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Lauren Townsend (footballer) Lauren Townsend (born 10 November 1990) is a footballer who plays as a defender for the Wales national team and most recently for the Women's Welsh Premier League club Cardiff Met.. Townsend won 20 caps for Wales at under-19 level. She made her senior debut on 30 January 2008; a 1–1 friendly draw with Portugal in Mafra, Portugal. References External links Category:1990 births Category:Living people Category:Yeovil Town L.F.C. players Category:Bristol Academy W.F.C. players Category:Wales women's international footballers Category:Welsh women's footballers Category:FA Women's Super League players Category:Cardiff City Ladies F.C. players Category:FA Women's National League players Category:Cardiff Met. Ladies F.C. players Category:Women's association football defenders

TNIK serves as a novel biomarker associated with poor prognosis in patients with pancreatic cancer. Traf-2 and Nck interacting kinase (TNIK) is one of the STE20/MAP4K family members implicated in carcinogenesis and progression of several human malignancies. However, its expression pattern and biological behavior in pancreatic carcinoma remains completely unclear. The present study is designed to investigate the clinical and prognostic value of TNIK in pancreatic carcinoma. TNIK mRNA and protein level was respectively detected by real-time quantitative RCR (qPCR) and Western blot in ten paired samples of pancreatic cancer. Immunohistochemical staining was also conducted to examine TNIK in the tissue microarray (TMA) consisting of 91 archived specimens of pancreatic cancer. The correlation between TNIK and prognosis was assessed by Kaplan-Meier curves and Cox regression. The mRNA and protein levels of TNIK in pancreatic cancer were both significantly higher than those in matched paratumor tissues. Immunohistochemistry analysis showed that TNIK was positively associated with pathologic T (P = 0.045) and TNM (P = 0.040) stage. In addition, The Kaplan-Meier survival curves indicated that patients with high expression of TNIK had a shorter overall survival (OS) and disease-free survival (DFS) than those with low expression. Our results demonstrated that TNIK might play a crucial role in pancreatic carcinogenesis and serve as a novel therapeutic target of pancreatic cancer.

Q: Should you edit out Flavour/Attitude from questions/answers I recently came across this self answer on SO. I solved my own question and not for the first time in my existence but with a nudge from some of you guys including MetaColon above. Thanks for the pointer MetaColon but I am the master once again. The truly correct answer which should be shared for the help and benefit of the ignorant population is as follows Looking back through previous questions, you can see a similar theme on answers. e.g. this Here is the correct answer to my question from the young middle aged loving master himself for the benefit of everyone angels and devils alike. and this. I guess I will have to also answer my own question for the benefit of everyone reading this question as not everyone knows what is inside your mind except you nor does anyone know the real motives of a novice when asking a question. You can also see similar in the questions. e.g. this Being a total newby, I felt like a virgin who had just lost his virginity after writing my first ever web service to do this in MS Visual Studio 2012 using an Ajax Web Service Project. and (to a lesser extent) this My favourite answer is this one and it worked In cases like these, should we be attempting to edit out any portions of the answer that contain this type superfluous flavour text? A: When a user, attempting to find their place as an upstanding member of this community, to contribute toward the noble goal of lovingly curating this vast and varied repository of knowledge we all hold so dear, which has aided us in our times of need, and which we endeavor to support so that it continues in this capacity as an invaluable resource to countless developers, working on solving any number of different problems of various levels of importance to the world in general, but each one personally valuable to its specific developer, in that we all take pride in our work, and feel the satisfaction that comes with not only achieving our goals, but truly understanding how the things that we have created work, encounters a question or an answer which contains some nugget of useful information, some shining insight which guides them to better understanding, but which may be obscured by an excess of additional verbiage, the user must attempt in good faith to apply their efforts to grasp the true intention of the writer, and to maintain that intention as they attempt to improve the question or answer, and in doing so the question of style often arises, and this prospective editor is confronted with the possibility that the style may detract from the key point of the post, but on the other hand, may also be found pleasing, or even possibly improve the readability or understanding of some other future reader, and the loyal user desires to seek the wisdom of the community to aid in this decision, and brings their concerns to meta for discussion, surely some different viewpoints will be voiced, and each contributor will have their own unique perspective on the content in question, and the user knows that they should take all of these points into consideration, and combine that input with their own judgement to strive to reach their own conclusion as to which words to preserve and which ones to strip away, but even when the best efforts have been made, and all the guidance of the community has been followed, some residue of doubt may still remain, and even when the edit is complete, the user may ask themselves if the edit was truly worthwhile, and was seen as an improvement to the post by the community, whether they really made a difference or if the post was actually a turd which should not have been polished, and these doubts are a burden for those of us who wish to edit, but we must not allow them to discourage us from our task, and we must put our best foot forward, or feet, actually, since there are more than one of us, but not feet in terms of both of the one persons feet, because you can't really put them both forward at the same time, and apply the edit with courage and confidence in the fact that our intentions are good, and that others will see that and judge us accordingly. A: This is all noise. It's not adding anything useful to the posts, so yes, you can edit it out of a post. The only exception being that portions of that first quote are giving credit to others for providing content that the answer is derived from, so that's important to keep. The half of that quote that isn't related to that is still noise though. A: Putting aside for a moment the specific case brought here, the general question shouldn't be answered with a blanket rule. Writing flair is only a problem if it distracts from or otherwise obscures the meaning of a post. It is a fruitless endeavour to go around excising all metaphors, colourful turns of phrase and touches of personal style without making that distinction. The end goal here is clarity, and not an impersonal voice.

Rinkeby-Kista Rinkeby-Kista is a borough (stadsdelsområde) in Stockholm, Sweden. The borough is located in Västerort. Overview The districts that make up the borough are Akalla, Husby, Kista, and Rinkeby. The population of Rinkeby-Kista borough is 48,604 as of December 2015. The borough was formed on January 1, 2007 when Kista borough and Rinkeby borough were merged. Rinkeby-Kista have, in recent years become a place of multiculturalism. Many immigrants or "newcomers" as Sweden refers to them, consider this their home, and a great deal of news has considered this a no-go zone. References External links Category:Boroughs of Stockholm Category:Västerort

Q: Some magic to remount /system First of all: Phone's model is Alcatel One Touch Idol Mini / 6012X Chipset model is MT6572 The short version: The device is in boot loop and to resolve this I must rename a file. The problem is that the file is in /system and I haven't granted ADB superuser permissions (So ADB simply hangs on "su", even when running scripts through ADB. Also "at" is not installed). Another problem is that I haven't installed a custom recovery and, more importantly, I haven't even unlocked the boot loader. I can't manage to install custom images via SP Flash Tool (SP Flash Tool doesn't find the device although the VCOM USB drivers are installed). What's worse than this? Alcatel doesn't provide a way to reflash the stock ROM. So, my question: Is there some kind of magic to force "su" to execute through adb without adb being granted permission by SuperSU? A: According to this thread, your device is rootable using framaroot. As you only need a temproot, the first thing to try would be to: extract the temproot binary used by framaroot and push it to /data/local/tmp or any folder where you can set permissions flag this file as executable then run it $ chmod 777 filename $ ./filename if successful, you have temp root and can remount the system read/write # mount -o remount,rw /system /system

The present invention relates to a prosthetic acetabular cup inserter and impactor. A prosthetic cup inserter and impactor is shown in U.S. Pat. No. 7,396,357 and U.S. Patent Application Publication No. 2008/0255568, the disclosures of which are incorporated herein by reference which comprises an expandable annular cup engaging element which can be expanded to engage in the inner surface of a cup to be inserted. The structure to expand the engaging element in this construction comprises a screw threaded element which causes relative movement between an extension which carries an expander member and an inner rod which is fastened to the cup engaging element. The relative movement causes the expander to be pressed into the cup engaging element and to cause it to expand. There are a large number of separate parts in this construction which, of necessity, must be disconnected in order to sterilize it.

House Delivers Major Victory to Gov. Blunt It takes two years, but the legislature has approved one of Governor Blunt’s top priorities. The House has approved, without revision, the Senate’s version of the MOHELA bill on a 91-to-64 vote. Strong partisan rhetoric, some harsh, punctuate House debate on the measure that would use the sale of assets from the Missouri Higher Education Loan Authority to fund $350 million in capital improvements on college campuses throughout the state. Democrats have been very critical of Republicans, claiming the majority party abused its power to push the bill through the Senate through the unusual move of cutting off debate and then limited debate to two hours in the House. House sponsor Carl Bearden (R-St. Charles) made no secret of the fact that he didn’t want any amendments accepted on SS#6 SCS SB 389 . Any changes in the bill would have sent it back to the Senate. Bearden succeeded in fending off any changes, easily defeating a handful of amendments sponsored by Democrats. The Republican unity in the House paved the way for the bill to move to the governor. Bearden points out the bill isn’t just a capital improvement bill. It contains scholarships fro college students and places restrictions on tuition increases. Rep. Clint Zweifel (D-Florissant) has been a vocal critic of the bill. Zweifel criticizes the governor for pushing the bill without giving enough information about the plan. He says the governor failed to lay a good foundation upon which to make a good decision. Zweifel says the bill will undercut the ability of MOHELA to provide low-interest loans to students and sets a bad precedent. He says future legislatures will go back to the student loan agency to get money for pet projects. A deal last year fell apart at the end of the session. The bill ran into unexpected opposition this year, when pro-life legislators worried that money generated from the MOHELA sale would fund embryonic stem cell research. The governor agreed to strip life science funding from the bill, gaining more than enough votes to win approval.

Q: iPhone XR / XS / XS Max CSS media queries What are the correct CSS media queries used to target Apple's 2018 devices: iPhone XR/XS/XS Max ? A: iPhone XR /* 1792x828px at 326ppi */ @media only screen and (device-width : 414px) and (device-height : 896px) and (-webkit-device-pixel-ratio : 2) { } iPhone XS /* 2436x1125px at 458ppi */ @media only screen and (device-width : 375px) and (device-height : 812px) and (-webkit-device-pixel-ratio : 3) { } iPhone XS Max /* 2688x1242px at 458ppi */ @media only screen and (device-width : 414px) and (device-height : 896px) and (-webkit-device-pixel-ratio : 3) { } Looking for a specific orientation ? Portrait Add the following rule: and (orientation : portrait) Landscape Add the following rule: and (orientation : landscape) References: https://developer.apple.com/design/human-interface-guidelines/ios/visual-design/adaptivity-and-layout/ https://www.paintcodeapp.com/news/ultimate-guide-to-iphone-resolutions A: The above is correct, but designers need to target the true screen dimensions to avoid scaling, cropping etc. For example the default landscape screen size is actually 808px for an XR. So this may be more appropriate: @media (max-width: 808px) {... This will in fact override this query: @media (max-width: 896px) {... The problem is Apples safe area insets. These can be overcome and get true 896px edge to edge width by adding the following; Meta tag: viewport-fit=cover CSS: body { padding: env(safe-area-inset, 0px); } The 0px size padding can be changed, or left right top bottom variables added, or adapt for portrait/landscape. But most will already have sufficient padding in their design. Reference: https://webkit.org/blog/7929/designing-websites-for-iphone-x/ Not tested on other devices but seems they are all adopting same.

/** * Tests for the 'utils/thread' file. */ // Do not warn if these variables were not defined before. /* global QUnit */ QUnit.module("thread"); /** * Tests for {@link dwv.utils.ThreadPool}. * @function module:tests/utils~threadPool */ QUnit.test("Test ThreadPool.", function (assert) { var done = assert.async(); // create the thread pool and initialise it var pool = new dwv.utils.ThreadPool(20); // number of workers var nTestWorkers = 10; // called on pool end (successfull or not) pool.onworkend = function () { // check counters assert.equal(countWorkItem, nTestWorkers, "Count WorkItem"); assert.equal(countWork, 1, "Count Work"); // finish async test done(); }; // called on work var countWork = 0; pool.onwork = function () { ++countWork; }; // called on work item (end of task) var countWorkItem = 0; pool.onworkitem = function (event) { if (typeof event.index !== "undefined" && event.data[0] === "papageno papagena") { ++countWorkItem; } }; // create the workers and run them for ( var i = 0; i < nTestWorkers; ++i ) { // create worker task var workerTask = new dwv.utils.WorkerTask( "/tests/utils/worker.js", {"input": "papageno"}, i); // add it the queue and run it pool.addWorkerTask(workerTask); } });

Show HN: SideProjects v2.0 – A platform to share your side project - sakofchit https://sideprojects.net/changelog ====== breck What a well designed site! I was able to successfully post a project. I really like the left side bar. The dark mode slider was neat. Everything is very clear and simple. Nice job! ------ sakofchit Hey all! You may remember this from a little while ago. When I launched SideProjects v1.0 a few months ago, the goal was really just to help users increase the discoverability of their side projects whilst building a community simultaneously. I didn’t incline to do too much with it. It was fine as a link-sharing site, but as with all side projects, there was room for improvement. Soon after launching, Donji, (who runs a podcast with Taher called My Side Project which is about people who took their side projects to the next level) reached out to me, and ever since we’ve been working on redesigning and rebuilding SideProjects. Now we’re a team of 3 We’ve been beta testing v2 publicly with our community for the past 2 weeks and today we’re finally excited to launch it! Whats new in v2? * Reposting! What we’ve learned from our community is that Side Projects are always able to be improved upon. We added a little thing that allows you to repost your side project every 7 days, so long as your side project has undergone significant updates. * Discussion Module: With the podcast, we really want our community to be involved with everything we do. We’re currently using this module to source questions from the community to ask interviewees on our podcast. We’re also doing a 15-minute, fast-paced video interviews. More on that very soon! * In an effort to increase post engagement, upon clicking on a project’s title, you will now be taken to the post itself instead of the actual product. Direct links to the project are now placed below the title. This change also addresses the URL encoding issue FireFox users had been encountering. * Dark-Mode! Some people prefer dark-mode while others prefer light-mode. We finally added an option that lets you choose :) * oAuth! You can currently login using GitHub, Google, Twitter. Let us know if you think we should add support for some other login services :). * Newsletter sent out every Sunday containing a recap of some of the best side projects of that week. tl;dr We rebuilt SideProjects and we’re building community-friendly tools for it. Check it out! [https://sideprojects.net](https://sideprojects.net) Sakun P.S. We've also got a discord now :) [https://discord.gg/RbF3RuS](https://discord.gg/RbF3RuS)

Family Motor Coach Association The Family Motor Coach Association (FMCA) is an international organization of families who own and enjoy the use of recreational vehicles. Since 1963, FMCA has issued more than 500,000 memberships to families who look to the association as their source of information about all facets of RV ownership and travel. FMCA is a member-owned association that maintains its headquarters in Cincinnati, Ohio, United States, and employs a full-time office staff. FMCA is governed by volunteer officers who are elected from within the ranks of the association. Formation On July 20, 1963, 26 families met at the Good Will-Hinckley School in Hinckley, Maine, United States, to socialize and become acquainted with other "house car" owners. They decided to form a motor coach owners' common interest group. A monument to commemorate the founding was dedicated at the school on July 4, 1994. Membership Membership in FMCA is contingent upon ownership of a self-contained RV — a recreational vehicle that contains all the conveniences of a home, including cooking, sleeping, and permanent sanitary facilities. These can be original-manufacture RVs, or conversions from other types of vehicle, of which buses are the most common. In 2017, FMCA's members passed a historic vote. Previously, the club was open to motorhome owners only. Through the vote, the membership voted to expand the club's membership criteria. FMCA has more than 100,000 members from every state of the U.S.A as well as Canada, Mexico, Great Britain, and beyond. FMCA also has roughly 2,500 commercial members — dealers, suppliers, manufacturers, campgrounds, service facilities, and other firms servicing the RV owner or the RV industry. Most members are only occasional users, while others live in their coaches full-time. Code of Ethics Every member of FMCA agrees to follow the Association’s Code of Ethics, which requires members to comply with all federal, state, and local laws and regulations governing the ownership and use of RVs. The Code of Ethics also calls for members to be "good neighbors, careful and responsible RV owners and operators, and good citizens of our communities." Purpose The purpose of FMCA is to organize social activities, exchange RVing information, and supply benefits made possible, in part, by collective purchasing. The group publishes Family RVing, a monthly magazine. It provides news concerning RV technology, the RV industry, and the association. FMCA members can be identified by the FMCA “goose egg," or membership emblem, displayed on their RV. Chapters and conventions FMCA encourages the development of local, regional and specialty chapters. These chapters — FMCA has approximately 500 of them — organize events of particular interest to their members, including numerous rallies throughout the year. Regional rallies, composed of several chapters from a geographic area, are also held annually. Many FMCA chapters cover specific or general geographic areas. Others are dedicated to an RV brand, a hobby, or a special interest. For instance, special-interest chapters include golf, crafts, amateur radio, single RVers, and handicapped RVers. FMCA holds two international RV conventions each year at various locations in the United States, in which manufacturers, dealers, and RV suppliers display their latest products. The events take place over a four-day period and usually attract 3,000 to 5,000 RVs. See also Good Sam Club References Motorhome Owners Group Headed to Arizona in March 2017 Family Motor Coach Association website Family Motor Coaching magazine External links FMCA's Official website Category:Recreational vehicles Category:Transportation organizations based in the United States

Environmental exposure of small children to polycyclic aromatic hydrocarbons. The aim of the study was to assess the intake (by various routes of exposure) of polycyclic aromatic hydrocarbons (PAH) by children living in a Czech city, and its effect on excretion of 1-hydroxypyrene (1-OHP) in summer and winter periods. Four groups of children (3-6 years old) were chosen: (1) two groups from a kindergarten situated in the city center with a higher traffic density ("polluted" area); (2) two groups from a kindergarten situated in a green zone of the same city ("non-polluted" area). Food consumption was recorded in all children and PAH intake from foodstuffs was estimated. Ambient air samples were collected from the playground and inside the kindergartens. Soil samples were collected too. Morning and evening urine samples were collected during sampling days. In both seasons, the mean outdoor total PAH concentration (sum of 12 individual PAH) in the -polluted" area was approximately three-times higher than that in the "non-polluted" area. Indoor concentration in the "polluted" area was more than six-times higher than that in the "non-polluted" area in summer, and almost three-times higher in winter. The same trend was observed for pyrene and for the sum of carcinogenic PAH. The contribution to the total pyrene absorbed dose from food consumption was much more important than that from inhalation and from ingestion of soil dust. Significantly higher urinary concentrations of 1-OHP (evening samples) were found in children from the "polluted" kindergarten in both seasons. The number of significant relationships between 1-OHP and pyrene absorbed dose was weak. Food seems to be the main source of total pyrene and total PAH intake in small children, even under relatively higher air PAH exposure in the city. Estimated pyrene ingestion from soil had a negligible contribution to the total pyrene absorbed dose. Urinary 1-OHP seems to be an uncertain (non-sensitive) marker of the environmental inhalation exposure to pyrene (PAH) if the pollution of air by pyrene (PAH) is not excessive and the pyrene (PAH) dose by this route is much less than by ingestion. Usefulness of the urinary 1-OHP as an indicator of overall environmental exposure to PAH needs further investigation.

Jacques Blain Jacques "Jim" Blain (born July 19, 1947) is a Canadian former professional ice hockey defenceman. During the 1972–73 season, Blain played 70 games in the World Hockey Association with the Quebec Nordiques. References External links Category:1947 births Category:Living people Category:Canadian ice hockey defencemen Category:Beauce Jaros players Category:Greensboro Generals (SHL) players Category:Laval Titan coaches Category:London Nationals players Category:Long Island Ducks (ice hockey) players Category:Maine Nordiques players Category:Niagara Falls Flyers players Category:Ottawa 67's players Category:Quebec Nordiques (WHA) players Category:Syracuse Blazers players Category:Toronto Marlboros players Category:Tulsa Oilers (1964–84) players Category:Vancouver Canucks (WHL) players Category:Sportspeople from Gatineau Category:Ice hockey people from Quebec Category:Canadian expatriate ice hockey players in the United States Category:Canadian ice hockey coaches

TRADFRI Easy to get started with a TRÅDFRI smart kit which contains gateway, remote control and 2 E26 LED light bulbs (large base) with white spectrum. You can use TRÅDFRI gateway and app to create several groups of light sources and control them in different ways. Get The Smart Home Guide Now! Get your FREE copy of the Smart Home Guide by signing up for our newsletter. The Smart Home Guide is a 45 page ebook created here at GetSmartHomeDevices.com to provide you an overview of the best selling smart home devices from the most popular smart home brands. Think of it as an introduction to home automation that you can save to reference smart home solutions such as lighting, thermostats, security, and more. Search Store Get your FREE copy of the Smart Home Guide by signing up for our newsletter. The Smart Home Guide is a 45 page ebook created here at GetSmartHomeDevices.com to provide you an overview of the best selling smart home devices from the most popular smart home brands.

/* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Copyright by The HDF Group. * * All rights reserved. * * * * This file is part of HDF5. The full HDF5 copyright notice, including * * terms governing use, modification, and redistribution, is contained in * * the COPYING file, which can be found at the root of the source code * * distribution tree, or in https://support.hdfgroup.org/ftp/HDF5/releases. * * If you do not have access to either file, you may request a copy from * * help@hdfgroup.org. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * */ /* * Programmer: Quincey Koziol <koziol@hdfgroup.org> * Saturday, September 12, 2015 * * Purpose: This file contains declarations which define macros for the * H5B2 package. Including this header means that the source file * is part of the H5B2 package. */ #ifndef _H5B2module_H #define _H5B2module_H /* Define the proper control macros for the generic FUNC_ENTER/LEAVE and error * reporting macros. */ #define H5B2_MODULE #define H5_MY_PKG H5B2 #define H5_MY_PKG_ERR H5E_BTREE #define H5_MY_PKG_INIT NO #endif /* _H5B2module_H */

Marseille knife attack: Police investigate suspect’s terror links Story highlights Police are looking into whether attacker had links to terror organizations The incident is being treated as a terror attack and has been handed over to a special prosecutor in Paris, the prosecutor’s office told CNN. Military police killed the suspect. Authorities are investigating whether he had links to terror organizations. He was not carrying any identification, Marseille police said, but French Interior Minister Gérard Collomb said during a news conference, “The attacker had several identities.” Appearing on BFM, Collomb told the station that witnesses heard the attacker shout, “Allahu Akbar” — or, “God is the greatest” — and that the investigation was continuing. Surveillance footage showed the suspect attack his first victim, run away and come back to stab the second woman, the minister said. The suspect then ran toward soldiers arriving on the scene, Collomb said. “Again we measure the devotion and the exceptional engagement of our troops. They have my honors,” Collomb said in a tweet. The Saint-Charles station is the same one where four Americans studying abroad fell victim to acid attacks last month. The Boston College students, three of whom were studying in Paris and one in Copenhagen, were treated for burns and released. The attacker was a 41-year-old mentally unstable woman, police said. She was arrested and hospitalized, according to CNN affiliate BFM. There was no reason to believe the acid attacks were terror-related, police said.

Counter Recruiters On Capitol Hill in May, faith-based organizations announced the "I Will Not Kill" campaign to educate youth targeted by military recruiters. The campaign’s goal is to make youth more aware of their rights regarding military service, educate them about the impact of war, promote a culture of life in targeted communities, and promote conscientious objection to military service as a positive alternative to violence. "A new generation of youth from all sorts of backgrounds - including persons from disadvantaged communities - want to serve their country and global family without killing others," said David Whettstone, a legislative analyst for the Mennonite Central Committee. Under the No Child Left Behind Act, schools that receive federal funds must make 11th- and 12th-grade students’ contact information available to recruiters unless students fill out a form to opt out of the practice. U.S. high school students report getting multiple calls a day from recruiters. According to the Associated Press, Army officials have investigated 480 allegations of impropriety by recruiters since Oct. 1, 2004. Like what you're reading? Get Sojourners E-Mail updates! Sojourners Comment Community Covenant I will express myself with civility, courtesy, and respect for every member of the Sojourners online community, especially toward those with whom I disagree, even if I feel disrespected by them. (Romans 12:17-21) I will express my disagreements with other community members' ideas without insulting, mocking, or slandering them personally. (Matthew 5:22) I will not exaggerate others' beliefs nor make unfounded prejudicial assumptions based on labels, categories, or stereotypes. I will always extend the benefit of the doubt. (Ephesians 4:29) I will hold others accountable by clicking "report" on comments that violate these principles, based not on what ideas are expressed but on how they're expressed. (2 Thessalonians 3:13-15) I understand that comments reported as abusive are reviewed by Sojourners staff and are subject to removal. Repeat offenders will be blocked from making further comments. (Proverbs 18:7)

FIG. 9 shows a conventional cooling device wherein an engine 301 and a radiator 302 are connected to each other by conduits 304 through which a cooling fluid for cooling the engine 301 is circulated by a water pump 303. A bypass conduit 305 is connected to the conduits 304 at both an inlet portion and an outlet portion of the radiator 302. When the temperature of cooling fluid flowing out of the radiator 302 is above a predetermined value, the cooling fluid flows through bypass conduit 305 to bypass the radiator 302. When the temperature of the cooling fluid is below the predetermined value, a thermostat valve 306 closes the bypass conduit 305 so that the cooling fluid flows into the radiator 302 to be cooled. A heater core 308 is provided in the conduit 304. In order to cool the engine 301 efficiently, it is required that the cooling efficiency of the cooling device be controlled according to the condition of the engine 301, which varies frequently. The water pump 303 is driven by the engine 301 and the discharge capacity of water pump 303 is determined so as to prevent cavitation of the cooling fluid in the water pump 303 and to circulate plenty of cooling fluid even under extreme conditions, for instance, where the automobile climbs a slope at low speed. Recently, engines have become more powerful and transmit more heat to the cooling fluid. Therefore, the radiator and a cooling fan are required to be large enough to radiate the heat efficiently. However, the engine compartment has become increasingly smaller, making if harder to use large radiators and cooling fans. One idea to radiate the heat more efficiently is to make the discharge capacity of the water pump larger. However, the increment of the discharge capacity of the water pump causes cavitation when the water pump rotates at high speed, and a loss of power due to the water pump when cooling requirements are lower. Therefore, increasing the discharge capacity of the water pump is not practical and it is hard to increase the flow rate of circulating cooling fluid under a condition of low rotation and high load of the engine. Japanese unexamined utility model (Kokai) 63-190520 shows a cooling device which has an additional water pump 320 beside the main water pump 303 as shown in FIG. 10. Since the main water pump 303 is driven by the engine 301, the discharge volume of the main water pump 303 varies frequently according to the revolutions per minute (r.p.m.) of the engine. The shortage of cooling fluid or the surplus of cooling fluid arises under certain conditions of the main water pump 303 and the additional water pump 320. Sufficient cooling fluid is not supplied according to the engine rotation and load by merely providing the additional water pump 320. FIG. 3 shows the relation between the r.p.m. of the water pump and the discharge volume (flow rate) thereof. The flow rate of the main water pump increases in proportion to the r.p.m. as shown by line A in FIG. 3. When the r.p.m. is low, which means that the automobile is climbing a slope at low speed or the engine 301 is idling, the flow shortage of the cooling fluid becomes apparent. The total flow of the main water pump 303 and the additional water pump 320 is represented by broken line C, which shows that the flow is not increased tremendously. The reason why the sufficient increment of flow is not achieved is that the cooling fluid discharged from the additional water pump 320 recirculates into the inlet of the additional water pump 320 through the bypass conduit 330. Such a short-circuit of the cooling fluid can be prevented by providing a one way valve 331 in the bypass conduit 330. Since the one way valve 331 has a flowing resistance, the amount of cooling fluid flowing in the bypass conduit 330 and the additional water pump 320 is determined, based on the flowing resistance of the way valve 331 and the additional water pump 320. In other words, even if the engine 301 rotates at high speed and the pumping operation of the additional water pump 320 is not necessary, a certain amount of the cooling fluid flows into the additional water pump 320 according to the resistance of the one way valve 331. The resistance of the one way valve 331 also restricts the flow of the cooling fluid discharged from the main water pump 303. The resistance of the one way valve 331 is not variable according to the heat load of the engine 301. As described above, the conventional cooling device does not operate well according to the frequently varying condition of the engine.

PAF Base Masroor PAF Base Masroor is the largest airbase operated by the Pakistan Air Force. It is located in the Mauripur area of Karachi, in the Sindh province. The base was originally known as RPAF Station Mauripur and after 1956, as PAF Station Mauripur. PAF Base Faisal is the other Pakistan Air Force base in Karachi. The new PAF Base Bholari near Karachi was inaugurated in January 2018. History The airbase at Mauripur was established by Britain (Royal Indian Air Force, RIAF) during World War II in 1940-1941. On establishment of the Royal Pakistan Air Force (RPAF) the base became RPAF Station Mauripur. PAF Base Mauripur was renamed PAF Base Masroor in honour of former Base Commander, Air Commodore Masroor Hussain, who died in June 1967 due to a bird strike on his aircraft. He managed to direct the burning aircraft away from a populated area before crashing. Features Masroor base has the distinction of not only being the largest base, area wise, in Pakistan but also in Asia. Before Karachi Airport, this airport had been used for domestic flights and also by Quaid-e-Azam Muhammad Ali Jinnah, the founder of Pakistan. It is of immense strategic importance considering it has been entrusted upon the task of defending the coastal and Southern region of Pakistan. It houses the 32 Tactical Attack (TA) Wing which comprises four separate squadrons. See also List of Pakistan Air Force Bases List of airports in Pakistan Masroor Colony References External links Category:Pakistan Air Force bases Category:Airports in Karachi Category:Military installations in Karachi

It is well known in the art to use an inkjet printer for applications that require a hardcopy printout on a sheet of media. For example, it is commonplace to use an inkjet printer to print on sheets of paper, transparencies, labels, and the like. In a typical inkjet printer, a carriage holds one or more ink cartridges. Each cartridge has an inkjet printhead (pen) that includes several nozzles from which ink is ejected in a direction that causes the ink to impinge on the sheet of media. Typically, the carriage must travel across the media so that each pen can reach the full area of the media. The media to be printed on is usually driven along a media axis of motion and the pen is driven along a carriage axis of motion that is perpendicular to the media axis. In color inkjet printers, two or more cartridges are needed to print color images. For instance, a color inkjet printer can have four cartridges (black, cyan, magenta, and yellow) with a pen for each color. Consequently, in a four cartridge printer, the carriage must travel the width of the media, plus the width of the four pens, plus the space between pens. Therefore, the width of the inkjet printer is determined to a large extent by the distance the carriage must travel in order to print images on the full area of the media. For example, in an inkjet plotter, the carriag may have to travel a distance greater than the width of a D-size sheet of media. Because the carriage must travel across the media, the time it takes to print images includes the travel time for the carriage. Additionally, the mechanical components that move the carriage add to the complexity, size, and weight of the printer and are a source of noise and vibration that can be annoying to a user of the printer. Moreover, the pens in inkjet printers require periodic alignment to ensure consistent quality in the printed image. Because the pens are mounted in separate cartridges, there is always a risk of misalignment between pens, particularly when one or more cartridges are replaced. Prior attempts to solve the above mentioned limitations and disadvantages of multiple cartridge inkjet printers include mounting a plurality of inkjet printheads onto a wide substrate such as a multi-layer ceramic substrate or flexible substrate. Those solutions have several disadvantages. First, expensive precision tooling is required to align the printheads to the substrate. Second, a mismatch between the coefficient of thermal expansion for the printhead and the substrate can result in thermal induced stress on the interconnect used to electrically connect the substrate to the printheads. Additionally, the mismatch can result in misalignment between the substrate and the printheads. Third, the interconnect, the materials used for the substrate, and adhesives used to attach the printheads to the substrate are subject to failures due to the corrosive effects of the ink used in inkjet printers. Forth, the inkjet pens are sensitive to temperature variations caused by waste heat from the printheads. The substrate must have a high thermal conductivity so that the waste heat can be dissipated. If the substrate has a low thermal conductivity, then the waste heat can raise the temperature of the pens resulting in an increase in the pens drop volume. Subsequently, a temperature differential exists among the printheads so that the drop volumes of the printheads can vary depending on their location on the substrate. Ideally, th thermal conductivity of the substrate and the printheads would be identical so that there is no temperature differential between the printheads resulting in consistent drop volumes among the printheads. One manner in which multiple printhead alignment can be achieved is described in an application filed by the assignee of the present application. According to this technique, a common carrier substrate is formed having one or more precisely formed pockets. The sides of each pocket are formed to have a side profile that is a near perfect compliment of the side profile of each of a set of fully integrated chips. Due to the complementary side profiles, the chip can be positioned in near perfect self-alignment with all other chips on the substrate. Hence alignment according to this technique is achieved by the precise formation of the pockets and the precise formation of the complimentary edges of the chips. Therefore, there is a need for a carrier that can mount one or more inkjet printheads in alignment with one another without the need to form precise pockets within the carrier.

At this rate, between North Korea, Charlottesville and the climate crisis, it's unclear if America can survive being too much "greater", as the political cartoonists in PDiddie's latest weekly collection illustrate... [UPDATED TWICE: Good news! Morrissey quickly corrected his report after we notified him of the incorrect coverage. Bad news! His correction was also incorrect. SECOND UPDATE: Morrissey has copped to his second error as well, and has finally corrected appropriately. Details on all, at bottom of this article. -BF] Once again, the accurate reporting of facts, truth, and reality doesn't seem to be required when it comes to the Rightwing's continuing, years-long attempt to villainize the community organization ACORN for having the temerity to help legally register millions of low- and middle-income voters (who tend to vote Democratic) to legally vote so that they may legally participate in their own democracy. Today, [Wisconsin’s Attorney General J. B.] Van Hollen announced indictments in five cases — including two felony indictments against ACORN for scheming to have registrants vote multiple times in November 2008. Unfortunately, Morrissey and Hot Air are patently --- and apparently knowingly --- incorrect. The "two felony indictments," which Morrissey even links to [PDF] and quotes from in his inaccurate hit piece, are not "against ACORN," but against two workers who defrauded ACORN, even as the pair defrauded the voter registration process... Much more soon on Rightwing propagandist Andrew Breitbart and James O'Keefe's quickly unraveling ACORN "Pimp" Hoax, just how much of a hoax it really was, how the media and Democrats shamefully failed their due diligence in reporting and/or acting on it, and coverage of a lot of new commentary on it all that has been coming in rapidly from the Left, Right, and Other over the last week or so. Until then --- and as we still wait for Breitbart and O'Keefe to release the unedited versions of the videos which they've charged for six months demonstrate serious crimes they apparently don't want to show us, and while we continue to wait for the embarrassingly discredited hard rightwing L.A. County District Attorney Patrick Frey, who blogs pseudonymously as "Patterico" both at his own site and in comments at The BRAD BLOG and at Breitbart's websites, to explain how it is that as a Deputy D.A. he's authenticated the "unedited audio" that he claims proves some form of criminality by ACORN that neither the Brooklyn D.A. nor the former MA Attorney General [PDF] nor the Congressional Research Service have been able to find --- here is a short, instructive video worth a quick look. It's from 2007 and demonstrates just how simple it is to edit raw video in order to show something other than what actually occurred... Given her own history of documented voter fraud felonies, you'd think Ann Coulter would want to stay away from the whole ACORN issue (particularly since there is no evidence that, unlike her, they've ever committed any). So what did Coulter do to shore up the wingnut hoax that is falling apart faster than Andrew Breitbart himself? She quoted some "seemingly crime-encouraging answers" from the video, "out of context so as to appear more sinister," naturally. And, even more naturally, those folks who have been played and conned by "Andrew Breitbart Presents...Big Journalism" and "Andrew Breitbart Presents...Big Government," etc., ate it all up... Earlier this week, the Brooklyn D.A. concluded a five-month investigation of the Brooklyn ACORN videos, finding "no criminality." Following the release of the findings, Rupert Murdoch's own New York Post, of all places, reported it this way: ACORN set up by vidiots: DA The video that unleashed a firestorm of criticism on the activist group ACORN was a "heavily edited" splice job that only made it appear as though the organization's workers were advising a pimp and prostitute on how to get a mortgage, sources said yesterday. ...Many of the seemingly crime-encouraging answers were taken out of context so as to appear more sinister, sources said. In the meantime, as the Times continues to fail, last night Stephen Colbert mocked the entire ACORN "pimp" hoax as we've been revealing it over the last several weeks and, along with it, James O'Keefe, Andrew Breitbart, Fox "News" --- and, yes, indirectly, the New York Times --- by sharing his own "exclusive," damning, and heavily-edited video interview... Related: Yesterday ACORN launched a campaign to fight back and "Demand Accountability" from the Times and the other media outlets that have grotesquely misreported this story and have still failed to correct their damagingly inaccurate coverage. More on that campaign and how you can add your voice to it, right here... Following on our weeks-long coverage here at The BRAD BLOG, and at other sites who've similarly jumped in demanding accountability from the New York Times, ACORN itself is now launching a "Letter to the Editor" campaign to "Demand Accountability" from the paper for their repeated misreporting of the James O'Keefe/Andrew Breitbart ACORN "pimp" hoax. The community group's heavily-footnoted email blast, signed by "CEO and Chief Organizer" Bertha Lewis, quotes several articles from The BRAD BLOG's detailed coverage, including NYTimes Public Editor Clark Hoyt's outrageous emailed justifications for refusing to recommend the paper correct its multiple misreports. The BRAD BLOG, however, has indeed shown "conclusive evidence" to Hoyt that the paper was wrong, and even Hannah Giles (who played the fake prostitute) and even Andrew Breitbart (who published the videos to help launch his new BigGovernment.com website) have both now admitted that the reports of James O'Keefe dressing as a "pimp" in the offices of ACORN were flat out wrong. Whelan says the group is "asking people to contact either the New York Times OR their local paper and ask for a correction to the erroneous reporting regarding O'Keefe and his video scams." "Bradblog and a handful of online writers have been way ahead in looking at the facts on this story," Whelan wrote, "just as you were in exposing the great voter fraud fraud in 2006." (Our indexed coverage of that particular Rightwing fraud campaign is here.) We are asking people to contact papers all around the country because nearly everyone has reported on this story erroneously at some point-O'Keefe's purpose after all, was to deceive and confuse. The New York Times has a special responsibility to correct the facts though-both as the paper of record and because they reported based on a combination of wild misconceptions (as they admitted to you) and pressure from the radical right. Moreover, even Rupert Murdoch'sNew York Post reported on the finding, noting the D.A. described the video as a "'heavily edited' splice job" where "many of the seemingly crime-encouraging answers were taken out of context so as to appear more sinister." And yet, the New York Times, the "paper of record," continues to misreport the story, even in the wake of the D.A.'s finding, as we detailed last night. It's not particularly worth my time, or anybody's time (unless they are involved in suing or pressing charges against the GOP hoaxsters), to get into the detailed weeds on how the ACORN "pimp" hoax videos were doctored to show something other than what they really were, in comparison to what the text transcripts (which may or may not be accurate) actually show, since: the entire scam was a political hit job and a scam from the jump, and; since accused felon James O'Keefe and his employer and publisher Andrew Breitbart have refused to release the unedited video tapes, and; since nobody but low-level workers and volunteers are even seen on the tapes, and; since ACORN immediately fired those who violated the organization's own written protocols. As The BRAD BLOG has been detailing over the last several weeks, the highly-edited, heavily-overdubbed, secretly (and likely illegally) taped videos, and those who published them, have already proven to have discredited themselves. Now that O'Keefe's ACORN "pimp" hoax has been acknowledged, even by Andrew Breitbart, as a deceptive fraud --- where he once called it Pulitzer Prize-worthy "journalism" he now compares it to Borat --- it doesn't seem to matter to the same rightwing bloggers who trumpeted it in the first place that O'Keefe lied about playing his now-infamous 70's-era blaxploitation "pimp" character in ACORN offices. What's important, those foolish enough to keep backing O'Keefe and Breitbart now claim, is not that the purveyor of the information has been shown to be a fraud himself, but what he purports to have caught ACORN workers saying and doing on his highly-edited video productions. The quote in the above panel is taken from the mindblowing emails Hoyt sent to me recently, as one of his reasons for not recommending the "paper of record" issue retractions for their repeatedly inaccurate and misreported coverage of the James O'Keefe/Andrew Breitbart ACORN video "pimp" hoax, as The BRAD BLOG has now been covering for weeks. In addition to the absurd justifications that Hoyt (who can be emailed at Public@NYTimes.com) offered for refusing to responsibly recommend corrections, the paper's Senior Editor for Standards, Greg Brock, offered equally absurd reasons for standing by their reporting earlier, including O'Keefe's appearance on Fox News, "wearing what HE said was the same exact costume he wore to ACORN's offices." Kings County, New York District Attorney Joe Hynes put out a statement just now: On Sept. 15, 2009, my office began an investigation into possible criminality on the part of three ACORN employees. The three had been secretly videotaped by two people posing as a pimp and prostitute, who came to ACORN’S Brooklyn office, seeking advice about how to purchase a house with money generated by their ‘business.’ The ‘couple’ later made the recording public. That investigation is now concluded and no criminality has been found. Brooklyn prosecutors on Monday cleared ACORN of criminal wrongdoing after a four-month probe that began when undercover conservative activists filmed workers giving what appeared to be illegal advice on how to hide money. While the video by James O'Keefe and Hannah Giles seemed to show three ACORN workers advising a prostitute how to hide ill-gotten gains, the unedited version was not as clear, according to a law enforcement source. "They edited the tape to meet their agenda," said the source. UPDATE 3:24PM ACORN issues a statement following the announcement from the King County, D.A. noting what The BRAD BLOG has been reporting for years: O'Keefe and the Fox attack machine targeted ACORN because of our successful work to empower hundreds of thousands of low and moderate families as voters and active citizens. Observers who looked closely at the filmmakers' own transcripts have already noted that O'Keefe presented low level employees with a bogus scenario in which he presented himself as a boyfriend trying to rescue a prostitute from a violent pimp. Although no employees took any actual action to file papers for loans or taxes, ACORN already conducted its own review in order to move forward serving our communities. Hopefully today's announcement, and similar results from independent reviews, will make politicians and media examine the facts more carefully the next time a valuable community organization is attacked. I recently attended the Conservative Political Action Conference (CPAC) in D.C., with video camera in hand, to report on the attendees. I was particularly interested in interviewing James O'Keefe, the miscreant (and accused felon) responsible for the ACORN video media hoax that The BRAD BLOG has been meticulously detailing for several weeks, including the important focus on how the mainstream corporate media (the old-media) have been had by the scam. O'Keefe's phony "pimp" story has been debunked, but, as Brad Friedman has shown, the old-media remain remarkably reticent to admit their errors, and the publisher of the videos, O'Keefe's employer and promoter Andrew Breitbart, has been unwilling to help them off the hook. Witness the outrageous email responses from the NYTimes' Senior Editor for Standards Greg Brock and then from their Public Editor Clark Hoyt, when it was shown to them that "the paper of record" had been had --- that O'Keefe had never "visited Acorn offices...dressed so outlandishly" in the now-infamous "pimp" costume as the paper had reported, as O'Keefe had represented, and as Breitbart himself had claimed in his own column, to the public. While I didn't get the chance to speak with O'Keefe, I did catch up with his partner in fraud, Hannah Giles. Alas, she was surrounded by a protective coterie and fled without answering any questions when one of her entourage recognized me. But then my luck turned. I trekked to the basement to cover the "XPAC" party and found myself standing shoulder to shoulder with Breitbart, O'Keefe's promoter, publisher, and employer, and owner of the website which launched the infamously damaging, misleading, deceptive, and highly doctored video tapes. I had previously questioned Breitbart at a press conference at the National Press Club press last October. He's had a pretty easy ride of it since then, facing questioning only from a largely adulatory press. Though old-media, as Brad has shown, have been remarkably reluctant to demand answers to hard questions from Breitbart --- or any of the players involved in the ACORN secret video scheme --- I felt it important to do so for a number of reasons. The results were revealing, both in Breitbart's insanely manic demeanor, and in the substantive content of his answers to my questions. Ultimately, as I believe you'll find in the video, he reveals a lot about his own editorial judgment, professionalism, and reliability --- none of it is good... * * * The Breitbart/O'Keefe media fraud has been wildly successful for the pair, helping to launch Breitbart's BigGovernment.com site late last year. But, unfortunately, it's hurt a great number of innocents. Lost in the outrage against the New York Times for having fallen for the scam without bothering to fact-check, as The BRAD BLOG has been detailing for the past several weeks, is the fact that Breitbart and his ward O'Keefe have accomplished a despicable goal: They've all but destroyed an organization committed to helping those Americans most in need. Real people --- thousands of children amongst them --- will suffer hardship as a direct consequence of Breitbart's and O'Keefe's mendacious and malicious hoax, and singularly partisan political agenda. When will the media get around to telling that story? And what of the damage that disreputable propagandists like Breitbart and O'Keefe bring to the real citizen journalists in the new media --- those of us striving not to sell a political agenda under false pretenses, but, rather, hoping to document facts, truth, and on-the-record positions of those who would corrupt our system through disingenuousness, self-enrichment, and lies?... The 'rave reviews' just keep pouring in for the massive fails by New York Times Senior Editor for Standards Greg Brock and Public Editor (what they call their ombudsman) Clark Hoyt to recommend corrections for the repeated misreporting of the ACORN video "pimp" hoax. At least one of them is absolutely devastating in highlighting both the extraordinary hypocrisy and sheer stupidity demonstrated by the "paper of record" in refusing to set the record straight on its incontrovertibly inaccurate coverage of the false "pimp" story peddled by rightwing propagandists last year... The New York Times' independent Public Editor, Clark Hoyt, after sending me an email originally standing by the paper's misreporting of the James O'Keefe ACORN 'pimp' story, now describes the rightwing activist's misrepresentation of his highly-edited and heavily-overdubbed hit videos as "journalistically unethical." O'Keefe's deceptive editing of those infamous tapes implied that he had presented himself in ACORN offices as a 70's-era blaxploitation "pimp." It was the eye-popping, media-friendly, marquee headline that news outlets, including the Times, latched onto and ate up. Except that it never happened. The tapes were purposely manipulated in order to give the appearance that ACORN workers were so dumb they didn't even recognize that skinny little white kid as a phony pimp. And that's exactly how O'Keefe, and his employer Andrew Breitbart who published the misleading tapes on his websites, wanted them to be perceived. We've spent the last several weeks here reporting and demonstrating how the O'Keefe/Breitbart ACORN video hoax was exactly that --- a political partisan scam that was publicized uncritically by the New York Times, and dozens of otherwise reputable outlets. Despite the Times' repeatedly misreporting that O'Keefe was dressed or posed as a "pimp" while meeting with ACORN employees in those videos, and even after being shown in no uncertain terms that he did not, the Times' Public Editor has declined to recommend the paper retract its reporting on this story. The coverage at the "paper of record" undoubtedly helped lead to Congressional passage of federal legislation attempting to defund the community organization, and helped to bring on a subsequently crippling decline in other funding sources for the non-profit group which serves to provide support for low- and middle-income American families. At the end of the remarkable email exchange between Hoyt and myself (published in full at the end of this article), he says he recommended only that "Times editors ...avoid language that says or suggests that O'Keefe was dressed as a pimp when he captured the ACORN employees on camera." Hannah Giles played the "prostitute" in the highly-edited, heavily-overdubbed, secretly-taped ACORN sting videos, while James O'Keefe played her college student, aspiring politician boyfriend trying to save her from abuse at the hands of a dangerous pimp. She seems very nice Unfortunately, she's also the same person who joined --- likely horribly disinformed --- in to the GOP's anti-ACORN junta (attacking, for purely partisan political reasons, those who help the least fortunate in our society), and then explained afterwards that "one day I was jogging after work and I saw an ACORN, um, I was like, hmm, you know, I’ve never seen them before, I don’t like them." So when, in this Max Blumenthal video compilation of his weekend with the loons at the Conservative Political Action Conference (CPAC), she seems to confuse "minstrel show" with "menstrual cycle," I guess it shouldn't be much of a surprise. As she did with Washington Independent's David Weigel last week, she also, again, confirms that O'Keefe never wore his "pimp" costume into ACORN offices, despite the lies from propagandist Andrew Breitbart (employer of both Giles and O'Keefe, and publisher of the videos) about that point and others when he sold his original blockbuster, but fake, story to the public and one media outlet after another who bought it all hook, line and uncritical sinker... Just a quick reminder that none of The BRAD BLOG's recent series of detailed reporting on the MSM's failure to properly report on the ACORN "pimp" video hoaxes is actually about Andrew Breitbart, in truth. He'd love it to be. But it's not. He's just one overly-influential cancer cell in the quickly metastasizing illness over-taking the mainstream media. That illness is best illustrated, of late, by the willingness of the once-credible New York Times (and many others) to treat Andy --- as well as his band of GOP propaganda mongers and dirty tricksters --- as a respectable source, rather than the confirmed liar, desperate flip-flopper, self-defining hypocrite, and Republican con-man that he is. Yeah, we get that. Which must be why, during his series of insane, paranoid, meltdown rants (see videos below) at the Conservative Political Action Conference (CPAC) in D.C. all weekend long, where he fingered an imaginary Vast Leftwing Conspiracy at the heart of his epic fail, he forgot to mention The BRAD BLOG for some reason! It's as if he were entirely "ignoring" our "line of questioning" for some reason. That, even as he was forced to admit at the very top of his Saturday morning speech at CPAC --- undoubtedly due to having finally been sold out by his own fake "prostitute," Hannah Giles, the day before --- that he did, "apparently," lie about his phony ACORN "pimp" story... Speaking to Washington Independent reporter David Weigel today at CPAC, Hannah Giles, who posed as a prostitute in James O'Keefe and Andrew Breitbart's infamous, highly-doctored, heavily-overdubbed, secretly-taped, ACORN hit videos, confirms what we've been reporting for several weeks here: O'Keefe never dressed as a pimp in the offices of ACORN. I asked Giles about a criticism that’s often been leveled against them — that they hyped up the video by wearing outrageous clothes in promotional materials and the videos’ introductions that they didn’t wear in the actual stings. “We never claimed that he went in with a pimp costume,” said Giles. “That was b-roll. It was purely b-roll. He was a pimp, I was a prostitute, and we were walking in front of government buildings to show how the government was whoring out the American people.” "B-roll" refers to footage shot separately and later inserted during editing, as frequently seen in movies and television. E.g., an overhead helicopter shot of Las Vegas, used to establish where the scene takes place, before cutting to the interior of a casino where the main character is seen playing cards at a table. Breitbart's out-and-out lies in his own 9/21/09 column to help promote the videos by claiming they show O'Keefe and Giles "going to the Baltimore offices of ACORN ... dressed as a pimp and a prostitute and asking for - and getting - help for various illegal activities"; Greg Brock, the New York Times Senior Editor for Standards, as we documented exclusively some weeks ago, is even on email record as citing that Fox "News" appearance by O'Keefe (embedded again at right) as his only evidence to "stand by our reporting" in which the "paper of record" has, time and again, misreprested O'Keefe as having "visited Acorn offices ... dressed so outlandishly that he might have been playing in a risque high school play." Just two days after the Times described the "outlandish" dress of O'Keefe, the Congress of the United States passed legislation to remove federal funding for ACORN. (A federal judge later found the legislation to be "unconstitutional".)... But, as it turns out, evidence from Breitbart's own Sept. 21, 2009 Washington Times column reveals that Breitbart did, in fact, not tell the "truth every step of way." In fact, he out and out lied while selling O'Keefe's all together phony misrepresentation (some might call it a lie) that he "dressed as a pimp" while "asking for - and getting - help for various illegal activities," as Breitbart inaccurately reported in his column. Breitbart's promotion of those videos, as published on his own BigGovernment.com website, with the spectacular, media-friendly marquee selling point of low-level ACORN workers so stupid that they couldn't even spot a skinny white kid as a phony "pimp," kick-started the sting video campaign that was built and sold on an utter lie. More evidence has been published today at Media Matters highlighting the effectiveness of that lie, and how media outlets from one side of the country to the other --- not just the New York Timesas we've shown --- were utterly bamboozled and played for chumps by Breitbart and O'Keefe's phony scheme. Furthermore, when confronted with the lies --- yes, lies --- in his column, while on the air live last night, Breitbart chose to do what he always does...lie about them...

Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355-425) of the common beta 1 chain. The very late activation antigens (VLA) or beta 1 integrins mediate cell attachment to different extracellular matrix proteins and intercellular adhesions. The ligand binding activity of these adhesion receptors is not constitutive and can be regulated by temperature, presence of extracellular divalent cations, stimulatory monoclonal antibodies (mAbs), and cellular activation. We have generated three novel mAbs, HUTS-4, HUTS-7, and HUTS-21, recognizing specific epitopes on the common beta 1 subunit (CD29) of VLA integrins whose expression correlates with the ligand binding activity of these heterodimeric glycoproteins. This correlation has been demonstrated for several integrin heterodimers in different cell systems using a variety of extracellular and intracellular stimuli for integrin activation. Thus, the presence of micromolar concentrations of extracellular Mn2+, preincubation with the activating anti-beta 1 mAb TS2/16, and cell treatment with phorbol esters or calcium ionophores, induced the expression of the HUTS beta 1 epitopes on T lymphoblasts. Using a panel of human-mouse beta 1 chimeric molecules, we have mapped these epitopes to the 355-425 sequence of the beta 1 polypeptide. This segment represents therefore a novel regulatory region of beta 1 that is exposed upon integrin activation. Interestingly, binding of HUTS mAbs to partially activated VLA integrins results in maximal activation of these adhesion receptors and enhancement of cell adhesion to beta 1 integrin ligands collagen, laminin, and fibronectin.

Separate Effects of Exercise Amount and Intensity on Adipose Tissue and Skeletal Muscle Mass in Adults with Abdominal Obesity. To determine the effects of exercise amount (kilocalories per session) and intensity (percent of maximal oxygen consumption [% VO2 peak]) on adipose tissue (AT) and skeletal muscle (SM) in adults with abdominal obesity. Participants (n = 103; 52.7 ± 7.6 years) were randomized to the following groups: control; low-amount, low-intensity exercise (180 kcal/session [women] and 300 kcal/session [men] at 50% VO2 peak); high-amount, low-intensity exercise (HALI; 360 kcal/session [women] and 600 kcal/session [men] at 50% VO2 peak); or high-amount, high-intensity exercise (HAHI; 360 kcal/session [women] and 600 kcal/session [men] at 75% VO2 peak) for 24 weeks. Activities of daily living were measured by accelerometry. Magnetic resonance imaging was used to measure tissue mass. Reduction in all AT depots was greater in the exercise groups compared with control (P < 0.002); however, there were no differences between exercise groups (P > 0.05). Visceral and abdominal subcutaneous AT reduction was uniform across the abdomen. Total SM mass did not change with exercise compared with control (P = 0.32). However, while lower-body SM mass was maintained (P = 0.32), upper-body SM mass in the high-amount, high-intensity and the high-amount, low-intensity groups was reduced compared with controls (P < 0.008). In adults with abdominal obesity, substantial reductions in total, abdominal subcutaneous, and visceral AT with a preservation of total SM mass were observed independent of exercise amount or intensity.

The Beowulf mailing list provides detailed discussions about issues concerning Linux HPC clusters. In this article I review some postings to the Beowulf list about Parallel Memory and packing in motherboards. I think the discussion threads presented below provide some very useful information despite the age of the postings. And another good use for cookie sheets! Parallel Memory On Oct. 18, 2005, Todd Henderson posted a question about whether any tools, drivers, etc. that allowed distributed nodes to have their collective memory appear as shared memory. In essence a "PVFS" for memory. Todd also mentioned that he wasn't worried about speed but just memory capacity (his application had memory usage that scaled with the cube of the problem size). He wanted to know about any approaches to distributed shared memory before he embarked on a large MPI porting process. {mosgoogle right} The first one to reply was Mark Hahn (doesn't he ever sleep?). He said that there were some student projects around to do this kind of thing. But he didn't think it was too worthwhile, "... unless you have some pretty much completely sequential, high-locality access patterns." Mark also pointed out that a memory access on a node is on the order of 60 ns (nano-seconds), and to fetch a page of memory over a network would be on the order of 80 micro-seconds. So the difference is about a factor of 1000. One suggestion that Mark made was to look at Global Arrays Paulo Afonso Lopes, then suggested that Todd take a look at SSI (Single System Image) projects and DSM (Distributed Shared Memory) projects. One that he mentioned is, Kerrighed. Robert Brown then posted with a mention to a project at Duke called "Trapeze" but he wasn't sure of the project was still around or not. He then went on with an idea to let the node where the code is running to start swapping. But the swap space is over NFS and on the NFS server, rather than use disks, you create a ramdisk. Robert thought this would be an interesting experiment to try. Of course your swap space would be limited to the largest ramdisk on the NFS server node (about 64GB for current commodity hardware). So if you combined this with the memory of the node where the code is running, you could get about 128 GB of usable memory+swap. If you need to go larger you could create swap files on various nodes using the same approach so that the node where the code is running could swap to a number of swap files. Bogdan Costescu responded to Robert's post about swapping over NFS to a ramdisk by saying that there had been a discussion on some of the heavy duty Linux Kernel mailing lists about swapping over NBD (Network Block Device) or iSCSI. He discussed a situation where you could get a deadlock. (you need memory for the transfer, so what if you need to swap to do the swap ...) So he suggested that swapping over the network wasn't a good idea at the time (remember this is the end of 2005). Robert replied to Bogdan's post with some discussion about the details of creating a ramdisk. He then came up with a heuristic about the largest possible ramdisk size (a corner case really). But this corner case showed that you really don't get more than about 50% of the system memory for creating a ramdisk (if you want to make sure this corner case can never happen). His finishing comment was that it's probably better to just write a simple parallel application with routines that do the data management for you (Global Arrays, mentioned earlier, does this). Ashley Pittman wrote that in the 2.2 version of the kernel there was the ability to swap over the network. It used sockets to communicate to a remote server. The whole code was in user-space so it was probably simpler than using NFS. Michael Will chimed in that he used to swap over a 10/100 network to a remote ramdisk via NBD. He was using the swap to load, at that time, large gimp images. He said that, "Qualitative statement: It seemed faster than using the old IDE drive for swapping, maybe because the image data came from the IDE drive as well and so the extra 10MB/s channel via NBD was worth it." Randy Wright wrote with a link to a paper he listened to at Cluster 2005. He said that they had a large quicksort running at 1.7 times slower than the speed of doing it in local memory only, but up to 21 times faster than using a local disk. He said that on a good day, it worked, but it was fairly flaky. Richard Walsh also wrote with a suggestion to look at UPC project for C codes or the Co-Array Fortran project for Fortran codes. These are languages that allow you to use memory from other nodes and/or to thread the application. He said that there were some some libraries for common interconnects, allowing you to use memory on other nodes. Then went on to talk about some details of both UPC and Co-Array Fortran. I like this discussion because once you get into clusters you eventually ask the same question Todd asked - Isn't there a good way to do distributed shared memory on clusters? While there were some good suggestions, I recommend using Global Arrays. It allows you to grab memory from distributed nodes to use locally and it handles everything very simply. Cluster of Motherboards Once you get into building your own clusters you also ask the question, what about building a cluster just using motherboards and no cases? Well, Fernando asked this question on Nov. 4 2005. Of course, the universal answer was - yes. Glen Gardner wrote with a link to a cluster he built using mini-itx boards. He also said that the latest version of the cluster had 18 mini-itx motherboards in 12" space. He said that you could get up to 18 mini-itx motherboards in a 19" wide by 12" high by 26" deep rack space. It looks like Robert Brown wasn't immune to posting about gadgetry (he's a DIY kind of guy!). He said that using just motherboards has been done a number of times before. He did mention a couple of idea people have tried (e.g. directly mounting motherboards to shelving), and he also told Fernando to be careful when dealing with electricity. Robert then mentioned that the list's EE guru, Jim Lux should comment on the subject. Being the good cluster-er that he is, Jim promptly wrote to the list with some good comments. His opening comments were, Sure it's possible. Your problems are going to be power, cooling, and structures (assuming you're not in an environment where people care about electrical codes, RF interference, etc.) He then went to explain each of these in a little detail with some warnings (e.g. watch for grounding loops). Jim's comments led Robert to kick into "Watch Out There" mode and offer some warnings about creating dangerous conditions (he didn't mention anything about running with scissors though). But he did make one comment that I've seen in the past several times, Yeah, I think that Jim's observation that you should think carefully about the diminishing returns of building a free-form caseless cluster is very apropos -- you'll save a bit of money on space and cases -- maybe -- at the expense of more hands on work building the cluster and at the risk of having to resolve problems with shielding and so on. He did offer some very good suggestions though. He ended with this comment. If you go anywhere beyond this, I'd REALLY recommend that you only proceed if you completely understand electricity and electrical wiring and know what a ground loop IS and so on. A fitting comment if I've ever read one. This should be posted in every electrical section in Home Depot and Lowe's. But then again the Darwin Awards just wouldn't be the same. On a more serious note, Josip Loncaric wrote that it's possible to find cheap cases for about $20 and these can save you some work, but not necessarily shelf space. Marh Hann echoed these comments by explaining the lure of inexpensive hardware to make your cluster. He gave an interesting example of a 1,500 CPU cluster where you allow some money for the CPUs, motherboard, chassis, power supply, memory, and found that the sum was about 20% the cost of the real thing. (this is tempting isn't it?) He did mention that Google doesn't use cases. Rather they have bare motherboards on trays, perhaps much like Fernando wants to do. Mark finished his comments with the following. In summary, subtracting the chassis sounds smart, but really only makes sense if you follow through with the rest - cheap motherboard, cheap cpu, minimal cpu, minimal network, cheap labor, workload that is embarrassingly parallel, and not long-running... In short, you get what you pay for. (I've been burned on cheap memory several times in the past - never again). What's remarkable to consider is that one of the very largest (if not the largest?) data cluster systems in the world is a bare motherboard system, strapped together with lots of simple screws and Velcro. That's Google, in case you did not know. I was shocked to see this when I saw a presentation recently by one of the Google guns here in NYC (actually, the inventor of Froogle). He showed us pix of a bunch of nodes essentially sitting on some insulating material, screwed to a simple frame-style chassis with careful consideration of grounding and power. His point was to emphasize that google considers lots of very cheap, very simple nodes key to their growth, and cases are 'right out' when you go to this scale (he would not share the exact N of nodes with us, but alluded to something on the order of 100K, at that time, and this is *always* growing). I had heard about this in 2005. I think it's fairly common knowledge now. But it's still very interesting. After a brief discussion about Google, Jim Lux came back with some interesting back of the envelope calculations. He was interested in the amount of time it takes to drill holes in a piece of sheet metal or aluminum as a base plate for a motherboard. Assuming that you could do about 12 plates at the same time, he ended up with an estimate that it takes about 30 minutes to drill and screw in a single motherboard. If you guess about $10/hour in labor costs plus the price of materials, and that cheap $20 case looks pretty attractive. Jim then finished with a true "Tool Time" suggestion. There IS a faster way, for a bare system approach. Use double sided sticky foam tape. Plenty strong, it will last 2 or 3 years. Then Doug Eadline weighed in and strongly recommended using regular case. He mentioned our Kronos Project to build the fastest system we could for $2,500. At that time, we found a well engineered small for about $40. Now you can find them for $30 or less. Doug followed up these comments with a slightly philosophical comment. One of things I have learned when building clusters is to take advantage of mass produced anything (mostly hardware). Looking inside a diskless node, I often get the urge to build a better enclosure, but then realize that the cost and time to fuss around with everything is not worth it. As a hobby, sure, it might be fun, but my interest is software, a "good enough" solution that costs much less in both time and money always seems to win the day for me. YMMV I think this is well said (although I can think of situations where a custom case is warranted). But, the siren song of commodity pricing is very hard to resist. {mosgoogle right} Right after Doug, Andrew Piskorski wrote that his favorite custom packaging scheme du jour was cookie sheets! He just uses basic cookie sheets and mounts the systems to the sheets. He said that there are ready made racks for these sheets. It's a long posting with lots of details, but he talked about how many micro-ATX motherboards he could get in a single rack (up to about 78) and how the density was more efficient than using standard cases. Since my wife's family is in the doughnut business, I think this is a great idea! This is really taking advantage of commodity components. By the way, Andrew posted some links to bare bones motherboard systems. All of the links are still active. My favorite is the zBox. These types of discussions are always fun. You get to see the creative side of various people come out and the contrasts are always fun as well (I still love the cookie sheet idea). Some of the ideas are worthwhile I think, but in many cases, it may be more effective to just use micro-ATX cases with micro-ATX boards. Dr. Jeff Layton hopes to someday have a 20 TB file system in his home computer (donations gladly accepted) so he can store all of the postings to all of the mailing lists he monitors. He can sometimes be found lounging at a nearby Fry's, dreaming of hardware and drinking coffee (but never during working hours). Unfortunately you have Javascript disabled, please enable Javascript in order to experience the comments correctly

PROFILE|CECILIACHNG Having dreamed of being a makeup artist and salon owner ever since she was a schoolgirl, Cecilia Chng’s journey as a professional in the beauty industry began after clinching a prize two-week trip to Paris, France, from the Harriet Hubbard Ayer Makeup Awards when she was just 20 years old. There, she had the opportunity try her hand working on Pret-a-Porter at Paris Fashion Week, under the guidance of one of the world’s most famous makeup designers. Ms Chng went on to further her trade with the Complexions London School of Makeup in the 1990s. Upon returning to Singapore, her love and passion for the makeup and fashion industry drove her to co-found Faceworks and subsequently, Vive Salon – a hair and beauty boutique in Paragon (Orchard Road) established by Cecilia and a partner 20 years ago – before opening Cecilia Chng Beauty at LS Philosophy, Thong Teck Building. Over the years, she has built an outstanding reputation as one of Singapore’s leading celebrity makeup artists, with her works making regular appearances on the iconic Singapore Girl in television commercials for the Singapore Airlines ‘Great Way to Fly’ campaign in the 1990s, as well as MediaCorp events such as Star Search. Ms Chng has worked on the faces of world-renowned beauty, fashion and celebrity powerhouses including the likes of supermodels Kimora Lee Simmons Naomi Campbell, and even the late Anna Nicole Smith. Locally, she is regularly in demand among reputed artistes such as Dick Lee, Patricia Mok and Fiona Xie, as well as high-profile socialites Kim Lim, Jaime Chua and Chiang Yu Lan. Jet-setting professionals and industry luminaries have also entrusted their makeup and eyebrow enhancement needs to Ms Chng, such as Grace Ban, Managing Director of Estee Lauder Cosmetics; Medical Doctor Caroline Low-Heah; and Trina Liang-Lin, Managing Director of Templebridge Investments, just to name a few.

Accused of being mendacious, incapable of holding to a foundation of facts and indifferent to the world of evidence, President Donald J. Trump has stumped international relations watchers with metronomic regularity. He has also torn away the façade of decent, tolerable hypocrisy that is the “value system” of US foreign policy. In its place is violent and ugly calculation, the allure of unmitigated self-interest. Students of such policy have traditionally seen the American imperium as a swaying creature: the realist view shuns sentimentality and sees the international environment as a jungle writ large, teeming with power plays; the idealist, who shades into a liberal internationalist, accepts a moral coating, and a certain degree of sanctimony, regarding international institutions, protocols and the like. From the latter came the at times emetic pronouncements of President Woodrow Wilson, who insisted that the United States shoulder the burdens of making the world safe for democracy. (It was often making it safe for business, but the confusion is an accepted one.) One foreign policy tradition, identified by Walter Russell Mead, is the Jeffersonian strand. The eye here is turned inward, and promoting democracy overseas is a matter best left to others. Within Jefferson, two versions stood out like schizophrenic impulses: the first, keen on seeing the republic remain one of glorious yeomanry freed of imperial obligation; the second, interested to see the Republic embark on its imperial, manifestly deigned mission. Mead does not stop there. If Trump’s policy can ever find some classification – and here, the schemes are only illustrative, not dogmatic – he might well be part Jacksonian, that tradition Mead claims is hostile to Wilson’s view of international institutions and Alexander Hamilton’s insistence on pure open markets, freedom of the seas, and international financial and legal stability. The followers of Andrew Jackson’s view embrace the military establishment, will use it sparingly, but, when provoked, will be satisfyingly violent. The disturbing fascination of Trump’s contribution to this babble on foreign policy is his instinctive revulsion of any position that might prevent a worthy transaction. Murdering journalists might be “bad”, but worse is to hold a cashed-up medieval theocracy to account for it. There is no room for the grieving sentimentalist here: Jamal Khashoggi was dismembered, but why let his corpse dictate a change in approach to Riyadh? Trump has his own bogey states to worry about, and he sees Iran as, in the words of his November 20 statement, “responsible for a bloody proxy war against Saudi Arabia in Yemen”, behind the deaths of “many Americans and other innocent people”, a destabiliser of Iraq and a state sponsor of terrorism. Then there is the filthy lucre, the “record” amount of $450 billion promised by Saudi Arabia as part of investments in the US. Trump turns to dreamy fiction on this, imagining that “hundreds of thousands of jobs, tremendous economic development, and much additional wealth to the United States” will arise from Kingdom’s deep pockets. The Make America Great Again quotient is satisfied with some $110 billion to “be spent on the purchase of military equipment from Boeing, Lockheed Martin, Raytheon and other great US defence contractors.” Besides, Saudi Arabia had been “very responsive to my requests to keeping oil prices at reasonable levels – so important for the world.” True, the death of a man deemed an “enemy of the state” by Saudi Arabia (“my decision is in no way based on that”) was a “an unacceptable and horrible crime” but “great independent research” suggested that 17 were directly connected with his death, deserving sanction. “It could very well be that the crown prince had knowledge of this tragic event – maybe he did and maybe he didn’t!” This turn of brutal honesty does not sit well with the hucksters in the GOP who prefer to hawk the wares of the Republic with counterfeit concerns for human rights and free expression. “When we lose our moral voice, we lose our strongest asset,” argues Senator Lindsey Graham (R-SC), who also claims that the crown prince “has shown disrespect for the relationship”. This is the sort of fabled nonsense that has shielded US power from proper analysis, ignoring the giant’s cool, if often bungling calculations, while hiding in the comforting duvet of an exacting morality. One such stonking bungle featured the Saudi-dominated terrorist attacks of September 11, 2001 on US soil. To the US, both oil and apocalyptic terrorism. Others speak of a complex situation, one that requires a ginger approach. This leaves room for much crawling cant. Senator Bob Corker (R-Tennessee), chairman of the Senate Foreign Relations Committee, told Chattanooga TV station WTVC that, “It is a delicate situation when we have a long-term ally that we’ve had for decades, but we have a crown prince that I believe ordered the killing of a journalist.” Corker’s focus is wearingly slanted, finding specific fault in a regime for one savage incident, and clearly ignoring its otherwise extensive butcher’s bill. The brutalities of the Saudi security services, the kingdom’s famine inflicting war in Yemen, are chickenfeed matters relative to the sanguinary fate of Khashoggi. “Everything points to the fact that [the crown prince] knew about it and directed it.” Doing so enables Corker and his like-minded colleagues to ignore the security and economic dimension of the Saudi-US relationship, one that excuses casual atrocity while affecting a broader concern for the human subject, a sentiment otherwise absent in broader strategic discussions. Secretary of State Mike Pompeo is more businesslike in tone, suggesting that enough house cleaning has already taken place. The governing Saudi royal family is never mentioned; specific individuals are, a point that keeps the House of Saud distant from the bloody matter. “We’ve sanctioned 17 people – some of them very senior in the Saudi government,” he told KCMO in Kansas City, Missouri. Rounding off such an approach is the extravagant claim by Trump that he controls the levers, holds the strings, and is captain of the ship. The world is his market, his veritable playground. He can influence interest rates; he can control oil prices. “Oil prices getting lower,” he tweeted. “Great! Like a big Tax Cut for America and the World. Enjoy!” Khashoggi should be remembered as much as the victim of state-sanctioned murder as one of unjust ennoblement at the hands of his morally infatuated exploiters. Trump’s diminution of his fate is crude but violently frank: the US has preferred a different approach to other states whose governments have seemed fit to suspend arms sales. All will quietly normalise matters in due course, keen to avoid losing market share to competitors. “Enjoy!” as Trump might well toot, followed by triumphant tones of “Told you so!” Immediate action is needed to save the future The central problem which the world faces in its efforts to avoid catastrophic climate change is a contrast of time scales. In order to save human civilization and the biosphere from the most disastrous effects of climate change, we need to act immediately. But it is difficult to mobilize public opinion behind[Read More…]

Q: Remove rows with ngx-datatable I'm trying to delete my first row from my ngx-datatable. I have created a button at the top of my work with this html : <button (click)="onRemoveRow(0)">Remove First Row</button> <ngx-datatable #table class='material' [columns]="columns" [columnMode]="'force'" [rowHeight]="'auto'" [rows]='temp' [headerHeight]="50" [footerHeight]="50" [limit]="5" [rowClass]="getRowClass" [selected]="selected" [selectionType]="'checkbox'"> </ngx-datatable-column> <ngx-datatable-column name="Site" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> Site </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="Filiere" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> Filiere </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="Type" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> Type </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="TypeSource" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> TypeSource </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="MotifNotif" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> MotifNotif </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="Canal"> <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> Canal </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="Modele" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> Modele </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> <ngx-datatable-column name="ChoixDefaut" > <ng-template let-value="value" let-sort="sortFn" ngx-datatable-header-template> ChoixDefaut </ng-template> <ng-template let-value="value" ngx-datatable-cell-template> {{ value }} </ng-template> </ngx-datatable-column> </ngx-datatable> And I tried to use the splice method : rows = [ { site : 'Site1', filiere: 'ADE', type : 'AAAB', typeSource : 'ADH', motifNotif : 'AR', canal: 'EMAIL', modele: 'ME1', choixDefaut: ''}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'AR', canal: 'EMAIL', modele: 'ME2'}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'AR', canal: 'EMAIL', modele: 'ME22', choixDefaut: ''}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'RET', canal: 'EMAIL', modele: 'ADH'}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'RET', canal: 'EMAIL', modele: 'MEX', choixDefaut: ''}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'TRT', canal: 'SMS', modele: 'MS1'}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'ADH', motifNotif : 'TRT', canal: 'EMAIL', modele: 'EMY', choixDefaut: ''}, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'RH', motifNotif : 'AR', canal: 'SMS', modele: 'MSA', choixDefaut: '' }, { site: 'Site1', filiere: 'ADP', type: 'AAAA', typeSource : 'RH', motifNotif : 'RET', canal: 'EMAIL', modele: 'MEF'}, ]; onRemoveRow(index : number) { this.rows.splice(0, 1); this.rows = [...this.rows]; } However, i don't know why it is my last row which is deleted. Even if I change the index of my function, the result is the same. First of all, i wonder if there is a better way to remove rows from my table. Also I'm pretty interested learning why my code is not working properly. Thanks. A: So after I've done some research my array was "filtered". // Remove file //row is passed by (click)="removeFile(row) in html" removeFile(row) { // you need this due to https://swimlane.gitbook.io/ngx-datatable/change-detection this.filetitle = this.arrayRemove(this.filetitle, row.name) } arrayRemove(array, rowName) { return array.filter(function(element){ return element.name != rowName; }); } You can get your values by passing $event in (click) and furthermore get event.target.value.

Q: Function $f: \mathbb{R}^n \to \mathbb{R}^k$ totally differentiable at zero Problem: Let $f : \mathbb{R}^n \to \mathbb{R}^k$ be a function that satisfies $\Vert f(x) \Vert \leq \Vert x \Vert^2$ for all $x \in \mathbb{R}^n$. Prove that $f$ is totally differentiable at $0$ and determine $(df)(0)$. Attempt: We need to prove that there exists a matrix $A \in \mathbb{R}^{k \times n}$ such that $$ \forall \epsilon > 0, \exists \delta > 0, \forall x \in \mathbb{R}^n : 0 < \Vert x \Vert < \delta \Rightarrow \frac{ \Vert f(x) - f(0) - A(x) \Vert }{\Vert x \Vert} < \epsilon. $$ I was trying to manipulate the inequality: $$ \frac{ \Vert f(x) - f(0) - A(x) \Vert }{\Vert x \Vert} \leq \frac{1}{\Vert x \Vert } \bigg( \Vert f(x) - f(0) \Vert + \Vert A(x) \Vert \bigg) \\ \leq \frac{1}{\Vert x \Vert } \bigg( \Vert f(x) \Vert + \Vert f(0) \Vert + \Vert A \Vert \Vert x \Vert \bigg) \leq \frac{1}{\Vert x \Vert } \bigg( \Vert x \Vert^2 + \Vert f(0) \Vert + \Vert A \Vert \Vert x \Vert \bigg) = \\ \Vert x \Vert + \frac{ \Vert f(0) \Vert}{\Vert x \Vert} + \Vert A \Vert . $$ I can get $\Vert x \Vert$ small, but I don't know what to do with the norm of the matrix. Also, there is no information given on what $f(0)$ is. How to solve this problem? Help appreciated. A: First see for yourself the case $n=k=1$. It will help you see that this is easy. You have $\|f (0)\|\leq\|0\|=0$, so $f (0)=0$ (there are three different meanings of "$0$" ther, make sure you are comfortable with that). As in the dimension 1 case, take $A=0$. Then $$\frac {\|f (x)-f (0)-0\|}{\|x\|}=\frac {\|f (x)\|}{\|x\|}\leq\frac {\|x\|^2}{\|x\|}=\|x\|\to0. $$

Many industries often encounter particulate matter suspended in the atmosphere. In some industries, this particulate matter is a valuable product, for example, starch; it would be beneficial if these suspended particulate could be recovered and reintroduced into the process. For other industries, such as metal or wood working, the particulate matter may be simply dust; it is desirable to remove dust particles from the air in order to provide a clear working environment. Systems for cleaning an air or other gas stream laden with particulate matter include air filter assemblies that have filter elements disposed in a housing. The filter element may be a bag or sock of a suitable fabric or pleated paper. The gas stream, contaminated with particulate, typically is passed through the housing so that the particulate are captured and retained by the filter element. Cleaning is accomplished by periodically pulsing a brief jet of pressurized air into the interior of the filter element to reverse the air flow through the filter element, causing the collected contaminants to be collected. Such air filter assemblies are disclosed in, for example, U.S. Pat. No. 4,218,227 (Frey) and U.S. Pat. No. 4,395,269 (Schuler), which patents are hereby incorporated by reference. Cylindrical filter elements are usually used in an air filter assembly to process dust particles from an airstream. In a standard design of air filter assembly, an air filter assembly has a clean air chamber and a dirty air chamber. The two chambers are separated by a sheet metal, commonly referred to as a tube sheet. The tube sheet has a number of openings from which cylindrical filters are aligned. The filters suspend downwardly with or without an angle from the tube sheet openings into the dirty air chamber. Particulate-laden air is introduced into the dirty air chamber, and the particulates collect onto the filter. The filtered air passes through the filters to the interior of the filters, and upwardly out through the openings in the tube sheet into the clean air chamber. From the clean air chamber, the cleaned air is exhausted into the environment, or recirculated for other uses. For example, U.S. Pat. No. 4,424,070 (Robinson), U.S. Pat. No. 4,436,536 (Robinson), U.S. Pat. No. 4,443,237 (Ulvestad), U.S. Pat. No. 4,445,915 (Robinson), U.S. Pat. No. 5,207,812 (Tronto et al.), U.S. Pat. No. 4,954,255 (Muller et al.), U.S. Pat. No. 5,222,488 (Forsgren), and U.S. Pat. No. 5,211,846 (Kott et al.) are prior art examples of prior art cylindrical filter elements of the pleated cartridge type. Non-cylindrical filter elements are sometimes used to process dust particles from an airstream and provide increased filtration area within a housing than cylindrical filter elements. For example, U.S. Pat. No. 5,730,766 (Clements) discloses a non-round unitary filter cartridge having a unitary structure with pleated filter media formed securely about a perforated interior core in a dust collector. U.S. Pat. No. 4,661,131 (Howeth) discloses non-cylindrical filters having a greater clean air flow area than a plurality of cylindrical elements fitted within the same dimensional envelope. In one conventional design of air filter assembly with non-cylindrical filter elements, non-cylindrical filter elements simply replaces cylindrical filter elements. With less space between adjacent filter elements, more non-cylindrical filter elements are placed within a housing than cylindrical filter elements. U.S. Pat. No. 5,730,766 (Clements) discloses this type of use of non-cylindrical filter elements. In another conventional design of air filter assembly with non-cylindrical filter elements, a plurality of cylindrical elements are replaced by a single non-cylindrical filter element. U.S. Pat. No. 4,661,131 (Howeth) discloses this type of use of non-cylindrical filter elements. Unfortunately, each of these conventional designs which utilize non-cylindrical filter elements has its disadvantages and drawbacks.

Calverley Bewicke Calverley Bewicke (1755–1815) was a commander of the Durham Militia and an MP for Winchelsea from 1806 to 1816. Sources entry on portrait of Bewicke's wife by Sir Thomas Lawrence External links Category:1755 births Category:1815 deaths Category:Place of birth missing Category:Members of the Parliament of the United Kingdom for English constituencies Category:UK MPs 1806–1807 Category:UK MPs 1807–1812 Category:UK MPs 1812–1818

Sweet Lily Bakery Self-taught pastry chef Melinda Gipson opened this treat shop in a handsome little adobe right next to the Georgia O’Keefe Museum. Warning: Not all of Gipson’s muffins, scones, cinnamon rolls, and pies on display are gluten free, so be careful not to get too distracted by that flaky, gluten-filled crust in the strawberry rhubarb pie. Sweet Lily Bakery Self-taught pastry chef Melinda Gipson opened this treat shop in a handsome little adobe right next to the Georgia O’Keefe Museum. Warning: Not all of Gipson’s muffins, scones, cinnamon rolls, and pies on display are gluten free, so be careful not to get too distracted by that flaky, gluten-filled crust in the strawberry rhubarb pie.

Finger, Tennessee Finger is a city in McNairy County, Tennessee. The population was 350 at the 2000 census. History According to tradition, the city received its name when the townspeople, during a heated discussion over what to name the city, noticed a man's passionate hand gestures. Other sources suggest the city was named for an early resident, Andrew Jackson Finger (1815–1888). The Finger Diner was the original model for the Hard Rock Cafe chain. Geography The city lies along State Route 199 at its junction with U.S. Route 45. Henderson lies along US 45 to the north, and Selmer lies to the south. According to the United States Census Bureau, the city has a total area of , all land. Demographics As of the census of 2000, there were 350 people, 122 households, and 96 families residing in the city. The population density was 231.1 people per square mile (89.5/km²). There were 134 housing units at an average density of 88.5 per square mile (34.3/km²). The racial makeup of the city was 49.86% White, 41.14% African American, 4.14% Native American, and 0.86% from two or more races. Hispanic or Latino of any race were 4.43% of the population. There were 122 households out of which 43.4% had children under the age of 18 living with them, 60.7% were married couples living together, 9.0% had a female householder with no husband present, and 20.5% were non-families. 18.9% of all households were made up of individuals and 9.8% had someone living alone who was 65 years of age or older. The average household size was 2.87 and the average family size was 3.28. In the city, the population was spread out with 31.7% under the age of 18, 8.3% from 18 to 24, 30.6% from 25 to 44, 17.4% from 45 to 64, and 12.0% who were 65 years of age or older. The median age was 31 years. For every 100 females, there were 93.4 males. For every 100 females age 18 and over, there were 86.7 males. The median income for a household in the city was $29,250, and the median income for a family was $36,250. Males had a median income of $28,250 versus $11,750 for females. The per capita income for the city was $11,654. About 19.1% of families and 21.6% of the population were below the poverty line, including 31.2% of those under age 18 and 18.2% of those age 65 or over. Newspapers Finger is served by two newspapers: the Independent Appeal and McNairy County News, both of which serve all of McNairy County. Notable people Jim Clayton, an American entrepreneur who founded Clayton Homes (now a subsidiary of Berkshire Hathaway) and built it into the United States' largest producer and seller of manufactured housing, was born in Finger. Buford Pusser, Sheriff of McNairy County, Tennessee, from 1964 to 1970 who was born in Finger. Several movies and a television series were based on his life. References External links Municipal Technical Advisory Service entry for Finger – information on local government, elections, and link to charter Let's Call It Finger: A History of North McNairy County and Finger, Tennessee and Its Surrounding Communities A High Sacred Place: A History of Mount Carmel Cemetery and Meeting House, McNairy County, Tennessee Category:Cities in Tennessee Category:Cities in McNairy County, Tennessee

Sirai® Sirai® began producing heating and air conditioning units in Milan, Italy in 1947. It has been producing solenoid valves since the 1950s when the increase of industrial automation resulted in the increase of demand for solenoid valves. Solenoid valves are used to control non-aggressive liquid and gaseous fluids controlled through an electric current. The company started producing off-the-shelf micro valves that became the current ‘Y’ series. It established an associated company producing solenoids and coils used in the production of the solenoid valves. Sirai was certified ISO 9001 compliant in 1991. In 1998 Sirai became part of US Emerson Electric Co Group and has introduced new products and customised solutions. Further mergers in 2009 with Asco Numatics and Sotrac to establish a new company called Asco Numatics Sirai.

Nasopharyngeal carcinoma: a delay in diagnosis. One hundred consecutive newly diagnosed patients with nasopharyngeal carcinoma (NPC) since January 1994 were the subjects for studying various factors that contribute to the delay in the confirmation of the diagnosis. Seventy-nine of them were males and the peak age of incidence was the fifth decade. Ninety two percent were Chinese, 7% Malay and 1% Indian. Seventy six percent were agriculture workers or labourers with 66% having either no formal education (16%) or only primary level education (50%). In 50% of patients neck swelling was the first presenting symptom, 26% had nasal symptoms, 12% ear symptoms and 11% has symptoms due to intracranial extension of tumour. As many as 80% were at UICC Stage IV at the time of diagnosis. While the median delay, on the part of patients, in consulting a doctor was 2.5 days, the median delay on the part of the doctors to confirm the diagnosis of NPC was 127 days, the delays was particularly worse when the patients presented with ear symptoms (266 days) followed by those with neck swelling (94 days). For those patients who were required to undergo more than one nasopharyngoscopy and biopsy the median doctor's delay was 144 days. Since 82% of patient's had first consulted general practitioners, it is suggested that their level of awareness with regards to the diagnosis of NPC be significantly raised so that the delay on their part be greatly minimized.

Q: Two questions are about past perfect There are 2 questions which the answer key says I'm wrong. First: By the time he was applying / he'd applied, the job had already gone. I think it should be "he was applying" Second: She left before anyone had had / was having a chance to explain the situation. I think the most suitable one is "was having", but answer key says the other one. If truly I am wrong, could you explain why ? Edit: A: I think you have some reason to dispute the first one, but with the second, no dialect but Indian English tends to use the continuous nowadays with having when the reference is to an action that occurs at a point in time or with reference to a present condition or with accumulated experience. CONTINUOUS OVER A PERIOD OF TIME I am having a hard time getting used to life in a rural village, after having grown up in New York City. DISCRETE ACTION AT A POINT IN TIME The CEO had left for another meeting before I had a chance to explain the numbers on the report. [The CEO was already gone when I explained the numbers to the other attendees at the meeting.] or with the past-perfect The CEO left for another meeting before I had had a chance to explain the numbers on the report to him. [I did not get a chance to explain the numbers to the CEO] or with the simple past The CEO left for another meeting before I had a chance to explain the numbers on the report to him. [I did not get a chance to explain the numbers to the CEO] A chance is perceived to be a momentary occurrence, not a prolonged period of opportunity. OK Here she comes. Now's your chance to ask her to the spring dance. not OK Here she comes. Now's your chance to be asking her to the spring dance.

This section provides background information related to the present disclosure that is not necessarily prior art. This section further provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features. Most current aircraft ice detection systems are based on measurements by ice-collecting probes, not placed directly on the areas where ice accumulation can cause problems. For example, U.S. Pat No. 7,104,502 is for a system capable of detecting the accumulation of ice by measuring changes in the vibration frequency of a strut mounted on the nose cone of an aircraft. The strut contains at least one feature that allows ice to accrete on it at higher rate than in other parts of the aircraft. U.S. Pat. No. 7,370,525 refers to a dual channel inflight system that detects ice accretion on a housing containing a light source, mounted on the aircraft surface. The system illuminates the housing with linearly polarized light. Light conductors with polarization sensitivity aligned to the transmitted light and with polarization sensitivity orthogonal to it acquire the backscattered light. The ratio of the intensities of the light in the two conductors is used to detect the presence of ice. The prior art systems described above detect ice on ice-collecting probes and housings, not directly on the places where ice accumulation can cause problems. Thus, they do not detect ice accumulation where it can be a hazard, such as on the air intake of pitot tubes, static ports, engines, wing surfaces and control surfaces. The aircraft ice detection system of the present teachings comprises an electromagnetic microwave resonator capable of measuring the complex dielectric permittivity of ice accumulated on aircrafts surfaces, air intakes and engines core. In some embodiments, the system contains a multiple frequency microwave resonator, a data processor unit, and interfaces with flight displays and flight systems. The present teachings provide, in part, a system capable of detecting the hazardous accumulation of ice on the surfaces, engines, instruments and air intakes of an aircraft or other objects of interest. Contrary to the previous art, the present system includes an electromagnetic microwave resonator capable of detecting the formation of ice directly where it could cause problems. The microwave resonator sensor can be mounted around the air intake of pitot tubes, static ports, on engines core, and can be embedded in the aircraft skin. The system uses algorithms based on the variations of the complex dielectric permittivity of water substance with frequency to distinguish the various types of ice from each other and from water. The system uses changes in the microwave resonant frequencies, their quality factors, and the transmitted and possibly received power to detect ice and to measure the ice thickness. The system is capable of determining the type and thickness of ice accumulated in the areas of interest as well as the rate of accumulation. In some embodiments, the system uses a dual frequency microwave resonator to distinguish water and the various types of ice from each other. A warning could be given when ice starts to accumulate. A hazards alert could be given when the thickness of the ice accumulated and/or the rate of accumulation reaches pre-established values regarded to be dangerous. Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings.

Join Us On Your Favorite Social Sites Stats Corner: New In Town Taylor Townsend won her first WTA main draw match at Indian Wells. Which four of the current Top 10 did that? Who was the only one to win her first two WTA main draw matches? Find out here... Published March 11, 2013 07:14 Maria Sharapova INDIAN WELLS, CA, USA - Sixteen-year-old American Taylor Townsend, the 2012 year-end ITF junior No.1, made her WTA main draw debut at the BNP Paribas Open last week and did not disappoint. She took out World No.57 Lucie Hradecka in her opener before falling to World No.13 Ana Ivanovic. Just winning a match in one's first event is no small feat, as only four of the current Top 10 did so and only one went further than the second round. Here is how their WTA main draw debuts went: No.1 Serena Williams- first main draw: 1997 Moscow- result: first round (l. to Po-Messerli)* sign of potential: reached semifinals of second WTA main draw at 1997 Chicago No.2 Victoria Azarenka- first main draw: 2005 Kolkata- result: first round (l. to Voskoboeva)* sign of potential: reached semifinals of second WTA main draw at 2005 Guangzhou

Belz (disambiguation) Belz is a town in Ukraine but also may refer to: Belz (Hasidic dynasty), a Hasidic dynasty from the Ukrainian town Belz (crater), a crater on Mars, named after the Ukrainian town Belz, Morbihan, Brittany, France Belz Enterprises, an American company Belz Great Synagogue Belz Museum of Asian and Judaic Art "The Belz", nickname of comedian Richard Belzer Duchy of Belz Gabrielle Belz, Australian molecular immunologist Joel Belz Christian Belz German spelling of Bălți, Moldavia which can also be spelled Belts

Attached are three documents for your consideration: --Q and As if there is a leak about the possible sale, but we don't want to admit it (qanoadmit) --News release if the leak runs amok and it is determined that we must divulge--either for shareholder reasons or severe reputation problems/miconceptions. (leaknr) --Q and As to accompany news release. I suppose another option is having a statement and Q and As ready without a release, but I don't think this gives us the control we would need. (qaadmit) Please review and comment by end of next week. Thanks.

Split Mountain (Montana) Split Mountain () is located in the Lewis Range, Glacier National Park in the U.S. state of Montana. See also Mountains and mountain ranges of Glacier National Park (U.S.) References Split Split Category:Lewis Range Category:Mountains of Montana

Mechanisms of chemopreventive effects of 8-methoxypsoralen against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung adenomas. Recently we reported that the occurrence of lung adenoma caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was completely prevented by pretreatment of female A/J mice with 8-methoxypsoralen, a potent inhibitor of cytochrome P450 (P450 or CYP) 2A [Takeuchi et al. (2003) Cancer Res., 63, 7581-7583]. Thus, the aim of this study was to confirm that 8-methoxypsoralen exhibits chemopreventive effects by inhibiting CYP2A in the mouse lung. The involvement of CYP2A in the metabolic activation of NNK in the lung was first evidenced by the fact that the mutagenic activation of NNK by mouse lung microsomes was inhibited by 8-methoxypsoralen, coumarin and antibodies to rat CYP2A1. Supporting this, the mutagenic activation of NNK was efficiently catalyzed by mouse CYP2A4 and CYP2A5 co-expressed with NADPH-P450 reductase in a genetically engineered Salmonella typhimurium YG7108. The expression of mRNA for CYP2A5, but not for CYP2A4 or CYP2A12, in the mouse lung was proven by reverse transcriptase-polymerase chain reaction, probably indicating that CYP2A5 present in the mouse lung was involved in the metabolic activation of NNK. In accordance with these in vitro data, treatment of gpt delta transgenic mice with 8-methoxypsoralen prior to NNK completely inhibited the mutation of the gpt delta gene. The in vivo chemopreventive effects of 8-methoxypsoralen towards NNK-induced adenoma was seen only when the agent was given to female A/J mice prior to, but not posterior to, NNK, lending support to the idea that NNK is activated by CYP2A5 in the mouse lung as an initial step to cause adenoma. The inhibition by 8-methoxypsoralen of NNK-induced adenoma was seen in a dose-dependent manner: the dose to show apparent 50% suppression was calculated to be 1.0 mg/kg. To our surprise, CYP2A protein(s) was expressed in the lesion of NNK-induced lung adenomas, probably suggesting that 8-methoxypsoralen could inhibit the possible occurrence of further mutation of the adenoma cells induced by NNK. Based on these lines of evidence, we propose that 8-methoxypsoralen inhibits the CYP2A5-mediated metabolic activation of NNK in the mouse lung, leading to the prevention of NNK-induced adenoma.

