate, cDNA synthesis and qPCR analysis (three runs in parallel) was repeated at least one time (two technical replicates). Statistical analysis of the obtained data was carried out using the Origin software package (OriginLaB). Enzyme assays {#sec005} ------------- The halophilic bacterium *Halomonas elongata* DSM 2581^T^ \[[@pone.0168818.ref009]\] was used in all enzyme activity measurements in this study. Batch cultures were first grown in 2 ml GM medium. In a second step, 100 ml GM medium (1 M NaCl) in 500 ml flasks were inoculated with an OD~600nm~ of 0.015 and left to grow over night. Subsequently, the cultures were respectively adapted to varying salt concentrations (0.1; 1; 2 M) during three over night cultures with inoculation ODs of below 0.015 being used. The following main cultures were left to grow in their adapted salt concentration and harvested for the enzyme activity measurements the following day, during late exponential phase, by pelleting for 20 min at 25°C with 3,200 x g. The enzyme assays were adapted for *H*. *elongata*, with enzyme activity being determined by monitoring the oxidation of the coenzymes NADH and NADPH (340 nm) or the formation of fumarate in the case of fumarase (240 nm), in a 96-well microplate reader (Infinite M200 PRO Series, Tecan) for 10 min at 30°C. Enzyme activity was defined as the micromoles of substrate consumed or product formed per minute and mg of total protein (Units mg^-1^). In each case, cell pellets were put on ice and resuspended in 65 mM ice cold phosphate buffer (pH 7.5) containing 1 mM EDTA. Cells were sonicated on ice with a 3 mm diameter probe using a Digital Sonifier S450D (Branson) and centrifuged subsequently for 20 min at 4°C with 15,000 x g to remove cell debris. Afterwards the supernatant was filtered (0.4 μm pore size) to remove any intact cells and the resulting cell free extract was used for subsequent activity measurements. Protein concentration in cell-free extracts was determined by a BCA Protein Assay Kit (Pierce, Thermo Scientific). ### Alanine dehydrogenase (*ald)* {#sec006} A modified version of the assay described by Hutter & Dick \[[@pone.0168818.ref030]\] was used to measure the enzyme activity of the alanine dehydrogenase. The co-substrates NADH and NADPH were measured each, to define the co-substrate specificity of the enzyme, while the substrate pyruvate alone was used as a negative control. The assay mixture consisted of 50 mM TRIS-HCl buffer (pH 8.5) containing 1 mM EDTA, 100 mM NH~4~Cl, 15 mM pyruvate and either 0.5 mM NADH or 2 mM NADPH. ### Fumarase (*fumC*) {#sec007} The enzyme activity of fumarase was determined by a modified protocol of Van der Werf and colleagues \[[@pone.0168818.ref031]\] where the formation of fumarate was tracked at 240 nm. The reaction mixture consisted of 90 mM TRIS-HCl buffer (pH 8.0) and the substrate 50 mM malat (pH 7.0), the absence of which was also used as a negative control. ### Glutamate dehydrogenase (*gdh*) {#sec008} The activity of the glutamate dehydrogenase was measured according to Tesch and colleagues \[[@pone.0168818.ref031]\] with modifications. To determine the co-substrate specificity of the dehydrogenase, NADH and NADPH were measured each, while the absence of the substrate α-ketoglutarate was used as a negative control. The master mix consisted of 50 mM TRIS-HCl buffer (pH 8.5) containing 1 mM EDTA, 100 mM NH~4~Cl, 15 mM α-ketoglutarate and either 0.5 mM NADH or 2 mM NADPH. ### Glutamate synthase (*gltDB*) {#sec009} The enzyme activity of the glutamate synthase was determined by following the oxidation of NADPH in an assay originally described by Singh & Srivastava \[[@pone.0168818.ref032]\]. The enzyme catalyzes a reaction with the substrates L-glutamine and α-ketoglutarate, both of which were left out in negative controls. The assay mixture contained 25 mM phosphate buffer (pH 7.5) with 1 mM EDTA, 2.7 mM L-glutamine, 0.67 mM α-ketoglutarate, 3.3 mM KCl and 0.4 mM NADPH. ### Malic enzyme (*Mae*) {#sec010} The activity of the malic enzyme was measured according to Van der Werf and co-workers \[[@pone.0168818.ref033]\] with slight modifications. The reaction mixture contained 0.1 M Tris-HCl (pH 7.5), 2.5 mM MgCl~2~, 2 mM NADP^+^ and the substrate 10 mM malate (pH 7), the absence of which was used as a negative control. ### Phosphofructokinase (*Pfk*) {#sec011} To measure the co-substrate specificity of the phosphofructokinase, we used an assay according to Peng & Mansour \[[@pone.0168818.ref034]\] with modifications. The enzyme activity was determined in a coupled enzyme assay, with the standard assay master mix containing 50 mM Tris buffer (pH 8.5) with 1 mM EDTA and 1 mM DTT, 5 mM MgCl~2~, 0.2 mg ml^-1^ NADH, 1.5 U aldolase, 15 U triosephosphate isomerase, 5.1 U glycerolphosphat dehydrogenase (all from Sigma Aldrich, Germany), 1 mM Fru-6-P, 1 mM ATP and 1 mM PPi. The assays were run with the following controls: without Fru-6-P and without co-substrate ATP or PPi, respectively. Metabolic labeling for quantitative proteomic analysis {#sec012} ------------------------------------------------------ *Halomonas elongata* was cultivated on MM63 agar plates and transferred onto LB agar. After two days at 30°C the cells were transferred into GM liquid medium (20 ml) with 0.1 M, 1.0 M, and 2.0 M NaCl, respectively. The medium with 1.0 M NaCl (6%) contained ^15^NH~4~Cl as the sole nitrogen source and the media with 0.1 M NaCl and 2 M NaCl (12%) contained ^14^NH~4~Cl as the sole nitrogen source. After overnight incubation the cells were transferred into 15 ml GM medium with the corresponding salt concentration of 0.1 M (0.6%), 1 M (6%), and 2 M NaCl (12%), respectively. After overnight growth, cells were transferred into fresh 25 ml GM medium and the OD~600~ was adjusted to 0.5. The cells were further grown at 30°C until they reached an OD~600~ of 1.0 and harvested by centrifugation (10,000 x g) at 4°C. The cell pellet was resuspended in 500 μl TRIS buffer (0.1 M, 1 M, 2 M NaCl, pH 7.4) and spun down again and resuspended in 1 ml TRIS buffer with the corresponding salt concentration. After washing, the OD~600~ for all three cell-samples was determined and the labeled cells (1.0 M NaCl, 6%) were mixed with the unlabeled cells from the cultures with 0.1 M NaCl (0.6%) and 2 M NaCl (12%), respectively, in a ratio of 1:1. Immediately afterwards, cells were lysed by French Pressing in 25 ml cell lysis buffer (0.1 mM TRIS, 0.5 M NaCl, which contained 187 mg MgCl~2~, 136 mg MnCl~2~, 250 μg DNase, 250 μg RNase (per 25 ml), one protease inhibitor tablet (Roche, Mannheim, Germany), pH 7.4). Cell debris was removed by centrifugation (10,000 x g) at 4°C and the supernatant was centrifuged at high speed (100,000 x g) for 1 h at 4°C in order to separate the membrane and cytoplasmic fraction of the cells. After ultracentrifugation, 250 μl supernatant containing the cytoplasmic fraction was removed from the membrane pellet and treated with 5 volumes ice-cold acetone in order to precipitate the proteins. After 24 h incubation at -70°C, the proteins were pelleted by centrifugation (15,000 x g) for 30 min at 4°C. After vaporizing the acetone, the sample was resuspended in 300 μl H~2~O by sonication. Methanol (25 μl) was added and the sample was frozen in liquid nitrogen for 2 min and dried by lyophilisation. The membrane pellet was resuspended in 2 ml TRIS buffer (0.1 M, pH 7.4) containing 0.5 M NaCl and filled up to 20 ml with TRIS-TWEEN buffer (0.1 M TRIS, pH 7.4, 0.5 M NaCl, 5% TWEEN). In order to remove remaining cytoplasmic proteins, the membrane was washed by stirring for 20 min at RT. The purified membrane was separated from the cytoplasmic proteins by high-speed centrifugation (100,000 x g, 1 h, 4°C). Afterwards the membrane pellet was resuspended in 10 ml TRIS buffer (0.1 M, pH 7.4, 0.5 M NaCl), centrifuged (100,000 x g, 4°C) for 1 h, again resuspended in TRIS buffer and centrifuged (100,000 x g, 4°C) for 30 min. Finally, the purified membrane was resuspended in 100 μl H~2~O and delipidated with chloroform/methanol according to Wessel and Flugge \[[@pone.0168818.ref035]\]. 1-D-gel electrophoresis {#sec013} ----------------------- Proteins were resuspended in 2x SDS-PAGE sample buffer (Rockland Immunochemicals) by vortexing and ultrasound treatment. Proteins were separated on NuPAGE Novex Bis-Tris Mini gels (Invitrogen) by one-dimensional SDS-gel electrophoresis at 200 V for 45 min. Gels were stained with Fermentas PageBlueProtein staining solution according to the manufacturer's instruction. Gel lanes were cut into 16 slices, which were then cut into small pieces of approximately 1 mm^3^ for in-gel proteolytic digestion. Gel pieces were destained by incubation in 100 μl acetonitrile (ACN; 50%, v/v) for 15 min at RT. After removal of the supernatant 100 μl ammonium bicarbonate (ABC; 50 mM) was added followed by incubation for 15 min. The destaining procedure and ABC incubation was repeated twice. Proteins were reduced in 50 mM ABC solution with 100 mM dithiothreitol (100 μl) for 45 min at 56°C. Proteins were alkylated by incubation in 100 μl ABC solution (50 mM) with 55 mM iodacetamide in the dark for 30 min. After alkylation, gel pieces were washed by incubation with 50% ACN for 15 min. ACN was completely removed and gel pieces were washed with 50 mM ABC for another 15 min. After complete removal of ABC, the ACN/ABC washing steps were repeated twice. For in-gel digestion 26 μl trypsin solution (20 μg trypsin dissolved in 20 μl storage buffer and diluted with 5.2 ml 50 mM ABC) was added to the gel pieces, which were incubated over night at 37°C and 300 rpm (Eppendorf Thermomixer comfort). To elute the peptides, the gel pieces were shortly spun down and the liquid supernatant was transferred into a new tube. Remaining peptides were eluted from the gel by subsequently adding and removing (after 20 min incubation) 50 μl extraction solution. Extraction solutions were in consecutive order: H~2~O, ACN (50% v/v), and 0.1% TFA in ACN (50% v/v). All supernatants from one slice were combined and the samples were desalted using self-made extraction tips as described by Rappsilber and co-workers \[[@pone.0168818.ref036]\]. Nano-LC-MS/MS analysis {#sec014} ---------------------- The LC-MS/MS analysis was carried out according to Dulla and co-workers \[[@pone.0168818.ref037]\]. Briefly, peptides were solubilized with acetic acid (0.5%, v/v) and the nano-LC-MS/MS analysis was performed on a linear trap quadropole (LTQ) Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA) equipped with a nanoACQUITY UPLC (Waters, Milford, MA). The peptide samples were separated via an analytical column (3 μm, ReproSil-Pur C~18~ AQ, Dr. Maisch GmbH) with a gradient from 100% buffer A (0.2% acetic acid (v/v) in water) to 100% buffer B (0.2% acetic acid (v/v) in acetonitrile) in a time frame of 180 min. Data analysis {#sec015} ------------- All MS/MS spectra obtained were searched against the *H*. *elongata* protein sequence database, which was exported from the HaloLex database ([www.halolex.mpg.de](http://www.halolex.mpg.de)) \[[@pone.0168818.ref038], [@pone.0168818.ref039]\], using a locally installed MASCOT server (version 2.0) \[[@pone.0168818.ref040]\]. For the database search, carbamidomethylation was set as a required cysteine modification, whereas oxidation of methionine was considered as a variable modification. As a further criterion the ^15^N-labeling strategy was chosen. Furthermore, a missed cleavage site in trypsin digestion was enabled, the decoy database option was activated and the threshold was set to 5 ppm for MS and 0.5 Da for MS/MS. The obtained dataset was quantified using the Mascot Distiller software with the following settings: Using the ^15^N-labeling strategy the minimum ion score was set to 15. The function Bold Red was activated in order to allow for only non-ambiguous protein and peptide hits. The occurrence of both, light and heavy peptides (^14^N and ^15^N) was set as a prerequisite condition. For quantification the correlation threshold was set to 0.9 and the standard error threshold to 0.16. The peak-area of the light and heavy species of a peptide was considered for quantification. The ratio of the peak-area for ^14^N/^15^N was computed and normalized to result in 1.0 as the median value. Ratios below 1.0 were transformed by computation of the inverse value, being represented as a negative number. For the membrane proteome, datasets were generated from three independent experiments. Only proteins that were identified in at least two of the three datasets and had a regulation factor of 1.8 or higher were considered for final quantification. The cytoplasmic proteome was measured once and up-regulated proteins were further investigated by mutagenesis and quantitative RT-PCR in order to verify the proteome data. Outliers were identified by a modified Box-Plot analysis and removed. Proteins showing a regulation factor of \>5 were manually inspected and adjusted if required. Flux Balance Analysis (FBA) and metabolic modeling {#sec016} -------------------------------------------------- A stoichiometric model was formulated \[[@pone.0168818.ref041]\], which includes 85 reactions accounting for the function of 129 loci identified during genome annotation and a number of additional reactions. In addition to the ectoine synthesis pathway, the model includes other relevant pathways such as: Embden-Meyerhoff-Parnas, Pentose-phosphate cycle, Entner-Doudoroff (cytoplasmic and periplasmic variants), tricarboxylic acid cycle (TCA cycle), anaplerotic reactions, glyoxylate shunt and nitrogen assimilation through glutamate and alanine. It also includes lumped reactions to reflect the impact of different physiological states: Overall ATP consumption by the cell, overall NADPH consumption e.g. due to oxydative stress formation of PP~i~ by polymerization processes, proton leak through the membrane and uptake of compatible solute transporters. Proton sodium antiporters with the usual stoichiometries are also included. The latter reactions have not been linked to any locus because even though the transporters are identified (see section on sodium economy) the specific stoichiometry of each antiporter has not yet been established. Optimal flux distributions for ectoine production were obtained by linear programming as commonly used for FBA. Optimization was carried out using python and the linear programming solvers GLPK (<http://www.gnu.org/software/glpk/glpk.html>) and Gurobi (<http://www.gurobi.com>). Results and Discussion {#sec017} ====================== General remarks {#sec018} --------------- In the present study we employed a ^14^N/^15^N metabolic labeling method for LC-MS/MS analysis in order to identify *H*. *elongata* proteins with a potential role in adaptation to different salinities. Proteins of interest identified by this method were further characterized by measuring transcriptional regulation of the corresponding genes and by measuring changes in enzyme activity. Cultures of *H*. *elongata* were propagated in minimal medium containing 0.1 M (0.6%), 1 M (6%), and 2 M NaCl (12%) and harvested in the exponential growth phase for quantitative MS-analysis of the proteome, transcript quantification by RT-qPCR and quantification of enzyme activity. For measuring the protein content by Nano-LC-MS/MS, cells of the halophilic bacterium grown at an optimal salt concentration of 1 M NaCl (6%) were labeled with ^15^NH~4~Cl and mixed with unlabeled cells from low-salt (0.1 M NaCl, 0.6%) and high-salt (2 M NaCl, 12%), respectively. According to genome annotation, *H*. *elongata* possesses 3473 proteins \[[@pone.0168818.ref017]\]. We were able to detect 1488 proteins, which represent 43% of the predicted proteome. In total, the protein content of 470 proteins was up or down regulated with increasing and decreasing salinity. We considered a protein as regulated and worthwhile for further investigation if the protein content was 1.8 times higher or lower at 0.1 M NaCl (0.6%) or 2 M NaCl (12%), respectively, compared to the protein level at 1 M NaCl (6%). From these 470 proteins, we chose 24 corresponding genes for transcript quantification by RT-qPCR. These genes encode proteins with function in glucose degradation (quinoprotein glucose dehydrogenase, phosphogluconate dehydratase, 2-dehydro-3-deoxy-6-phosphogalactonate aldolase of the ED-pathway), in anaplerosis and the TCA cycle (including malic enzyme, isocitrate lyase, fumarase), in nitrogen metabolism (including glutamate synthase, glutamate dehydrogenase), ectoine synthesis, ectoine degradation and ectoine transport. Furthermore, the activity of the enzymes glutamate synthase, glutamate dehydrogenase, alanine dehydrogenase, malic enzyme and fumarase at low, optimal and high salinity was determined. The activity of 6-phosphofructokinase was tested in the presence of ATP and PP~i~ to determine the source of phosphate for the reaction. Genes and proteins, respectively, that are regulated according to the combined analyses by RT-qPCR, MS-analysis and enzyme assays have been grouped into functional categories and are listed in Tables B and C in the [S2 File](#pone.0168818.s002){ref-type="supplementary-material"} (Supplementary Material). Carbohydrate metabolism {#sec019} ----------------------- A recent detailed survey of a wide range of marine bacteria found that most of them had the required genes to metabolize glucose using three different pathways, namely the Entner-Doudoroff (ED), the Embden-Meyerhof-Parnas (EMP) and the pentose-phosphate pathway (PPP) \[[@pone.0168818.ref042]\]. ^13^C flux-profiling experiments showed that all of them catabolized glucose using either ED or EMP, sometimes complemented by PPP. All bacteria using EMP were shown to express an ATP-dependent 6-phosphofructokinase but no glucose-6-dehydrogenase while the opposite was found with those using ED. All Halomonadaceae included in the study used ED exclusively, and so does *C*. *salexigens*, the close relative of *H*. *elongata* \[[@pone.0168818.ref026]\]. The genome of *H*. *elongata* seems to follow the pattern, since it has the genes for all three pathways plus an additional non-phosphorylated ED, as it can be seen in [Fig 1](#pone.0168818.g001){ref-type="fig"} depicting the upper glycolysis as annotated in the genome. It is noteworthy that no gene for fructose-1,6-bisphosphatase has been found in the genome of *H*. *elongata*, although it is reported that *H*. *elongata* is able to grow on lactate \[[@pone.0168818.ref009]\]. Another peculiarity is that the enzymes for both ED and EMP pathways were detected in the proteomic analysis unlike the cases studied by Klingner and co-workers \[[@pone.0168818.ref042]\]. However, only the expression of the ED-pathway is up regulated with increasing salinity (phosphogluconate dehydratase, 2-keto-3-deoxyphosphogluconate aldolase), while none of the enzymes participating in the EMP-pathway and the pentose-phosphate pathway are significantly regulated by salt. It should be pointed out that these findings are only based on the MS-analysis. It has been shown recently that the glucose catabolism in *C*. *salexigens* and other bacteria of the Halomonadaceae proceeds entirely via the ED-pathway \[[@pone.0168818.ref026], [@pone.0168818.ref042]\]. A possible explanation from these differences can be attributed to the specificity of the 6-phosphofructokinase present in *H*. *elongata*. All metabolic reconstructions of Halomonadaceae presented so far \[[@pone.0168818.ref043], [@pone.0168818.ref044]\] have assigned ATP specificity to the phosphofructokinase. However, the protein Helo_2186, which is annotated as 6-phosphofructokinase, shares only 30% similarity or less to experimentally characterized phosphofructokinases from bacteria such as *E*. *coli* and *B*. *subtilis*. The potential 6-phosphofructokinase from the closely related halophile *C*. *salexigens* is very similar to Helo_2186, and likewise, only remotely similar to experimentally characterized PFKs. [Fig 2](#pone.0168818.g002){ref-type="fig"} shows the results of enzyme assays performed in crude extract. It can clearly be seen that the enzyme uses PP~i~ instead of ATP as phosphate donor. This can have deep implications since the reaction with pyrophosphate has a standard free energy of roughly one third of that with ATP (-4.4 kJ/mol vs -15.0 at pH 7.0 and ionic strength 0.1 according to the thermodynamic database Equilibrator at <http://equilibrator.weizmann.ac.il/>). The PP~i~ dependent 6-phosphofructokinase is reversible and a plausible substitute for the missing phosphatase and explains a functional gluconeogenesis in *H*. *elongata*. ![Metabolic pathways in *Halomonas elongata* that are regulated with increasing salt concentration (0.1 M, 1 M, and 2 M NaCl).\ Metabolic reactions shown in solid red (down regulated) and solid green (up regulated) lines are regulated by salinity according to mass spectrometry (MS) and RT-qPCR analysis. Dashed arrows show reactions that are regulated based on MS data only. In addition, the regulation of activity by salinity was determined for the enzymes phosphofructokinase, malic enzyme, glutamate synthase, glutamate dehydrogenase, alanine dehydrogenase and fumarase (for details see paragraphs Carbohydrate metabolism, Tricarboxylic acid cycle and Ammonia assimilation).) Depicted is an overview of glycolysis (EMPEmbden-Meyerhof-Parnas; ED = Entner-Doudoroff) and the TCA cycle with the affiliated pathways of ectoine synthesis and glutamate synthesis. Pathway for arginine degradation via ornithine/carbamoyl-P is shown as well. Gray arrows show pathways that remain unchanged or escaped detection by proteome profiling ([ND]{.ul}). Proteins detected by quantitative MS-analysis were considered for further investigation (RT-qPCR of the corresponding genes, enzyme assay) if the protein content changed by the factor ≥1.8 with increasing salinity. The protein content of phosphogluconate dehydratase and 2-keto-3-deoxy-phosphogluconate aldolase (dashed green arrows) was up regulated (MS-analysis) but the transcription appeared unchanged (RT-qPCR). The protein content of alanine dehydrogenase appeared up regulated according to the MS data but the transcription and enzyme activity were unchanged by salt. However, the activity of this enzyme was much higher than any other enzyme included in this study. Quantitative MS analysis revealed down regulation of glutamate dehydrogenase (*gdh*) at 1 M NaCl by the factor 1.79 (threshold 1.8) but was still further analyzed by enzyme assay and RT-qPCR, which proved a significant decline in enzyme activity and transcription at high salinity. The exact regulation factors derived from the MS data and the qPCR results can be found in the Supplementary Material (Figures A to W in [S1 File](#pone.0168818.s001){ref-type="supplementary-material"} and Tables B and C in [S2 File](#pone.0168818.s002){ref-type="supplementary-material"}). DABA: L-2,4-diaminobutyrate; MS: mass spectrometry.](pone.0168818.g001){#pone.0168818.g001} ![Phosphofructokinase (PFK) specificity.\ Activity of PFK in crude extract with fructose-6-phosphate and different co-substrates.](pone.0168818.g002){#pone.0168818.g002} Tricarboxylic acid cycle {#sec020} ------------------------ Among the anaplerotic reactions, the expression of the malic enzyme (MaeB, Helo_3763) seemed to be upregulated by salt in the proteome and at the level of transcription. The second putative NAD-dependent malic enzyme (MaeA, Helo_3817) could not be identified by MS analysis. All optimal flux distributions calculated using FBA to determine theoretical maximum yields of ectoine channeled the flux through malic enzyme: PEP is converted via pyruvate and malate to oxaloacetate, which can then be converted to ectoine via aspartate. Using this pair of reactions, the overall conversion of glucose to ectoine results in the generation of one ATP. Thus, the route via malic enzyme would be the most energy-efficient pathway. According to our previously reported thermodynamic calculations \[[@pone.0168818.ref017]\], the overall conversion is thermodynamically feasible. RT-qPCR showed a similar trend to that seen in the prospective proteome profiling but only a small, albeit statistically significant overexpression was detectable. This can be explained by the results of the enzyme assays ([Fig 3](#pone.0168818.g003){ref-type="fig"}), which show an extremely low activity of malic enzyme under all three conditions. The activities of the malic enzyme in *H*. *elongata* where consistently one order of magnitude below the values of *P*. *putida* reported in literature \[[@pone.0168818.ref045]\] and below the values measured by us. Our findings indicate that the malic enzyme plays no significant role as an anaplerotic reaction. ![Activity of malic enzyme in crude extract of *H*. *elongata*.