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Q: TFS in VS2015 works for .csproj, not for adding .cs Three computers all running Visual Studio 2015 with all current updates. All three machines have Bitlocker running. Same problem occurs on all three machines, all three were working fine perhaps a week ago (last time I used this solution). I use VisualStudio.com for TFS. Today I got latest, added a file to a project I was working on, edited it and went to check in. I noticed it wasn't in the pending list. HOWEVER, the .sln was checked out and the .csproj was updated. I could manually add the .cs file to TFS and it happily checked it in. It just won't do it automatically. I then created a new project and added it to TFS and this worked fine. I opened another existing solution and that also works fine. So I duplicated the whole solution directory and attempted to add it with TFS power tools and NOW I see the problem. Excluded by the global exclusion list: *.lib My guess, and it's only a guess, is that in the last update, pushed out in the last couple of weeks they've added some exclusion for something "webby" which is screwing up my solution that happens to have a project with .lib at the end. Or perhaps file level filters are now applying to directories? 1) Where are these exclusions set? 2) Anyone know if this is a new exclusion added recently? As I said, I've worked on this solution for a year or more on and off without problem until today. 3) Which language prefers *.lib to be excluded? It makes sense for files, but this is applied to entire directories called MyProject.Lib (for example). Thanks A: The global exclusion list is configured by the server, there isn't any way to change it. You can get the detailed list from following path: %LocalAppData%\Microsoft\Team Foundation\X.0\Configuration\VersionControl\LocalItemExclusions.config And I can get the same behavior as you with VS2015 Update3, but cannot see this issue with VS2015 Update2.
2024-02-18T01:27:15.642919
https://example.com/article/1826
2001-2002 Worcester, MA - May 8, 2002 - Dr. Timothy R. Gerrity has been named Director of Worcester Polytechnic Institute’s (WPI) Bioengineering Institute. He will assume his directorship on July 1, 2002. Gerrity is currently executive director of the Chronic Pain and Fatigue Research Center at Georgetown University School of Medicine in Washington D.C.. Gerrity’s appointment is funded in part by a two-year grant from the Fairlawn Foundation, a Worcester-based charitable fund, which enabled the University to pursue candidates of the highest caliber. "The foundation sees the Bioengineering institute as an ideal vehicle to foster excellence and innovation in healthcare delivery, education and research," said Karl Bjork, chair of the Fairlawn Foundation. "We are especially mindful of the positive impact that the Institute might have on the economic development of Worcester." "WPI’s bioengineering institute provides a unique opportunity to integrate academic research, technology development and commercialization," said Dr. Gerrity. "The Institute will be an important bridge from the laboratory bench to the consumer, supported by the quality of the research at WPI and the talent and excitement of the researchers. We are ready to go!" "The discoveries being made in the biological sciences will be the basis for significant industrial growth in the next decades," said William W. Durgin, associate provost for academic affairs at WPI. "Just as rapid progress in understanding physical and chemical phenomena fueled industrial growth and prosperity throughout the last century, we will see the biological sciences drive advances in environmental quality and human health, and that is why WPI created the Institute for Bioengineering, to be able to create a new interface discipline," explained Durgin. "Tim Gerrity brings to the bioengineering institute his broad experience as a researcher, research leader and administrator," said Durgin. "His work has taken him to the U.S. Department of Veterans’ Affairs in Washington, the U.S. Environmental Protection Agency, and the Westside VA Medical Center in Chicago. We are excited about his vision for the bioengineering institute." Gerrity has also served on the faculty of Georgetown University, the University of North Carolina at Chapel Hill, and the University of Illinois, at Chicago where he received his BS, MS and Ph.D. in Physics. About the WPI Bioengineering Institute The WPI Bioengineering Institute was created in 2001 to promote job creation and economic vitality by facilitating conversion of research discoveries into new products and new companies; to conduct research and development, tap the intellectual capital of the region and invoke the innovation process to create high-wage industries in the region. The institute focuses on applied research, product development and product realization and will create a network of universities, hospitals, research organizations and development organizations linked electronically through design studios. It is based at Worcester Polytechnic Institute in Worcester, Massachusetts, and draws from WPI’s expertise in biosensors, wireless communication, information technology and database analysis. About the Fairlawn Foundation The Fairlawn Foundation was established in 1991 upon the transfer of Fairlawn Hospital, a provider of local community care since 1921, to a for-profit rehabilitation corporation. The proceeds of that transaction were used to establish the Fairlawn Foundation. It is managed by the Greater Worcester Community Foundation, a public charity. The Fairlawn Foundation's mission is to support excellence and innovation in healthcare delivery, education and research in the Worcester, Massachusetts area. About WPI WPI is a pioneer in technological higher education, and is recognized as one of the leading outcomes-oriented undergraduate programs preparing people for success in our technological world. Since its founding in 1865, WPI has broadened and perfected an influential curriculum that balances theory and practice. This innovative and unique combination of educational methods, learning environment and a worldwide network of project centers is located in Worcester, Massachusetts, WPI supports the academic and research pursuits of over 2,500 students and 200 faculty pursuing opportunities to blend technological research and practice with societal needs, delivering meaningful real-world benefits. For over a century, WPI has awarded advanced degrees in the sciences and engineering disciplines, as well as the management of technology and business. Our alumni include Robert Goddard, the father of modern rocketry; Harold Black, inventor of the principle of negative-feedback; Carl Clark, inventor of the first practical airbag safety system; Dean Kamen, inventor of the first wearable drug infusion pump; and many others who contribute to the transformation of our technological world.
2023-09-09T01:27:15.642919
https://example.com/article/8921
Thread (yarn) Thread is a type of yarn but similarly used for sewing. It can be made out of many different materials including cotton, linen, nylon, and silk. Materials Thread is made from a wide variety of materials. Where a thread is stronger than the material that it is being used to join, if seams are placed under strain the material may tear before the thread breaks. Garments are usually sewn with threads of lesser strength than the fabric so that if stressed the seam will break before the garment. Heavy goods that must withstand considerable stresses such as upholstery, car seating, tarpaulins, tents, and saddlery require very strong threads. Attempting repairs with light weight thread will usually result in rapid failure, though again, using a thread that is stronger than the material being sewn can end up causing rips in that material before the thread itself gives way. Thread is a type of yarn but similarly used for sewing. It can be made out of many different materials including cotton, linen, nylon, and silk. Polyester/polyester core spun thread is made by wrapping staple polyester around a continuous polyester filament during spinning and plying these yarns into a sewing thread. Core Spun Thread Different Types Thread gauges Yarns are measured by the density of the yarn, which is described by various units of textile measurement relating to a standardized length per weight. These units do not directly correspond to thread diameter. Wt and Gunze count The most common weight system specifies the length of the thread in kilometres required to weigh 1 kilogram. Therefore, a greater weight number (indicated in the American standard by the abbreviation wt) indicates a thinner, finer thread. The American standard of thread weight was adopted from the Gunze Count standard of Japan which uses two numbers separated by a forward slash. The first number corresponds to the wt number of the thread and the second number indicates how many strands of fiber were used to compose the finished thread. It is common to wrap three strands of the same weight to make one thread, though this is not a formal requirement in the US standard (which is therefore less informative). Denier A denier weight specification states how many grams 9,000 meters of the thread weighs. Unlike the common thread weight system, the greater the denier number, the thicker the thread. The denier weight system, like the common weight system, also specifies the number of strands of the specified weight which were wrapped together to make the finished thread. Tex Tex is the mass in grams of 1,000 meters of thread. If 1,000 meters weighs 25 grams, it is a tex 25. Larger tex numbers are heavier threads. Tex is used more commonly in Europe and Canada. Aughts Some thread manufacturers, especially those producing very fine silk threads, apply their own scales of thread measurement using "aughts" or zeroes (not unlike the zeros used in measuring the sizes of seed beads). Within a given manufacturer's spectrum, a higher "aught count" indicates a finer thread: this is usually given as a single digit followed by a forward slash and a zero— for example, 3/0 indicates a three-aught thread or a thread size "000", but this number only has significance when compared to other threads produced by the same manufacturer: one manufacturer's 4/0 will always be more fine than that same manufacturer's 2/0, but will mean nothing if compared to the 4/0 of another manufacturer. The aught scale therefore is not suitable for conversion or comparison to other more-generalized weight scales, though it is in common use. Conversion information Thread weight conversion table For example: 40 weight = 225 denier = Tex 25. A common Tex number for general sewing thread is Tex 25 or Tex 30. A slightly heavier silk buttonhole thread suitable for bartacking, small leather items, and decorative seams might be Tex 40. A strong, durable upholstery thread, Tex 75. A heavy duty topstitching thread for coats, bags, and shoes, Tex 100. A very strong topstitching thread suitable for luggage and tarpaulins, Tex 265-Tex 290. But a fine serging thread, only Tex 13. For blindstitching and felling machines, an even finer Tex 8. High-temperature sewing threads High temperature sewing threads provide durability and resistance to extreme temperatures. Some threads can be used for applications up to 800 °C (1472 °F). There are a variety of different sewing threads available which have different applications and benefits. Kevlar-coated stainless steel sewing threads have a high-temperature and flame-resistant steel core combined with Kevlar coating designed to facilitate easier machine sewing. The stainless steel core has a temperature resistance of up to 800 °C (1472 °F) and the Kevlar coating is heat-resistant up to 220 °C (428 °F). PTFE coated glass sewing threads have an excellent temperature resistance combined with a PTFE coating to provide easier machine sewing. The glass core has a temperature resistance of up to 550 °C (1022 °F) and the PTFE coating is heat-resistant up to 230 °C (446 °F). Nomex sewing threads are inherently flame-retardant and heat-resistant with a tough protective coating which resists abrasion during the sewing operation. It is temperature resistant up to 370 °C (698 °F). Bonded nylon sewing threads are tough, coated with abrasion resistance, rot proofing, and have good tensile strength for lower temperature applications. They are temperature-resistant up to 120 °C (248 °F). Bonded polyester sewing threads are tough, coated with abrasion resistance, rotproofing, and have exceptional tensile strength for lower temperatures but heavier-duty sewing operations. They are temperature-resistant up to 120 °C (248 °F). See also Eisengarn ('iron yarn') Hank (textile) Sewing needle Staple (textiles) Stitch (textile arts) Notes Category:Yarn Category:Textiles
2023-11-26T01:27:15.642919
https://example.com/article/7292
Online Backup Company Carbonite Loses Customers’ Data, Blames And Sues Suppliers - peter123 http://www.techcrunch.com/2009/03/23/online-backup-company-carbonite-loses-customers-data-blames-and-sues-suppliers/ ====== Brushfire Jungledisk is down, and Carbonite (who I have never heard of) is over. Sounds like growing pains for a new and awesome industry. Too bad seeing a fail whale when trying to get to your files isnt nearly as amusing at it is on something somewhat trivial like Twitter. ~~~ niels_olson > Jungledisk is down did I miss something? ~~~ Brushfire <http://news.ycombinator.com/item?id=528178> ------ vaksel The danger of storing your data in the cloud, part n. Shouldn't that be n+1? ------ axod FWIW: "David Friend, Carbonite’s CEO said, “The failures of the Promise equipment occurred primarily during 2007″" ------ chris11 It looks like no data was lost, which is really fortunate. And Carbonite may have been defrauded. But it is not reassuring to no that Carbonite was surprised by the equipment's failure. Their business depends on the reliability of their hardware, so Carbonite should have been checking it themselves. ------ Dilpil Well... that's the end of Carbonite. ------ zacharypinter Time to change their name... ------ patrickg-zill I am trying to think of a joke involving Hans Solo frozen in Carbonite ...
2024-05-24T01:27:15.642919
https://example.com/article/9308
CFO William J. Janetschek sold 150,000 shares of KKR stock on 08/21/2012 at the average price of $14.53. The price of the stock has decreased by 2.48% since. Kohlberg Kravis Roberts & Co. provides a range of asset management services to its investors and provides capital markets services to its firm, its portfolio companies and its clients. KKR & Co. LP has a market cap of $3.37 billion; its shares were traded at around $14.17 with a P/E ratio of 12.6 and P/S ratio of 4.7. The dividend yield of KKR & Co. LP stocks is 3.6%. KKR & Co. has released its second quarter 2012 results. In this quarter, the company reported GAAP net income of $146.3 million, up from the $39.6 million reported in the same quarter last year. The company reported ENI of $546.1 million in the second quarter of 2012, up from $315.0 million reported prior year quarter. Vice Chairman and CFO Moray P. Dewhurst sold 100,000 shares of NEE stock on 08/20/2012 at the average price of $68.95. Moray P. Dewhurst owns at least 257,527 shares after this. The price of the stock has decreased by 1.61% since. Nextera Energy, Inc. has a market cap of $29.03 billion; its shares were traded at around $67.84 with a P/E ratio of 15.4 and P/S ratio of 1.9. The dividend yield of Nextera Energy Inc. stocks is 3.4%. Nextera Energy Inc. had an annual average earnings growth of 5.9% over the past 10 years. NextEra Energy Inc. reported second quarter 2012 GAAP net income of $607 million ($1.45 per share), compared with $580 million ($1.38 per share) prior year quarter. On an adjusted basis, NextEra reported earnings of $527 million, compared with $500 million last year. Executive Vice President and CFO Glenn P. Muir sold 68,750 shares of HOLX stock on 08/22/2012 at the average price of $19.66. Glenn P. Muir owns at least 773,414 shares after this. The price of the stock has decreased by 1.02% since. Hologic Inc. is a supplier of high quality, innovative and clinically valuable diagnostic systems and tests. Hologic Inc. has a market cap of $5.26 billion; its shares were traded at around $19.46 with a P/E ratio of 14.6 and P/S ratio of 2.9. Hologic Inc. has released its third quarter 2012 results ended June 23, 2012. In this quarter, the company generated revenues of $470.2 million, an increase of 4.2% over prior year quarter. GAAP net income was $23.6 million ($0.09 per share), and Non-GAAP income was $92.6 million ($0.35 per share). CFO Alan Krock sold 55,182 shares of INVN stock on 08/23/2012 at the average price of $13.62. The price of the stock has decreased by 1.32% since. InvenSense Inc. provides motion processing solutions that enable a motion-based user interface for consumer electronics. Invensense Inc. has a market cap of $1.11 billion; its shares were traded at around $13.44 with and P/S ratio of 7.2. InvenSense Inc. has released its first quarter 2013 results. First quarter net revenues was $39.2 million, up from $35.6 million prior year quarter. Net income for this quarter was $7.7 million, or $0.09 per diluted share. At the end of this quarter, InvenSense Inc. had $157.5 million in cash and cash equivalents. President, CEO, Chairman and 10% Owner Steven Saeed Nasiri sold 10,000 shares of INVN stock on 08/21/2012 at the average price of $13.87. Executive Vice President and CFO Edward J. Resch sold 50,000 shares of STT stock on 08/22/2012 at the average price of $41.81. Edward J. Resch owns at least 383,847 shares after this. The price of the stock has decreased by 0.93% since. State Street Corporation is the world's specialist in providing sophisticated global investors with investment servicing, investment management, investment research and trading services. State Street Corporation has a market cap of $20.48 billion; its shares were traded at around $41.42 with a P/E ratio of 11.2 and P/S ratio of 2.1. The dividend yield of State Street Corporation stocks is 2.3%. State Street Corporation had an annual average earnings growth of 1% over the past 10 years. State Street Corporation reported second quarter 2012 EPS of $0.98, down from $1.00 in the same quarter last year. Revenue in the second quarter was $2.42 billion, down 3% from prior year quarter. Return on average shareholders equity was 10%, compared to 10.6% in 2011. For the complete list of stocks that Sold by their CFOs, go to: Insider Buys. Disclaimers: GuruFocus.com is not operated by a broker, a dealer, or a registered investment adviser. Under no circumstances does any information posted on GuruFocus.com represent a recommendation to buy or sell a security. The information on this site, and in its related newsletters, is not intended to be, nor does it constitute, investment advice or recommendations. The gurus may buy and sell securities before and after any particular article and report and information herein is published, with respect to the securities discussed in any article and report posted herein. In no event shall GuruFocus.com be liable to any member, guest or third party for any damages of any kind arising out of the use of any content or other material published or available on GuruFocus.com, or relating to the use of, or inability to use, GuruFocus.com or any content, including, without limitation, any investment losses, lost profits, lost opportunity, special, incidental, indirect, consequential or punitive damages. Past performance is a poor indicator of future performance. The information on this site, and in its related newsletters, is not intended to be, nor does it constitute, investment advice or recommendations. The information on this site is in no way guaranteed for completeness, accuracy or in any other way. The gurus listed in this website are not affiliated with GuruFocus.com, LLC. Stock quotes provided by InterActive Data. Fundamental company data provided by Morningstar, updated daily.
2024-02-03T01:27:15.642919
https://example.com/article/5904
Q: TSQL How to find a patern inside a string? I have a string: 'This is some random text so you don't get upset [rethink]' or this string 'This is some random text so you don't get upset [me] and [123]' Is it possible using TSQL to find and replace the [text] strings? The result: 'This is some random text so you don't get upset ' or this string 'This is some random text so you don't get upset and ' EDIT: I have modified the accepted answer so that the function to be more dynamic: CREATE FUNCTION [dbo].[StripTagWithChar] (@TagLeft NVARCHAR(1),@TagText NVARCHAR(MAX),@TagRight NVARCHAR(1)) RETURNS NVARCHAR(MAX) AS BEGIN DECLARE @Start INT DECLARE @End INT DECLARE @Length INT SET @Start = CHARINDEX(@TagLeft,@TagText) SET @End = CHARINDEX(@TagRight,@TagText,@Start+1) SET @Length = (@End - @Start) + 1 WHILE (@Start > 0 AND @End > 0 AND @Length > 0) BEGIN SET @TagText = STUFF(@TagText,@Start,@Length,'') SET @Start = CHARINDEX(@TagLeft,@TagText) SET @End = CHARINDEX(@TagRight,@TagText,@Start+1) SET @Length = (@End - @Start) + 1 END RETURN Replace(LTRIM(RTRIM(@TagText)),' ',' ') END Now this function accepts the enclosing brackets as an input: select [dbo].[StripTagWithChar]( '{' , 'this is {not} awesome' , '}' ) And the most cool thing is that now it will filter tags with identical brackets like this: select [dbo].[StripTagWithChar]( '=' , 'this is =not= awesome' , '=' ) A: I would suggest making some slight modifications to a previously created UDF that strips out HTML tags... simply replace the < and > with [ and ]: CREATE FUNCTION [dbo].[udf_StripTag] (@TagText VARCHAR(MAX)) RETURNS VARCHAR(MAX) AS BEGIN DECLARE @Start INT DECLARE @End INT DECLARE @Length INT SET @Start = CHARINDEX('[',@TagText) SET @End = CHARINDEX(']',@TagText,CHARINDEX('[',@TagText)) SET @Length = (@End - @Start) + 1 WHILE (@Start > 0 AND @End > 0 AND @Length > 0) BEGIN SET @TagText = STUFF(@TagText,@Start,@Length,'') SET @Start = CHARINDEX('[',@TagText) SET @End = CHARINDEX(']',@TagText,CHARINDEX('[',@TagText)) SET @Length = (@End - @Start) + 1 END RETURN LTRIM(RTRIM(@TagText)) END GO
2024-06-08T01:27:15.642919
https://example.com/article/2010
This is the place where I will share my daily goings-on in my life. Probably nothing especially exciting in my life for most people, but hey it's my life and does get adventurous now and again. Sunday, November 04, 2007 computer update Circuit City FINALLY came through for me last night. I took my computer back to have them see why the USB ports didn't work when they did before I took it downAND they reinstalled the drivers. This guy was super helpful. I think because he could tell when I talked to him on Friday I was at my wit's end and ready to start crying again. I took it down yesterday morning around 10 and he called me about 6 to say it was ready. He said he had a heck of a time figuring out what was wrong and spent a good bit of time on the phone with Dell to ensure he did everything correctly. (BTW, as it turns out the guy who worked on it the first time two weeks ago is no longer there. Not sure if he quit or was fired but I got the impression he was fired or he quit because he knew he was going to be fired.) Anyhow, long story short, the guy yesterday discovered I have one bad USB port and that's why the computer kept freezing. Every time I tried to use that port it messed everything up. But the other port works fine. So he said as long as I remember not to use the bad port, I should be fine and it'll get through a little longer without having to buy a new one. So I put a piece of tape over the bad port so I don't accidentally plug something in to it. He even told me to bring some of my USB port peripheral stuff to test and see if they worked before he gave me back my computer. They worked! So now I'm in the process of reinstalling everything AGAIN and had to set up my Outlook all over again. But I was able to plug in my external hard drive and access all my files so YAY!!! 0 Comments: About Me I live in the DFW area with my three "children" of the four-footed and furry variety: Sheba, Aker, and Amun, affectionately known as cats. I recently started a new job at ITW Polymers Sealants North America as the Environmental Health and Safety Specialist. I have been reviewing books since 2001 and got started on it completely by accident. That accident turned out to be a blessing in disguise as I discovered a hobby I thoroughly enjoy and an outlet for my opinions about the books I love... or love to hate. Now I don't think I'll ever stop!
2024-01-25T01:27:15.642919
https://example.com/article/1018
Identification of retinamides that are more potent than N-(4-hydroxyphenyl)retinamide in inhibiting growth and inducing apoptosis of human head and neck and lung cancer cells. The synthetic retinoid, N-(4-hydroxyphenyl)retinamide (4HPR), which is currently being evaluated in clinical trials for cancer prevention and therapy, inhibits the growth of a variety of malignant cells through induction of apoptosis. However, in the majority of tumor cells, this inhibitory effect of 4HPR requires high concentrations (>1 microM), which exceed the peak plasma level measured in humans. In the present study, we compared and contrasted the effects of several synthetic retinamides on the growth of human lung and head and neck cancer cells in vitro. We found that some retinamides, especially N-(2-carboxyphenyl)retinamide (2CPR), exhibited better growth inhibitory effects than 4HPR in some of the cell lines. 2CPR exerted potent growth inhibitory effects in 5 of 10 head and neck cancer cell lines and in 1 of 10 lung cancer cell lines (IC(50), <0.8 microM). 2CPR (1 microM) induced apoptosis ranging from 10 to 60% in four of five cell lines, whereas 4HPR was ineffective at the same concentration. Unlike 4HPR, 2CPR (up to 10 microM) failed to induce reactive oxygen species production in these sensitive cell lines but could activate caspases 3 and 7 as well as increase poly(ADP-ribose)polymerase cleavage. Interestingly, the effect of 2CPR on cell growth could be suppressed by the specific retinoic acid receptor pan antagonist AGN193109. Our results suggest that 2CPR acts via retinoic acid receptors and may be a good candidate for prevention and treatment of some head and neck and lung cancers.