Atherosclerotic aneurysms of the superficial femoral artery: report of two ruptured cases and review of the literature. Isolated arteriosclerotic aneurysms of the superficial femoral artery are rare. In citing the literature a total of 30 cases in 28 patients in the last 25 years were found. In addition to the above cases, two aged patients with ruptured aneurysms of the superficial femoral artery are reported; these were managed successfully with partial aneurysmectomy and restoration of the circulation of the extremity with a synthetic graft. The prognosis for this type of aneurysm following surgical therapy is good, despite the advanced age of the patients, and amputation is relatively rare, occurring in only two out of the 30 aneurysms (6.6%) reported. The risk of rupture is 46.6% (14/30) and is greater than that found in peripheral aneurysms. This, in association with the possibility of the creation of thrombosis (5/30; 16.6%) or embolization (1/30; 3.3%), threatens the extremity itself as well as the life of the patient, increasing the risk of complications and even death at a rate of 66.6% (20/30). Timely diagnosis, immediate surgical reconstruction and prompt mobilization, however, can guarantee a good prognosis for these aged patients.

Opinion issued April 27, 2012 In The Court of Appeals For The First District of Texas ———————————— NO. 01-11-00768-CV ——————————— In re STATE FARM LlOYDS, Relator     Original Proceeding on Petition for Writ of Mandamus       MEMORANDUM OPINION           On September 12, 2011, relator, State Farm Lloyds, filed a petition for writ of mandamus in this Court.*  See Tex. Gov’t Code Ann. § 22.221 (Vernon 2004); see also Tex. R. App. P. 52.1.  Relator also filed a motion for temporary stay, which was granted.  See Tex. R. App. P. 52.10.            On November 23, 2001, the parties filed a joint motion to abate the original proceeding on the ground that the parties were in the process of settling the underlying case.  The motion was granted, and the original proceeding was abated.            Relator has now filed an unopposed motion to reinstate the original proceeding and dismiss the petition for writ of mandamus because the underlying case has been settled.  The motion is granted.            Accordingly, the original proceeding is reinstated, the temporary stay is lifted, and the petition for writ of mandamus is dismissed.  PER CURIAM Panel consists of Chief Justice Radack and Justices Jennings and Higley. *         This original proceeding arises out of Mark Jordan and Monica Jordan v. State Farm Lloyds, No. 10CV0633 in the 212th District Court of Galveston County, Texas, the Hon. Susan Criss, presiding.

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The C. elegans homeodomain gene unc-42 regulates chemosensory and glutamate receptor expression. Genes that specify cell fate can influence multiple aspects of neuronal differentiation, including axon guidance, target selection and synapse formation. Mutations in the unc-42 gene disrupt axon guidance along the C. elegans ventral nerve cord and cause distinct functional defects in sensory-locomotory neural circuits. Here we show that unc-42 encodes a novel homeodomain protein that specifies the fate of three classes of neurons in the Caenorhabditis elegans nervous system: the ASH polymodal sensory neurons, the AVA, AVD and AVE interneurons that mediate repulsive sensory stimuli to the nematode head and anterior body, and a subset of motor neurons that innervate head and body-wall muscles. unc-42 is required for the expression of cell-surface receptors that are essential for the mature function of these neurons. In mutant animals, the ASH sensory neurons fail to express SRA-6 and SRB-6, putative chemosensory receptors. The AVA, AVD and AVE interneurons and RME and RMD motor neurons of unc-42 mutants similarly fail to express the GLR-1 glutamate receptor. These results show that unc-42 performs an essential role in defining neuron identity and contributes to the establishment of neural circuits in C. elegans by regulating the transcription of glutamate and chemosensory receptor genes.

Q: Computing numeric derivative via FFT - SciPy I wrote the following code to compute the approximate derivative of a function using FFT: from scipy.fftpack import fft, ifft, dct, idct, dst, idst, fftshift, fftfreq from numpy import linspace, zeros, array, pi, sin, cos, exp import matplotlib.pyplot as plt N = 100 x = linspace(0,2*pi,N) dx = x[1]-x[0] y = sin(2*x)+cos(5*x) dydx = 2*cos(2*x)-5*sin(5*x) k = fftfreq(N,dx) k = fftshift(k) dydx1 = ifft(-k*1j*fft(y)).real plt.plot(x,dydx,'b',label='Exact value') plt.plot(x,dydx1,'r',label='Derivative by FFT') plt.legend() plt.show() However, it is giving unexpected results, which I believe is related to the incorrect input of the wavenumbers given by the array k: I know that different implementations of the FFT handle the wavenumbers order differently, so what am I missing here? Any ideas will be very appreciated. A: FFT returns a complex array that has the same dimensions as the input array. The output array is ordered as follows: Element 0 contains the zero frequency component, F0. The array element F1 contains the smallest, nonzero positive frequency, which is equal to 1/(Ni Ti), where Ni is the number of elements and Ti is the sampling interval. F2 corresponds to a frequency of 2/(Ni Ti). Negative frequencies are stored in the reverse order of positive frequencies, ranging from the highest to lowest negative frequencies. For an even number of points, the frequencies corresponding to the returned complex values are: 0, 1/(NiTi), 2/(NiTi), ..., (Ni/2–1)/(NiTi), 1/(2Ti), –(Ni/2–1)/(NiTi), ..., –1/(NiTi) where 1/(2Ti) is the Nyquist critical frequency. For an odd number of points, the frequencies corresponding to the returned complex values are: 0, 1/(NiTi), 2/(NiTi), ..., (Ni–1)/2)/(NiTi), –(Ni–1)/2)/(NiTi), ..., –1/(NiTi) Using this information we can construct the proper vector of frequencies that should be used for calculating the derivative. Below is a piece of Python code that does it all correctly. Note that the factor 2$\pi$N cancels out due to normalization of FFT. from scipy.fftpack import fft, ifft, dct, idct, dst, idst, fftshift, fftfreq from numpy import linspace, zeros, array, pi, sin, cos, exp, arange import matplotlib.pyplot as plt N = 100 x = 2*pi*arange(0,N,1)/N #-open-periodic domain dx = x[1]-x[0] y = sin(2*x)+cos(5*x) dydx = 2*cos(2*x)-5*sin(5*x) k2=zeros(N) if ((N%2)==0): #-even number for i in range(1,N//2): k2[i]=i k2[N-i]=-i else: #-odd number for i in range(1,(N-1)//2): k2[i]=i k2[N-i]=-i dydx1 = ifft(1j*k2*fft(y)) plt.plot(x,dydx,'b',label='Exact value') plt.plot(x,dydx1, color='r', linestyle='--', label='Derivative by FFT') plt.legend() plt.show()

Colicin receptors and the mechanisms of colicin uptake. This review deals in detail with the nature, synthesis, physiologic functions, and the regulation of colicin receptors, which represent components of transportsystems, as well as with the two mechanisms of the colicin uptake within the groups A and B of colicins.

Outcomes of One Anastomosis Gastric Bypass in 472 Diabetic Patients. The positive impact of Roux-en-Y gastric bypass (RYGB) on metabolic syndrome and glycemic control has been proven in obese patients. One anastomosis gastric bypass (OAGB) is a simple, effective and easy to learn procedure. OAGB provides encouraging results for the treatment of diabetes obese patients, but does it have the ability to be an alternative procedure to RYGB in the treatment of these patients? The aim of this study is to evaluate the outcomes of OAGB on diabetic obese patients at the bariatric centre of our university hospital. By extension, we evaluated the possibility of BMI and the preoperative antidiabetic medication usage to be predictive factors for postoperative diabetes resolution. This is a retrospective single-centre study of 472 diabetic patients who underwent OAGB from November 2009 to December 2015. All patients were followed-up for at least 1 year, and up to 3 years, where available. Weight, HbA1c, and anti-diabetic medications were recorded at baseline, 3, 6, 12, 24 and 36 months. A total of 472 patients have been followed-up for 1 year and 361 for 3 years. The mean BMI decreased from 46.8 ± 7.2 to 29.5 ± 2.8 kg/m2 and HbA1c from 9.6 ± 1.3 to 5.7 ± 1.5% at the 12-month follow-up. At the 3-year follow-up, the mean BMI was 32.1 ± 3.3 and HbA1c mean was 5.8 ± 0.9%. Diabetes remission was achieved by 84.1% of patients. OAGB can be an excellent alternative to RYGB for the treatment of diabetes and obesity. Pre-operative medications may be used to predict postoperative diabetes remission, but not BMI.

Summer is over and, for many of our clients, this means that the kids are back in school. After a busy summer filled with kids activities, vacations, beach and pool days, you deserve to take some time for yourself! Did your skin get a little over-exposed to the sun this summer? Now is a great time to address skin issues such as sun or “liver” spots, hyperpigmentation or uneven pigmentation. We have a variety of aesthetic medical spa treatments to address skin damage, and many medical-grade skincare products that will complement your procedure or start you on the path to healthier skin.

This is a proposal for the NHLBI R21 Innovative Research Grant Program, which encourages the analysis of existing data sets to explore new hypotheses. Endotracheal intubation (ETI) is the insertion of a plastic tube into the trachea (throat) to assist the breathing of a patient with a critical illness such as cardiopulmonary arrest, heart failure, respiratory failure or major trauma. While ETI is performed by physicians in the hospital, resuscitation usually begins in the out-of- hospital setting under the care of paramedics. In many fields of clinical practice, medical errors are known to be associated with both practitioner procedural volume as well as patient outcome. Many studies have found that paramedics commit errors when performing ETI. Furthermore in a preliminary study, we found that paramedics perform ETI infrequently in clinical practice and at frequencies far below that needed to maintain procedural proficiency, safety and effectiveness. Few direct links between the procedure, success and errors, and patients outcomes (including hospital course or resource utilization) exist. We posit that ETI performed by paramedics with low procedural experience may adversely affect patient outcome and hospital course of care. The goal of this study is to determine if paramedic (ETI) procedural experience is associated with patient outcomes and in-hospital course of care. In the proposed study we will probabilistically link three publicly- available statewide administrative databases encompassing paramedic patient encounters, admitted inpatients and deaths. We will apply multivariable regression to the linked data set to evaluate the connection between paramedic ETI procedural experience (annual volume of ETI), outcomes (mortality and in-hospital adverse events) and in-hospital resource utilization. We propose a new collaboration between research teams at the Universities of Pittsburgh and Utah, which have expertise in the areas of out-of-hospital care, health services research, the analysis of large-scale data sets and probabilistic linkage. These findings may demonstrate that paramedic ETI experience directly impacts patient outcome, and may promote major changes in the design and delivery of this life-saving out- of-hospital intervention. These findings would also confirm this linkage method as a new, powerful tool to evaluate the earliest portion of acute medical care - that begun in the out-of-hospital setting. [unreadable] [unreadable] [unreadable]

Posts This spoke to me so deeply. I wanted to share part, but what part?!?! Soooo, I think you should read it all. I know there are others needing to read it....I just know it......millions actually!Blessings Peter 1 (NIV)1 Peter, an apostle of Jesus Christ, To God's elect, strangers in the world, scattered throughout Pontus, Galatia, Cappadocia, Asia and Bithynia, 2 who have been chosen according to the foreknowledge of God the Father, through the sanctifying work of the Spirit, for obedience to Jesus Christ and sprinkling by his blood: Grace and peace be yours in abundance.Praise to God for a Living Hope3 Praise be to the God and Father of our Lord Jesus Christ! In his great mercy he has given us new birth into a living hope through the resurrection of Jesus Christ from the dead, 4 and into an inheritance that can never perish, spoil or fade—kept in heaven for you, 5 who through faith are shielded by God's power until the coming of the salvation that is ready to be revealed in the … Yesterday my beautiful kids spent a couple of hours outside playing in the leftover snow and just having a blast. Then in the afternoon it started to rain and within minutes the lovely snow was gone. Just like Western Oregon. At least it wasn't freezing rain. I hate that stuff. So the rest of the night I would occasionally check outside and it was still wet, unfrozen rain. This morning we get up....lightly raining...still unfrozen. Start to make plans for the day such as shopping for stocking stuffers. Got the baby up, took her to change her clothes, diaper, make a bottle and walked into the kitchen and what the heck? White stuff coming down like crazy. Everything already white outside. Wow. Turned my cell phone on and message after message coming through. lol Doesn't take western oregonians much to get excited! It is soooo beautiful. From a previous post..... Ahhhh O Holy Night playing on the radio....kids are playing in their rooms....baby is cooing....give me a moment..... Playing with Nana on the floor A with rosy cheeks LB, neighbor friend V, and MK S and J standing against the wind Trudged through the snow to see Nana What a sweet Sunday it has been. We had snow in Portland Oregon!!! More specifically at our house. We don't have snow often, so it's a treat and this is the first time in YEARS I have been happy to see the snow fall. To see the wind blowing like crazy swirling the snow around. One big difference? I don't have to go to work tomorrow. I didn't have anywhere to go today. Even church was cancelled. I just stayed home, decorated the tree, made home made soup and muffins, dressed and undressed kids several times today. Picked up wet clothes and sheets off the floor. My eldest son and his wife and the owners of my beautiful grandson bundled up and trudged through the snow to get here. My son wanted to play with the kids in the snow. :-) They only live about 4 blocks away. CJ slept like, um...like a baby on the way here. He was… So, there are several (all but me) in my family who think we need to load the family up, drive to a farm, search in the rain and mud, then saw down the perfect Christmas tree. Then sell my fine china (not that I have any) in order to pay for said tree (it USE to be cheaper to cut your own). I have done this for many years and to be honest. The only part of it I like is seeing the smiles on the faces of my kids. But when I was a single mom, I had an artificial tree (aka FAKE) and guess what? The kids still smiled. When we would dig it out of storage, place the synthetic boughs appropriately, hang the lights and ornaments it still brought joy. But then I remarried and thus back to the trudging for a tree again. Yes there is an aspect I love about real trees. The smell...but pretty much...that's it! I have had my fill for a lifetime.After last years hunt (because the cut your own trees are so expensive) I had actually talked my husband into letting me get an artificial so I was prepa… As part of our homeschooling we always do bible study first. What I have chosen to do is pick a scripture each week and we talk about it for the entire week. We have discussions and we have exercises I have created to help them (us) memorize the scripture. I have NEVER been able to memorize scripture. I have just never had the memory for such things. Same reason I have never been able to memorize multiplication facts and MANY other things. It's frustrating but it is what it is.Some of what we have studied has been the Ten Commandments, the two greatest commandments (Matthew 22:37) and others. This week our study is one of my favorite scriptures. Philippians 4:8. I love this scripture. It's beautiful. It's what I want to attain. I want to daily have my thoughts on such things but for anyone who knows me this is opposite of my personality. I am a worrier. I am a fretter. I am judgmental. Life has not be horrible to me but most of my life has been a struggle. Be it my life d… Dinner with my friend was great. It's always great to share some time with her. It's never enough time, but sweet it was. Dinner was fantastic. My fav...Olive Garden.We had a good day yesterday. We took the kids to see Santa and have photo's taken. We were there my grandson also. Last year my adult son J was working at the same place and was the photographer. We took the two girl (S and A) and as he got ready to take their pic he said "Girls I have a surprise...Emily is pregnant" and he caught them in midst's of gasps! So that is how they found out about their nephew coming. Yesterday we had their pics taken with their little nephew. We don't get the pics til today so can't post yet. Then I had a pic taken with the foster kiddos. First M and L and then baby P. She wouldn't smile because she was ready for a nap and the photographer didn't try very hard but she still looked darling.Then we spent the afternoon at my house. Eating lunch and watch… Wow...I can't believe it. I get to go to dinner with my best friend and with no kids in tow. Will I know how to carry on a conversation without interruptions from little ones? Will I know how to finish a thought? That's the great thing about best friends. You can go weeks months and even years without actually talking and just pick right back up again and talk for hours. God truly brought this friend into my life. He is the one that connected us. Her name is Amy. A name very dear to my heart. It was through working at the Red Cross we met. We didn't really become friends though until she encouraged me to apply for a job in her department. God blessed me with that job. That was the best years of my life within the Red Cross. I had many good times in my 10 years there, but the time I was in Special Collections (for 4 of those years) was the best. The people in the department were funny, loving, and oh so supportive. We all became very good friends. At one point Amy even becam… I'm not sure why it's so easy to get on a pitty pot but it is. This darn flesh is so consuming sometimes. It's been a rough week but then unexpected events happen and your perspective is changed. A dear sister in the Lord may have a cancerous tumor on her shoulder. I know she will have complete victory in this but consider the fact she went in to see about a torn rotator cuff. Wham...then she is hit with the big C word. Life changed.Another sister in the Lord has been working on getting an adoption of two older siblings. Siblings to her 3 adopted children. It has not be an easy road for her and on top of that she is expecting her 3rd bio in February. Her husband planning to go to Ethiopia in January to get the older two. Then this morning, however, the unexpected. She starts bleeding, goes to the hospital and the baby is delivered by C section within an hour. Now she is recovering from surgery and we are all praying her and baby will be fine. Life changed.So do I REAL… It is Thanksgiving Eve and I am looking forward to tomorrow. My mom, one of the greatest women to have ever walked this earth, has had Thanksgiving at her home for several years now. She was able to buy a new home a few years ago and is so in love with it. Prior to that, she lived in a tiny 2 bedroom fourplex that had a 1 step kitchen. Any direction you turned it only took one step (if that) to reach each counter, the stove, or the fridge. The dining room only a tad larger than that. So? Now she has a huge kitchen with a breakfast nook, a large dining room and a large living room just off the dining room. One year we were able to get over 40 people (excuse me...not just people but family) in there. It was GREAT! My mom was flying high and we all had a great time. We won't have that many this year (darn) but because it blesses my Mom so to have Thanksgiving there I am MORE than happy to go to her house. To see her so happy makes me happy. To see her up and able to fix the meal make… It's windy and cold here in Portland today but with the sun shining the kids just HAD to go outside. Baby is taking a nap, A is off to basketball practice, S is at Grandma and Poppies (her other home) and the 3 left are outside riding scooters terrorizing the neighborhood. We have neighbors who have yelled at the kids for making too much noise. The neighbors down the road just sold their home because they were so tired for being harassed about their kids. Kids playing outside yelling and screaming and riding bikes. It's sad. Kids can't be kids anymore. They need to be outside. Kids need to make noise. Kids need to be free to have some fun. I like the sound of them playing outside. I temper the screaming sometimes (it gets a bit much) but other than that.....noise outside made by kids is great. The same neighbors who have yelled at my kids are also the ones who have a dog who would bark everytime we went outside AND you can hear the football game blaring on weekends. Funny … I can't imagine what it would be like to not be able to feed my children. I can't imagine it and I pray to God I never experience it. Have we become complacent to children starving? Is that possible? I believe so. I have. I have not thought about it for a while. I have not done anything about it for a while. On other blogs I have seen pictures and read stories of children starving in Haiti's. Is this even on the news? I admit I watch the news rarely but what I have watched never showed the devastation of the floods, I NEVER saw a story about the schools that collapsed, and I never see stories about starving children in Haiti or anywhere for that matter. I see an occasional newspaper or magazine story. I see an occasional commercial, but no story on tv news. Then I read the blogs who share this information and it breaks my heart. As I get so tired of cooking, I see pics of little kids on the brink of death. Literally on the brink. Having no food for my kids.....watching the… So our lovely M just turned 8. She is a blessed girl because she was able to have 3 THREE birthdays. She had a 'Princess Tea Party' on Saturday, her real birthday (celebrated with a powdered/raspberry filled donut with a candle in the middle for breakfast) on Tuesday, then a family party tonight with cupcakes and presents. She LOVED every sugared moment of it. This special attention has made her very happy. I even received a random hug yesterday which is unlike her. We have several Hannah Montana and High School Musical items now floating around the bedroom. Her life is not the way she would have it. Her parents are not where they should be. But right now, by God's Grace she is loved, she is safe, and she is being blessed by His goodness. God knows what the plans for her future are and I pray with all my heart she walks in those plans. I pray God will be the father she desires. I pray she allows him to consume her heart. I pray she is blessed beyond words all the days of h… We had a our date night last night. I must say the movie 'Fireproof' ....wow it is AWESOME! We loved it. I teared up I don't know how many times ,and I actually laughed OUT loud. I am anxious to see it again. We are sending my son J and his wife (you know, the two that graced us with a grandson!!!) to see it tonight. Kirk Cameron is fantastic. What a great actor. The woman who played his wife...not so much. She just wasn't a great actress but she did ok. I am glad we saw it. I would love a miracle or two in my marriage but....it was a movie. All my life I have hoped for the scenario's in the movies and it just doesn't happen. The drama in the movie last night was very true to life though and the only thing that gives me hope about the ending to that movie being a possibility is because of the God I serve. He can do all things. I have mentioned my moose dogs on my blog before and I actually got a picture the other day of both of them together. Usually if they are together, Lilly (the Dane) is sprawled on the floor and Sirion (the Weimer) is snuggled all up into her belly. Sorry for the bright eyes (no time for editing)...they are not alien dogs...only Moose Dogs! They drive me crazy and yet I just love them. Especially Sirion. He is a rescue. We found him at the animal shelter and he was nothing but skin and bones. I took a huge leap of faith (or made a really stupid decision at the time) and adopted him. He was 3 years old, not altered, starved and we had no history of him. I can't believe I wanted to bring him home. It could have been a huge disaster. BUT...he has turned out to be the GREATEST dog I have ever owned....and my family can attest I have owned plenty. He did great with the kids, with Lilly, and the cat. He is house broken and he is not food aggressive. He is a lover and he loves to be calle… We had a wicked storm move through yesterday that hit Washington harder than Oregon. I enjoyed it though. There was no thunder and lightening (which I hate) and I no longer live in a home that is surrounded by huge fir trees so I was able to enjoy it. Lots of blowing rain. Maybe it was just my mood but it was just peaceful to me.Found out yesterday the foster baby will be with us a least until February, that is when the next court session will be held. So, it was good news and bad news. We of course are not ready to lose her. She is so precious, so beautiful and we enjoy her very much but on the other hand the longer we have her the harder it will be when she goes back to her bio Mom. I pray God's will for her life. I pray for protection over her. I pray if she does go back that she will be loved and kept safe. This is not an easy road for me but I know it's the road I am to be walking and I know God will get me through what I need to get through. I pray victory over the situa… Not sure why, but felt led to post this scripture. Must be for someone especially for today....maybe even me?!?! Ephesians 6:12 (NIV)12For our struggle is not against flesh and blood, but against the rulers, against the authorities, against the powers of this dark world and against the spiritual forces of evil in the heavenly realms. He is a God of ALL people. Not a select few. Not just those that are wealthy or those that are poor. Not just for those who great teachers and those that are not. Not just for those who are healthy and those that are not. He is the One and True God. He is the Almighty and He is Love! Football season has come to an end. The hardest part of the season, aside from hoping your son doesn't get creamed on the field, is the cold weather. We were fortunate this year. Only a couple of 'cool' games and only one rainy one. Wow...that's a first. We had the football banquet last Tuesday and our son received an award, making us quite proud. His award is...... 'Defensive Lineman of the Year' As of Wednesday, we have already started basketball.....no rest for the weary! lol My public school kids have today off and tomorrow also for Veterans day. It's a nice break. They slept in until 7:00 which was nice. The best part was not having to get up and out. We could stay in our p.j.'s and take our time with breakfast. I am sitting at my pc drinking a cup of coffee while they play. Two baskets of laundry are staring at me. Yes...staring! Laundry takes on a life of it's own! It know I can not ignore it all day so it is taunting me. But until then, I will drink my coffee and posts these pics and try not to look out the corner of my eye.Saturday I took 4 of the 6 six kids coat and clothes shopping and they were good and I didn't have to pull my hair out. They had so much fun. The highlight for L was us finding him not only a Spiderman Coat but also a Spiderman robe. He was overly excited. This boy loves soft fluffy blankets so a robe for the mornings and evenings are the perfect thing for him and to find one with Spiderman....wow! We purchased some … Well I still feel as though I am just keeping my head above water but that's a good thing right? I would rather be playing in the sand on a warm beach but at least I am not sinking like a stone.One of the challenges I am facing right now with working with the state is ALL the people in my life. They warn you but it's not until you are experiencing that the reality sinks in. I am a pretty private person when it comes to my home and my family so I knew God was going to stretch me. I wish I was like Mrs. Incredible. I love what she says "wife, mother, superhero!" yep....that's us mom's, but boy do I wish I could flexible like her. Mold and bend easily in whatever direction God would have me go. Why does my flesh have to resist.So, back to my state visitors. I have at minimum two calls a day (except Fridays usually), at least one person comes to my house 3 days of the week and then I take one of my kids to counseling once a week. So, Friday, Saturday, and Sunda… Some weeks would just be better being skipped, but since we don't have that choice we just work at keeping our head above water.If anyone reads this blog/post...please pray for my household...pray for me. Bind the darkness in Jesus' name. I am going to attempt to do some catch up. This little baby of mine is going to be the death of me. We can not get her on any kind of schedule and she can not be pacified very easily except for juggling her in your arms. So, this will be an attempt to post a very important event. The event was missed by me on my blog because I was consumed by packing and cleaning and organizing before the 'big' trip to Dland. The event? My parents anniversary....56th anniversary to be exact which was October 18th. I felt so guilty about not saying anything to them that day, I then called them from the hotel in Anaheim on Sunday the 19th. My mom informed me they too had forgotten their own anniversary! LOL....that's a first ever. They too were consumed with thoughts of the girls and I taking our trip. Anyways...here is my tribute to some WONDERFUL people...my parents! Ed and Deanna............My mom was 14 when she married my dad and my dad was 19. Oh so young. They went on to have 6 kids. Tw… Greetings. I have returned from our Fantasy vacation. My feet are an inch flatter and the muscles in my calves are an inch bigger. Walk, walk, walk. It was fantastic though. To see the joy and wonder on the faces of my two girls was worth every cent and every drop of sweat and every burn of every muscle in my body. The highlights were walking in between my two girls and holding their hands, or having them hug and kiss on me without notice. Two of our nights we came back to the hotel, stripped off our shoes and pants and sat on the edge of the tub (all 3 of us) and soaked our feet. Laughing, cringing, drying off at the silly 3 D shows together. Going to a 'Princess Dinner' all beautiful and glimmering with 'Pixie Dust.' Just being together and sharing in 'Magic' moments. I love them so much and I am so grateful for the blessing of them and the blessing of this trip. The day we left (Sunday the 19th) my dad fell at church, broke his hip, and had emergency surgery … I will be spending today finishing packing and getting the home and family left behind set up to survive without me.I feel incredibly burdened with the fact I am leaving my hard working husband home to spend his week vacation with 4 kids one of which is almost 4mths old and very needy. I am thrilled and thankful to be taking the girls on 'our' dream vacation but that doesn't remove the sadness I feel leaving the others behind. Why can't blessings in my life come without a hitch?!?! They never have....all the blessings in my life have come with burdens. Not sure why but they have.So, with a heavy heart I will do all my preparations for my hubby and the kids. I will do it with sensitivity to the ones left behind and yet with a big smile for the two going on the trip. What a tight rope!Pics of Mickey and friends will be posted next week.Blessings to you all in the name of Lord.

728 F.Supp. 1483 (1989) Randall MORGAN; William K. Chisholm; Ned Swisher; Dianne Elasick; Idaho Conservation League, Inc. and Hagerman Valley Citizens Alert, Inc., Plaintiffs, v. Lt. Col. James A. WALTER, United States Army Corps of Engineers; Delmar Vail, United States Bureau of Land Management; Earl M. Hardy; and Box Canyon Trout Co., Inc., Defendants. Civ. No. 89-1233. United States District Court, D. Idaho. October 30, 1989. *1484 Jeffrey C. Fereday, Givens, Pursley, Webb & Huntley, Boise, Idaho, for plaintiffs. D. Marc Haws, Office of the U.S. Atty., William F. Ringert, Ringert, Clark, Harrington, Reid, Christenson & Kaufman, Chartered, Boise, Idaho, for defendants. ORDER GRANTING PLAINTIFFS' MOTION FOR PRELIMINARY INJUNCTION DAVID A. EZRA, District Judge. Plaintiffs' motion for preliminary injunction came on for hearing on September 29, 1989. Jeffrey Fereday, Esq. appeared on behalf of the plaintiffs; Assistant United States Attorney D. Marc Haws appeared on behalf of defendants Lt. Col. James A. Walter, United States Army Corps of Engineers, Delmar Vail, and United States Bureau of Land Management; and William Ringert, Esq. appeared on behalf of defendants Earl M. Hardy and Box Canyon Trout Co., Inc. The court having reviewed the pleadings, affidavits and exhibits submitted in support of and opposition to the motion, having heard the oral arguments of counsel and the testimony of witnesses, and being fully advised as to the premises herein, grants plaintiffs' motion. BACKGROUND Since 1969, Defendant Earl M. Hardy ("Hardy") has owned approximately 260 acres of land in southern Idaho which includes a large portion of an area commonly known as Box Canyon and a substantial portion of an area commonly known as Blind Canyon. Box Canyon is largely unspoiled and contains many fresh water springs which feed into the 1.5 mile long Box Canyon Creek which empties into the Snake River. *1485 Approximately 41.2 acres within Box Canyon is owned by the United States and is administered by defendant Bureau of Land Management ("BLM"). Due to the admittedly unique natural values of this area, BLM designated its holdings in and around Box Canyon as an Area of Critical Environmental Concern ("ACEC"). This was done as part of the Monument Resource Area Management Plan ("MRAMP") which was completed by BLM in December, 1985. In order to operate a fish propagation facility on his property near the mouth of Blind Canyon, Hardy proposes to build a diversion facility and a flume on Box Canyon Creek. The dam would divert water to the adjacent Blind Canyon where the hatchery is to be located. The diversion structure is proposed to be built on lands owned by the United States and administered by BLM. The natural flow of Box Canyon Creek is approximately 720 cubic feet per second ("cfs"). This flow has already been reduced considerably by the Clear Springs facility which is located on the south side of the Snake River opposite Box Canyon. Hardy's project proposes to divert an additional 257 cfs leaving a flow of 75 cfs, or approximately 10% of the creek's natural flow.[1] Hardy joined in an application for a right of way in 1970. In 1982, after conducting environmental studies, BLM denied Hardy's application but later reinstated the application to allow Hardy to submit additional information and mitigation proposals. In connection with evaluating Hardy's proposed project, BLM began a series of land planning procedures, which resulted in the MRAMP and the ACEC plan. BLM prepared an Environmental Impact Statement ("EIS") in connection with the MRAMP which covers both Box and Blind Canyons. In November 1986, BLM eventually issued a right of way to Hardy which authorizes the construction, operation, and maintenance of his proposed diversion facility and flume on BLM property. In connection with its issuance of a right of way, BLM prepared an Environmental Assessment[2] ("EA") which addressed the environmental impacts of the proposed right of way agreement with Hardy on the ACEC. The EA specifically addressed two possible alternatives:[3] (1) denying the right of way proposal ("Alternative One"); and (2) granting the right of way but including specific mitigation measures to accomplish certain levels of environmental protection and/or enhancement to assure the objectives of the ACEC Management Plan are met ("Alternative Two"). The environmental assessment treated Hardy's proposal as an environmentally adverse action and not in conformance with the ACEC Management Plan. In determining the environmental impact of denying Hardy's right of way proposal under Alternative One, BLM considered the potential consequences of the denial in terms of Hardy's other development alternatives. BLM recognized that should it deny Hardy the right of way on public lands he requested, he had several options including constructing a diversion at the mouth of Box Canyon; developing the upper Box Canyon; diverting water bypassing the existing Clear Springs diversion; or "us[ing] other means to recover investment." BLM EA, p. 3. The BLM environmental assessment separately addressed each of these possible actions which Hardy *1486 might take as a consequence of BLM's outright denial of a right of way. Giving consideration to the possible consequences inherent in Alternative One, BLM determined in its EIS that Alternative Two, which required several mitigation measures to be taken by Hardy to protect the environment, was preferable to Alternative One and would satisfy the concerns of all relevant agencies. The right of way agreement as negotiated between BLM and Hardy contained twenty-four stipulations which impose specific restrictions and requirements on Hardy with respect to both building the dam and maintaining the property. BLM determined, in its EA, that an Environmental Impact Statement ("EIS") would not be required since the restrictions and requirements of the right of way agreement adequately addressed the environmental impacts of the project. In June of 1989, the Army Corps of Engineers ("the Corps") issued a 404 permit[4] to Hardy authorizing construction of the diversion structure and flume. The Corps initially rejected Hardy's application in November 1987 because by-pass flow features and a fish ladder were not included in the proposal. On March 1, 1989, the Corps accepted Hardy's amended application after it was revised to include the by-pass flow and fish ladder. The Corps relied extensively on the EA prepared by BLM and the mitigation proposal which it contained in reaching its own decision not to prepare an EIS. The Corps' EA which considered four alternatives, determined that the issuance of the 404 permit would not have a significant impact on the quality of the human environment and therefore an EIS was not mandated. The permit was issued on June 30, 1989 and included terms and conditions designed to protect the environment and to mitigate any adverse effects that the project might have. Plaintiffs filed their complaint on August 29, 1989 against BLM, the Corps and their officers and agents seeking declaratory judgment and injunctive relief. Plaintiffs amended their complaint to join defendant Hardy shortly thereafter. Plaintiffs include two environmentally concerned citizens groups and individual citizens residing in the Hagerman Valley, an area adjacent to the Box and Blind Canyons. They allege violations of the National Environmental Policy Act ("NEPA"), the Clean Water Act ("CWA"), the Federal Land Policy and Management Act ("FLPMA"), and the Administrative Procedure Act ("APA"). Plaintiffs now seek a preliminary injunction to prohibit Hardy from beginning construction on the diversion structure until an EIS has been prepared in compliance with NEPA. Plaintiffs assert that an EIS is required since the Corps and BLM failed to adequately address important issues with respect to the project's impact on candidate species,[5] the aquatic ecosystem, water quality, riparian vegetation and on Blind Canyon. Plaintiffs also argue that the defendants did not consider the cumulative impacts of existing and proposed projects in Box Canyon or the impact of ACEC classification. On September 29, 1989, a hearing was held on plaintiffs' motion. Plaintiffs presented the testimony of Michelle Stevens, a wetlands expert and former EPA employee who was involved in the assessment of the Hardy project. Ms. Stevens testified in accordance with a memorandum she prepared as an EPA employee which listed several environmental concerns which she recommended be addressed prior to project approval. She testified that in her opinion Hardy's mitigation proposal was inadequate and did not meet EPA's mitigation policy or address the previously stated concerns. She also testified that in her opinion the Corps' EA inadequately considered the direct and cumulative impacts *1487 of the Hardy project including the impact on wetlands. Defendants presented the testimony of Robert Cordell who is the Bennett Hills Resource Area Manager for BLM and the employee responsible for the issuance of the right of way to Hardy. Mr. Cordell testified with respect to the considerations that went into the preparation of the BLM EA and the procedures which were followed. After testimony and argument were presented at the hearing, defendant Hardy agreed to delay commencing construction of the dam pending the court's decision on plaintiffs' motion. The court took the matter under advisement. On October 12, 1989, the government defendants filed a motion to hold the court's decision in abeyance for a period of fourteen days in order to allow BLM and the Corps to evaluate the presence of Lanx in Box Canyon.[6] The court granted the government's motion on the condition that Hardy not begin construction activities during the additional stay. The court also allowed further briefing on the Lanx issue. STANDARD FOR PRELIMINARY INJUNCTION To obtain a preliminary injunction plaintiffs must show either: (1) a combination of probable success on the merits and the possibility of irreparable injury or (2) that serious questions are raised and the balance of hardships tips in its favor. U.S. v. Odessa Union Warehouse Co-Op, 833 F.2d 172, 174 (9th Cir.1987). A. Likelihood of Success on the Merits Plaintiffs are challenging the decisions of two federal agencies not to prepare EIS's — BLM's failure to prepare an EIS in connection with the Right of Way Agreement and the Corps' failure to prepare an EIS before issuing the 404 permit. Plaintiffs assert that in failing to prepare EIS's, BLM and the Corps have violated NEPA. Plaintiffs also assert violations of the Clean Water Act, the Federal Land Policy and Management Act ("FLPMA") and the Administrative Procedures Act ("APA"). 1. Standard of Review NEPA requires that an environmental impact statement be prepared when substantial questions are raised on whether a project may "significantly impact the human environment." 42 U.S.C. § 4332(2)(C) (1982); Friends of Endangered Species, Inc. v. Jantzen, 760 F.2d 976, 986 (9th Cir.1985). The decisions by BLM and the Corps not to prepare EIS's in accordance with NEPA before issuing the right of way and the 404 permit to Hardy will be upheld unless they are unreasonable.[7]Sierra *1488 Club v. U.S. Forest Service, 843 F.2d 1190, 1192 (9th Cir.1988). The court "should not substitute its judgment for that of an agency if the agency's decision was `fully informed and well-considered.'" Friends of Endangered Species, Inc., 760 F.2d at 986 quoting Vermont Yankee Nuclear Power Corp. v. National Resources Defense Council, Inc., 435 U.S. 519, 558, 98 S.Ct. 1197, 1219, 55 L.Ed.2d 460 (1978); Jones v. Gordon, 792 F.2d 821, 828 (9th Cir.1986). However, an agency's decision not to prepare an EIS is unreasonable under current Ninth Circuit law "[i]f substantial questions are raised regarding whether the proposed action may have a significant effect upon the human environment." Save the Yaak Committee v. Block, 840 F.2d 714, 717 (9th Cir.1988); Foundation for North American Wild Sheep v. United States Department of Agriculture, 681 F.2d 1172, 1178 (9th Cir.1982). An agency's decision not to prepare an EIS may also be unreasonable "if the agency fails to `supply a convincing statement of reasons why potential effects are insignificant.'" Save the Yaak Committee, 840 F.2d at 717, quoting The Steamboaters v. FERC, 759 F.2d 1382, 1393 (9th Cir.1985). 2. The BLM Environmental Assessment Both BLM and the Corps prepared EA's which concluded that there was no significant impact on the environment and therefore an EIS was unnecessary. The court will first consider BLM's EA since the Corps relied extensively on it in preparing its own and in reaching its conclusion with respect to this project. Plaintiffs raise several issues to demonstrate that BLM's EA is inadequate. They assert, among other things, that BLM's EA inadequately addresses the project's impact on candidate species, its cumulative effects, its impact on wetlands and its impact on the ACEC. a. Impact on Candidate Species NEPA requires an EIS if the action significantly affects the quality of the human environment. 42 U.S.C. § 4332(2)(C); 40 C.F.R. § 1508.8. In determining if a proposed action "significantly" effects the human environment the CEQ regulations[8] require the agency to consider both "context" and "intensity". 40 C.F.R. § 1508.27. "Context" refers to the effect of an action on society as a whole, the affected region, the affected interests and the locality. Id. "Intensity" refers to the severity of the impact. The specific factors the agency must consider in determining whether the effects of a project are significant include, inter alia, "the degree to which the possible effects on the human environment are highly uncertain or involve unique or unknown risks" and "the degree to which the effects on the quality of the human environment are likely to be highly controversial." 40 C.F.R. § 1508.27(4), (5) (1987); See Also Sierra Club, 843 F.2d at 1193. Plaintiffs have presented expert testimony, with respect to the Shoshone Sculpin, the Bliss Rapids Snail, the fisherola nuttalli and the Lanx which raise issues of uncertainty and unknown risks. Plaintiffs have also raised issues of controversy[9] through the critical testimony of various wildlife scientists and other experts. See Foundation for North American Sheep, 681 F.2d at 1182; Sierra Club at 1193, 1194. *1489 (1) Shoshone Sculpin[10] To mitigate impact to the shoshone sculpin, the BLM right of way agreement with Hardy requires artificial pools to be maintained behind the diversion structure in order to offset the loss of sculpin downstream. BLM representative Robert Cordell testified at the hearing that he believed the mitigation requirements of the Hardy proposal would actually enhance the sculpin population in Box Creek. Cordell's opinion, however, is directly contraverted by the expert testimony of Dr. Griffith, the fisheries biologist who actually prepared a 1981 study of shoshone sculpin which BLM relied upon in preparing their environmental assessment for this project. Dr. Griffith states in his affidavit in support of plaintiffs' motion that he believes the preservation zone and the resulting impoundment of water behind the diversion will not mitigate the significant impact the diversion will have on the shoshone sculpin. In considering the Hardy proposal, BLM must weigh many competing environmental factors. The court recognizes that the agency has expertise which the court does not in considering a variety of environmental issues. An agency may even choose to disagree with an expert's findings in evaluating a proposed project. The court, however, must insure that the agency has taken a "hard look" at the environmental consequences. Sierra Club, 843 F.2d at 1192. In this instance, BLM makes an assertion which is directly in conflict with the opinion of an expert which it supposedly relied upon. And, while Mr. Cordell of BLM asserted that the mitigation requirements in his opinion are more than adequate to offset impacts, he does not set forth his reasoning or reconcile his determination with the clear expert testimony to the contrary. The court does not address, nor can it address at this stage in the proceedings, who is correct with respect to the issue of the proposed project's impact on shoshone sculpin. The court merely finds that a "substantial question" has been raised with respect to whether the project may have a significant effect on the environment. The conflicting testimony demonstrates that the possible effects are at best "highly uncertain." 40 C.F.R. § 1508.27(4). In addition, plaintiffs have shown that the project is controversial in that a substantial dispute exists as to its effect. Foundation for North American Sheep, 681 F.2d at 1182. (2) Fisherola Nuttalli[11] An issue of uncertainty also arises with respect to the Fisherola Nuttalli candidate species. Mr. Steve Langenstein, the BLM wildlife biologist who contributed to the BLM EA, stated that no known living examples of this species had been found in Box Canyon Creek at the time the EA was prepared, although he suspected that some did exist. Therefore, he was unable to determine whether the mitigation proposal would adequately address any probable harm to the species. "[A]n agency decision to act now and deal with environmental concerns later ... is plainly inconsistent with the broad mandate of NEPA." Foundation for North Am. Wild Sheep, 681 F.2d at 1181. Approval of the Hardy project, without identifying the actual existence of a sensitive species, nor the impact that the diversion might have on them, is inappropriate under the Act. Id. Since the EAs were made, however, a study by Beak Consultants revealed that the species does, in fact, exist in Box Canyon.[12] Both of the agencies considered the *1490 recent discovery of Fisherola Nuttalli in Box Canyon Creek and concluded that the discovery did not change their determinations of no significant impact. Again, however, the agencies failed to specify why the finding is not significant or how the mitigation proposal would adequately address the impacts to this species. The Steamboaters, 759 F.2d at 1382, ("The agency must supply a convincing statement of reasons why potential effects are insignificant.") Mr. William McDonald of the Corps supported his finding stating that "[t]his species was already considered in our original determination as stated in our Department of the Army Permit Evaluation and Decision Document." An examination of the Corps' EA, however, reveals that the Corps only concurred with BLM's findings that the proposed mitigation would "provide adequate populations for future study." As previously discussed, the BLM's findings, although mentioning the Fisherola Nuttalli, did not consider the actual impact of the proposed project on the species since none had been believed to exist in the area of concern. Under these circumstances, Mr. McDonald's statement, without further explanation, does not meet the required standard of reasonableness. (3) Bliss Rapids Snail and Lanx With respect to the Bliss Rapids Snail,[13] the BLM EA concedes that little is known about this species and its streamflow requirements. BLM relied on the MRAMP which encompassed the proposed diversion site and its surrounding area. The EIS prepared in connection with that plan included the Taylor Report which addressed Bliss Rapids Snail and other molluscs. Plaintiffs' experts assert that there may be no Bliss Rapids Snails in the preservation zone. Plaintiffs' expert also asserts that Bliss Rapids Snails are not found in areas where there is the strongest current, and the reduction of streamflow may extirpate what snails exist in Box Canyon Creek. Defendants, on the other hand, contend that a 1987 study done by Beak Consultants revealed that Bliss Rapids Snails do, in fact, exist in the preservation zone. While this weighs in favor of the adequacy of the mitigation proposal, the court finds that this study, prepared after BLM issued the right of way in 1986, was not considered by the agency in making its finding of no significant impact. Once again, the issue is one that is "uncertain" and "controversial" and BLM's failure to adequately address this uncertainty and substantiate, in accordance with the relevant statutes, its findings of no significant impact in its EA indicates that there are substantial questions regarding whether the proposed action may have a significant effect upon the human environment. See Save the Yaak Committee, 840 F.2d at 717. With respect to the Lanx, issues have certainly been raised as to the species' existence in Box Canyon Creek. According to the government's recent study, discussed previously, no Lanx were discovered there.[14] Plaintiffs' expert, Dr. Frest,[15] on the other hand, asserts that he has located living examples of this candidate species in Box Canyon Creek in an area not sampled by Beak Consultants. Without determining how these findings should be reconciled, the court finds that there exists some substantial questions as to the existence of this species in the affected area and the possible impacts upon that species. Accordingly, plaintiffs have raised substantial questions with respect to the impact of the project on the four candidate *1491 species,[16] and BLM and the Corps have failed to provide "a convincing statement of why the impacts will not be significant." See Save the Yaak Committee, 840 F.2d at 717; The Steamboaters, 759 F.2d at 1393. The government defendants argue that they have already considered the impact to these candidate species and have determined that the impact, in light of the mitigation measures, will not be significant. The defendants do not, however, specifically state in their EA's how the mitigation measures will address these adverse impacts. See LaFlamme v. FERC, 842 F.2d 1063 (9th Cir.1988), opinion superceded by 852 F.2d 389 (9th Cir.1988). In fact, plaintiffs' experts[17] assert that the mitigation measures will not reduce the impact on the four candidate species and raise substantial questions as to the harm that these species will suffer. b. Mitigation At the heart of this dispute is the government agencies' laudable attempt to protect at least a portion of Box Canyon from private development by requiring a preservation zone. The object is to mitigate the effects of the proposed diversion project. The agencies' main argument supporting their determinations of no significant impact rests on defendant Hardy's extensive concessions in allowing restrictions to be placed on his use of the upper third of Box Canyon. Clearly, mitigation measures may be considered by an agency in determining whether to prepare an EIS. Friends of Endangered Species, 760 F.2d at 987; 40 C.F.R. § 1508.20(e). An EIS must be prepared, however, where substantial questions are raised as to whether these mitigation efforts are adequate. Foundation for North Am. Wild Sheep, 681 F.2d at 1181; LaFlemme v. FERC, 852 F.2d 389, 399 (9th Cir.1988). Although the Ninth Circuit has held off-site mitigation to be acceptable under appropriate circumstances, it has not addressed the issue where there has been a specific challenge to the adequacy of the off-site mitigation area. Friends of the Earth, 800 F.2d 822, 838, f.n. 17. (A substitute wetlands site was sufficient to mitigate impact of landfill and justified the Corps' decision not to prepare an EIS where plaintiffs did not specifically attack the adequacy of the substitute mitigation site.) In this case, Hardy's most significant mitigation measure is his designation of the upper third of Box Canyon as a preservation zone. Plaintiffs challenge the adequacy of this proposal by alleging that the candidate species in question are not known to exist in this portion of the canyon.[18] Without determining the validity of their argument at this time, the court finds that substantial questions have been raised with respect to the adequacy of the agreed upon preservation zone to mitigate the the adverse environmental impacts of the proposed project. The test the court must apply is whether "the plaintiff has alleged facts which, if true, show that the proposed project may significantly degrade some human environmental factor." Columbia Basin Protection Ass'n v. Schlesinger, 643 F.2d 585, 597 (1981); The Steamboaters, 759 F.2d at *1492 1392. If plaintiffs' experts are correct,[19] which the court does not determine at this time, with respect to the lack of population of candidate species in the preservation zone, the project may significantly reduce or threaten these species' existence. Defendants additionally assert that the minimum streamflow requirement of 75 cfs will mitigate the environmental impacts of the Hardy proposal. Three of plaintiffs' experts, however, argue that this reduction in streamflow will likely result in extreme reduction or extirpation of the candidate species in question. The court cannot at this stage determine who is correct, nor does it mandate a methodology or rule to apply to determine an acceptable level of streamflow;[20] however, the court finds that the plaintiffs have raised sufficient questions with respect to the adequacy of the minimum streamflow to mitigate the significant impact the proposed project may have on candidate species. Despite the mitigation agreement between Hardy and the government, the court finds on the record before it that it is likely that the building of the diversion structure on BLM lands within an Area of Critical Concern is a major federal action which "may significantly degrade some human environmental factor." Columbia Basin Protection Ass'n v. Schlesinger, 643 F.2d 585, 597 (1981). 3. The Corps' Environmental Assessment Plaintiffs also assert that the Corps violated NEPA by failing to prepare an EIS in connection with the issuance of the 404 permit. Again, as discussed previously, the court will only reverse the Corps' determination not to prepare an EIS if it finds it to be unreasonable. Sierra Club at 1192. Plaintiffs criticize the Corps' EA for relying too heavily on BLM's EA rather than doing its own independant evaluation. The court cannot fault the Corps' EA on this ground alone, however, since the Corps asserts that it independantly verified the information. Friends of the Earth, Inc., 800 F.2d at 834-35. In March 1987, the Environmental Protection Agency ("EPA") indicated concerns to the Corps with regard to impacts of the project on candidate species, the aquatic ecosystem, stream flow integrity, and water quality. The EPA also expressed concern about the cumulative impacts of existing and proposed projects. The Corps EA addressed these concerns almost entirely by relying on the BLM EA. Although their reliance on BLM's EA was not in itself improper, as the court previously discussed, substantial questions have been raised with respect to the significant environmental impacts of the Hardy proposal which BLM's EA did not address. In particular, by relying on BLM's EA which was prepared over two years before, the Corps failed to adequately explain how the proposed measures would mitigate the impacts on candidate species. There is no dispute that the EPA ultimately approved of the Corps' issuance of *1493 the 404 permit. A letter from EPA officials to the Corps on June 13, 1989 stated that the Corps draft decision "satisfactorily addresses the concerns raised in our previous comment letter and in discussions with you and your staff." The standard the court must apply to the Corps decision, however, is not whether the EPA was satisfied,[21] but rather, whether the Corps "stated convincing reasons" for their determination of no significant impact. Save the Yaak Committee 840 F.2d at 717. The Corps' reasons for determining that an EIS was not necessary, with respect to candidate species, cumulative impacts, and water quality are based on BLM's EA which, as discussed above, probably is inadequate. 4. Connected Actions CEQ regulations require that "connected actions" be considered together in a single EIS. 40 C.F.R. § 1508.25(a)(1); Thomas v. Peterson, 753 F.2d 754, 758 (9th Cir.1985). "Connected actions" are defined as actions that: (i) automatically trigger other actions which may require environmental impact statements. (ii) cannot or will not proceed unless other actions are taken previously or simultaneously. (iii) are interdependent parts of a larger action and depend on the larger action for their justification. Id. Plaintiffs assert that Hardy's proposed fish propogation facility in Blind Canyon is a "connected action" and defendants have violated NEPA by failing to consider it in their EAs. Defendants argue that the Blind Canyon facility does not need to be considered in conjunction with the proposed diversion since no discharge will be made, it is not currently impacting wetlands, and if it does, such discharge will be covered by a nationwide permit. The Corps basically asserts that it has no obligation to consider Hardy's purely private project in connection with issuing the 404 permit. Recently, in Sylvester v. U.S. Army Corps of Engineers, the Ninth Circuit Court of Appeals held that the Corps was not required by NEPA to consider the impact of an entire resort when issuing a 404 permit for a golf course which would be built on wetlands within the resort. 884 F.2d 394 (9th Cir.1989). The court distinguished the case from previous holdings which required the consideration of connected actions. The court described the actions in Sylvester, as "a separate segment of chain" as opposed to previous cases which dealt with "links in the same bit of chain." Id. The court stated "[w]e do not understand how [defendant's] desire to place the course in a meadow that contains wetlands can federalize the entire resort complex." The inquiry here, then, is whether the proposed diversion and the Blind Canyon Creek propogation facility are "links in the same bit of chain." The Ninth Circuit decision indicates that the court should be more deferential to the Corps' determination with respect to what actions should be considered in issuing a 404 permit. In applying the enunciated standard, however, for purposes of this motion for preliminary injunction, the court finds that the fish propogation facility is probably more "like a link in the same bit of chain." Unlike the golf course and resort in Sylvester, Id., the fish propogation facility could not exist absent a diversion. Therefore, the propogation facility should probably have been considered by the Corps in preparing its EA. Having so found, the court, however, does not decide whether the agencies were required to also consider the potential hydroelectric plant which plaintiffs assert Hardy might construct in the area at some future point. The court defers to the agencies' finding that the hydroelectric project was not "reasonably foreseeable." 40 C.F.R. § 1508. *1494 B. Irreparable Injury Having determined that the plaintiffs have a strong probability of showing that, under the Ninth Circuit's "reasonableness test," substantial questions are raised regarding whether the proposed project may have a significant effect on the environment, the court next determines whether the plaintiffs have shown the possibility of irreparable injury. Odessa Union Warehouse Co-Op, 833 F.2d at 174. Although irreparable damage may not be presumed in environmental cases, "Environmental injury, by its nature, can seldom be adequately remedied by money damages...." Amoco Production Co. v. Village of Gambell, Alaska, 480 U.S. 531, 107 S.Ct. 1396, 94 L.Ed.2d 542 (1987). "If such injury is sufficiently likely, therefore, the balance of harms will usually favor the issuance of an injunction to protect the environment." Id. Three different experts have asserted that the proposed diversion structure is likely to impose irreparable harm to the environment, in particular to the candidate species in question. BLM, in its resort to the mitigation proposal, has conceded that there will be a significant impact in lower Box Canyon if this project goes forward. This court has no basis to determine otherwise. Although the court must issue the preliminary injunction pursuant to the standards which the law imposes, it does so with great reservation in this case. While plaintiffs have successfully raised questions as to the environmental impacts of Hardy's proposed project and the irreparable harm which might ensue, they may not have considered, as the government claims to have done, the impacts to Upper Box Canyon of not allowing Hardy to begin construction of the dam. Nevertheless, the court finds plaintiffs have shown that Hardy's proposed project probably will result in irreparable harm to some elements of the environment and, under the standards set forth by the Ninth Circuit, this court must issue a preliminary injunction until a further and more detailed examination of the merits of this case may ensue. C. Bond Fed.R.Civ.P. 65(c) provides for the imposition of a bond upon the applicant for preliminary injunction "for the payment of such costs and damages as may be incurred or suffered by any party who is found to have been wrongfully enjoined or restrained." The court, however, may dispense with the requirement of a bond "where requiring a security would effectively deny access to judicial review." California v. Tahoe Regional Planning Agency, 766 F.2d 1316, 1325 (1985). Plaintiffs request that the court not impose a bond pursuant to Fed.R.Civ.P. 65(c). Plaintiffs have submitted an affidavit indicating that they are private citizens and citizens groups with very limited financial resources and no financial interest in the outcome of this lawsuit. Defendants have not submitted evidence to the contrary. The court finds that although the economic hardship to defendant Hardy may be significant, imposition of a bond upon plaintiffs would be unreasonable and tantamount to denying them access to judicial review in this matter. Therefore, no bond will be imposed at this time. CONCLUSION The court is not unmindful of the many steps that defendant Hardy and the government defendants have taken over the past several years to strike a balance between Hardy's interest in productive use of his property and the public and environmental interests in preserving this unique and pristine natural area. The proposed mitigation proposal, wherein Hardy designates a significant portion of his land as a preservation zone, is to be commended and demonstrates the sincere efforts which he has made toward reaching a sensible solution to the competing interests involved in this matter. Nevertheless, the law requires certain steps to be taken to ensure that agencies carefully consider the specific impacts that a major federal action will have on the environment. One *1495 of these steps is the preparation of an environmental impact statement when the project may significantly effect the environment. Despite the efforts of the government to comply with the requirements of NEPA, the court is compelled, through the application of the "reasonableness" standard, to find that the plaintiffs probably have raised substantial questions as to the significance the Hardy proposal, even with the proposed mitigation measures, may have on the human environment. The court's decision is limited to finding that substantial questions have been raised which have not adequately been addressed by the government in preparation of its environmental assessments and therefore, in light of the possibility of irreparable harm to the environment, a preliminary injunction is warranted. Therefore, for all the reasons stated above, the court GRANTS plaintiffs' motion for preliminary injunction. IT IS SO ORDERED. NOTES [1] By the time the creek reaches the mouth of the Snake River, the streamflow will increase to approximately 162 cfs as a result of other spring contributories. [2] The purpose of an environmental assessment is to "briefly provide sufficient evidence and analysis for determining whether to prepare an environmental impact statement or a finding of no significant impact." 20 C.F.R. § 1508.9(b) (1987). [3] BLM actually considered four alternatives; however, two were unacceptable to defendant Hardy and therefore were not considered viable. Hardy rejected Alternative Three which proposed selling his entire interest in Box Canyon to BLM. Hardy also rejected Alternative Four which proposed adoption of Alternative Two with BLM assistance to a privately owned preservation group, in order to accomplish the purchase of Hardy's entire interest in Box Canyon. [4] This permit is required by the § 404 of the Clean Water Act for any action which would result in discharge of fill material into the waters of Box Canyon Creek. 33 U.S.C. § 1344(a). [5] A "candidate species" is a species which is not listed but is a candidate for listing as a threatened or endangered species by the U.S. Fish and Wildlife Service. [6] The issue of the Lanx, a freshwater mollusc, arose when the plaintiffs' expert, Dr. Frest, indicated in his affidavit accompanying plaintiffs' motion that he had discovered a Lanx shell in Box Canyon Creek. The government responded to this new information by requesting this court to stay its decision on plaintiffs' motion for preliminary injunction until it could further investigate the existence of Lanx in the creek to determine whether there would be a change in their finding of no significant impact. After a study done by Beak Consultants, Inc. which revealed no Lanx in the creek, the BLM and the Corps concluded that their decisions of no significant impact would remain undisturbed. [7] The "reasonableness" standard applied to an agency's decision to not prepare an EIS under NEPA differs from the "arbitrary and capricious" standard which would be applied to the Corps' decision to issue a 404 permit under the Clean Water Act. Friends of the Earth v. Hintz, 800 F.2d 822, 830-831 (9th Cir.1986); APA 5 U.S.C. § 706(2). Although a recent United States Supreme Court case held that the "arbitrary and capricious" standard of review should be applied to an agency's decision whether to prepare a supplemental EIS, it did not adequately address the question of what standard should apply to the agency's decision of whether to prepare an EIS in the first instance. Marsh v. Oregon Natural Resource Council, ___ U.S. ___, 109 S.Ct. 1851, 1859-1860, 104 L.Ed.2d 377 (1989). There is disagreement among the circuits with respect to the standard for reviewing the initial decision of whether to prepare an EIS. See River Road Alliance, Inc. v. Corps of Engineers, dissenting opinion, cert. denied, 475 U.S. 1055, 106 S.Ct. 1283, 89 L.Ed.2d 590 (1986). Some circuits have adopted the "arbitrary and capricious standard." See e.g. Grazing Fields Farm v. Goldschmidt, 626 F.2d 1068, 1072 (1st Cir.1980); River Road Alliance, Inc. v. Corps of Engineers, 764 F.2d 445 (7th Cir.1986), cert. denied, 475 U.S. 1055, 106 S.Ct. 1283, 89 L.Ed.2d 590 (1986). The Ninth Circuit, nonetheless, continues to adhere to the "reasonableness" standard and this court is compelled to apply that standard here. Sierra Club, 843 F.2d at 1192. Were the court to apply the more deferential standard of "arbitrary and capricious" the result might be very different in this case. [8] The Council of Environmental Quality ("CEQ") regulations list several factors the agency should consider in determining the intensity of impact. [9] "The term `controversial' refers to `cases where a substantial dispute exists as to the size, nature or effect of the major Federal action rather than to the existence of opposition to a use'" Foundation for North American Wild Sheep, 681 F.2d at 1182 (quoting Rucker v. Willis, 484 F.2d 158, 162 (4th Cir.1973)); See also Sierra Club, 843 F.2d at 1193. [10] The shoshone sculpin is a small fish which requires cold, clean water and very specific food and cover. [11] Also known as the Giant Columbia River limpet, this relatively small mollusc usually occurs in large streams, but suitable habitat also exists in Box Canyon Creek. [12] The court does not address the issue of the agencies' duty to supplement their findings of no significant impact. The recent study for potential Lanx was done by the defendants in efforts to comply with their duty to address "significant new information." 40 C.F.R. § 1502.9(c) (1987); See Marsh v. Oregon Natural Resources Council, 109 S.Ct. at 1858. [13] This candidate 1 species is a small snail which lives on the underside of instream rocks and may require flowing water to survive. [14] As noted earlier, the court does not address the government's duty with respect to new information. Since the government, however, initiated the study, and in part based their decision of no significant impact on it, the court considers that study prepared by Beak Consultants, as well as the research submitted by plaintiffs. [15] Dr. Terrence Frest, Ph.D. is an invertebrate paleontologist and freshwater mollusc expert from the University of Washington. [16] The BLM environmental assessment identified four candidate species existing in the Box Canyon Region: the Shoshone Sculpin; the Bliss Rapids Snail; the Fisherola Nuttalli (a.k.a. Giant Columbia River Limpet) and the Utah Volvata Snail. [17] Plaintiffs' experts include: (1) Dr. Terrence Frest, an invertebrate paleontologist and expert on freshwater molluscs; (2) Tim Cochnauer, a fisheries biologist who works for the Idaho Fish and Game Department; and (3) Dr. Griffith, a fisheries biologist who prepared a report on shoshone sculpin for BLM in 1981. [18] Defendants' recent study of Lanx revealed that fisherolla nuttalli did exist in the preservation area. Although this discovery helps to substantiate the government's position with respect to Hardy's mitigation proposal, it does not remedy their failure at the EA stage to reasonably determine whether substantial questions were raised with respect to the significance of the proposed project's environmental impact. [19] Defendants present evidence showing that the Bliss Rapids snail is known to exist in the upper canyon region. This finding was made by Beak Consultants in a 1987 study done for the City of Tacoma, Washington. The study, however, was done subsequent to BLM's EA and accompanying mitigation proposal. BLM had not investigated the existence of candidate species in the upper canyon. [20] Plaintiffs argue that the environmental assessments are inadequate because the methodology used by BLM to determine a minimum stream flow was both out-dated and improperly applied. NEPA, however, does not require that the court resolve disagreements between scientific methodologies. Friends of Endangered Species 760 F.2d at 986. Nor does NEPA require an environmental assessment to be based on the best scientific methodology available. Id. BLM presents documentation which outlines the lengthy process which it went through to reach a 75 cfs minimum acceptable bypass flow. To determine this figure a combination of methods was used — the Wetted Perimeter Technique and the Tenant Method. The Idaho Fish and Game Department ("Idaho Fish and Game") and U.S. Fish and Wildlife Service responded to the various Hardy proposals, and ultimately supported the 75 cfs determination; however, Mr. Jerry Conley of Idaho Fish and Game has since clarified his position with respect to the minimum streamflow level and claims that Idaho Fish and Game does not endorse Hardy's project. [21] This is not to say that the EPA's input is not important. See Friends of Endangered Species, 760 F.2d at 986. The fact that the EPA did finally approve of the project does have some weight; however, the record fails to indicate at this point what factors the EPA considered.