\ The box-plot shows data from a representative experiment in which three cultures were grown in each of the salt concentrations (0.1 M, 1 M and 2 M NaCl). Four crude extracts were prepared from each of the nine cultures, so each box summarizes twelve data points.](pone.0168818.g003){#pone.0168818.g003} According to our metabolic modeling (see below), flux through the glyoxylate cycle at increased salinities cannot improve ectoine synthesis. The proteome analysis data indicate a down-regulation of the isocitrate lyase (Helo_3070) and the RT-qPCR data revealed a strong down-regulation of Helo_3070 transcription at salinities of 1 M (6%) and 2 M NaCl (12%) compared to 0.1 M NaCl (0.6%). Furthermore, experiments with labeled substrates have shown that the glyoxylate shunt plays no role in osmotic stress response in *H*. *elongata* \[[@pone.0168818.ref046]\]. The two remaining anaplerotic reactions catalyzed by oxaloacetate decarboxylase (Oad, Helo_3734--3736) and phosphoenolpyruvate carboxylase (Ppc, Helo_3010) can supply the required oxaloacetate to the TCA cycle through carboxylation of either phosphoenolpyruvate (PEP) or pyruvate. Carboxylating pyruvate through the Oad reaction enables the generation of one extra ATP molecule in comparison to the route via PEP-carboxylase. However, the Oad reaction leads to the influx of two sodium ions per carboxylation. The comparative metabolic costs of these two options will therefore depend on the active sodium transport systems. Sodium economy {#sec021} -------------- In bacteria, sodium efflux is mediated by four principal types of ion transporters: proton-driven Na^+^/H^+^-antiporters \[[@pone.0168818.ref047]\], Na^+^-coupled respiratory enzymes (NADH:quinone oxidoreductases; NQR) \[[@pone.0168818.ref048]\], V-type ATPases \[[@pone.0168818.ref049]\], and biotin-containing decarboxylases \[[@pone.0168818.ref050]\]. We found at least 10 genes in the *H*. *elongata* genome encoding putative Na^+^ efflux systems that belong to these four groups of transporters. The presence of the anaplerotic reaction oxaloacetate decarboxylase, a biotin-containing decarboxylase that also functions as a sodium pump, ties the relative performance of anaplerotic alternatives to sodium transport. Transporting the two sodium ions \[[@pone.0168818.ref051]\] needed for a carboxylation of pyruvate has an "opportunity cost\'\' in terms of ATP, since the sodium ions must be extruded at the expense of protons. When the sodium translocation occurs through the NADH:quinone oxidoreductase (NQR) at the respiratory chain, each sodium ion is transported instead of a proton. Since the Oad reaction for the carboxylation of pyruvate leads to the influx of two Na^+^, the export of two Na^+^ via NQR costs 2 protons. This is equivalent to 1/2 ATP opportunity cost for every carboxylation, since the ATPase stoichiometry is four protons per ATP \[[@pone.0168818.ref052]\]. The sodium/proton antiporters have diverse stoichiomeries, with 2:3 and 1:2 being the most common, which would result in opportunity costs of 3/4 ATP and 1 ATP, respectively. To investigate the impact of these different costs within the context of the whole metabolic network, different combinations of active reactions were compared ([Fig 4](#pone.0168818.g004){ref-type="fig"}). When the full network is active, different combinations of anaplerotic and sodium transport strategies can result in maximum ectoine yield, which vary depending on the ATP load. For high ATP loads, the cost considerations stated above clearly make carboxylation through Oad and subsequent extrusion of the sodium ions through the respiratory chain the optimal choice. When the ATP load is low, the most efficient solution is the carboxylation through Oad and extrusion of sodium through the 2:3 antiporter. The least efficient solutions, although not by a large margin, are PEP carboxylase and the combined action of Oad and the 2:3 pump, which can be easily seen to be equivalent by inference from the opportunity costs. The reasons for NQR not always being the best solution instead of being the most efficient in terms of ATP costs results from the translocation of 2 H^+^ together with the 2 Na^+^, which results in the production of more ATP than needed. ![Maximal ectoine yield for different ATP loads (ATP demands external to the network) calculated using Flux Balance analysis (FBA).\ The black solid line shows the values when the full network is operational. Additional lines show yields when only the indicated subset of anaplerotic pathways and Na transporters are active (see text for details).](pone.0168818.g004){#pone.0168818.g004} Thus, the tandem of anaplerotic enzymes Oad and PEP carboxylase, in conjunction with the different sodium transport mechanisms, seems to be a very efficient method to obtain extra exergonism in the carboxylation by coupling it to the sodium gradient while remaining flexible under a variety of conditions. Potassium influx {#sec022} ---------------- In a first response to increasing NaCl concentrations in the surrounding, *H*. *elongata* accumulates K^+^ and the counter ion glutamate. Potassium is taken up into the cell by the two transporters TrkH (Helo_1371) and TrkI (Helo_1450) \[[@pone.0168818.ref013]\] and, in salt adapted cells, the cytoplasmic K^+^ concentration reaches a final concentration of approximately 500 mM \[[@pone.0168818.ref011]\]. The TrkH and TrkI membrane proteins, including the auxiliary protein TrkA, could not be detected in the *H*. *elongata* proteome. However, the putative potassium efflux system KefB (Helo_3903) could be quantified and was shown to be down regulated at elevated salinities, which in addition to potassium uptake, contributes to maintaining a potassium gradient. The membrane protein Helo_2045, which was formerly annotated as KefA, is also down regulated at elevated salinity. It was shown for the related KefA from *E*. *coli* that this protein functions as a K^+^ regulated mechanosensitive channel (now called MscK) \[[@pone.0168818.ref053]\] and we have re-annotated Helo_2045 accordingly. Ectoine metabolism and transport {#sec023} -------------------------------- The enzymes EctB (aspartate-semialdehyde transaminase, Helo_2589), EctA (diaminobutyrate acetyltransferase, Helo_2588) and EctC (ectoine synthase, Helo_2590), which catalyze the conversion of aspartate-β-semialdehyde into ectoine \[[@pone.0168818.ref007], [@pone.0168818.ref014]\], are up regulated in cells grown at 1 M NaCl (6%) compared to cells from 0.1 M NaCl (0.6%). The protein level of EctB was shown to remain elevated at 2 M NaCl. EctA and EctC escaped detection at 2 M NaCl (12%). However, it can be assumed that both enzymes remain elevated at high salinity because the cytoplasmic ectoine concentration increases linearly along with the salt concentration of the medium \[[@pone.0168818.ref054]\] and the transcription of all three genes, *ectABC*, significantly increases at high salinity. Ectoine is catabolized by the enzymes for *d*egradation *o*f *e*ctoine (Doe). This pathway allows its utilization as a carbon and nitrogen source by *H*. *elongata* \[[@pone.0168818.ref017]\]. The degradation ([Fig 1](#pone.0168818.g001){ref-type="fig"}) proceeds via Nα-acetyl-diaminobutyric acid to diaminobutyric acid (DABA). DABA can either flow off to aspartate or re-enter the ectoine synthesis pathway. This closes the cycle of synthesis and degradation, which is powered by acetylation and deacetylation of DABA and Nα-Ac-DABA, respectively. The enzymes DoeA (ectoine hydrolase, Helo_3665), DoeB (Nα-acetyl-L-2,4-diaminobutyrate deacetylase, Helo_3664) and DoeD (L-2,4-diaminobutyrate transaminase, Helo_3661) are up regulated at 0.1 M NaCl (0.6%) compared to 1 M NaCl. Whether the protein content of DoeA and DoeB is further regulated at 2 M NaCl (12%) cannot be stated at the moment, since both enzymes escaped detection at 2 M NaCl. However, the transcription of the genes *doeA*, *doeB*, and *doeD* is down regulated with increasing salinity showing a very pronounced decline in transcription from 0.1 M NaCl to 1 M NaCl (0.6% to 6% NaCl). Aspartate can be generated by transamination of oxaloacetate and is a biosynthetic precursor of ectoine. Interestingly, the enzymes aspartokinase (ASK) (LysC, Helo_3742) and aspartate-β-semialdehyde dehydrogenase (Asd, Helo_2235), leading from aspartate to aspartate-β-semialdehyde, are not affected by increasing salinity. In many organisms, the ASK is an important target for regulating the synthesis of amino acids that belong to the aspartate family \[[@pone.0168818.ref053]\]. *H*. *elongata* possesses only one ASK, namely LysC, which belongs to the ASKβ homology subdivision \[[@pone.0168818.ref017]\]. According to the allosteric-specificity grouping of ASKβ enzymes, LysC from *H*. *elongata* is predicted to be sensitive to allosteric regulation by Thr and Lys \[[@pone.0168818.ref055]\]. Recently, experimental data have been provided by the Galinski group indicating that LysC in *H*. *elongata* is only feed-back regulated by Thr alone \[[@pone.0168818.ref056]\]. No connection of LysC to the regulation of the ectoine metabolism could be found so far \[[@pone.0168818.ref017]\] and the unchanged protein level of LysC at all tested salinities is in agreement with this notion. *Halomonas elongata* possesses two putative transaminases that can potentially convert oxaloacetate to aspartate namely the aspartate transaminase AspC (Helo_4120) and the aromatic amino acid aminotransferase PhhC (Helo_2252), which may also function as an aspartate transaminase (EC 2.6.1.1) \[[@pone.0168818.ref057], [@pone.0168818.ref058]\]. According to the MS analysis the AspC content remains unchanged at all salinities while PhhC is increase by the factor 2.5 at 1 M NaCl (6%). The transcription of the ectoine-specific transporter operon *teaABCD* is increased at high salinity according to the RT-qPCR analysis. This is in agreement with previous Northern hybridization experiments, which showed an increased transcription of *teaA* at high salt concentration. The protein content of the substrate binding protein TeaA (Helo_4274) \[[@pone.0168818.ref059], [@pone.0168818.ref060]\] and the regulatory cytoplasmic ATP-binding protein TeaD (Helo_4277) \[[@pone.0168818.ref061]\] was elevated in cells grown at 1 M NaCl (6%). The two membrane components of the ectoine transporter, TeaB (Helo_4275) and TeaC (Helo_4276), could not be quantified from the membrane proteome. However, since the *teaABCD* genes are organized as an operon \[[@pone.0168818.ref059]\] there is no reason to doubt that the content of all four Tea proteins is increased at high salinity. Ammonia assimilation {#sec024} -------------------- Being the entry point for ammonia into metabolism, glutamate is always important, but in the case of *H*. *elongata* this importance is even greater, since glutamate itself acts as an osmoregulatory solute and provides the amino groups for the synthesis of ectoine. Immediately after an osmotic up-shock, *H*. *elongata* increases the cytoplasmic K^+^ concentration by uptake via transporters TrkH and TrkI. Concomitantly, the cytoplasmic glutamate concentration is increased. Contrary to other investigated bacteria \[[@pone.0168818.ref010]\], the levels of potassium and glutamate in *H*. *elongata* remain increased for an extended period of time (\>120 min) even in the presence of ectoine \[[@pone.0168818.ref011]\]. The dual function of glutamate as an osmolyte and nitrogen source for ectoine synthesis might also explain why the K^+^-glutamate concentration in *H*. *elongata* is increased for more than 2 h following an osmotic up-shock. Together with glutamate, the level of glutamine increases as well and reaches its maximum concentration 15 min after the osmotic up-shock, which is approximately half the concentration of glutamate \[[@pone.0168818.ref011]\]. However, glutamine increases only transiently and falls back to the level before the osmotic shock after approximately 90 min. The two major pathways for nitrogen assimilation end in glutamate: Glutamate can be synthesized either by glutamate dehydrogenase via reductive amination of α-ketoglutarate or by glutamate synthase (GOGAT, Helo_3752--3753), which, in combination with glutamine synthetase (GS, Helo_1126), allows for high affinity nitrogen assimilation. ### Glutamate synthase {#sec025} Proteomic profiling indicates higher levels of glutamate synthase at higher salt concentrations. The protein level increases at 1 M NaCl (6%) and remains elevated at 2 M NaCl (12%). The same observation was made for the transcription of the glutamate synthase genes, *gltD* and *gltB*. The genes *gltD* and *gltB* encode the small and large subunit of glutamate synthase and are strongly transcribed at high salt concentration. Finally, enzyme assays also show significantly higher activities at high salt concentrations (see [Fig 5A](#pone.0168818.g005){ref-type="fig"}). ![Activity of ammonia assimilating enzymes.\ A) GOGA, B) Glutamate dehydrogenase (GDH), C) Alanine dehydrogenase (Ala-Dh). Three cultures were grown at each salt concentration (0.1 M, 1 M and 2 M NaCl) and four extracts per culture were prepared (three for Ala-Dh).](pone.0168818.g005){#pone.0168818.g005} ### Glutamate dehydrogenase {#sec026} The expression of glutamate dehydrogenase (*gdh*, Helo_3049) is not up regulated by salinity, according to the proteomics. This was confirmed both at the transcriptional level and measuring enzyme activities (see [Fig 5B](#pone.0168818.g005){ref-type="fig"}) ### Alanine dehydrogenase {#sec027} The proteome data indicate up regulation of the enzyme alanine dehydrogenase (Ald, Helo_3819). Although a certain trend was observed, no statistically significant increase in enzyme activity by salt could be measured. It is, however, noteworthy that the activities of the enzyme were much higher than those of any other enzyme included in this study (see [Fig 5C](#pone.0168818.g005){ref-type="fig"}). Although direct extrapolation from *in vitro* to *in vivo* cannot be made, activities one order of magnitude higher definitely deserve attention. Alanine dehydrogenase catalyzes the reductive amination of pyruvate to alanine, and it is a less frequent but also viable reaction for the assimilation of ammonia \[[@pone.0168818.ref062]\]. The assimilated nitrogen can be transferred from alanine to glutamate by alanine transaminase (AlaA, Helo_2013). Thus, these two enzymes together represent a yet undescribed low affinity nitrogen assimilation system. The enzyme assays also established the cofactor specificity of the enzymes, showing that both GDH and Ala-DH use NADH instead of NADPH as electron donor, which is unusual but still possible for assimilation reactions \[[@pone.0168818.ref063]\]. Taken together, all these results show that ammonia assimilation in *H*. *elongata* deviates from the known pattern, probably due to the need of coordinating the multiple roles of glutamate, and deserves more attention. Further observations {#sec028} -------------------- We want to point to a couple of other osmoregulatory mechanisms that have been identified by analysing the proteome data. 1. There is an up regulation of ribosomal proteins at 1 M NaCl (6%), which indicates a down regulation of protein biosynthesis when cells of *H*. *elongata* encounter low salt stress. From a total of 18 quantified ribosomal proteins, 17 were up regulated at 1 M NaCl (6%). Northern analysis of ribosomal RNA carried out in our laboratory corroborates this finding, which showed an increase in 16S rRNA after a sudden shift in salt concentration from 170 mM (1%) to 690 mM (4%) NaCl \[[@pone.0168818.ref059]\]. 