2024-06-25T01:27:15.642919
https://example.com/article/8263
Q: How to send code, pressing a button and receiving output of a website? Sorry if the title is not clear enough, English is not my main language and I have trouble writing technical stuff. There's this website: https://www.cleancss.com/javascript-obfuscate/index.php I need to be able to send code to this website obfuscating input and to receive its output. I have NO idea how to to this. I was thinking on using web browser module but I'd prefer that this is done in the background, so no explorer window is opened. Please help me approach a solution for this! A: The obfuscated code is inside the textarea with id packed. Javascript obfuscate API import requests from bs4 import BeautifulSoup with open('file.js') as s: source= s.read() cookies = { 'PHPSESSID': 'foln2l1v1564o66vmbs19mk0j1', } headers = { 'Connection': 'keep-alive', 'Cache-Control': 'max-age=0', 'Origin': 'https://www.cleancss.com', 'Upgrade-Insecure-Requests': '1', 'Content-Type': 'application/x-www-form-urlencoded', 'User-Agent': 'Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) Chrome/74.0.3729.169 Safari/537.36', 'Accept': 'text/html,application/xhtml+xml,application/xml;q=0.9,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3', 'Referer': 'https://www.cleancss.com/javascript-obfuscate/index.php', 'Accept-Encoding': 'gzip, deflate, br', 'Accept-Language': 'en-US,en;q=0.9,ta;q=0.8', } data = { 'ascii_encoding': '62^', 'fast_decode': 'on^', 'src': source } response = requests.post('https://www.cleancss.com/javascript-obfuscate/index.php', headers=headers, cookies=cookies, data=data) soup=BeautifulSoup(response.text,'lxml') with open('file2.js') as f: print(soup.select('#packed')[0].text,file=f)
2024-02-28T01:27:15.642919
https://example.com/article/3572
Introduction {#s1} ============ Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is the most frequent form of autosomal dominant predisposition to colorectal cancer (CRC) \[[@B1]\]. Genetic diagnosis of germline defect carriers in affected families is fundamental for an efficient clinical surveillance and allows targeted chemoprevention that was recently shown to substantially reduce cancer incidence in these patients \[[@B2]\]. However, the identification of pathogenic germline defects in this syndrome is not trivial, as reflected by the wide fluctuation in the rate of genetic alterations identified in different studies and by the relevant number of variants with uncertain significance (VUS) detected \[[@B3]-[@B6]\]. The variable rate of alterations detected reflects in part differences in sensitivity of the molecular methods utilized and in part the fact that clinical diagnosis does not completely account for the underlying genetic heterogeneity, even when the selection of probands is based on strict Amsterdam criteria I (AC-I) or Amsterdam criteria II (AC-II) \[[@B7]\]. The majority of HNPCC patients are linked to germline mismatch repair (MMR) defects and develop tumors with high levels of microsatellite instability (MSI-H), the hallmark of MMR deficiency. Germline *MLH1* or *MSH2* variants are identified in most of these patients, whereas variants in other MMR genes are detected in a smaller fraction of cases \[[@B1]-[@B6]\]. Notably, also germline deletions affecting the 3' end of the epithelial cell adhesion molecule gene (*EPCAM*) may cause HNPCC through hypermethylation and silencing of the downstream *MSH2* promoter in EPCAM-expressing tissues \[[@B8]\]. *EPCAM* deletions were reported at a relatively high frequency (16-21%) in different studies conducted in cases negative for germline MMR defects \[[@B9],[@B10]\]. The highest frequency (up to 33%) of *EPCAM* rearrangements was observed in the subset of MSI-H patients negative for germline MMR alterations and lacking MSH2 tumor expression \[[@B11],[@B12]\], but the overall frequency of these rearrangements in series of HNPCC probands, unselected for mutational status or MSH2 tumor immunostaining, has not been evaluated. In addition to MMR genes and *EPCAM*, other genes play a role in this genetically heterogeneous syndrome. A relatively high proportion of families meeting AC has "familial colorectal cancer type X" (FCCTX), a colorectal cancer aggregation with no evidence of germline or tumor-associated MMR defects \[[@B4]\]. For the majority of these families, the genetic alteration responsible for colon cancer predisposition is not known, although defects in non-MMR genes, such as *MUTYH*, *OGG1* or *BMPR1A*, are occasionally detected \[[@B13]-[@B15]\]. In this regard, also *APC* variants associated to very attenuated phenotypes may overlap with HNPCC \[[@B16]\], further widening the range of CRC predisposing genes to be screened. Based on the above considerations, traditional genetic testing in HNPCC focused on the analysis of MMR genes and several diagnostic algorithms were proposed to optimize this screening \[[@B17]-[@B21]\]. However, these algorithms may limit the sensitivity of genetic testing, underestimating carriers of pathogenic variants in MMR genes. Recently, a highly processive gDNA assay (ColoSeq, University of Washington, Seattle, WA) based on targeted capture and next-generation sequencing (NGS) was designed to simultaneously analyze MMR-related and -unrelated genes in HNPCC \[[@B22]\]. NGS-based testing can overcome some of the limitations of low-throughput methods, but even this approach has some drawbacks. For instance, NGS does not provide insights into the pathogenic role of VUS that are more likely to be detected by these highly processive methods. Moreover, genomic-based approaches are not designed to define the pathogenic potential of *cis*- and trans-acting variants that affect gene expression. These limitations might be in part overcome by cDNA-based assays, such as the analysis of allele-specific expression (ASE) that has the potential to uncover germline defects predisposing to colorectal cancer even when a pathogenic variant has not been ascertained or the role of the variants detected is unclear \[[@B23]-[@B27]\]. In the present study, we illustrate the results of integrative analyses conducted on a series of 132 Italian HNPCC patients using previously developed and novel assays for the screening of germline and tumor defects. We show that germline ASE analysis complements gDNA-based assays in the identification and characterization of defects predisposing to CRC. Our integrative approach also shows that inclusion of *MUTYH* and *APC* in the screening increases the number of pathogenic variants detected. Considering the number of patients analyzed, the panel of genes screened and the range of methods employed, this study provides indications for clinical translation of HNPCC genetic testing that may be applied to traditional or NGS approaches. In particular, our results support the inclusion of ASE analysis and screening of polyposis genes in algorithms for genetic diagnosis of HNPCC. Materials and Methods {#s2} ===================== Patients and integrative screening strategy {#s2.1} ------------------------------------------- We studied 132 unrelated AC-I or AC-II patients previously recruited at different Italian institutions. DNA and RNA were extracted as previously described \[[@B25]\]. All study participants gave written informed consent after verbal counseling and the study was approved by the Ethics Committee of the University of Chieti. Tumor MSI and IHC analyses were conducted in probands with available tumor samples. All patients, irrespective of the results of tumor MSI and IHC analyses, underwent screening for germline nucleotide substitutions in MMR genes as detailed below. Probands negative for pathogenic nucleotide substitutions were further tested for extended germline rearrangements in *MSH2*, *MLH1* and *EPCAM*, followed by screening for germline *MSH2* and *MLH1* promoter methylation. ASE analyses of MMR genes were performed in patients with available RNA and heterozygous for at least one allelic marker, independently from the results of the above screenings. Patients negative at the above analyses were tested for *APC* and *MUTYH* sequence variants as described below. The variation data identified in this study have been submitted to the International Society for Gastrointestinal Hereditary Tumours (InSiGHT, [[http://www.insight-group.org/variants/database/]{.ul}](http://www.insight-group.org/variants/database/)) database. Screening for germline nucleotide substitutions in MMR genes {#s2.2} ------------------------------------------------------------ Patients were initially screened for sequence variants in *MSH2* and *MLH1* using single strand conformation polymorphism (SSCP) analysis or denaturing gradient gel electrophoresis (DGGE). All cases negative at SSCP or DGGE were further screened for variants in *MSH2*, *MLH1* and *MSH6* by denaturing high performance liquid chromatography (dHPLC) and automated sequencing, which detected a few additional mutations escaped at the initial screening (data not shown). To predict potential deleterious effects of novel VUS we used the following *in silico* tools: PolyPhen-2 (<http://genetics.bwh.harvard.edu/pph2/>), SIFT (<http://sift.jcvi.org/>), HSF (<http://www.umd.be/HSF/>), FruitFly (<http://www.fruitfly.org/seq_tools/splice.html>), Mutation Taster (<http://www.mutationtaster.org/>), Alamut ([[http://www.interactive-biosoftware.com]{.ul}](http://www.interactive-biosoftware.com)). We also used MAPP-MMR (<http://mappmmr.blueankh.com/>) and PON-MMR (<http://bioinf.uta.fi/PON-MMR/>) prediction algorithms that were specifically validated for missense variants in MMR genes. Analysis of extended germline rearrangements in *MSH2, MLH1* and *EPCAM* {#s2.3} ------------------------------------------------------------------------ Genomic *MSH2* and *MLH1* rearrangements were screened by multiplex ligation-dependent probe amplification (MLPA) in 78 patients negative at initial analysis for pathogenic sequence variants or with VUS. Confirmation of rearrangements was obtained by non-fluorescent multiplex PCR coupled to HPLC (NFMP-HPLC) or by lab-on-a-chip technology for the analysis of copy number variations (LOC-CNV), as previously described \[[@B28],[@B29]\]. Since the original version of the *MSH2/MLH1* MLPA kit (SALSA P003, MRC-Holland, Amsterdam, The Netherlands) employed did not include probes corresponding to *EPCAM*, we developed 3 novel NFMP-HPLC assays for screening and confirmation of genomic rearrangements affecting the 3' end of *EPCAM* and the intergenic *MSH2*-*EPCAM* region ([Table S1](#pone.0081194.s003){ref-type="supplementary-material"}). These assays were performed in a subset of 33 cases with VUS or negative at previous screenings and for whom DNA had not been used up in previous analyses. Breakpoint analysis was performed as previously described \[[@B28],[@B29]\]. Germline *MSH2* and *MLH1* promoter methylation {#s2.4} ----------------------------------------------- Bisulphite DNA conversion was performed in in 44 cases negative at initial screening for pathogenic sequence variants and genomic rearrangements using the Imprinting DNA modification kit (SIGMA, Saint Louis, MO), according to the manufacturer\'s instructions. Screening for germline *MLH1* promoter methylation was conducted by methylation-specific PCR (MSP) using a degenerate and a methylation-specific primer designed by Suter et al \[[@B30]\]. Furthermore, we designed a control PCR in which the degenerate primer used for MSP was paired to a primer specific for unmethylated DNA ([Table S2](#pone.0081194.s004){ref-type="supplementary-material"}). DNA from the SW48 cell line was used as positive *MLH1* promoter methylation control. Screening for germline *MSH2* promoter methylation was conducted by MSP using primers specific for methylated and unmethylated alleles, as described by Chan et al \[[@B31]\]. Positive controls for *MSH2* promoter methylation were obtained using control DNAs that had been universally methylated using S-adenosylmethionine (SAM) and M.SssI CpG methyltrasferase (New England BioLabs, Ipswich, MA). ASE analysis {#s2.5} ------------ ASE analyses of *MSH2*, *MLH1* or *MSH6* were performed by primer extension in patients with available RNA and heterozygous for at least one allelic marker, independently from their mutational status. ASE analyses were carried out as previously described using either ^32^P-labeled or unlabeled primers coupled to analysis by Molecular Imager (Bio Rad Laboratories, Hercules, CA) or by DHPLC (Transgenomic, Omaha, NE), respectively \[[@B23],[@B25]\]. Three ASE assays were performed both with ^32^P-labeled primers and with the DHPLC-based method, which yielded comparable results ([Table S3](#pone.0081194.s005){ref-type="supplementary-material"}). For each ASE assay, the mean ratio obtained with gDNA templates was employed to normalize the data generated in primer extension experiments conducted using cDNA templates. These normalized cDNA/gDNA ratios were designated as ASE values. Based on previous studies, only marked imbalances in relative allele expression corresponding to twofold imbalances in allelic ratios ([\<]{.ul}1:2 or [\>]{.ul}2:1 ratios, equivalent to ASE values [\<]{.ul}0.5 or [\>]{.ul}2, respectively) were conservatively considered evidence of a pathogenic alteration \[[@B23],[@B25],[@B26]\]. These ASE values deviate more than 3 SDs from mean values observed in heterozygous controls for two CRC predisposing genes that we have previously analyzed based on the availability of ASE markers frequent in the Italian population (ASE of *MLH1* in controls, mean 1.04, SD 0.11, using rs1799977; ASE of *APC* in controls, mean 1.25, SD 0.21, using rs2229992) \[[@B24],[@B25]\]. Overall, ASE in *MLH1*, *MSH2* and *MSH6* was measured using 8 previously described \[[@B23],[@B25]\] and 3 novel assays. Primers for novel assays are described in [Table S4](#pone.0081194.s006){ref-type="supplementary-material"}. Tumor MSI and IHC analyses {#s2.6} -------------------------- Tumor assays were performed at the collaborating institutions that recruited the patients. MSI was analyzed in most of the probands (93/102) with available tumor samples, according to international guidelines \[[@B32]\]. Immunohistochemical expression of MSH2, MLH1 and MSH6 proteins was analyzed for 73/102 cases with available tumor samples as previously described \[[@B13]\]. Screening for *APC* and *MUTYH* nucleotide substitutions {#s2.7} -------------------------------------------------------- The coding sequence and intron-exon borders of *APC* and *MUTYH* were analyzed by direct sequencing in 19 probands negative at MMR gene screening. These patients were selected based on availability of DNA and on the presence of at least one polyp at diagnosis in the probands and/or in their relatives. Results {#s3} ======= Multiple approaches were used to analyze 132 unrelated HNPCC patients for pathogenic defects in MMR and non-MMR genes. MSH2, MLH1 and MSH6 nucleotide variants {#s3.1} --------------------------------------- We detected 41 previously described and 15 novel MMR gene variants ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). These included 27 loss-of-function nucleotide changes (nonsense and frameshift) introducing premature termination codons (PTCs), 14 variants located at splice sites, 3 in-frame deletions and 12 missense substitutions. Eight of the splice site variants were experimentally verified to associate with altered splicing, including 7 analyzed in previous studies \[[@B33]-[@B38]\] and 1 in the present study (see below), while 5 were considered pathogenic being located at the almost invariant dinucleotides at intron ends ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). Two in-frame deletions and 9 missense variants were reported as pathogenic or potentially pathogenic based on *in silico* analyses, functional assays, qualitative classifier or multifactorial prediction model in previous reports \[[@B39]-[@B44]\], as specified in [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}. 10.1371/journal.pone.0081194.t001 ###### Overview of MSI, IHC and mutational status in 132 HNPCC unrelated patients meeting AC. **Patients** **AC** **MSI** **MMR defective IHC** **Germline defects^[*a*](#ngtab1.1){ref-type="table-fn"}^** ----------------- -------- --------- ----------------------- ------------------------------------------------------------------------------- -------- LCH-1 I MSI-H MLH1 *MLH1* c.301GA (p.Gly101Ser) GDLM-2\#III-1 I MSI-H MSH2 *MSH2* c.942+3AT GDLM-7\#III-3 I MSI-H MLH1/MSH2 *MSH2* Del exon 7 LCH-8 I MSI-H MSH2 GDLV-11\#II-9 I MSI-H MLH1 96\#1636 II MSI-H MLH1 GDLM-9\#II-2 I MSI-H MSH2 ***MSH2* c.1549_1550delGCinsT (p.Ala517Tyrfs\*9)** *MSH2* GDLG-18\#III-19 I MSI-H n.i. *MSH2* Del exon 3 LCH-19 I MSI-H MSH2 *MSH2* c.2245GT (p.Glu749\*) GDLG-20\#II-1 I MSI-H MLH1 *MLH1* LCH-27 I MSI-H MSH2 *MLH1* GDLG-49\#IV-2 I MSI-H MSH2 *MSH2* c.1024GA (p.Val342Ile) GDLV-52\#II-2 I MSI-H MLH1 *MLH1* LCH-57 I MSI-H MLH1 *MLH1* c.1989GT (p.Glu663Asp) LCH-58 I MSI-H MSH2 *MSH2* c.2005+3_2005+14del12 LCH-59 I MSI-H MSH2 ***MLH1* c.1679delT (p.Phe560Serfs\*31)** LCH-88 I MSI-H n.a. *MLH1* c.1731GA (p.Ser577Ser) LCH-93 II MSI-H n.a. *MSH2* c.1046CG (p.Pro349Arg) 19\#719 II MSI-H MSH2 *MSH2* c.1444dupA (p.Arg482Lysfs\*6) 297\#875 I MSI-H MLH1 *MLH1* c.1852_1854delAAG (p.Lys618del) 307\#2619 I MSI-H MLH1 *MLH1* c.199GA (p.Gly67Arg) 309\#3478 I MSI-H MSH2 *MSH2* Del exons 9-10 311\#2042 I MSI-H n.i. *MLH1* c.731GA (p.Gly244Asp) 338\#1489 I MSI-H MLH1/MSH6 *MLH1* c.382GC (p.Ala128Pro) 349\#1581 I MSI-H MSH2 *MSH2* c.942+3AT 363\#2541 I MSI-H MSH2 *MSH2* Del exons 9-10 412\#3342 II MSI-H MSH2 *EPCAM* Del exon 3 *- MSH2* exon 7 459\#2809 I MSI-H MSH2 *MSH2* Del 5\'upstream region - exon 8 476\#R26 I MSI-H MSH2 *MSH2* Del exons 1-6 667\#2412 I MSI-H MSH2 *MSH2* c.942+3AT 668\#2371 I MSI-H MLH1 *MLH1* c.545+3AG 670\#2413 I MSI-H MLH1 *MLH1* c.1989GT (p.Glu663Asp) 727\#AA I MSI-H MSH2 ***MSH2* c.942+2TA** 814\#DGR I MSI-H n.a. ***MSH2* c.\[376GγA(;)2251G\>C**\]**(p**.\[**Gly126Ser**(;)**Gly751Arg**\]) 986\#3487 I MSI-H MLH1 ***MLH1* c.1731+4AG** 1068\#3015 I MSI-H MLH1 *MLH1* c.1050delA (p.Gly351Aspfs\*16) 1070\#2957 I MSI-H MSH2 ***MSH2* c.2287G\>C (p.Ala763Pro)** 1080\#2974 II MSI-H n.a. *MSH2* c.2089CT (p.Cys697Arg) 1251\#3260 II MSI-H MSH2 ***MSH2* c.374C\>T (p.Gln125\*)** 1256\#3479 II MSI-H MSH2 *MSH2* c.1786_1788delAAT (p.Asn596del) 1293\#3286 I MSI-H MLH1 *MLH1* Del exon 6 1301\#3323 II MSI-H MSH2 ***MSH2* c.2519_2530del12 (p.Val840_Cys843del)** 1459\#3324 II MSI-H MLH1 *MLH1* c.1852_1854delAAG (p.Lys618del) LES1\#LP II MSI-H n.a. *MLH1* c.731GA (p.Gly244Asp) 298\#668/1584 I MSI-H MSH2 *MSH2* c.1077-2A\>C 319\#1004 I MSI-H MSH2 *MSH2* c.1046CG (p.Pro349Arg) 350\#1933 I MSI-H MLH1 *MLH1* c.676CT (p.Arg226\*) 360\#2916 I MSI-H MLH1/MSH6 ***MLH1* c.1731+4AG** *MLH1* 903\#2630 II MSI-H MSH2 *MSH2* Del exon 3 1218\#3238 I MSI-H MLH1 *MLH1* Dup exons 2-3 1515\#3442 II MSI-H MSH2 *MSH2* c.1255CT (p.Gln419\*) 334\#1170 I MSI-H MSH2 *MSH2* c.278_279delTT (p.Leu93Profs\*6) *MSH2* 711\#2495 II MSI-H MLH1 *MLH1* c.1459CT (p.Arg487\*) 1205\#BA II MSI-H MLH1 *MSH2* c.1215CA (p.Tyr405\*) 1206\#GE I MSI-H MSH2 *MSH2* c.1046CG (p.Pro349Arg) 357\#2038 I MSI-H n.a. *MSH2* c.2294delC (p.Ala765Valfs\*47) 600\#2237 I MSI-H n.a. *MSH2* Del exons 4-6 1138\#3149 I MSI-H n.a. *MLH1* c.1852_1854delAAG (p.Lys618del) 737\#2838 I MSI-H n.a. *MLH1* c.1989GT (p.Glu663Asp) TO9726 I MSI-H n.a. *MLH1* c.2040CA (p.Cys680\*) GE9804 I MSI-H n.a. *MSH2* c.1705_1706delGA (p.Glu569Ilefs\*2) GE9726 I MSI-H n.a. *MSH2* c.2536CT (p.Gln846\*) SI9744 I MSI-H n.a. *MSH2* c.942+3AT GE9914 I MSI-H n.a. *MLH1* c.677+1GA F102 I MSI-H n.a. *MLH1* c.546-2A\>G SI9606 I MSI-H n.a. *MLH1* c.911AT (p.Asp304Val) LCH-4 I MSI-H n.i. LCH-12 I MSI-H n.i. LCH-85 I MSI-H n.a. LCH-47 I MSI-H n.a. 871\#R08 I MSI-H n.a. GE0101 I MSI-H n.a. GE9801 I MSI-H n.a. GE9903 II MSI-H n.a. LCH-6 I MSS n.a. LCH-13 I MSS n.i. LCH-79 I MSS n.a. 296\#776 I MSS n.i. 303\#2547 I MSS n.i. 308\#1260 I MSS n.i. *MUTYH* c.\[1145G\>A\];\[1395_1397delGGA\] (p.\[(Gly382Asp)\];\[(Glu466del)\] 313\#1381 I MSS n.a. 342\#2803 I MSS n.i. 365\#2192 II MSS n.a. 368\#2506 I MSS n.i. 369\#2169 I MSS n.a. 370\#3105 I MSS n.i. *APC* c.1100_1101delCT (p.Ser367Cysfs\*10) 633\#3114 I MSS n.i. 728\#2509 I MSS n.i. 818\#2543 I MSS n.i. 933\#R14 I MSS n.a. 1165\#3159 I MSS n.i. 1193\#3187 I MSS n.i. SV0001 I MSI-L n.a. TO9913 I n.a. MLH1 705\#3035 I n.a. MLH1 ***MLH1* c.1367C\>A (p.Ser456\*)** 1008\#2829 I n.a. MSH2 ***MSH2* c.1757C\>G (p.Ser586\*)** 1077\#2979 I n.a. MLH1 ***MLH1* c.453+1GA** 1420\#3343 II n.a. MSH2 *MSH2* c.868GT (p.Glu290\*) LCH-15 I n.a. n.i. *MLH1* c.1918CT (p.Pro640Ser) LCH-23 II n.a. n.a. *MSH2* Del exon 1 GDLG-29\#III-8 II n.a. n.a. *MLH1* c.1852_1854delAAG (p.Lys618del) GDLG-31\#III-11 I n.a. n.a. *MLH1* c.954delC (p.His318Glnfs\*49) *MLH1* LCH-86 I n.a. n.a. *MSH2* c.212-1G\>A 83\#3103 I n.a. n.a. *MLH1* Del exon1 *MLH1* 601\#2307 I n.a. n.a. *MSH6* c.3013CT (p.Arg1005\*) 1157\#834 I n.a. n.a. *MSH2* c.119delG (p.Gly40Alafs\*24) 324\#R10 I n.a. n.a. *MLH1* c.1896GA (p.Glu632Glu) 337\#2224 I n.a. n.a. *MLH1* c.1989GT (p.Glu663Asp) 359\#2578 I n.a. n.a. ***MLH1* c.1639_1643dupTTATA (p.Leu549Tyrfs\*44)** 463\#3031 I n.a. n.a. *MLH1* c.1852_1854delAAG (p.Lys618del) 602\#2416 I n.a. n.a. *MLH1* c.1011delC (p.Asp338Ilefs\*29) 985\#2683 I n.a. n.a. *MLH1* Del exon 6 1074\#3001 I n.a. n.a. *MSH2* c.1059delG (p.Asn354Thrfs\*3) 1200\#3221 I n.a. n.a. ***MSH6* c.738_741delAAAA (p.Lys246Asnfs\*32)** GE0201 I n.a. n.a. *MSH2* Del exon16 GE9911 I n.a. n.a. *MLH1* c.1011delC (p.Asp338Ilefs\*29) TO0012 I n.a. n.a. ***MLH1* c.1888_1892delATTGA (p.Ile630\*)** TO0225 I n.a. n.a. *MLH1* c.2040CA (p.Cys680\*) GE0410 I n.a. n.a. *MSH2* c.942+3AT GE0330 I n.a. n.a. *MSH2* c.1216CT (p.Arg406\*) 162\#2696 I n.a. n.a. *MLH1* c.1559-2A\>G LCH-10 I n.a. n.i. LCH-16 I n.a. n.a. LCH-51 I n.a. n.a. LCH-53 I n.a. n.a. 54\#982 I n.a. n.i. 314\#1200 I n.a. n.i. 353\#1114 I n.a. n.a. 455\#2186 I n.a. n.a. 1082\#2982 I n.a. n.a. F435 I n.a. n.a. GE0002 I n.a. n.a. na, data not available; ni, IHC not informative. Novel variants are in bold. Germline MMR gene defects for some patients have been previously reported (see [Table 2](#pone-0081194-t002){ref-type="table"} and [Tables S3, S5, S6](#pone.0081194.s005){ref-type="supplementary-material"} and [S7](#pone.0081194.s009){ref-type="supplementary-material"}). We also detected several variants previously reported as nonpathogenic (see [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). ASE value [\<]{.ul}0.5 or [\>]{.ul}2. We performed *in silico* analyses to infer the functional effect of 4 variants (3 missense and 1 intronic) for which no such information was available from previous reports. For the 3 novel missense variants a deleterious effect on protein function was predicted by *in silico* tools including PON-MMR and MAPP-MMR ([Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). *In silico* tools indicated a potential effect on splicing for the novel intronic variant (*MLH1* c.1731+4AG) (see below) ([Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). An additional variant, the novel *MSH2* in-frame deletion (c.2519_2530del12, p.Val840_Cys843del), was considered potentially pathogenic because it removes 4 amino acid residues highly conserved in other species and is located in the ATPase domain of the MSH2 protein, where variations were previously reported to cause defects in mismatch binding or release \[[@B45],[@B46]\]. One patient (814\#/DGR) was found to carry two missense substitutions in *MSH2* (c.376GA and c.2251GC) predicted to be pathogenic (see [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). Unfortunately, no relatives of this patient were available for gene testing and the phase of the two variants could not be ascertained. Overall, screening for sequence variants in HNPCC related genes allowed the detection of 56 different substitutions with a definite or potential pathogenic significance in 72 patients, including 26 in *MLH1* (46.5%), 28 in *MSH2* (50%) and 2 in *MSH6* (3.5%) ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). Genomic rearrangements of MSH2, MLH1 and EPCAM {#s3.2} ---------------------------------------------- Screening of *MLH1* and *MSH2* by MLPA, followed by confirmatory tests using LOC-CNV and/or NFMP-HPLC, indicated the presence of genomic rearrangements (including 14 deletions and 1 duplication) in 15 of the 78 patients analyzed (19%) ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S6](#pone.0081194.s008){ref-type="supplementary-material"}). The gene affected by the rearrangement was *MSH2* in 10 probands (13%) and *MLH1* in 5 probands (6.5%). *EPCAM* rearrangements were screened by NFMP-HPLC in patients without detectable pathogenic variants or with VUS. Furthermore, *EPCAM* rearrangements were evaluated in 3 patients (476\#R26, 459\#2809 and 412\#3342) that based on MLPA and NFMP-HPLC screening had evidence of *MSH2* deletions involving the first exon of the gene ([Table S6](#pone.0081194.s008){ref-type="supplementary-material"}). One of these patients (476\#R26) had a deletion of *MSH2* exons 1-6 and NFMP-HPLC-based EPCAM assays indicated that the rearrangement did not extend to the *EPCAM-MSH2* intergenic region ([Table S6](#pone.0081194.s008){ref-type="supplementary-material"}). In another patient (459\#2809), previously reported to have a deletion spanning exons 1-8 of *MSH2* \[[@B28]\], EPCAM assays showed that the deletion included the *MSH2* 5' upstream region, but spared the 3' end of *EPCAM* ([Figure S1](#pone.0081194.s001){ref-type="supplementary-material"}). In the third patient (412\#3342) the deletion affected all *EPCAM* exons included in the EPCAM assays (exons 3, 8 and 9) ([Figure S1](#pone.0081194.s001){ref-type="supplementary-material"}). This deletion extended up to exon 7 of *MSH2*, as indicated by MLPA and NFMP-HPLC ([Table S6](#pone.0081194.s008){ref-type="supplementary-material"}). No *EPCAM* rearrangements were detected in the other patients analyzed. All *MLH1, MSH2* and *EPCAM* rearrangements were confirmed by at least 2 independent assays based on MLPA, NFMP-HPLC or LOC-CNV. In 9 cases confirmation of the rearrangements could be also obtained by breakpoint analysis or RT-PCR ([Table S6](#pone.0081194.s008){ref-type="supplementary-material"}), as previously reported \[[@B28],[@B29]\]. Germline promoter methylation {#s3.3} ----------------------------- Germline MMR gene promoter methylation was analyzed in cases negative at initial screening for pathogenic nucleotide variants and genomic rearrangements. CpG promoter methylation was observed only with positive control DNAs (SW48 cell line for *MLH1* and universally methylated control DNA for *MSH2*, respectively -- data not shown). Germline ASE analysis {#s3.4} --------------------- Among the 22 patients that could be analyzed, we observed altered germline ASE of *MLH1* in 6 patients and of *MSH2* in 2 patients ([Table 2](#pone-0081194-t002){ref-type="table"} and [Table S7](#pone.0081194.s009){ref-type="supplementary-material"}). Of these patients, 2 showed monoallelic expression of *MLH1* (GDLV-52\#II-2 and 83\#3103) and 6 had markedly imbalanced expression of *MLH1* (360\#2916, GDLG-20\#II-1, GDLG-31\#III-11 and LCH-27, mean ASE values 4.7, 2.01, 2.24 and 2.64, respectively) or *MSH2* (GDLM-9\#II-2 and 334\#1170, mean ASE values 3.58 and 9.20, respectively). The remaining patients had modestly imbalanced or balanced ASE ([Table 2](#pone-0081194-t002){ref-type="table"} and [Table S7](#pone.0081194.s009){ref-type="supplementary-material"}). ASE values observed in the 22 probands are depicted in [Figure 1](#pone-0081194-g001){ref-type="fig"}. For reference, the figure depicts also the values that we have previously measured in control individuals heterozygous for the frequent c.655AG variant (rs1799977) of *MLH1* \[[@B25]\]. 