module.exports = require('./toPairs');

Leave a Reply Hospital turn off life support machine because family couldn’t pay £7k bill The family of British man have been left devastated and furious after an Egyptian hospital because staff switched off his life support without their permission. Despite this the hospital claim Adrian King suffered cardiac arrest however his family have told the local courts it’s because they didn’t have the money to pay a £7k insurance bill. Adrian aged 39 became ill while he was on holiday with his friend in Hurghada, on Egypt’s east coast. All of a sudden he fell unconscious and was being treated in hospital, during his time in hospital it was discovered his insurance policy have been voided and they demanded an upfront payment while he laid on his death bed. The inquest heard how the insurance was void as he had not declared a bacterial infection he had within his stomach two years before his holiday. Adrian’s dad Charles Bumford told the hearing: “A man at the hospital stood in my son’s room and told me: ‘The insurance is null and void – you pay now or I switch off the machines.’ “I didn’t have the £7,000 ($9,800) he was asking for at that time. As he walked out of the room he started switching things off.” Charles added that he tried contacting the hospital ’50 times’ but he never received an answer. The friend Adrian was with at the time, Nicola, was similarly confused by the situation occurring in the medical facility. “They did the second dialysis and then said that the insurance was voided,” she told the inquest. “They never said he had a cardiac arrest or anything, they said it was stopping, because the funding was stopped.” Comments Police have taken a zero tolerance approach to a woman who left a note on an ambulance. The note left paramedics disgusted police have now confirmed they have arrested a woman after the abusive note was left on an ambulance demanding it parked somewhere else while it was attending a 999 emergency call. The note stated ‘I couldn’t give a s**t if the whole street collapsed” We have arrested a 26 year old female for public order offences. Emergency Services must be able to carry out their roles without fear of abuse/intimidation of any kind. https://t.co/xHSbdtl54S

// Copyright 2000-2019 JetBrains s.r.o. Use of this source code is governed by the Apache 2.0 license that can be found in the LICENSE file. package com.jetbrains.lang.dart.xml; import com.intellij.openapi.project.Project; import com.intellij.psi.xml.XmlAttribute; import com.intellij.psi.xml.XmlTag; import com.intellij.xml.XmlAttributeDescriptor; import com.intellij.xml.XmlElementDescriptor; import com.intellij.xml.XmlElementsGroup; import com.intellij.xml.XmlNSDescriptor; import com.jetbrains.lang.dart.analyzer.DartServerData; import org.jetbrains.annotations.NotNull; import org.jetbrains.annotations.Nullable; /** * Descriptor for DartAngular-specific tag that serves for resolving tag name reference and also for making * {@link com.intellij.codeInspection.htmlInspections.HtmlUnknownTagInspection} happy. * Information from the Dart Analysis Server is used. */ class DartHtmlElementDescriptor extends DartHtmlDescriptorBase implements XmlElementDescriptor { DartHtmlElementDescriptor(@NotNull Project project, @NotNull String name, @NotNull DartServerData.DartNavigationTarget target) { super(project, name, target); } @Override public String getDefaultName() { return getName(); } @Override public String getQualifiedName() { return getName(); } @Nullable @Override public XmlAttributeDescriptor getAttributeDescriptor(@NotNull XmlAttribute attribute) { return DartHtmlAttributeDescriptorProvider.getAttributeDescriptor(attribute); } @Nullable @Override public XmlAttributeDescriptor getAttributeDescriptor(String attributeName, @Nullable XmlTag context) { return null; } @Override public XmlAttributeDescriptor[] getAttributesDescriptors(@Nullable XmlTag context) { return XmlAttributeDescriptor.EMPTY; } @Override public XmlElementDescriptor[] getElementsDescriptors(XmlTag context) { return XmlElementDescriptor.EMPTY_ARRAY; } @Nullable @Override public XmlElementDescriptor getElementDescriptor(XmlTag childTag, XmlTag contextTag) { return null; } @Nullable @Override public XmlNSDescriptor getNSDescriptor() { return null; } @Nullable @Override public XmlElementsGroup getTopGroup() { return null; } @Override public int getContentType() { return CONTENT_TYPE_UNKNOWN; } @Nullable @Override public String getDefaultValue() { return null; } }

Pinellas County company, individuals alleged to owe $65,000 for note CLEARWATER – Two Pinellas County individuals and a limited liability company are alleged to have defaulted on a promissory note. George A. Scribano filed a complaint on May 15 in the 6th Judicial Circuit Court of Florida - Pinellas County against Sun Pass Apartments LLC, John W. Grewe and Jodi Y Grewe alleging breach of promissory note. According to the complaint, the plaintiff alleges that on Jan. 30, 2015, defendants executed and delivered a promissory note in the amount of $65,000 payable to plaintiff. To date, said amount allegedly remains due and unpaid. The plaintiff seeks judgment against defendants for the principal amount due, plus interest, attorney's fees and costs and all other relief as the court may deem just and proper. He is represented by Jon B. Coats Jr. and Ryan M. Schmidt of Law Offices of Jon B. Coats Jr. PA in St. Petersburg.

Treatment of stable and unstable intertrochanteric fractures with selfdynamisable internal fixator (concept of double dynamisation). BACGROUND/AIM. Intertrochanteric fractures of the femur are the third most common fractures among all bone fractures. Today in everyday orthopedic practice a number of different methods of treatment of trochanteric fractures of the femur are applied. Despite the improvement in the development of new implants, the percentage of serious complications of the treatment of these fractures remains very high, varying from 10% to 20%. One of the most serious complications of internal fixation of intertrochanteric fractures is nonunion of fractures due to the lack of additional axial dynamisation of implants. The aim of this study was to determine the efficacy of double dynamisation in stable and unstable intertrochanteric fractures treatment using the self dynamisable internal fixator. During the period from 2000 to 2009 we analyzed the use of selfdynamisable internal fixator (SIF implant) in the treatment of 247 patients with stable and unstable intertrochanteric fractures. Fracture types were classified according to the AO Fracture Classification/Orthopaedic Trauma Association Scheme. Salvati and Wilson scoring systems were used for functional assessment considering pain, walking ability and hip movements of operated patients. Of the total number of treated patients, 134 were males and 113 females, aged 19 to 90 (average 49.6) years. More than a half of the patients were older than 50 years. Monitoring of the patients after the operation was carried out clinically and radiographically for a period of three to six months in all the patients, whereas a 2-year follow-up was conducted in 176 (71.2%) patients. The average duration of surgery was 47 min, the average blood loss 145 mL, and the average fluoroscopy time was 16 sec (8-97 sec). The average time for union was 3.7 months (3-6.6 months). Double dynamisation (dynamisation along the neck and shaft of the femur) was observed in 85 (34.4%) patients, and was on average 4.3 mm (1.5-8 mm). All fractures managed with dynamisation implants healed completely within no later than six months after the surgery. In 17 cases there was a cut-out phenomenon of implant, while in seven cases there was mechanical implant failure. Complications were detected within 3 to 6 weeks after surgery, and treated by the method of intramedullary fixation. During the study, there were no cases of infection and thromboembolic complications detected. The concept of double dynamisation improves the fracture healing in the stable and unstable intertrochangeric fractures using the selfdynamisable internal fixator. This biological method of fixation provides healing of intertrochanteric fracture in the optimum period of time, significantly reducing the risk for mechanical failure.

There have been some approaches taken to estimating travel times on arterial links that include speed versus volume to capacity ratios, but these approaches have lacked the ability to accurately determine in real time what the travel time is on a link. Other approaches use a velocity estimate combined with inductive loop measurements, but have not reached the level of accuracy needed to be trusted in realtime arterial information systems. Methods and apparatus are needed to efficiently match or associate an incoming vehicle signature to an outgoing vehicle signature so that estimates of arterial movement can be effectively and accurately calculated in real time.

Processor arrangements of the aforementioned type contain functional units that operate in parallel to one another and that are controlled at every clock cycle by an instruction word. The particular instruction word is extracted from a program word that is taken from a program memory. For their part, the instruction words consist of a plurality of instruction word parts, where each individual instruction word part serves to control one functional unit. To improve the performance of processor arrangements, the goal is an increase in the processing width, which makes it necessary to increase the number of functional units. In general, this increases the bit width of the instruction words and thus also of the program words. The consequence of this is the provision of corresponding storage space in the program memory, which occupies the majority of the area on the semiconductor chip. Since the size of the program words determines the size of the program memory, the goal is to reduce the size of the program words in order to reduce the need for memory space. A number of compression methods for this purpose are known. The most obvious method is described in the report by H. Weiss and G. Fettweis, [in English:] “Dynamic Codewidth Reduction for VLIW Instruction Set Architectures in Digital Signal Processors” (Proceedings of the 3rd International Workshop on Signal and Image Processing IWSIP '96, pages 517 to 520). In this method, the program words are assembled from sequential primary instruction words in such a way that secondary instruction words can be subsequently reproduced therefrom in that a secondary instruction word (VLIW), once it has been created, is written to an instruction word memory, and, in order to produce the next secondary instruction word, only those instruction word parts in the stored secondary instruction word are exchanged which differ between the stored secondary instruction word and the secondary instruction word to be generated. Consequently, the program word need only contain the information specifying which instruction word part differs and with what content it differs. It is thus possible to design the program words to be very narrow and thus save memory space. However, when there are great differences between the stored secondary instruction word and the secondary instruction word to be created, the width of the program word must be increased if these relatively great differences occur frequently, which entails the disadvantage of a relatively large memory space, or else the differences must be distributed over multiple program words. Thus, the secondary instruction word must be created from multiple program words over multiple clock cycles. This results in the disadvantage that it requires a relatively long time. Consideration is now being given to ways of overcoming this disadvanatge. In particular, attention is directed to specific ways of increasing the operating speed in an application while retaining a small program word widths.

Q: What is the maximum version of PHP that Joomla 1.5 will run? I have a client with an old Joomla 1.5 they dont want to upgrade this year but their host wants to upgrade the server. What is the maximum version of php that Joomla 1.5 will run rather than the min that is listed? http://www.joomla.org/technical-requirements.html#footnote-1xPHP Joomla! versions 1.5.15 and later are compatible with PHP 5.3. Would it run ok on 5.3.10? I would guess it would break on 5.4 but I find it hard to build a test machine with old versions to test. So more question from experience. thanks A: If you're running Joomla 1.5.14 or below then you should stick to PHP 5.2 as there may be a few functions and/or code snippets that may not work on PHP 5.3 However, if you're running Joomla 1.5.15 or above, you should be fine with upgrading to PHP 5.3. If you're using the OpenID library, then this won't be compatible with PHP 5.3 and thus you will either need to find an alternative or stick with PHP 5.2 For more information on which versions of PHP, MySQL and Apache, have a look at theTechnical Requirements I would suggest you upgrade to Joomla 1.5.26 which is the latest version of the 1.5 series. Hope this helps A: I'm running a Joomla 1.5.26 site alongside a new J3 site under construction on the same PHP installation. The J1.5 site is running perfectly on PHP 5.6 without any changes to anything at all. The J1.5 site is a very simple site with only a few extensions. A: I confirm Joomla 1.5.24 running on PHP 5.5.9-1ubuntu4.17. PHP-FPM was installed with apt. Web server is nginx. All features seems to be running smoothly.

TouchThinkLearn Board Books The new TouchThinkLearn books present a format unlike standard board books. Created by Xavier Deneux, Colors and Opposites are two titles that combine scooped-out die-cuts with raised, shaped elements, providing a multi-sensory experience for new “readers.” This allows them to see the image, trace its shape, and hear/say its name. The use of negative space is also completely refreshing.

Q: Regex to repeatedly capture group within a larger match? Context, syntax highlighting in gedit. Problem: I want to capture all occurrences within a specific area. Toy example: other text here $5 keyword1 -> (( ran$3dom$6t:,ext$9 )) keyword1 -> (( ran$2dom$4t:,ext$6 )) other text here $7 I want to capture (highlight) al the $0-9 (single digit) occurrences, within the (( text )) of the keyword1. (here $3, $6, $9, $2, $4, $6 but NOT $5 and $7). This boils down to: How can I repeatedly capture a group within a larger match? I can grab all the text where the groups can occur with: (?<=keyword1)|\(\(.*\)\) (gedit uses \g by default) <context id="keyword1" style-ref="argument"> <match>(?<=keyword1)|\(\(.*\)\)</match> </context> I have found this related question: How can I write a regex to repeatedly capture group within a larger match? but that answer uses infinite repetition inside look-behind which is, unfortunately, not supported by gedit (as far as i know). Any suggestion? A: Description To ensure you're only working on lines starting with your keyword, then I see this as a two step operation. collect each of the lines you're interested extract the $[0-9] substrings Step 1 This regular expression captures lines that resemble keyword1 -> ((...)) keyword1\s*->\s*\(\(.*\)\) Step 2 \$[0-9](?![0-9])(?=(?:(?!\(\().)*\)\)) This regular expression will do the following: find all dollar signs followed by a single digit that exist inside the ((...)) Example Live Demo https://regex101.com/r/wY3jM6/1 Sample text other text here $5 keyword1 -> (( ran$3dom$6t:,ext$9 )) keyword1 -> (( ran$2dom$4t:,ext$6 )) other text here $7 Sample Matches $3 $6 $9 $2 $4 $6 Explanation NODE EXPLANATION ---------------------------------------------------------------------- \$ '$' ---------------------------------------------------------------------- [0-9] any character of: '0' to '9' ---------------------------------------------------------------------- (?! look ahead to see if there is not: ---------------------------------------------------------------------- [0-9] any character of: '0' to '9' ---------------------------------------------------------------------- ) end of look-ahead ---------------------------------------------------------------------- (?= look ahead to see if there is: ---------------------------------------------------------------------- (?: group, but do not capture (0 or more times (matching the most amount possible)): ---------------------------------------------------------------------- (?! look ahead to see if there is not: ---------------------------------------------------------------------- \( '(' ---------------------------------------------------------------------- \( '(' ---------------------------------------------------------------------- ) end of look-ahead ---------------------------------------------------------------------- . any character ---------------------------------------------------------------------- )* end of grouping ---------------------------------------------------------------------- \) ')' ---------------------------------------------------------------------- \) ')' ---------------------------------------------------------------------- ) end of look-ahead ----------------------------------------------------------------------

Carmen Maria Machado Carmen Maria Machado is an American short story author, essayist, and critic frequently published in The New Yorker, Granta, Lightspeed Magazine, and other publications. Her story collection Her Body and Other Parties was published in 2017. A finalist for the National Book Award and the Nebula Award for Best Novelette, her stories have been reprinted in Year’s Best Weird Fiction, Best American Science Fiction & Fantasy, Best Horror of the Year, The New Voices of Fantasy, and Best Women's Erotica. Her memoir In the Dream House was published in 2019. Machado lives in Philadelphia with her wife. Early life Carmen Maria Machado was raised by her parents in Allentown, an hour north of Philadelphia. Her father was the son of two immigrants, with his own father moving to the United States from Cuba at the age of 18. Machado's grandfather worked in the US Patent Office and met his future wife when she immigrated to the U.S. from Austria after World War II. Education Machado earned an MFA from the Iowa Writers' Workshop and has received fellowships and residencies from the Michener-Copernicus Foundation, the Elizabeth George Foundation, the CINTAS Foundation, the Speculative Literature Foundation, the University of Iowa, the Yaddo Corporation, Hedgebrook, and the Millay Colony for the Arts. Machado also attended the Clarion Workshop where she studied under authors such as Ted Chiang. Influences Machado says her writing has been influenced by Ray Bradbury, Shirley Jackson, Angela Carter, Kelly Link, Helen Oyeyemi, and Yōko Ogawa. In particular, Machado says she was heavily influenced by Gabriel García Márquez's One Hundred Years of Solitude, which was given to her to read by an "insightful and amazing English teacher" when she was in the 10th grade of high school. Career Machado's short stories, essays, and criticism have been published in a number of magazines including The New Yorker, Granta, The Paris Review, Tin House, Lightspeed Magazine, Guernica, AGNI, National Public Radio, Gulf Coast, Los Angeles Review of Books, Strange Horizons, and other publications. Her stories have also been reprinted in anthologies such as Year’s Best Dark Fantasy & Horror 2017, Year's Best Weird Fiction, Best American Science Fiction & Fantasy, Best Horror of the Year, and Best Women's Erotica. Machado's short story "Horror Story," originally published in Granta in 2015, details a lesbian couple's difficulty coping with a haunting in their new house. Machado's fiction has been called "strange and seductive" while also noting that her "work doesn't just have form, it takes form." Her fiction has been a finalist for the Nebula Award for Best Novelette, the Shirley Jackson Award, the Franz Kafka Award in Magic Realism, the storySouth Million Writers Award, and the Calvino Prize from the Creative Writing Program at the University of Louisville; as well, an analysis by Io9 indicated that if not for the Sad Puppies ballot manipulation campaign, Machado would have been a finalist for the 2015 John W. Campbell Award for Best New Writer. In 2018, she won the Bard Fiction Prize. Her horror-inspired short story collection, Her Body and Other Parties, was published by Graywolf Press in 2017. It was a 2017 finalist for the National Book Award for fiction, won the 2017 National Book Critics Circle Award John Leonard Prize, and was shortlisted for the 2018 Dylan Thomas Prize. The collection has been optioned by FX and a television show is in development by Gina Welch. As of 2018, she is the Writer in Residence at the University of Pennsylvania. Machado is a 2019 recipient of a Guggenheim fellowship. Machado was Guest Editor of the Best American Science Fiction and Fantasy 2019 edition. Bibliography Short stories "The Lost Performance of the High Priestess of the Temple of Horror" (Granta) "Once Upon a Time in Hollywood" (Harper's Bazaar) "Mary When You Follow Her" (VQR) "Eight Bites" (Gulf Coast) "Blue" (Tin House) "The Husband Stitch" (Granta) "Horror Story" (Granta) "Inventory" (Strange Horizons) "Help Me Follow My Sister into the Land of the Dead" (Lightspeed Magazine) "Especially Heinous" (The American Reader) "Mothers" (Interfictions) “The Book of the Dead” (BBC Radio 4) “Haunt” (Conjunctions) "A Cat, a Bride, a Servant" (Garage) "A Brief and Fearful Star" (Slate/Future Tense) "Relaxation Technique" (McSweeney's Quarterly Concern) "Miss Laura's School for Esquire Men" (Tin House) "Vacation" (Wigleaf) "The Old Women Who Were Skinned" (Fairy Tale Review) "Descent" (Nightmare Magazine) "My Body, Herself" (Uncanny Magazine) "Observations About Eggs from the Man Sitting Next to Me on a Flight from Chicago, Illinois to Cedar Rapids, Iowa" (Lightspeed Magazine) Books Especially Heinous: 272 Views of Law & Order SVU (novella, The American Reader, May 2013) Her Body and Other Parties (Graywolf Press, 2017) In the Dream House (Graywolf Press, 2019) References External links Category:Living people Category:American science fiction writers Category:American women short story writers Category:Hispanic and Latino American short story writers Category:LGBT writers from the United States Category:LGBT people from Pennsylvania Category:LGBT Hispanic and Latino American people Category:Lambda Literary Award for Lesbian Fiction winners Category:21st-century American short story writers Category:21st-century American women writers Category:Weird fiction writers Category:Writers from Allentown, Pennsylvania Category:Guggenheim Fellows Category:1986 births Category:American University alumni Category:Iowa Writers' Workshop alumni

Q: Split strings into separate lists by regex match I have a text file that looks like this 127.0.0.1 159.187.32.13, 3:00:15, flags: S Incoming interface: Ethernet51/1 RPF route: [U] 151.177.45.0/27 [20/0] via 190.150.1.2 Outgoing interface list: Vlan4054 159.187.32.20, 2:20:11, flags: S Incoming interface: Ethernet51/1 RPF route: [U] 151.177.45.59/27 [20/0] via 190.150.1.2 Outgoing interface list: Vlan4054 Vlan4056 198.140.45.77, 2:36:15, flags: S Incoming interface: Ethernet51/1 RPF route: [U] 151.177.45.88/27 [20/0] via 190.150.1.2 Outgoing interface list: Vlan4054 127.0.0.2 188.125.45.13, 3:00:15, flags: S Incoming interface: Ethernet51/1 RPF route: [U] 199.150.45.0/27 [20/0] via 195.32.1.2 Outgoing interface list: Vlan4054 Vlan4056 221.125.45.77, 2:20:11, flags: S Incoming interface: Ethernet51/1 RPF route: [U] 199.150.45.10/27 [20/0] via 195.32.1.2 Outgoing interface list: Vlan4054 Vlan4056 I'm trying to create a dictionary of the data so it is parseable, currently attempting to do so via regex import re content = [] content_dict = {} group_ip = re.compile("^(\d+\.\d+\.\d+\.\d+$)") ip_subnet = re.compile("^(\d+\.\d+\.\d+\.\d+\/+\d+)") two_space_start = re.compile("^( {2})\S") four_space_start = re.compile("^( {4})\S") six_space_start = re.compile("^( {6})\S") I had planned on applying regex to each line and creating a dictionary like below if group_ip.match(line): content_dict["group"] = line.strip() elif two_space.match(line) and "RP" in line: line = line.split(",") content_dict["source"] = line[0].strip() content_dict["uptime"] = line[1].strip() content_dict["rp"] = line[2].split(" ")[-1] content_dict["source_flags"] = line[-1].split(":")[-1].strip() content.append(copy.copy(content_dict)) But have realised that this won't work on scale as each group IP (127.0.0.1, 127.0.0.2) will have a variable amount of subgroups that I am overwriting. What I'm trying to get to is something along the lines of "127.0.0.1": [ "159.187.32.13": [ "uptime": "3:00:15", "flags": "S", "rpf_ip": "151.177.45.0/27", "via": "190.150.1.2", "outgoing_interface": ["vlan4054"] ], "159.187.32.20": [ "uptime": "2:20:11", "flags": "S", "rpf_ip": "151.177.45.59/27", "via": "190.150.1.2", "outgoing_interface": ["Vlan4054", "Vlan4056"] ] ] Is it possible to get this data structure from the text through regex or some other way? A: Since the input is fairly easy to tokenize, regex may be overkill. You can instead use str.startswith, str.isdigit and str.split for your purpose: from pprint import pprint content = {} with open('file.txt', 'r') as f: for line in f: line = line.rstrip() if line[0].isdigit(): group = line content[group] = {} elif line.startswith(' ') and line[2].isdigit(): ip, uptime, flags = line.lstrip().split(', ') _, flags = flags.split() content[group][ip] = {'uptime': uptime, 'flags': flags, 'outgoing_interface': []} elif line.startswith(' RPF route:'): _, _, _, rpf_ip, _, _, via = line.split() content[group][ip]['rpf_ip'] = rpf_ip content[group][ip]['via'] = via elif line.startswith(' '): content[group][ip]['outgoing_interface'].append(line.lstrip()) pprint(content) This outputs (with your sample input): {'127.0.0.1': {'159.187.32.13': {'flags': 'S', 'outgoing_interface': ['Vlan4054'], 'rpf_ip': '151.177.45.0/27', 'uptime': '3:00:15', 'via': '190.150.1.2'}, '159.187.32.20': {'flags': 'S', 'outgoing_interface': ['Vlan4054', 'Vlan4056'], 'rpf_ip': '151.177.45.59/27', 'uptime': '2:20:11', 'via': '190.150.1.2'}, '198.140.45.77': {'flags': 'S', 'outgoing_interface': ['Vlan4054'], 'rpf_ip': '151.177.45.88/27', 'uptime': '2:36:15', 'via': '190.150.1.2'}}, '127.0.0.2': {'188.125.45.13': {'flags': 'S', 'outgoing_interface': ['Vlan4054', 'Vlan4056'], 'rpf_ip': '199.150.45.0/27', 'uptime': '3:00:15', 'via': '195.32.1.2'}, '221.125.45.77': {'flags': 'S', 'outgoing_interface': ['Vlan4054', 'Vlan4056'], 'rpf_ip': '199.150.45.10/27', 'uptime': '2:20:11', 'via': '195.32.1.2'}}}