2. The expression of the Hda protein (*h*omologous to *D*na*A* protein \[[@pone.0168818.ref064]\]; Helo_2294) is down regulated at 1 M NaCl (6%). Hda participates in the regulatory inactivation of DnaA. DnaA is the initiator of chromosome replication at the *oriC* site. Hda (like DnaA) belongs to the AAA^+^ family of ATPases and is thought to stimulate the hydrolysis of ATP bound to DnaA and thereby inactivating DnaA function \[[@pone.0168818.ref065]\]. This finding indicates a down regulation of DNA replication at low salt. The proteome data obtained for protein synthesis and DNA replication are in agreement with the poor growth of *H*. *elongata* at low salt, which reaches growth rates of only μ≈0.2 h^-1^ at 0.17 M NaCl (1%) compared to μ = 0.4 h^-1^ at 0.5 M to 1 M NaCl (3% to 6% NaCl). 3. *E*. *coli* and other Gram-negative bacteria synthesize so-called osmoregulated periplasmic glucans (OMG) at low osmolarity \[[@pone.0168818.ref066], [@pone.0168818.ref067]\]. In *H*. *elongata*, three enzymes potentially involved in biosynthesis of the core glucans are down regulated at 1 M NaCl (6%) according to the proteome data, namely glucosyltransferase OpgH (Helo_3146), and the paralogous pair OpgG (Helo_3145) and OpgD (Helo_1814). Thus, it seems that *H*. *elongata* also synthesizes OMGs under low osmolarity stress conditions. 4. We found 9 outer membrane proteins (OMP; β-barrel proteins) whose expression is affected by salt and all 9 proteins are up regulated with increasing salinity. The putative sucrose porin ScrY (Helo_3673) is the most strongly regulated OMP and one of the most significantly regulated proteins in this study, which increases its content by a factor of 335 at 1 M (6%) compared to 0.1 M NaCl (0.6%). The up regulated OMP Helo_3304 (*iutA*) belongs to the family of TonB receptor proteins and displays strong similarities to OMPs involved in iron sequestration. The potential role in iron uptake is supported by the fact that gene *iutA* is located next to a gene encoding a putative ferric iron reductase. For *B*. *subtilis* it was shown that cells of this species coping with high salt stress experience iron limitation \[[@pone.0168818.ref068]\]. Metabolic modeling {#sec029} ------------------ The new findings reported in this study led to extend and modify a previously reported \[[@pone.0168818.ref017]\] model of ectoine metabolism (see [Material and Methods](#sec002){ref-type="sec"} and Supporting Information Table D in the [S3 File](#pone.0168818.s003){ref-type="supplementary-material"}). Previous sections have already discussed how the modified model helps to understand different subsystems. The question that remains is how the new information modifies our global view. [Fig 6](#pone.0168818.g006){ref-type="fig"} shows the maximum theoretical yields of ectoine as calculated through FBA for different ATP loads, both before and after modifying the model. The black line shows the theoretical yield of ectoine calculated by direct optimization of the full network. The optimal flux distributions were in all cases dominated by EMP and subsequent anaplerosis of the TCA cycle by the malic enzyme. These solutions can be understood as the potential of the network. Modifying the model incorporates the following new findings, namely i) the Entner-Doudoroff pathway is the main pathway for glycolysis, ii) a PPi-dependent 6-phosphofructokinase that alters the ATP-balance of the EMP pathway, and iii) the malic enzyme does not catalyze any relevant anaplerotic reaction. These new findings bring the model closer to how the network actually works and changes the results both quantitatively and qualitatively. Quantitatively, the theoretical yields are lower once the above mentioned constraints are included. The difference may not seem too large, and FBA is known to be robust in this sense, but these relatively small variations in yield hide a completely different qualitative behaviour. There is no single dominant solution anymore but a range of possible solutions that can perform better or worse depending on the circumstances. That involves the concerted action of tightly coupled subsystems for instance the anaplerotic pathways and sodium transport in order to work efficiently. The three shaded areas in [Fig 6](#pone.0168818.g006){ref-type="fig"} show the performance of the network depending on which sodium transport mechanism is active. The upper line in each case is the yield when all ammonia is assimilated through AlaDH or GDH while the lower line corresponds to full assimilation through GOGAT. ![Maximal ectoine yield for different ATP loads (ATP demands external to the network) calculated using Flux Balance Analysis (FBA).\ The black line shows the potential of the network as inferred from the genome. These yields correspond to EMP glycolysis, TCA cycle anaplerosis through the TCA cycle and ammonia assimilation through GDH or Ala-DH. The three shaded areas show the maximal yields once the experimental findings of this paper are included as constraints (see text for details).](pone.0168818.g006){#pone.0168818.g006} Concluding remarks {#sec030} ------------------ Quantitative proteome profiling analysis combined with RT-qPCR analysis and enzyme activity measurements of *H*. *elongata* revealed that not only the obvious mechanisms involved in osmoadaptation are affected by salt (such as compatible solute transport, sodium efflux etc.), but even in central metabolism osmoregulatory changes occur. Most eminent in our opinion, is the necessary shift of carbon flow towards oxaloacetate and the interplay between anaplerotic enzymes and sodium transport. This finding points to a different regulation of ectoine synthesis in *H*. *elongata* compared to less salt tolerant ectoine producers. The formation of aspartate semialdehyde is often the regulatory step in synthesis of aspartate-derived amino acids and many microorganisms have evolved different types of aspartokinase in order to fine-tune these pathways \[[@pone.0168818.ref053]\]. A number of bacteria synthesizing ectoine possess a specialized aspartokinase ASK-Ect, which is less prone to feedback regulation (by threonine) at high salinity and seems to be adapted to the synthesis of ectoine \[[@pone.0168818.ref069]\]. *H*. *elongata* (and related halophiles such *C*. *salexigens*) does not possess aspartokinase ASK-Ect and only relies on aspartate kinase LysC. There is no evidence indicating a role of LysC in osmoregulating ectoine synthesis. Based on our investigation we propose that in *H*. *elongata* the significant (osmo)-regulatory event occurs earlier in the metabolic pathway namely at the PEP-pyruvate-oxaloacetate node. This view is also supported by our metabolic modeling. Our experimental and modelling results indicate that the tandem of anaplerotic enzymes Oad and PEP carboxylase is the most efficient anaplerotic pathway for ectoine synthesis while the glyoxylate shunt is the worst. This explains the inverse correlation in the regulation of these two. Under low salt, ectoine synthesis is not a priority and the glyoxylate shunt (and maybe low activities of the other anaplerotic reactions) provides enough material for biosynthetic processes branching out of oxaloacetate. Upon increases in the salinity of the medium, the anaplerotic reactions catalyzed are up regulated and the glyoxylate shunt fades out. With respect to the glycolytic pathways, there are some indications (for instance, PPi-dependent phosphofructokinase) that the EMP-pathway might not be active in *H*. *elongata* except for gluconeogenesis and glucose degradation most likely proceeds solely via the ED-pathway, as reported for *C*. *salexigens* \[[@pone.0168818.ref026]\]. Diverting the carbon flow as an osmoregulatory mechanism implies to throttle back glucose degradation at low salinity to avoid dissipation of carbon source. Our results are in agreement with this notion and indicate down regulation of the ED-pathway at low salinity. However, it might be arguable how well the regulatory mechanisms function at low salt. The work on the metabolic fluxes in *C*. *salexigens* revealed a certain metabolic rigidity that leads to metabolic overflow at low salt \[[@pone.0168818.ref026]\]. It is known that *H*. *elongata* performs only poorly at low salt and growth rates at that salinity are as low as at 2 M NaCl (12%). In this context, the regulation of certain processes at low salt (0.1 M NaCl, 0.6%) such as periplasmic glucose dehydrogenase (ED-pathway), down regulation of protein biosynthesis and DNA replication can be interpreted as *low salt stress* adaptation. The combination of high throughput techniques and metabolic reconstructions makes a powerful tool. However, it has to be carefully considered, which of the multiple alternative processes encoded by the genome are indeed active. The tendency of automated tools based on Flux Balance Analysis to find stoichiometrically optimal solutions may shift the focus away from the really important processes. This was shown in the present paper in the case of the pathways for glucose catabolism, nitrogen assimilation and anaplerotic reactions. With the help of a few well-targeted experiments, we can guide the application of these modelling tools and achieve a much better understanding of the metabolic network that is actually operating in *H*. *elongata*. This leads to a completely different list of priorities for the development of industrial producer strains of *H*. *elongata*. Supporting Information {#sec031} ====================== ###### Supporting Information PCR. Figures A to W and Table A. (DOCX) ###### Click here for additional data file. ###### Supporting Information Proteome. Tables B and C. (DOCX) ###### Click here for additional data file. ###### Supporting Information Model. Table D. (XLSX) ###### Click here for additional data file. We are grateful to Roman Körner (MPI of Biochemistry) for his help with the Orbitrap measurements. We also would like to thank Karin Schwibbert (BAM) for her support with the RT-qPCR experiments. This work was supported in part by a grant (Ku 1112/3-1) from the Deutsche Forschungsgemeinschaft (DFG). AMS was funded by a project from the Bundesministerium für Bildung und Forschung (e:Bio 0316197). [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: **Conceptualization:** HJK AMS DO.**Formal analysis:** HJK AMS NK FS.**Funding acquisition:** HJK AMS.**Investigation:** VK SR NK KPG BS FS.**Methodology:** FS AMS.**Writing -- original draft:** HJK AMS FP.**Writing -- review & editing:** HJK AMS FP DO.
Cis-acting structural element in 5' UTR is essential for infectivity of porcine reproductive and respiratory syndrome virus. It is believed that the genomic 5' untranslated region (UTR) of Arterivirus plays crucial roles in viral genomic replication, subgenomic mRNA transcription and protein translation, yet the structure and function still remain largely unknown. In this study, we conducted serial nucleotide truncation, ranging from 1 to 190 nucleotides, to the 5' UTR of the porcine reproductive and respiratory syndrome virus (PRRSV) infectious full-length cDNA clone pAPRRS. In vitro synthetic RNAs were transfected into MARC-145 cells for further genetic and virologic analysis. Our results demonstrated that the first three nucleotides of PRRSV 5' UTR were dispensable for virus viability, which however was repaired with foreign sequences. In order to assess if the primary sequence or structural element play more important regulatory roles, the CMV promoter-driven 5' UTR truncation mutant cDNA clones were directly transfected into the BHK-21 cell lines. We found that PRRSV tolerated the first 16 nucleotides sequence alteration of 5' UTR without losing virus viability. However, these revertant viruses contained a range of non-templated with unknown origin exogenous nucleotides in the repaired 5' end. Further analyses revealed that the 5' proximal stem-loop 1 (SL1) in the highly structured 5' UTR was invariably required for virus infectivity. Taken together, we conclude that authentic 5'-proximal primary sequence is nonessential, but the resultant structural elements are probably indispensable for PRRSV infectivity.
168 F.3d 480 U.S.v.Paul Brown NO. 97-5572 United States Court of Appeals,Third Circuit. October 21, 1998 1 Appeal From: D.N.J. 2 Affirmed.
File "w04_failure.ml", lines 20-23, characters 2-17: 20 | ..match r1, r2, t with 21 | | AB, _, A -> () 22 | | _, XY, X -> () 23 | | _, _, _ -> () Warning 4: this pattern-matching is fragile. It will remain exhaustive when constructors are added to type repr. File "w04_failure.ml", lines 20-23, characters 2-17: 20 | ..match r1, r2, t with 21 | | AB, _, A -> () 22 | | _, XY, X -> () 23 | | _, _, _ -> () Warning 4: this pattern-matching is fragile. It will remain exhaustive when constructors are added to type ab. File "w04_failure.ml", lines 20-23, characters 2-17: 20 | ..match r1, r2, t with 21 | | AB, _, A -> () 22 | | _, XY, X -> () 23 | | _, _, _ -> () Warning 4: this pattern-matching is fragile. It will remain exhaustive when constructors are added to type xy.