10.1371/journal.pone.0081194.t002 ###### Results of primer extension ASE analyses performed in this study. **Patients^[*a*](#ngtab2.1){ref-type="table-fn"}^** **Pathogenic germline variants** **ASE analysis** ----------------------------------------------------- ------------------------------------------------ ------------------ ---------------- ------------------------- ------------------------- GDLM-2\#III-1 *MSH2* c.942+3AT *MLH1* c.655AG p.Ile219Val 1.00 ([+]{.ul}0.07) LCH-8 *MSH2* c.984CT p.(=) 1.09 ([+]{.ul}0.07) *MLH1* c.655AG p.Ile219Val 0.97 ([+]{.ul}0.16) GDLG-18\#III-19 *MSH2* Del exon 3 *MLH1* c.655AG p.Ile219Val 0.91 ([+]{.ul}0.10) LCH-27 *MLH1* c.655AG p.Ile219Val **2.64 ([+]{.ul}0.38)** GDLG-31\#III-11 *MLH1* c.954delC (p.His318Glnfs\*49) *MLH1* c.655AG p.Ile219Val **2.24 ([+]{.ul}0.07)** LCH-51 *MLH1* c.655AG p.Ile219Val 0.84 ([+]{.ul}0.10) LCH-59 *MLH1* c.1679delT (p.Phe560Serfs\*31) *~MLH1~* c.655AG p.Ile219Val 0.97 ([+]{.ul}0.11) GE9804 *MSH2* c.1705_1706delGA (p.Glu569Ilefs\*2) *MLH1* c.655AG p.Ile219Val 1.09 ([+]{.ul}0.05) 96\#1636 *MLH1* c.655AG p.Ile219Val 1.17 ([+]{.ul}0.06) 334\#1170 *MSH2* c.278_279delTT (p.Leu93Profs\*6) *MSH2* c.278_279delTT p.Leu93Profs\*6 **9.20 ([+]{.ul}3.97)** 359\#2578 *MLH1* c.1639_1643dupTTATA (p.Leu549Tyrfs\*44) *MLH1* c.655AG p.Ile219Val 1.33 ([+]{.ul}0.04) 314\#1200 *MLH1* c.655AG p.Ile219Val 1.01 ([+]{.ul}0.03) 1082\#2982 *MLH1* c.655AG p.Ile219Val 1.07 ([+]{.ul}0.02) *MSH6* c.540TC p.(=) 1.10 ([+]{.ul}0.12) 83\#3103**^[*c*](#ngtab2.3){ref-type="table-fn"}^** *MLH1* Del exon 1 *MLH1* c.655AG p.Ile219Val **Loss of G allele** In [Table S7](#pone.0081194.s009){ref-type="supplementary-material"} we summarize the results of ASE analyses for additional 8 patients included in the present study, whose ASE results had been previously reported \[[@B23],[@B25]\]. Markedly imbalanced ASE values are in bold. For this patient PE analysis performed in the present study confirmed the loss of expression for the G allele previously shown by cDNA sequencing \[[@B28]\]. ![ASE values observed.\ ASE values between the 2 dashed lines correspond to less than twofold imbalances in allelic ratios (see Methods).](pone.0081194.g001){#pone-0081194-g001} Three patients with altered germline ASE (GDLG-31\#III-11, 83\#3103 and 334\#1170) were known carriers of *MLH1* or *MSH2* deletions. Conversely, in 2 patients with imbalanced ASE initial screening for pathogenic variants by SSCP or DGGE was negative, but subsequent re-analysis by DHPLC and sequencing identified a frameshift of *MSH2* (case GDLM-9\#II-2) and an intronic *MLH1* variant with a potential effect on splicing (case 360\#2916, see below) ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S7](#pone.0081194.s009){ref-type="supplementary-material"}). Overall, variants with a clear or potential pathogenic role were detected in 5 of the 8 patients with imbalanced ASE ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S7](#pone.0081194.s009){ref-type="supplementary-material"}), whereas in 3 patients (GDLG-20\#II-1, LCH-27 and GDLV-52\#II-2) altered ASE was the only germline defect detected \[[@B23],[@B25]\]. Analysis of a novel putative splicing variant {#s3.5} --------------------------------------------- *In silico* analysis by different splice prediction software tools (see Methods) indicated that the effect of the novel *MLH1* c.1731+4AG variant shared by 2 probands (360\#2916 and 986\#3487) was uncertain. However, they suggested that this change might affect splicing by decreasing the strength of the donor site (average decrease 13%, range 7.4-22%). The availability of cDNA in patient 360\#2916 allowed us to test whether the c.1731+4AG variant was associated to a splicing defect. This alteration was elusive at initial testing of RT-PCR amplified cDNA because only wildtype transcripts were revealed by direct sequencing or by electrophoretic analysis (data not shown). However, based on the results of ASE analysis showing a marked imbalance in allelic expression (average normalized allelic ratio 4.7, derived from radioactive and DHPLC-based assays, [Table S3](#pone.0081194.s005){ref-type="supplementary-material"}), we hypothesized that an altered splicing might be revealed by DHPLC. As predicted, the more sensitive DHPLC analysis allowed the detection of a major peak with a retention time corresponding to the wildtype transcript and of a minor peak corresponding to a less expressed shorter transcript. Sequencing confirmed that the less expressed *MLH1* transcript carried an out-of-frame exon 15 skipping ([Figure S2](#pone.0081194.s002){ref-type="supplementary-material"}). Tumor MSI and IHC {#s3.6} ----------------- Among the 93 cases screened for MSI ([Table 1](#pone-0081194-t001){ref-type="table"}), 74 cases (79.5%) were MSI-H and 19 cases were MSS or MSI-L (20.5%). Germline MMR gene defects, including sequence variants, genomic rearrangements or altered ASE were identified in most cases (63/74, 85%) with MSI-H tumors ([Table 1](#pone-0081194-t001){ref-type="table"}). No germline MMR gene alteration was detected in MSS or MSI-L cases. MLH1, MSH2 or MSH6 protein immunohistochemistry was available for 73 cases and loss of at least one MMR protein was detected in 53 cases (72.6%). Lack of expression affected MLH1 in 21 cases and MSH2 in 29 cases. Moreover, in 1 case (GDLM-7\#III-3) IHC showed the loss of both MLH1 and MSH2, whereas in other 2 cases (338\#1489 and 360\#2916) IHC indicated the loss of both MLH1 and MSH6. We observed discrepancies between the results of IHC and those of other analyses in 12 patients. Among the 20 cases displaying normal MMR protein expression by IHC, 2 cases (LCH-4 and LCH-12) displayed tumor MSI-H phenotype, one case (GDLG-18\#III-19) carried a germline deletion of *MSH2* exon 3 and 2 cases (311\#2042 and LCH-15) carried missense *MLH1* variants (c.731GA and c.1918CT, respectively) previously reported as potentially pathogenic based on functional or *in silico* analyses, respectively ([Table 1](#pone-0081194-t001){ref-type="table"}) \[[@B41],[@B42]\]. Furthermore, in 2 patients (LCH-59 and LCH-27) IHC indicated the loss of MSH2 expression, but molecular screening revealed germline *MLH1* defects, including a frameshift and a markedly imbalanced ASE, respectively ([Table 1](#pone-0081194-t001){ref-type="table"}). In one additional patient (1205\#BA) IHC indicated the loss of MLH1 expression, whereas sequencing revealed a nonsense variant in *MSH2* ([Table 1](#pone-0081194-t001){ref-type="table"} and [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). Finally, in 4 cases IHC indicated the loss of either MSH2 (patient LCH-8) or MLH1 (patients GDLV-11\#II-9, 96\#1636 and TO9913), but no pathogenic variants in MMR genes were detected. APC and MUTYH screening in probands negative for germline MMR defects {#s3.7} --------------------------------------------------------------------- Germline defects in polyposis-associated genes were detected in 2 of the 19 patients screened for *APC* and *MUTYH* ([Table 1](#pone-0081194-t001){ref-type="table"}). One patient (370\#3105) with an unspecified number of adenomas carried the c.1100_1101delCT variant of *APC*, in the alternatively spliced portion of exon 9. The same nucleotide substitution had been previously reported to associate with attenuated polyposis phenotypes displaying less than 10 adenomas \[[@B47]\]. Another patient (308\#1260), with recurrent adenomas at endoscopic follow-up, was a compound heterozygote for the c.1145GA (p.Gly382Asp) and the c.1395_1397delGGA (p.Glu466del) variants of *MUTYH* that were previously reported as pathogenic \[[@B13]\]. Overall results of germline integrative analyses {#s3.8} ------------------------------------------------ The overall results of integrative germline analyses performed in this study are summarized in [Figure 2](#pone-0081194-g002){ref-type="fig"}. Nucleotide variants or rearrangements of MMR genes with a definite pathogenic role were identified respectively in 42 (45.7%) and 15 (16.3%) of the 92 patients with ascertained germline alterations. VUS classified as pathogenic or potentially pathogenic based on previous studies (see [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}) were identified in 28 (30.4%) of the probands with ascertained germline defects. None of the probands tested showed germline *MSH2* or *MLH1* promoter methylation. Overall, the above analyses identified pathogenic variants in 85 (92.4%) of the probands with ascertained germline alterations. ASE allowed the detection of pathogenic alterations in 5 (5.4%) additional probands, including 3 negative at other screenings and 2 bearing a VUS that caused decreased expression of the corresponding allele. Furthermore, *APC* and *MUTYH* screening allowed the detection of pathogenic variants in 2 (2.2%) additional probands. ![Results of integrative germline analyses performed in this study.\ VUS included in-frame deletions, sequence variants with uncertain effect on splicing and missense variants. Evidence of a pathogenic, possibly pathogenic defect in 28 probands with VUS derived from previous studies (see [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). In one additional case (360\#2916) availability of RNA allowed ASE analysis that helped to characterize a VUS shared also by another proband (986\#3487, see Results). ASE analysis was conducted in 22 individuals, including 12 with ascertained germline defect that are not shown in the figure. *APC* and MUTYH screening was conducted in a subset of patients negative for MMR defects (see Methods). Inclusion of ASE analysis and screening for *APC* and MUTYH sequence variants in the integrative analyses increased the number of probands with germline alterations detected.](pone.0081194.g002){#pone-0081194-g002} Discussion {#s4} ========== In this study we summarize the results of extensive analyses conducted in 132 AC probands providing insights that may help clinical translation of genetic testing in HNPCC. In line with other studies \[[@B3]-[@B5]\], the majority of the germline MMR gene defects detected were nucleotide variants or rearrangements in *MSH2* or *MLH1*. Among MMR genes less commonly mutated in HNPCC, pathogenic *MSH6* variants were identified only in 2 probands. We did not analyze either genomic rearrangements of *MSH6*, which account for 5% (17/320) of the variants of this gene reported in the June 2013 release of the Human Gene Mutation Database \[[@B48]\], or its germline methylation status. Furthermore, we did not screen *PMS2* or other genes occasionally mutated in HNPCC. It is possible that a fraction of cases negative at our analyses carries unscreened defects in these genes. A substantial proportion of patients (30/72 showing nucleotide changes in MMR genes, 42%) presented VUS, such as missense variants, in-frame deletions and nucleotide substitutions with uncertain effect on splicing. Characterization of these variants is complex and may require the use of assays that are not routinely available \[[@B6]\]. To facilitate classification of VUS many algorithms have been developed including software tools, such as MAPP-MMR, PON-MMR and CoDP, specifically dedicated to MMR genes \[[@B42]-[@B44],[@B49]-[@B52]\]. Moreover, the pathogenic potential of many VUS recurring in HNPCC was established in previous studies \[[@B33]-[@B44]\]. In this regard, 25 of our 30 probands with VUS carried variants that had been previously reported to be pathogenic or possibly pathogenic ([Table S5](#pone.0081194.s007){ref-type="supplementary-material"}). The remaining 5 probands carried 5 novel VUS, including 3 missense variants (2 occurring in the same proband) predicted to have a deleterious effect using previously developed *in silico* tools (see [Table S5](#pone.0081194.s007){ref-type="supplementary-material"}), one in-frame deletion that was considered potentially pathogenic based on previous studies showing the crucial function of the amino acids removed and one intronic variant (occurring in 2 probands) whose deleterious effect on allele expression and splicing was characterized in this study based on the results of ASE analysis, as discussed below. One remarkable observation in this study is the high proportion (8/22, 36.5%) of germline defects revealed by ASE analysis in the informative probands analyzed. Notably, in a relevant proportion of cases ASE contributed to identify germline alterations that were not detected by other analyses or that were of uncertain significance ([Figure 2](#pone-0081194-g002){ref-type="fig"}). In particular, in 3 of these cases, negative for pathogenic variants or VUS, imbalanced ASE was the only germline MMR gene defect identified ([Table 1](#pone-0081194-t001){ref-type="table"}). The 3 patients showed also independent evidence of MMR defects, as indicated by the presence of tumor MSI-H phenotype. These observations show that ASE analysis has the potential to reveal alterations in germline transcript expression even when these are due to defects that may escape detection with traditional sequencing, MLPA or NGS approaches. Such defects include germline epigenetic allele silencing, or nucleotide changes occurring in genomic regions not comprised in the screening, such as *cis*- or trans-acting variants that alter gene regulation and lower the expression of the corresponding allele. In addition to identifying defects in cases negative at other integrative germline screenings, ASE may provide evidence for the pathogenic potential of VUS helping to characterize these variations, as exemplified in this study by the splice site variant detected in patients 360\#2916 and 986\#3487, both displaying tumor MSI-H phenotype. For this novel VUS, *in silico* analyses provided inconclusive results, whereas ASE analysis with two different markers readily revealed a marked alteration in allelic expression. ASE also guided the characterization of the mutant transcript, which was initially hindered by its lower expression, allowing the detection of exon skipping. Thus, ASE cost-effectively complements molecular analyses in probands negative at other screenings and may be helpful for the characterization of VUS with potential effects on gene expression that may be detected by gDNA-based methods, both traditional or NGS. In fact, NGS is bound to uncover novel coding and non-coding variants with potential effects on gene expression and testing their functional effect appears currently challenging \[[@B53]\]. In these cases, ASE may represent a practical tool to reveal pathogenic germline alterations in the corresponding genes. None of the probands tested in our study had germline *MSH2* promoter hypermethylation. This epigenetic modification was previously shown to be heritable and associated to deletions affecting the last exon of *EPCAM*, but sparing the contiguous *MSH2* promoter \[[@B8],[@B31]\]. In line with the lack of germline promoter hypermethylation in our probands, the only patient displaying an *EPCAM* rearrangement in this study had a deletion that removed also the *MSH2* promoter and extended up to exon 7 of this gene. Thus, our results indicate that *EPCAM* rearrangements and *MSH2* promoter hypermethylation were not frequent among the probands tested in the present study. We did not detect germline hypermethylation of the *MLH1* promoter and this finding in our probands belonging to families with vertical transmission is consistent with the non-Mendelian inheritance mostly reported for constitutional *MLH1* epimutations \[[@B54],[@B55]\]. Several studies supported the value of tumor IHC and MSI prescreening and these analyses are included in models for multifactorial classification of VUS pathogenicity \[[@B6],[@B19],[@B44],[@B51]\]. In this study, tumor IHC and MSI were generally concordant with the results of germline analyses, but there were several exceptions that limited their practical value. IHC provided indications useful to target germline mutational screening in 46 of the 73 (63%) cases analyzed. In several of our probands (12/73, 16%) the results of IHC were in contrast with those of germline screening for MMR gene defects and/or tumor MSI analysis. The occurrence of discrepancies between IHC, MSI and germline screening for defects in MMR genes was reported also in previous studies \[[@B5],[@B19]\]. As far as MSI, germline MMR gene defects were detected in the majority of MSI-H cases and no MMR gene pathogenic variants were detected in patients with MSS or MSI-L tumors in our study. However, previous studies showed that patients with MSS or MSI-L tumors may occasionally harbor germline MMR gene defects \[[@B5],[@B20]\]. Moreover, the occurrence of somatic *MLH1* silencing was previously shown to be responsible of inconsistencies between germline and tumor MMR defects \[[@B5]\]. In addition to the potential causes of inconsistencies described in previous studies, we cannot exclude that technical issues, such as sample quality and differences in IHC and MSI procedures and interpretation among centers might be responsible for some of the discrepancies between germline and tumor observed in our study. In any case, the occurrence of false positive or negative results with both IHC and MSI also in previous studies \[[@B5],[@B19],[@B20]\] indicates that these tumor assays should be used with caution to include or exclude probands from screening for germline MMR gene defects. In particular, a germline screening based on the results of IHC analyses obtained in this study would have missed germline defects in 6 probands. Furthermore, with the advent of cost-efficient NGS technologies, allowing simultaneous analysis of several CRC predisposing genes, IHC and MSI prescreening may become unnecessary. On the other hand, tumor assays, such as IHC and MSI, may provide evidences that contribute to multifactorial models for VUS classification, as indicated by previous studies \[[@B43],[@B44],[@B52]\]. One important issue in genetic testing of HNPCC is the considerable proportion of patients negative for MMR gene variants observed in several studies \[[@B19]-[@B21]\], including the present. This reflects at least in part limitations of MMR gene screenings that are shared by this and other studies and in part the fact that a significant percentage (up to 40%) of families meeting Amsterdam criteria are FCCTX unrelated to MMR defects \[[@B4]\]. It is noteworthy that in our study 2 of the 19 (\~10%) probands negative for MMR gene variants and undergoing mutation screening of *APC* and *MUTYH* carried germline defects in one of these two genes. Thus, despite the limited number of patients screened, this finding highlights the importance of analyzing polyposis-associated genes in families negative for MMR gene alterations with a clinical HNPCC phenotype. In this regard, testing of multiple genes is now facilitated by the use of NGS approaches \[[@B22]\]. On the other hand, despite extensive screening of known CRC predisposition genes by NGS, the genetic basis of most cases negative for germline pathogenic defects in those genes remains elusive, as indicated by a recent study that identified only 6 pathogenic variants and 3 VUS among 31 Lynch or polyposis syndrome patients negative at previous analyses \[[@B22]\]. This observation indicates that NGS approaches focusing on candidate genes improve detection of gene variants, but are not sufficient to achieve a definite genetic diagnosis in all probands and that further studies are necessary to clarify the genetic basis of cases negative for pathogenic defects. Our results provide a number of indications that may help to improve current diagnostic algorithms for HNPCC. Analysis of several CRC predisposing genes was necessary to reveal germline defects and low-throughput methods are not cost-efficient for this task, especially when IHC results do not help to prioritize germline screening, as it occurred for several probands in this study. The recent development of gDNA-based NGS assays for parallel analysis of CRC predisposing genes (including MMR genes, *APC* and *MUTYH* tested in this study) opens a new possibility for more efficient genetic screening of HNPCC at reasonable costs. This technology has the potential to reveal both sequence variants and rearrangements that are the most frequent pathogenic defects detected in HNPCC. We screened for MMR gene rearrangements using MLPA that may still represent a cost-efficient approach for these relatively frequent defects. Confirmation of putative rearrangements was obtained using low-throughput methods, preferably by direct demonstration of breakpoints. Considering that breakpoint determination may be time-consuming and impractical, indirect methods may be applied, as exemplified by a recent study that confirmed by MLPA the putative rearrangements indicated by NGS \[[@B22]\]. The use of NFMP-DHPLC or LOC-CNV for rearrangement confirmation may represent a cost-effective alternative to MLPA, because these methods have lower analytical costs and assays validated in this or previous studies are already available \[[@B28],[@B29]\]. In our study none of the probands analyzed showed germline hypermethylation of MMR gene promoters. However, when such alterations are identified ASE analysis of the corresponding gene may provide an independent evidence of a pathogenic effect. In this study, ASE analysis helped to characterize one VUS with potential effects on splicing and revealed germline defects in 3 probands where only common nonpathogenic variants were detected. Thus, inclusion of ASE in our integrative screening ([Figure 2](#pone-0081194-g002){ref-type="fig"}) contributed to increase the proportion of patients with germline MMR defects identified as compared to previously proposed diagnostic algorithms that do not include ASE \[[@B17]-[@B21]\]. In conclusion, this study provides an overview of some relevant issues encountered in the genetic diagnosis of HNPCC using a variety of methods and supports the notion that ASE analysis and *APC* and *MUTYH* screening should be integrated in diagnostic algorithms to improve clinical translation of genetic testing in CRC predisposing syndromes. Supporting Information ====================== ###### **NFMP-HPLC assays for EPCAM genomic rearrangements.** Probes for EPCAM-1 and EPCAM-2 assays are indicated based on their position in the region encompassing EPCAM and the 5'upstream region of MSH2 (panel **a**). Examples of EPCAM-1 (panel b) and EPCAM-2 (panel c) profiles are shown for control individuals (top of each panel) and 2 representative patients (459\#2809, middle of each panel; 412\#3342, bottom of each panel). Control peaks are labeled "c" and arrows indicate amplicons with decreased peak heights, indicative of genomic deletions. EPCAM-1 (panel **b**): in patient 459\#2809 the chromatographic profile shows decreased peak heights for the 2 amplicons corresponding to the MSH2 5' upstream region (proximal and distal); in patient 412\#3342 all the *EPCAM-MSH2* amplicons included in the assay show decreased peak heights compared to the control peaks. EPCAM-2 (panel **c**): in patient 459\#2809 no alterations in the chromatographic profile are observed, confirming the absence of deletions in the EPCAM amplicons tested; in patient 412\#33428 the peaks corresponding to the EPCAM probes show decreased heights compared to the control peaks, confirming the deletion of the EPCAM amplicons tested. (TIF) ###### Click here for additional data file. ###### **Molecular analysis of exon skipping in patient 360\#2916.** Panel **a**: Location of RT-PCR primers in *MLH1* exons 14 and 17. Panel **b**: DHPLC chomatographic profiles obtained with cDNAs from patient 360\#2916 and a control. The chromatogram of patient 360\#2916 shows a major peak corresponding to the wt transcript and a minor peak corresponding to a less expressed shorter transcript (average allelic ratio 4.50, derived from 3 independent experiments). Panel **c**: DHPLC profiles derived from PCR amplification of the chromatographic fractions corresponding to the purified wt or shorter transcript. Panel **d**: Sequences corresponding to the two purified peaks (sequences of reverse strands are shown). The longer peak displays the wildtype sequence (top sequence), whereas the shorter peak shows the skipping of exon 15 (bottom sequence). (TIF) ###### Click here for additional data file. ###### **Primers for NFMP-HPLC analysis of *EPCAM-MSH2* rearrangements.** The first NFMP-HPLC multiplex for *EPCAM* (EPCAM-1) consisted of 7 amplicons, including 2 located in exons 3 and 8 of *EPCAM*, 3 located within the intergenic *MSH2*-*EPCAM* region and 2 reference amplicons corresponding to *MSH2* exon 9 and *MLH1* exon 5. The second NFMP-HPLC multiplex for *EPCAM* (EPCAM-2) consisted of 4 amplicons, including 2 located in exons 8 and 9 of *EPCAM* and 2 reference amplicons corresponding to *MSH2* exon 9 and *MLH1* exon 5. The third NFMP-HPLC multiplex for *EPCAM* (EPCAM-3) differed from EPCAM-2 assay only for the reference amplicon that was located within a copy number invariant region in chromosome 2q36.1. Multiplex PCRs were performed using a touchdown protocol in a total of 23 cycles. Reactions were carried out on a GeneAmp PCR System 2720 thermocycler (Applied Biosystems), in a final volume of 10 µl containing 30-50 ng of template DNA and 0.5 unit of AmpliTaq Gold DNA polymerase (Applied Biosystems). (DOC) ###### Click here for additional data file. ###### **Primers for analysis of germline *MLH1* promoter methylation.** (DOC) ###### Click here for additional data file. ###### **Comparison between results of ASE analyses performed using 32P-labeled primers or DHPLC.** (DOC) ###### Click here for additional data file. ###### **Primers for ASE assays developed in this study.** (DOC) ###### Click here for additional data file. ###### ***MSH2*, *MLH1* and *MSH6* nucleotide variants detected.** (DOC) ###### Click here for additional data file. ###### **Analysis of genomic rearrangements.** (DOC) ###### Click here for additional data file. ###### **Correlations between the results of ASE and other analyses.** (DOC) ###### Click here for additional data file. [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: AC. Performed the experiments: LDL GMA MCC TC SM SV FF. Analyzed the data: LDL GMA MCC TC SM SV FF PR AC. Contributed reagents/materials/analysis tools: PB VS LM CM PS LB PR AC. Wrote the manuscript: LDL AC. Recruitment of patients: VS LM CM PS LB PR. Critical revision of the manuscript: LB PR.