Background ========== *Anopheles sinensis*, *An. anthropophagus*, *An. minimus,* and *An. dirus* are the major vectors of malaria transmission in China \[[@B1]\], and species in the *An. maculatus* complex may be major transmission vectors in Tibet Autonomous Region \[[@B2]\]. Among these species, *An. minimus* and *An. dirus* are mostly distributed in southern China (Yunnan and Hainan provinces), where the geographical environment is markedly different from the central region. *An. sinensis* and *An. anthropophagus* are relatively more widely distributed in China. According to the updated distribution records of the *An. hyrcanus* species group (Diptera: Culicidae), *An. sinensis* is found in over 29 provinces and regions in China \[[@B3]\]. It is noteworthy that *An. sinensis* has become the only major vector in central China, where *Plasmodium vivax* is the only prevalent, locally transmitted, malaria parasite; however, a few imported *falciparum* malaria cases have been reported among travellers \[[@B4]\]. *An. sinensis* and *An. anthropophagus* are both members of the *An. hyrcanus* complex, sharing similar morphological characteristics, and a ribosomal DNA-internal transcribed spacer 2 (rDNA-ITS2) -based method is required to distinguish the two species \[[@B5],[@B6]\]. However, in addition to the distinct distributions of *An. sinensis* and *anthropophagus,* the species differ strongly in host preference, resting habitat, and other features involved in malaria transmission. First, *An. anthropophagus* prefers to bite humans rather than animals, whereas *An. sinensis* is a more zoophilic mosquito and demonstrates a marked preference for cattle and other warm-blooded animals. Second, *An. anthropophagus* prefers indoor resting after blood feeding; residual insecticide spraying in areas of central China where *An. anthropophagus* predominated as the major vector for *falciparum* effectively reduced malaria mortality and morbidity, from 1980 to 1990. As a result, *falciparum* malaria has been eliminated in central China. However, *An. sinensis* tends toward outdoor resting after indoor blood feeding, which has made vector control of this species more difficult. Third, *An. anthropophagus* is much more susceptible to *vivax* malaria parasites \[[@B7]\]. The regions in China containing both *An. anthropophagus* and *An. sinensis* have suffered more serious malaria epidemics than those areas where *An. sinensis* is the only vector \[[@B8]\]. Taking the above-mentioned factors into consideration, one possible conclusion is that *An. sinensis* plays a less important role in malaria transmission than other species in central China. Unexpectedly, frequent outbreaks of *vivax* malaria started appearing in areas where *An. sinensis* was the main vector, with over 40,000 reported *vivax* cases in 2005, accounting for 67% of all cases in China \[[@B9]\]; this suggests that the susceptibility and other features of *An. sinensis* that affect its interaction with *vivax* parasites have changed. Thus, the comparative malaria-transmission ability of *An. sinensis* with other major vectors should be reassessed. In this study, we assessed the susceptibility of *An. sinensis* to *P. vivax* in central China by membrane-feeding assay and compared the results with *An. anthropophagus* and a field strain of *An. sinensis*. This study will help to explain the *vivax* epidemic situation in central China better, and improve the current elimination programmes of this species in China. Methods ======= Study site and patients ----------------------- The study was conducted in Bengbu, Anhui Province, central China (Figure [1](#F1){ref-type="fig"}). *P. vivax* is the only malaria parasite in this region. In 2004, the total number of malaria cases in Anhui reached 8,909, which was 22.9% of all cases in China (Figure [2](#F2){ref-type="fig"}). Patients aged 18 years of age or more, who sought clinical treatment for malaria, were included in this study. Thick and thin blood smears were prepared from each individual and stained with 10% Giemsa by experienced microscopists to exclude mixed infection with *P. falciparum*. In addition, gametocyte and asexual parasite densities were determined for all *P. vivax*-positive patients by counting the number of parasites per 500 leukocytes in a thick blood smear under oil immersion microscopy. The raw counts were converted into parasites/microliter by assuming a count of 8,000 leukocytes/μL. If gametocytes were present, the patient was asked to enrol in the study. After the patients were briefed on the project and completed consent forms, approximately 5 mL of blood was collected by venepuncture and used for membrane blood feeding (detailed below) of starved mosquitoes. After mosquito feeding, the volunteers were released from the study and received antimalarial treatment. {#F1} {#F2} Mosquitoes ---------- *An. sinensis* and *An. anthropophagus* have been maintained in the insectary of the Key Technical Laboratory for Prevention and Control of Parasitic Diseases of the Ministry of Health (MOH) in the Jiangsu Institute of Parasitic Diseases (JIPD), Wuxi, China, for over 30 years. The mosquitoes were reared at 27 ± 1°C with a relative humidity of 70--80% and provided with 10% (w/v) glucose in water. One hundred mosquitoes in each carrying cage were transported from JIPD to the field sites in a cooler box. Next, 6- to 8-day-old mosquitoes were provided only water for 12 hours prior to blood feeding. In this study, engorged female anopheline mosquitoes from Bengbu, Anhui, were also collected, and their progeny (F1) were identified via both morphological characteristics and an rDNA ITS2-based method \[[@B5]\] to confirm species. The mosquitoes were maintained as described above, prior to blood feeding. Membrane feeding ---------------- Five hundred microliters (500 μL) of whole blood from each patient were centrifuged at 5,000 g for 5 minutes. The serum was then removed and replaced with approximately 300 μL of AB serum from a *P. vivax-*naive donor. The packed red blood cells and donor sera were carefully mixed and added to the membrane feeder. A constant-temperature (37°C) circulating-water system was used to prevent exflagellation of microgametocytes \[[@B10]\]. The blood feeding lasted for 30 minutes, after which the glass membrane feeder was removed from the top of the carton and all the unengorged mosquitoes were removed and freeze-killed. After feeding, all engorged mosquitoes were transported back to JIPD's insectary in Wuxi, where they were provided with a 12-h light/dark cycle and daily sugar solution before dissection. Mosquito dissection ------------------- On day 7 post-blood feeding, the mosquitoes were aspirated into glass tubes and immobilized by placing the tube on ice. At least 10 midguts of each species were dissected in a drop of mercurochrome in phosphate-buffered saline, and the number of oocysts per midgut was counted under 10× or 40× microscopic examination. On day 14 post-feeding, if the mosquitoes were oocyst-positive, another 10 mosquitoes of each species were dissected, and the number of oocysts per midgut was first counted, as above. Then, the infecting sporozoite level was recorded after direct determination under phase contrast microscopy (Leica DM2500, US) without staining. The level was recorded as follows: "+", 1--10 sporozoites; "++", 11--100 sporozoites; "+++", 101--500 sporozoites and "++++", \>500 sporozoites. Statistical analysis -------------------- The chi-square test was used to compare the proportion of mosquitoes infected with oocysts, the proportion of mosquitoes infected with sporozoites, and the proportion of infected mosquitoes per positive feeding, between paired lab-colony *An. anthropophagus* and *An. sinensis*, and between paired F1 and lab-colony *An. sinensis*. Paired T tests were used to compare oocyst loads (mean oocyst number per infected midgut) between the feeding groups. A regression test was used to detect any linear correlation between parasite load and infection rate. Ethical approval ---------------- All human-subject research conducted in this study was reviewed and approved by the Institutional Ethics Committee of the National Institute for Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention. All the patients involved in this study read and signed the informed consent forms. Results ======= Patient data ------------ From 2005 to 2007, over 200 symptomatic malaria patients came to the clinic in Bengbu, Anhui. In total, 142 volunteers were finally enrolled in this study after excluding subjects aged less than 18 years and those with mixed infections with *falciparum* malaria, or zero gametocytes by thick blood-smear count. Patient age and parasite density data are shown in Table [1](#T1){ref-type="table"}. ###### Age and parasite density of the study patients (n = 142)   **Minimum** **Maximum** **Average** -------------------------------- ------------- ------------- ---------------- Age of patients (years) 18 71 34.6 ± 3.1 No. of asexual parasites (/μL) 0 21696 4332.8 ± 371.2 No. of macrogametocytes (/μL) 32 6560 1057.6 ± 88 No. of microgametocytes (/μL) 64 4800 486.4 ± 51.2 Membrane feeding ---------------- In total, the blood of 142 *vivax* patients was fed via membrane feeding to the laboratory colonies of *An. sinensis* and *An. anthropophagus*. Among these 142 patients, blood from 10 patients was also fed to lab-colony and F1 *An. sinensis* mosquitoes. The engorged feeding percentages of the paired laboratory strain *An. sinensis* and *An. anthropophagus* were 64.86% (9210/14200) and 62.86% (8926/14200), respectively. The F1 *An. sinensis* had the lowest engorged feeding rate, at 16.5% (165/1000) (χ2 = 934.05, p \< 0.01). Oocyst number and sporozoite index were counted and recorded using a normal and phase-contrast microscope, respectively (Figure [3](#F3){ref-type="fig"}). The positive oocyst feed rate (positive feeds/total feeds) and positive mosquito infection rate (positive mosquitoes/total mosquitoes) of the lab-colony *An. sinensis* and *An. anthropophagus* did not differ at day 7 post-blood feeding (χ2 = 0.82, P \> 0.05, χ2 = 3.22, P \> 0.05, respectively). Likewise, the positive sporozoite feed rate and positive mosquito infection rate at day 14 post-blood feeding did not differ (χ2 = 0.09, P \> 0.05, χ2 = 0.21, P \> 0.05, respectively) (Table [2](#T2){ref-type="table"}). In 10 paired cases, both the F1 and laboratory strain had the same positive oocyst feed (80%) and sporozoite feed (30%) rates. In the 10 paired membrane feeding tests, the lab-strain *An. sinensis* had a higher oocyst infection rate at day 7 than F1 (Figure [4](#F4){ref-type="fig"}), as did the laboratory strain *An. sinensis* in the 142 paired feedings with laboratory strain *An. anthropophagus* (Figure [4](#F4){ref-type="fig"}). However, interestingly, the two laboratory strains had similar sporozoite levels at day 14 post-feeding (z = 0.866, *p* = 0.38, Table [3](#T3){ref-type="table"}). {#F3} ###### **Comparison of blood feeding, and oocyst and sporozoite infection, for*An. sinensis*and*An. anthropophagus*** **Species** **% of feeds infecting mosquitoes** **% of mosquitoes that fed on all infectious patients that developed parasite infection** **Mean number of oocysts per positive mosquito** ---------------------------- ------------------------------------- ------------------------------------------------------------------------------------------- -------------------------------------------------- ----------------- ------------------ Days post-feeding 7 14 7 14 7 *An. sinensis* (Lab) 72.5 (103/142) 28.9 (41/142) 45.7 (15536/340) 11.1 (135/1216) 45.7 (15536/340) *An. sinensis* (F1) 80.0 (8/10) 30.0 (3/10) 13.4 (281/21) 20.0 (9/45) 13.4 (281/21) *An. anthropophagus* (Lab) 67.6 (96/142) 26.8 (38/142) 21.0 (6437/306) 11.84 (96/811) 21.0 (6437/306) {#F4} ###### **Sporozoite infection of*An. sinensis*and*An. anthropophagus*14 days' post-feeding** **Sporozoite infective level** **No. of sporozoites** -------------------------------- ------------------------ ---- \+ 12 10 ++ 42 24 +++ 31 19 ++++ 50 43 Total 135 96 \*: "+", 1--10 sporozoites; "++", 11--100 sporozoites; "+++", 101--500 sporozoites and "++++", \>500 sporozoites. Correlation of parasitemia and infection ---------------------------------------- In total, 41/103 and 38/96 infected lab-colony *An. sinensis* and *An. anthropophagus*, respectively, developed sporozoites in the salivary glands at 14 days' post-blood feeding. The other 62 and 58 respective cases only had oocysts in the midgut at day 7 post-feeding, and 32 of 142 cases were negative for both oocyst and sporozoite infection in both *An. sinensis* and *An. anthropophagus* (Table [4](#T4){ref-type="table"}). The effects of parasite density (macrogametocyte, microgametocyte, asexual-stage parasite) and ratio of macrogametocytes to microgametocytes, in the five groups referred to above, were evaluated. The parasite density or the ratio of macrogametocyte to microgametocyte had no effect on parasite infection as the data showed that there was no significant difference between the negative and positive cases. However, in cases of positive infection, regression analysis revealed a significant linear correlation between blood gametocyte density and midgut parasite infection load in both *An. sinensis* and *An. anthropophagus.* The cases with more oocysts or sporozoites had higher gametocytemia levels, particularly in the sporozoite-positive cases (Figure [5](#F5){ref-type="fig"}). ###### **Parasitemia and oocyst and sporozoite infection in*An. sinensis*and*An. anthropophagus*** **Species** ***An. sinensis*** ***An. anthropophagus*** ***An. sinensis/An. anthropophagus*** ------------------------------------- -------------------- -------------------------- --------------------------------------- ---------------- ---------------- Cases 62 41 58 38 32 Mean oocysts/midgut 20.81 58.03 18.36 53.68 0 Mean gametocyte density (/μL) 1579.6 ± 154.8 1682.3 ± 255.4 1618.2 ± 163.4 1652.2 ± 267.9 1386.5 ± 254.0 Mean asexual parasite density (/μL) 4308.2 ± 444.4 5061.8 ± 709.6 4325.0 ± 456.6 4329.7 ± 663.2 3781.5 ± 714.2 Female gametocytes/male gametocytes 3.24 ± 0.25 3.41 ± 0.46 3.31 ± 0.26 3.07 ± 0.35 3.98 ± 0.92 {#F5} Discussion ========== This is the first study to evaluate the susceptibility of *An. sinensis* to *vivax* parasites in central China by membrane feeding, after the re-emergence of malaria in central China. In this study, *An. sinensis* (both laboratory colony and F1) were equally susceptible to *vivax* malaria parasites as *An. anthropophagus,* which was believed for many years to be the major vector in central China. Despite that belief, the laboratory colony of *An. sinensis* had a higher oocyst infection rate. Although the same was not found in the F1 mosquitoes, their low observed *vivax* susceptibility could have been due to their low engorged feeding rate, caused by the switch of emergent environment from field to laboratory. In addition, the difficulty of maintaining the engorged mosquitoes under laboratory conditions cannot be ignored \[[@B11]\], as this definitely reduced the quantity of mosquitoes dissected at day 7 post-feeding. Furthermore, in the 10 paired cases, both laboratory and field *An. sinensis* mosquitoes presented the same infection rate and 100% concordance with the positive case selection (both positive oocyst and sporozoite feedings), suggesting the lab-colony *An. sinensis* in this study could well represent actual current vector susceptibility to parasites in the field. In this case, *An. sinensis* was more able to carry *P. vivax* in the midgut stage than *An. anthropophagus,* given an equal opportunity to feed on malaria patients. This contrasts with previous results in central China \[[@B12]\]. Indeed, only mosquitoes with sporozoites in the salivary glands can infect humans, although both *An. sinensis* and *An. anthropophagus* had similarly low sporozoite infection rates in this study, which should raise some suspicion \[[@B13]\]. However, it is reasonable to note that malaria parasites also reduce mosquito survival rates \[[@B14]\]. In addition, our objective was to evaluate the susceptibility of *An. sinensis* compared with *An. anthropophagus* and not to count sporozoite quantities long-term. Both mosquito species had more sporozoites after 14 days' post-feeding than at 14 days. Thus, oocyst infection in the midgut stage could reflect potential transmission capacity. A well-known preference for human biting, a tendency to rest indoors, and great susceptibility to parasites with sufficient longevity, are essential criteria for evaluating vectors for malaria transmission capacity. In China, although *An. sinensis* is the most widely distributed, with a large population in most mainland regions, the species had for decades been judged not to be the predominant vector for malaria due to its exophilic and exophagic features, and relatively low susceptibility to parasites compared with other vectors. Nevertheless, the *vivax* malaria outbreak in 2005 in central China, in which *An. sinensis* served as the main vector, suggested an updated evaluation of the vector capacity and transmission role of this species was necessary \[[@B15]\]. Along with agricultural and industrial progress in China, frequently moving populations have become an important group at risk of carrying parasites from malaria-epidemic areas to malaria-free or low-transmission regions. During the malaria transmission season, from June to September, farmers and construction workers habitually sleep in the open without net protection, which increases the chance for *An. sinensis*, which in this study had a strong propensity to develop *vivax* malaria parasites following blood-feeding from infected humans, to bite several different people. Due to the exophilic nature of *An. sinensis* and continuously increasing insecticide resistance \[[@B16]-[@B21]\], the regular insecticide residual spray (IRS) methods used in malaria-transmission regions do not kill all mosquitoes \[[@B22]\]. Another possible reason for the malaria outbreak in central China is climatic and environmental change \[[@B10]\]. If *An. sinensis* mosquitoes are unable to find their usual animal blood feeding targets, because of the construction of buildings or other such changes, they may resort to biting humans \[[@B23]\]. Only macrogametocytes and microgametocytes can develop in the mosquito midgut; all other asexual parasites are digested after blood feeding. This study supports the previous finding that although the average asexual parasitemia counts in the negative feed groups were lower than the positive feed groups, no significant differences were found \[[@B24]\]. This was also supported by some positive feeds with zero asexual parasites somehow achieving a high oocyst infection number; however, the oocysts were absent in the midgut in some cases with high asexual parasite counts. Although the same phenomenon was noted with the relationship of gametocytemia to midgut infection in the negative and positive groups, oocyst load (oocysts per positive mosquito) increased with gametocyte density in all infection-positive groups, suggesting that the blood of patients with high levels of gametocytemia had a greater potential to induce mosquitoes, post-feeding, to develop oocysts in the midgut and thereby be at higher risk of transferring parasites to other humans. Although the results from this study confirm the previous finding that oocysts developed well in the mosquito midgut, with a ratio of macrogametocytes to microgametocytes of less than 4 \[[@B25]\], the number of negative-infection cases producing oocysts in this study demonstrated that the presence of oocysts in the midgut following feeding is not a good indicator of infectivity, a conclusion supported by a study in west Thailand \[[@B26]\]. The malaria parasite is under intense attack from the mosquito's innate immune system during its development in the midgut and salivary glands \[[@B27]\]. Several mosquito immune genes play important roles in the parasite evasion stage by influencing parasite-mosquito interactions \[[@B28]-[@B30]\]. In other words, the susceptibility of mosquitoes to malaria infection could be related to an enhanced or weakened immune response of mosquitoes to parasite infection \[[@B31]\]. Additionally, the genotypes of the invading parasites play an important role, i.e., parasites with VK210 and VK247, two main genotypes of circumsporozoite protein (CSP), have an obvious preference for infecting mosquitoes \[[@B32]\]. Therefore, further study of the susceptibility of *An. sinensis* to parasites from various geographic areas in China is necessary. Although the direct-feeding method more accurately reflects epidemiologic reality \[[@B33]\], most volunteers prefer to provide blood by venepuncture rather than allowing mosquitoes to bite their skin directly \[[@B34]\]. In the membrane-feeding assay used in this study, patient sera were replaced by naive malaria-free human AB serum, to avoid interference from varying antibody levels in patient blood samples \[[@B35]\]. Furthermore, the constant-temperature cycling system allowed unlimited maintenance of parasite activity and equalised blood-feeding conditions among the mosquito groups \[[@B36]\]. The membrane feeding assay is a valuable tool for the evaluation and validation of candidate markers of transmission-blocking vaccine (TBV) following the modification of target genes \[[@B37],[@B38]\]. Because *An. sinensis* is the largest of the four major vectors in China, as well being relatively easier to maintain under laboratory conditions, and with high susceptibility to *vivax* parasites, it could be used as a valuable candidate species to evaluate TBV, in particular. Compared to the previous studies \[[@B39],[@B40]\] the *An sinensis* from this study showed higher susceptibility rates to *P. vivax* isolates in Central China, although it is known that the *An. sinensis* strain from Korea, China and Japan was compatible genetically and/or nearly identical to that from Thailand, based on the crossing experiments and comparative sequence analyses of the ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS2) \[[@B41]\]. The genetic diversity of the parasites and their compatibility to the vectors in each location may contribute to the difference in vector susceptibility. In this study we did not analyse the genetic diversity of the parasites as the study aimed to compare the susceptibility of *An. sinensis* and *An. anthopophagus* in Central China to the same parasite isolates collected in this region. Conclusions =========== To our knowledge, this is the first report of the susceptibility of the widely distributed malaria vector *An. sinensis* to *P. vivax* following artificial membrane feeding after the re-emergence of malaria in central China. The *An. sinensis* mosquitoes in the laboratory maintained a similar capacity to become infected with *vivax* parasites as the field mosquitoes, and their parasite-carrying ability was also similar to that of *An. anthropophagus*. The vector capacity of *An. sinensis* for malaria transmission during the *vivax* re-emergence period, particularly in central China, has probably been underestimated. Due to its morphological characteristics and high susceptibility to parasites, *An. sinensis* could be a good vector candidate for *vivax* malaria TBV evaluation. Competing interests =================== The authors declare that they have no competing interests. Authors' contributions ====================== GD, QG, and JS contributed equally to the study design and data analysis. HX, HY, JL, FL, YB and JC managed the parasites and mosquitoes in the field. GD, HY, JL and YB contributed to the dissection of mosquitoes. GD drafted the manuscript. QG provided scientific supervision. JS revised the manuscript. All authors read and approved the final manuscript. Acknowledgements ================ We acknowledge the outstanding technical support of the entomology teams of the Armed Forces Research Institute of Medical Sciences (AFRIMS, Bangkok, Thailand). We are grateful to Qiang Fang, Zhiyong Tao and Kaiming Hu from Bengbu Medical College for their assistance in field work and are grateful to Ming-chieh Lee from the Program in Public Health, University of California at Irvine, USA, for drafting the map. This research was supported by the US Military Infectious Diseases Research Program, Jiangsu Province's Construction project (BM2009902) and Jiangsu Province's Medical High Tech Platform (ZX201108).

Plesná (Cheb District) Plesná () is a town in the Czech Republic. History The first written record of the town dates back to 1185, when it belonged to Waldsassen Abbey. The population was 1,953 inhabitants in 2016. Local districts Lomnička (Lomnička u Plesné) Plesná (Plesná a Šneky) Smrčina Vackov Sights There are ruins of Neuhaus castle located approximately two kilometres to the south of the town. It could be a mansion of ministeriales of Plesná mentioned in 1197, but according to another source, it is a different mansion of unknown origin. Crucifix. Gallery References External links Municipal website Category:Cities and towns in the Czech Republic Category:Populated places in Cheb District

Application of baited remote underwater video stations to assess benthic coverage in the Persian Gulf. A baited remote underwater video station (BRUVS) is generally considered an appropriate sampling tool for fish. The applicability of BRUVS to determine the substrate coverage was assessed by comparing stills from BRUVS videos to traditional point intercept transect (PIT) data to estimate percentage cover (PC) of different benthic substrate categories. Mean PCs of hard corals, rock, sand, and coral growth forms yielded statistically identical values with the two survey methods, while PCs of motile epibenthic invertebrates were underestimated by BRUVS in areas of both high and moderate relief. Yet, multivariate analyses revealed that the two methods yield similar substrate assemblage in an area of moderate relief. Results of our study suggest that the BRUVS can be effectively used to quantify both the presence/absence of a basic set of benthic habitat characteristics and diversity of coral growth forms on coral reefs in the Persian Gulf.

Grand Theft Auto 5 Trailer: First-Person Mode 2.0 We had no idea that seeing Los Santos through the eyes of Trevor would be so beautiful. Rockstar Games has revealed that it redefined the first-person perspective of Grand Theft Auto V. While most GTA games have had some form of a first-person perspective in the past, it was always limited. Most of the time, you could only look around in first-person and the camera would zoom back out to a third-person view once your character started moving. While driving, the first-person perspective was always placed in front of the bumper of the car to give you an optimal view. Now, Rockstar Games is redefining GTA's first-person experience, letting you play the entire game from the eyes of either Trevor, Michael or Franklin, depending on who you are controlling of course. Just look at that trailer and see all the changes. Each vehicle has had its interiors redone to have authentic tachometer and speedometers that react to how you drive. If your character is wielding a gun, you will see the gun in front of you like an FPS. We were scared that piloting helicopters would be a pain, but this trailer proved us wrong. Grand Theft Auto V will launch for the PlayStation 4 and Xbox One on Nov. 18 and PC on Jan. 27, 2015.

Q: Why doesn't OnProgressUpdate in an AsyncTask get called? Using Xamarin.Android, however, I don't think it's the reason behind my issue. The problem I am facing is that the OnProgressUpdate method only gets called once in an AsyncTask object I'm using handle a background task. Here is my class: public class DBInflater : AsyncTask { private int progress; private ProgressBar progressBar; public DatabaseInflater(ProgressBar progressBar) { this.progressBar = progressBar; } protected override void OnPreExecute() { base.OnPreExecute(); } protected override Java.Lang.Object DoInBackground(params Java.Lang.Object[] @params) { System.Threading.Tasks.Task.Run([some heavy task]); while (progress < 100) { Java.Lang.Thread.Sleep(500); PublishProgress(progress); progress += 1; } return true; } protected override void OnProgressUpdate(params Java.Lang.Object[] values) { progressBar.Progress = progress; } protected override void OnPostExecute(Java.Lang.Object result) { base.OnPostExecute(result); } } I've managed to narrow down the problem to this line: Java.Lang.Thread.Sleep(500); If I use a smaller value for the sleep, the OnProgressUpdate won't get called after the first time. I landed on 500 because with this value, OnProgressUpdate gets called properly and the progressBar updates on the screen. Is there a reason why I have to sleep the Thread at a certain interval? I'd like the progressBar to update in real time, not every half second. A: Running something in Task thread within DoInBackground method that does not report its progress does not make any sense. When DoInBackground is called you are not on the UI thread but a background thread, you can check via checking the value of Looper.MainLooper.IsCurrentThread, so using Task.Run is not necessary. So once in DoInBackground your DB Inflater will assumably do a series of steps, creating the DB, creating tables, indexes, etc.. then loading each of the tables with data, etc... It is up to you to determine the amount of progress that has happened and publish it (PublishProgress). In this example, I have three steps and report a 33% increase in the competition after completing each step. public class DBInflaterAsyncTask : AsyncTask { protected override Object DoInBackground(params Object[] @params) { // You are not on the UI thread Task.Delay(1000); // create db PublishProgress(new Object[] { 33 }); Task.Delay(1000); // create tables PublishProgress(new Object[] { 66 }); Task.Delay(1000); // load table data PublishProgress(new Object[] { 99 }); return null; } protected override void OnProgressUpdate(params Object[] values) { // You are on the UI thread Log.Debug("SomeTag", values[0].ToString()); } }

Alice Timbilil Alice Jemeli Timbilil (born 1 February 1983 in Moiben, Uasin Gishu District) is a Kenyan professional long-distance runner. She is a two-time Olympian, having competed over 10,000 metres at both the 2000 and 2004 Summer Olympics. She initially started her career on the track, becoming the World Youth Champion in the 10,000 m and running at the 1999 World Championships in Athletics at the age of sixteen. She won a junior silver medal at the 2000 IAAF World Cross Country Championships and made her Olympic track debut the following year. She continued to mix track and cross country, making her second Olympic appearance at the 2004 Athens Games and securing a senior silver at the 2005 IAAF World Cross Country Championships. After taking 2006 out due to the birth of her first child, she returned in 2007 and switched her focus to road running competitions. She represented Kenya at the 2007 IAAF World Road Running Championships and won the Saint Silvester Road Race. She made her marathon debut in 2008 and took her first win in the event two years later at the 2010 Amsterdam Marathon. Career World youth champion Timbilil started running while at Kemeliet Primary school. She won Kenyan Championships in 10,000 metres in 1999, aged only 16. At the 1999 World Youth Championships in Athletics she won 3000 metres gold medal. She competed also at the 1999 World Championships, but did not finish the 10,000 metres final after seemingly miscalculating the number of laps. She did not start high school until 2000, aged 17, when she joined Kapkenda Secondary School. It was in the field of cross country running that she gained her first major junior medal, running at the 2000 IAAF World Cross Country Championships. Timbilil took the silver medal behind Vivian Cheruiyot, completing a Kenyan sweep of the medals which led the junior women to the team gold. At the age of seventeen, she gained selection for the 2000 Sydney Olympics and reached the 10,000 m final, finishing in fourteenth place with a personal best run of 31:50.22. She was still eligible for the junior competition at the 2001 IAAF World Cross Country Championships, but she was far from medal-winning form and finished in sixteenth place. World cross country medallist She took a cross country circuit wins at the Cinque Mulini in 2003 and the Oeiras International Cross Country in 2004. At the 2004 IAAF World Cross Country Championships she just missed out on the medals by finishing in fourth place behind Werknesh Kidane, although she did lead the Kenyan women to a team silver medal in the long race. She took to the Olympic stage for a second time later that year, but she failed to build on her cross country success at the 2004 Athens Games and finished in sixteenth place in the 10,000 m Olympic final. She delivered in the long race at the 2005 IAAF World Cross Country Championships the following year, however, as she edged between Tirunesh Dibaba and Werknesh to take her first major senior medal, and also leading Kenyan to a consecutive team silver behind Ethiopia. Returning to the track, she ran at the 2005 World Championships in Athletics but did not manage to finish the race, repeating her disappointing World performance of six years earlier. Focus on road running Timbilil won the Saint Silvester Road Race in 2007, running 15 km in 53:07. At the 2007 IAAF World Road Running Championships she finished in ninth place. She made her marathon debut at the 2008 Paris Marathon and she set a time of 2:26:45 for fifth position. Her first major race of 2010 came at the Roma Ostia Half Marathon in February, which she won in a time of 1:10:34, beating home favourite Rosaria Console. Timbilil took part in the 2010 BIG 25 road race in Berlin in May and took second place with 1:24:38, although this was over three and a half minutes slower than Mary Keitany who set a world record. She took on Keitany at the Portugal Half Marathon and was second best again, although she beat the rest of the field by some twenty seconds. At the 2010 Amsterdam Marathon, she was among the leaders from the start and by the 35 km mark she had outrun the field, eventually winning the race by a margin of two minutes with a personal best of 2:25:03. She ended the year by setting a course record at the Saint Silvester Road Race. In 2010, she not only won her first marathon, but had improved all her personal bests over 10K, 15K, 25K and the marathon. She was runner-up at the Goyang Half Marathon then placed eighth at the 2011 Boston Marathon the following month. In July she was runner-up at the Peachtree Road Race and winner of the Boilermaker Road Race, but did not compete again until late 2013. After a runner-up finish at a half marathon in Kisii she returned to the major circuit with a third-place finish at the Amsterdam Marathon. Personal life She is married to Mark Sinyei (a farmer) and she gave birth to their first son, Collins Kimutai, in March 2006. She comes from an athletic family which includes runner and African Champion Nancy Lagat – her aunt. Timbilil is managed by Federico Rosa and is based at the Nike camp in Kaptagat. She comes from the same village as another female runner Vivian Cheruiyot Competition record 5 km Cross Country in Grand Prix Media Blenio Philadelphia Half Marathon Saltillo Half-Marathon New Delhi Half Marathon. 2009 Lisbon Half Marathon. 2010 Roma Ostia Half Marathon References External links Marathon Info profile Category:1983 births Category:Living people Category:People from Uasin Gishu County Category:Kenyan female long-distance runners Category:Kenyan female marathon runners Category:Olympic athletes of Kenya Category:Athletes (track and field) at the 2000 Summer Olympics Category:Athletes (track and field) at the 2004 Summer Olympics Category:World Athletics Championships athletes for Kenya Category:Kenyan female cross country runners

Developmental changes in myocardial mechanical function and subcellular organelles. This study investigates the developmental changes in myocardial mechanical function and the function of subcellular organelles. Mechanical function was determined at various Ca2+ concentrations ( [Ca2+]0) in the isolated, arterially perfused heart of the fetus (28th day of gestation), newborn (3-5 day old), and adult rabbit. Maximal force of contraction in the fetus (observed at 7.5 mM [Ca2+]0) was significantly less than that in the newborn (observed at 30 mM ( [Ca2+]0), and both the fetus and newborn values were significantly less than that in the adult (observed at 15 mM [Ca2+]0). The myofibrillar content in the fetus and ATPase activity in the fetus and newborn were significantly less than in the adult at pCa 4 and 5 where this enzyme was maximally activated. Both the amount of sarcoplasmic reticulum (SR) and SR Ca2+ uptake per gram of muscle increased with age. Mitochondrial Ca2+ uptake was not observed at pCa more than 6 (physiological range) in all age groups. At pCa less than 6, mitochondrial Ca2+ uptake (per g muscle) in the newborn was significantly greater than in the fetus and adult. Ca2+ uptake by crude homogenate in the newborn was also greater than in the fetus and adult. These data suggest that the age-related change in myocardial contractility is due to the differences in intracellular Ca2+ concentration and myofibrillar content as well as ATPase activity. Intracellular Ca2+ concentration may vary with development depending on the relative capability of Ca2+-releasing system and Ca2+-sequestering system.

Q: Why doesn't my if-then statement in Scratch ever trigger? I have been using Scratch for a few months, but am suddenly completely and inexplicably stuck. I can't get a simple if-then condition to trigger. After stripping down to the bare essentials, I have this: the variable d successfully changes when I press space, but never triggers the if-then, even when d=5, as confirmed by the display. What am I missing? A: You need to add the variable to the expression, like this (Notice the orange color of d, drag it from the section "Variables"):