Interferons are proteins which are produced by a number of different kinds of organisms and which are presently grouped into three major classes designated leukocyte interferon (IFN-.alpha.), fibroblast interferon (IFN-.beta.) and immune interferon (IFN-.gamma.). These interferons have antiviral and antiproliferative activites, a potent ability to confer a virus-resistant state in targeted cells and immunomodulatory activities. These biological properties have led to the clinical use of interferons as therapeutic agents for the treatment of viral infections and malignancies, which in turn has prompted a demand for a greater supply. Interferons have been produced from natural sources such as buffy coat leukocytes and fibroblast cells, optionally using known inducing agents to increase the production of interferon. Interferons have also been produced by recombinant DNA techniques, i.e. by expression from a microorganism which has been transformed with an expression vector containing an interferon gene under the control of a promoter-operator sequence. (Leukocyte, fibroblast and immune interferons produced by recombinant techniques are designated rIFN-.alpha., rIFN-.beta. and rIFN-.gamma. respectively.) Regardless of the method of production employed, the resulting interferon must be purified, preferably to homogeneity, before it may be employed as a therapeutic agent. Interferons may be purified to homogeneity using methods described in U.S. Pat. Nos. 4,289,689 and 4,289,690 or by monoclonal antibody affinity chromatography. Presently available purification methods are carried out under conditions which can favor the formation of dimers, trimers and higher oligomers of the interferon. These oligomeric forms of interferon result from two or more interferon molecules becoming irreversibly associated with one another through intermolecular covalent bonding, such as by disulphide linkages. This problem has been observed particularly will respect to leukocyte and fibroblast interferons. The oligomeric form in many cases has either no biological activity or lower activity than the monomeric form, or it has the potential for causing deleterious side effects if used therapeutically. It is important, therefore, to have available a method for obtaining interferons in monomeric form. A method for obtaining fibroblast interferon in monomeric form is described in U.S. Pat. No. 4,278,661. Serum-free human fibroblast interferon is purified by adsorption on immobilized Cibacron Blue and elution of the adsorbed interferon with an aqueous buffer solution containing ethylene glycol, to provide a mixture of interferon in monomeric and dimeric form. The dimeric form is converted to monomeric form by heating the mixture in the presence of an organic thiol compound such as thioglycolic acid, 2-mecaptoethanol or dithiothreitol. The use of elevated temperatures, however, is generally not desirable in protein preparation because of a resulting diminution or complete loss of biological activity for the heated protein.
#ifndef PLATFORM_H_ #define PLATFORM_H_ #define USB_DISCONNECT GPIOB #define USB_DISCONNECT_PIN GPIO_Pin_5 #define RCC_APB2Periph_GPIO_DISCONNECT RCC_APB2Periph_GPIOB #define LED_WRITE(x) GPIO_WriteBit(LED_GPIO, LED_PIN, x) #define LCD_RESET_WRITE(x) GPIO_WriteBit(LCD_RESET_GPIO, LCD_RESET_PIN, x) #define JOY_CENTER_READ GPIO_ReadInputDataBit(JOY_CENTER_GPIO, JOY_CENTER_PIN) #endif
--- ebtables-v2.0.6/ebtables.c.old Thu Sep 9 22:39:49 2004 +++ ebtables-v2.0.6/ebtables.c Thu Sep 9 22:40:18 2004 @@ -1170,7 +1170,7 @@ static int check_rule_exists(int rule_nr if (!t->compare(t->t, u_e->t)) continue; return i; -letscontinue: +letscontinue:; } return -1; }
I have this new customer, that has this PHP App. It was written by a single developer that wanted to "make yet another framework" back in 2005. About 3 Years later the developer left the company, and ...
Q: Combine one value from an array to all the values of another array php For the building of a url query I need to combine one value(key) of an array to all the values(value) of another array. Each combined key => value needs to be added to an array. The problem here is that I can combine the values of the two arrays in two foreach statements, but it creates for every instance a new array. Update Having duplicates is impossible so mine initial output is correct. $array1 array( [0] => music [1] => product ) $array2 array( [0] => '));waitfor delay '0:0:TIME'--1 [1] => '[TAB]or[TAB]sleep(TIME)=' ) public static function create_combined_array($array1, $array2) { $newArray = array(); foreach ($array1 as $key){ //key = [music] foreach ($array2 as $value) { //one of the values is = '));waitfor delay '0:0:__TIME__'--1 array_push($newArray, [$key => $value]); } } return $newArray; } Implementation $query_array = Utils::create_combined_array($params, $payload_lines); print_r($query_array); $query = http_build_query($query_array); $this->url = $baseUrl . '?' . $query; Build query output protocol://localhost:8000?music='));waitfor delay '0:0:TIME'--1 Sample output [54] => Array ( [music] => ));waitfor delay '0:0:__TIME__'--[LF]1 ) [55] => Array ( [music] => '));waitfor delay '0:0:__TIME__'--1 ) [56] => Array ( [music] => '));waitfor delay '0:0:__TIME__'--[LF]1 ) [57] => Array ( [music] => "));waitfor delay '0:0:__TIME__'--1 ) What I wanted to achieve is impossible in PHP. Example duplicates Array( [music] => "));waitfor delay '0:0:__TIME__'--1 [music] => '/**/or/**/benchmark(10000000,MD5(1))#1 ) A: Use code below: public static function create_combined_array($array1, $array2) { $newArray = array(); foreach ($array1 as $key){ foreach ($array2 as $i => $value) { $newArray[$i][$key] = $value; } } return $newArray; } The key line is $newArray[$i][$key] = $value;. It appends an array to the $newArray at $i index which is the index of your second array $array2.
The Kingdom Hearts 3 release date to be announced soon? For those who have been waiting for news on the Kingdom Hearts 3 release date, it’s been quite a long road. Fans have had 12 years between Kingdom Hearts 2 and 3, with the first title launching back in 2002 for the PS2. But having first been announced in 2013, it appears KH3 will finally arrive on PS4 and Xbox One in 2018. According to an online source, the popular Square Enix franchise will be launched in the fiscal third-quarter of this year. This still provides a pretty wide range of dates to choose from, meaning that the game could launch as soon as July, or as late as September. The same rumours also suggest that Square Enix will officially announce the new Kingdom Hearts 3 release date in February. Something similar happened with the launch of Final Fantasy 15, although that was eventually delayed and pushed back to another month.
[Clinical features and diagnosis of cerebral venous thrombosis]. To investigate the clinical features and imaging diagnosis of cerebral venous thrombosis. 65 cases of cerebral venous thrombosis (CVT) were proved by angiography (n = 34) or MR (n = 44), 30 by both procedures and 6 by pathology as well. Their age ranged from 13 to 59 years (mean age 32.5), 31 were male and 34 were female. The clinical manifestations were variable, but most patients had symptoms and signs of intracranial hypertension (91%)such as headache and papilledema. Nearly half of the patients had focal neurological dysfunction (49%) such as weakness of limbs and seizures and half of the patients had intracranial hypertension (51%) only. The occluded dural sinus and the clot could be visualised directly by means of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). MRI and MRA are becoming the imaging investigation of choice for the diagnosis of CVT, Anticoagulation, thrombolysis and dextran may be effective measures in the treatment of cerebral venous thrombosis.
Gucio shoes are available in Euro sizes 18-28 ( Us Sizes 5-12 ). The difference in length between each shoe size is 0,66 mm ( 0,3 inches ).It may seem difficult to choose a child's shoe size for an internet shoe purchase, but it's actually quite straightforward. Our customers have had great success by following one of the 2 simple methods - download PRINTABLE CHARThere or follow the steps below. PLEASE MEASURE BOTH FEET - use bigger feet measurement to choose the right size (if applicable). Place a piece of paper on the floor next to a wall or in a box. Place your child's right foot on the piece of paper with her/his heel against the wall or a side of the box. ( Then make the same with your child's left foot. ) Mark the length of your child's foot at the tip of the longest toe.( Then make the same with your child's left foot. ) Then, take a ruler and measure this distance. Now, compare the length of your child's feet in cm with the table below: ( FREE SPACE FOR TOES IS INCLUDED )
The original Wreck-It Ralph looked more like Cookie Monster than the lovable lug we know today. Artist Joe Pitt, character designer on "Wreck-It Ralph" (as well as most recently on the Disney Channel hit "Gravity Falls"), shows off some early designs for Ralph on his Tumblr, "Joe Draws Stuff" -- in which the movie's protagonist was covered in orange hair: ...and here's one that we're more familiar with: There's also some early designs for Fix-It Felix, like this one: Plus: tons of early storyboarding art, 8-bit renderings of the "Fix-It Felix" game environment, and tons more -- be sure to check this Tumblr out, "Wreck-It Ralph" afficionados!
Tag Archives: Yogita Bali A court here on Saturday granted anticipatory bail to Bollywood star Mithun Chakraborty’s son Mahaakshay and wife Yogita Bali who have been booked for rape and cheating. Special Judge Ashutosh Kumar granted bail to the two asking them to furnish a personal bond of Rs 0.1 million (1 lakh) with two ...
GOTHENBURG, Sweden: April 18, 2017. A report by the Swedish Transport Administration (STA) says the SEK4.0 billion cost of deepening the approach to the Port of Gothenburg to accommodate the world's largest container ships will result in a threefold gain to the country's economy. Gothenburg Port Authority CEO Magnus Kårestedt called the deepening of the five kilometers approach to the container port from 13.5 meters to 16.5 meters "one of the most profitable projects for the future in Sweden". Kårestedt said that at present box ships with a capacity of over 5,000 TEU can only load 50 percent of their capacity while some are so large they are unable to make a port call and are forced to bypass Sweden completely. The STA calculates that Swedish importers and exporters could reduce their transport costs substantially if there was greater opportunity to ship their freight directly to and from Gothenburg. "With this record-breaking [cost-benefit] ratio, we are hopeful that the deepening of the fairway will be prioritized," said Kårestedt. "The government has also expressed an ambition to invest in shipping as it is the most cost-effective and environmentally wise means of transporting freight," he added. Gothenburg port traffic figures last year indicate the deepening of the approach is overdue: While overall volumes rose by almost three million tonnes in 2016 - up from 38.2 million to 40.9 million - container volumes fell three percent to 798,000 TEU handled. "The upturn can be attributed largely to the rise in the number of cars shipped via the port but also to higher volumes at the Energy Port and a good rate of activity at our RoRo terminals," explained Kårestedt. A total of 538,000 RoRo units were shipped last year, up two percent on 2015. Gothenburg is the largest automotive gateway in Sweden - handling imports from Mazda, Nissan and Renault and exports from Volvo. Last year saw a 15 percent increase in throughput to 246,000 cars, up 15 percent on 2015 and the highest figure since the financial crisis of 2008.