2023-12-13T01:27:15.642919
https://example.com/article/2161
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2023-08-23T01:27:15.642919
https://example.com/article/2823
People are very curious about Terry Wogan. Specifically, they are curious about his hair. 'Come on,' they whisper. 'It's got to be a wig.' A few days ago, when I first discovered that I was going to meet him, I dismissed this kind of talk, among my own friends at least, with a stern click of my tongue. Forget the thatch, I said. Wogan is a Light Entertainment Genius, a gentle humourist in the tradition of his idols Thurber and Perelman, and you'd do well to treasure him while his wonderful waffly warble - a sort of absurdist stream of consciousness - can still be heard on our airwaves. Oh dear. Now he's sitting opposite me, I feel quite embarrassed by this. My friends, it turns out, were right. The hair is absolutely captivating, every bit as darling as last season's fur tippets. It's all I can do not to reach over and stroke it. We are drinking coffee in a hotel in what used to be County Hall, on the south bank of the Thames. Wogan has hot-footed it here straight from the studio of his Channel Five chatshow, the very last edition of which was broadcast on Friday (another failure for Chris Evans, whose company was behind it). Tomato of face and darty of eye, he is dressed in high-Tarby style: baby blue blazer, slip-on shoes and novelty tie featuring a cartoon of a fox chasing a chicken. It is the hair, though, that is his, well, crowning glory. I am certain it is not a wig (for one thing, it is convincingly threaded with grey; for another, it doesn't cover the bald patch at the back of his head). Then again, neither have I seen its like before. At the grand old age of 65, Wogan is in possession of a hedge so wildly exuberant there could be three songbirds and an old tramp living in it. It takes him a while to settle down and listen to my questions; at first, he just chunters away, willy-nilly. In part, this is probably because there is still adrenaline chugging around his roly-poly body. But mostly, I think, he is just so used to hamming it up as the public Terry Wogan - a daffy, self-deprecating chap who imagines he has only just jumped off the boat from Ireland - that he is almost incapable of playing the real Terry Wogan. Joke follows joke, and he is the butt of them all. Why is his Radio 2 breakfast show so amazingly successful? 'People make a decision: they want news or music or wall-to-wall rubbish. In my case, it's wall-to-wall rubbish.' What is the secret of his staying power? 'People confuse longevity with merit. Look at Cliff Richard.' What is he doing later? 'I'm sorry. I can't tell you that.' This last is deadpan but then, as ever, an endearing titter somehow escapes his beetroot lips. 'Hee, hee. You're obviously trying to find out if I have a mistress.' He has taken the axing of The Terry and Gaby Show (his co-presenter was Gaby Roslin) in his stride. After all, he has been here before; in 1992, he lost his thrice-weekly BBC1 chatshow in similar fashion. Moreover, he is older now, and already gets up at 5.30 every morning to do Wake Up to Wogan. 'It's finished, that's all,' he says. 'It's a pity. In my humble and unbiased opinion, it's a terrific show. On the other hand, the old bones are creaking.' Lately, he admits, his thoughts have - whisper it softly - been turning to retirement. His contract at the BBC, where eight million devoted listeners tune in to him each weekday, runs only until next March. 'Will I have the guts to retire? What you have to avoid is leaving with a bad taste, hanging on too long. But what is too long?' He worries that, were he to give it all up, he might annoy Helen, his wife of 39 years. 'She has developed a social life of her own. She's better than I am socially. In my job, you work with three people. You don't get to build up a whole new set of friends. I don't think she'd welcome my stopping at home.' A pause, then another wheezy chuckle. 'But the BBC air conditioning is not good for your health. If you don't come out with legionnaire's disease, you're extremely lucky.' Still, he has the luxury of being able to pontificate about such matters in public because, however pathological his desire to make light of his abilities ('I just found something I could do,' he insists), there is a dearth of talent in radio and TV right now. Wogan, a broadcaster of consummate brilliance, is a precious commodity, a 22-carat performer in a world of fool's gold. Has he noticed any talent coming up behind him? Apparently not. 'I like Jonathan Ross,' he says. 'Ant and Dec are great little fellas. But there are a lot of people - I won't name names - who you think: why have they been given a long-term contract? They buy up people who've made it on a minor channel and expect them to make it on a major channel.' He looks momentarily glum. 'You hope that people will emerge but it's so difficult to produce anything popular nowadays. Universal appeal is a thing of the past.' By now, I am ready for the ironic pay-off line. 'I mean, not even the Eurovision Song Contest is watched by everybody.' Terry Wogan was born in Limerick, where his father ran a grocer's shop. He has one brother, who is six years younger than him. 'My parents were shy people and the worst sin in the Catholic church, after sex, was vanity. So how any of us came out of it with any self-regard, I don't know. But I always had self-esteem. I think it came from being on my own for so long before my brother was born.' But the Limerick of his childhood was 'cursed' with religion and not even the scepticism of his parents - 'They knew it was a lot of rubbish' - could entirely protect him from it. 'There were hundreds of churches, all these missions breathing fire and brimstone, telling you how easy it was to sin, how you'd be in hell. We were brainwashed into believing.' When he lost his faith, at the age of 17, it came as a relief. 'My whole life changed. If you haven't any doubts, you've no brain.' Even so, something in him responded to his Jesuit education and it still informs many of his attitudes - duty and control are his watchwords - that I would not rule out a return to the fold. 'Well, people do tend to come back when they're looking for the exit,' he mutters. He married Helen, a house model for Balmain, in 1965. The two of them were virgins on their wedding night. 'This idea that we were deprived of sex!' he yelps, when I express amazement at this. 'Romance is predicated on the non-fulfilment of the sexual urge. The frisson of non-fulfilment is probably more exciting than sex. I'd be hopeless, nowadays. Things are too confrontational. I could never take to promiscuity. I'm too fastidious. Anything used to put me off. Anything! Oh, God! Ugh! Ugh!' He sounds quite shrill. 'Women think that men will take anything going. No, they won't.' But when he married, didn't he hear a door slamming? Didn't he mourn all the women that might have been? 'No, I wouldn't have. I could never... no... no ! I couldn't have done. It was right for me to get married.' The Wogans have two sons and a daughter (their first baby, Vanessa, had heart problems and never came home from hospital) and the family is, he tells me, the reason for everything he ever does. Is he easy to live with? 'We're careful of each other. The things that we argue about are so small and inconsequential, like, "Where are me socks?" or, "These handkerchiefs are dirty." We never shout at each other for more than 10 seconds and then we regret it. She's a great cook and she's very kind, gentle and loving.' Very softly, he adds: 'I think she's the best person I've ever met.' Wogan's career, or so he maintains, was a kind of happy accident. After he left school, he spent five years working for the Royal Bank of Ireland, the permanent pensionable position his parents had always dreamed of for him. Then at 21, he entered, and won, a competition to become an announcer for the Irish station, RTE. Finally, in 1969, after two years doing Late Night Extra on Radio 1, for which he used to fly over from Dublin, he came to London as holiday cover for Jimmy Young and stayed. 'I was never really ambitious,' he says. 'I was never good at knocking on doors. I make it up as I go along.' Perhaps because of this insouciance, which may - who knows? - mask insecurity, he has never let success go to his head (others have hinted that he is being disingenuous when he says this, but I have an ego detector like you wouldn't believe and in his presence it didn't bleep once). 'People who are successful should never forget that it's 90 per cent luck. You've got to be an eejit to be an egomaniac. I had my glory years - Blankety Blank, the talk show, when I was winning every award going. But now half the population doesn't know who I am.' Unsurprisingly, the stars he interviewed during the decade he presented Wogan used to drive him up the wall. It wasn't just drunk George Best and grumpy Prince Philip who were a problem; the professionals made his blood boil, too. Take Anne Bancroft. She appeared in his dressing room in tears; she hadn't realised the programme was live. She went on to answer only 'yes' and 'no' to all his questions, which didn't exactly make for riveting television. Then there were the cases when guests had obviously taken drugs. 'I used to get furious inside. I'm not a great fan of anybody, so I'd be looking at them... ' His face is congested with disdain. 'You get a bloody actor who's on an upper or a downer - too far over the top because he's taken something up his nose or another pill - and you think: why come on the show if you don't want to talk? Idiot.' Wogan has now been presenting the Radio 2 breakfast show, mark two, for 11 years; he has worked at the BBC, in one guise or another, for nearly 40. These days, however, he fears for its future. 'Morale is not good. As for the preposterous idea of funding it through voluntary contributions; if that ever came to pass, it would be dreadful. If they take away the licence fee, it'll all over.' His prescription, for the time being, is for the corporation to err on the side of quality. 'This extraordinary mantra of appealing to "yoof", as if youth were a specific section of society that never grows older.' Is Chris Moyles, the swollen loudmouth who presents the Radio 1 breakfast show, an example of what he means? In the past, the two have slagged one another off. 'Ye-es. But we don't know each other at all. Chris has got an Irish mother. He respects me, I respect him.' Hmm. He cannot stand reality TV. 'They can only go one way with that. It's got to get seamier and seamier. Eventually, we'll end up with soft porn.' The other day, he had to interview the pre-operative transsexual who is the star of a reality show on Sky One called There's Something About Miriam (men were asked to compete for her affections without being told that 'she' was in fact a 'he'). 'It's called I'm Miriam, Come and Get Me! or something,' he splutters. 'How low can you go? Footballers' Wives! I've never seen anything like it! Nip/Tuck! It's got nothing to do with plastic surgery - it's all about bonking. How did we get to this? But perhaps I am an old fart... ' Suddenly, he is back to pondering his retirement. 'When is enough?' he says. 'Alistair Cooke, with the greatest respect, went on 10 years too long. Jimmy Young left under a cloud, which was a great pity. Ah, to be able to recognise when the tide is going out, when to get off the beach.' I am just starting to worry about him when distraction arrives in the form of a fan. She has Elnet hair and pink lips and a nice line in lilac lambswool. 'Ooh, Terry,' she gasps, grabbing him by both elbows. 'Me and my friend are having a lovely day. We saw you doing the show and now we're having a spot of lunch.' She looks at me. 'Sorry to interrupt,' she says, though she clearly isn't sorry at all. Terry springs up, kisses her twice and signs an autograph. Only once she has disappeared into the restaurant does he lower himself back into his seat. 'A groupie!' I chirrup, encouragingly. 'Ah, yes, I have a strange effect on old women,' he replies, all smiles. Wogan on his guests Dressed from head to toe in a turquoise shellsuit, David Icke claimed he was the Son of God. 'Why you?' asked an incredulous Wogan. 'People would have said the same thing to Jesus,' Icke replied. As the audience dissolved, Icke insisted: 'The best way of removing negativity is to laugh and be joyous, Terry.' 'But they're laughing at you,' said Wogan, 'they're not laughing with you.' George Best got drunk in the hospitality suite before appearing and proceeded to ring out a string of swear words. He then kissed Omar Sharif, the other guest on the show. Viewers flooded the station with complaints. 'Let's just say his communication skills weren't working too well that day,' said Wogan. 'We were only supposed to have about eight or nine million viewers but everyone in Britain seemed to be watching.' David Bowie nearly provoked violence. 'I didn't hit him, but it came close. For reasons best known to him, he came on unwilling to talk.' 'Bette Davis was a real hero of mine who I'd been really looking forward to having on the show. But she was a right pain because we didn't mention her book in the first sentence and she was cross about it.' The critics on Wogan According to the Guardian: 'Wogan was so star-struck when he met Madonna [below] he made Jonathan Ross's effort, itself in the first rank of sycophancy, look like Jeremy Paxman with piles.' Victor Lewis-Smith: 'He's never invaded Poland, of course, nor (to the best of my knowledge) has he ever set fire to the Reichstag, but his annual contribution to the Eurovision Song Contest has surely done (in peacetime) for European brotherhood what the Third Reich only achieved by war.'
2023-10-28T01:27:15.642919
https://example.com/article/2507
/** * Copyright (c) 2017-present, Facebook, Inc. * All rights reserved. * * This source code is licensed under the BSD-style license found in the * LICENSE file in the root directory of this source tree. An additional grant * of patent rights can be found in the PATENTS file in the same directory. * * @flow * @format */ import type {NuclideUri} from 'nuclide-commons/nuclideUri'; export type FindReferencesProvider = { // Return true if your provider supports finding references for the provided TextEditor. isEditorSupported(editor: TextEditor): Promise<boolean>, // `findReferences` will only be called if `isEditorSupported` previously returned true // for the given TextEditor. findReferences( editor: TextEditor, position: atom$Point, ): Promise<?FindReferencesReturn>, }; export type Reference = { uri: NuclideUri, // Nuclide URI of the file path name: ?string, // name of calling method/function/symbol range: atom$Range, }; export type FindReferencesData = { type: 'data', baseUri: NuclideUri, referencedSymbolName: string, references: Array<Reference>, title?: string, // defaults to 'Symbol References' }; export type FindReferencesError = { type: 'error', message: string, }; export type FindReferencesReturn = FindReferencesData | FindReferencesError; export type FindReferencesViewService = { viewResults(results: FindReferencesData): Promise<void>, }; export type ReferenceGroup = { references: Array<Reference>, // Start and end range of the preview text. startLine: number, endLine: number, };
2023-09-27T01:27:15.642919
https://example.com/article/5546
Juliette de Baïracli Levy Juliette de Baïracli Levy (11 November 1912 – 28 May 2009) was an English herbalist and author noted for her pioneering work in holistic veterinary medicine. After studying veterinary medicine at the Universities of Manchester and Liverpool for two years, Bairacli Levy left England to study herbal medicine in Europe, Turkey, North Africa, Israel and Greece, living with Romani people, farmers and livestock breeders, acquiring a fund of herbal lore from them in the process, most notably from the Romani people. She has written several well-known books on herbalism and nomadic living in harmony with nature, in addition to fiction and poetry illustrated by Olga Lehmann. After living for some time on the Greek island Kythira, de Bairacli Levy resided in an old age home in Burgdorf, Switzerland. Partial bibliography of works by Juliette de Bairacli Levy Medicinal Herbs: their use in Canine Ailments, London: A.P.Tayler & Co, 1943. Look! The Wild Swans (novel), illustrated by Olga Lehmann, London: C.W. Daniel Co.; Manchester: Rochford, Bairacli Books, 1947. Puppy Rearing by Natural Methods, New York: Sirius House, 1948. The Cure for Canine Distemper, London: Fowler & Co., 1930, (revised and enlarged) 1950. Herbal Handbook For Farm and Stable, London: Faber & Faber, 1952, 1963. As Gypsies Wander: Being an account of life with gypsies in England, Provence, Spain, Turkey, London: Faber & Faber, 1962. The Bride of Llew (novel), illustrated by Olga Lehmann, London: Faber & Faber, 1953. Spanish Mountain Life: the Sierra Nevada, London: Faber & Faber, 1955. The Complete Herbal Book for the Dog, London: Faber & Faber, 1955, 1975. Wanderers in the New Forest, London: Faber & Faber, 1958, . Summer in Galilee, London: Faber & Faber, 1959. A Gypsy in New York, London: Faber & Faber, 1962. A Herbal Handbook for Everyone, London: Faber & Faber, 1966. The Natural Rearing of Children, London: Faber & Faber, 1970. The Complete Herbal Handbook for the Dog and Cat, London: Faber & Faber, 1971. Traveler's Joy, . Nature's Children, . Common Herbs for Natural Health, The Yew Wreath (a book of twenty poems), illustrated by Olga Lehmann. The Willow Wreath (a book of twenty poems). The Cypress Wreath (a book of twenty poems). A Gypsy in New York (new edition, back in print), Woodstock, NY: Ash Tree Publishing, 2011 Spanish Mountain Life (new edition, back in print), Woodstock, NY: Ash Tree Publishing, 2011 Summer in Galilee (new edition, back in print), Woodstock, NY: Ash Tree Publishing, 2011 References and description of Bairacli Levy's work External links Juliette of the Herbs - documentary that encapsulates Bairacli-Levy's life and teachings, her various herbal medicine methodologies along with the importance of Romani (Gypsy) culture in forming and shaping her knowledge and worldview, highlighting her intense love for animals, particularly cows and the Afghan Hound Category:1912 births Category:2009 deaths Category:British veterinarians Category:Herbalists Category:Women veterinarians
2023-12-20T01:27:15.642919
https://example.com/article/8052
The Tom Ewell Show The Tom Ewell Show is an American sitcom that aired on CBS during the 1960-61 television season under the alternate sponsorship of Quaker Oats and Procter & Gamble. Summary Tom Ewell stars in this half-hour sitcom as Tom Porter, a real estate agent whose entire life, away from the office, was dominated by females: Wife Fran (played by Marilyn Erskine), Live-in mother-in-law, Grandma Irene Brady (Mabel Albertson). Three daughters: 15-year-old Carol (played by Cindy Robbins, stage name for Cynthia Chenault), 11-year-old Debbie (played by former Mouseketeer Sherry Alberoni), 7-year-old Sissie (played by Eileen Chesis) Family-dog Mitzi Recurring characters included Norman Fell as co-worker Howie Fletcher, heavy-set actor Barry Kelley as friend Jim Rafferty, and child-actor Vance Meadows as a neighborhood youngster. List of episodes Production notes The Tom Ewell Show was created by Madelyn Martin and Bob Carroll, Jr. (of The Lucy Show fame), and produced by Tom Ewell's own production company (in partnership with Martin and Carroll, and with Four Star Productions). Broadcast schedule The thirty episodes of the show were broadcast 9–9:30 PM (EST) on Tuesday nights in the United States from September 27, 1960 through May 23, 1961 on the CBS network. Eight of the episodes were shown as summer repeats in the same timeslot from May 30, 1961 through July 18, 1961. This series was sponsored alternately by The Quaker Oats Company and Procter & Gamble. Critical reception TIME magazine said: "The Tom Ewell Show (CBS) leads a relentless parade of situation comedies, all designed to show that American family life is as cute as a freckle on a five-year-old. The show, which might also be titled Father Knows Nothing, presents the comic with the excavated face as a bumbler named Potter who is trapped in the customary format: Harassed Man Beaten Down by Wife, Three Daughters, Mother-in-Law. In the opening episode, Ewell could find no better way to outsmart his spendthrift women than closing his bank account and ruining his own credit. For those who may have tuned out early, the women were all set to start spending again." References External links Category:1960 American television series debuts Category:1961 American television series endings Category:1960s American television series Category:1960s American sitcoms Category:Black-and-white television programs Category:CBS original programming Category:English-language television programs Category:Television series about families Category:Television series by Four Star Television
2024-02-16T01:27:15.642919
https://example.com/article/9171
597 N.E.2d 616 (1992) 149 Ill.2d 302 173 Ill.Dec. 642 Kalan D. RODGERS, Sr., Adm'r of the Estate of Brenda Marie Rodgers, Deceased, Appellee, v. ST. MARY'S HOSPITAL OF DECATUR, Appellant. No. 70722. Supreme Court of Illinois. July 30, 1992. *618 Graham & Graham, of Springfield (Richard J. Wilderson, of counsel), for appellant. Robert M. Owen, Popkin, Stern & Owen, Decatur and Charles H. Fendell, Popkin & Stern, St. Louis, Mo., for appellee. Chief Justice MILLER delivered the opinion of the court: On September 25, 1987, plaintiff, Kalan Rodgers, Sr., filed suit against defendant, St. Mary's Hospital, in the circuit court of Macon County. The complaint alleges that the hospital failed to preserve for litigation all X rays taken of his wife, Brenda Rodgers, who had been a patient at the hospital for several days before she died there. Rodgers claims that the hospital's loss of an X ray caused him to lose a malpractice suit he had filed earlier against his wife's radiologists. The circuit court dismissed the complaint and Rodgers appealed. The appellate court reversed and remanded. (198 Ill.App.3d 871, 145 Ill.Dec. 295, 556 N.E.2d 913.) We granted the hospital's petition for leave to appeal (134 Ill.2d R. 315(a), 135 Ill.2d 566, 151 Ill.Dec. 392, 564 N.E.2d 847), and now affirm the judgment of the appellate court. Facts Rodgers filed a medical malpractice action in the circuit court of Macon County on May 27, 1986, alleging the wrongful death of his wife, Brenda, who died at the hospital two days after giving birth to their son. Named as defendants in the medical malpractice action were Brenda's obstetricians, her radiologists, and the hospital. The circuit court entered summary judgment in favor of the hospital on May 13, 1988. Rodgers did not appeal the summary judgment in favor of the hospital. Rodgers proceeded to trial against the obstetricians and radiologists. On June 10, 1988, the jury found in favor of Rodgers on his claims against the obstetricians and assessed damages at $1.2 million. The jury found the radiologists not liable and Rodgers did not appeal that finding. The obstetricians appealed, but the appeal was dismissed by stipulation of the parties on May 24, 1989, when Rodgers and the obstetricians agreed to settle the medical malpractice claim for $800,000. In the meantime, on September 25, 1987, Rodgers had filed a separate complaint for damages against the hospital alleging that the hospital breached its statutory duty to preserve for five years all of the X rays taken of Brenda (see Ill.Rev.Stat.1987, ch. 111½ par. 157-11 (X-Ray Retention Act)). He claimed that the X rays were crucial to proving his case against the obstetricians and radiologists. On April 12, 1988, on motion of the hospital, the circuit court dismissed that complaint without prejudice. Rodgers amended his complaint and brought the present action against the hospital on May 25, 1989, the day after he reached the $800,000 settlement with the obstetricians. In his complaint, Rodgers alleged that Brenda's death was caused by a sigmoid colonic volvulus, and that the condition appeared on an X ray that the hospital had a duty to preserve. Rodgers alleged that the hospital's failure to preserve the X ray was a breach of its duty arising from the X-Ray Retention Act and from the hospital's internal regulations. Rodgers asserted that because the hospital failed to preserve the X ray, Rodgers was unable to prove his case against the radiologists. He further alleged that had he recovered against the radiologists and the obstetricians jointly and severally, the verdict would have been paid in full and would not have been appealed. He thus sought $400,000 in damages from the hospital, the difference between the $1.2 million verdict and the $800,000 settlement. The trial court dismissed the amended complaint on the grounds that Rodgers' settlement with the obstetricians and failure to appeal the judgment in favor of the radiologists *619 barred his loss-of-evidence claim against the hospital. Rodgers appealed. The appellate court reversed the judgment of the circuit court. The appellate court held that Rodgers' amended complaint stated a statutory cause of action that was not barred by res judicata or waived by Rodgers' post-judgment settlement with the obstetricians. (198 Ill. App.3d at 876-81, 145 Ill.Dec. 295, 556 N.E.2d 913.) We granted the hospital's petition for leave to appeal (134 Ill.2d R. 315). The issues presented are whether there is a statutory cause of action under the X-Ray Retention Act and whether Rodgers' suit is barred by his earlier settlement with the obstetricians or by res judicata. Discussion We first address whether the statute grants Rodgers a private cause of action by implication. The X-Ray Retention Act, formally titled "An Act concerning the retention for use in litigation of X-ray or roentgen films of the human anatomy," provides in relevant part: "Hospitals which produce photographs of the human anatomy by the X-ray or roentgen process on the request of licensed physicians for use by them in the diagnosis or treatment of a patient's illness or condition shall retain such photographs or films as part of their regularly maintained records for a period of 5 years provided that retention of said photographs or film may be by microfilm or other recognized means of minification that does not adversely affect their use for diagnostic purposes. However, if the hospital has been notified in writing by an attorney at law before the expiration of the 5 year period that there is a litigation pending in court involving a particular X-ray or roentgen photograph in their records as possible evidence, and that the subject person of such photograph is his client, or is the person who has instituted such litigation against his client, then the hospital shall keep such photograph or film or minified copy thereof in its regular records until notified in writing by the plaintiff's attorney with the approval thereon of the defendant's attorney of record that the case in court involving such photograph has been concluded, or for a period of 12 years from the date that the X-ray photograph film was produced, whichever occurs first in time." Ill.Rev.Stat.1987, ch. 111½, par. 157-11. Implication by a statute of a private right of action is appropriate when: "(1) plaintiff is a member of the class for whose benefit the Act was enacted; (2) it is consistent with the underlying purpose of the Act; (3) plaintiff's injury is one the Act was designed to prevent; and (4) it is necessary to provide an adequate remedy for violations of the Act." Corgan v. Muehling (1991), 143 Ill.2d 296, 312-13, 158 Ill.Dec. 489, 574 N.E.2d 602. It is clear that the X-Ray Retention Act was designed to prevent the loss of evidence that may be essential to the pursuit or defense of a medical malpractice claim. Therefore, there can be little dispute that Rodgers, a plaintiff with a malpractice claim, is a member of the class for whose benefit the statute was enacted, and that Rodgers' injury is one the statute was designed to prevent. The hospital argues that the statute is merely an administrative regulation to be enforced exclusively by the Department of Public Health. We disagree. As in Corgan, nothing in the statute suggests that the legislature intended to limit the available remedies to administrative ones (143 Ill.2d at 314, 158 Ill.Dec. 489, 574 N.E.2d 602). Indeed, the statute enumerates no specific administrative remedies and administrative remedies would not provide an adequate remedy to those injured by violations of the Act. Additionally, the threat of liability is a much more efficient method of enforcing the regulation than requiring the Public Health Department to hire inspectors to monitor the compliance of hospitals with the provisions of the Act. Thus, it is reasonable to believe that the legislature intended that those persons protected by the Act have a right to bring a private action against the offending hospital for damages caused by a breach of the statute. We therefore conclude that a private cause *620 of action is necessary to provide an adequate remedy for violations of the Act, and that it is consistent with the underlying purpose of the Act. The hospital also argues that its loss of one X ray out of a series of six should be considered de minimus and not a violation of the statute. We disagree. The statute requires that all X rays be preserved, not just some of them. We therefore hold that a jury could find that the hospital's admitted loss of one X ray is a violation of the X-Ray Retention Act. The appellate court held that a violation of the X-Ray Retention Act gives rise to a statutory cause of action and that the violation is prima facie evidence of negligence. (198 Ill.App.3d at 875-76, 145 Ill.Dec. 295, 556 N.E.2d 913.) The issue of whether the action implied by the X-Ray Retention Act should be governed by the principles of negligence or strict liability has not been raised in this appeal, and we therefore do not address that issue here. We note, however, that in any case based on a violation of the X-Ray Retention Act, the plaintiff must still plead and prove an injury and damages proximately caused by the loss of an X ray. Rodgers asserts that as a result of the hospital's actions, he lost his medical malpractice case against the radiologists. Rodgers further alleges that, were the radiologists liable as joint tortfeasors with the obstetricians, he would not have been forced to settle for $400,000 less than the judgment. He thus claims harm to his litigation rights, totaling $400,000. Because this case comes to us on the pleadings, all well-pleaded facts must be taken as true. (Teter v. Clemens (1986), 112 Ill.2d 252, 97 Ill.Dec. 467, 492 N.E.2d 1340; see also Triangle Sign Co. v. Weber, Cohn & Riley (1986), 149 Ill.App.3d 839, 843, 103 Ill.Dec. 294, 501 N.E.2d 315.) Rodgers has pleaded $400,000 in damages. Whether the damages are in fact $400,000 and whether they were proximately caused by the loss of the X ray and Rodgers' inability to obtain a verdict against the radiologists are questions for the trier of fact and are not at issue here. We note, however, that $400,000 would be the upper limit on Rodgers' recovery. The jury's verdict against the obstetricians was in the amount of $1.2 million, and Rodgers has admitted that the verdict was complete compensation for his loss. Even if the radiologists had been found jointly liable with the obstetricians, Rodgers might not have received the full $1.2 million verdict. The radiologists as well as the obstetricians would still have had the right to appeal the judgment and a trier of fact could find that Rodgers would have been willing to settle with both defendants for a payment of less than $1.2 million in order to avoid an appeal. We conclude that Rodgers has stated a cause of action against the hospital for failure to preserve the X ray for use in litigation. Whether the missing X ray proximately caused Rodgers to lose his case against the radiologists and to settle for less than the full amount of the judgment is a question for the trier of fact. The hospital next contends that Rodgers' settlement with the obstetricians operated as a waiver of any subsequent claims against the parties in the original malpractice case and that Rodgers' claimed damages of $400,000 were self-imposed when Rodgers voluntarily settled for less than the amount of the judgment. We find nothing to support the hospital's waiver argument. As the appellate court pointed out, a rule that a post-judgment settlement bars an action for loss of evidence in this situation would be contrary to well-established principles of joint liability. (198 Ill.App.3d at 878, 145 Ill.Dec. 295, 556 N.E.2d 913.) When a plaintiff settles with one party, the remaining tortfeasors remain jointly and severally liable for the full amount of the judgment, minus the amount of the settlement. (Henry v. St. John's Hospital (1990), 138 Ill.2d 533, 543, 150 Ill.Dec. 523, 563 N.E.2d 410.) Additionally, such a rule would discourage settlement of disputed claims. Accordingly, we believe that the present claim against the hospital must remain *621 intact, despite Rodgers' settlement with the obstetricians. The hospital also argues that Rodgers' failure to appeal the jury's finding of no liability in favor of the radiologists should bar his loss-of-evidence claim against the hospital. We reject this argument as well. As the appellate court observed, such a rule would encourage frivolous appeals in order to preserve loss-of-evidence claims, and would thus be a waste of judicial resources. 198 Ill.App.3d at 879, 145 Ill.Dec. 295, 556 N.E.2d 913. Finally, the hospital argues that even if Rodgers' amended complaint states a cause of action, the action is barred by the summary judgment rendered on May 13, 1988, in favor of the hospital in the malpractice case. The doctrine of res judicata provides that a final judgment on the merits is conclusive as to the rights of the parties, constituting an absolute bar to a subsequent action involving the same claim, demand, or cause of action. Housing Authority v. Young Men's Christian Association (1984), 101 Ill.2d 246, 251, 78 Ill.Dec. 125, 461 N.E.2d 959. To determine whether causes of action are the same for res judicata purposes, Illinois courts have adopted two tests. (Hagee v. City of Evanston (7th Cir.1984), 729 F.2d 510 (applying Illinois law); Best Coin-Op, Inc. v. Paul F. Ilg Supply Co. (1989), 189 Ill.App.3d 638, 136 Ill.Dec. 957, 545 N.E.2d 481.) The first is called the "same evidence" test. Under that test, res judicata bars a second suit if the evidence needed to sustain the second suit would have sustained the first, or if the same facts were essential to maintain both actions. (Pfeiffer v. William Wrigley Jr. Co. (1985), 139 Ill.App.3d 320, 322, 92 Ill.Dec. 332, 484 N.E.2d 1187; Village of Northbrook v. County of Cook (1980), 88 Ill.App.3d 745, 750, 43 Ill.Dec. 792, 410 N.E.2d 925; Palya v. Palya (1980), 87 Ill. App.3d 472, 475, 42 Ill.Dec. 638, 409 N.E.2d 133.) The second test is the "transactional" approach, which considers whether both suits arise from the same transaction, incident, or factual situation. The transactional approach provides that "`the assertion of different kinds of theories of relief still constitutes a single cause of action if a single group of operative facts give rise to the assertion of relief.'" Pfeiffer, 139 Ill. App.3d at 323, 92 Ill.Dec. 332, 484 N.E.2d 1187, quoting Baird & Warner, Inc. v. Addison Industrial Park, Inc. (1979), 70 Ill.App.3d 59, 64, 26 Ill.Dec. 1, 387 N.E.2d 831; see also Phillips v. Elrod (1985), 135 Ill.App.3d 70, 74, 88 Ill.Dec. 470, 478 N.E.2d 1078. We conclude that under either test, res judicata does not bar the present action. Here, Rodgers' amended complaint against the hospital is based on a different cause of action than that underlying his prior claim against the hospital, obstetricians, and radiologists. The present action is for loss of evidence; the first was for medical malpractice. The same evidence would not sustain both verdicts, and the facts essential to each suit did not arise from the same transactions or incidents. To obtain a favorable verdict on the present cause of action, Rodgers must show that but for the hospital's failure to preserve all X rays of Brenda, he would have prevailed against the radiologists and that in so doing he would have recovered more than $800,000 of the damages awarded by the jury in the medical malpractice suit. These facts would not have sustained a verdict in the medical malpractice action. There the issue was whether the doctors or hospital negligently caused Brenda's death. The X ray was lost after Brenda died and could therefore not have affected the defendants' exercise of care in treating Brenda. Furthermore the existence of the duty to preserve the X ray, the incidents causing the X ray to be missing at trial, and the facts surrounding the potential evidentiary value of the missing X ray are circumstances unrelated to determining medical malpractice liability in the first cause of action. Thus, under either test for identical causes of action, res judicata does not bar the present action. In a supplemental brief, the hospital argues that Rodgers has divided his cause of action and should have been required *622 to try all of his claims against both the doctors and the hospital in a single suit. Because this argument was not presented in the hospital's petition for leave to appeal, we deem the argument to be waived. Dineen v. City of Chicago (1988), 125 Ill.2d 248, 265, 126 Ill.Dec. 52, 531 N.E.2d 347. In sum, Rodgers' amended complaint states a cause of action implied by statute. It is for the trier of fact to determine whether the hospital's failure to preserve the X ray proximately caused Rodgers to lose his malpractice case against the radiologists, and if so, to what damages Rodgers is entitled. The present action is not barred by Rodgers' settlement with the obstetricians in the earlier medical malpractice suit, or by res judicata. Accordingly, we affirm the judgment of the appellate court. Judgment affirmed.