Secretion of N-terminal fragment of gamma-human atrial natriuretic polypeptide. To elucidate the posttranslational processing of gamma-human atrial natriuretic polypeptide (human atrial natriuretic factor-[1-126]), which is a prohormone of alpha-human atrial natriuretic polypeptide (human atrial natriuretic factor-[99-126]), and the secretion of gamma-human atrial natriuretic polypeptide-derived peptides from the heart, we established a radioimmunoassay specific for the N-terminal sequence of gamma-human atrial natriuretic polypeptide, gamma-human atrial natriuretic polypeptide-(1-25), as well as a radioimmunoassay for alpha-human atrial natriuretic polypeptide. With the aid of the radioimmunoassays for gamma-human atrial natriuretic polypeptide-(1-25) and for alpha-human atrial natriuretic polypeptide, we detected 290 +/- 35.6 pg/ml of gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity in plasma from healthy humans, while the simultaneously determined plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity level was 20.9 +/- 2.8 pg/ml. Correlation between the two values was significant. High performance gel permeation chromatographic analysis revealed that the plasma gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity was composed of a component (molecular weight, 10,000) without alpha-human atrial natriuretic polypeptide-like immunoreactivity, while the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity was composed of alpha-human atrial natriuretic polypeptide with a molecular weight of 3000. In patients with heart diseases, the plasma gamma-human atrial natriuretic polypeptide-(1-25)-like immunoreactivity level showed a concomitant and graded increase, with the plasma alpha-human atrial natriuretic polypeptide-like immunoreactivity level in agreement with the severity of the disease. There were significant positive correlations between the two immunoreactivity levels and right or left atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Background {#Sec1} ========== *Helicobacter pylori* is a Gram-negative, spiral-shaped bacterium that colonizes the gastric mucosa in humans. In many cases, it can persist without causing symptoms, although in some cases it can produce chronic gastritis. The persistent colonization of the gastric mucosa by *H. pylori* can lead to the development of gastroduodenal diseases like peptic ulcer, gastric lymphoma, and gastric cancer \[[@CR1]\]. *H. pylori* has two main virulence factors, the *cag* pathogenicity island (*cag*PAI) and the pore forming toxin *vacA*, whose presence or absence identifies highly virulent (type-1) from less virulent (type-2) strains, respectively, thus being strong predictors of severe disease outcome \[[@CR2], [@CR3]\]. The *cag*PAI is a 40-kb chromosomal region that contains 27--31 genes that encode the type IV secretion system (T4SS) and an effector protein \[[@CR4]\]. The T4SS forms a needle-like surface appendage called the T4SS pilus, which is induced upon contact with the host cell membrane \[[@CR5]\]. The effector protein CagA is encoded by the *cagA* gene. This protein is translocated into the cytoplasm of the gastric epithelial cells through the T4SS, where it is phosphorylated at the tyrosine residues of the EPIYA motifs, causing multiple cellular alterations \[[@CR6], [@CR7]\]. One of the genes that encode the T4SS is *cagL*, which encodes for the 26-kDa protein CagL. It has been shown that this protein is localized on the surface of the T4SS of *H. pylori* and in intracellular pools, is necessary for CagA translocation, and interacts with CagI \[[@CR5], [@CR8]\]. It also contributes to transient hypochlorhydria by disrupting the interaction between the integrin and metalloprotease ADAM17 and the integrin α~5~β~1~, thus activating NF-κB-mediated repression of the gastric H, K-adenosine triphosphatase α-subunit (HKα) \[[@CR9]\]. The role of some regions or motifs of CagL in different phenotypes has been assessed. For example, its C-terminal coiled-coil region is involved in IL-8 secretion, host cell elongation, and binding of the T4SS to the host cell \[[@CR10]\]. CagL also contains an arginine--glycine--aspartate (RGD) motif at residues 76--78, located within the second large α-helix \[[@CR11]\], which is essential for binding to the human integrin α5β1 receptor \[[@CR5]\], as well as integrins α~v~β~5~ and α~V~β~3~ \[[@CR12], [@CR13]\], although it can also bind to human fibronectin in a RGD independent manner \[[@CR14]\]. This motif is also responsible of CagL fibronectin-like effect on host cells, since it is involved in cell spreading triggering, formation of focal adhesions, and activation of several tyrosine kinases \[[@CR15]\]. The RGD motif is right next to the sequence LXXL, of which, the two-leucine residues (L79 and L82) contribute to the adhesion to different cell lines through interaction with integrin α~V~β~6~ \[[@CR16]\]. CagL also contains a second motif named RHS (RGD helper sequence), which contains residues phenylalanine--glutamic acid--alanine--asparagine--glutamic acid (FEANE). This motif also contributes to CagL binding to integrins \[[@CR17]\]. The third important region in CagL is the CagL hypervariable motif (CagLHM), which spans residues 58 to 62 \[[@CR18]\]. It is located in an unresolved flexible region between helices α1 and α2 \[[@CR19]\]. Although its function is still controversial, it has been shown that certain polymorphisms correlate with diseases in a geographical-dependent manner. For example, polymorphism Y58/E59 is associated with gastric cancer in patients from Taiwan, while in India the polymorphism associated with this disease is D58/K59 \[[@CR20], [@CR21]\]. In Mexico, only the polymorphism N58 has been associated with a higher risk of gastric cancer \[[@CR22]\]. So far, 33 combinations of polymorphisms in the hypervariable motif have been identified worldwide, the most common being DKMGE, NEIGQ, NKIGQ, and DKIGK. Of these, all are found in North and South American strains, except for DKIGK, which is more prevalent in East/Southeast Asia/Australasia \[[@CR23]\]. The aim of this work was to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the *vacA* genotype of *H. pylori*. Results {#Sec2} ======= *Helicobacter pylori* prevalence {#Sec3} -------------------------------- We analyzed 164 patients with histopathological diagnosis of chronic gastritis, of which 61.6% (101/164) were female, and 38.4% (63/164) were male. The mean age of the patients was 48 years old (± 17), ranging between 19 and 89 years old. The frequency of *H. pylori* isolation was 30.5% (50/164). All strains identified as *H. pylori* by culture were confirmed by PCR amplification of a fragment of the 16S rRNA gene (Fig. [1](#Fig1){ref-type="fig"}a).Fig. 1Representative gels of PCR amplified fragments. **a** 16S RNA fragment. Lanes: MW---molecular weight marker (bp), NC---negative control, PC---positive control (DNA from strain ATCC 43504), 4 to 7---clinical isolates UEGE-640, UEGE-697, UEGE-748, and UEGE-752. **b** *cagL* fragment amplified with the first set of primers (651 bp). Lanes: MW---molecular weight marker (bp), NC---negative control, PC---positive control (DNA from strain ATCC 43504), 4 to 7---clinical isolates UEGE-640, UEGE-696, UEGE-847, and UEGE-752. **c** *cagL* fragment amplified with the second set of primers (165 bp). Lanes: MW---molecular weight marker (bp), NC---negative control, PC---positive control (DNA from strain HP26695), 4 to 7---clinical isolates: UEGE-845, UEGE-652, UEGE-748, and UEGE-752. **d** *cagL* fragment amplified with the third set of primers (611 bp). Lanes: MW---molecular weight marker (bp), NC---negative control, PC---positive control (DNA from strain HP26695), 4 to 7---clinical isolates: HG-65, HG-155, HG-177, and UEGE-748 Thirty-six of the 50 clinical isolates (72%) were *cagA* positive, and 40 (80%) had the most virulent *vacA* genotype (s1/m1). Of the *cagA* positive strains, 94.4% were *vacA* s1/m1 (Table [1](#Tab1){ref-type="table"}). In the *cagA* negative isolates, absence of the *cag*PAI was confirmed by empty site PCR.Table 1Frequency of *cagA* and *vacA* genotypes in clinical isolates of *H. pylori* from patients with chronic gastritis*cagA*PositiveNegativen = 36 (100%)n = 14 (100%)*vac*A s1/m134 (94.4%)6 (42.9%) s1/m21 (2.8%)0 s2/m21 (2.8%)8 (57.1%) Prevalence of *cagL* {#Sec4} -------------------- A PCR product of 651 bp was amplified in 24 of the 36 *cagA* positive clinical isolates (Fig. [1](#Fig1){ref-type="fig"}b) using primers cagL sense and cagL antisense (Table [4](#Tab4){ref-type="table"}). To determine if the 12 remaining strains were *cagL* negative, we performed a second PCR using primers cagL-Fwd-2 and cagL-16 (Table [4](#Tab4){ref-type="table"}). A product of 165 bp was amplified in the 12 strains (Fig. [1](#Fig1){ref-type="fig"}c), indicating that all *cagA* positive strains contain the *cagL* gene. In order to obtain sequences suitable for uploading in the GenBank (\> 200 bp), the DNA from those strains that were positive with the second set of primers was subjected to a third PCR using primers cagL-Fwd-2 and cagL antisense. With the new combination of primers, a product of 611 bp was amplified in 9 of the 12 strains (Fig. [1](#Fig1){ref-type="fig"}d), and the 33 PCR products amplified were sequenced. CagL polymorphisms {#Sec5} ------------------ The sequences of 33 of the 36 *cagL*^+^ clinical isolates were aligned with the sequence of strain ATCC 26695, showing a high level of conservation (Fig. [2](#Fig2){ref-type="fig"}). Motifs RGD and RHS are 100% identical in all strains.Fig. 2Sequence alignment of CagL from 33 clinical isolates registered in GenBank. Sequence from strain ATCC 26695 was used as reference. CagLHM, RGD, and RHS (FEANE) motifs are indicated in squares, black squares indicate the polymorphic region (residues 58 to 62), and the RDG and RHS motifs in the reference sequence. Polymorphisms are shown in gray. Accession numbers: MG051618-MG051641 and MG214979-MG214987 The most prevalent sequence in the polymorphic region (residues 58--62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33, respectively), DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33, respectively) (Fig. [3](#Fig3){ref-type="fig"}). One clinical isolate had four polymorphisms (3%) (UEGE-740), two had three polymorphisms (6.1%) (HG-193 and HG-211), one had only one polymorphism (3%) (HG-02), and the rest (87.9%) had two (Fig. [2](#Fig2){ref-type="fig"}). Interestingly, one of the clinical isolates with three polymorphisms (HG-193), and the one with four (UEGE-740) had the sequence DKI, which is more prevalent in East-Asian strains \[[@CR24]\].Fig. 3Frequency of sequences in the CagLHM motif (positions 58 and 62). Sequence DKMGE was found in 25 of 33 clinical isolates, sequences NKMGQ and NEIGQ in 2, and sequences DEIGQ, NKMGE, DKIGE, and DKIGK in 1 clinical isolate each. Frequencies are shown in percentages Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33) (Fig. [4](#Fig4){ref-type="fig"}). Only two isolates (6.1%) contained residues N58/E59 (HG-43 and HG-210), which correspond to those found in *H. pylori* strain ATCC 26695.Fig. 4Frequency of CagL polymorphisms in positions 58 and 59. Polymorphism D/K was found in 27 clinical isolates, polymorphism N/K in 3, polymorphism N/E in 2, and polymorphism D/E in 1. Frequencies are shown in percentages Our sequence alignment (Fig. [2](#Fig2){ref-type="fig"}) revealed that, besides the polymorphisms found in the CagLHM motif, there were other 19 polymorphisms both upstream and downstream of this region (Table [2](#Tab2){ref-type="table"}). The most common were A41, M73, K122, I134, and I175, being found in \> 9 strains; while the rest (F48, V48, T56, V99, A112, G140, A170, V171, I181, Q200, I203, K210, S216, and N221) were identified in \< 6 strains.Table 2CagL polymorphisms in strains isolated from patients with chronic gastritisResidue in 26695PolymorphismFrequency n (%)Strain (s)CagL regionV41A9/33 (27.3%)HG-44, -51, -150, -162, -189, -199, -224\ UEGE-640, -826α1I48F2/33 (6%)HG-70, UEGE-826L1V1/33 (3%)UEGE-696A56T2/33 (6%)HG-66, HG-193L1N58D28/33 (84.8%)HG-44, -51, -65, -66, -150, -155, -162, -177, -179, -189, -190, -193, -199, -211, -224,\ UEGE-640, -666, -696, -740, -748, -751, -752, -753, -843, -845, -846, -847, -852L1E59K30/33 (90.9%)HG-02, -44, -51, -65, -66, -70, -150, -155, -162, -177, -179, -189, -190, -193, -199, -224\ UEGE-640, -666, -696, -740, -748, -751, -752, -753, -826, -843, -845, -846, -847, -852L1M60I5/33 (15.1%)HG-43, -193, -210, -211,\ UEGE-740L1E62Q5/33 (15.1%)HG-43, -70, -210, -211\ UEGE-826α2K1/33 (3%)UEGE-740I73M20/33 (60.6%)HG-43, -51, -65, -66, -150, -162, -179, -189, -190, -224,\ UEGE-640, -666, -696, -748, -751, -752, -753, -843, -846, -852.α2I99V2/33 (6%)HG-44, UEGE-696α2T112A1/33 (3%)HG-70α3N122K27/33 (81.8%)HG-02, -44, -51, -65, -66, -70, -150, -155, -162, -177, -179, -190, -193, -199, -210, -211, -224\ UEGE-666, -696, -748, -751, -753, -826, -843, -845, -847, -852α4V134I27/33 (81.8%)HG-02, -44, -51, -65, -66, -70, -150, -155, -162, -177, -179, -190, -193, -199, -210, -211, -224\ UEGE-696, -748, -751, -752, -753, -843, -845, -846, -847, -852α5E140G6/33 (18.2%)HG-51, -66, -162\ UEGE-740, -753, -852α5T170A1/33 (3%)UEGE-740α5A171V1/33 (3%)HG-190α5T175I14/33 (42.4%)HG-02, -44, -65, -150, -155, -162, -179, -190, -199\ UEGE-748, -752, -826, -843, -846α5V181I1/33 (3%)UEGE-640α6H200Q6/33 (18.2%)HG-02, -44, -66, -177, -210\ UEGE-753α6V203I1/33 (3%)HG-43α6E210K2/33 (6%)UEGE-740, -843α6R216S2/33 (6%)HG-224, UEGE-740α6S221N2/33 (6%)HG-02, -66α6 CagL polymorphisms and *vacA* genotypes of *H. pylori* {#Sec6} ------------------------------------------------------ As mentioned before, polymorphisms in residues 58 and 59 have been associated with a higher risk of gastric disease, so we analyzed their relationship with the genotype of *vacA*. As seen in Table [3](#Tab3){ref-type="table"}, 80.6% (25/31) of the strains carrying the *vacA* genotype s1/m1 had the polymorphism D58/K59, while of the five isolates with polymorphism N58, 100% had the genotype *vacA* s1/m1 regardless of the polymorphism in position 59. These results suggest that the polymorphism D58/K59 correlates with genotype *vacA* s1/m1.Table 3CagL polymorphisms and *vacA* genotypes of clinical isolates of *H. pylori*CagL polymorphisms*vacA* genotype*p* values1/m1\ n = 31s1/m2\ n = 1s2/m2\ n = 1N58/E592 (6.5%)00N58/K593 (9.7%)00D58/K5925 (80.6%)1 (100%)1 (100%)\< 0.05\*D58/E591 (3.2%)00\* Fisher's exact test Phylogenetic relationship of CagL sequences {#Sec7} ------------------------------------------- Since we identified 4 polymorphic region sequences that have been found predominantly in Asian strains (NKMGQ, NEIGQ, DEIGQ, and DKIGK), we performed a phylogenetic analysis to determine if they are related. As shown in Fig. [5](#Fig5){ref-type="fig"}, at the bottom of the tree is a group formed by strains containing sequences NEIGQ and DEIGQ (HG-43, HG-210, and HG-211), and the reference strain ATCC 26695, which has the sequence NEMGE (found only in Europe). Related to this group is the strain carrying the sequence DKIGK (UEGE-740). Forming part of a second major group, which contains strains with sequences DKMGE and NKMGE, are the strains carrying the sequence NKMGQ. However, these are more related to the strain carrying the DKIGE sequence than to the rest.Fig. 5Phylogenetic tree of CagL sequences. Neighbor-Joining tree analysis of the CagL sequences of the 33 clinical isolates and strain ATCC 26695 Discussion {#Sec8} ========== Gastric diseases are of diverse etiology, and although chronic gastritis and more severe gastroduodenal disorders are attributed to *H. pylori*, Epstein--Barr virus and human Cytomegalovirus can also cause these diseases \[[@CR25]\]. In this study we found that the prevalence of *H. pylori*, determined by bacterial isolation, was 30.5%. This percentage is similar to that reported by Román-Román et al. (47.8%) \[[@CR26]\], but lower than that reported by other authors \[Paniagua et al. (60.1%); Martínez-Carrillo et al. (77%)\] \[[@CR27], [@CR28]\]. This variation in frequencies may be due to bias in the information provided by the patients; also, it is impossible to rule out that they have received antimicrobial treatment against *H. pylori* or any other infection in the recent past. Among the Mexican population self-medication is common and, although the sale of antibiotics without medical prescription is prohibited, in the state of Guerrero the metronidazole, an antiparasitic that is part of the treatment scheme for *H. pylori*, is available over the counter. Additionally, the probability of finding *H. pylori* in biopsies decreases as structural and functional changes appear in the infected mucosa. Another factor that may have contributed to the low frequency found in this work, is that the prevalence of *H. pylori* infection was determined by culture, which is a very specific method (95--100%) but not very sensitive (80--90%), since the results depend on the number of viable bacilli in the biopsy \[[@CR29]\]. Among infected patients, the clinical outcome is determined by the genetic background and lifestyle of the host, as well as by *H. pylori* virulence factors. It has been proposed that the *H. pylori* virulence factor CagL has an important role in the pathogenesis of gastroduodenal diseases, and that its function can be determined by the amino acid sequence in specific positions \[[@CR11], [@CR12]\]. We analyzed the prevalence of *cagL* in *H. pylori* clinical isolates from Mexican patients with chronic gastritis, which was 72%. This is a lower percentage than those found in Asian patients, \> 85% in Chinese, Indian, Iranian, Taiwanese and Malay patients \[[@CR20], [@CR21], [@CR30], [@CR31]\]; however, these patients had more severe diseases, like gastric cancer, peptic ulcer disease, and duodenal ulcer. Nevertheless, our result is higher to that found in Iranian patients with gastritis (64.2%) \[[@CR32]\]. Apparently, the prevalence of *cagL* in clinical isolates from patients with gastritis is lower than that found in isolates from patients with peptic ulcer disease or gastric cancer. All our *cagA*^+^ isolates were *cagL*^+^, which is in accordance with previous reports that have shown that the prevalence of *cagL* is higher than, or very close to that of *cagA* \[[@CR20], [@CR30], [@CR33]\]. We also analyzed the polymorphic region (residues 58 to 62) of CagL. We found that the most common polymorphism in position 58 corresponds to aspartic acid (D) (84.8%), followed by asparagine (N) (15.2%). It has been proposed that strains carrying aspartic acid at this position lead to a lower risk of gastric cancer in comparison with the asparagine carrying strains. In agreement with this, the polymorphism N58 was significantly associated with gastric cancer in Mexican patients from Mexico City \[[@CR22], [@CR32]\]. Regarding residue combinations in positions 58 and 59, polymorphism D58/K59 has been associated with gastric cancer in India, where patients carrying bacteria with this polymorphism are 3.8 times more likely to develop this disease \[[@CR20]\]. However, our results showed that D58/K59 was the most common polymorphism in Mexican patients with chronic gastritis and it is associated with the *vacA* genotype s1/m1. We also found a high frequency of the polymorphisms M60 (85%), which has been previously shown to increase the chance of developing gastritis \[[@CR32]\], and E62 (81.8%), which has been shown to be the most common polymorphism in strains from Iranian patients with chronic gastritis \[[@CR32]\]. It is worth noting that in this region the only invariable residue is G61. Besides the polymorphisms in the polymorphic region, Cherati et al. \[[@CR32]\], reported other polymorphisms outside this region associated with different disease outcomes. They found that the polymorphism K122 had frequency of 88.8% in strains from patients with gastritis. Similarly, we found that the frequency of K122 in our isolates was 82%. In fact, 24/33 strains (73%) had the combination M60/K122. They also found that the frequency of polymorphism V134 is significantly higher in patients with gastric cancer than gastritis. In our strains, V134 had a prevalence of only 18.2%, being the most common the polymorphism I134 (81.8%). This result shows that in Mexican patients, polymorphism I134 is more common in chronic gastritis. We also identified two more residues with high variability, I73 and T175 (in *H. pylori* ATCC 26695). In strains isolated from Mexican patients with chronic gastritis, polymorphisms M73 and I175 have a frequency of 60.6% and 42.4%, respectively, however, in the literature there is no information regarding these residues or their association with clinical outcome, hence, the clinical significance of these results as well as the biological function of these polymorphisms need to be addressed in more detail. With respect to the I73 M mutation, isoleucine (I) and methionine (M) are nonpolar amino acids without charge, therefore, it is likely that this change has no important effects on the structure and function of CagL. The I175 mutation consists of the change of a polar threonine residue by one of nonpolar isoleucine, next to the TASLI motif and it is probable that this change influences the functions of CagL. It has been proposed that the TASLI region binds to integrin in an RGD-independent manner and it is probably that I175 residue contributes also to this function and to other functions of CagL. The TASLI motif is involved in binding to the cell, although only in the absence of another host cell ligands. Deletion of TASLI is related with a moderate reduction in IL-8 secretion and CagA translocation. In addition, it has been shown that the deletion of TASLI reduces de CagL binding to integrin \[[@CR34]\]. Interestingly, the most common CagLHM sequence found in our study population was DKMGE, which is the most frequent worldwide, mainly in Africa and the American Continent. The second most frequent sequences were NEIGQ and NKMGQ. NEIGQ is also the second most common worldwide mainly in Europe, Asia, and North America, while NKMGQ has been found in Asia/Australasia but not in the American Continent. Additionally, we also found three sequences that are prevalent in East/Southeast Asia/Australasia (DKIGK), West/Central/South Asia (DEIGQ), and Central/South America (NKMGE) \[[@CR23]\], as well as a new sequence not informed before (DKIGE). This sequence was found in only 1 clinical isolate (HG-193), and contains the sequence DKI, which is found mainly in strains from Asia/Australasia \[[@CR23], [@CR24], [@CR35]\]. Despite of this, this isolate seems to be more related with those carrying sequence DKMGE, and in a lesser degree to strains carrying sequence NKMGQ (Fig. [5](#Fig5){ref-type="fig"}). These results show that the CagLHM sequences found in Mexican strains are diverse, with sequences not only common in our continent, but also in Asia, although all the CagA sequences are Western according to the EPIYA motifs \[[@CR36]\]. The sequence diversity of CagL in the locally circulating strains may reflect the mobility and complex human interactions with the bacteria, but it may also be related to differences that modify the pathogenic function of the protein. More studies are needed on the diversity of CagL and the relationship of its polymorphisms with gastric diseases, as well as on the role of variations in the CagL hypervariable motif on the structure and function of the protein, and on the inflammatory process. In the population of the state of Guerrero, Mexico, a high frequency of gastric diseases related to *H. pylori* persists, therefore, it is important to identify the virulence factors that confer a higher risk of developing serious diseases. The knowledge about these virulence factors will allow a better understanding of this process, facilitating the identification and characterization of biomarkers helpful in the detection of patients with greater risk of developing gastric cancer. It will also help to determine schemes and priorities of eradication treatments with anti--microbial compounds, as a measure to prevent gastric cancer. Conclusions {#Sec9} =========== Most of the clinical isolates of *H. pylori* analyzed in this study were *cagL* positive, and all of them carried conserved RGD and RHS motifs. In Mexican patients with chronic gastritis, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are the most common. CagLHM polymorphisms D58/K59 are related with the virulent genotype *vacA s1m1* of *H. pylori.* Methods {#Sec10} ======= Patients {#Sec11} -------- We performed a cross-sectional study among 164 patients that attended to the Gastroenterology Service at the General Hospital Dr. Raymundo Abarca Alarcón, and to the Specialized Unit in Gastroenterology Endoscopy, both in Chilpancingo, Guerrero, Mexico. Patients who attended for an endoscopic study due to dyspepsia symptoms, and that have had no *H. pylori* eradication treatment during 1 month prior to the endoscopic procedure were selected. None of the patients included in this study were under treatment with proton pump inhibitors or with gastric pH neutralizing agents within 15 days prior to biopsy. Patients receiving non-steroidal anti-inflammatory therapy were excluded from the study. All patients signed a letter of consent. This project was approved by the Bioethics Committee of the Autonomous University of Guerrero, by the Department of Education and Research of the General Hospital Dr. Raymundo Abarca Alarcón, and by the authorized personnel of the Specialized Unit in Gastroenterology Endoscopy. Biopsies {#Sec12} -------- The endoscopic study was performed after a fasting night with a video processor and video gastroscope (Fujinon, Wayne, NJ USA). Two biopsies were taken from the antrum of patients with chronic gastritis, one was immediately fixed in 10% formalin for histological examination, and the other one was placed in Brain Heart Infusion Broth (BHI) (Becton--Dickinson, North Carolina, USA) with 10% glycerol for the isolation of *H. pylori*. The biopsies were transported at 4 °C, and those intended for isolation of *H. pylori* were processed immediately. Isolation and identification of *H. pylori* {#Sec13} ------------------------------------------- Each biopsy transported in BHI broth with 10% glycerol was macerated with a sterile wood applicator. Fifty microliters of the homogenates were cultivated on Columbia Agar plates (Becton--Dickinson, North Carolina, USA) supplemented with 10% ram blood, IsoVitaleX Enrichment and Helicobacter pylori selective supplement Dent (10 mg/L of vancomycin, 5 mg/L of trimethoprim, 5 mg/L of cefsulodin, 5 mg/L of amphotericin B) (Oxoid, Basingstoke, UK) at pH 6.8 to 7.0. The homogenates were distributed on the culture medium by isolation strip. The inoculated plates were incubated under microaerophilic conditions with 5% O~2~ and 5% CO~2~ at 37 °C in GasPak jars for 3--7 days. *H. pylori* was identified by colony morphology (small, transparent colonies, 1 mm in diameter), Gram staining and biochemical tests (urease, catalase and oxidase positive). *H. pylori* strain ATCC 43504 was used as positive control. Bacterial DNA extraction {#Sec14} ------------------------ Isolates identified as *H. pylori* were subcultured and incubated for 72 h. A pool of colonies from each isolate was resuspended in extraction solution (10 mM Tris pH 8, 10 mM EDTA, 0.5% SDS) for digestion with proteinase K. Total DNA was obtained by phenol: chloroform: isoamylic alcohol technique \[[@CR37]\]. Total DNA concentration was determined using a NanoDrop 2000. DNA samples were stored at − 20 °C until use. Molecular confirmation and genotyping of *vacA* and *cagA* of *H. pylori* strains {#Sec15} --------------------------------------------------------------------------------- Confirmation of *H. pylori* strains was done using oligonucleotides HP16SF and HPGR16SR (Table [4](#Tab4){ref-type="table"}), which amplify a fragment of the 16S rRNA gene, according to the method described by Román-Román et al. \[[@CR38]\]. *vacA* and *cagA* genotyping was assessed by multiple PCR with specific oligonucleotides VAIF and VAIR, VAGF and VAGR, and F1 and B1, respectively (Table [4](#Tab4){ref-type="table"}). The reaction mixture contained 1.5 mM MgCl~2~; 0.2 mM dNTPs; 2.5 pmol of oligonucleotides F1 and B1, or 5 pmol of VAGF and VAGR, or 2.5 pmol of VAIF and VAIR; 1.5 U of Taq DNA polymerase (Invitrogen, Carlsbad, CA, USA) and 200 ng of DNA, in a total volume of 25 μL. Amplification conditions were: 1 cycle at 94 °C for 10 min; 35 cycles at 94 °C for 1 min, 57 °C for 1 min, 72 °C for 1 min; and a final extension cycle at 72 °C for 10 min. The PCR products were subjected to 2.5% agarose gel electrophoresis, stained with ethidium bromide and visualized with ultraviolet light (UV). In each PCR, DNA from strain ATCC 43504 (*vacA s1m1*/*cagA*^+^) was used as positive control, and as negative control DNA was replaced with sterile deionized water. All reactions were done in a Mastercycler Ep gradient thermal cycler (Eppendorf, Hamburg, Germany).Table 4Oligonucleotides used in this workGeneOligonucleotideSequence 5′--3′Amplicon size (bp)References*16S rRNA*HP16SFGCTAAGAGATCAGCCTATGTCC522\[[@CR39]\]HPGR16SRCAATCAGCGTCAGTAATGTTC*vacAs1*VAIFATGGAAATACAACAAACACAC259\[[@CR40]\]*vacAs2*VAIRCTGCTTGAATGCGCCAAAC286*vacAm1*VAGFCAATCTGTCCAATCAAGCGAG570\[[@CR41]\]*vacAm2*VAGRGCGTCTAAATAATTCCAAGG645*cagA*F1GATAACAGGCAAGCTTTTGAGG349\[[@CR42]\]B1CTGCAAAAGATTGTTTGGCAGAEmpty siteESfACATTTTGGCTAAATAAACGCTG360\[[@CR43]\]ESrTCATGCGAGCGGCGATGTG*cagL*cagL senseGAAGATATAACAAGCGGTTT651\[[@CR44]\]cagL antisenseTTTAACAATGATCTTACTTGAcagL-Fwd-2ACVAAGAGACCAACCARCAAG165This workcagL-16TCGCTTCAAAATTGGCTTTC\[[@CR31]\]cagL-Fwd-2ACVAAGAGACCAACCARCAAG611This workcagL-16TTTAACAATGATCTTACTTGA\[[@CR44]\] Confirmation of *cag*PAI empty site {#Sec16} ----------------------------------- The absence of *cagA* and the pathogenicity island *cag*PAI in the *cagA*^−^ strains was confirmed by the empty-site assay by conventional PCR, using the ESf and ESr oligonucleotides (Table [4](#Tab4){ref-type="table"}), which bind upstream and downstream, respectively, of the region where the *cag*PAI is inserted in the genome of the reference strain NCTC 12455 (NCTC: National Collection of Type Culture) \[[@CR45]\]. The PCR mixture contained 50 ng of DNA, 0.08 mM dNTPs (Invitrogen, Carlsbad, CA, USA), 1 mM MgCl~2~, 5 pmol of each oligonucleotide and 1 U of Platinium Taq DNA Polymerase (Invitrogen, Carlsbad, USA), in a final volume of 15 μL. The amplification conditions were: 1 cycle at 94 °C for 5 min; 35 cycles at 94 °C for 30 s, 61 °C for 30 s and 72 °C for 45 s; and one final extension cycle at 72 °C for 7 min. PCR products were subjected to 2% agarose gel electrophoresis, followed by ethidium bromide staining and UV light observation. As negative control, DNA was replaced with sterile deionized water. DNA from strain ATCC 43504 (*cagA*^+^, *cag*PAI^+^) was used as a second negative control, and strain UEGE-644 (*cagA*^−^, *cag*PAI^−^) as positive control. The presence of a 360 bp product was considered indicative of the absence of *cagA* and *cag*PAI \[[@CR43], [@CR45]\]. CagL amplification by PCR {#Sec17} ------------------------- A fragment of 651 bp from gene *cagL* (*hp0539*) was amplified by PCR using primers cagL sense and cagL antisense (Table [4](#Tab4){ref-type="table"}). The reaction mixture had a final volume of 15 μL, and contained 2.5 mM MgCl~2~, 0.25 mM dNTP's, 5 pmol of each oligonucleotide, 1 U of Taq recombinant DNA polymerase (Invitrogen, Massachusetts, USA) and 50 ng of DNA. The conditions used were: 1 cycle at 94 °C for 5 min; 45 cycles at 94 °C for 30 s, 55 °C for 30 s, and 72 °C for 1 min; and 1 cycle at 72 °C for 7 min. Each reaction included a positive (DNA from strain 26695) and a negative (DNA was substituted with water) control. All reactions were performed in a Mastercycler Ep gradient thermocycler (Eppendorf, Hamburg, Germany). PCR products were analyzed by agarose gel electrophoresis at 1.5% and stained with ethidium bromide. A second PCR was performed with DNA from those strains that were negative in the first reaction, using primers cagL-Fwd-2 and cagL-16, which amplified a 165 bp product (Table [4](#Tab4){ref-type="table"}). The reaction mixture had a final volume of 15 μL, and contained 1.5 mM MgCl~2~, 0.25 mM dNTP's, 5 pmol of each oligonucleotide, 1 U of Taq recombinant DNA polymerase (Invitrogen, Massachusetts, USA) and 50 ng of DNA. The conditions used were: 1 cycle at 94 °C for 5 min; 35 cycles at 94 °C for 45 s, 54 °C for 30 s, and 72 °C for 1 min; and 1 cycle at 72 °C for 7 min. Each reaction included a positive (DNA from strain 26695) and a negative (DNA was substituted with water) control. PCR products were analyzed by agarose gel electrophoresis at 1.8% and stained with ethidium bromide. A third PCR was performed with DNA from those strains that were negative in the first reaction, using primers cagL-Fwd-2 and cagL antisense (Table [4](#Tab4){ref-type="table"}), in order to amplify a fragment of 611 bp suitable to upload in the GeneBank. The reaction mixture had a final volume of 25 μL and contained 1.5 mM MgCl~2~, 0.25 mM dNTP's, 5 pmol of each oligonucleotide, 1 U of Taq recombinant DNA polymerase (Invitrogen, Massachusetts, USA) and 50 ng of DNA. The conditions used were: 1 cycle at 94 °C for 5 min; 35 cycles at 94 °C for 45 s, 56 °C for 30 s, and 72 °C for 45 s; and 1 cycle at 72 °C for 3 min. PCR products were analyzed by agarose gel electrophoresis at 1.8% and stained with ethidium bromide. Purification and sequencing of PCR products {#Sec18} ------------------------------------------- PCR products were purified by the isopropanol method and sequenced in the Unidad de Síntesis y Secuenciación of the Instituto de Biotecnología, UNAM, using primers cagL sense and primer cagL-Fwd-2 (Table [4](#Tab4){ref-type="table"}). All sequences were deposited in GenBank with accession numbers MG051618-MG051641 and MG214979-MG214987. Bioinformatic analysis {#Sec19} ---------------------- Nucleotide sequences were translated to aminoacidic sequences using the ExPASy Translate Tool (<http://web.expasy.org/translate/>). Multiple sequence alignment of translated sequences and phylogenetic analysis were performed using Molecular Evolutionary Genetics Analysis version 7.0 (MEGA7) software \[[@CR46]\]. The evolutionary history was inferred using the Neighbor-Joining method \[[@CR47]\]. The tree was drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The analysis involved 34 amino acid sequences of CagL. Conception and design: GF-T, AR-R. Experiments: AJA-M, PG-M, CAC-S, DGS-F. Data analysis: VIM-S, GF-T, AR-R, DNM-C. Drafting the manuscript: VIM-S, GF-T, AR-R, DNM-C. Sample collection: AJA-M, PG-M. All authors read and approved the final manuscript. Acknowledgements {#FPar1} ================ We acknowledge the endoscopist gastroenterologists who carried out the endoscopic study and obtained the biopsies, and the histopathologists who performed the histological diagnosis of the biopsies. Competing interests {#FPar2} =================== The authors declare that they have no competing interests. Availability of data and materials {#FPar3} ================================== All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Consent for publication {#FPar4} ======================= Not applicable. Ethics approval and consent to participate {#FPar5} ========================================== This project was approved by the Bioethics Committee of the Autonomous University of Guerrero, by the Department of Education and Research of the General Hospital Dr. Raymundo Abarca Alarcón, and by the authorized personnel of the Specialized Unit in Gastroenterology Endoscopy. Patients signed informed consent statements. All procedures performed in this study 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. Funding {#FPar6} ======= This work was supported with funding granted by the Ministry of Public Education, through ProDES 2014 and 2015. Publisher's Note {#FPar7} ================ Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Hot Topics: At a former Colorado Springs hospital, St. Francis Health Center, the walls do talk By Ned Hunter The Gazette Posted: 11/28/2013 10:16:22 PM MST Updated: 11/28/2013 10:17:31 PM MST COLORADO SPRINGS -- Sometimes, the walls can talk. Thousands of notes to God, surgeons and dead family members, scribbled on scraps of paper and then slid into the cracks between century-old red bricks, tell the tales of tragedy brought by tuberculosis and other diseases as well as the wonders of childbirth at Colorado Springs' first major hospital. If it's not the walls talking, then perhaps it's "Charlie" or one of several other ghosts said to wander the halls of St. Francis Health Center, originally St. Francis Hospital. The hospital that opened as a one-story building in 1887 and expanded over the next 100 years is on the selling block; its future, like some of its past, is a mystery. St. Francis Hospital merged with Penrose Hospital in 1989, creating Penrose-St. Francis Health Services. To avoid confusion, St. Francis Hospital changed its name to St. Francis Health Center. The downtown hospital stopped treating trauma patients five years later. It did, however, house mentally ill patients until 2010. Now, the only ones walking the operating rooms, tuberculosis treatment centers and psychiatric ward are eight security guards -- or are they? On the third floor of the 29 building, a wall clock encircled by peeling beige paint permanently reads 12:15. The 29 was the first of three modern buildings that formed St. Francis Hospital. It is named after the year it was constructed, as are the other two -- the 65 and 73; all are connected. Advertisement Roger Bost has spent plenty of time in all three buildings, working the 4 p.m. to midnight security shift. He said the sounds of footsteps and doors opening and closing are the norm. Bost recalls one night when someone opened the south entrance door, paused a moment and then closed the door. That door is always locked, he said. Bost speaks of small shadows, such as those cast by children, moving across hospital walls. The most distressing shadow was adult-size. Bost said the dark figure once stopped on the wall for several seconds, as if staring at him. "It never feels dark or malevolent," he said, "just like someone is not ready to move on yet." The four-story 29 building was a sanatorium used to house tuberculosis patients. Each of the private rooms has a sun porch where patients received the only known treatment of the time: rest, sunlight and fresh air. Yellow tiles that line the second-floor hallway are streaked with thin, red lines. Some who have visited the floor in recent years said they could hear patients hacking, even though no one has been treated there for nearly half a century. The building does not have central heat or air, despite housing administration offices from the 1960s to 2000. But it does have a tunnel; an underground passage from the three main buildings to the boiler room along Colorado Avenue, where the red-brick chimney that once belched coal smoke still stands. There is another tunnel, too, and it was closed decades ago, said Clark Ulam, a security guard. This passage ran from the hospital underneath Pikes Peak Avenue to a small building at the corner of Institute Street in front of The Colorado School for the Deaf and the Blind. "I was told that at the time, the bodies of people who died from TB were not allowed to be taken into the open air," Ulam said. "So, they took them underground to the crematorium where the white chimney is." The Springs' first medical treatment center was a small infirmary built around 1887 to treat injured railroad workers hired to build a line to Leadville. In September of that year, four sisters from the Lafayette, Ind., chapter of St. Francis of Perpetual Adoration came to the Springs to help care for the injured and dying, said Sister Nadine Heimann. "There were so many accidents, especially through the Continental Divide," she said. "It took a heavy toll on the lives and limbs of a lot of people with falling rock and explosions and derailments because of unsettled road beds." The infirmary admitted 20 patients the day the sisters arrived; 12 had typhoid fever. The sisters treated a total of 81 patients that first year. In October 1887, the sisters bought the first bit of land off Pikes Peak Avenue that would become St. Francis Hospital. The cost was $350. About six months later, St. Francis Hospital opened its doors. The hospital's second major expansion was the 65 building. The surgical areas were state of the art at the time, and steel drums used to sterilize tools still stand between rooms. Outpatient surgery and other procedures were performed on the second floor until 2005. The fifth floor was home to long-term acute care and cafeteria services. The dining room's immense windows offer a grand look at Pikes Peak. "People would come from the surrounding community because it was such a great view," said Liz Benavidz, nutrition supervisor. The sisters have been preparing for the eventual razing of their hospital since 2008. The majority of all salvageable equipment, religious items and other memorabilia have been removed. The hospital held open houses to allow families to visit rooms where children and grandchildren were born and parents and grandparents died, said Larry Seidl, vice president for Mission Ministry. It was after the open houses when Seidl and others discovered the notes visitors had stuck into the cracks of walls, the corners of rooms and other crevasses. "Dad I will always love you. Walking into this room reminds me how much I miss you. I will always love you dad," read one note, according to Seidl. Another note from a couple in their mid-40s who did not have a child until after several tries thanked God for the miracle, he said. "It was like seeing the Wailing Wall in Jerusalem," Seidl said. All of the notes were put back in their sacred places, Seidl said. They will become a part of the rubble and dust if the hospital is razed, leaving only the memories of births and deaths and the wonderment of whether "Charlie" and the hospital's other ghosts finally will find peace or seek another location to reside. The Boulder alt-country band gives its EPs names such as Death and Resurrection, and its songs bear the mark of hard truths and sin. But the punk energy behind the playing, and the sense that it's all in good fun, make it OK to dance to a song like "Death." Full Story

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List Of Greek Myths Stories Feb 21, 2013 · This is a four week unit i prepared for my year 3 class. I have including 4 weekly plans and 4 powerpoints with all the resources needed. The most difficult step is choosing the learning objective. Ask yourself what you want the students to achieve by the end of the class. Think about: Why the students are learning English What they. Dickens A Christmas Carol Pdf This holiday season, McCarter is proud to present a reimagined production of Dickens' classic, A Christmas. Carol. Follow Ebenezer Scrooge on a magical. Charles Dickens’ Christmas Carol. These images are I'm aiming to get an A in the class and a 4 or 5 on the exam. Hey junior2016 – I took AP English Language and Composition last year as a junior as. yourself with ethos, logos, pathos, syntax, and other literary devices. My school has us buy 5 steps to a 5, but I think that the book is completely useless. 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Q: Is there a way to stop laravel files in phpunit getting infected by Trajon virus I find unexpected files different from what i uploaded in phpunit laravel files. Even emails in cpanel are manipulated. Some of the created files /home/~/public_html/vendor/phpunit/phpunit/src/Util/PHP/to.php /home/~/public_html/vendor/phpunit/phpunit/src/Util/PHP/X_Bsend.php /home/~/public_html/vendor/phpunit/phpunit/src/Util/PHP/unit.php /home/~/public_html/vendor/phpunit/phpunit/src/Util/PHP/tshop.php /home/~/public_html/vendor/phpunit/phpunit/src/Util/PHP/smtpp8.php Anyone who can help stop this Attack on laravel, please help A: When you install composer dependencies use the --no-dev flag. composer install --no-dev you don't want dev dependencies in your production environment. This will result in you not having phpunit in your vendor directory. Disclaimer: This is not a virus fix, your vulnerablity could be elsewhere.

Zippy Party Roll-Ups Recipe A guaranteed Christmas crowd-pleaser, these zesty appetizers are a great way to pep up a party! The recipe won a blue ribbon at the county fair, and even though I always double it, I never seem to make enough. Nutritional Facts Directions Spread about 3 tablespoons of cream cheese over each tortilla; layer each with 6 spinach leaves and 3 slices ham. Sprinkle with olives and chilies. Roll up tightly and wrap in plastic wrap. Refrigerate until firm. Unwrap and cut each roll-up into 12 slices.Yield: 6 dozen. Originally published as Zippy Party Roll-Ups in Country Woman Christmas Annual 2005, p23

The late effects of childhood cancer therapy. In this article the difficulties that face survivors of childhood cancer therapy are presented, and the late effects of such therapy, separated into nonmalignant and malignant late effects, are discussed according to organ system. Recommendations for monitoring the late effects are set forth. A table listing radiation-therapy site and chemotherapeutic agents and selected late effects that result from their use is provided. Finally, a brief recommendation regarding the establishment of a late-effects clinic is also presented.

Lezayre Lezayre ( ; ), formally Kirk Christ Lezayre, is one of the seventeen historic parishes of the Isle of Man. It is located in the north of the island (part of the traditional North Side division) in the sheading of Ayre. Administratively, part of the historic parish of Lezayre is now part of the town of Ramsey. Other settlements in the parish include Glen Auldyn and Sulby. Local government For the purposes of local government, most of the historic parish forms a single parish district with Commissioners. Since 1865, an area in the east of the historic parish of Lezayre has been part of the separately administered town of Ramsey, with its own town commissioners. The Captain of the Parish (since 2005) is Denis Duggan. Politics Lezayre parish is part of the Ayre & Michael constituency, which elects two Members to the House of Keys. Before 2016 it was in the Ayre constituency, and since 1867 Ramsey has formed its own constituency. Geography The parish is bounded by Michael and Ballaugh to the west, Andreas and Bride to the north, the town of Ramsey and the parishes of Lonan and Maughold to the east, and Braddan to the south. Its area is about . The name means "of", "at" or "towards" the Ayre. Lezayre is primarily rural and mountainous, and includes the summit of Snaefell, the highest point of the island, and much of the mountain sections of the TT course. It also includes most of the course of the Sulby river, the longest river on the island; Tholt-y-Will Glen; and part of Sulby Reservoir. Most of the settlement in the parish is stretched along the main road from Ramsey towards Peel, including the village of Sulby and the small village of Churchtown centred on the parish church. Much of the northern part of the Millennium Way passes through the parish. Demographics The Isle of Man census of 2016 returned a parish population of 1,276, a decrease of 0.5% from the figure of 1,282 in 2011. Churches The Church of England parish church of Kirk Christ, Lezayre was built in 1835. It is likely that it is so called to distinguish it from the other Kirk Christ, located in the sheading of Rushen. One of its windows was erected by stained glass painter and art dealer Daniel Cottier, whose father and grandfather were born in the parish. In 2013, it was closed and the diocese is looking to sell the building. There are two other Church of England churches in the parish: St. Stephen's, Sulby and St. Fingan's, a small converted Methodist chapel in Glen Auldyn. Sulby has a prominent Methodist church. References Sources Lezayre Parish community and local government information Manxnotebook - Lezayre with full description of the parish Isle of Man Building Control Districts showing parish boundaries Glenology - Manx Glens An ongoing study of Manx glens, their locations and meanings. Category:Parishes of the Isle of Man

Anxiety symptoms in crack cocaine and inhalant users admitted to a psychiatric hospital in southern Brazil. The occurrence of psychiatric comorbidity among individuals with crack or inhalant dependence is frequently observed. The objective of this study was to investigate anxiety symptoms among crack cocaine and inhalant users in southern Brazil. The study investigated two groups of volunteers of equal size (n=50): one group consisted of crack cocaine users, and the other group consisted of inhalant users. Research volunteers completed the Portuguese versions of the State-Trait Anxiety Inventory (STAI), Hamilton Anxiety Rating Scale (HAM-A), and Self-Report Questionnaire (SRQ). Both crack and inhalant users experience significant symptoms of anxiety. Inhalant users presented significantly more anxiety symptoms than crack users according to the HAM-A questionnaire only. In contrast to the results of the HAM-A, the STAI failed to demonstrate a significant difference between the two groups of substance users. SRQ scores revealed that crack and inhalants users had significant degrees of morbidity. A significant difference regarding anxiety symptomatology, especially state anxiety, was observed among inhalant and crack users. Anxiety and overall mental psychopathology were significantly correlated in this sample. The results indicate that screening initiatives to detect anxiety and additional psychiatric comorbidities among crack and inhalant users are feasible and relevant.

Q: query multi-level entity with filter at the lowest level So I have 3 entity classes: public partial class Event { public Event() { Recurrences = new HashSet<Recurrence>(); } public int Id { get; set; } public ICollection<Recurrence> Recurrences { get; set; } } public partial class Recurrence { public Recurrence() { AspNetUsers = new HashSet<AspNetUser>(); } public int Id { get; set; } public int EventId { get; set; } public ICollection<AspNetUser> AspNetUsers { get; set; } } public partial class AspNetUser { public AspNetUser() { Recurrences = new HashSet<Recurrence>(); } public string Id { get; set; } public string UserName { get; set; } public ICollection<Recurrence> Recurrences { get; set; } } I would like to get the event given the aspnetuser.id using line to entity. so far this is what I have but it's returning an error: // GET: api/Events?userId={userId} public IQueryable<Event> GetEvents(string userId) { return db.Events .Include(e => e.Recurrences .Select(u => u.AspNetUsers.Where(i => i.Id == userId))); } When I exclude the where clause it works fine. Please help. Thanks in advance! A: I don't think Include() means what you think it means. (https://msdn.microsoft.com/en-us/library/bb738708%28v=vs.110%29.aspx) What it does is tell the db set to be sure to bring in relationships for that object. By default (last I checked), the db context will auto pull in all relationships, so this isn't necessary. However, if you've turned off the lazy-loading (http://www.entityframeworktutorial.net/EntityFramework4.3/lazy-loading-with-dbcontext.aspx) then you'll need to .Include() all the relationships you want to have in the query. This should solve your problem. I don't guarantee the SQL generated won't be silly, though. If you have lazy-loading turned on: db.Events.Include("Recurrences").Include("Recurrences.AspNetUsers") .Where(e => e.Recurrences .Any(r => r.AspNetUsers .Any(u => u.Id ==userId))); If you have lazy-loading turned off: db.Events .Where(e => e.Recurrences .Any(r => r.AspNetUsers .Any(u => u.Id ==userId))); Also, if you have trouble seeing errors, you can .ToList() the query before returning so that it fails in your code and not deep inside the Web API stack. Personally, I like to do this so that I can try/catch the query and handle it properly.

Q: Win32 API GetMenuItemInfo returns only the first character of the item text I'm trying to gather the text of a menu item using GetMenuItemInfo API. This is the code I'm using: [DllImport("user32.dll", CharSet = CharSet.Auto, SetLastError = true)] public static extern bool GetMenuItemInfo(IntPtr hMenu, uint uItem, bool fByPosition, ref MENUITEMINFO lpmii); [StructLayout(LayoutKind.Sequential)] public struct MENUITEMINFO { public uint cbSize; public uint fMask; public uint fType; public uint fState; public uint wID; public IntPtr hSubMenu; public IntPtr hbmpChecked; public IntPtr hbmpUnchecked; public IntPtr dwItemData; public String dwTypeData; public uint cch; public IntPtr hbmpItem; // Return the size of the structure public static uint sizeOf { get { return (uint)Marshal.SizeOf(typeof(MENUITEMINFO)); } } } MENUITEMINFO mif = new MENUITEMINFO(); mif.cbSize = MENUITEMINFO.sizeOf; mif.fMask = MIIM_STRING; mif.fType = MFT_STRING; mif.dwTypeData = null; bool res = Win32.GetMenuItemInfo(hMenu, (uint)0, true, ref mif); //To load cch into memory mif.cch += 1; mif.fMask = MIIM_STRING; mif.fType = MFT_STRING; mif.dwTypeData = new String(' ', (Int32)(mif.cch)); res = Win32.GetMenuItemInfo(hMenu, (uint)i, true, ref mif); //To fill dwTypeData Unfortunately after those lines dwTypeData results a string with only 1 character instead of mif.cch characters. Note: this character is the first one of the menu item! It seems that there's some misalignment in the marshaling of data when returning MENUITEMINFO structure, isn.t it? Please let me know how to solve such issue! Best cghersi A: Your header translation is pretty good, but you've not got dwTypeData quite right. That cannot be marshalled from caller to callee using string. You need to do that with manual marshalling like this. [DllImport("user32.dll", CharSet = CharSet.Unicode, SetLastError = true)] public static extern bool GetMenuItemInfo(IntPtr hMenu, int uItem, bool fByPosition, MENUITEMINFO lpmii); [StructLayout(LayoutKind.Sequential)] public class MENUITEMINFO { public int cbSize; public uint fMask; public uint fType; public uint fState; public uint wID; public IntPtr hSubMenu; public IntPtr hbmpChecked; public IntPtr hbmpUnchecked; public IntPtr dwItemData; public IntPtr dwTypeData; public uint cch; public IntPtr hbmpItem; public MENUITEMINFO() { cbSize = Marshal.SizeOf(typeof(MENUITEMINFO)); } } .... MENUITEMINFO mif = new MENUITEMINFO(); mif.fMask = MIIM_STRING; mif.fType = MFT_STRING; mif.dwTypeData = IntPtr.Zero; bool res = GetMenuItemInfo(hMenu, 0, true, mif); if (!res) throw new Win32Exception(); mif.cch++; mif.dwTypeData = Marshal.AllocHGlobal((IntPtr)(mif.cch*2)); try { res = GetMenuItemInfo(hMenu, 0, true, mif); if (!res) throw new Win32Exception(); string caption = Marshal.PtrToStringUni(mif.dwTypeData); } finally { Marshal.FreeHGlobal(mif.dwTypeData); }

Copyright (c) 2011 Juan Mellado 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.

The Western Wall Overview The Western Wall, or Kotel, in the Old City of Jerusalem has figured prominently in the Jewish consciousness for centuries. Generations dreamed of appearing before the old stone wall, even just once. Now, the Wall is active 24 hours a day, 365 days a year, and the cracks between the rectangular stones are crammed with paper. Spiritual Significance When King Solomon built the first Holy Temple in 826 BCE, he wanted it to be the heart of the Jewish nation—a place where people felt inspired to talk to G-d, a place where no one would feel alone. "Please, G-d," he said during the Temple's inauguration, "Hear the prayers that are said in this place." Solomon's prayers were answered, and G-d's presence enlivened the Temple. The Second Temple, built 480 years later, also was a home to G-d's presence. The midrash says that "the Shechinah never left the Western Wall." Specifically the Western Wall, because the Holy of Holies was on the west side of the Temple. "This is the Western Wall of the Temple, which is never destroyed because the Shechina is in the west." The holiness of the Western Wall is due to its close proximity to the Temple area. Click here for more about the Holy Temple, and the reasons why it is the Gateway to Heaven. Click here for more readings on the Western Wall. Basic History The wall we call today the Western Wall, while not a part of the Holy Temple itself, was part of the Temple Mount retaining wall that Herod the Great built in the 1st century BCE when he ambitiously expanded the Temple Mount and renovated the then-dilapidated Second Temple. When the Romans destroyed the Temple in 69 CE, this wall was not destroyed. And nearly two thousand years later, the wall still stands. Of the visible part of the wall, only the bottom seven layers of stones, consisting of large stones with indented borders, date from Herod's project. The next section, consisting of four layers of smaller, plainer stones, dates from the Byzantine period. The next layer up was added sometime after the Moslem conquest in the seventh century, and the topmost layer was added in the 19th century, paid for by the famed British philanthropist and financier, Sir Moses Montefiore. Jews throughout the ages have visited the Western Wall to offer prayers at this holy location, because, our sages teach, the Shechinah (Divine Presence) that was manifest in the Temple never departed. Furthermore, access to the holiest site in the world, the Temple Mount itself, is prevented by Jewish law, which forbids entry to the Temple site while in a state of ritual impurity. Thus the Western Wall constitutes the closest possible point to the "Gateway to Heaven." In the second half of the 16th century, Suleiman the Magnificent gave the Jews exclusive rights to worship at the Western Wall. The prayer area was small, closed off by a wall running parallel to the Wall and hemmed in by a slum area. It stayed that way until 1947. In 1930, a British appointed commission sanctioned by the League of Nations reaffirmed the Jews' right to pray at the Wall—but severely limited the sort of religious objects that could be brought to the Wall, and prohibited the blowing of the shofar at the site. Between 1948 and 1967, the Old City of Jerusalem was under Jordanian control and Jews were altogether banned from visiting the Wall. Israeli paratroopers liberated the Temple Mount on June 7th 1967, the third day of the Six Day War, marking a rare, euphoric moment in our nation's history. A few weeks later, on the holiday of Shavuot, a quarter of a million Jews streamed to the Wall. Until then, the accessible portion of the Wall had been a 100 foot-long stretch of the massive wall, and the open area before the Wall was only ten feet wide. The many buildings in front of the wall were immediately razed, all the way to its southern corner. The entire area was leveled and paved, creating a large open plaza. Today, the part of the Wall visible from the plaza is 187 feet long. The entire length of the Western Wall, however, is actually 1,600 feet long. The northern portion of the Wall is still hidden by buildings in the adjacent Muslim Quarter. Seventeen more layers of Western Wall stones are buried under the ground. Due to many generations of destruction and rebuilding, city upon city, the ground level is now higher and the bottom part of the western side of the Temple Mount is buried. Today Walking with throngs of people to the Wall, it is possible to feel like an anonymous person in an anonymous crowd. Paying a curious visit, it is possible to feel distant, like a tourist observing some other culture. But it is very possible that there will be a moment of presence, of sensation; like the Zohar says, a feeling of being held close by a benevolent parent. The Temple is the heart of the Jewish people, and as such, when standing at its foot it is easy to feel the pulse of the beating heart. When visiting the wall it is important to respect the sanctity of the location. Modest attire should be worn, and no photography is allowed on Shabbat or Jewish holidays. "One who sees the site of the Holy Temple should say, 'Our holy house, our glory, where our parents praised you has been consumed by fire, and all that is precious to us has been destroyed' (Isaiah 64:10), and tear his garments as a symbol of mourning" – Code of Jewish Law. So if visiting the Wall (after an absence of at least thirty days), it is advisable to take along a shirt or jacket that has already seen its best days. (There are certain days when we don't rend our garments, such as Shabbat, Jewish holidays, Friday afternoons or Rosh Chodesh.) The area directly in front of the Wall is a large outdoor synagogue, divided into a men's and women's section. At the entrance to the men's section there is a tefillin booth, manned by Chabad volunteers throughout the daytime hours. Make your visit to the holiest Jewish site a spiritual experience—donning tefillin will only take five minutes or so; a friendly volunteer will lead you through from start to finish. When you approach the wall, take a moment to meditate and express your thoughts to the One whose presence pervades this holy site. There is an age-old custom to write your supplications on a note, and insert it into a crack in the wall. Ever since the Western Wall was liberated in 1967, archeological excavations have been ongoing beneath the Wall. While only a small section of the length of the wall is visible aboveground from the plaza, one can walk the entire length of the Wall in the underground tunnels and see all the subterranean layers of the wall, and even the bedrock beneath the wall. At the point directly opposite where the Holy of Holies once stood, there is an underground synagogue. These tunnels are an absolute must see! Touring these tunnels can only be done with a guide, and can be scheduled with the Western Wall Heritage Foundation (http://english.thekotel.org/content.asp?Id=226). Interesting Facts The Roman General Titus allowed the Western Wall to remain standing as a tribute to his power, a testament to the grandeur of the structures that he destroyed. While Titus may have had his reasons, G-d had His own, too. Though He was about to subject His children to a long and harrowing exile, He desired that a remnant of the Temple remain intact—a holy place where we can gather and pray. Many of the Wall's subterranean stones uncovered by archeologists in the course of their excavations are extraordinarily large, bigger than any stone found in the pyramids. Some of the stones weigh hundreds of tons. The Western Wall is also known as the "Wailing Wall." This name was given by non-Jewish observers who were accustomed to see Jews gathering at the Wall and "wailing"; wailing in prayer, and wailing in mourning for the destroyed Holy Temples. Following basic training, many IDF combat units hold their swearing-in ceremonies at the Western Wall. Many people come from all parts of the world come to celebrate the bar and bat mitzvahs of their sons and daughters at the Western Wall.