--- address: | Physics Department, Indiana University\ Bloomington, IN 47405, U.S.A.\ E-mail: [email protected] author: - RALF LEHNERT title: 'SOME CONSIDERATIONS REGARDING LORENTZ-VIOLATING THEORIES' --- =cmr8 1.5pt \#1\#2\#3\#4[[\#1]{} [**\#2**]{}, \#3 (\#4)]{} \#1\#2[[[\#1]{} ]{}]{} Introduction ============ From a theoretical point of view, the minimal SU(3)$\times$SU(2)$\times$U(1) standard model leaves unresolved a variety of issues. It is therefore believed to be the low-energy limit of an underlying framework that also includes a quantum description of gravity. On the other hand, the standard model is phenomenologically successful, so observable effects from the presumed underlying physics must be minuscule. It then becomes an interesting challenge to identify possible experimental signals from such a fundamental theory accessible with present techniques. A candidate signal of this type is the violation CPT and Lorentz invariance: In conventional renormalizable gauge theories including the standard model, these two symmetries are linked by CPT theorem[@pauli] and hold exactly. In contrast, attempts to construct an underlying framework often involve ingredients that bypass the CPT theorem. For example, string (M) theory is known to admit spontaneous Lorentz and CPT violation.[@str] Other frameworks can also lead to similar low-energy effects.[@klink; @ch] For the microscopic description of possible observable signals at presently accessible energy scales, an extension of the minimal standard model of particle physics has been developed.[@ck] This standard-model extension has provided the basis for numerous experimental investigations discussed during this meeting and elsewhere, which constrain CPT and Lorentz violation.[@exp] In this talk, we study the fundamental properties of causality and stability in the context of the Lorentz-violating standard-model extension. These two properties appear essential for realistic theories, for it would be difficult to make meaningful experimental predictions without either causality or stability. In particular, it is of interest whether these two requirements constrain the parameter space and the range of validity of the standard-model extension, and whether insight into the underlying theory can be gained. Although the calculations presented here are carried out for free massive fermions, we expect that most of our results can be straightforwardly generalized to the other sectors of the standard-model extension. Framework ========= The general Lorentz-violating Lagrangian for a single spin-$\frac{1}{2}$ fermion [@ck] can be cast into a variety of forms. One such form reminiscent of the ordinary Dirac Lagrangian and emphasizing the derivative structure is [@kl99] $${\cal L} = \frac{1}{2}{\it i}\overline{\psi} {\Gamma}^{\nu}\hspace{-.15cm} \stackrel{\;\leftrightarrow} {\partial}_{\!\nu}\hspace{-.1cm}{\psi} -\overline{\psi}M{\psi} \label{lagr} \quad ,$$ where $${\Gamma}^{\nu}:={\gamma}^{\nu}+c^{\mu \nu} {\gamma}_{\mu}+d^{\mu \nu}{\gamma}_{5} {\gamma}_{\mu}+e^{\nu}+if^{\nu}{\gamma}_{5} +\frac{1}{2}g^{\lambda \mu \nu} {\sigma}_{\lambda \mu} \label{Gam} \quad ,$$ and $$M:=m+a_{\mu}{\gamma}^{\mu}+b_{\mu}{\gamma}_{5} {\gamma}^{\mu}+\frac{1}{2}H^{\mu \nu} {\sigma}_{\mu \nu} \label{M} \quad .$$ The gamma matrices $\{1, \gamma_5,\gamma^{\mu}, \gamma_5\gamma^{\mu}, \sigma^{\mu \nu}\}$ have conventional properties, and the signature of the Minkowski metric $\eta_{\mu\nu}$ is $-2$. The extent of Lorentz violation is described by the parameters $a_{\mu}$, $b_{\mu}$, $c_{\mu \nu}$, $d_{\mu \nu}$, $e_{\mu}$, $f_{\mu}$, $g_{\mu \nu \lambda}$ and $H_{\mu \nu}$. As a consequence of the presumed hermiticity of the Lagrangian, all these coefficients are real, with $c_{\mu \nu}$ and $d_{\mu \nu}$ traceless, $g_{\mu \nu \lambda}$ antisymmetric in its first two indices and $H_{\mu \nu}$ antisymmetric. While all the parameters violate Lorentz invariance, only $a_{\mu}$, $b_{\mu}$, $e_{\mu}$, $f_{\mu}$ and $g_{\mu \nu \lambda}$ break CPT symmetry as well. Since no departures from Lorentz symmetry have been observed to date, all Lorentz-breaking parameters must be minuscule in a certain class of observer inertial frames called [*concordant frames*]{}, and the Earth must move nonrelativistically with respect to these frames. Throughout this talk, we shall work under the assumption that the size of the Lorentz violation is such that, in a concordant frame, a hermitian hamiltonian can be found and the dispersion relation still exhibits two positive- and two negative-valued roots,[@kl01; @kljmp] paralleling the conventional Dirac case. The lagrangian can then be canonically quantized such that the energy is positive definite.[@kl01] Microcausality and Stability ============================ A quantum field theory is microcausal if any two local observables with spacelike separation can be measured independently. This is guaranteed if any two local, spatially separated operators commute. In the present case, such local operators are fermion bilinears and the above condition is satisfied if $$iS(x-x^{\prime})=\{\psi(x), \overline{\psi}(x^{\prime})\}=0 \quad, \qquad(x-x^{\prime})^2<0 \label{anticom}$$ holds. Note that the anticommutator function $S(x-x^{\prime})$ only depends on the coordinate differences due to translational invariance. To determine an integral representation for the $S(z)$, we insert the plane-wave expansion of the field operators[@kl01] into the anticommutator and use the generalization of the conventional spinor projectors.[@kljmp] This gives the following expression: $$S(z)=\int_{C}\fr{d^4\lambda}{(2\pi)^4} e^{-i\lambda\cdot z} \fr{{\rm cof}(\Gamma_{\mu}\lambda^{\mu}-M)} {\det(\Gamma_{\mu}\lambda^{\mu}-M)} \label{pwexp2} \quad,$$ where $C$ is the usual contour encircling all poles in clockwise direction, and ${\rm cof}(\cdot)$ denotes the matrix of cofactors. Notice that $\lambda^{\mu}$ can be replaced by $i\partial^{\mu}$ in the numerator of the integrand. It is then possible to pull the cofactor matrix outside the integral, because the contour $C$ can be deformed such that the integrand is analytic in a neighborhood of $C$.[@sg] We obtain for the anticommutator function $$S(z)= {\rm cof}(\Gamma^{\mu} i\partial_{\mu}-M) \int_{C} \fr{d^4\lambda} {(2\pi)^4} \fr{e^{-i\lambda\cdot z}} {\det(\Gamma^{\mu}\lambda_{\mu}-M)} \quad. \label{ffgreen}$$ Next, we study $S(z)$ outside the lightcone. We can take advantage of observer Lorentz invariance and boost to a frame such that $z^{\mu}=(0,\vec{z})$. To make further progress, it is necessary to investigate the pole structure of the integrand. Due to the above observer transformation we may no longer assume to be working in a concordant frame. In particular, it may not be possible to find a hermitian hamiltonian, so that complex eigenenergies may occur. Since the eigenenergies determine the location of the poles of the integrand, the contour $C$ may fail to encircle them all. Thus, the case where a hermitian hamiltonian (and therefore real eigenenergies) exist in all frames has to be distinguished. We consider this case first. A sufficient condition for the hermiticity of the hamiltonian in all observer frames is that the derivative structure of lagrangian (\[lagr\]) is the conventional one, [*i.e.,*]{} $\Gamma^{\mu}=\gamma^{\mu}$. Then, all four roots $E_{(j)}(\vec{\lambda})$, $j=1,\ldots,4$, of the dispersion relation appearing in the denominator of the integrand in Eq. (\[ffgreen\]) are real. In this case, the contour integration can be directly performed.[@kl01] This argument confirms microcausality for the case $\Gamma^{\mu}=\gamma^{\mu}$. In cases when there exist observer frames that fail to admit the definition of a hermitian hamiltonian, the above line of reasoning cannot be employed, and microcausality may break down. For example, consider a model with $c_{00}$ parameter only. The anticommutator function for this model is given explicitly by $$S(z)=(i\zeta\gamma^0\partial^0 -i\gamma^j\partial^j+m) \fr{1}{4\pi\zeta r} \fr{\partial}{\partial r}[\Theta(w^2) J_0(m\sqrt{w^2})] \quad, \label{prop}$$ where $\zeta=1+c_{00}$, $r=|\vec{z}|$, $w^2=(z^0/\zeta)^2-\vec{z}^2$, $\Theta$ denotes the Heaviside step function and $J_0(y)$ is the zeroth-order Bessel function. It follows that the anticommutator function $S(z)$ vanishes only in the region defined by $z^0<(1+c_{00})|\vec{z}|$. The propagation of signals therefore could occur with maximal speed $1/(1+c_{00})$. For negative values of $c_{00}$, this exceeds 1 and hence violates microcausality. The question arises, at which energy scale this breakdown of microcausility occurs. To this end, it is useful to introduce a definition of the velocity of a particle valid for arbitrary 3-momenta. Even in the conventional Lorentz- and CPT-symmetric case, the notion of a quantum velocity operator is nontrivial. The issue is further complicated in the present context.[@ck] Here, we consider the group velocity defined for a monochromatic wave in terms of the dispersion relation. This choice seems appropriate for a variety of reasons.[@kl01] Insight about the scale $\tilde{M}$ of microcausality violations can then be gained by determining the value of the 3-momentum at which the the group velocity reaches 1. Analyses for a variety of parameter combinations yield $$\tilde{M}\gsim {\cal O}(M_P) \quad . \label{mscale1}$$ Here, we have assumed that the parameters $c_{\mu\nu}$, $d_{\mu\nu}$, $e_{\mu}$, $f_{\mu}$ and $g_{\mu\nu\lambda}$ are of order $m/M_P$, where $M_P$ denotes the Planck scale. We mention in passing that the conclusion of microcausality breakdown at ${\cal O}(M_P)$ may be invalid if the $c_{\mu\nu}$ coefficient is nonzero. For example, in the above model with only a coupling $c_{00}<0$, one can show that $\tilde{M}\gsim{\cal O}(\sqrt{mM_P})$. The effect of the $c_{\mu\nu}$ parameter on the dispersion relation is special for the following reason: The general spinorial and derivative structure of the associated quadratic field term is identical to the conventional Dirac kinetic term. Thus, it is a first-order correction to an existing zeroth-order term. None of the other Lorentz-violating couplings exhibits this feature. The above analysis shows that the standard-model extension can develop problems when the symmetry-breaking scale is approached. This should not come as a surprise because the effects of the presumed underlying theory are likely to be no longer negligible at these energies. However, given the impracticality of achieving Planck-scale momenta in the laboratory, the issue of microcausality breakdown is largely unimportant at the level of the standard-model extension. Another important ingredient for realistic field theories is the requirement of stability. A field theory is stable if the energy is positive definite [*in all observer frames*]{}. This implies that the 4-momenta of all one-particle states in a particular frame must be timelike or lightlike with nonnegative 0th component. Only under this last condition, does energy positivity become an observer-invariant notion. This is satisfied in the conventional Dirac case. In the present context, the energy is positive definite in concordant frames. In these frames, the dispersion relation has still two positive- and two negative-valued roots, which yield positive particle energies after the usual reinterpreta-tion.[@kl01] However, contrary to the conventional case, these energies are in some instances 0th components of spacelike 4-momenta. As a result, energy positivity becomes observer-dependent. As an example, consider a model that has all Lorentz-violating parameters except $b_{\mu}$ set to zero. The dispersion relation for this model is given by $$(\lambda^2-b^2-m^2)^2+4b^2\lambda^2 -4(b\cdot\lambda)^2=0 \quad . \label{bdisp}$$ It is straightforward to show that observer frames in which $b_{\mu}=(b_0,0,0,b_3)$ and ${b_3}^2>m^2+|b^{\mu}b_{\mu}|$ can always be chosen. In such a frame, the spacelike 4-vectors ${\lambda^{\mu}}_{\pm}=(0,0,0,p_{\pm})$ satisfy the dispersion relation (\[bdisp\]). Here, the real quantities $p_{\pm}$ are defined by $${p_{\pm}}^2=(2{b_3}^2+b^2-m^2) \pm\sqrt{(2{b_3}^2+b^2-m^2)^2-(m^2+b^2)^2} \quad . \label{moment}$$ Moreover, the existence of these spacelike solution remains unaffected, when a nonzero $a_{\mu}$ coefficient is included. The instabilities resulting from these spacelike 4-momenta are most transparent for sufficiently boosted observers: It is always possible to convert a spacelike vector with a positive 0th component to one with a negative 0th component by an appropriate observer Lorentz transformation. In the present case, this means that there exist otherwise acceptable observer frames in which a single root of the dispersion relation involves both positive and negative energies for varying 3-momenta. In such observer frames, the canonical quantization procedure fails. In concordant frames, the energy is positive definite. However, the physics is independent of the observer, so the appearance of negative energies in a boosted frame must also lead to instabilities in the concordant frames. The above discussions implies that these instabilities can only be associated with the spacelike momenta satisfying the dispersion relation. To illustrate this, let us introduce a U(1) gauge interaction for the moment because in the free fermion model the particle number is conserved. As an example, consider the following process in a concordant frame: A high-energy fermion emits a virtual photon, which then decays into a fermion-antifermion pair. We can write this as $$f_{+1}\longrightarrow f_{+1} +f_{+1}+\bar{f}_{-1} \quad , \label{decay}$$ where $f$ and $\bar{f}$ denote fermions and antifermions, respectively, and the subscript labels the helicity state. In ordinary QED, such a process is kinematically forbidden even though both the U(1) charge and angular momentum are conserved. However it can occur in the present context if the incoming fermion has an appropriate spacelike 4-momentum.