2023-10-08T01:27:15.642919
https://example.com/article/3576
Concentration-dependent exsorption of quinidine in the rat intestine. During intravenous infusion, the luminal concentration of quinidine was higher than the plasma concentration. The intestinal clearance (CLi) of the drug was measured by dividing the rate of appearance of the drug in the intestinal luminal perfusate by the plasma concentration. The CLi of quinidine was therefore much higher than the rate of luminal perfusion. Over the infusion dose range of 0.1-2 mg h-1, the CLi of quinidine decreased with increasing plasma concentration of quinidine. Adding quinidine into the luminal perfusate had little effect on the CLi of quinidine. Co-administration of quinidine with other agents intravenously did not alter the CLi of salicylic acid and urea, while the same treatment decreased the CLi of theophylline and S-disopyramide. In-vitro experiments on brush-border membrane vesicles showed that quinidine decreased the rate of Na+ uptake and H+ efflux. The inhibition was significant at quinidine concentrations above 20 microM. Quinidine was a more potent inhibitor than amiloride. At quinidine infusion rates less than 2 mg h-1, quinidine concentration in plasma or in the luminal perfusate was at the lower limit of the inhibitory concentration. Microclimate pH at the intestinal surface was also measured. At mid-jejunum, the microclimate pH increased 0.3 pH units by infusing 2 mg h-1 of quinidine, while the microclimate pH at most other measuring sites was not significantly altered by quinidine infusion. It was concluded that quinidine is exsorbed from blood into the intestinal lumen by a carrier-mediated pathway in addition to the passive diffusion. At high plasma concentration, quinidine exsorption becomes saturated.(ABSTRACT TRUNCATED AT 250 WORDS)
2024-05-14T01:27:15.642919
https://example.com/article/1466
[Explosion of the subjective world]. This text was inspired by an article in psycho-oncology: "The influence of psychotherapy on the extension of life in people with advanced cancer". I intend to show that cancer causes disintegration ("explosion") of a person's subjective world. (philosophical discourse): Categories of the personal world and the subjective world are introduced and the reality of the subjective world is accepted. The following connotations are essential to further discussion: The mind acts on the body. The psychic state (therefore the state of the brain) is reflected in states and processes localized outside the brain. The epistemologist desires to discover the causal mechanism that explains these effects. The body may act on the mind. Overwhelming evidence has accumulated that disorders of the mind may be caused by disturbances of processes in the nervous system. I reject the view that "the brain is the cause of the mind". Every person lives in his or her own, private, subjective world. It is a relatively stable world of personal memories, observations and imaginations. This world extends in subjective time and space. Its content is composed of conscious psychic experiences, one after another. Experiences create the stream of consciousness. Serious illness leads to the explosion or disintegration of subjective world, destruction of one's sense of personal identity, impossibility of autoreflection, and loss of sense of living. In such cases, individualized psychotherapeutic intervention proves to be irreplaceable.
2023-12-10T01:27:15.642919
https://example.com/article/3702
’50 Shades of Grey’ Movie to Be Produced by ‘Social Network’ Duo 50 Shades of Grey originated as an erotic Twilight fan-fiction series titled “Master of the Universe” (not kidding). E.L. James published her work online for a period of time, but eventually decided to rework her kinky Bella/Edward stories into an original piece – about the very adult relationship between college student Anastasia Steele and 27-year-old billionaire, Christian Grey. The rest, as they say, is history. 50 Shades of Grey is a best-selling monster, and has spawned two sequels (“50 Shades Darker” and “50 Shades Freed”). James’ three books have sold some 31 million copies in e-book and print form worldwide, breaking the Harry Potter series’ record for fasted-selling paperbacks of all time (again, not kidding). Universal Pictures and Focus Features secured the film rights to 50 Shades of Grey earlier this year, and now Oscar-nominated producers Dana Brunetti and Mike De Luca (The Social Network) have put in a bid to back the project. Here are the official statements from studio heads, professing confidence in the duo’s ability to adapt James’ novel (which is full of explicit sex scenes involving bondage, sadism, and masochism, among other things): “At its core, ‘Fifty Shades of Grey’ is a complex love story, requiring a delicate and sophisticated hand to bring it to the big screen,” said Universal Pictures Co-Chairman Donna Langley. “Mike and Dana’s credits more than exemplify what we need in creative partners and we’re glad to have them as part of our team.” “Michael De Luca is a dream producer, whose combination of vision, taste and fearlessness is the perfect match for ‘Fifty Shades of Grey’,” said Focus Features’ Chief Executive Officer James Schamus. Early rumors about the potential writers and directors for the 50 Shades of Grey movie are (in many ways) as mind-boggling as the origins of James’ original work. American Psycho author Bret Easton Ellis has lobbied for the opportunity to pen the screenplay, while Angelina Jolie’s been reported as a potential contender to sit in the director’s chair (take all that with a grain of salt, of course). Brunetti and De Luca are going to have their hands full, convincing the masses that 50 Shades of Grey can turn out as anything but a glorified treatment of late-night adult entertainment you might find on Cinemax (ie. a “Skinemax” TV movie). The project is starting to move ahead full-steam now, and it will be… well, interesting to see how moviegoers respond – especially as more and more people learn about the history of the property (and its connection to the love-it-or-hate-it Twilight franchise). Expect to hear more about 50 Shades of Grey in the future (whether you like it or not).
2024-03-15T01:27:15.642919
https://example.com/article/4251
HONO and its potential source particulate nitrite at an urban site in North China during the cold season. Characteristics and transformation of nitrous acid (HONO) and particulate nitrite were investigated with high time-resolution field measurements at an urban site in Ji'nan, China from Nov. 2013 to Jan. 2014. During the sampling period, averages of 0.35ppbv HONO and 2.08μgm(-3) fine particulate nitrite were observed. HONO and particulate nitrite exhibited similar diurnal variation patterns but differed in the time at which concentration peaks and valleys occurred. Elevated nocturnal HONO concentration peaks were mainly associated with primary emissions from vehicle exhaust and secondary formation via heterogeneous reactions of NO2. In fresh air masses dominated by vehicle emissions, the average HONO/NOx ratio was 0.58%. The nocturnal heterogeneous reactions of NO2 contributed to about half of the elevated HONO concentration peaks, with the conversion rates in the range of 0.05% to 0.96%h(-1). Meanwhile, a large amount of particulate nitrite, which greatly exceeded the concentration of the gas-phase HONO, was also produced through the heterogeneous reactions of NO2. The large yields of particulate nitrite were facilitated by abundant ammonia and particulate cations in urban Ji'nan. Notably, in the daytime, particulate nitrite acted as a potential source of HONO, especially in conditions of low humidity and acidic aerosols, which possibly has subsequent effects on photochemistry in the boundary layer.
2024-05-05T01:27:15.642919
https://example.com/article/8778
1. Field of the Invention This invention relates to new pesticidal compositions comprising phoxim and certain pyrethroids and to a method of using such compositions to combat pests. 2. Description of the Prior Art Certain oxime phosphorothioates pesticides are disclosed in U.S. Pat. Nos. 3,591,662 and 3,689,648 which correspond to Belgian Pat. No. 678,139. On the other hand, there are litterally hundreds of articles and patents directed to synthetic pyrethroids, and in particular to their use as insecticides. Examples of compounds of diverse chemical structures which have been found to demonstrate pyrethroid-like activity are shown in U.S. Pat. Nos. 3,835,176, 3,996,244, 4,024,163, 4,161,537, and Belgian Pat. Nos. 862,133 and 865,114. For certain uses, an increase in the pesticidal spectrum of either the oxime phosphorothioates or the pyrethroid compounds would be desirable.
2024-06-27T01:27:15.642919
https://example.com/article/6000
[Understanding Opioid-induced Adverse Effects and its Managements]. Opioids are potent analgesics and improve both noci- ceptive and neuropathic pain. However, some patients suffer opioid-induced adverse effects, including not only somnolence, nausea and vomiting, and constipation (bowel dysfunction) but also osteoporosis, immunode- ficiency, paradoxical hyperalgesia and addiction. These adverse effects could derive from stimulating opioid receptors either in the central nervous system or at the periphery. Here, we explain the mechanisms of opioid-induced adverse effects and respective manage- ments of them. To control opioid-induced constipation, the peripheral-acting mu-opioid receptor antagonists (PAMORAs) have been widely used in USA. We dis- cuss features of and expectations for PAMORAs in Japan. Further, to avoid developing opioid addiction, we introduce the concept of 'Health literacy' and the measuring tool 'Newest Vital Sign Japanese version'. Controlling pain by opioids adequately and preventing and managing opioid-induced adverse effects ade- quately can result in improvement of QOL of patients with chronic pain.
2024-07-31T01:27:15.642919
https://example.com/article/2695
Ways to Give Cash Gifts of cash are the easiest and most direct way to give to Texas A&M University-Corpus Christi and are tax-deductible to the extent permitted by law. Gifts of cash can be made online, by check, or by phone.
2024-05-31T01:27:15.642919
https://example.com/article/9110
sociology essay The Taboo Subject Of Death Sociology Essay Published: 23, March 2015 This essay has been submitted by a student. This is not an example of the work written by our professional essay writers. The Oxford English Dictionary defines Taboo as being a social or religious custom placing a ban or restriction on a particular thing or topic. The Adjective added to that definition was banned or restricted by social custom ( Oxford University Press - 2001, 2002, 2005, 2006). For many people, death is a taboo subject in spite of the fact that it is of universal concern, but is this statement necessarily true across cultures and countries? This essay will explore both the topical statement and the question. We will look at death from a brief historical context and how, if at all, the passage of time has altered the perception and the acceptance of death. We will take a look at two research studies undertaken in the United Kingdom and in the United States and then look at New Zealand's diverse multi - cultural society. Does a different cultural perspective of death change when absorbed into a western culture? We will also show that whilst death is still a taboo subject in some cultures, it is more the inability of people to be comfortable in dealing with the terminally ill and our awkwardness in accepting that death is the inevitable end to our physical life as we know it. Coupled with this, is the fear of the great unknown and these three factors combine to contribute to our unwillingness to talk about of death, rather than death being a taboo subject per say. The fact is, is that we just don't know how. Space is often described as the 'final frontier'. But could death be defined within the same context? Often, the subject of death is easier to discuss in general terms rather than on a personal level. Some of the factors that may give reason to this are as follows: Death in the media may often be portrayed as being violent, traumatic or speedy. This image usually involves some disaster or trauma in order to become 'newsworthy'. In contrast, most 'real-life' deaths are usually 'un-newsworthy', but this may lead to the developing of a stereotyped view of death that relates to the media image, rather than reality. Today death is not usually encountered on a personal level as frequently as history portrays, or in some other cultures outside of our western world. Science has reduced the incidence of infant mortality and there is a greater perception that technology will also prolong our life as well. There is a reduction in the spiritual belief of an afterlife. Death may now be seen as a final event and hence, becomes a more difficult subject to discuss. Families now tend to be separated and there are not the same support systems as in the past. Different bereavements and factors can affect a person's acceptance. Denial protects the individual from the initial impact of the loss. Not just the individual, but whole groups and societies deny. From a historical perspective, one can begin to see how patterns of During the period of the great Roman Empire, death was common place and more often than not, a public spectacle. The question was not of when they would die; it was more one of how. Would it be through natural causes, or, if their crime was worthy of such a death, crucifixion or rotting in some Roman dungeon. Maybe they would be promoted to the position of Gladiator. At least then they would only have to face war chariots, lions, or the choice of a blood thirsty crowd if they survived at all. And the Roman Legion was not much better. In Medieval times, death was perceived as a much greater presence than in today's societies. Not surprisingly, life expectancy was about half of that today. People had to be prepared to face death. And death was more likely to be violent, cruel and extremely painful. *Lendrum, S. & Syme, G. Gift of Tears, (second edition, 2004). Death was unpredictable and uncontrollable. People had to live with a greater awareness of death around them and of their own mortality. There was always the constant reminder of death in the midst of life. One could not deny the existence of death and were forced to be more prepared to meet their deaths than today. In the last century death crossed over two distinct boundaries. With the occurrence of World Wars 1 & 2, Vietnam, Korea, China, Afghanistan and China, you had the violent deaths of both combatants and civilians alike. Civilians had to try and carry on with their lives as best they could and at the same time, knowing that this day could be their last. And for those left at 'home', it wasn't overly better. Not that they were openly threatened with death, but had, to a certain extent, live with a 'living' death.... trying to live a reasonably normal life, yet constantly living in the fear of whether or not their loved one would return. Admittedly, death within the context of the above is portrayed in somewhat violent and uncertain terms but throughout, there are three poignant observations that arise: 1/ There are those that live with death face to face on a daily basis. 2/ There are those that live in a somewhat removed position from the turmoil of what is happening. Not isolated but knowing that at some stage they will have to face reality. 3/ Death is something that we will all face head on. The question is, do we acknowledge our mortality and learn to be open about it, or do we hide from the reality and repress our innermost fears? In their book "Awareness of dying", Glaser and Strauss (2005), researched the average Americans' attitude to death and dying. One key point that they found was the strangely paradoxical attitude that revealed itself. Whilst Americans' were seemingly able to accept that death was an everyday affair in that on a daily basis, newspapers confronted the brutal fact of death directly - (from front page headlines to back page funeral notices, someone was always dying somewhere), they generally seemed to prefer to talk about a particular death rather than about death in the abstract. Characteristically, Americans are unwilling to talk openly about the process of dying itself and also prone to not telling a dying person that they are dying. This, in part, is a moral attitude - life is preferable to whatever may follow it. One should not look forward to death. Feifel, H. Death, (as cited in Farberow, N.L., 1963). Social and Psychological problems involved in terminality are perhaps most acute when the dying person knows that they are dying. For this reason, Physicians in America are quite reluctant to disclose impending death to their patients. Fieifel, H. Death, (1961, p 17). The problem of "awareness" is crucial as to what happens both to the dying patient and to the people who give medical and nursing care, as well as those supporting the patient. Whilst one view of awareness is a technical one: should the patient be told they are dying and what is to be done if they don't know or only suspect, there is also a moral one involving professional ethics, social issues, and personal values. Should a dying person be denied the opportunity to make peace with their conscience and with their God, and to settle their affairs and provide for the future of their family? Do they have the right to control their style of dying, much as they controlled their style of living? Does anyone have the right to withhold such information? Fulton, R. Death and Self, (July 1964) In their article titled "Dying Conversation" - Death remains a taboo subject among Brits' (25th Sept. 2002), Norwich Union wrote the following: "Death is a taboo subject when it comes to conversation. The topic is the most avoided conversation item for around 1 in 5 people nationwide. Women feel more at ease discussing the subject than men". Research also revealed that: ....Death is seen as less of a taboo by the youngest (16 - 24) and oldest (65+), than all other age groups, while religion was the biggest conversational taboo among the 30 - something group. ....Both death and sex are considered equally taboo subjects by woman. ....Death is seen as the biggest taboo by 24% of Londoners - far more than anywhere else in Britain. ....People in the Northwest are the most likely to openly discuss death - only 12% of people asked described death as the biggest taboo. Forty eight percent of people questioned also said that they were treated differently by others after their friend or loved one died and nearly 54% said advice on how to support someone who has suffered bereavement would be useful. "Research showed that 2 out of every 3 people in the UK have lost either a close family member or a friend in the last 3 years - yet as a nation, we still find it extremely difficult to discuss death and to cope with bereavement". Does culture have any direct influence on how people handle death? In many cultures, there are 'taboos' surrounding death - do not touch a dead body least you inherit the disease; do not cremate the body as then the spirit will not rest and will return to persecute (the family). But are these taboos about openly discussing death or merely cultural beliefs as to how to treat the deceased. And what happens to such culture when 'absorbed' into another, larger culture? Such is the case within New Zealand where the country boosts one of the highest cross cultural populations in the western world. For example and from a Maori perspective, serious illness, dying, death and grieving are among the most sacred and important in Maori life. Sanctity (tapu), Ceremony (kawa) and Language (reo), are intertwined in all of Maori life and traditions, and held in the highest regard. Unity, harmony and balance are central to their culture and are maintained through the systems of customary practices and the law of Tapu. For the Maori, serious illness or the process for a terminally ill person is very much a 'living', family (Whanau) affair. Relatives and friends gather daily beside the patient, either at home or at the hospital, each providing spiritual, moral, emotional and physical support for the patient and for the family. The interests of the patient and family are of paramount concern. Karakia (prayers and incantations) are an integral part and often both traditional Maori and modern Christian believes are combined and whilst traditional healing practices are still practiced, acknowledgement is given for the place and role of scientific medicine. Without great expansion on Maori culture and even given the current cultural climate, Maori traditions and practices continue to be an integral part of Maori life and will undoubtedly continue to be so. It is, perhaps, one of the truly sacred and time honoured cultures that have withstood the test of time in what is basically, a strong western culture. Maori do not appear to have any taboos when it comes to the overall aspect of sickness and Death. In fact, they seem to embrace and encompass it within their Tapu and Kawa. Other cultural groups within New Zealand have very similar views and practices in their attitude towards death and dying. In the case of either serious illness and/or in dealing with the terminally ill, it is very much a strong family time with both practical and spiritual/moral support being on constant avail. Of one major exception is that of the Niueans. For them, death is regarded as taboo. Discussion of death amongst themselves or with the dying is forbidden unless the dying raises their impending death. However though, within the same context, the family and friends of the dying/seriously ill person will maintain a constant bedside vidual. People have always grappled with the meaning of death. This was probably mitigated during the Middle Ages by a belief in an afterlife - a belief that death was not the end and that the soul moved to another place. Christianity and other faiths expand on this belief. This discomfort about death has lead to shame and embarrassment and an avoidance of talking or writing about death. Euphemisms are often used, especially when talking to children. Such euphemisms as: Snuffed it; Kicked the bucket; Passed away/on; Pushing up daisies; all serve to distance ourselves from the effects of death. We experience great uncomfortableness in attempting to talk to the terminally ill, even if they are family. Out of shear awkwardness, we may say nothing at all and in doing so deprive both ourselves and the dying person of physical touch, words of comfort, and the recognition and emotional connectedness that we all desire. The very words and the valuable proof of our affection and tenderness go unsaid. Hockey, J. (1990, as cited in Lendrum, S. & Syme, G., 2004). Freud et al, (as cited in Lendrum, S. & Syme, G. 2004), pointed out the connection between the fear of death and the feeling of guilt. Putting into a simple example, Adam and Eve were immortal in Paradise but once they had sinned, became mortal and were condemned to die. That death was punishment for evil committed. The notion that death is a punishment could be used as a way of trying to make sense of death. This same notion could also have contributed to our fear of death and in turn, our guilt. Guilt is a strong emotion that is almost always experienced both by the dying and by those who survive. Not only are the feelings of "if only I had.....," I only wish that I .....," experienced, but even in death, the deceased can be tainted with guilt by those who can find no better way of dealing with their own guilt and fears........Aids is caused by promiscuity.....serves them right! An awareness of this might allow us to understand the value of confession and forgiveness. As a personal comment, I have experienced more than 15 deaths in my 53 years of life. These include both of my birth Parents (I was adopted at birth), My Parents, My first 'real girlfriend' (as a result of a plane crash), and numerous motor vehicle accidents involving death where I just 'happened' to be first on the scene. In particular, I recall the deaths of my Father and Mother. My Father died as a result of lung cancer, at home in 1968. I was 12 years old. Throughout the period of 8 months including major lung surgery, my Mother never once said anything to myself or my brother about Dads' impending death. In fact we didn't really comprehend it until the day that Dad wasn't at home anymore and the house was totally silent. My mother died from cancer in a Hospice at Lower Hutt. I was 34 and in my first marriage. Mum had been living with my then wife and me for 6 months prior and when she finally died, I wasn't even present. I had struggled to talk to her or even my wife of her death and took solace in alcohol big time. In conclusion, throughout the research of this topic I have found that there are certainly some situations and circumstances in which the subject of death is taboo. However, I am personally of the belief that it is not that the subject is taboo per say; it is more the case of that we just don't know how to speak of, let alone handle death. Society is slowly changing in both the dialogue of, and the acceptance of death on deaths' terms, but in saying that, I firmly believe that we, as New Zealand Europeans, can learn a lot from the vast array of other cultures within our country. The question is.....Do we want to?? Our experts can help you with your essay question Writing Services Essay Writing Service Find out how the very best essay writing service can help you accomplish more and achieve higher marks today. Assignment Writing Service From complicated assignments to tricky tasks, our experts can tackle virtually any question thrown at them. Dissertation Writing Service A dissertation (also known as a thesis or research project) is probably the most important piece of work for any student! 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2024-04-18T01:27:15.642919
https://example.com/article/4941
Share This On Social Iraq has quickly become a global oil leader, winning a seat in the Organization of Petroleum Exporting Countries (OPEC) and this year overtaking Canada as the fourth-biggest oil exporter in the world. But the country, which was seriously damaged by the war, has nothing to celebrate this fact. While oil markets are discussing Saudi Arabia’s ability to increase its production to offset the impact of US sanctions on Iran and the limitation of oil production in the Islamic Republic, Iraq has quietly increased supplies to Asia, Europe and the Mediterranean region. Iraq produces a record 4.78 million barrels per day, according to the oil minister Jabbar al-Luaibi. According to him, the country’s output will grow to 5 million barrels per day in 2019 and to 7.5 million barrels per day in 2024. The consulting company Wood Mackenzie predicts that Iraq can produce up to 6 million barrels per day by 2025 and its output will continue to grow faster than other countries, except the United States. On the background of its oil power, Iraq suffers from underdeveloped electricity distribution networks and electricity supplies. The increase in oil production is good news, but Iraq still fails to provide basic utilities such as clean drinking water and electricity for its citizens. Most economic indicators in Iraq, apart from oil, show little or no growth. The political tensions continue to shake Baghdad – conflicts with local Kurds, problems with minority groups, dissatisfaction with the Shiite majority of unreliable public services. The oil prices have doubled since 2016, as well as oil production in Iraq. But the country’s stock index fell by 30% over the same period, with nearly 32 billion USD in foreign direct investment leaving the country. Over 75% of oil supply growth by 2025 will come from the US, Canada and Iraq. The citizens are disappointed that they do not have 24-hour electricity, the infrastructure and healthcare are in a miserable situation. The international oil companies are responsible for two-thirds of Iraq’s current production, with their capital and technology remaining crucial factors for maintaining this capacity. As the government pays to the companies in question, manufacturers can get a good return on their investments even if the price of oil drops to 30 USD per barrel.
2024-02-01T01:27:15.642919
https://example.com/article/1863
Ivanhoe Australia is 57.7 percent owned by Turquoise Hill Resources, which in turn is majority owned by world no.3 miner Rio Tinto. Ivanhoe Australia last year tried to sell stakes in its projects to shore up its balance sheet but called off the process after Rio Tinto won majority ownership of Turquoise Hill and instead raised $76 million through a share sale. The money raised was used to pay off a loan to Turquoise Hill and will ensure the company's exploration and Osborne copper-gold projects are fully funded.