71 F.3d 879 Bennettv.Little* NO. 95-10236 United States Court of Appeals,Fifth Circuit. Nov 22, 1995 Appeal From: N.D.Tex., No. 3:89-CV-1282 1 AFFIRMED. * Fed.R.App.P. 34(a); 5th Cir.R. 34.2

Background {#Sec1} ========== Acute respiratory distress syndrome (ARDS) is a life-threatening condition with an approximate 40% hospital mortality rate \[[@CR1]\], costing 3.6 million hospital days annually in the USA and accounting for 10.4% of intensive care unit (ICU) admissions around the world \[[@CR1], [@CR2]\]. In recent decades, progress has been achieved in the development of possible treatments for ARDS, including protective ventilation strategies, prone positioning, neuromuscular blockade, and extracorporeal membrane oxygenation \[[@CR1]\]. Some pharmacologic compounds have also been suggested to be effective in ARDS prevention \[[@CR3]\]. However, no Food and Drug Administration approved treatment for ARDS is currently available \[[@CR4]\]. ARDS is characterized by uncontrolled inflammation and coagulation with increased capillary permeability, inflammatory cell accumulation in the lung compartments, and pulmonary microvascular coagulopathy \[[@CR5]\]. Platelets play a key role in the pathogenesis and resolution of ARDS as mediators of hemostasis and coagulation, modulators of inflammation and the immune system, and defenders of microbes \[[@CR6]--[@CR8]\]. Antiplatelet therapy can attenuate lung injury by impeding platelet activation and surface adhesion protein expression, such as glycoprotein IIb/IIIa receptor, P-selectin, and intracellular adhesion molecule 1 (ICAM-1) \[[@CR9]\], which is a key step in microvascular thrombus formation and tissue injury \[[@CR10], [@CR11]\]. Platelet inhibition also suppresses the secretion of inflammation mediators such as cytokines, chemokines and granules \[[@CR11], [@CR12]\] and thereby attenuates inflammation in the lung and its interaction with the immune system. Moreover, platelet activation is reported to initiate the innate immune response through pathogen recognition patterns and proinflammatory neutrophil extracellular trap (NET) formation in acute lung injury \[[@CR13]\]. In addition, platelets can produce functional progeny through self-regulation \[[@CR14]\] and generate a positive feedback loop, amplifying both the homeostatic and inflammatory responses \[[@CR15]\]. Inactivation of platelets may impede this positive feedback and improve outcomes among high-risk patients. Preclinical studies have identified beneficial effects of antiplatelet therapy in ARDS prevention, as evidenced by improved oxygenation, diminished lung edema, attenuated inflammation, and increased survival \[[@CR5]\]. In contrast, antiplatelet therapy also exhibited biphasic behavior in an animal study, with benefit in the early phase followed by worsening of gas exchange in the late phase \[[@CR16]\]. Pretreatment with antiplatelet therapy has also been reported to increase inflammation in the lung \[[@CR17]\]. The results of a meta-analysis based on observational studies suggested that antiplatelet therapy with aspirin was significantly associated with reduced incidence of ARDS in mixed critically ill patients \[[@CR5]\]. However, a recent, well-designed, randomized controlled clinical trial showed that neither the incidence of ARDS at 7 days nor the incidence of adverse effects was significantly different between antiplatelet therapy and placebo groups \[[@CR18]\]. Therefore, the effect of antiplatelet therapy on ARDS prevention remains controversial. The objective of the present meta-analysis was to compare the incidence of newly developed ARDS and mortality between patients with and without antiplatelet therapy, who were at a high risk of ARDS. Methods {#Sec2} ======= Protocol and search strategy {#Sec3} ---------------------------- This meta-analysis was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) \[[@CR19]\] (see Additional file [1](#MOESM1){ref-type="media"}). A study protocol was established prior to the literature search (see Additional file [2](#MOESM2){ref-type="media"}). Electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Medline, and the Web of Science were searched for published studies. The last search was performed on 26 October 2017 (details of the search strategies are provided in Additional file [2](#MOESM2){ref-type="media"}). The reference lists of review articles were manually screened for other potential studies. Study selection and data extraction {#Sec4} ----------------------------------- Randomized and observational studies (prospective or retrospective cohort studies and case-control studies) were included. The inclusion criteria were adult patients presenting to the hospital or ICU with a high risk of ARDS, administration of antiplatelet therapy at any time or dose, comparison between patients with and without antiplatelet therapy, and a report of newly developed ARDS. High-risk factors for ARDS identified in previous studies to be closely associated with the development of ARDS were defined as sepsis, non-cardiogenic shock, trauma, high-risk surgery, aspiration, pneumonia, pancreatitis, and massive transfusion \[[@CR1], [@CR20]--[@CR22]\]. The exclusion criteria were inclusion of patients without a risk factor for ARDS, inclusion of patients who had already developed ARDS upon arrival to the hospital or ICU, lack of a comparison group, and healthy volunteer studies. Non-English-language studies were also excluded. The primary outcome was the incidence of newly developed ARDS in high-risk patients. Secondary outcomes were hospital and ICU mortality. Two authors (WW and JS) independently screened the titles and abstracts of records to identify potential studies. Baseline patient characteristics, interventions, controls, and outcomes were extracted after full-text review using a standard data extraction form (see Additional file [2](#MOESM2){ref-type="media"}). Disagreements were resolved by discussion with a third author (ZW). Quality assessment {#Sec5} ------------------ The risk of bias in randomized studies was evaluated with the Cochrane Collaboration tool for assessing the risk of bias \[[@CR23]\]. For observational studies, the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies was applied accordingly \[[@CR24]\]. Observational studies with NOS scores of 8 or 9, 6 or 7, and \< 6 were judged as low, medium, and high risk of bias, respectively \[[@CR25]\]. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to judge the quality of evidence for each outcome \[[@CR26]\]. The quality of evidence was judged as high, moderate, low, or very low using GRADE profiler 3.6 (GRADEpro; McMaster University 2014, Hamilton, Canada). Data analysis {#Sec6} ------------- Randomized and observational studies were analyzed separately. If adjusted odds ratios (ORs) were reported, then they were extracted and used for data combination. Otherwise, calculated ORs were used for data combination. The chi-square test was used to combine data with 95% confidence intervals (CIs). A fixed-effect model was used for combination when heterogeneity was absent according to the *Q* statistic (*p* ≥ 0.1) and Higgins *I*^2^ test (*I*^*2*^ \< 30%). Otherwise, a random-effect model was used. Pre-specified subgroup analyses were conducted for the primary outcome. Sensitivity analysis was performed on the primary outcome by omitting one study at a time to assess the robustness of the results \[[@CR27], [@CR28]\]. A funnel plot was not applicable because of the limited number of studies included in this analysis \[[@CR29]\]. Publication bias was examined by Egger's test. A *p* value \< 0.05 was considered statistically significant. All statistical analyses were performed in STATA, version 13.0 (Stata Corporation, College Station, TX, USA). Results {#Sec7} ======= Our search identified 1767 relevant publications. After duplicates were removed, 1340 study titles and abstracts were screened, and 29 studies were selected for full-text review. Finally, we included 9 studies (2 randomized studies \[[@CR18], [@CR30]\] and 7 observational studies \[[@CR11], [@CR31]--[@CR36]\]) with 7660 patients in this meta-analysis. Details of the study selection procedure are shown in Fig. [1](#Fig1){ref-type="fig"} (see studies excluded and reasons for exclusion in Additional file [3](#MOESM3){ref-type="media"}: Table S1). Study characteristics are shown in Table [1](#Tab1){ref-type="table"}.Fig. 1Search, inclusion and exclusion flow diagram. ARDS, acute respiratory distress syndromeTable 1Main characteristics of the randomized and observational studiesAuthor, yearStudy designNumber of centers; countryStudy scale, total number (anti/non-anti)Study populationDefinition of antiplatelet therapyDefinition of ARDSKor, 2016 \[[@CR18]\]RCT16; USA390 (195/195)Patients aged 18 years or older with an elevated risk of developing ARDS (LIPS ≥4)AspirinBerlin definitionVincent, 1985 \[[@CR30]\]RCT1; Belgium43 (16/17)Patients developed an episode of non-cardiogenic shock due to hemorrhage, trauma or sepsisDipyridamoleSevere hypoxemia and generalized lung infiltrates with PAWP \<14 mmHgMazzeffi, 2015 \[[@CR32]\]Retrospective cohort1; USA375 (181/194)Patients received aortic valve replacement surgery with cardiopulmonary bypassAspirinBerlin definitionChen, 2015 \[[@CR31]\]Prospective cohort1; USA1149 (287/862)Patients admitted to the ICU with a high risk of ARDSAspirinAECC definitionValerio, 2013 \[[@CR11]\]Retrospective cohort1; USA651 (272/379)Patients admitted to the medical ICU with severe sepsis and septic shock on antiplatelet therapy before diagnosis of severe sepsis or septic shock.Aspirin, clopidogrelAECC definitionKor, 2011 \[[@CR33]\]Prospective cohort20; USA, 2; Turkey3855 (976/2879)Adult, non-surgical patients admitted to the hospital with at least one major risk factor for ALIAspirinAECC definitionErlich, 2011 \[[@CR34]\]Retrospective cohort1; USA161 (79/82)Adult patients admitted to the ICU with at least one major risk factor for ALIAspirin, clopidogrel bisulfate, ticlopidine, hydrochloride, cilostazol, dipyramidole, anagrelide, or persantineAECC definitionAhmed, 2014 \[[@CR36]\]Population-based, nested case-control2; USA828 (414/414)^a^Patients with hospital-acquired ARDS and matched controlsAspirin, abciximab, cilostazol, clopidogrel,dipyridamole, eptifibatide, ticlopidineAECC definitionTuinman, 2012 \[[@CR35]\]Nested case-control1; Netherlands218 (109/109)^a^Adult patients admitted to the medical-surgical ICU diagnosed with TRALI and matched controlsAspirin, clopidogrelThe 2004 consensus definition of TRALI*Abbreviations: RCT* randomized controlled trial, *anti/non-anti* antiplatelet/non-antiplatelet, *ICU* intensive care unit, *ARDS* acute respiratory distress syndrome, *ALI* acute lung injury, *LIPS* Lung Injury Prediction Score, *AECC* American-European Consensus Conference, *PAWP* pulmonary artery wedge pressure, *TRALI* transfusion-related acute lung injury^a^In case-control studies, the numbers represent the total number of patients (number of cases/number of controls) Randomized studies {#Sec8} ------------------ Two randomized studies with 433 patients were identified. In these studies, 39 (9.0%) patients developed ARDS during the study periods. Baseline patient characteristics, antiplatelet interventions and outcomes are shown in Additional file [3](#MOESM3){ref-type="media"}: Tables S2--S4. The overall risk of bias was considered unclear as assessed by the Cochrane risk of bias tool (Additional file [4](#MOESM4){ref-type="media"}: Figures S1 and S2). The incidence of newly developed ARDS (OR 1.32, 95% CI 0.72--2.42; *I*^*2*^ = 0.0%, *p* = 0.329) (Fig. [2](#Fig2){ref-type="fig"}) and hospital mortality (OR 1.15; 95% CI 0.58--2.27; *I*^*2*^ = 0.0%; *p* = 0.440) (Additional file [4](#MOESM4){ref-type="media"}: Figure S3) was not significantly reduced in the antiplatelet groups, with low heterogeneity among the results. ICU mortality was not pooled due to a lack of data. Subgroup analyses and sensitivity analysis were not performed because only two studies were included.Fig. 2Effect of antiplatelet therapy on newly developed acute respiratory distress syndrome, based on randomized studies. An odds ratio (OR) \<1 favors antiplatelet therapy The evidence was considered low quality for both newly developed ARDS and hospital mortality according to the GRADE system (Additional file [3](#MOESM3){ref-type="media"}: Table S5). Observational studies {#Sec9} --------------------- Seven observational studies with a total of 7227 patients were identified. Among them, 844 patients (11.6%) developed ARDS. Patient characteristics, antiplatelet interventions, and outcomes are shown in Additional file [3](#MOESM3){ref-type="media"}: Tables S6--S8. The average NOS scores of cohort studies and case-control studies were 7 (6--8) and 7, respectively, and the overall risk of bias was determined to be medium (Additional file [3](#MOESM3){ref-type="media"}: Table S9). The pooled OR in a random model (OR 0.68, 95% CI 0.52--0.88; *I*^2^ = 68.4%, *p* = 0.004) indicated an association between antiplatelet therapy and a reduced incidence of newly developed ARDS (Fig. [3](#Fig3){ref-type="fig"}), with high heterogeneity among the results. Neither hospital mortality (OR 0.80, 95% CI 0.62--1.03; *I*^2^ = 31.9%, *p* = 0.221) nor ICU mortality (OR 0.84, 95% CI 0.63--1.11; *I*^2^ = 0.0%, *p* = 0.851) (Additional file [4](#MOESM4){ref-type="media"}: Figures S4--S5) was reduced in antiplatelet groups.Fig. 3Effect of antiplatelet therapy on newly developed acute respiratory distress syndrome based on observational studies. An odds ratio (OR) \< 1 favors antiplatelet therapy Subgroup analyses demonstrated that heterogeneity was not significant between groups with respect to the definition of antiplatelet therapy, the timing of antiplatelet therapy, the definition of ARDS, or the sample size of the study population. Heterogeneity was not observed in terms of the risk factors for ARDS, except for high-risk surgery. The heterogeneity between studies significantly decreased in the subgroups of study design (*I*^2^ from 68.4 to 0.0%) and high-risk surgery (*I*^2^ from 68.4 to 0.0% and 8.2%). The dose of antiplatelet therapy was not well-documented in the studies. Notably, antiplatelet therapy showed slightly greater protective effects in patients when the analysis was restricted to studies that included patients who used aspirin only, patients receiving antiplatelet therapy before hospitalization, patients with a diagnosis of ARDS according to the American-European Consensus Conference (AECC) definition, and patients without sepsis, shock, pneumonia, aspiration, trauma, high-risk surgery, pancreatitis, or massive transfusion. All results of the subgroup analyses are summarized in Table [2](#Tab2){ref-type="table"} (forest plots are shown in Additional file [4](#MOESM4){ref-type="media"}: Figures S6--S17). Combined ORs were not substantially altered in the sensitivity analysis (Additional file [4](#MOESM4){ref-type="media"}: Figure S18). Notably, the heterogeneity between groups significantly decreased (I^2^ = 2.2%) when the study conducted by Ahmed et al. was removed (forest plot shown in Additional Figure S19) \[see Additional file [4](#MOESM4){ref-type="media"}\]. The publication bias was not evident (Egger test *P* = 0.206).Table 2Summary of the subgroup analyses in observational studiesSubgroupsNumber of studiesSample sizeOR95% CIPI^2^Definition of antiplatelet therapy Aspirin only353790.67(0.52--0.86)0.8290.0% Aspirin in combination418480.67(0.44--1.02)0.00378.8%Time of antiplatelet therapy Before hospitalization353790.67(0.52--0.86)0.8290.0% Before and/or after hospitalization418480.67(0.44--1.02)0.00378.8%Risk factors for ARDS Sepsis  Yes557030.69(0.50--0.95)0.00474.3%  No215240.64(0.46--0.90)0.6030.0% Shock  Yes348340.74(0.52--0.88)0.06263.9%  No423930.61(0.48--0.77)0.3645.8% Pneumonia  Yes348340.74(0.52--0.88)0.06263.9%  No423930.61(0.48--0.77)0.3645.8% Aspiration  Yes348340.74(0.52--0.88)0.06263.9%  No423930.61(0.48--0.77)0.3645.8% Trauma  Yes348340.74(0.52--0.88)0.06263.9%  No423930.61(0.48--0.77)0.3645.8% High-risk surgery  Yes314110.90(0.85--0.95)0.6090.0%  No458160.59(0.48--0.73)0.3528.2% Pancreatitis  Yes348340.74(0.52--0.88)0.06263.9%  No423930.61(0.48--0.77)0.3645.8% Massive transfusion  Yes12180.91(0.49--1.69)----  No570090.65(0.48--0.87)0.00273.6%Definition of ARDS Berlin definition13750.46(0.12--1.74)---- AECC definition566340.66(0.48--0.89)0.00177.9% The 2004 consensus definition of TRALI12180.91(0.49--1.69)----Size of the population Small522230.65(0.44--0.98)0.00473.5% Large250040.68(0.52--0.88)0.8190.0%Study design Prospective cohort225020.68(0.52--0.88)0.8190.0% Retrospective cohort311870.48(0.35--0.66)0.7580.0% Case--control study210360.90(0.85--0.95)0.9720.0%*ARDS* acute respiratory distress syndrome, *AECC* American-European Consensus Conference, *TRALI* transfusion-related acute lung injury The quality of evidence for both newly developed ARDS and hospital mortality was considered low according to the GRADE system, and the quality of evidence for ICU mortality was judged as very low in the cohort studies (Additional file [3](#MOESM3){ref-type="media"}: Table S10). In the case-control studies, the quality of evidence for newly developed ARDS was low (Additional file [3](#MOESM3){ref-type="media"}: Table S11). Discussion {#Sec10} ========== Antiplatelet therapy has been suggested as an option for ARDS prevention, but its impact on patients at a high risk of ARDS remains controversial. We performed a meta-analysis of both randomized and observational studies, focusing on the potential preventive effects of antiplatelet therapy in patients at high risk of ARDS. The analysis of the observational studies suggested that antiplatelet therapy was associated with a reduced incidence of newly developed ARDS. However, the analysis of the randomized studies showed no difference between groups. Antiplatelet therapy was not significantly associated with improved mortality in randomized or observational studies. The result of the pooled analysis of the randomized studies contradicted the conclusions of the observational studies on the incidence of newly developed ARDS. As randomized studies have a higher evidence level, this finding may suggest that antiplatelet therapy could not protect high-risk patients from ARDS. However, only two randomized studies were included, and the pooled results were mainly influenced by the study conducted by Kor et al. There are some noticeable differences between randomized and observational studies. All observational studies recruited patients who had received antiplatelet therapy before being admitted to the hospital or the ICU. Although a propensity-adjusted analysis was performed for each observational study, potential heterogeneity among baseline characteristics in the studies cannot be ruled out. Patients on pre-hospital antiplatelet therapy were older and had more comorbidities \[[@CR11], [@CR31], [@CR33], [@CR34]\]. Antiplatelet therapy is widely used for secondary prevention of malignant cardiovascular events in older patients with atherosclerotic vascular disease. Atherosclerosis, which is regarded as a chronic low-grade systemic inflammation, may predispose patients to excessive acute inflammation and may increase resistance to inflammation-associated cytokine production and organ failure \[[@CR37]\]. A history of vascular disease had an additional benefit on hospital outcomes \[[@CR37]\]. In the well-designed randomized studies conducted by Kor et al., potential cofounding effects of pre-hospital use of antiplatelet therapy were mitigated by excluding patients who received antiplatelet therapy at the time of hospitalization \[[@CR18]\]. Additionally, the incidence of ARDS in patients who discontinued antiplatelet therapy during hospitalization was not significantly different from that in patients who continued antiplatelet therapy \[[@CR31]\]. These findings implied that long-term pre-hospital antiplatelet therapy may protect high-risk patients from ARDS, but this benefit was not evident when patients received antiplatelet therapy after the onset of risk factors. Pre-hospital antiplatelet therapy may protect patients by suppressing platelet aggregation before initial insults occur, but the protective effect may be compromised if this process has already been triggered. Use of a low dose of 81 mg of aspirin in randomized studies did not significantly reduce the incidence of ARDS \[[@CR18]\]. Four of seven observational studies included patients with antiplatelet therapy other than aspirin. A subgroup analysis of the observational studies indicated that patients who used aspirin only had a lower risk of developing ARDS compared with patients using mixed medications. Most patients in the observational studies used low-dose aspirin (81-100 mg), but the data on dosage were insufficient for subgroup analysis. It is reasonable to assume that aspirin will be a prospective treatment. Previous studies have proven that low-dose aspirin is more potent in inhibiting cyclooxygenase I (COX I) than cyclooxygenase II (COX II) \[[@CR38], [@CR39]\]; the former is responsible for normal homeostatic processes and the latter inhibits inflammation. Although low-dose aspirin has also been shown to have anti-inflammatory effects due to aspirin-induced lipoxin formation, high-dose aspirin may be more effective in preventing ARDS as all preclinical studies showed beneficial effects of high-dose aspirin in ARDS \[[@CR5]\]. Since high-dose aspirin may be related to an increased risk of bleeding, it should be considered with caution pending further clinical investigation. In another randomized pilot study performed by Vincent et al., patients with circulatory shock received aspirin plus dipyridamole versus aspirin plus placebo \[[@CR30]\]. The active comparator was dipyridamole and was therefore included in our analysis. As a small pilot study, they focused on a group of patients with circulatory shock, which is a common risk factor for ARDS in critically ill patients. This study included a relatively large number of patients presenting with hemorrhagic shock, but arterial hypotension was corrected in less than 12 h to avoid coagulation abnormalities in severe or prolonged states of shock. Considering that including patients with hemorrhagic shock and trauma may be confounding, we performed a subgroup analysis on studies with and without patients with shock or trauma. This analysis revealed a slightly greater effect on the decreased incidence of ARDS compared with the overall analysis (0.61 versus 0.68); however, the on pooled analysis of the studies of patients with shock or trauma, the decreased incidence of ARDS was no longer significant (*p* = 0.062). Continuing antiplatelet therapy in patients without hemorrhage may be safe, but antiplatelet therapy in patients with a risk of hemorrhage may be risky. The present analysis extends the findings of a recent meta-analysis conducted by Panka et al. in which similar inclusion and exclusion criteria were applied \[[@CR5]\]. In observational studies, antiplatelet therapy was associated with a reduced incidence of ARDS but not of mortality. A previous meta-analysis conducted by Wang et al. and Mohananey et al. revealed decreased mortality among critically ill patients receiving antiplatelet therapy \[[@CR25], [@CR40]\]. Notably, they included studies that did not report the incidence of ARDS \[[@CR37], [@CR41]--[@CR51]\] and possibly included patients at a lower risk of ARDS, which may confound the result \[[@CR43], [@CR48]--[@CR51]\]. Most would expect that if patients were less likely to develop ARDS, then their risk of death would decrease. These results prompted us to review the reported adverse events in the included studies. The most concerning bleeding-related adverse events and acute kidney injury were not significantly different between patients who received or did not receive antiplatelet therapy \[[@CR11], [@CR18]\]. The case-control study conducted by Ahmed et al. indicated that adverse events were strongly associated with ARDS development, as were inadequate antimicrobial therapy, mechanical ventilation with injurious tidal volumes, hospital-acquired aspiration, and the volumes of blood products transfused and fluids administered \[[@CR36]\]. Vincent et al. also reported that total blood transfusion volume and the ratio of thrombocytopenia was significantly higher in patients who developed ARDS \[[@CR30]\]. Most observational studies did not consider these important factors in their analyses \[[@CR31], [@CR32], [@CR34]\], potentially contributing to an overestimated benefit of antiplatelet therapy in ARDS prevention. To our knowledge, this is the first study to explore the potential preventive effects of antiplatelet therapy in patients at a high risk of ARDS in both randomized and observational studies. Nonetheless, this investigation also has important limitations. First, the studies included in this meta-analysis varied considerably in the definition of ARDS, baseline patient characteristics, interventions, and study design. To address this limitation, subgroup analyses and a sensitivity analysis were performed. The subgroup analyses demonstrated that heterogeneity was mainly caused by study design and the inclusion of high-risk surgical patients, but the results remained consistent between subgroups. The sensitivity analysis indicated that the heterogeneity was significantly influenced by the study conducted by Ahmed et al., but the effect of the pooled result did not substantially change after this study was removed. Second, although the search was rigorous and comprehensive and focused on high-risk patients, interpretation of the synthesized results was limited since only two randomized studies and seven observational studies were included. Third, despite a strict selection process, the overall risk of bias was judged as unclear in the randomized studies and as medium in the observational studies. Observational studies have limitations by nature. Therefore, we used the GRADE system to assess the quality of evidence for outcomes. The quality of the evidence provided by the cohort and case-control studies was equal to the quality of the randomized studies, suggesting that the results from the observational studies should also be seriously considered. Furthermore, most of the patients included in this meta-analysis used aspirin alone, and conclusions on other antiplatelet agents should therefore be interpreted with caution. Finally, unpublished studies or conference abstracts were not included, which may be of great significance as well. Conclusions {#Sec11} =========== In this analysis, antiplatelet therapy did not significantly reduce mortality in high-risk ARDS patients. However, whether antiplatelet therapy is associated with a decreased incidence of ARDS in patients at high risk of ARDS is still unclear. Therefore, series of large, well-designed randomized trials, especially those focusing on the timing of antiplatelet therapy, the dose of antiplatelet drugs, and the indication for antiplatelet therapy according to the cause of ARDS, are advocated in this area. Additional files ================ {#Sec12} Additional file 1:PRISMA 2009 checklist. (DOC 64 kb) Additional file 2:Study protocol. (DOCX 44 kb) Additional file 3:Supplemental Tables. Studies excluded with reasons. Data regarding baseline patient characteristics, interventions and outcomes. Quality of the included studies. (DOCX 128 kb) Additional file 4:Supplemental Figures. Risk of bias of the included studies and funnel plots. (DOCX 12877 kb) AECC : American-European Consensus Conference ARDS : Acute respiratory distress syndrome GRADE : Grading of Recommendations Assessment, Development, and Evaluation ICU : Intensive care unit NOS : Newcastle-Ottawa Scale OR : Odds ratio PRISMA : Preferred Reporting Items for Systematic Reviews and Meta-Analyses RCT : Randomized controlled clinical trial **Electronic supplementary material** The online version of this article (10.1186/s13054-018-1988-y) contains supplementary material, which is available to authorized users. We are grateful to Wensen Chen (Office of Infection Management, the First Affiliated Hospital of Nanjing Medical University) for providing advice in the process of data analysis and in revising the manuscript. We would like to thank the authors of the studies that were included in this analysis. Their work is very much appreciated. Funding {#FPar1} ======= This research was sponsored by the Natural Science Foundation of Shanghai (Grant number 14ZR1407000). Availability of data and materials {#FPar2} ================================== The datasets used during the current study are available from the corresponding author upon reasonable request. YW and MZ had full access to all the data in the study and accept responsibility for the integrity of the work as a whole, including the data and the analysis, and the entire submission process from inception to publication. YW and MZ were also responsible for the study design, study selection, data analysis, interpretation of the data, and drafting and revision of the manuscript. DZ was responsible for the conception and design of the study. JS and WW assisted with the electronic search and data acquisition. ZW contributed to interpretation of the data. All authors read and approved the final manuscript. Ethics approval and consent to participate {#FPar3} ========================================== Not applicable. Consent for publication {#FPar4} ======================= Not applicable. Competing interests {#FPar5} =================== The authors declare that they have no competing interests. Publisher's Note {#FPar6} ================ Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Fernando Espinosa (Mexican footballer) Fernando Espinosa Barrera (born 9 May 1983) is a Mexican football midfielder who currently plays for Celaya F.C. in the Ascenso MX Club career Espinosa plays for Club Universidad Nacional (commonly called Pumas UNAM), a Mexico City team. He joined the Pumas youth system at age 14 and worked his way through the ranks to make his Primera División debut in 2004. On December 18, 2014 Espinosa signed for Atlante on loan from Pumas Unam on a season-long loan deal. Honours Pumas UNAM Primera División de México: Apertura 2004, Clausura 2009 Champion of Champions: 2004 Santiago Bernabéu Cup External links Category:1983 births Category:Living people Category:Footballers from Mexico City Category:Association football midfielders Category:Mexican footballers Category:Club Universidad Nacional footballers Category:Atlante F.C. footballers Category:Club Celaya footballers Category:Liga MX players

Raking in the Rewards Do you ever hear stories about people who use rewards programs to save extra money, then have a hard time believing they were really able to save that much? You and me both. Then one day I saw a Facebook post from a good friend of mine who said she was able to save more than $4,000 in the past year using rewards and coupons. In other words, she saved 46% off her total year’s spending goals! I’ll admit it, that had me intrigued. I immediately reached out to her and begged her to tell me how she did it. Interested in finding out? Read on for some great tips from my friend and budgeter extraordinaire, Elizabeth Rauf. These tips will focus on how she did it with rewards – then we’ll check back in to share how she did it with coupons. What is a Rewards Program? First off, let’s take a minute to discuss what a rewards program is. Store rewards programs – also known as loyalty programs – offer you incentive to continue shopping at that particular store through discounts and prizes. This can take on many forms. Some retailers like CVS and Walgreens will give you a loyalty card for free. Other loyalty cards come at a premium but promise to pay off in dividends later (Amazon Prime is an online example of this). Finally, there are special retail credit cards that offer discounts every time you buy and pay with that card. So what’s the point? The store wants you to remain loyal to them, of course! Aside from that, this also gives you more incentive to spend when you wouldn’t otherwise. While these programs can be a slippery slope for your budget, done right they can save you a boatload of money. How to Maximize Your Rewards Programs Signing up for a rewards program is generally quite easy…it’s maximizing them that takes a little bit of effort. According to Elizabeth, the key to making these programs work for you is to: 1) have a deep understanding of the program and 2) remember to use the program. Understanding Your Rewards Programs Let’s start with understanding the program. This is especially important if you’re signing up for a rewards program that costs money. Compare the price of the program with the amount you could save by using it. Elizabeth breaks this down, using book buying as an example: “Barnes and Noble, for example, has a membership you can buy for $25/year. You get percentages off books and free shipping. And if you regularly buy new books from that store, it might be worth it, especially with the free shipping. But if you prefer to buy used books on Amazon or at your local Friends of the Library sale, $25 is too much.” The next aspect of understanding your rewards program is knowing what you get and when it expires. According to Elizabeth, Kohl’s rewards points expire one year after they’re earned, MyCokeRewards expire three months after an account has been inactive, and Delta Skymiles never expire (although Elizabeth used to work at Delta and learned the rewards can expire after three years of account inactivity). If you have rewards that have already expired, all hope may not be lost. Some stores have a loose policy on what “inactive” means, such as the Delta example mentioned above. To play it safe if you are thinking of signing up for a rewards program, evaluate when things do expire and whether or not you’re likely to use the rewards in that amount of time. So which rewards programs are the best? Elizabeth’s answer: any rewards program that allows you to continually earn rewards. That way you can ensure you’re gaining (and keeping) rewards over a reasonable amount of time and that you don’t have to overspend to take advantage of the rewards. Check your rate using ReadyForZero's free debt consolidation tool. People have saved thousands by consolidating higher-interest debts using a single, personal loan, this will not negatively impact your credit. Check Your Rate Now Remembering to Use Your Rewards Programs What’s worse than spending money on a rewards program that doesn’t make your money back and then some? Spending money on a rewards program and forgetting to use it! Unfortunately, this can be easy to do. One way to remember is plan ahead. Before you head out to a restaurant, shopping trip, or social function, double check to see if you have a corresponding rewards card and grab it before you go. Another option is to have these cards in your wallet at all times and/or to register with your phone number so the retailers can find you easily in their system. Remembering to use your rewards programs isn’t just about remembering to bring your card. There are many ways you can get rewards that aren’t obvious. Elizabeth explains how she managed to earn travel rewards without stepping foot on a plane last year: “You can earn airline miles by flying, but did you know you can also earn them by eating out? Delta, United and American all participate in a dining program in which you sign up, register as many credit or debit cards are you want, and then eat at participating restaurants. Once you’ve dined, they send you an email to fill out a 30-second survey, and you’re finished…I earned Skymiles last year without flying. And since Delta’s definition of ‘account activity’ is any time miles are earned or used, this keeps my Skymiles account active.” So how can you find out what exactly will earn you rewards? Visit the retailer’s rewards page online frequently. New partners could pop up at any time! Utilizing Rewards Programs to Boost Your Budget As you can see, rewards programs are often flexible. And that flexibility allows you to earn rewards for following your already planned out budget. But to make sure these rewards are boosting your budget (not just giving you more stuff) you’ll want to be extra strategic. Don’t just strategize on how your current spending could earn your rewards. Optimize for the rewards that will prevent you from spending on already planned future expenses. That’s how you can ensure that using rewards programs will truly save you money when all is said and done. For example, Elizabeth explains that BP and Shell let you earn points that save you money on future gas purchases. Pretty great, right? Well, Speedway lets you do that – but also gives you a chance to redeem points for food, drinks, and gift cards. Which one would be more beneficial to your budget? (The answer could still be the first two if you’d rather focus your points on gas alone – that’s where being strategic really comes into play.) Once you understand your strategy, then you’re ready for the final step – stacking. This is how Elizabeth was able to save more than $4,000 in one year! Here’s an example of how she did it: “Let’s say I need to buy ink. I have a Staples Rewards card that gives me free shipping, as well as a percentage back later. So where do I start? I start at ebates.com, because they will give me 2 percent cash back on Staples purchases. From ebates.com, I follow their link to Staples.com, where I buy my ink. My rewards program gives me the free shipping and I’ve earned a percentage toward my next reward. I paid with my bank credit card, so I’m earning 1 percent cash back through them. I also registered that credit card with Plink, so I’m earning points toward gift cards there, too. So I saved money (shipping) with the store loyalty program and earned cash and points with four other programs, all on one transaction.” Now that’s what I call some serious rewards program skill! Remember, when it comes to rewards programs, you want to start slow and then strategize. When you get comfortable with the system, you could find more ways to save than you might ever have imagined before. Apply that savings to your debt payoff plan and financial freedom will be just around the corner! Don’t forget to stay tuned for our next post from Elizabeth to find out how coupons played a part in her huge savings! This post was published by Shannon, Community and Customer Support Manager for » ReadyForZero. ReadyForZero is a company that helps people get out of debt on their own with a simple and free online tool that can automate and track your debt paydown. Subscribe to the ReadyForZero Blog Receive updates: DailyWeeklyMonthly You can always unsubscribe by clicking on the link at the bottom of each e-mail. Related Posts You have to switch your thinking about Rewards programs. They don’t put a single dollar in your savings account. All they do is reduce the price to a point where you are enticed to purchase something that otherwise you’d walk away from because it is too expensive. Like most, I find myself buying more from Amazon because of my Prime membership than I would if I had to pay shipping. I am loyal to certain airlines because I tote their credit card and will often justify paying more to get the points. Rewards are valuable if they are nothing more than a bonus on something that you would otherwise purchase, but they are insidious because they convince us to spend money because of the rewards. Its Pavlovian. Shoona I was thinking the exact same thing! They can be “rewarding”, but only if you were going to spend the money in the first place. Becareful not to overspend just because it’s “going to be” a good deal on your rewards. 🙂 Shannon_ReadyForZero You both are absolutely right – rewards can lead to overspending if you’re not careful. However, if you are diligent with your budget and don’t spend outside of planned purchases, then you’ll stand to save a lot by using rewards to purchase items or experiences that were already part of your plan. The key is to stick to your plan, avoid impulse buying, and view rewards as a way to save money and not buy more. Joseph Plink is a good suggestion from the article, as I had never heard of the service. The last free cashback rewards program I used (Envaulted) went belly up and cost me about $50 in promised rewards payout. I understand the point of Cynic and Shoona that you can end up paying more (by purchasing more) when tempted by a rewards/cashback program. But the point Shannon (via Elizabeth) was trying to make is to utilize all rewards programs available if you need to make planned purchases. My wife and I have a variety of no-cost rewards programs that cover most – if not all – online retailers. Between ShopDiscover, Upromise, Corporate Shopping and a health/wellness-based cashback program, we’ve been able to combine program cashback with credit card cashback to earn anywhere from 2%-16%, depending on the vendor. Our recent purchases from Apple, Container Store, Overstock, Groupon, Home Depot, etc. were all planned and researched, rather than instinctive. We view targeted rewards programs like Plink as a bonus; if we are going to make a purchase from a promoted retailer anyways, why not get something back in return. I don’t think either of us have ever been pressured into wasteless spending from the promise of future rewards. Shannon_ReadyForZero Joseph, this is the perfect example of how to use rewards programs in a way that won’t be detrimental to your finances. Choosing cash back rewards can be especially helpful since you can determine what to use the extra money for. While some rewards programs can bring with them temptation to buy more, it looks like you two found the ones that will prevent you from feeling that way. Take control of your financial life Link all your debts or tell us what you owe, sit back while we create a personalized plan, then prepare to conquer your debt. Include credit card debt, student loan debt, mortgages, auto loans, medical debt, and any other type of debt you want to tackle.

Mechanisms and targets involved in maternal and paternal age effects on numerical aneuploidy. Trisomy in the human appears to be predominantly associated with maternal age. The maternal-age effect, however, shows considerable variability across affected chromosomes. Chromosome-specific variation has been reported in the shapes of the maternal-age-effect curves, including very small effects for the large chromosomes (groups A and B), linear increases (chromosome 16), and exponential increases (chromosome 21). There is also variation among chromosomes in whether the segregation errors occur predominantly at maternal meiosis I, meiosis II, and/or postfertilization mitotic divisions. There is also limited epidemiological evidence for a paternal-age effect, which was recently supported by the findings of age-related increases in sperm aneuploidy using fluorescence in situ hybridization methods. The paternal-age effect is considerably smaller than the maternal and is more likely to involve meiotic II errors of the sex chromosomes, whereas the maternal-age effect is more likely to arise from meiotic I errors producing autosomal trisomies. These and other differences suggest that constitutional aneuploidy arises by multiple mechanisms that may affect (1) the nature and timing of an initiating lesion affecting the oocyte or sperm; (2) the cellular physiology of the time of the nondisjunction event at meiosis I, II, or postfertilization; and (3) the selection against specific chromosomal aneuploidies during embryonic development. Multidisciplinary research is needed to understand the maternal and paternal-age effects on aneuploidy, to (1) identify and characterize the genes that control meiosis, recombination, and segregation; (2) identify the micro-environmental factors around the oocyte and mole germ cells that are involved in the age effects; (3) develop a laboratory animal model for the age effects; (4) characterize the role of genetics, physiology, and environmental toxicology for the paternal-age effects; and (5) identify cohorts of men and women of differing ages who have been exposed to high doses of candidate aneugens and conduct epidemiological investigations of aneuploidies transmitted to their offspring.

Q: What is the `edit` attr in a meta tag I was looking at jsfiddle's code and saw these lines: <meta name="description" edit="mootools shell, easy test you snippets before implementing"> <meta name="keywords" edit="mootools,javascript,javascript framework,shell,test"> <meta name="robots" edit="all"> I've never seen the edit attr before. What does it do? I couldn't find any info on w3.org or google A: I would bet it's just mistake on their part and the "edit" attribute should have been "content". Maybe you should send them a note and let them know. Update: I just sent Piotr a note, letting him about it. I'll update my answer with his response (if any).

[Lymphography in cancer of the prostate]. The frequency and area of lymphogenic metastasis with relation to the histological structure, differentiation and degree of local dissemination of a primary tumor were determined at lymphography of 114 patients with prostatic cancer. Lymph node involvement was often observed in poorly differentiated and solid trabecular adenocarcinoma, scirrhous cancer and locally disseminated tumors extending beyond the prostatic capsule. Metastases were usually located in the external and common inguinal lymph nodes. Lymphography was shown to be indicated to patients with a local spread of prostatic cancer (T2, T3 and T4).

好奇心原文链接：[一个 26 岁的人成了出版集团康泰纳仕的新星，这是怎么发生的？_商业_好奇心日报-Sydney Ember](https://www.qdaily.com/articles/50779.html) WebArchive归档链接：[一个 26 岁的人成了出版集团康泰纳仕的新星，这是怎么发生的？_商业_好奇心日报-Sydney Ember](http://web.archive.org/web/20190623192355/https://www.qdaily.com/articles/50779.html) 