[@kl01] Thus, there exist unstable single-particle states. The scale $\tilde{M}$ of the 3-momentum at which spacelike 4-momenta occur can be calculated explicitly for various parameter combination. We find that $$\tilde{M} \gsim {\cal O}(M_P) \quad , \label{bscale}$$ where we have assumed that the derivative-coupling coefficients have the same suppression as in the microcausality case, and the remaining parameters $a_{\mu}$, $b_{\mu}$ and $H_{\mu\nu}$ are of order $m^2/M_P$. This estimate shows that the instabilities appear only for Planck-scale 4-momenta in a concordant frame. The corresponding negative energies occur only for Planck-boosted observers relative to this frame. Since the Earth moves nonrelativistically with respect to concordant frames, the model maintains stability for all experimentally attainable physical momenta and in all experimentally attainable observer frames. As for microcausality, the presence of a $c_{\mu\nu}$ parameter can invalidate (\[bscale\]). For example, a model with a positive $c_{00}$ coefficient only, exhibits spacelike momenta at a scale of order $\sqrt{mM_P}$. It follows that when microcausality and stability are imposed on a model with a $c_{\mu\nu}$ coupling, effects from the presumed underlying theory are likely to become non-negligible already at energies close to the geometric mean of $M_P$ and $m$. As this scale is within reach of some experiments, a theoretical analysis of such effects may require high-energy corrections to the standard-model extension. In the next section, we discuss a possible type of such corrections. High-Energy Effects =================== The results from the previous section indicate that quantum field theories of massive fermions containing terms explicitly breaking Lorentz invariance can develop difficulties with mircocausality or stability. However, in concordant frames, these difficulties primarily appear as the Planck scale is approached. The question arises, whether there exist combinations of Lorentz-violating coefficients that maintain both causality and stability. Many parameter combinations eliminate one of the two difficulties. However, we are unaware of any set of values of the couplings $a_{\mu}$, $b_\mu$, $\ldots$, $H_{\mu\nu}$ that simultaneously guarantee microcausality and stability at all energy scales. Moreover, it has been shown rigorously that in [*conventional*]{} quantum field theory, such a set of parameters would have to yield the ordinary Lorentz-symmetric dispersion relation.[@be] It is then likely that these Lorentz-breaking parameters can be absorbed into a field redefinition and remain unobservable. The Lorentz-violating standard-model extension was developed following a top-down approach. The original motivation was the possibility of spontaneous Lorentz-symmetry breakdown in an underlying framework such as strings.[@str] Indeed, the standard-model extension includes all Lorentz-violating, but observer-invariant, terms compatible with renormalizability and the usual gauge structure. It is thus the low-energy limit of any potential spontaneous Lorentz breaking in a more fundamental theory. It is therefore not surprising that difficulties develop as the Planck-scale is approached. One would expect higher-order nonrenormalizable operators to gain importance. On the other hand, the essential status of the requirements of causality and stability suggests to adopt the inverse line of reasoning. Such a bottom-up approach could provide valuable insights into the nature of the underlying theory at the Planck scale. The standard-model extension breaks Lorentz invariance explicitly. However, a desirable feature of the fundamental theory is spontaneous symmetry breaking. One immediate advantage of this mechanism is that the dynamics remains Lorentz covariant. Therefore it does not come as a surprise that such an underlying framework avoids at least some of the difficulties plaguing more general models involving Lorentz and CPT violation. For instance, one consequence of the spontaneous character of the Lorentz violation is that observer invariance is naturally maintained. In the previous section, this property has proved to be an important advantage. In contrast, if observer Lorentz invariance is imposed in a theory with explicit Lorentz breaking, an additional *ad hoc choice is required.* Another effect of spontaneous Lorentz violation is that the parameters $a_{\mu}$, $b_\mu$, $\ldots$, $H_{\mu\nu}$ are only fixed at low energies. As the Planck scale is approached, they must be associated with dynamical fields. A natural question is, whether these fluctuations alone can simultaneously maintain microcausality and stability. This issue has been previously been discussed in the context of a toy model. It was shown that a satisfactory resolution within the context of ordinary point-particle field theory seems unlikely.[@kl01] This is consistent with other ideas.[@be] As expected, ingredients beyond conventional quantum field theory appear necessary. A class of theories with free-field terms maintaining causality and stability must contain terms beyond the ones in Eq. (\[lagr\]). The new terms have to be nonrenormalizable, and in a realistic scenario with spontaneous Lorentz violation they would correspond to higher-order nonrenormalizable operators correcting the standard-model extension at energies determined by the Planck scale. The first step is to investigate whether any type of dispersion relation can satisfy all the requirements for consistency. In a concordant frame, such a dispersion relation would reproduce the physics of Eq. (\[lagr\]) for small 3-momenta but would avoid group velocities exceeding 1 and spacelike 4-momenta for large 3-momenta. These requirements could be implemented by combining the Lorentz- and CPT-breaking parameters with a suitable factor suppressing them only at large 3-momenta. This factor must be essentially constant at small 3-momenta and must overwhelm polynomial powers at large 3-momenta. Since the the size of 3-momenta is frame dependent, it is to be expected that a suitable factor would also be frame-dependent and hence involve Lorentz- and CPT-violating coefficients. To make further progress, it is useful to consider explicit examples. To simplify the discussion, the masses and the Lorentz-violating parameters are taken to be of order 1 in appropriate units. This makes it possible to focus on resolving the problems of stability and causality at Planck-scale energies in a concordant frame without the complications introduced by the hierarchy of scales. Consider a model with a negative $c_{00}$ parameter only. As discussed in the previous section, this model violates microcausality at high energies. The replacement $c_{00}\rightarrow c_{00}\exp (c_{00}{\lambda_0}^2)$ in the dispersion relation has been shown to result in subluminal group velocities for all 3-momenta without introducing instabilities.[@kl01] In an arbitrary frame, this modification takes the form $$c_{\mu\nu}\rightarrow c_{\mu\nu} \exp (c_{\mu\nu}\lambda^{\mu}\lambda^{\nu}) \quad , \label{crepl}$$ establishing observer invariance of the resulting dispersion relation. It can also be shown that introducing similar exponential suppression factors in models with instabilities can also resolve this problem while maintaining subluminal group velocities. The above demonstrations prove that stable and causal dispersion relations violating Lorentz and CPT symmetry can exist. The occurrence of transcendental functions of the 4-momenta corresponds to derivative couplings of arbitrary order in the lagrangian. A satisfactory framework incorporating Lorentz and CPT violation appears necessarily to be nonlocal in this sense. Although it is in principle conceivable that a model with explicit Lorentz breaking might satisfy the requirements of causality and stability, it would appear somewhat contrived to implement both the necessary observer Lorentz invariance and nonlocal couplings by hand. On the other hand, one can see that spontaneous Lorentz and CPT violation in a nonlocal theory can naturally yield the desired ingredients for stability and causality at all scales. It would be interesting to identify theories from which these dispersion relations emerge naturally. A promising candidate for this type of framework is string theory. It provided the original motivation for the construction of the standard-model extension. Moreover, strings are known to admit spontaneous Lorentz violation and they have nonlocal interaction. A complete treatment of this question would be desirable, but is hampered by the absence of a satisfactory realistic string theory. Instead, we consider the field theory of the open bosonic string as an example and show that its structure is compatible with dispersion relations of the desired type. The open bosonic string has no fermion modes. We will therefore consider the scalar tachyon. The relevant quadratic terms of the lagrangian for the tachyon in the presence of Lorentz violation are given by:[@str] $$\begin{aligned} {\cal L} &\supset & \fr{1}{2} \partial_\mu \phi \partial^\mu \phi + (\alpha^{\prime -1} + k_0) \phi^2 + \ldots + k_1 \langle B_{\mu\nu} \rangle \partial^\mu \phi \partial^\nu \phi \nonumber\\ &&\qquad + \ldots + k_2 \langle D_{\mu\nu\rho\sigma} \rangle \partial^\mu \phi \partial^\nu \phi \partial^\rho \phi \partial^\sigma \phi + \ldots \quad . \label{string}\end{aligned}$$ Here, the scalar parameters $k_0$, $k_1$, $k_2$, $\ldots$ are determined by the theory, but their specific values are irrelevant for the present considerations. Each ellipsis represents quadratic terms involving vacuum expectation values of other tensors and terms with powers of $\lambda^2$. For a plane-wave tachyon solution, the structure of the dispersion relation resulting from lagrangian (\[string\]) indeed exhibits features needed to maintain causality and stability. For example, it contains all terms of the dispersion relation that results from the replacement (\[crepl\]) in the $c_{00}$ model, as the reader is invited to verify. We emphasize that the purpose of the above discussion is only to provide an outline indicating how a satisfactory dispersion relation for Lorentz violation could emerge in the context of string theory. In particular, we do not claim that the tachyon itself must *necessarily obey such a relation, although it is conceivable that it does.[@str] Here, the tachyon dispersion relation is used merely as an illustration to display explicitly the appearance of nonlocal couplings in string theory that could be appropriate for a stable and causal theory with spontaneous Lorentz violation. This type of coupling is generic both for other fields in the open bosonic string and for fields in other string theories, including ones with fermions.* References {#references .unnumbered} ========== [99]{} J.S. Bell, Birmingham University thesis (1954); G. Lüders, Det. Kong. Danske Videnskabernes Selskab Mat.fysiske Meddelelser [**28**]{}, 5 (1954); W. Pauli, in [*Niels Bohr and the Development of Physics*]{}, edited by W. Pauli (McGraw-Hill, New York, 1955). V.A. Kostelecký and S. Samuel, Phys. Rev. D [**39**]{}, 683 (1989); V.A. Kostelecký and R. Potting, Nucl. Phys. B [**359**]{}, 545 (1991); Phys. Lett. B [**381**]{}, 89 (1996). F.R. Klinkhamer, Nucl. Phys. B [**578**]{}, 277 (2000). S.M. Carroll [*et al.*]{}, Phys. Rev. Lett. [**87**]{}, 141601 (2001). D. Colladay and V.A. Kostelecký, Phys. Rev. D [**55**]{}, 6760 (1997); Phys. Rev. D [**58**]{}, 116002 (1998). Reviews of various experimental approaches can be found, for example, in these proceedings and V.A. Kostelecký, ed., [*CPT and Lorentz Symmetry*]{} (World Scientific, Singapore, 1999). V.A. Kostelecký and C.D. Lane Phys. Rev. D [**60**]{}, 116010 (1999); J. Math. Phys. [bf 40]{}, 6245 (1999). V.A. Kostelecký and R. Lehnert, Phys. Rev. D [**63**]{}, 65008 (2001). V.A. Kostelecký and R. Lehnert, in preparation. See, e.g., G. Sansone and J. Gerretsen, [*Lectures on the Theory of Functions of a Complex Variable, Vol.1*]{}, Noordhoff, Groningen, 1960. H.J. Borchers and D. Buchholz, Commun. Math. Phys. [**97**]{}, 169 (1985); J. Bros, H. Epstein and V. Glaser, Nuovo Cimento [**31**]{}, 1265 (1964). V.A. Kostelecký and S. Samuel, Phys. Lett. B [**207**]{}, 169 (1988); Nucl. Phys. [**B336**]{}, 263 (1990); Phys. Rev. D [**42**]{}, 1289 (1990); Phys. Rev. Lett. [**64**]{}, 2238 (1990); Phys. Rev. Lett. [**66**]{}, 1811 (1991).