2024-04-11T01:27:15.642919
https://example.com/article/4108
Tom Black (basketball) Thomas Donald Black (July 9, 1941 - September 9, 2017) is a retired American professional basketball player. He was a 6'10" (208 cm) 220 lb (100 kg) center and played collegiately at the University of Wisconsin–Madison and South Dakota State University. He graduated from high school in West Salem, Wisconsin. Black was selected by the Baltimore Bullets in the 9th round (2nd pick) of the 1964 NBA draft. In his brief NBA career in 1970–71, he played for the Seattle SuperSonics and the Cincinnati Royals. Notes Category:1941 births Category:2017 deaths Category:Baltimore Bullets (1963–73) draft picks Category:Basketball players from Wisconsin Category:Centers (basketball) Category:Cincinnati Royals players Category:Phillips 66ers players Category:Seattle SuperSonics players Category:South Dakota State Jackrabbits men's basketball players Category:Wisconsin Badgers men's basketball players Category:American men's basketball players
2024-06-10T01:27:15.642919
https://example.com/article/7391
The Michigan Shakeapeare Festival in Jackson is this year's top-nominated theater, seen here with its 2014 production of "Cymbeline." Photo: MSF A Season Of Excellence And Off-Stage Drama: The 2014 Wilde Awards Theater professionals from across Michigan will gather together Sept. 22 when The 2014 Wilde Awards are presented at The Berman Center for the Performing Arts in the Detroit suburb of West Bloomfield. Presented by EncoreMichigan.com, the most comprehensive resource for news and information about the state's professional theater industry, The Wilde Awards were established in 2002 to honor the excellent work produced by Michigan's professional theaters. And this past season was "wilder" than most, said Donald V. Calamia, co-founder and editorial director of EncoreMichigan.com. "With the sudden closure of Performance Network in the middle of a run, a surprising announcement from Magenta Giraffe, the planned shuttering of Broadway Onstage, the unexpected passing of long-time theater critic Michael Margolin, executive downsizing at The Jewish Ensemble Theatre Company, the shutdown of the Michigan Equity Theatre Alliance - our most recent owner - and a ferocious winter that saw record-setting snowfalls, this has been the most tumultuous season I can recall in my 40 years of involvement in our state's professional theater community." Yet despite the turmoil and challenges they faced, Calamia continued, "our producers and artists turned out work of the highest caliber all season long, which presented us with quite a challenge: How do you single out a handful of people and shows to honor when the season was filled with so many noteworthy accomplishments? But as I've said many times in the past, when times get tough, thespians get more creative - and once again the proof was seen on stages from Lake Michigan to the Detroit River and everywhere in between. So whether a producer has a million-dollar budget or a buck ten, it doesn't matter. It's how well they spend their budget and tell their story that makes the difference - and that's what we considered most as we debated our nominations for The 2014 Wilde Awards." Now in its 13th year, The Wilde Awards honors the best productions, performances and technical work produced or presented by professional theaters across the state. Nominations are based on reviews written by EncoreMichigan.com's team of professional critics. This year's team of critics included Dana Casadei, Carolyn Hayes Harmer, Martin F. Kohn, Michael H. Margolin, Jenn McKee, Sue Merrell, John Quinn, Bridgette M. Redman and Judith Cookis Rubens. "And for the first time since the inception of The Wilde Awards, I had no horse in the race," Calamia said. "I reviewed a grand total of one-third of a play festival this past season, and that's it. But I certainly had a lot of input based on the number of shows I saw throughout the season." For this year's awards, Calamia noted, the season under review was longer than in the past. "When The Wilde Awards were created, we were part of Pride Source Media Group, publishers of Between The Lines, which is the state's gay and lesbian weekly newspaper. And so we timed the announcement of our nominations to match the annual Gay Pride event in Metro Detroit, which was generally the first weekend of June. So for our purposes, the season ran from mid-May to mid-May - which was a bit confusing for everyone. With META taking ownership of us a few years back, we decided to move to a more-traditional season, but we had to catch up first - so this year's nominations include shows from May 24, 2013, through July 27, 2014. And those additional two months had some pretty unusual ramifications." The most notable, Calamia explained, was the number of summer theaters that competed against themselves across two different seasons. "That won't happen again, as our season from this point forward will be August through July. But to account for this, what we did in some cases was to expand the number of nominations in certain categories. And because of the large increase in the number of shows and individual accomplishments we had to consider, we also added honorable mentions to many of the categories. Even then, however, there were many notable shows that might have received nominations under normal circumstances, but didn't." In total, EncoreMichigan.com's team of critics reviewed 225 productions produced or presented by 49 professional theater companies across the state during the 2013-14 season. Shows had to be performed for four consecutive days or more or over two weekends or more to be eligible for a review. And only shows reviewed by EncoreMichigan.com could be nominated for a Wilde Award. Not every professional theater in the state was eligible to be reviewed, however. "This was the second season - and hopefully the last - in which we operated as a non-profit media company supported in part by annual membership fees charged to participating theaters," Calamia said. "With ad sales, grants and sponsorships negligible and unable to meet our expenses, META adopted a revenue model for us that was similar to other 'Encore-like' projects around the country, one that offers member theaters a package of services and benefits not available to non-members. And one of those exclusive services was the eligibility to be reviewed." Awards this year will be given out in 27 categories, including one that is new this year, Calamia noted. "After the 2013-14 season was well underway, we were asked by a professional company that stages shows for young audiences if we would review a show of theirs. So we did - and then continued to review shows for young audiences as long as they featured professional adult actors in major roles. Although we had missed several shows by this point, we decided it was still important to honor the best of those shows we reviewed, so late in the process we went ahead and established a single 'best production' category for them this year. And this coming season, we'll add a 'best performance' category as well." As in previous years, a number of special awards will also be presented. After sifting through hundreds of potential nominees, 85 productions earned at least one nomination - as did 28 of the producing or presenting theaters. The top nominated theater is the Michigan Shakespeare Festival (Jackson) with 19, followed by Williamston Theatre (Williamston) with 13, Hope Summer Repertory Theatre (Holland) with 12, and Planet Ant Theatre (Hamtramck) and Tibbits Summer Theatre (Coldwater), both with 11. The only other theater with double-digit nominations is Farmers Alley Theatre (Kalamazoo) with 10. "With three of the top six nominated theaters having two complete summer seasons in the running - Michigan Shakespeare Festival, Hope Summer Rep and Tibbits - it's easy to see how our lengthened season impacted the results," Calamia said. "But one thing is clear: Their West Michigan cousins are giving our Southeast Michigan theaters some great competition!" Of the 85 nominated shows, no single production leaped to the forefront. Four shows tied for the top spot with five nominations each: "10:53" (Williamston Theatre); "Cymbeline" and "The Importance of Being Earnest" (Michigan Shakespeare Festival); and "The Producers" (Tibbits Summer Theatre). Three others tied with four each, while 13 productions each earned three. "That means that 65 out of 85 shows are being honored with two or less nominations, which to me means that quality is spread out pretty equally across our state, and that high-quality, entertaining productions can be found in theaters of all sizes and budgets," Calamia said. A similar indicator is the number of artists - actors, directors, designers and playwrights - whose work is honored this year. "Of the 140 people we've nominated, only 16 have two nominations, and just three individuals - Janice L. Blixt, John Manfredi and Michelle Raymond - earned three. This shows we have a ton of very talented people working - and mostly living - in this state, and we're pleased to acknowledge at least some of them and their craft with these nominations," Calamia said. And that, Calamia said, is what he hopes people come to recognize about professional theater in Michigan. "One of the world's best-kept secrets is not only how much professional theater exists in the state, but how much of it is so well done. Our producers, directors, artists and staff people work very hard to offer our communities the highest quality shows they can, and we're honored to shine the spotlight on them for their endeavors. Congratulations to all our nominees and non-nominees alike. They staged one heck of a season, and everyone should be very proud of their accomplishments - especially during a season that saw so much upheaval and off-stage drama! And I encourage them to aim even higher this upcoming season!" But will EncoreMichigan.com be there to cover it? And what is the future of The Wilde Awards? "With no owner and no budget right now, it seems like we're adrift without a paddle," Calamia said. "But there are plans afoot - and people have reached out with some ideas that may make us stronger and better able to serve our readers and our theaters. So be on the lookout: Encore 2.0 might be right around the corner!" The 2014 Wilde Awards The 2014 Wilde Awards, sponsored by Pride Source Media Group, will be held Monday, Sept. 22 at The Berman Center for the Performing Arts in West Bloomfield. Doors will open at 6:30 p.m. with an hors d'oeuvre and cocktail reception. The awards show, co-hosted by Calamia and noted actress Naz Edwards, will begin promptly at 8 p.m.; a dessert afterglow will follow. Admission is $21 per person; VIP admission is $46 per person, which includes unlimited bar service. Drink tickets for all others will be available for purchase on the day of the event. Tickets are available now at The Berman's box office, by phone at 248-661-1900, or online at http://theberman.org. The Berman Center for the Performing Arts is located at 6600 W. Maple Road, on the campus of the Jewish Community Center at the northwest corner of Maple and Drake Roads in West Bloomfield. Parking is free. "Our 13th annual celebration of professional theater in Michigan will be a great way to salute the previous season and kick off the next," said Calamia. "And as always, it will truly be 'one Wilde night' to remember!" SOUTHFIELD - This year the BTL Ultimate LGBT Wedding and Anniversary Expo was held on the anniversary weekend of Judge Friedman's decision in DeBoer v. Snyder. That decision struck down Michigan's same-sex marriage ban, for less than 24 hours, allowing 323 couples to become legally married in the state.
2023-12-08T01:27:15.642919
https://example.com/article/4056
Bug Description If the Kobo driver is not configured to maintain shelves on the Kobo device, the collection column for books that are on the device and in the library is empty. It should show the reading states and any shelves created on the device. The issue was that the device_collection was being emptied and built even when there was no shelf column specified. Will now skip this step if there are no shelf columns. Also moved a database commit. There was a circumstance where this would not happen.
2023-11-20T01:27:15.642919
https://example.com/article/3557
When the amazing 4.5-billion-year history of life on Earth is compressed into two minutes and 20 seconds, it quickly becomes apparent that humans are the new kids on the block. The new "Evolution of Life on Earth" video starts with the planet's first single-celled organisms and goes all the way to the evolution of modern-day humans. The whole story is told as if all those years were compressed into a single 24-hour day. And guess what: humans don't show up until 11:58 p.m. No, that was not a typo: 11:58 p.m. "All of the recorded human history fits within a few seconds," narrator Mitchell Moffit says in the video, which was made by AsapSCIENCE, the online video team that brought us "The Science of Orgasms." "We thought it would be most effective/interesting to have a grand vision that follows the path towards humanity," Moffit, a co-creator of AsapSCIENCE, told The Huffington Post in an email. "Makes you feel somewhat insignificant, but also showcases the beauty and awesomeness of life." Moffit wrote that this new video was inspired by an excerpt from the book "A Short History of Nearly Everything" by writer Bill Bryson. From there, Moffit and co-creator Gregory Brown took the idea to YouTube. Watch "The Evolution of Life on Earth" above.
2024-03-18T01:27:15.642919
https://example.com/article/2810
Universal power law behaviors in genomic sequences and evolutionary models. We study the length distribution of a particular class of DNA sequences known as the 5' untranslated regions exons. These exons belong to the messenger RNA of protein coding genes, but they are not coding (they are located upstream of the coding portion of the mRNA) and are thus less constrained from an evolutionary point of view. We show that in both mice and humans these exons show a very clean power law decay in their length distribution and suggest a simple evolutionary model, which may explain this finding. We conjecture that this power law behavior could indeed be a general feature of higher eukaryotes.
2024-02-26T01:27:15.642919
https://example.com/article/1671
1. Introduction {#sec1} =============== Hydatid disease is endemic in many areas, especially in the Middle East, Turkey, South America, South Europe, New Zealand, and Australia \[[@B1]--[@B3]\]. The patients are usually asymptomatic or their symptoms are nonspecific since growth of the cysts is generally slow and therefore clinical manifestations tend to be nonspecific complaints due to compression of involved organs \[[@B2], [@B4]\]. The diagnosis depends on clinical suspicion, typically based on a history of living in, or having travelled to, an endemic area and contact with cattle or dogs and is confirmed with serologic tests and imaging \[[@B3]\]. The most common locations for hydatid cysts are the liver, followed by the lung \[[@B1], [@B2]\]. However, many parts of the body can be affected, including bones, pericardium, orbits, and brain \[[@B1], [@B5]\]. Cerebral localization is extremely rare, being seen in 2-3% of systemic disease and forming 2% of all intracranial space occupying lesions \[[@B2], [@B3], [@B5]\]. This rarity, coupled with nonspecific symptoms, necessitates a high degree of clinical suspicion and thus presents a diagnostic difficulty. We present a case of infratentorial cerebral hydatid disease with an exceedingly rare location, followed by a review of the literature regarding typical characteristics and imaging findings of cerebral echinococcosis. 2. Case {#sec2} ======= A 45-year-old woman applied to a different center with complaints of nausea, vomiting, and headache that has been going on for three months. Following tests and examination, she was referred to our center with the initial diagnosis of a mass. Her physical examination revealed monoparesis in the left lower extremity and hypoesthesia on the left but was otherwise normal. Magnetic resonance imaging (MRI) in our center revealed an extra-axially located cystic lesion with a thin wall in the premedullary location compressing brain stem. The patient was operated and the lesion was revealed to be hydatid cyst ([Figure 1](#fig1){ref-type="fig"}). 3. Discussion {#sec3} ============= Hydatid disease, also called echinococcosis, is a parasitic disease caused by larvas of*Echinococcus* tapeworms \[[@B1]\].*E. granulosus* and*E. multilocularis* are responsible for the majority of human disease, the former being more common. Even though places where the disease is endemic, namely, the Middle East, Turkey, Central and Southern Europe, Australia, South America, and New Zealand, are widely known, it should be kept in mind as a differential diagnosis even in nonendemic areas due to the ease of travel and migration from endemic to nonendemic places \[[@B1]--[@B3], [@B6]\]. Liver is the most commonly affected organ (50--77%), followed by the lung (8.5--43%) \[[@B1], [@B2]\]. Even though rare compared to the involvement of these two organs, many other tissues such as muscle, heart, kidney, bone, eye, skin, and spinal cord can also be affected \[[@B1], [@B5]\]. Cerebral involvement is seen in 2-3% of cases with systemic disease and is a rare cause of intracerebral space occupying lesions even in endemic areas. It is observed more often in children and young adults and several case series reported a slight male prevalence \[[@B7a]--[@B9]\]. Patients may have hydatid cysts in other organs, with studies reporting extracerebral disease in 6--70% of patients \[[@B2], [@B4], [@B9]\]. They can be seen in any part of the brain but are usually supratentorial and located in the middle cerebral artery territory, most commonly the parietal lobe \[[@B2], [@B3], [@B10]\]. Sometimes large, single cysts can be observed in the frontoparietotemporal region \[[@B10], [@B11]\]. Infratentorial localization is exceedingly rare, and intraventricular, pontine, meningeal, cerebellar, intrasellar, cavernous sinus, aqueduct of Sylvius, and skull cysts, despite being even rarer, have been reported \[[@B3]\]. In the brain,*E. granulosus* caused cerebral cystic echinococcosis, where lesions are usually single and occurrence of multiple cysts is very rare. Cerebral alveolar echinococcosis, caused by*E. multilocularis*, may have single or multiple cysts but is much rarer compared to cystic disease \[[@B3]\]. The signs and symptoms are nonspecific and the most common ones are reported to be headache, papilledema, and vomiting; however, any symptom due to increased intracranial pressure can be seen \[[@B2], [@B3], [@B7b], [@B9]--[@B12]\]. Focal symptoms like hemiparesis, seizures, gait, or sight disorders can be observed depending on the size and location of the lesion \[[@B9], [@B10]\]. In cerebral cystic echinococcosis both computerized tomography (CT) and MRI reveal a spherical cystic lesion with well-defined borders, a smooth thin wall with or without septae or calcification. The cyst wall is iso- or hyperdense with respect to the cerebral parenchyma on unenhanced CT and usually shows a rim of low intensity in both T1W and T2W images. Daughter cysts, if present, are considered pathognomonic but are rarely seen \[[@B2], [@B7a]\]. Wall calcification is seen in less than 1% of cases \[[@B3], [@B7a]\]. Mass effect, with compression of midline structures and the ventricles, is a common finding, but surrounding edema and rim enhancement are generally not seen in uncomplicated cases \[[@B2], [@B3], [@B13]\]. The imaging findings of alveolar echinococcosis include a solid, semisolid, or multiloculated cystic mass with well-defined margins. In contrast to cystic disease, calcification, edema in the surrounding tissues, and contrast enhancement in the inflammation region around the lesion are common \[[@B3]\]. The differential diagnosis of an intracerebral hydatid cyst with mainly typical characteristics includes supratentorial cystic lesions like arachnoid cysts, cystic tumors, abscess, and porencephalic cysts \[[@B2], [@B3], [@B5]\]. Arachnoid cysts are not spherical, porencephalic cysts are usually connected to the ventricular system and neither are entirely surrounded by brain tissue, cystic tumors usually have soft tissue components that are enhanced after contrast injection, and abscesses typically demonstrate enhancement and perifocal edema \[[@B2], [@B3], [@B5]\]. When the location is atypical, such as an infratentorial location as in our case, cystic lesions of the involved region, for example, neurenteric cysts for posterior fossa lesions, are first considered in the differential diagnosis. However, hydatid disease should be kept in mind in the setting of appropriate medical history. MR spectroscopy has potential, albeit experimental, application in diagnosing cerebral hydatid disease. In a series, three cases of hydatid cysts have been reported to show lactate, acetate, and succinate peaks, and one case with surrounding edema revealed a choline and mannitol peak. Arachnoid cysts, on the other hand, showed only small lactate peaks and tumoral lesions demonstrated increases in choline and lactate with decreased NAA \[[@B14]\]. In conclusion, imaging is useful, but not always conclusive, in diagnosing cerebral hydatid disease. CT detects calcification in the lesion better than MRI, whereas MRI is superior in defining the exact location and anatomic relationships of the lesion \[[@B2], [@B3], [@B10]\]. Nevertheless, in some cases, despite use of advanced imaging techniques, the diagnosis remains problematic \[[@B10]\]. Hydatid disease should be considered especially with supratentorial cystic lesions in young male patients with a history of living in an endemic area or having contact with cattle or dogs; however, as in our case, atypical cases of infratentorial localization in an older woman are possible and, thus, the differential diagnosis for any cystic lesion of the brain in a patient with appropriate medical history should include echinococcosis. Conflict of Interests ===================== The authors declare that there is no conflict of interests regarding the publication of this paper. ![(a) T1W sagittal, (b) FLAIR transverse, and (c) postcontrast T1W transverse images. An unhanced cystic mass is seen in the premedullary space. The slightly left parasagittally located mass is compressing the brainstem left anteriorly.](CRIM2014-271365.001){#fig1} [^1]: Academic Editor: Mark E. Shaffrey
2024-01-20T01:27:15.642919
https://example.com/article/2933
Pages Monday, June 02, 2008 Brussels, May 29 - Disappointed by the Commission's inaction and focus on voluntary actions in the field of Corporate Social Responsibility (CSR), European NGOs and national coalitions working on corporate accountability decided in 2005 to launch the European Coalition for Corporate Justice (ECCJ). Noreena Hertz, author of 'The Silent Takeover' and 'The Debt Threat', gave a very optimistic introduction to the day. She stressed the increased forces pressuring for change: more consumers buy fair trade, more investors value environmental standards. "History has shown us that most of the calls have been heard", Hertz explained, referring to the abolition of slavery or the mainstreaming of the green movement. "There are precedents, and the timing is good." she continued, referring to the window of opportunity opening with the appointment of a new Commission next year. "Together we can create a new global order! Together, we can change the course of history!" The first and most ambitious proposal, Extending Parent Company Liability, suggests that parent companies should be held liable for for any environmental and human rights violations caused by their subsidiaries and contractors. As lawyer David Chivers explained, the extension of the EU law to non-EU companies that have a direct or indirect presence in the EU is necessary to avoid unfair competition. Lee Swepston, former ILO Senior Advisor on Human Rights, added that higher costs are not an argument. "In former times, business also argued that limiting child labour to 12 hours per day will ruin business. And it didn't!" Raül Romeva i Rueda, MEP for the European Greens, closed arguing that we "should not care about how realistic the proposal is, but how real it is." We should fight for the proposal which should be real one day, and not for the one which is most realistic. Olivier de Schutter, recently appointed UN Special Rapporteur on the Right to Food, presented the second ECCJ proposal, the Duty of Care. According to the proposal, companies should take reasonable steps to identify and prevent human rights or environmental abuses within their sphere of responsibility. If the parent company does not take all reasonable steps, it can be held legally liable. De Schutter did not conceal the problems of the proposal, for example that the Duty of Care could be interpreted as the imposition of Northern standards on Southern countries. Moreover, the question of remedies remains. The aim is to push Northern companies to support their partners with technical and financial support, building up local capacities to comply with the social and environmental standards, instead of cutting relations. Kate MacDonald from the London School of Economics strongly underlined de Schutter's last point, which she called "external misalignment between power and responsibility." The third area of legal reform, Mandatory Social and Environmental Reporting, seemed to be the most feasible proposal, because it is already practiced in eight EU Member States, including France. CEO's could be held legally liable if reporting standards are not observed. According to Filip Gregor, ECCJ lawyer, the resulting increased transparency would spur voluntary improvements. However, the risk of greenwashing, and weak comparability between reports persist. Crucial support came from Matt Christensen, Executive Director of the European Social Investment Forum. He was "very positive regarding the proposal," if it is not too much work for the directors, and if investors can find the information in one document. Inspired by Christensen, Diana Wallis, liberal MEP, already thought there are some concrete steps to realize mandatory social and environmental reporting to be seen within the window of opportunity opened by climate change, such as the UK carbon reporting. According to its website: the ECCJ "believes that these [three] proposals would lead to a coherent and harmonised approach to business regulation, putting an end to the unfair competition caused by companies who profit from human rights and environmental abuses," says Ruth Casals, coordinator of the network. "These proposals will provide long needed justice for victims of environmental or human rights abuses by companies based in Europe." No comments: ShareThis Euforic Services supports development organisations to communicate, collaborate, share knowledge and manage information using digital and social media tools. We are continuing and developing the work of the Euforic Cooperative, learning from its 14 years of original, high quality programming and bringing together many of the original staff and associates. More on our work
2023-10-11T01:27:15.642919
https://example.com/article/4449
Product Details A contemporary, solid mango dining set comprised of four elegant seats with a bench on one side. Made entirely from solid mango wood with a dark walnut stain. The chairs have built-in leather seat pads for comfort and easy cleaning The table and bench both require simple home assembly. Delivery FREE 2-Man Furniture Delivery A pre-booked, Monday-Friday, 2-Man delivery service to the room of your choice, usually within 15 working days. FREE for most England and Wales postcodes (a delivery charge applies to Scotland and other selected postcodes
2024-01-30T01:27:15.642919
https://example.com/article/4431
framework: csrf_protection: ~
2024-06-15T01:27:15.642919
https://example.com/article/7181
The Coronavirus is upending life as we know it. Fast and effective communication across teams matters now more than ever. At Speakap, our goal remains unchanged: to help you reach your employees wherever they are. More than 450 companies trust us to communicate in live-time with their entire workforce. To meet the needs of these unprecedented circumstances, we’re enhancing our services. You can now get your communication platform up and running within 24 hours; quickly and hassle-free. The qualitative research took place between 2008 and 2013. For each time period of the study, around thirty millennials were recruited with about half of them majoring in tourism (heritage management and tourism management) and another half majoring in hospitality (event management and hotel management). The following eight career choice categories reflect their expectations. These refer to monetary and non-monetary benefits employees seek as compensation for their work. High salary, overtime pay, bonus, complimentary pay, paid sick leave, family subsidies, and good quality of staff canteen were often suggested by the informants. In fact, some millennials mentioned that “a competitive salary, at least no less than competitive firms” would be a must. Another informant added, “I can make a good living with a high salary. It is especially important as the inflation is high.” Retaining millennials solution 2: Stability and security Stability and security reflects the desire for employment opportunities that offer them stable income and working hours. Millennials prefer not to worry about being laid off even during financial difficulties of the economy or employer. A millennial informant expressed that “the employer should guarantee no layoff like the government does”. Another male informant added that he preferred a job that is “stable without having to be on shift”. A female informant further suggested that “for ladies, working overnight would be a torture”. Retaining millennials solution 3: Flexibility and autonomy These expectations refer to informants' desire to work for organizations that offer them job independence, freedom, and the ability to work in a flexible schedule. Some informants expressed grievances that they were being monitored by their superiors and surveillance cameras: “I don't want someone watching me behind my shoulders.” They feel tremendous pressure from work under such a condition. Instead, they prefer to work for companies that offer them job autonomy, which allows them to enjoy more freedom do to things they like instead of working like a robot: “I don't like to follow the procedure all the time because sometimes it may not make sense to me. However, if the company allows me to express my creativity, I will be more willing to work hard.” Most of these concerns relate to operational positions that deal with customers directly and routinely. Some informants suggested that employers should empower them and allow them to work independently. As an informant said: “The organizations should give freedom to employees, and provide enough resources for them to finish their work.” A flexible working environment and schedule also help to reduce job pressure and prompt job autonomy and creativity. Retaining millennials solution 4: Work environment Work environment embodies a wide range of organizational properties including the tangible working atmosphere such as the location, surrounding office environment, and more. As one informant pointed out, “the environment should be modern with nice decoration and facilities.” Others look for staff rest area and WiFi services. A comfortable work environment also has an effect on employees' emotions, as one informant described: “It directly influences my mood and enhances my spirit.” Some informants emphasized the importance of organizational leadership style and management culture in that companies should strive to have clear rules and policies that employees can follow. Retaining millennials solution 5: Achievement Achievement corresponds to tasks that could bring challenges to employees and at the same time empower them to complete tasks. Employees also want their ability and job performance to be recognized by management, and as a result, to receive promotion offers. As one informant noted, “I want to be promoted to be a manager within five years. With the knowledge that I learn from college, my previous working experience, and my ability, I am confident that can achieve this goal.” Some informants also wanted to work for firms not only for internal promotion opportunities; they also wanted to help the company to succeed. For example, one informant said, “I want to work for organizations that could expand and be the top company in the industry.” Retaining millennials solution 6: Self-development Self-development refers to opportunities for employees to learn and enhance their skills. One informant expressed, “I want my boss to provide a clear guideline to me and teach me clearly in order to help me pick up my job quickly”. Other informants focused on learning from their jobs and improving their qualifications: “I hope that I can learn everything from my boss because it can help me to take care of complicated tasks and reduce the risk of making mistakes and getting fired.” Another informant added: “my superior should care about the subordinates, respect each other, give more learning opportunities and teach them useful skills.” Organizational practices that promote a learning organization are often desirable, as one informant mentioned: "I always seek opportunities for future development such as overseas training and job rotation.” Retaining millennials solution 7: Communication Communication refers to an organization's effort and willingness to listen to employees, recognize employees' feedback, engaging employees regularly, and hear honestly from employees without retaliation. An effective communication channel between employees and the top management also was deemed important. As one millennial mentioned: “I want to be able to talk to the top management directly as they often ignore our requests.” Effective communication among co-workers and superiors also play a role in job performance, as one respondent suggested: “I like to work as a team because many ideas will be inspired through the cooperation with others… communication can make teamwork more efficient and effective.” Retaining millennials solution 8: Superior and peer relationships Superior and peer relationships represent interpersonal relationships with co-workers and superiors. Being able to work with superiors who are friendly, caring, and responsible is important to many of the informants. As one respondent noted: “I hope my boss is a kind person because then I can do my job without pressure. I also want to know more about my colleagues and wish the companies can bring employees together more often.” Others look for friendly and helpful co-workers and superiors: “My superior should be generous and friendly. My peers should be nice and helpful to me”. Another added: “My superior should be responsible and not too strict on me.”