Laminins are large extracellular glycoproteins that are important components of all basement membranes. They are involved in several biological processes, including self polymerization, binding to the extracellular matrix (ECM) and cellular interactions.[@R1]^,^[@R2] All laminins are composed of three different gene products, termed α, β and γ chains assembled into a cross-shaped heterotrimer αβγ. The three chains assemble within the endoplasmic reticulum through their C-terminal domains to form a triple stranded α-helical coiled coil rod.[@R3]^,^[@R4] Sixteen laminin isoforms of different subunit composition selected from five individual α chains (α1 to α5), three β chains (β1 to β3) and three γ chains (γ1 to γ3), are known with variable cell and tissue specific expression, and they are differentially recognized by cellular receptors.[@R5] All laminin α chains possess a large globule at the carboxyl-terminal end that consists of five similar domains LG1 to LG5 each containing about 200 residues.[@R6]^,^[@R7] Laminin 332 and Its Maturation Events ===================================== Laminin 332, composed of the α3, β3 and γ2 chains, is an epithelial-basement membrane specific variant. The α3 chain is encoded by the LAMA3 gene, which has two transcript variants α3A and α3B. As the truncated LAMA3A variant is expressed and incorporated into laminin 332 heterotrimers,[@R8] we will refer to the α3Aβ3γ2 trimer as representing laminin 332 in this review. Its main role in normal tissues is the maintenance of epithelial-mesenchymal cohesion in tissues exposed to external forces including skin and stratified squamous mucosa.[@R9]^,^[@R10] To fulfill this function, laminin 332 undergoes several physiological post-translational processing events allowing its supramolecular integration into the basement membrane. In other situations such as wound healing or carcinoma, additional cleavages may take place delivering pro-migratory signals to cells therefore compromising the adhesive function of the protein. Laminin 332 processing and integration into the skin basement membrane ---------------------------------------------------------------------- In skin, laminin 332 is synthesized by keratinocytes as a high molecular weight precursor protein of 460 kDa. After secretion and deposition into the ECM, the α3 and γ2 chains undergo maturation events consisting in specific processing to smaller forms.[@R4]^,^[@R11] The 190--200 kDa α3 chain (α3~200~) can be successively processed at both C- and N-terminal extremities producing 165 (α3~165~) and 145 kDa (α3~145~) maturation products. The 155 kDa γ2 chain (γ2~155~) is processed in the N-terminal region leading to a 105 kDa product (γ2~105~). Processing of the α3 chain consists of cleavage of the C-terminal globular domains 4 and 5 (LG45) within the spacer between LG3 and LG4 ([Fig. 1A and B](#F1){ref-type="fig"}).[@R12]^,^[@R13] In vitro studies using human laminin 332 have revealed that enzymes involved in the processing include plasmin,[@R12] MMP-2, MT1-MMP and the C-proteinase family of enzymes, especially mammalian tolloid (mTLD) and the bone morphogenic protein 1 (BMP-1).[@R14]^,^[@R15] In addition, thrombin was shown to have the potency to cleave LG45 specifically.[@R16] Alternatively, there may be other mechanisms that control the rate of laminin α3 LG45 processing, such as the tissue plasminogen proteolytic cascade.[@R12] N-terminal amino acid sequencing of human LG45 purified from the conditioned medium of either primary or immortalized human keratinocytes and of the human gastric adenocarcinoma cells STKM-1 revealed that the α3 chain is cleaved between Q~1337~ and D~1338~ within the hinge region between LG3 and LG4 suggesting that a proteolytic cleavage site of the LG45 domain matches the minimal consensus sequence LLQD ([Fig. 1B](#F1){ref-type="fig"}).[@R17]^,^[@R18] It is not known what endopeptidase catalyzes the hydrolysis of this cleavage sequence, and the existence of additional proteolytic cleavage sites has been suspected both in the hinge and the adjacent regions of the LG3 and LG4 domains.[@R7]^,^[@R13]^,^[@R14]^,^[@R19] This hypothesis is compatible with the spacer length of the laminin α3 chain, which is longer than those of the α1, α2 and α5 chains.[@R7] Punctual mutations within the spacer region and/or deletion of the sequence LLQD did not protect the α3 LG3-LG4 linker from cleavage.[@R14]^,^[@R19] As proteolytic processing of LG domains occurs in all α chains except α1, the substitution of the α3 LG3-LG4 hinge with that of the α1 chain was an elegant way to render the laminin α3 chain uncleavable.[@R19] This was also the case when a 46 amino-acid portion within the α3 LG3-LG4 hinge was deleted.[@R16] These LG45-uncleavable α3 chain constructs were expressed in human[@R19] or mouse[@R16] skin keratinocytes deficient for expression of the α3 chain, and in both cases the resulting LG45-uncleavable heterotrimeric laminin 332 was deposited in the ECM. Information gained from the structure of the mouse α2 chain LG45 domain pair revealed an unusual path of the LG3-LG4 linker as it forms an inter-domain disulfide bridge to LG5.[@R20] Being integrated into the LG45 tandem the linker is therefore an integral part of the structure, a feature that is conserved in all laminin α chains. It is tempting to speculate that proteinases may have easy access to the LG3-LG4 cleavage sites located within a well-exposed linker.[@R7] ![**Figure 1.** Structure of human laminin 332 and its physiological maturation process. (**A**) Laminin 332 is composed of three subunits α3A, β3 and γ2. Each chain is composed of different domains that are indicated. Domain L4 in the γ2 chain corresponds to an LE domain with a \~180 residues insert between the third and fourth cysteine of the canonical 8-Cys pattern. LE4\' and LEb4\' of the α3A and γ2 chain are truncated LE repeats containing only the first four and six cysteines, respectively, of the pattern. Based on the odd number of cysteines, β3LN, α3ALE4\', β3LE6 and γ2LEb1 (after maturation), and the coiled coil of α3 have free SH groups as indicated. The coiled coil is stabilized by disulfide bonds at the N-terminus (dotted lines) though the connectivity is yet unknown. The large LG structure located at the C-terminal end of the α3 chain contains five repeating LG domains. The first three repeats (LG1--3) interact with α3β1, α6β1 and α6β4 integrins while the last two (LG45) contain binding sites for syndecan-1 and -4. Laminin 332 is synthesized as a precursor molecule that undergoes maturation by proteolytic processings at the α3Α chain N- and C-terminus as well as at the γ2 chain N-terminal extremity. The cleavage sites are indicated by arrows as well as enzymes involved identified so far. (**B**) Schematic structures of LG. The five LG domains contain numerous cysteines that are numbered. Disulfide bridged and free cysteines (SH) within the human sequence are indicated. At the bottom, an alignment of the human and mouse LG3-LG4 linker is shown. Each sequence displays the same cleavage site (underlined) and a cysteine (printed in inverse font) that forms an inter-domain disulfide bond to LG5.[@R20] The sequence P~1312~PFLMLLKGSTR supposed to be crucial for integrin α3β1 binding[@R58] is double underlined.](cam-7-122-g1){#F1} Further cleavage occurs in the N-terminal LE region of the α3 chain releasing the full short arm which might be important for laminin 332 function ([Fig. 1A](#F1){ref-type="fig"}).[@R14]^,^[@R21] A mutation causing an N-terminal deletion of 226 amino acids in the human α3A isoform was identified in the laryngo-oncho-cutaneous syndrome, a rare autosomal recessive disorder characterized by chronic production of vascularized granulation tissue.[@R22] Cultured keratinocytes obtained from patients revealed that heterotrimeric laminin 332 carrying the mutant α3 chain is assembled and secreted. The mutated laminin was regularly expressed in the skin basement membrane and only very subtle ultrastructural changes were seen such as focal widening of the lamina lucida in places where hemidesmosome plaques were smaller. These studies suggest that the laminin α3 N-terminal domain may be a key regulator of the granulation tissue response during wound healing. In human skin laminin 332, the processing of the γ2~155~ chain leads to the γ2~105~ subunit and was shown to be achieved by BMP-1 and mTLD metalloproteinases.[@R11]^,^[@R14]^,^[@R15]^,^[@R23]^,^[@R24] The N-terminal processing is complex as it occurs within a disulfide-linked loop of the L4 domain followed by reshuffling of disulfide bonds for release of the cleaved fragments.[@R24] The immunohistochemical analysis of laminin 332 in mTLD/BMP-1-deficient mouse skin revealed a strong expression of the precursor γ2 chain confirming that these enzymes are involved in the γ2 chain maturation in vivo.[@R25] In contrast, the processing of the LG45 domain in the α3 chain seemed, at least partially, unaffected reinforcing the hypothesis that several enzymes are involved in this maturation process. Laminin 332 was shown to be the major component of anchoring filaments in skin[@R9] where it mediates cell adhesion via interaction of the α3 carboxyl-terminal LG1--3 triplet domain with both α3β1 and α6β4 integrins,[@R26]^-^[@R29] while the N-terminal short arms connect to basement membrane components. Laminin 332 can be incorporated into the basement membrane through at least two mechanisms. The first involves cross-linking of laminin 332 with laminin 311 (α3β1γ1) in the skin basement membrane.[@R21] The complex of laminin 311 with laminin 332 is most likely to derive from an interaction of domain LN in the β3 chain of laminin 332 with domain LE of the α3 chain short arm in laminin 311 (see below). As seen on rotary shadowing electron micrographs of the complex, the LN domain of the short arm interacts with a laminin 311 domain near the intersection of the laminin 311 short arms.[@R21] These complexes are most likely stabilized by a disulfide bridge between an unpaired cysteine in domain LN of the β3-chain and domain LE of processed α3 in laminin 311. A similar complex between laminin 332 and laminin 321 (α3β2γ1) is found in the basement membrane of the amnions. According to the 3-arm interaction hypothesis of laminin polymerization,[@R30] the dimers could self-associate. The second mechanism reports a direct interaction between anchoring filaments and anchoring fibrils. Anchoring fibrils are disulfide bond stabilized dimers of type VII collagen.[@R31] Monomeric laminin 332 as well as the laminin 332/311 dimer directly bind the N-terminal globular domain NC1 of type VII collagen.[@R10]^,^[@R32] The interaction is likely to occur within the short arm of the β3 and/or γ2 subunit.[@R32] Other processing events in laminin 332 -------------------------------------- In addition to the laminin 332 maturation aimed at regulating the skin basement membrane structural integrity, other studies have reported two specific migration-inducing MMP-2 cleavages of the laminin γ2 N-termini producing γ2 chain fragments of 100 and 80 kDa.[@R33] These γ2 processing could also be carried by MT1-MMP in colon and breast carcinoma cells.[@R34] Both enzymes, that were first shown to cleave rat laminin 332, were proposed to also cut down human laminin 332 in both physiological and pathological situations such as tumorigenesis.[@R35]^,^[@R36] MMP-3, -12, -13, -19 and -20 were also shown to process the γ2 chain inducing epithelial cell migration.[@R37]^,^[@R38] Migration events might therefore result from the interaction of newly exposed laminin domains with cell surface signaling receptors. Rat recombinant γ2LEb1-LEb4\' was shown to bind and activate the EGF receptor to stimulate cell migration.[@R39] Studies with cancer cells have reported that MMP-7, MT1-MMP and hepsin cleave laminin β3 leading to increased migration.[@R40]^-^[@R42] The molecular mechanisms of laminin 332 in squamous carcinoma have been reviewed in detail by Marinkovich.[@R43] Laminin 332 Sequence-Structure Relationship =========================================== The structure of the heterotrimeric laminin 332 molecule consisting of disulfide-linked α3, β3 and γ2 chains was first revealed by rotary shadowing electron microscopy, which showed a rod 107 nm in length terminated by one large and two small globules at opposite ends[@R9] which correspond to the C-terminal LG and N-terminal LN and LE/L4 domains, respectively ([Fig. 1A](#F1){ref-type="fig"}). This length is consistent with the later determined sequences which indicate that ca. 570 residues per chain contribute to the three stranded α-helical coiled coil structure giving a length of \~80 nm, and \~7 tandem LE domains accounting for a further 20 nm. Circular dichroism spectroscopy revealed an α-helical content of \~30%[@R44] similar to that determined for laminin 111[@R45] suggesting that most of this secondary structure contribution relates to the coiled coil. Assembly of the laminin 332 trimer occurs in the endoplasmic reticulum where first a disulfide linked β3-γ2 dimer is formed to which the α3 chain aligns via the coiled coil. Trimer formation is a prerequisite for transport to the Golgi complex and secretion but does not require N-linked glycosylation.[@R4] Laminin β3 LN domain -------------------- So far no high resolution structures of laminin 332 domains have been solved. However, based on sequence similarity, some insight into the molecular organization of various domains can be anticipated from homology modeling. Recently, the crystal structure of the N-terminal LN domain together with four adjacent LE modules of the mouse laminin β1 chain has been solved (pdb code: 4aqs).[@R46] The corresponding regions of human laminin β3 can be fitted to this structure ([Fig. 2](#F2){ref-type="fig"}) suggesting that LN (residues 18--248; accession number NP_000219) forms a β-sandwich consisting of eight β-strands folded into a jelly roll motif. The first LE domain (res. 249--314) is tightly integrated into LN, which starts with a disulfide-bonded reverse turn connected by C~21~--C~26~, and the N-terminal region (res. 18--28) associates to LE1. Pro~28~, which is conserved in all laminin LN sequences, fits into a pocket of LE1. Further disulfide bonds can be expected between C~47~-C~69~, C~56~-C~66~ and C~153~-C~173~ ([Fig. 2A](#F2){ref-type="fig"}). This leaves C~67~, which is unique for β3 LN domains and surface accessible ([Fig. 2B](#F2){ref-type="fig"}), in a reduced state making it available for covalently binding to other proteins like laminin 331. The N-linked glycosylation sites found within β1 LN at N~120~ and in γ1 LN at N~58~/N~132~ are absent in the β3 chain. The critical residues D~106~ and T~114~ of γ1 LN involved in calcium binding,[@R46] which might be important for laminin polymerization, are replaced by S~70~ and R~76~ in the β3 chain indicating that this site will not be functional. ![**Figure 2.** Structural model of the human laminin β3 LN-LE1--4 domains. (**A**) The structure shows residues Q~18~ to Q~464~ as a cartoon with red cylinders and blue arrows indicating α-helices and β-strands, respectively. Disulfide bonded cysteines within the LE domains are depicted in ball-and-stick presentation using different colors. Domain boundaries are indicated by dashed lines. P~28~ fits into a pocket shared by the LN and LE1 domain, and the N-terminal residues are interacting with LE1. Disulfides and the free cysteine residue of the LN domain are indicated. (**B**) The electrostatic surface potential is represented in the same orientation and on the same scale as in (**A**). Negative and positive potentials are shown in red and blue, respectively. Homology based modeling was performed using Swiss-Model[@R106] in manual alignment mode with the mouse β1 structure (pdb code 4aqs[@R46]) as a template.](cam-7-122-g2){#F2} Laminin 332 LE and L4 domains ----------------------------- A common feature of LE modules is their connectivity of the eight cysteine residues as C1-C3, C2-C4, C5-C6 and C7-C8. The loop formed between C5-C6 usually consists of eight residues with a glycine in position six. In human laminin 332, the following LE domains deviate from the 8-Cys pattern ([Fig. 1A](#F1){ref-type="fig"}): β3-LE6 preceding the coiled coil contains one extra cysteine (C~572~) between C7 and C8 whereas the corresponding region within α3A-LE4\' is truncated after the fourth cysteine (C~185~; accession number AAA59483) followed by an irregular cysteine (C~199~) just before C~202~/C~205~, which are presumably forming intrachain disulfides at the N-terminus of the coiled coil. The α3A chain is processed just after LE4\' between K~191~ and D~192~.[@R14] LEb1 following domain L4 of the human γ2 chain is missing the fifth cysteine of the 8-Cys pattern and does not contain the glycine residue N-terminal to the sixth cysteine (C~442~; accession number NP_005553). This probably results in an increased mobility of the loop between C~431~ and C~442~ allowing for protease susceptibility. Indeed, major processing occurs by cleavage of the G~434~-D~435~ site ([Fig. 1A](#F1){ref-type="fig"}).[@R23] The L4 domain separating LEa3 and LEb1 can be regarded as a specialized LE domain with a large, \~180 residues long insert between the third (C~196~) and fourth (C~382~) cysteine of the regular pattern. In case of the γ2 chains, the L4 insert is highly conserved from human down to Xenopus and zebrafish, and contains one unique cysteine absent in all other L4 domains. For L4-LEb1 it was shown that this C~309~ is covalently linked with the last cysteine C~459~ of LEb1, which contains an unusual S-S bridge between C~442~-C~445~ corresponding to C6-C7. After cleavage by BMP-1 between G~434~ and D~435~, protein disulfide isomerase was required to release the fragments.[@R24] It remains unclear whether after processing C~459~ stays in a reduced state, or whether disulfide reshuffling might form the usual C7-C8 connectivity and leaves C6, i.e., C~442~, with a free SH group.[@R24] The mouse L4-LEb1 domain pair was modified probably via one or both of the two putative NxT acceptor sites for N-linked glycosylation, which are also found in the human sequence (N~342~ and N~362~). The N~342~xT site is conserved down to zebrafish. Mouse L4-LEb1 binds heparin, nidogen-1 (but not -2), and fibulin-1 and -2; it remains unclear whether these interactions occur between L4 or LEb1, or whether epitopes from both are required.[@R24] In conclusion, besides the β3 LN domain, each of the three irregular LE modules, α3A-LE4\', β3-LE6 and γ2-LEb1 after processing, have one free cysteine which could participate either in interchain disulfide bonding or covalent binding to other proteins like laminins 311 and/or 321. Based on the canonical cysteine pattern, the most likely residues are α3A-C~199~, β3-C~572~ and γ2-C~442~ or γ2-C~459~. Laminin 332 coiled coil and Lβ domain ------------------------------------- Carboxyl terminal to the LE modules, the three laminin chains have a C-x-x-C motif (α3A: C~202~- C~205~; β3: C~581~-C~582~; γ2: C~609~-C~612~) which cysteines are conserved in all laminins and most likely serve for interchain covalent linkage of the heterotrimer.The actual disulfide pattern has not yet been established. The following \~570 residues associate via formation of an α-helical coiled coil represented on the sequence level by a 3--4 heptad pattern of hydrophobic residues.[@R3] As it is the case for all β chains, the β3 coiled coil is interrupted by domain Lβ \~200 residues away from the C-x-x-C motif containing six cysteines (human β3: C~788~-C~818~) probably forming intrachain disulfide bonds. The α3 chain coiled coil contains one cysteine (human α3: C~551~) about 50 nm from the C-x-x-C motif, which has no adjacent counterpart in the other two chains. The coiled coil region is terminated by cysteines close to the C-terminus (human β3: C~1171~; γ2: C~1184~), which based on similarity to the β1 and γ1 chains most probably form an interchain disulfide bond.[@R48] Besides its structural importance for assembly, it has recently been found that in the absence of the LG domains the laminin 111 coiled coil has anti-adhesive properties. When cultured on such truncated laminin 111, cell adhesion and spreading were inhibited; genes compatible with a pro-migratory and pro-invasive function like MMPs and various matricellular proteins were upregulated.[@R47] No comparable studies have yet been performed for laminin 332, but an antagonistic interplay between coiled-coil and LG domains (see below) could be of importance in cancer metastasis. Laminin α3 LG domain~~s~~ ------------------------- The large globule seen in electron micrographs at the tip of the long arm consists of five LG domains formed by the α chains. Domains LG4-LG5 are separated from LG1 to LG3 by a flexible linker ([Fig. 1B](#F1){ref-type="fig"}). As these domains are involved in many interactions (see below), particular interest has been focused on their structural characterization (for a review, see ref. [@R7]). X-ray structures have been solved for the mouse α5 LG1-LG3 triplet (pdb code: 2wjs),[@R49] mouse α1 and α2 LG45 pair (2jd4,[@R50] 1dyk,[@R20] 1okq[@R51]), and mouse α2 LG5 (1qu0[@R52]) which can be used to model the corresponding α3 LG1-LG5 domains ([Fig. 3](#F3){ref-type="fig"}). LG domains fold to a β-sandwich consisting of 14 strands, where the two sheets form a concave and convex interface. Close to the C-terminus, each LG sequence contains two cysteines \~30 residues apart, which form intradomain disulfide bonds ([Fig. 3A and C](#F3){ref-type="fig"}). In contrast to electron micrographs suggesting close proximity of LG1 to LG3,[@R53]^,^[@R54] the α2 LG1--3 structure shows LG1 dissociated from the LG2-LG3 pair.[@R49] Previous work suggested that trimerization of the α with β and γ chains is required for the LG domain to exert its integrin binding activity, and that specifically a glutamic acid two residues apart from the C-terminus of the γ chain is essential.[@R55] This residue is indeed highly conserved in the γ1 and γ2, but not γ3 subunits. A lack of integrin α3β1 binding activity in the absence of at least short β3 and γ2 segments has been shown for α3 LG1-LG3.[@R54]^,^[@R56] The absence of such crucial parts of the β and γ chains could result in the open LG1-LG2 conformation ([Fig. 3A and B](#F3){ref-type="fig"}) and might not reflect the conformation of the native molecule.[@R49] {ref-type="fig"}. All cysteine residues are depicted in space filling (CPK) style. The disulfide bridge between C~941~ and C~971~ (red dotted line) could not be correctly modeled as the template sequence has a shorter loop between the corresponding residues. All other cysteines form disulfide bridges except for C~840~ in LG1 which side chain points into the inner space of the β-sandwich. (**B**) The electrostatic surface potential is represented in the same orientation and on the same scale as in (**A**). Negative and positive potentials are shown in red and blue, respectively. (**C**) A model of LG45 corresponding to residues C~1354~ to Q~1713~ is shown with all cysteines in CPK style. C~1354~ from the loop region connecting LG3 and LG4 forms an interdomain disulfide bond with C~1617~. C~1443~ in LG4 and C~1587~ in LG5 are pointed to the space between the β sheets of the sandwich structures and are not surface accessible, whereas C~1507~-C~1530~ and C~1682~-C~1710~ form disulfide bonds. (**D**) A model of LG4 interacting with a heparin-like carbohydrate chain consisting of four GlcNS(6S)-IdoA(2S) disaccharides (ball-and-stick representation with a surface envelope) is shown. The side chains of K~1434~, R~1436~, and K~1438~, which were shown to be critically involved in syndecan-1 interaction are depicted in red, whereas those of K~1440~ and K~1442~ involved in syndecan-4 interaction are shown in green.[@R59] The ε-amino and guanidinium groups of the lysine and arginine residues, respectively, point to the sulfate groups of the carbohydrate chains. (**E**) The surface view of the model shown in (**D**) indicates the tight packing of the heparin fragment into the groove formed by the concave surface of the LG4 β-sandwich with positive surface potential spaced to fit the distance of sulfate groups. The template structures used for modeling were mouse laminin α2 LG1-LG3 (pdb code: 2wjs)[@R49] and mouse laminin α1 LG4-LG5 (2jd4, chain B).[@R50] Docking of a heparin fragment (1hpn)[@R60] to LG4 was performed with PatchDock.[@R107]](cam-7-122-g3){#F3} The LG3 and LG4 domains are connected by a flexible linker, which was realized very early by the proteolytic susceptibility of mouse laminin 111.[@R45] Based on the C- and N-terminal residues, which can be resolved in the mouse α5 LG1--3 (2wjs[@R49]) and α1 LG4--5 (2jd4[@R50]) structures, respectively, for human α3 the termini of the corresponding loop can be defined as N~1310~ and D~1352~ ([Fig. 1B](#F1){ref-type="fig"}). Close to the middle, α3 LG is processed between Q~1337~ and D~1338~.[@R17]^,^[@R57] This leaves a segment P~1312~PFLMLLKGSTR attached to LG3 which, based on a recombinantly overexpressed LG and synthetic peptide approach, was reported as crucial for integrin α3β1 binding.[@R58] C-terminally truncated peptides, however, abolished this activity. The difference of this part in mouse α3 (PPFLMLFKSPKG, [Fig. 1B](#F1){ref-type="fig"}), however, would suggest that this interaction is rather species specific. Based on the structures of the mouse α1 and α2 LG4--5 pairs, modeling predicts that human α3 C~1354~ within the loop region forms a disulfide bond with C~1617~ in LG5 ([Fig. 3C](#F3){ref-type="fig"}). Corresponding cysteines within the loop and LG5 are found in all laminin α chains down to Drosophila and *C. elegans*. Interestingly, human α3 LG4 (C~1443~) and α1 LG3 contain further cysteines in a similar position, which are not conserved in mouse and rat. Within the model ([Fig. 3C](#F3){ref-type="fig"}), the C~1443~ and C~1587~ SH groups point into the hydrophobic core of the β sandwich. The crystal structures of mouse α5 LG1, LG2, and α1, α2 LG4, LG5 contain tightly bound calcium or magnesium ions interacting with pairs of aspartate residues.[@R20]^,^[@R49]^-^[@R51] Our human α3 LG models ([Fig. 3](#F3){ref-type="fig"}) suggest that these cation binding sites are not conserved. Although within LG1 and LG2 D~827~ and D~1090~, respectively, are present, their partner residues are changed to N~910~ and R~1023~. Within LG4 and LG5, the corresponding residues are replaced by S~1413~/S~1481~ and K~1584~/S~1654~. This does not exclude that α3 LG domains might contain other divalent cation binding sites, but so far no conclusive experimental data exist. Due to their physiological relevance, many studies have been performed to elucidate the interaction of laminins with proteoglycans. As a model for the complex glycosaminoglycan chains, most experiments are performed with heparin. We have recently reported on the specific interaction of human α3 LG45 with syndecans and found that K~1434~, R~1436~ and K~1438~ are crucial for syndecan-1 binding, whereas K~1440~ and K~1442~ show a preference for syndecan-4 (see below).[@R59] Using the modeled α3 LG4 domain and a truncated heparin-like structure (pdb code 1hpn),[@R60] docking simulations predict that the carbohydrate chain aligns to the concave surface of LG4 with the positively charged residues filling the grooves formed by the repeating sulfates ([Fig. 3D and E](#F3){ref-type="fig"}). Functions of LG45 in Precursor α3 ================================= A potential function for the tandem LG45 domains was initially suspected based on the ability of laminin 332 to trigger distinct cellular events depending on the level of processing of its α3 chain. A form of laminin 332 that lacked LG45 was found in mature basement membranes, where it was shown to play an important function in the nucleation and maintenance of anchoring structures through α3β1 and α6β4 integrin interactions.[@R61]^-^[@R63] In contrast, laminin 332 with intact LG45 (α3~200~) was found in migratory/remodelling situations such as epidermal repair.[@R64]^-^[@R66] Indeed, laminin 332 with an α3~200~ chain was found in the ECM of keratinocytes migrating on collagen I or after stimulation by TGF-β1.[@R67]^,^[@R68] In vivo, epidermal injury activates the transcription and deposition of laminin 332 into the provisional matrix by the leading keratinocytes in the process of epidermal outgrowth and migration at the wound edge.[@R8]^,^[@R61]^,^[@R69] Noteworthy, α3~200~ laminin 332 is found in this provisional matrix but is absent from mature basement membranes.[@R16]^,^[@R61]^,^[@R62] Recently, laminin 332 comprising an α3~200~ chain was proposed to be involved in the invasion of squamous cell carcinomas in vivo.[@R70] Polyclonal antibodies targeting the LG45 domains induced squamous cell carcinoma apoptosis in vivo and thus inhibited tumor proliferation.[@R70] Function in laminin 332/311 deposition into the ECM --------------------------------------------------- A function for LG45 in the deposition of laminin 332 in the ECM has been first hypothesized by Carter and coworkers,[@R16] who showed that exogenous human α3~200~ laminin 332, but not α3~165~ laminin 332, was trapped by cultured LAMA3 deficient mouse keratinocytes and deposited within their ECM. Moreover, when these keratinocytes were transfected with constructs encoding either an LG45-uncleavable or a precleaved α3 chain, they deposited a larger amount of the LG45-uncleavable laminin 332 into their ECM as compared with the LG45 pre-cleaved laminin 332 that was preferentially secreted into the culture medium. The importance of LG45 in laminin 332 deposition was confirmed by a study reporting that a mutant laminin 332 lacking the LG45 domain, stably expressed in laminin 332 null keratinocytes derived from a patient with junctional epidermolysis bullosa (JEB) with underlying LAMA3 gene mutations, was less retained in the ECM but rather found in the culture medium as compared with the WT.[@R70] Co-expression of LG45 in these α3~165~ laminin expressing keratinocytes enhanced laminin 332 deposition into the ECM, reinforced keratinocyte adhesion to the ECM and decreased migration. In these cells, LG45 co-localized with the α6 integrin subunit in stable adhesion contacts in a manner comparable to the LG45 domain of WT laminin 332 keratinocytes.[@R70] Another study, however, found no difference in laminin 332 deposited by keratinocytes expressing either LG45 uncleavable or pre-cleaved laminin 332.[@R19] Skin equivalents epithelialized with keratinocytes expressing the α3~165~ laminin 332 displayed a dermal-epidermal junction identical to that obtained with wild type keratinocytes suggesting that α3~165~ laminin 332 was properly deposited into the basement membrane or at least in an amount sufficient to allow dermal-epidermal cohesion.[@R19] Besides, skin equivalents designed with keratinocytes expressing the LG45 uncleavable laminin 332 revealed absence of hemidesmosomes accompanied by an appreciable thickening of the lamina lucida likely secondary to the reduced cohesion of the tissue.[@R19] These experiments show that LG45 cleavage appears to be a prerequisite for hemidesmosome formation in skin equivalent models. These studies show that LG45 has the ability to integrate into the keratinocyte ECM either on its own or when present in the α3~200~ chain. It targets α6β4 integrin containing stable adhesion contacts suggesting that it may play a role in α6β4 integrin clustering in vitro. Although LG45 removal decreased laminin 332 deposition in the ECM, it did not fully prevent it, suggesting that other mechanisms may contribute in controlling laminin 332 deposition. Defective α3 and γ2 processing was seen in cylindromatosis, a rare genetic human disorder characterized by the occurrence of multiple irregular benign epithelial tumors in the upper dermis.[@R63] These nodules display a dramatically enlarged basement membrane (up to 4.3 µm thickness) as well as ultrastructural abnormalities as no clear lamina densa could be detected. The different integrin receptors are found in improper ratios as β1 integrins are upregulated while α6β4 integrin expression and hemidesmosome numbers are decreased.[@R63] Despite a massive accumulation of laminin 332 throughout the entire basal lamina, a thin labeling of the LG45 domain detected at the interface between cylindroma cells and the basal lamina suggests that the LG45 processing may have been delayed. It is not clear whether laminin 332 accumulation in the basement membrane is related to this processing defect. Only one study reported a missense mutation in the LAMA3 gene affecting LG4 in a patient with a mild non-Herlitz JEB phenotype.[@R71] This mutation resulting in G1506E triggers an imperfect local protein folding that, without impairing trimerization of the coiled coil, causes laminin 332 intracellular accumulation within the endoplasmic reticulum. Only a small amount of the laminin 332 harboring the mutated α3 chain is secreted and physiologically processed thus providing partial adhesion functions and explaining the mild phenotype. Therefore structural changes caused by mutations of this highly conserved residue throughout laminin LG4 domains highlights potential important functions of LG45 in laminin secretion. When a laminin α3 cDNA was transfected into HT1080 cells, the exogenous α3 chain was assembled with the endogenous β3/γ2 and β1/γ1 to produce laminin 332 and laminin 311 heterotrimers.[@R72] Out of the two laminin isoforms found in the culture medium, laminin 311 was found primarily with a precursor α3~200~ chain while the laminin 332 was found with an α3~165~ chain.[@R72] Sigle et al.[@R16] showed that exogenous human α3~200~ laminin 311 was not trapped by cultured LAMA3 deficient mouse keratinocytes nor deposited within their ECM like α3~200~ laminin 332 (see above). When these keratinocytes were transfected with constructs encoding an LG45-uncleavable α3 chain, they deposited large amount of LG45-uncleavable laminin 332 within their ECM, and the LG45-uncleavable laminin 311 was found exclusively in the culture medium.[@R16] These results suggest that the two laminin isoforms integrate within the basement membrane through different mechanisms. That α3~200~ laminin 311 was not deposited within the ECM first shows that LG45 could not fulfil this event on its own. It also reinforces the hypothesis that a protein domain present in laminin 332 but absent in laminin 311, possibly in the γ2 chain,[@R73] may contribute to the laminin deposition. Since laminin 311 forms a complex with laminin 332 in vivo, it is tempting to speculate that laminin 311 deposition within the ECM might may depend on its covalent association with laminin 332. Most interestingly, co-polymers of perlecan with mature laminin 311 were identified in ECM formed by alveolar epithelial cells.[@R74]^,^[@R75] Through nidogen linkage to the laminin 311 γ1 chain, perlecan was proposed to nucleate formation of laminin 311 fibrils. Function in cell adhesion and migration --------------------------------------- It has been proposed that precursor laminin 332, together with integrin α3β1, plays a central role in the polarization and migration of cells.[@R12]^,^[@R66] Processing of the laminin 332 α chain was suggested to alter its binding ability to various integrins by differential exposure of binding sites/sequences to integrin receptors. Cell adhesion studies have shown that immobilized purified α3~200~ laminin 332 promotes adhesion of keratinocytes, but to a lesser extent than that obtained with mature laminin 332.[@R76] Further analysis revealed that the α3β1 integrin was the major receptor to interact with α3~200~ laminin 332, while both α3β1 and α6β4 integrins were involved in cell adhesion to α3~165~ laminin 332.[@R76] These findings correlate with previous results showing that cells plated on an α3~200~ laminin 332 rich matrix failed to form α6β4 integrin-dependent hemidesmosomes, whereas plasmin cleavage of the LG45 domain inhibited migration and promoted hemidesmosome formation.[@R12] These data were corroborated by studies showing that α3~200~ laminin 332 is a preferential ligand for integrin α3β1 and/or α6β1, whereas processed α3 LG domains are the preferred ligand for integrin α6β4.[@R65] Besides, the analysis of the binding capacity of soluble recombinant α3β1 integrin to a mini-laminin 332 comprising the five LG domains has revealed an increased affinity for integrin binding when LG45 was cleaved off.[@R56] Information gained from the structural model of the LG predicts that LG1--3 have the shape of a cloverleaf from which LG45 extends.[@R7] The specific length of the LG3-LG4 linker results in LG5 being closer to the LG1--3 cloverleaf than LG4 suggesting that the integrin-binding domain may be differently exposed in α3~200~ and α3~165~ laminin 332. Other studies have contradicted this hypothesis as both α6β4 and α3β1 integrins were found to interact with an LG45-uncleavable laminin 332[@R16] and were colocalized in precursor laminin 332 trails left behind migrating cells.[@R57] Moreover, α6β4 integrin containing stable anchoring complexes[@R77] were detected in cultured keratinocytes expressing precursor- or LG45-uncleavable laminin 332[@R16]^,^[@R19] in which LG45 and α6β4 integrins colocalized.[@R70] Although the β4 integrin was correctly expressed and localized at the apical side of the epidermal basal layer, LG45-uncleavable laminin 332 expressing keratinocytes failed to form hemidesmosomes when seeded over a dermal equivalent model.[@R19] Other studies have reported that soluble LG45 may have a function when released from laminin 332. Experiments have shown that adding either recombinant α3LG45 or LG4 to the culture medium could induce migration of keratinocytes in a MMP-9-dependent manner.[@R78] In similar experiments, LG4 induced activation of pro-migratory MMP-1.[@R79] Moreover, Ras/IkBα transformed keratinocytes that lacked the LG45 domain showed a deficiency in MMP-9 and MMP-1 expression. This deficiency was reversed by replacing LG45 through retroviral transduction.[@R70] Binding sites within α3 LG45 ---------------------------- The mechanism underlying the function of the LG45 domain in laminin 332 remains poorly understood. Several heparin-binding sites have been identified in the α3LG45 sequence ([Table 1](#T1){ref-type="table"}). Some of these conferred heparin-dependent cell adhesion properties, which suggested that this region in laminin 332 could interact with a heparan sulfate proteoglycan receptor.[@R29]^,^[@R59] An early report described the characterization of a heparin-binding synthetic peptide corresponding to residues K~1398~PRLQFSLDIQT derived from the murine α1 LG4 sequence.[@R80] This peptide induces adhesion of the melanoma cells B16F10 through an heparan sulfate proteoglycan type receptor that remains to be identified. A peptidic screening of the murine α3 LG45 domains allowed identification of three heparin binding sites with cell adhesion properties.[@R81] Peptidic screening of the human sequence lead to the identification of a motif that included residues N~1412~SFMALYLSKGR, which was shown to induce syndecan-2 and -4 mediated cell adhesion, neurite outgrowth and MMP-1 and -9 secretion.[@R78]^,^[@R79]^,^[@R82]^,^[@R83] Further work suggested that this motif also induced keratinocyte migration by triggering syndecan-4 clustering and subsequent β1 integrin activation.[@R84] Later, three novel heparin-binding sites were identified based on cross-linking the native protein to heparin beads.[@R85] Recently, through a site-directed mutagenesis approach to alter the most critical basic residues in a recombinant LG45 protein, we identified a unique heparin-binding site surrounded by a track of converging low affinity, positively charged residues ([Fig. 3D and E](#F3){ref-type="fig"}).[@R49] We further showed that this K~1433~KLRIKSKEK sequence region, which matches one of the sites identified by Vives et al.[@R85] harbours distinctive syndecan-1 and -4 interaction sites ([Table 1](#T1){ref-type="table"}). Besides, our group has reported that syndecan-1 is the cellular receptor involved in cell adhesion to the α3 LG45 domain[@R57]^,^[@R86] and this interaction may participate in keratinocyte migration by supporting the formation of actin-based cellular protrusions ([Fig. 4A and B](#F4){ref-type="fig"}).[@R76]^,^[@R87] The development of these membrane protrusions remarkably requires dephosphorylation of tyrosine residues in the cytoplasmic tail of syndecan-1, a condition essential for syntenin-1 recruitment.[@R87]^,^[@R88] In the epidermis, syndecan-1 is located in the pericellular region of keratinocytes and displays a modest expression in the basal cell layer, which becomes increasingly intense in the suprabasal layers. Remarkably, syndecan-1 is strongly induced in wound edge keratinocytes during wound healing.[@R89]^-^[@R91] This elevated expression in keratinocytes appears to be specific to syndecan-1 as no changes have been detected for other syndecans.[@R92] Moreover, syndecan-1 deficient mice display a defect in keratinocyte proliferation and migration during wound healing.[@R93] In light of these data, syndecan family members stimulate interest as potential laminin 332 co-receptors. Recent data has provided evidence that when human squamous carcinoma A431 cells are plated on laminin 332, syndecan-1 forms a complex with the α6β4 integrin. This triggers Fyn-mediated phosphorylation of the β4 integrin cytoplasmic tail activating PI3K- and Akt-mediated signaling, protecting the cells against apoptosis.[@R94] This is of particular interest as LG45 in α3~200~ laminin 332 was proposed as an essential PI3K pathway activation promoter.[@R70] ###### **Table 1.** Heparin binding sites identified within human and mouse LG45 domains -------------------------------------------------------------------------------------------------------- Laminin a3 LG45 heparin binding sites Method used for identification Binding partner References --------------------------------------- -------------------------------- ------------------ ------------ **Human**       N~1412~SFMALYLSKGR Peptide Syndecan-2\ [@R82] Syndecan-4 L~1428~GTDGKKLRIKSKEKCNDG LG45/heparin cross-link Heparin [@R85] K~1433~KLRIK Directed mutagenesis Syndecan-1 [@R59] R~1436~IKSKEK Directed mutagenesis Syndecan-4 [@R59] L~1488~GSPPSGKPKSL LG45/heparin cross-link Heparin [@R85] V~1610~TPKQSLCD LG45/heparin cross-link Heparin [@R85] **Mouse**       K~1336~ARSFNVNQLLQD Peptide Unknown receptor [@R81] K~1398~PRLQFSLDIQT Peptide Unknown receptor [@R81] D~1629~GQWHSVTVSIK Peptide Unknown receptor [@R81] -------------------------------------------------------------------------------------------------------- {#F4} Functions of Precursor γ2 N-Terminal Domain =========================================== It has been shown that in human skin basement membrane, the N-terminal domain of the γ2 chain is absent suggesting that the γ2 processing could have an important physiological role.[@R11]^,^[@R63] In contrast to these findings, antibodies specific for the released L4 domain were shown to label the basal epidermal cells in mouse skin.[@R24] A positive signal was also found in the basement membranes of early stages of skin development suggesting that the precursor γ2 chain or its released N-terminal domain expression might persist in vivo.[@R24] The analysis of mTLD/BMP-1 deficient mice revealed that although defaults in skin cohesion were not clinically apparent, ultrastructural examination of the basement membrane showed places where anchoring structures were disconnected at the level of the lamina densa with presence of rudimentary hemidesmosomes.[@R15]^,^[@R25] A strong expression of the precursor γ2 chain suggested that γ2 chain maturation takes part in the basement membrane cohesion and stability. Besides, defective γ2 processing was found in the rare inherited cylindromatosis disease (see above), in which abnormal basement membranes and excessive ectopic expression of collagen VII were found.[@R63]^,^[@R96] The defective processing of the γ2 chain may have resulted in a deficient interaction with its basement membrane partners collagen VII causing defaults in anchoring fibrils linkage.[@R32]^,^[@R95] Numerous studies conducted with normal breast epithelial and carcinoma cells have shown that cell migration-inducing functions of the γ2 chain rely on its proteolysis.[@R35] Recently, it has been reported that a syndecan-1 interaction with the N-terminal domain in precursor γ2 could negatively regulate β4 integrin phosphorylation leading to enhanced carcinoma cell adhesion and decreased motility[@R97] reinforcing the idea that the precursor γ2 chain does not support cell migration. In contrast, other reports have suggested that precursor γ2 may play a role in keratinocyte migration during the wound healing process. An interaction of its N-terminal portion with α2β1 integrin was shown to occur during TGF-β1 induced keratinocyte migration in vitro and was proposed to take place at the wound margin of the skin healing process in vivo.[@R68] Keratinocytes at the edge of wounds made in early passage cultures shown to co-express the laminin 332 γ2 chain and the cell cycle inhibitor p16^INK4a^, displayed increased directional motility.[@R98] Additional studies revealed that this keratinocyte hypermotility/growth arrest response relied on both the precursor state of the laminin 332 γ2 chain and the participation of a serum co-factor through a TGFβ receptor I dependent mechanism.[@R99] This apparent contradiction in experimental findings is likely due to tissue specific differences. A study indicated that the L4 module mediates the integration of laminin 332 into the extracellular matrix through intermolecular interactions.[@R73] The question arises whether the heparin-binding domains located within the α3 LG45 domains and the N-terminal portion of the γ2 chain are involved in laminin 332 deposition. Heparin was shown to inhibit laminin 332 deposition within the ECM suggesting that a heparan sulfate proteoglycan might be involved in binding to both precursor α3 and γ2.[@R13] Null mutation in syndecan-1[@R100] and -4[@R101] has not reported defects in laminin deposition, which suggests that any of these two receptors is solely responsible for this mechanism. Generation of double syndecan-1 and -4 knockout mice would reveal whether both these receptors are implicated. Future studies should examine whether a heparan sulfate proteoglycan cell surface receptor or a basement membrane components are is implicated in precursor laminin 332 deposition. Interestingly, a recent study has reported that the perlecan colocalizes with laminin 332 at the wound margin of healing full thickness wounds generated in mice suggesting proximity of these two components during basement membrane remodelling.[@R102] However, as perlecan was shown not to be essential for matrix assembly in perlecan-null mouse embryos,[@R103] its presence in the ECM might not be an absolute requirement for laminin 332 deposition. Considering the important function of laminin 332 in skin homeostasis, several extracellular ligands might be involved in its deposition in the basement membrane. Conclusions =========== Comprehension of the physiological significance of laminin 332 maturation events remains an open issue. Numerous studies have focused on the LG45 and γ2 N-terminal domains suggesting their involvement in diverse important functions such as laminin secretion, deposition and/or retention within the ECM; others have suggested a participation in epithelial cell adhesion and migration processes. However, their exact function remains unknown. While in vitro data sometimes disagree due to the cellular system's diversity, in vivo models firmly demonstrate that defects in laminin 332 maturation impede correct basement assembly as well as hemidesmosome formation. Molecular interaction abnormalities occur at the level of cellular receptors and basement membrane components causing both functional and organisational anomalies. Molecular characterization and structural definition of laminin domains open interesting and every so often unexpected questions. From its identification in the 1990s[@R9]^,^[@R26]^,^[@R104]^,^[@R105] to nowadays, laminin 332 has stimulated incessantly increasing interest in the scientific community due to its multifunctional properties and its involvement in human physiological processes and pathologies. We thank Dr. François Letourneur (CGMC, Lyon) for his help in designing the syndecan-1 GFP constructs. Original work by the authors was financially supported by the Agence Nationale pour la Recherche grants Chemispike and adhesioMab, the Association pour la Recherche sur le Cancer and the Ligue Nationale contre le Cancer. We acknowledge the contribution of the PLATIM platform of SFR Biosciences Gerland-Lyon Sud (UMS344/US8). Previously published online: [www.landesbioscience.com/journals/celladhesion/article/23132](http://www.landesbioscience.com/journals/celladhesion/article/23132/) ECM : extracellular matrix LG : laminin globular domain pre-laminin : precursor-laminin MMP : matrix metalloproteinase mTLD : mammalian tolloid BMP-1 : bone morphogenic protein 1 JEB : junctional epidermolysis bullosa pdb : protein data bank No potential conflicts of interest were disclosed.

iOS 11 Features Compilation (Advanced Siri, Secured Apple Pay & More) June 13, 2017 By Dzongo iOS 11 Features: Finally the moment has arrived. People all around the world was looking forward to the Apple’s annual keynote the Worldwide Developers Conference 2017 (WWDC) and Tim Cook, the CEO of the Cupertino-based tech conglomerate kicks off the event in style. After launching the brand new watchOS 4 and iMac, Apple has finally launched the iOS 11 with more than 10 brand new features. So in this article, we have discussed on the just launched iOS 11 and its stunning features at length. iOS 11 Features iOS 11 Features Compilation iOS, the operating system of the iPhones, iPads and iPods, is one of the most used and most loved operating systems of the world. People all around the world has been mesmerised with its sterling features. But in this latest iOS 11, Apple has solely focussed on improving the ‘core technologies’ apart from incorporating new features. The Senior Vice-President of Software Engineering of Apple, Craig Federighi demonstrated and explained all the new features of iOS 11. So let’s check out the brand new iOS 11 features below. iMessage The first feature Federighi explained is iMessage. Apple is planning to improve the iMessage for a long time and finally, they have included some major changes in this messaging application. The biggest feature of the iMessage in iOS 11 is the synchronisation between the iOS and the MacOS. Now, with the brand new iOS 11, if you delete a message from your iPhone or iPad, it will also be reflected on your Mac device. Apple Pay After the messaging application, the next feature which Federighi explained is the payment application of the company, the Apple Pay. The US-based tech giant has improved the Apple Pay exponentially and introduces the person-to-person payment system. Not only that, Apple brings in a new Apple Pay Cash Card in the iOS 11, in which the users will store their received funds in a peer-to-peer transaction and can also transfer the money to the personal bank account. Siri With each iteration of the iOS, Apple has bettered the personal voice assistant of the software, Siri. So there is nothing new in it. But the new thing is Apple has ensured Siri’s voice sounds more natural while answering to the users. Moreover, with the inception of the iOS 11, Siri will now be capable of translating various languages such as French, German, Italian, Chinese, Spanish and English. Apple has also included the ‘intelligence’ feature in Siri in this edition and now the voice assistant will suggest the things to the users which the users might find interesting. Just like a news article, Siri will now predict the users which they want to do next. The ‘intelligence’ feature made possible as Siri has finally accomplished to ‘on-device learning’. this on-device learning is synced with your other Apple devices too, but the company has made sure to “kept completely private, readable only by you and your devices.” Indoor Maps Fans were pretty disappointed with Apple Map system, especially when the arch-rival Google has done wonders with their Map application. So to satisfy their huge fanbase, Apple has revamped and improved the Apple Map system radically. Now, the Apple Map is capable of showing the indoor maps of airports and shopping malls of selected cities, with newly incorporated Indoor Maps feature. The selected cities include Boston, Chicago, Hong Kong, Los Angeles, London, Philadelphia, New York, San Francisco, Tokyo, San Jose, and Washington DC. As far the airports are concerned, Apple Maps will show the indoor maps of 20 major airports, including US and International airports. Driving Assistance Apple is very much concerned about the safety of their users, especially while they are driving and thus the company has introduced many driving assisting features in the iOS 11. This new iOS 11 feature has been incorporated in the Apple Map, and it includes lane guidance and speed limits which will help the users driving in the unfamiliar highways. Moreover, this new feature also comes with a brand new Do Not Disturb While Driving mode which will keep away all the potential distractions and will help you to keep your eyes on the road. With this mode on, the text messages won’t be shown on your screen automatically, albeit you will always have the option to reply in urgent cases. Control Center As expected, Apple has revamped the Control Center completely and now the users will be able to change songs while listening to music as well as can avail the frequent and important setting just by swiping up. Apple Music Federighi also mentioned that iOS 11 will now come with the support for multi-room audio between iPads,iPhones and a limited number of third-party speakers. Moreover, with the new iOS 11 features, Apple Music will now come with more social elements and will now notify you which songs your friends are liking on the app most. ARKIT Forget virtual reality, augmented reality is the latest trend which is set to rule the technological world and Apple has incorporated the AR into haert of the iOS. With the newly introduced ARKIT, the developers will get the perfect tool to blend the digital entertainment with the reality. App Store The biggest change in the iOS 11 comes with the App Store and Apple has redesigned the App Store completely. Apple has incorporated a “Today” tab which will highlight the notable releases and the company has finally dedicated a tab for the gaming section. Imaging Speaking of the upgraded camera app, the iOS 11 has upped their game with the imaging technology and therefore with the iOS 11, we are sure to get a more advanced version of the camera app than what we have in the iOS 10. What the new app does is allows users to take higher quality pictures with well over twice the compression support from before. So with greater picture quality picture and small size, it’s a win-win situation for iOS 11 users. It’s also worth mentioning that there are couples of gorgeous new filters that don’t just make you images more impressive but retains the natural look. Like a couple of other iOS 11 features, the Live Photos has got a facelift. You can now edit the video loops and use the Long Exposure effect to create fantastic blurry looks. In-camera Augmented Reality There is no doubt that Apple is gearing up to take moves towards augmented reality, especially since Apple CEO Tim Cook is constantly talking about the technology and how interesting he finds it. With the all new iOS 11, Apple is taking baby steps towards augmented reality, and clearly, it is a huge part of the company’s vision for the future. We have already talked about ARKIT, and that iOS 11 is rumored to come with AR support, now there are rumors that the iPhone 8 (supposedly Apple’s next flagship device) might come with a camera that’ll support. Of course what really happens remains to be seen! Wrap Up Well, iOS 11 does look very promising, and the beta version is likely to come with a number of other features that aren’t mentioned here. While we are very positive about the features we have mentioned here, other features that you might in the beta version may not ultimately come to the final version of the iOS 11. That said the all-new iOS 11 bring tons of things on the plate that we are sure to enjoy.

Q: HyperLink on the mail send from Unix I am sending some text messages from the unix box to the normal internet mail id. I Wanted to add a hyper link in those mails, but link to a file on the system not to a URL. I'm doing it on local machine and i'm sending mail to my email-id. In that mail, I need a link to file which resides on my system itself. How I can do this? A: Set your URL like this: file:///full/path/to/file Of course, that will only work locally. If clicked on another system, it'll refer to their local filesystem.

San Francisco Bay Diablos San Francisco Bay Diablos were an American soccer team that played in San Francisco, California as a member of the USISL from 1993 to 1995. History Owner Mario Chavez coached the team during its inaugural season in 1993. In 1994, he brought in former Nigerian international Tony Igwe to coach. Igwe lasted only four games with the team losing all four games. Chavez, then struck a deal with Salvador Lopez to bring in the 1993 Lamar Hunt US Open Cup Champions C.D. Mexico (aka, El Farolito Soccer Club) to take over the club and run the team. The team enjoyed immediate success and if not for an 18-point deduction in points for a rules violation, the club would have made their first and only playoff appearance. In 1995, Lopez withdrew his support and the cooperation between the two clubs ceased. The Diablos struggled their way to the end of the season and folded at that time after three seasons in the league. Year-by-year External links The Year in American Soccer - 1993 The Year in American Soccer - 1994 The Year in American Soccer - 1995 Category:Defunct soccer clubs in California D Category:USISL teams Category:1993 establishments in California Category:1995 disestablishments in California Category:Soccer clubs in California Category:Association football clubs established in 1993 Category:Association football clubs disestablished in 1995

Gilbertsville, Pennsylvania Gilbertsville is a census-designated place (CDP) in northwest Montgomery County, Pennsylvania, United States. It is located in Douglass Township at the junction of Routes 73 and 100. The population was 4,832 at the 2010 census, and the ZIP code is 19525. The name is also applied to an indeterminate adjacent section of New Hanover Township served by the Gilbertsville Post Office, and in fact the New Hanover Township offices are located in an area considered to be part of Gilbertsville. Boyertown School District covers the town of Gilbertsville. Gilbertsville is considered a rural area Northwest of Philadelphia. History Gilbertsville began when the descendants of William Gilbert, an English astronomer, physician, and physicist, decided to permanently move to America. Although many of the Gilberts fought for America in the Revolutionary War, Abijah Gilbert did not relocate his family until 1790. In the fall of 1789, of land were purchased for the modern-day price of $2000. It was the first land purchased from the Morris Trust in Montgomery County, Pennsylvania. The Gilberts purchased more land in later years. A Gilbert Family letter recalls that as Abijah Gilbert's son, Joseph Thomas Gilbert, was disembarking in Philadelphia, George Washington patted him on the head and said, "A fine, rosy-cheeked English boy, who will make a good American Citizen." The name Gilbertsville derived from the large number of Gilbert family, descended from Hans George Gilbert who relocated from Hoffenheim, Germany in 1750. He and his sons Bernhard and Johan George Gilbert are buried in the New Hanover Evangelical Lutheran Churchyard. The village was originally a part of McCall's Manor. Geography Gilbertsville is located at (40.319150, -75.614103). According to the United States Census Bureau, the CDP has a total area of , all of it land. Demographics As of the 2010 census, the CDP was 93.8% Non-Hispanic White, 1.4% Black or African American, 0.2% Native American and Alaskan Native, 1.1% Asian, 0.3% were Some Other Race, and 1.3% were two or more races. 2.4% of the population were of Hispanic or Latino ancestry. As of the census of 2000, there were 4,242 people, 1,621 households, and 1,209 families residing in the C.D.P. The population density was 1,258.7 people per square mile (486.0/km²). There were 1,668 housing units at an average density of 494.9/sq mi (191.1/km²). The strain composition of the C.D.P. was 97.24% White, 0.78% African American, 0.14% Native American, 1.01% Asian, 0.02% Pacific Islander, 0.12% from other races, and 0.68% from two or more strains. Hispanic or Latino of any strain were 0.45% of the human population. There were 1,621 households out of which 36.6% had children under the age of eighteen years living with them, 57.9% were married couples living together, 12.2% had a female householder with no husband present, and 25.4% were non-families. 20.9% of all households were composed of individuals and 9.9% had someone living alone who was sixty-five years of age or older. The average household size was 2.61 and the average family size was 3.03. In the C.D.P. the human population was spread with 26.8% under the age of eighteen years, 6.8% from eighteen to twenty-four years, 28.7% from twenty-five to forty-four years, 24.2% from forty-five to sixty-four years, and 13.5% who were sixty-five years of age or older. The median age was thirty-eight years. For every one hundred females there were 94.3 males. For every one hundred females age eighteen years and over, there were 87.2 males. The median income for a household in the C.D.P. was $51,268, and the median income for a family was $60,417. Males had a median income of $43,631 versus $26,601 for females. The per capita income for the C.D.P. was $21,633. About 4.0% of families and 4.1% of the human population were below the poverty line, including 5.9% of those under eighteen years old and 4.8% of those sixty-five years or older.and 3.9% are 5–13 years of age. Notable Landmarks Zern's Farmer's Market, which is now closed. Notable people Nicole Barnhart, American professional soccer player Elaine Irwin, American model. James Develin, American football player. Tony Chimel, Professional wrestling announcer. Selena Ortiz, Professional gymnast. .“Hamburger” Dave Johnson, Professional tailgater and internet persona. Gallery References Category:Census-designated places in Montgomery County, Pennsylvania Category:Census-designated places in Pennsylvania

Q: QML: Event which triggers when document was completly loaded I work now on an application witch loads QML file and makes screenshot of a window. That's how it looks now: QQmlApplicationEngine engine; engine.loadData(data); QQuickWindow *rootObject = qobject_cast<QQuickWindow *>(engine.rootObjects().first()); QImage image = rootObject->grabWindow(); image.save("window.png","PNG",90); In this case data is just simple QML structure: import QtQuick 2.3 import QtQuick.Window 2.2 Window { visible: true width: 360 height: 360 Text { anchors.centerIn: parent text: "Hello, world!" } MouseArea { anchors.fill: parent //onClicked: someSingleton.makeScreenshot(); } Component.onCompleted: someSingleton.makeScreenshot(); } But image I get from QQuickWindow::grabWindow() is empty and not saved. So I tried to make it in another way through Component.onCompleted and it still not works. (someSingleton.makeScreenshot() is a function with call to QQuickWindow::grabWindow() like the code above). The only way to get it work is to call to this function in MouseArea .onClicked when a window completely loaded. So I came to conclusion that in 2 first attempts QML tree was not fully loaded. I also tried this code: connect(rootObject,&QQuickWindow::afterRendering,[=] () { QImage image = rootObject->grabWindow(); image.save("window.png","PNG",90); }); But program's execution just hungs up on first line. So my question - is there some event witch triggers when a QML document completely loaded? P.S. In real app I cannot modify QML source so all functionality have to be in C++ part. Component.onCompleted and MouseArea .onClicked here are just for test purposes. A: Ok, after long search, I've found the solution.As usual I just had to read the Qt documentation more carefully. QImage QQuickWindow::​grabWindow() http://doc.qt.io/qt-5/qquickwindow.html#grabWindow Warning: This function can only be called from the GUI thread. void QQuickWindow::​afterRendering() http://doc.qt.io/qt-5/qquickwindow.html#afterRendering Warning: This signal is emitted from the scene graph rendering thread. So, the slot was executed in scene graph rendering thread and hangs up due to conflicts. I've just changed the example above to be sure the slot executes in GUI thread as described here. connect(rootObject,&QQuickWindow::afterRendering,this,[=] () { QImage image = rootObject->grabWindow(); image.save("window.png","PNG",90); },Qt::QueuedConnection);

Q: Apache2 - display auth only for public IP's, only on testing server I want to configure universal .htaccess file for my application to protect my testing server. I want to display basic auth for any request that comes from public IP, only if current server is testing. How to archieve this? I know how to protect domain and exclude some IP: AuthType Basic AuthName "Please Log In" AuthUserFile /some/path/.htpasswd Require valid-user Order deny,allow Deny from all Allow from 127.0.0.1 Satisfy any But how I can let this code run only if server is dev/testing? I can't change env variables. I thought about detecting domain (server that I want to protect is on subdomain), and place code from above in some sort of if block, but I don't know how. A: You use mod_setenvif to set an env variable based on current host and use it auth later: SetEnvIfNoCase Host ^sub\.domain\.com$ SECURED AuthType Basic AuthName "Please Log In" AuthUserFile /some/path/.htpasswd Require valid-user Order Allow,Deny Allow from 127.0.0.1 Deny from env=SECURED Satisfy any