/* See license.txt for terms of usage */ define([ "firebug/lib/trace", "firebug/lib/http", "firebug/chrome/firefox" ], function(FBTrace, Http, Firefox) { // ********************************************************************************************* // // Constants var Ci = Components.interfaces; var Cc = Components.classes; var wm = Cc["@mozilla.org/appshell/window-mediator;1"].getService(Ci.nsIWindowMediator); var Win = {}; var window = {}; // these declarations exist to cause errors if we accidentally var document = {}; // reference these globals // ********************************************************************************************* // // Crossbrowser API Win.getWindowProxyIdForWindow = function(win) { if (!win) return null; var id = Win.getWindowId(win).outerWindowID; // xxxJJB, xxxHonza: the id is often null, what could be the problem? // jjb: My guess: just another Mozilla bug if (!id) return Win.getTabIdForWindow(win); return id; }; Win.getTabForWindow = function(aWindow) { aWindow = Win.getRootWindow(aWindow); var tabBrowser = Firefox.getTabBrowser(); if (!aWindow || !tabBrowser || !tabBrowser.getBrowserIndexForDocument) { if (FBTrace.DBG_WINDOWS) FBTrace.sysout("getTabForWindow FAIL aWindow: "+aWindow+" tabBrowser: "+tabBrowser, tabBrowser); return null; } try { var targetDoc = aWindow.document; var tab = null; var targetBrowserIndex = tabBrowser.getBrowserIndexForDocument(targetDoc); if (targetBrowserIndex != -1) { tab = tabBrowser.tabContainer.childNodes[targetBrowserIndex]; return tab; } } catch (ex) { } return null; }; Win.getTabIdForWindow = function(win) { var tab = Win.getTabForWindow(win); return tab ? tab.linkedPanel : null; }; // ********************************************************************************************* // // Window iteration Win.iterateWindows = function(win, handler) { if (!win || !win.document) return; handler(win); if (win == top || !win.frames) return; // XXXjjb hack for chromeBug for (var i = 0; i < win.frames.length; ++i) { var subWin = win.frames[i]; if (subWin != win) Win.iterateWindows(subWin, handler); } }; Win.getRootWindow = function(win) { for (; win; win = win.parent) { if (!win.parent || win == win.parent) return win; // When checking the 'win.parent' type we need to use the target // type from the same scope. i.e. from win.parent // Iframes from different domains can use different Window type than // the top level window. if (!(win.parent instanceof win.parent.Window)) return win; } return null; }; // ********************************************************************************************* // // Firefox browsing Win.openNewTab = function(url, postText) { if (!url) return; var postData = null; if (postText) { var stringStream = Http.getInputStreamFromString(postText); postData = Cc["@mozilla.org/network/mime-input-stream;1"].createInstance(Ci.nsIMIMEInputStream); postData.addHeader("Content-Type", "application/x-www-form-urlencoded"); postData.addContentLength = true; postData.setData(stringStream); } var tabBrowser = Firefox.getTabBrowser(); if (!tabBrowser) { if (FBTrace.DBG_ERRORS) FBTrace.sysout("window.openNewTab; ERROR No tabBrowser!"); return; } return tabBrowser.selectedTab = tabBrowser.addTab(url, null, null, postData); }; // Iterate over all opened firefox windows of the given type. If the callback returns true // the iteration is stopped. Win.iterateBrowserWindows = function(windowType, callback) { var windowList = wm.getZOrderDOMWindowEnumerator(windowType, true); if (!windowList.hasMoreElements()) windowList = wm.getEnumerator(windowType); while (windowList.hasMoreElements()) { if (callback(windowList.getNext())) return true; } return false; }; Win.iterateBrowserTabs = function(browserWindow, callback) { var tabBrowser = browserWindow.getBrowser(); var numTabs = tabBrowser.browsers.length; for(var index=0; index<numTabs; index++) { var currentBrowser = tabBrowser.getBrowserAtIndex(index); if (callback(tabBrowser.mTabs[index], currentBrowser)) return true; } return false; }; Win.getBrowserByWindow = function(win) { var browsers = Firefox.getBrowsers(); for (var i = 0; i < browsers.length; ++i) { var browser = browsers[i]; if (browser.contentWindow === win) return browser; } return null; }; // ********************************************************************************************* // Win.getWindowId = function(win) { var util = win.QueryInterface(Ci.nsIInterfaceRequestor).getInterface(Ci.nsIDOMWindowUtils); var outerWindowID = null; var innerWindowID = "(none)"; try { outerWindowID = util.outerWindowID; innerWindowID = util.currentInnerWindowID; } catch(exc) { // no - op } return { outer: outerWindowID, inner: innerWindowID, toString: function() { return this.outer+"."+this.inner; } }; }; Win.safeGetWindowLocation = function(window) { try { if (window) { if (window.closed) return "(window.closed)"; if ("location" in window) return window.location+""; else return "(no window.location)"; } else return "(no context.window)"; } catch (exc) { if (FBTrace.DBG_WINDOWS || FBTrace.DBG_ERRORS) { FBTrace.sysout("TabContext.getWindowLocation failed "+exc, exc); FBTrace.sysout("TabContext.getWindowLocation failed window:", window); } return "(getWindowLocation: "+exc+")"; } }; // ********************************************************************************************* // return Win; // ********************************************************************************************* // });
9 Ill.2d 561 (1956) 138 N.E.2d 487 HAROLD M. BOHAN et al., Appellants, v. THE VILLAGE OF RIVERSIDE et al., Appellees. No. 34078. Supreme Court of Illinois. Opinion filed November 26, 1956. *562 WALLACE B. KEMP, of Chicago, for appellants. TENNEY, SHERMAN, BENTLEY & GUTHRIE, and ROBERT W. MURPHY, both of Chicago, (S. ASHLEY GUTHRIE, of counsel,) for appellees. Judgment affirmed. Mr. JUSTICE BRISTOW delivered the opinion of the court: Plaintiffs-appellants appeal directly to this court from a final order and declaratory judgment of the circuit court of Cook County in favor of the defendants, entered upon their motion for judgment on the pleadings, which held certain amendments to a zoning ordinance valid and denied plaintiffs' prayer for an injunction restraining the construction and use of a building for a youth center. The trial judge certified that the validity of a municipal ordinance is involved and in his opinion the public interest requires a direct appeal. Consequently, this court properly has jurisdiction. *563 The ultimate question at issue is the validity of an amendment to the zoning ordinance of the village of Riverside adding to the specific uses permitted in a Residence District B-4 (an office-residence district) the following: "Clubs, associations, or recreation rooms and quarters not involving, however, the conduct of a retail business on the premises." Prior to adoption of the zoning amendment in question, the permitted uses in Residence District B-4 included business and professional offices; medical clinics and hospitals; private, vocational and professional schools; portrait studios; funeral parlors and mortuaries, and uses permitted in more restricted residence districts. The more restricted districts permitted single, duplex and multiple family residences; municipally owned or operated public library, park, playground, recreation or field house or public utility; churches; public, private or parochial elementary or high schools; hotels, lodging or boarding houses; and free parking lots appurtenant to such uses. The plaintiffs are owners of property adjacent to and in the vicinity of a tract of land purchased by defendant District 208 Youth Center, Inc., in Residence District B-4 on which it is proposed to construct and operate a youth center, with its usual activities including dancing and youth parties. Plaintiffs allege they purchased their property in reliance on the continued existence and benefits and advantages of the use limitations. The amended complaint alleges that on August 17, 1955, the village board of trustees adopted an amendment to its zoning ordinance known as ordinance No. 833 which permitted club, association or recreation rooms or quarters in Residence District B-4 on which ordinance no hearing was ever had before a committee appointed by corporate authorities nor notice of hearing published as required by section 73-8 of the Revised Cities and Villages Act, (Ill. *564 Rev. Stat. 1955, chap. 24, par. 73-8,) and that such ordinance was therefore invalid and void. The amended complaint further alleges that subsequent to filing the original complaint the village adopted a new ordinance, No. 838, incorporating the same provisions as the prior ordinance, by publishing notice thereof in the form of a legal notice. It is charged such ordinance is illegal and void in that it was manipulated so as to avoid any notice of the pendency of such ordinance or hearing thereon reaching plaintiffs or their counsel by not giving personal notice or publishing notice in a spread two columns wide as such ordinances were normally published in the past. The amended complaint further alleges that prior to adoption of the ordinances in question the use of the youth center property for dances for large numbers of persons was forbidden; that the youth center threatens and intends to construct on its property a building to accommodate 180 couples to be used primarily for dancing Friday and Saturday nights, or more often, for its members who are all under 18 years of age; that the village is aware of such intentions and proposes to permit the same; that the character of the neighborhood is overwhelmingly residential and peaceful; that the operation of the youth center will greatly increase traffic and traffic hazards on a road of narrow dimensions traversing the area, will disturb the peace and tranquility expected by bereaved relatives and friends of deceased persons from time to time in a funeral home adjacent to the youth center property, will seriously and detrimentally affect the business of the funeral home, will increase fire hazards, will cause the neighborhood to deteriorate seriously as a residential neighborhood, and will greatly damage the market value of plaintiffs' property. By virtue of the foregoing, the amendments to the zoning ordinance were alleged to be unconstitutional, illegal and invalid in that they were not passed for the purpose *565 of public health, safety, comfort, morals and welfare, were special legislation, and deprive plaintiffs of property without due process of law. Answers by defendants, replies thereto by plaintiffs, motions to strike portions of answers, and defendants' motion for judgment on the pleadings were thereafter filed. The trial court in its order and judgment found that ordinance No. 838 was legally passed and approved after lawful publication and hearing thereon, that the ordinance was valid and effective, that the youth center property was in Residence District B-4, and that the proposed use of such property was lawfully permitted under the ordinance. Plaintiffs in their appeal argue that the action of the trial judge in allowing defendants' motion for judgment on the pleadings and in making findings of fact and law was improper and that the ordinances were invalid. Plaintiffs first contend that the motion for judgment on the pleadings does not comply with the requirements of section 45 of the Civil Practice Act (Ill. Rev. Stat. 1955, chap. 110, par. 45,) that motions directed to pleadings shall point out specifically the defects complained of, and the motion was so transparently insufficient in law that the chancellor should have refused to entertain it, citing Lederer v. St. Clair Hotel, Inc. 339 Ill. App. 214. When the motion for judgment was filed, the case was pending on the complaint, answers thereto, and plaintiffs' motions to strike. Replies were later filed by leave of court before judgment was entered. Plaintiffs did not question the form of motion for judgment on the pleadings although they had ample opportunity. Even if the motion was questionable as to form, it could have been corrected if objection on that ground had been seasonably made in the trial court. The objection to the form of the motion will not be considered when raised for the first time on appeal. Thomas v. Durchslag, 404 Ill. 581. Although plaintiffs attack the legality and validity of *566 ordinance No. 833, the first amendment to the zoning act in question, its validity is of importance only if the later ordinance No. 838 repealing the prior amendment and enacting a new amendment is invalid. Ordinance No. 838 is first attacked from a procedural and technical point of view for the reason that it was passed after the filing of the original complaint herein without personal notice to the court or to the plaintiffs. The amended complaint itself shows that notice of hearing on the ordinance was given by a legal publication and hearing had thereon, all as required by section 73-8 of the Revised Cities and Villages Act. The mere pendency of a suit by plaintiffs does not affect the powers of a municipality to pass an ordinance or the manner of exercise of such power as prescribed by statute. There was no requirement that the village give personal notice to the plaintiffs or to the court of the proposal to pass an ordinance amending the zoning ordinance and correcting alleged technical defects in the old ordinance, other than the statutory notice. From a procedural and technical point of view, ordinance No. 838 was lawfully passed and we need not consider the alleged circumstances surrounding passage of ordinance No. 833. But plaintiffs' main contention is that the ordinance must comply with the enabling act, that allegations of fact in the amended complaint must be taken as true, and that those allegations establish that the ordinance failed to comply with the substantive requirements of the enabling act. There is no question but that the validity of an amendatory zoning ordinance must be determined by the same rules and tests as those applied in ascertaining the validity of original zoning ordinances. (Trust Company of Chicago v. City of Chicago, 408 Ill. 91.) The same case, and many others too numerous to cite, clearly establish that a zoning ordinance to be valid must not be arbitrary and unreasonable, *567 but must bear a substantial relation to the public health, safety, comfort, morals or welfare. Plaintiffs argue that the motion for judgment admits the allegations that the ordinance will greatly increase traffic and traffic hazards, will increase fire hazards, will disturb the peace, will decrease the value of lands, and will change existing conditions and uses to which the property is presently devoted. Therefore, they argue, the ordinance violates the enabling act, is arbitrary and unreasonable, and beyond the power of the village. They further argue that plaintiffs were entitled to rely on the classification of the property. However, all presumptions are in favor of the validity of a zoning ordinance, the courts will not overrule the legislative decision as to granting a variation where the question is fairly debatable, and the burden is on objecting parties to show that an ordinance is unreasonable, arbitrary and capricious. Bullock v. City of Evanston, 5 Ill.2d 22; Kinney v. City of Joliet, 411 Ill. 289. The complaint clearly shows that plaintiffs' property for many years has been situated in a district where permitted uses included parks, playgrounds, recreation and field houses, churches, schools, hotels, business and professional offices, and hospitals. Although plaintiffs have a right to rely upon the classification of property and that classifications will not be changed unless required for the public good, (Kennedy v. City of Evanston, 348 Ill. 426,) they also acquired their property knowing amendments could be made to the ordinance within the limits of the law. The allegations of the complaint nowhere indicate in what manner the proposed use is dissimilar to presently permitted uses, or will create more traffic hazards, fire hazards, reduction in property values, disturbance of the peace or interference with a funeral home than playgrounds, recreation houses, schools or hotels. There is no factual basis alleged in the complaint for holding that use of the *568 property for clubs, associations or any other recreational establishment is more onerous than the uses previously specifically permitted. The fact that such club or association may consist of youths does not render the ordinance invalid. Organizations composed of youths are not, for that reason, undesirable as a matter of law. Youth is a vital and integral segment of our community life and must be given an opportunity to become responsible members of society. The allegations of injury or damage that may result from wrongful operation and conduct of the youth center are necessarily speculative. If and when a wrong occurs it may be corrected but it cannot be assumed in advance that the wrong will occur. Because a privilege may be abused is no reason why it shall be denied. City of Chicago v. Drake Hotel Co. 274 Ill. 408. In view of the character of uses permitted in the district in question as appears in the complaint, there is no sound basis appearing in the complaint for the assertion that the action of the village was unreasonable, arbitrary or capricious, or that the ordinance was in any sense invalid. The judgment of the trial court is affirmed. Judgment affirmed.