2024-01-08T01:27:15.642919
https://example.com/article/8809
Activity of medullary reticular formation neurons in the unrestrained cat during waking and sleep. Single units, recorded in the medial medullary reticular formation (RF) in unrestrained, behaving cats, discharged in conjunction with specific movements and postures. Most cells were also active during REM sleep. Discharge rates in active waking and REM sleep were positively correlated and discharge patterns in these states were similar. We conclude that activity in these cells is related to the motor activation occurring in both active waking and REM sleep. We found no cells whose discharge was related in a non-specific way to motor tone or to REM sleep atonia. We discuss mechanisms by which medullary units with specific motor relations may give rise when stimulated to the relatively non-specific motor effects previously reported.
2023-10-28T01:27:15.642919
https://example.com/article/2683
{ "name": "ISO8601DateFormatter", "version": "0.7", "summary": "A Cocoa NSFormatter subclass to convert dates to and from ISO-8601-formatted strings. Supports calendar, week, and ordinal formats.", "description": "TL;DR: You want to use ISO 8601 for any and all dates you send or receive over the internet, unless the spec for the protocol or format you’re working with specifically tells you otherwise. See http://xkcd.com/1179/ .\n\nISO 8601 is most recognizable as “year-month-date” (a.k.a. “calendar date”) strings, such as “2013-09-08T15:06:11-0800”. Of course, as you might expect of a formal standard, it’s more sophisticated (some might say complicated) than that: it also provides “week date” and “ordinal date” formats.\n\nThis formatter can both parse and unparse dates in all three ISO 8601 formats. (By “unparse”, I mean “produce a string from”—the reverse of parsing.)\n", "authors": "Peter Hosey", "homepage": "http://boredzo.org/iso8601dateformatter/", "license": { "type": "BSD", "file": "LICENSE.txt" }, "platforms": { "ios": "5.0", "osx": "10.7" }, "source": { "git": "https://github.com/boredzo/iso-8601-date-formatter.git", "tag": "0.7" }, "source_files": "ISO8601DateFormatter.{h,m}", "exclude_files": [ "test*.m", "timetrial.m", "unparse*.m", "ISO8601ForCocoa/ISO8601ForCocoa{,Touch}Tests/**/*.m" ], "public_header_files": "ISO8601DateFormatter.h", "requires_arc": false }
2024-05-10T01:27:15.642919
https://example.com/article/9771
Purification, crystallization and preliminary X-ray analysis of two crystal forms of ribonuclease Sa3. RNase Sa3 produced by Streptomyces aureofaciens strain CCM 3239 belongs to the T1 family of microbial ribonucleases. It is closely related both to RNase Sa, studied in detail earlier, and to RNase Sa2 produced by the same microorganism. The most important property of RNase Sa3 is the relatively high cytotoxic activity, which was not observed for RNase Sa and Sa2. Recombinant RNase Sa3 was overexpressed in Escherichia coli and purified to high homogeneity. The hanging-drop vapour-diffusion method was used for crystallization. The two crystal forms are trigonal P3(1)21 and tetragonal P4(1)2(1)2, with unit-cell parameters a = b = 64.7, c = 69.6 A, gamma = 120 degrees and a = b = 34.0, c = 147.2 A, respectively. They diffract to 2.0 and to 1.7 A resolution, respectively, using synchrotron radiation. The asymmetric units of crystal forms I and II contain one molecule of the enzyme, which corresponds to V(M) = 3.8 A(3) Da(-1) with a solvent content of 68% and V(M) = 1.9 A(3) Da(-1) with a solvent content of 37%, respectively.
2023-08-10T01:27:15.642919
https://example.com/article/5013
Q: Make a div scroll instead of expanding to fit its contents I have a layout where I have a scrollable list of items in the center, with some stuff above and below it in a column. The list should take up as much empty space as is available to it in the column (I don't want to specify a specific height on it), and should scroll when the empty space in the column is not enough to fit all the items. Here is a JSFiddle of the situation. Notice that with just a few items in the scroller, it expands to fill the empty space in the column (as is intended). But then if you add several more items to the scroller, it expands to fit the entirety of its contents instead of staying at its original size, and then scrolling its overflowing contents; even though the it has overflow-y: scroll set! However, if you then set the scroller to have a height of 0, the problem is fixed and the items scroll as is intended, with the scroller at its original height before the extra items were added. But WHY!? Can someone please explain to me what's going on here? Also, is there any consequences of this "solution" that I'm not seeing? <div class="column"> <div class="title">Header</div> <div class="scroller"> <div class="item">Child</div> <div class="item">Child</div> </div> <div class="title">Footer</div> </div> , .column { display: flex; flex-direction: column; height: 200px; } .title { height: 50px; flex-shrink: 0; } .scroller { flex-grow: 20; flex-shrink: 0; overflow-y: scroll; } .item { height: 20px; margin-top: 2px; } A: Some quick background for anyone who runs across this later: Elements that have flex-grow expand to take up x units of the available space minus the other flex content. In your case, .scroller is the only one with flex-grow but the other flex elements have defined heights so their content takes up space. Elements that have flex-shrink contract as the space decreases. A zero value means they don't contract, a value >=1 allows scaling down. However flex-shrink ONLY works if the element DOES NOT also have a flex-grow applied to it. Elements with both shrink & grow will only shrink to the size of their content In your example, overflow doesn't kick in when the element is as big as the content (see above) which it is because you have both grow/shrink applied. Adding an explicit height (height: 0) overrides the computed "content" height allowing the flex-shrink to compress the element smaller than its content. This, in turn, makes the scrollbar work. I don't know if this will cause any oddities at some point but it's an interesting solution to the problem and does seem to work pretty well.
2023-10-16T01:27:15.642919
https://example.com/article/1186
[Endometriosis: physiopathology and investigation lines (part two)]. Sampson's menstrual reflux theory (1927) is widely accepted as an explanation of endometriosis physiopathology, it proposes five basic necessary processes to its development: adhesion, invasion, recruitment, angiogenesis and proliferation. Several factors and physiologic processes are necessary for the survival and growth of endometrial tissue. Clinical manifestations of these disease are: dysmenorrhoea, dyspareunia, and peritoneal adhesions, that with other findings reveal an inflammatory process that requires cytokines, macrophages, NK cells, lymphocytes and prostaglandins whose qualitative functions may be compromised or may contribute to the peripheral generation of estrogens. Angiogenesis benefits the development of these endometrial tissue foci and probably stimulates several vascular growth factors, and sexual steroids. Endocrine factors are capital for this entity, as is demonstrated by the presence of estrogen receptors in macrophages, fibroblasts and endometrium among others, as well as the clinical symptoms control trough the blockage of the hypothalamus-pituitary-ovary axis. Studies on the genetic and antioxidant factors have revealed key points that may be helpful in determining a proper diagnosis and treatment for endometriosis.
2024-02-05T01:27:15.642919
https://example.com/article/3941
class PrayerRequestAuthorizer < ApplicationAuthorizer def readable_by?(user) if resource.person == user true elsif resource.group && user.member_of?(resource.group) true end end def creatable_by?(user) if resource.group && user.member_of?(resource.group) && resource.group.prayer? true end end def updatable_by?(user) # my prayer request if resource.person == user true # group admin elsif resource.group.try(:admin?, user) true end end alias deletable_by? updatable_by? def self.readable_for_group_by_user(group, user) if user.member_of?(group) group.prayer_requests else group.prayer_requests.none end end end
2024-05-22T01:27:15.642919
https://example.com/article/1427
HTML5 Security Cheat Sheet - dhruvbhatia https://www.owasp.org/index.php/HTML5_Security_Cheat_Sheet ====== UnoriginalGuy I've tried to get Content Security Policy (CSP) rolled out in our new development at work, and to be frank I'm starting to lose faith that it is workable. We're on report only at the moment, and it seems like every major JavaScript library depends on Eval() in one way or another (mostly new function()). Just this week someone wanted to use Angular (1.3.1) and it generates dozens of CSP reports without ng-csp in the HTML element, but when the attribute exists $http responses (which depend on function()) aren't working (e.g. success(function(data, status, headers, config) {}). Unfortunately Angular's documentation on CSP is a single page with nothing particularly helpful, and tons of stackoverflow results about Google Chrome extension development. This is just the tip of the iceberg. Seems like every single major JavaScript library (even things you just take for granted) break CSP or need tons of exceptions. ~~~ homborg As far as I can tell, the are no issues with the `function` keyword in csp mode, but the `Function` constructor, eg. `Function("a", "console.log(a);")` Your example is a callback with an anonymous function. Do you have any links to discussions about your issue? ------ borski You can scan for a huge chunk of this with [https://www.tinfoilsecurity.com](https://www.tinfoilsecurity.com), and we're adding more every day. Most importantly, you should make it a regular part of your Dev cycle. Note: this isn't an ad, it just seemed relevant to those interested in a "cheat sheet." Automating it by calling out to our API seems really relevant. :) ~~~ passfree The problem with your approach is that you are assuming that people are fine that scan for in production for security issues. While it is true that everyone does it, this arguments falls flat because there are plenty of systems which will avoid the risk and for good reasons. ~~~ borski Nope, in fact you can scan in staging or Dev too, by using Bifrost: [https://www.tinfoilsecurity.com/developer/bifrost](https://www.tinfoilsecurity.com/developer/bifrost)
2023-09-30T01:27:15.642919
https://example.com/article/8822
Ted Cruz hugs wife, then nearly knocks her out Ted Cruz hugged his wife immediately after announcing the suspension of his presidential campaign, but when he went in for a second hug, he elbowed her in the face.
2023-09-16T01:27:15.642919
https://example.com/article/4821
The study found that Americans will save about $44.3 billion at the gas pump. The study estimates Michiganders will save $976 million — an average of $240 per household. The new standards are fleet average requirements, which means that some vehicles would have higher fuel efficiency and some would be lower. The standards are pegged to specific laboratory tests instead of real-world driving conditions. In 2025, cars and trucks will average closer to 40 miles per gallon in actual driving, which is nearly double today’s on-road average of 22 mpg.
2023-12-03T01:27:15.642919
https://example.com/article/8794
Definition of an amino-terminal domain of the human T-cell leukemia virus type 1 envelope surface unit that extends the fusogenic range of an ecotropic murine leukemia virus. Murine leukemia viruses (MuLV) and human T-cell leukemia viruses (HTLV) are phylogenetically highly divergent retroviruses with distinct envelope fusion properties. The MuLV envelope glycoprotein surface unit (SU) comprises a receptor-binding domain followed by a proline-rich region which modulates envelope conformational changes and fusogenicity. In contrast, the receptor-binding domain and SU organization of HTLV are undefined. Here, we describe an HTLV/MuLV envelope chimera in which the receptor-binding domain and proline-rich region of the ecotropic MuLV were replaced with the potentially corresponding domains of the HTLV-1 SU. This chimeric HTLV/MuLV envelope was processed, specifically interfered with HTLV-1 envelope-mediated fusion, and similar to MuLV envelopes, required cleavage of its cytoplasmic tail to exert significant fusogenic properties. Furthermore, the HTLV domain defined here broadened ecotropic MuLV envelope-induced fusion to human and simian cell lines.
2024-03-04T01:27:15.642919
https://example.com/article/3309
Boris Johnson’s stance on climate change has flip-flopped Originally published by E&E News The United Kingdom's new leader is being labeled an enemy of climate science and an ally of President Trump, but his public record paints a murkier picture. Take an October 2011 report in which Boris Johnson, then London's mayor, touted his green credentials and policies to reduce the city's greenhouse gas emissions. "London was the first city to experience mass urbanization in the modern era," Johnson began in his treatise, titled Delivering London's Energy Future: The Mayor's Climate Change Mitigation and Energy Strategy. "It was the imagination of our forebears—among them Bazalgette, Brunel, Prince Albert—who pioneered solutions to tackle some of the city's more mundane but critical challenges," Johnson continued. "I want now to unleash the same entrepreneurial drive and creative genius to achieve what is now the 21st century's environmental imperative, to cut carbon output and secure the city's energy supply, whilst making services more efficient and better value for money." In later years, Johnson, who was named prime minister yesterday, wrote articles deemed sympathetic to climate skepticism. Environmentalists fume at his climate record in Parliament, including votes against carbon capture and storage technology investments and in favor of taxation on renewable energy projects. But Johnson flipped again during his time as U.K. foreign secretary. He openly criticized the Trump administration's decision to withdraw from the Paris Agreement on climate change and urged the United States to return to the fold. "We continue to lobby the U.S. at all levels to continue to take climate change extremely seriously," he told Sky News in 2017. Johnson's public comments regarding climate change have been summarized by the group DeSmog UK in a thorough overview posted on their website. Given the pattern of contradictions on climate, it might be said that Prime Minister Johnson could continue demonstrating an inconsistent track record on climate change moving forward. Global warming, however, does not rank high on his agenda, as Johnson has made abundantly clear. In his acceptance speech, Johnson insisted that his priority is "Brexit," the name given to the United Kingdom's looming withdrawal from the European Union. "We are going to energize the country," Johnson said. "We are going to get Brexit done on Oct. 31, and we're going to take advantage of all the opportunities that it will bring in a new spirit of can-do. And we are once again going to believe in ourselves and what we can achieve." He never mentioned climate change. The Conservative Party's website doesn't mention it either. Rather, it lists Johnson's six-point plan "to get the country back on the road to a brighter future." Brexit tops the list, followed by more money for health care and schools, and a promise to hire 20,000 new police officers. Climate change was very much a priority for Johnson during his term as mayor of London, however. He left that office in 2016. In his 2011 mayoral report, Johnson said his policies promised to deliver to the city 14,000 "green-collar" jobs by 2025. He is also credited with introducing London's bike-sharing program and for floating the idea of emissions-free zones. His plan envisioned retrofitting buildings to reduce carbon emissions. "The policies and actions detailed here put London firmly on course to cut its carbon output by 60 percent by 2025," Johnson wrote in that report. A 2012 paper issued as part of his "Better Off With Boris" reelection campaign also pulls on environmental heartstrings. He promised to expand the city's green space, and he highlighted climate change as "one of the most serious challenges we face." Johnson's emphasis today is squarely on protecting Britain's economy while negotiating its withdrawal from the European Union. "If you look at the history of the last 200 years of this party's existence, you will see that it is we Conservatives who have had the best insights, I think, into human nature, and the best insights in how to manage the jostling sets of instincts in the human heart," Johnson said this week.
2023-11-08T01:27:15.642919
https://example.com/article/2963
Beer Cheese Served as an appetizer or topping a burger this culinary tradition was born in Kentucky in the 1940's. From pimento cheese to Benedictine, you may get the idea that Kentuckians need to something to snack on while preparing the fried chicken or afternoon bourbon cocktail! Another great addition to the pub menu and certainly something to have on hand while watching the state’s favorite pastime (after horse-racing) college basketball is a Winchester, KY creation….beer cheese. The savory spread is a distinctive mix of sharp cheddar, beer, and spices and was introduced to the Kentucky palate in the 1940’s by brothers John and Joe Allman. Unlike many fondue-style cheese and beer creations, Kentucky’s version is typically served cold with crackers, chips and carrots or celery. Louisville chefs have kicked it up a notch with their own unique twists on this culinary tradition. For true devotees, just 90 minutes down the road , The Beer Cheese Festival is celebrated every June in Winchester. www.beercheesefestival.com
2024-03-02T01:27:15.642919
https://example.com/article/5037
FWIW Virginia: Breaking Down the House Welcome to FWIW Virginia, where we analyze digital spending trends on both sides of the aisle in advance of the 2019 Virginia legislative elections. Each week, we look at whose digital spending is up, whose is down, and whose is non-existent across the Commonwealth. For what it’s worth, some of it might surprise you. With less than two weeks until the primary, campaigns in Virginia are finally starting to put some money behind digital advertising. But is it too little too late? This week we take a look at the most important primary contests on the House side and how their digital programs are shaping up ahead of June 11 election. But first… 2019 by the numbers We’re tracking digital investment by party committees, statehouse leadership, and candidates in some of the most competitive state house and senate races in Virginia in advance of the 2019 state legislative elections. Here is how investment by Republicans and Democrats compare since the 2018 midterm elections. Here is a list of top Virginia political spenders on Facebook the week of May 22-28. Days until the primary election: 12 Days until the general election: 159 Deep Dive: Breaking Down the House Though there are a number of competitive primaries for the House of Delegates, there are only a few with major implications for control of the General Assembly. So, we are going to take a look at the digital programs for the four most crucial races. House District 28: Bob Thomas vs. Paul MildeDue to his vote in favor of Medicaid expansion, Delegate Bob Thomas is facing a primary challenge from former Stafford County Supervisor and far-right conservative Paul Milde. The two candidates have been spending heavily on Facebook advertising since last summer, turning this primary into the most expensive and damaging on the House side. Bob Thomas has used digital advertising to shore up his base among conservative voters but has refrained from directly attacking his opponent. The primary has pushed Thomas to campaign further to the right, and he recently spoke in favor of the extreme abortion ban in Georgia and said Republicans would pass a similar one in Virginia if they take back the Governor’s Mansion and hold the General Assembly. Meanwhile, Milde has aggressively attacked Thomas for his vote to expand Medicaid and continues to portray him as an unreliable conservative in the House. Regardless of who comes out on top, it’ll be interesting to see how this primary weakens the Republican nominee going into November. House District 50: Lee Carter vs. Mark WolfeDelegate Lee Carter stands out in the General Assembly as an unabashed Democratic Socialist who flipped a Republican-held seat in the 2017 wave election, but he’s drawn a primary challenge from Manassas City Councilmember Mark Wolfe for his staunch opposition to corporate interests. Lee Carter’s digital ads are primarily issue-driven and reflective of his broader policy agenda. Carter also has a massive Twitter following that he leverages to raise money and drive strategic narratives for his campaign. Mark Wolfe is a former Republican who switched parties during the 2016 election. He was the top vote getter that year in the seven-way race for Manassas City Council but has been consistently outraised and lacks Carter’s digital savvy and online following. House District 68: Garrison Coward vs. Lori LosiGarrison Coward and Lori Losi are competing for the Republican nomination to take on Delegate Dawn Adams in the general election. Adams only narrowly won her seat in the 2017 wave election and has not run a single dollar of paid digital advertising this cycle. Garrison Coward has run one of the more sustained digital programs so far this cycle, and it may have helped him build a Facebook following over 10 times the size of his opponent. He’s currently putting all of his digital spending behind just one ad that resembles a piece of campaign literature in advance of the June primary. Lori Losi was running Facebook ads touting her conservative positions to attract page likes – a few of which were about her anti-choice beliefs. Coincidentally, these ads stopped running on May 15, the day Alabama passed its extreme ban on abortion. 🤔 House District 91: Michael Wade vs. Martha MuglerHD-91 was one of the districts most affected by the court-ordered map of the House of Delegates – swinging 19.8 percentage points towards Democrats according to the Virginia Public Access Project. The incumbent, Republican Delegate Gordon Helsel, is not running for reelection, which makes the district an even stronger pick up opportunity for Democrats if the new map stays in place. Michael Wade won the Democratic nomination in 2017 but lost to Gordon Helsel by 13 points in the general election. And now he’s running for the nomination again. Martha Mugler is an at-large member of the Hampton School Board. According to her website, Senator Tim Kaine was scheduled to appear at her most recent fundraiser, and one of her active Facebook ads features testimonials from Congressman Bobby Scott and a myriad of other local elected officials supporting her candidacy. Bonus: Democrats flipped the script on abortion We noted several weeks ago that Democrats have historically run and won on the issue of choice in Virginia, but controversy in the General Assembly at the start of the year put Republicans on the offensive. That changed recently as extreme abortions bans passed in state legislatures across the country, and Delegate Bob Thomas came out in favor of such bans. Now, Republicans have gone nearly silent on the issue in their advertising – except for the few candidates that are running to the right in contested primaries. Meanwhile, the Virginia House Democrats, Senate Democrats, and state party are all up with attack ads on the subject, and nearly every Democrat is touting their pro-choice credentials in the primary.
2024-04-02T01:27:15.642919
https://example.com/article/4660
USS Trenton (LPD-14) USS Trenton (LPD-14), an Austin-class amphibious transport dock, was the third ship of the United States Navy to be named for the capital of New Jersey. In 2007, it was sold to the Indian Navy and renamed INS Jalashwa (L41). History Building process Her keel was laid down at Seattle, Washington, on 8 August 1966 by the Lockheed Shipbuilding and Construction Company. She was launched on 3 August 1968 sponsored by Mrs. Richard J. Hughes, and commissioned on 6 March 1971 with Captain Karl R. Thiele in command. Initial operations Trenton got under way on 9 April for the East Coast and reached her home port, Norfolk, Virginia, on 12 May. The amphibious transport dock remained in port until 1 June when she departed Hampton Roads for shakedown training out of Guantanamo Bay Naval Base in Cuba. However, on 28 June, her shakedown cruise was interrupted when a steam valve in her number two engine room ruptured, killing four sailors instantly and severely injuring six others. The injured men were evacuated first to Guantánamo Bay and thence to the burn ward of the Army Hospital at Fort Sam Houston, Texas. There, two of the six subsequently died as a result of their injuries. Trenton returned to Guantánamo Bay for interim repairs and then made her way back to Norfolk on one engine, arriving on 6 July. After repairs at the Norfolk Naval Shipyard, she completed shakedown training off the Virginia Capes and in the Guantánamo Bay operating area. On 9 November, the ship returned to Norfolk and remained there through the end of 1971. 1972–1973 On 17 January 1972, Trenton rounded Cape Charles and headed north to participate in Exercise "Snowy Beach." She arrived off Reid State Park, Maine, three days later and participated in the cold weather amphibious exercise until 23 January when she headed home. On 4 February, she stood out of Hampton Roads bound for the Gulf of Mexico in company with Ponce (LPD-15). The two ships reached New Orleans, Louisiana, on 9 February and, for the next six days, served as "hotel" ships for ROTC and military participants in Mardi Gras. Trenton returned to Norfolk on 20 February and resumed her East Coast-West Indies routine. Following amphibious training at Onslow Beach, North Carolina, and sea trials near Norfolk, she visited the Caribbean Sea in April with other units of Amphibious Squadron (PhibRon) 4. She then devoted the rest of the early summer to exercises and training at Onslow Beach and at Norfolk before preparing for her first Mediterranean deployment. The ship departed Norfolk on 28 July, embarked Marines at Morehead City, North Carolina, on 29 July, and headed across the Atlantic on 30 July. She reached Rota, Spain, on 10 August and, with the other units of PhibRon 4, was incorporated into the Sixth Fleet as Task Force (TF) 61. She spent the remainder of the year and most of the first month of 1973 in the Mediterranean Sea. During that six-month period, Trenton participated in six amphibious landing exercises (Phiblexes), most of which were conducted in cooperation with the military services of foreign nations. In September, she conducted a landing exercise at Timbakion, Crete, with units of the Italian Navy. Greek and Italian ships joined her later that month for Phiblex 3–73 conducted at Alexandroupolis, Greece. In mid-October, troops of the French Foreign Legion provided the opposition for a landing exercise at Corsica. Trenton visited Izmir, Turkey, in mid-September and, in mid-December, concluded her exercise schedule at Porto Scuda, Sardinia, with Phiblex 6–73. On 16 January 1973, she headed home; and, ten days later, she entered the Naval Amphibious Base at Little Creek, Virginia. On 1 March, Trenton shifted to the administrative command of PhibRon 10. On the 27th, she embarked Marines at Morehead City and headed for Onslow Beach, where she participated in Exercise "Exotic Dancer VI." On 7 April, the warship headed south to Vieques Island, near Puerto Rico. From 10 to 14 April, Trenton joined other Navy ships in Exercise "Escort Tiger XIV," which consisted of training for disaster assistance to the island countries of the Caribbean. During this Caribbean cruise, she visited Maracaibo, Venezuela, San Juan, Puerto Rico, and St. Thomas in the U.S. Virgin Islands before embarking the Marines at Vieques on 3 May. After a port visit at Ponce, Puerto Rico, Trenton carried her Marines to Guantánamo Bay for a four-day exercise. On 14 May, she departed the Caribbean and, after disembarking the Marines on 17 May, reached Norfolk on 18 May. On 11 June, Trenton steamed out of Hampton Roads for northern Europe. She reached Kiel, Germany, on 22 June, and, for the next week, participated in the annual "Kiel Week" naval celebration. Early in July, she visited Portsmouth, England, and, at mid-month, put into Rotterdam in the Netherlands. The amphibious transport dock bade farewell to Europe at Rotterdam on 21 July and headed back to the United States. Trenton spent the remainder of the summer conducting drills in the Virginia Capes Operating Area and in preparation for her second Caribbean deployment of the year. On 1 October, she shifted from PhibRon 10 to PhibRon 8. On the last day of that month, she embarked Marines at Morehead City and headed south. For the remainder of the year, she cruised the Caribbean, visiting ports in Puerto Rico, the Virgin Islands, and in the Netherlands Antilles as well as conducting amphibious exercises at Vieques Island. The amphibious transport dock returned to Norfolk on 14 December. 1974–1975 During the first four months of 1974, Trenton conducted operations out of Little Creek and Norfolk and prepared for duty in the Mediterranean. On 10 May, she embarked Marines at Morehead City and put to sea. Ten days later, she reached Rota, Spain, and joined the Sixth Fleet. For the next six months' she cruised the Mediterranean, visiting ports and conducting exercises. In July, Trenton participated in the evacuation of 286 refugees from strife-torn Cyprus to Beirut, Lebanon. While with the Sixth Fleet, she participated in four amphibious exercises. One Operation – "Good Friendship/Double Effect" – included ships of the Turkish Navy. On 20 October, she steamed out of Rota to return to the United States. She arrived in Norfolk on 31 October and operated in the western Atlantic through the end of 1974. On 7 March 1975, she embarked Marines at Morehead City and headed south. After an amphibious assault exercise at Onslow Beach from 8 to 10 March, she continued south to the Caribbean. During the two-month cruise, Trenton participated in four exercises, two of which – "LantReadEx 2–76" and "Rum Punch" – were held in cooperation with units of the Royal Navy and the Dutch Navy. She returned to Norfolk on 28 April. In May, she hosted a class from the Naval War College, conducted a midshipman training cruise for the United States Naval Academy, and returned to Onslow Beach for joint service Exercise "Solid Shield." During the early summer, Trenton prepared for overhaul. On 14 August, she headed north to New York, moored at the Coastal Drydock and Repair Company on the following day, and commenced a nine-month overhaul. 1976–1980 On 12 May 1976, Trenton completed her overhaul and, following loadout at Little Creek, Virginia, she deployed to Guantánamo Bay, Cuba on 6 July for refresher training. Returning to Norfolk on 17 August, the ship's next three months was spent in preparation for a forthcoming Mediterranean deployment. On 15 November, Trenton, with embarked elements of Marine Battalion Landing Team 1/6, formed Mediterranean Amphibious Ready Group 3–76 and operated with the Sixth Fleet until she returned to Norfolk on 12 May 1977. Following post-deployment stand down which ended on 30 June, Trenton spent the remainder of 1977 conducting midshipman training cruises, engaging in amphibious exercises, and participating in Comptuex 3–77, which involved units of the Standing Naval Force Atlantic. The year 1978 found Trenton embarking elements of Battalion Landing Team 1/2 and deploying to the Caribbean from 30 January to 7 March to participate in Atlantic Fleet Readiness Exercise 1–78. The succeeding four months were spent in preparations for a return to the Mediterranean. The ship, with embarked elements of Marine Battalion Landing Team 2/8, departed Morehead City on 27 July, as part of Mediterranean Amphibious Ready Group 2–78. The remainder of 1978 was spent with the Sixth Fleet in that sea. In September 1980, Trenton served as the Advance Force flagship for the three-week NATO Exercise Teamwork – 80, in the fiords of Norway. Trenton embarked the flag staff of Commander Service Force Atlantic, including two female officers – the first time that female officers were embarked on Navy ships for long-term major exercises. As the Advance Force flagship, Trenton inserted SEALs and Marine Recon units as the first phase of the exercise, before landing other Marine units. After the exercise, the ship made port visits to Malmo, Sweden; Bremen, Germany; and Portsmouth, England before returning to Norfolk. 1981–1996 In January 1981, Trenton departed Norfolk for a six-month deployment with the Sixth Fleet in the Mediterranean as part of the Marine Amphibious Ready Group (MARG 1-81)and Battalion Landing Team 2/8 Commanded by then Lieutenant Colonel Anthony Zinni (laterGeneral) and XO Major Raymond Smith (later Major General). The ship with its embarked Marines conducted amphibious landings and exercises with Spain, Italy and Greece. During operations in Spain, the Marines lost a Cobra helicopter with the pilot and 2/8 Battalion Aid Station Surgeon killed. Plans to transit the Suez Canal and operate in the Red Sea and Indian Ocean were cancelled in order to remain south of Crete for possible Non-combatant Evacuation Operations (NEO) in Lebanon. The ship remained at sea more than 70 days, allowing the ship to splice the mainbrace and serve two cans of beer to each crewmember. Port visits were made in Malaga, Spain; Naples, Italy; Bari, Italy; and Alexandria, Egypt. On 27 April 1981, during the five-day port visit to Alexandria, Trenton and USS Jack (SSN-605) were slightly damaged when the Jack, surged against Trenton in heavy sea swells. In June, the Chief of Naval Operations, Admiral Hayward, visited the ship. Trenton returned to Norfolk in July 1981. On 17 October 1983 the Trenton departed Norfolk for the Mediterranean Sea. Somewhere east of Bermuda, she was diverted to Grenada to take part in Operation Urgent Fury. Trenton transited to the Eastern Mediterranean in November and took station off the coast of Beirut. While there she lost the hydraulic operating system for the port sterngate, as a result of operating in high sea conditions, and had to retire to Larnaca Bay, Cyprus to raise it lest it be lost to heavy seas. Further repairs were made at Haifa, Israel during December and until 3 January 1984. In April 1988, the Trenton participated in Operation Praying Mantis, a one-day naval battle between the United States and Iran, one helicopter Cobra is lost. the ship and its crew were awarded the Combat Action Ribbon, the Joint Meritorious Unit Award, Navy Meritorious Unit Commendation, and the Armed Forces Expeditionary Medal for various operations. In September 1990 the Trenton was ordered to the Persian Gulf in support of Operation Desert Shield and Desert Storm. Her crew received a Navy Unit Commendation, the Southwest Asia Service Medal with 2 bronze stars for both Operation Desert Shield and Operation Desert Storm, the Kuwait Liberation Medal by the Kuwaiti government and the Kuwait Liberation Medal by the Saudi Arabian government. On 26 December 1990, Navy Seals, Marine Recon, and Marine MP's from the Trenton boarded the Libyan ship IBN Kahldoon to search for prohibited cargo which was found and confiscated. It was determined that the Libyan vessel was in violation of the supply embargo placed on Iraq. On 2 January 1991, the Trenton along with the USS Guam were dispatched from anchorage off Oman to Somalia to airlift the US embassy in Somalia's capital Mogadishu, which had been suddenly enveloped by violence when rebels entered the city and the central government collapsed. On 5–6 January, 281 US and foreign nationals were airlifted from the embassy, including all of the embassy's staff along with diplomats from several nations (notably, the Soviet ambassador to Somalia and 38 Soviet diplomats). The vessels returned to Oman and the evacuees disembarked on 11 January, ending Operation Eastern Exit. The ship and crew were awarded the Navy Unit Commendation as part of PHIBRON 6. In April 1996, President Clinton ordered the ship to steam towards the coast of Liberia to assist in the evacuation of U.S. citizens and foreign nationals. This operation became known as Operation Assured Response. Her crew received the Joint Meritorious Unit Award. End of United States Navy career In July 2006, the U.S. tasked the vessel with evacuating citizens from Lebanon. The ship took some 3,500 Americans in two trips one to Cyprus and the other to Turkey. During the deployment, the ship's crew also conducted maritime security operations off the Somali Peninsula in Africa. USS Trenton (LPD-14) and its nearly 400 sailors made their final homecoming 21 September 2006 before the ship's decommissioning and transfer to the Indian Navy on 17 January 2007. On 16 February 2007, Trenton was awarded the 2006 Battle "E" award. Sale to the Indian Navy In 2006, the Indian government purchased Trenton for US$48.44 million (Rs 2.18 billion). The ship was turned over to the Indian Navy on 17 January 2007. The Indian Navy renamed the ship as the INS Jalashwa (Sanskrit for Hippopotamus). It remained at Norfolk Naval Base for refitting until May 2007. Six H-3 Sea King maritime utility transport helicopters will be operated from the ship. The ship is based at Visakhapatnam under the Eastern Naval Command. References Navsource.org: USS Trenton This article also includes text from Military.com External links LPD-14 Crew List and Info at NavySite.de Category:Austin-class amphibious transport docks Category:Cold War amphibious warfare vessels of the United States Category:United States Navy New Jersey-related ships Category:Ships built in Seattle Category:1968 ships
2023-12-08T01:27:15.642919
https://example.com/article/7471
export default function (format) { function clockFormat(seconds, decimals) { const hours = parseInt(seconds / 3600, 10) % 24; const minutes = parseInt(seconds / 60, 10) % 60; const secs = (seconds % 60).toFixed(decimals); const sHours = (hours < 10) ? `0${hours}` : hours; const sMinutes = (minutes < 10) ? `0${minutes}` : minutes; const sSeconds = (secs < 10) ? `0${secs}` : secs; return `${sHours}:${sMinutes}:${sSeconds}`; } const formats = { seconds(seconds) { return seconds.toFixed(0); }, thousandths(seconds) { return seconds.toFixed(3); }, 'hh:mm:ss': function hhmmss(seconds) { return clockFormat(seconds, 0); }, 'hh:mm:ss.u': function hhmmssu(seconds) { return clockFormat(seconds, 1); }, 'hh:mm:ss.uu': function hhmmssuu(seconds) { return clockFormat(seconds, 2); }, 'hh:mm:ss.uuu': function hhmmssuuu(seconds) { return clockFormat(seconds, 3); }, }; return formats[format]; }
2024-01-10T01:27:15.642919
https://example.com/article/6278
Q: How do I make my child theme re-apply the settings that were customised when its parent was active? Scenario Pick 2015 theme. Customize various settings, such as background picture, header picture, site name and tagline. But don't touch the contents of any of the theme's files. Use Codex' Child Themes to create a bare minimum child theme of the 2015 theme. Activate the new child theme. Oops? The site with this bare minimum child theme activated looks completely different from the parent theme. Background and header image were gone, and all manner of sidebar (or header) widgets had been activated that were not active (by default) in the parent 2015 theme. Original look of the site with just a few customised settings for the 2015 theme: The site as it looks with the 2015 theme derived child theme, which has just the required header in style.css and only enqueues the styles as suggested by the Child Theme page of the Codex in its function.php. Question How do I make it so that activating the child theme keeps the customisations and defaults of the parent theme? In this case: the header and background pictures and the removal (deactivation?) of the default (sidebar/header) widgets. Notes Create a child theme of an already heavy customised theme may sound like a duplicate, but that is about customisations by editing the theme's files. This question When activating a child theme, what core settings have to be reset ie; Custom Menus etc? seem to ask exactly what I seem to be after. Unfortunately, the only answer speculates about a mismatch in features, which is not the case for me and didn't pick up on the OP's comment to the same effect. I also looked at When activating a child theme, what core settings have to be reset ie; Custom Menus etc?. It is related, but it doesn't answer my question. This: Register theme customizer settings when theme activates [duplicate] also seems related, but doesn't address what I want. Nor does the question it was marked a duplicate of: Settings API enable default settings on theme install? which is about saving the child theme's settings, not about re-using or re-applying the parent theme's settings for the child. A: I gave a +1 to the @webtoure's answer because it gives you the right direction, however I think it lacks some checks. First of all it does not check that the theme that's being activated is a child theme, and does not check that the theme previously active is the parent theme of the child theme being activated. Per my understanding of OP these conditions are required. Moreover, one issue that you need to take into account is what to do with the theme mods of the child theme being activated, if they already exist. In @webtoure answer, they are stored in a backup, that might save you under some circumstances, but WordPress will not recognize them by default and so they require some additional code to be used. I think it would be better, to inherit the theme modifications from parent theme only the first time a child theme is activated. In short, the conditions I want to check before to inherit theme mods from parent theme are: the previously active theme must be the parent of the child theme that is being activated the child theme that is being activated has to never been activated before To ensure the second condition I'll use a custom option, because WordPress does not provide a way to do this check. This is the code, please read inline comments for explanation of what is going on: add_action( 'switch_theme', function( $new_name, \WP_Theme $new_theme ) { // get the previously active theme $previous = get_option( 'theme_switched', -1 ); // get the parent of current theme, will be false if no parent $parent = $new_theme->parent() ? $new_theme->get_template() : false; // current stylesheet name $stylesheet = get_option( 'stylesheet' ); // has the theme being activated ever been activated before? $lastActive = get_option( $stylesheet . '_last_active', false ); // if previouly active theme is the parent of the the child theme being activated // and it has never been activated before.. if ( ! $lastActive && $parent === $previous ) { // update "last_active" option so following code won't run again for this theme update_option( $stylesheet . '_last_active', current_time( 'timestamp', 1 ) ); // get the theme mods of the parent $previousMods = get_option( 'theme_mods_' . $parent, array() ); // inherit current theme mods from parent theme mods update_option( 'theme_mods_' . $stylesheet, $previousMods ); } }, 10, 2 );
2024-04-09T01:27:15.642919
https://example.com/article/3458
Voters like being told what they want to hear and Donald Trump is only guilty in so far as he reflected back exactly what US voters wanted to hear. Politifact fact-checked statements made by Trump during his campaign and they identified him as lying 70 per cent of the time. Yet voters never bothered to discover if there was any truth behind his statements. Instead, voters fell into two camps: The 'gullible voter' - those who believe everything they read or heard without applying any critical thought and the 'rabid partisan' - those who sought out ‘facts’ that reinforced their own opinion. Worse still, many didn’t even have the knowledge or skills to think critically about his claims. A 2014 study by the University of Pennsylvania, found that two-thirds of Americans could not name all three branches of the federal government, more than one-third could not even name one, and that 60 per cent could not correctly identify which political party controlled the US House of Representatives or Senate. US Election: New president Donald Trump in numbers To secure their support, all Trump supporters needed to hear was someone echoing their concerns surrounding immigration. The billionaire made it the centrepiece of his campaign, promising to build a wall to keep out Mexican migrants, and ban all Muslim migration. Before the election poll by ABC News/The Washington Post found that 37 per cent of his supporters strongly believed that white Americans are being economically disadvantaged because of a perceived preference for Hispanics and African Americans. In June 2016, a study by the University of California at Santa Barbara, and Stanford University, found that many white Americans were more likely to support Trump when they are reminded that according to the US Census Bureau by 2044, non-white ethnicities will comprise the majority of the population. The proof was in the exit poll pudding: According to The New York Times 64 per cent of voters felt that immigration was their main concern. President Donald Trump life in pictures Show all 16 1 /16 President Donald Trump life in pictures President Donald Trump life in pictures Donald Trump poses in a rocking chair once used by President John F. Kennedy at his New York City residence Reuters President Donald Trump life in pictures Developer Donald Trump with his new bride Marla Maples after their wedding at the Plaza hotel in New York Reuters President Donald Trump life in pictures Donald Trump and Celina Midelfart watch the match between Conchita Martinez and Amanda Coetzer during U.S. Open. She was the date whom Donald Trump was with when he met his current wife Melania at a party in 1996 Reuters President Donald Trump life in pictures U.S. Supreme Court Justice Clarence Thomas serving as the grand marshal for the Daytona 500, speaks to Donald Trump and Melania Knauss on the starting grid at the Daytona International Speedwa Reuters President Donald Trump life in pictures Developer Donald Trump talks with his former wife Ivana Trump during the men's final at the U.S. Open Reuters President Donald Trump life in pictures Donald Trump and his friend Melania Knauss pose for photographers as they arrive at the New York premiere of Star Wars Episode : 'The Phantom Menace,' Reuters President Donald Trump life in pictures Billionaire real estate developer Donald Trump talks with host Larry King. Trump told King that he was moving toward a possible bid for the United States presidency with the formation of a presidential exploratory committee Reuters President Donald Trump life in pictures Donald Trump answers questions as Minnesota Governor Jesse Ventura looks on in Brooklyn Park. Trump said on Friday he 'very well might' make a run for president under the Reform Party banner but had not made a final decision Reuters President Donald Trump life in pictures Billionaire Donald Trump makes a face at a friend as he sits next to Panamanian President Mireya Moscoso before the start of the 2003 Miss Universe pageant in Panama City Reuters President Donald Trump life in pictures Entrepreneur Donald Trump is greeted by a Marilyn Monroe character look-a-alike, as he arrives at Universal Studios Hollywood to attend the an open casting call for his NBC television network reality series 'The Apprentice.' Reuters President Donald Trump life in pictures Donald Trump and Simon Cowell present an Emmy during the 56th annual Primetime Emmy Awards at the Shrine Auditorium in Los Angeles Reuters President Donald Trump life in pictures Donald Trump and Megan Mullally perform at the 57th annual Primetime Emmy Awards at the Shrine Auditorium in Los Angeles Reuters President Donald Trump life in pictures Donald Trump, poses with his children, son Donald Trump, Jr., and daughters Tiffany and Ivanka Reuters President Donald Trump life in pictures Billionaire Donald Trump told Miss USA 2006 Tara Conner on Tuesday she would be given a second chance after reported misbehavior Reuters President Donald Trump life in pictures Donald Trump holds a replica of his star on the Hollywood Walk of Fame as his wife Melania holds their son Barron in Los Angeles Reuters President Donald Trump life in pictures U.S. property mogul Donald Trump stands next to a bagpiper during a media event on the sand dunes of the Menie estate, the site for Trump's proposed golf resort, near Aberdeen, north east Scotland Reuters The National Socialist Movement, various factions of the Ku Klux Klan, and the white nationalist American Freedom Party are ardent supporters of Trump. Last week, a US federal judge announced a judicial hearing into claims that the Trump campaign had violated the Voting Rights Act of 1965 and the Ku Klux Klan Act of 1871 in Nevada, Arizona, Ohio and Pennsylvania. Today a former KKK leader congratulated Trump on his win. In his 1964 book, Anti-Intellectualism in American Life, Richard Hofstadter described how the dismissal of the science, arts, and humanities have been infused into America’s political and social fabric. We are living through the paradox of existing in the Information Age where to be an educated thinker is viewed by many as a bad thing. We shouldn’t blame politicians for taking the path of least resistance by telling us what we want to hear – it is our job to be better informed and critical in our choices. Today is a consequence of our intellectual laziness.
2024-02-03T01:27:15.642919
https://example.com/article/7322
Translucent (manga) is a Japanese seinen manga series written by Kazuhiro Okamoto and serialized in Comic Flapper. It was licensed by Dark Horse Comics for release in the United States in July 2007. Synopsis The protagonist of the series is a shy young girl named Shizuka and her outgoing male friend Mamoru. The series revolves around Shizuka's high school life after she contracts "Translucent Syndrome", a mysterious condition which has only one symptom: The victim's body randomly turns translucent (and later completely invisible), but is otherwise left perfectly normal and healthy. Unfortunately for Shizuka, there is no known cure or treatment for Translucent Syndrome, other than it is tied to the emotional state of the person affected; positive emotions like happiness and love cause it to retract, negative emotions like stress and sadness cause it to accelerate. Initially Shizuka's condition only affects her arms and legs, and only partially, at seemingly randomly times and durations. However, as it worsens it begins to affect her entire body, leaving her increasingly more translucent and for increasingly longer random periods of time. Shizuka is also in danger of gaining "Fully Transparent Syndrome", or otherwise having her translucency become permanent, which will occur if she spends too long a stretch in her translucent stage. Fully Transparent Syndrome is marked by complete and permanent invisibility, rather than the temporary partial invisibility of the normal syndrome. The fictional condition is used in the series as a metaphor for the common childhood anxiety of feeling lonely and disconnected from other people, as well as—through the threat of the condition worsening—a fear of growing up. Characters The shy 14-year-old main character of the manga. Shizuka contracted the strange "Translucent Syndrome" 3 years before the manga started, which cuts her off from both normal social interaction with her peers, and from her dreams of becoming a stage actress. Shizuka is very talented for a young actress, but this is offset by her very timid and insecure nature. She has decided that she wishes to be a "cherry tree actress" -- one that is mostly ignored unless she is on stage, where she will blossom like a cherry tree. Mamoru is an outgoing, childish extrovert, who encourages Shizuka to come out of her shell, despite (or because of) her condition. He is a painter, and assists Shizuka in creating better skin tone greasepaint tones to hide her condition when it is minor. He is obsessed with monsters as well as Gundam models. He also likes to create silly games, like walking in lockstep with Shizuka spontaneously, seeing "old men" in housing architecture, or monsters in cloud formations. Seems to have feelings for Shizuka, but is too immature to articulate them. An adult friend of Shizuka, whom Shizuka meets during a checkup for her Translucent Syndrome. Keiko's Translucent Syndrome has progressed to the permanent "Fully Transparent Syndrome" stage, and as such she is completely invisible. She is not drawn at all in most of the manga, instead her trademark glasses, cigarette, and bandanna float in midair. In a small bit of irony, Keiko is a professional glass artist, and comments on Glass's translucency when she is introduced. She also has a boyfriend named Koichi. Koichi (No last name given) Keiko's on-again/off-again boyfriend. He is an architect, and is fascinated by old buildings. He is also an old fan of Gundam models. He is very similar in personality to Mamoru, only older. (No first name given) The student body president of Shizuka and Mamoru's school, and a friend of Shizuka's. Ms. Okouchi dislikes the constant attention her family and peers give her, and is jealous of Shizuka's condition. She attempts to get Translucent Syndrome from Shizuka, but cannot due to Translucent Syndrome being non-contagious. Later, she attempts to further Mamoru and Shizuka's relationship, growing increasingly frustrated (up to and including drop kicking, which she starts to do as a running gag) with Mamoru's obliviousness. She also seems to have a slight crush on Mamoru herself. Dr. Momoko Takazawa The world's foremost expert in Translucent Syndrome, and Shizuka's doctor. Dr. Takazawa is a young woman who takes an interest in furthering Shizuka and Mamoru's relationship. She enjoys teasing Shizuka with more than slight sexual innuendo, for example asking her if Shizuka and Mamoru have had sex, and insinuating that Shizuka is perfectly healthy, except for her breast size. However, her intentions appear to be noble, as she recognizes that Mamoru is having a healthy effect on Shizuka's Translucent Syndrome, primarily her emotional state. US Localization Delay In a post on the Dark Horse Forums, Philip Simon, the editor behind the US translation of Translucent announced an ETA of Translucent, Books 4 and 5—Vol. 4 on sale July 2009, and Vol. 5 (the final volume) on sale November 2009. Anticipating a reaction due to the extreme delay (Volume 4 will be translated 11 months after said forum post, and just over 18 months after Volume 3's release), he said ""Why the wait with some of these?" you may ask. Well, I had to find new translators after three great teammates had to bow out of their projects. Tried out several possibilities, found two amazing new translators, and now we're on our way to finishing these series off!" A later reply notified readers that the translation is on hiatus, with Mr. Simon expressing a desire to get the series back into production at some later date. Notes Further reading External links Translucent volumes 1, 2, and 3 at Dark Horse Comics Category:Dark Horse Comics titles Category:Media Factory manga Category:Romance anime and manga Category:School life in anime and manga Category:Seinen manga Category:Supernatural anime and manga
2024-01-10T01:27:15.642919
https://example.com/article/5529
1. Field of the Invention The present invention relates in general to the field of information handling system power control, and more particularly to a method and system for feed forward control loop optimization of processor power. 2. Description of the Related Art As the value and use of information continues to increase, individuals and businesses seek additional ways to process and store information. One option available to users is information handling systems. An information handling system generally processes, compiles, stores, and/or communicates information or data for business, personal, or other purposes thereby allowing users to take advantage of the value of the information. Because technology and information handling needs and requirements vary between different users or applications, information handling systems may also vary regarding what information is handled, how the information is handled, how much information is processed, stored, or communicated, and how quickly and efficiently the information may be processed, stored, or communicated. The variations in information handling systems allow for information handling systems to be general or configured for a specific user or specific use such as financial transaction processing, airline reservations, enterprise data storage, or global communications. In addition, information handling systems may include a variety of hardware and software components that may be configured to process, store, and communicate information and may include one or more computer systems, data storage systems, and networking systems. One reason that information handling systems have grown in capability over time is that the microprocessors that run as central processing units (CPUs) for information handling systems have packed an increasing number of circuits in a given space. Microprocessors with greater numbers of circuits have greater processing power to perform information processing but also have greater power demands and greater variations in power demand over time. For instance, present state-of-the-art microprocessors have relatively large load steps, such as 80 amps at rates of 400 amps per microsecond, which require power supplies to have relatively low output impedance. Future microprocessors will likely have even greater step loads and higher slew rates as microprocessor circuit density continues to increase. Further, as microprocessors grow more complex, the tolerances for power supply processor voltage requirements will narrow so that power supplies must respond to changes in microprocessor power use even more rapidly and with greater accuracy, which will result in increasingly expensive power supply solutions. One solution for control of power supplied to a microprocessor is to use feedback of voltage and current provided by the power supply with conventional loop optimization techniques and sufficient output capacitance to meet the microprocessor current and voltage requirements. One difficulty with this solution is that, as the current slew rates expected of the power supply increase and the tolerances of the microprocessor tighten, the number and/or size of output capacitance increases to keep processor voltage within desired tolerances. The capacitors are added at the output of the power supply and the microprocessor to supply current rapidly enough to maintain voltage at the microprocessor within the desired tolerances. However, the addition of capacitance to meet slew rate and tolerance requirements generally increases the size and expense of the power supply. Increased processor current slew rates and narrowing voltage tolerance requirements of present and future microprocessors will result in expensive and large capacitance-based solutions to ensure proper operation of information handling systems.
2023-11-21T01:27:15.642919
https://example.com/article/4686
The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase. DNA double-strand break repair through the RAD52 homologous recombination pathway in the yeast Saccharomyces cerevisiae requires, among others, the RAD51, RAD52, and RAD54 genes. The biological importance of homologous recombination is underscored by the conservation of the RAD52 pathway from fungi to humans. The critical roles of the RAD52 group proteins in the early steps of recombination, the search for DNA homology and strand exchange, are now becoming apparent. Here, we report the purification of the human Rad54 protein. We showed that human Rad54 has ATPase activity that is absolutely dependent on double-stranded DNA. Unexpectedly, the ATPase activity appeared not absolutely required for the DNA repair function of human Rad54 in vivo. Despite the presence of amino acid sequence motifs that are conserved in a large family of DNA helicases, no helicase activity of human Rad54 was observed on a variety of different DNA substrates. Possible functions of human Rad54 in homologous recombination that couple the energy gained from ATP hydrolysis to translocation along DNA, rather than disruption of base pairing, are discussed.
2024-03-29T01:27:15.642919
https://example.com/article/5841
Q: cgroups memory 16GB ceiling I am trying to use cgroups to limit memory usage of user processes on servers with a large amount of ram (128 GB or more). What we want to achieve is to reserve about 6GB of ram for OS and root processes and leave the rest to users. We want to make sure we have free memory at all times and we don't want servers to swap aggressively. This works fine if limit is set low enough ( < 16GB ). User processes are correctly assigned to the right cgroup by cgred and once the limit is reached, oom will terminate memory hungry processes. The issue rise when we set the limit higher. Then, the server will start swapping if a process is using more than 16G of ram even if memory usage is still well below the limit and there is plenty of ram is available. Is there any setting or some sort of maximum that would limit the amount of memory we can grant access to under cgroups? Here is more info: I use the following code to simulate user processes eating memory. The code keep track of allocated memory in a linked list so the memory is used and accessible from within the program, as opposed to just being reserved with malloc (and overwrite pointer each time). /* Content of grabram.c */ #include <stdlib.h> #include <stdio.h> #include <sys/types.h> #include <sys/stat.h> #include <fcntl.h> #include <unistd.h> #include <string.h> struct testlink { void *ram; struct testlink *next; }; int main (int argc, char *argv[]) { int block=8192; char buf[block]; void *ram=NULL; FILE *frandom; int nbproc,i; pid_t pID; struct testlink *pstart, *pcurr, *pnew; if (argc < 2) { //nbproc = 1 by default nbproc=1; } else { if (sscanf(argv[1], "%d", &nbproc) != 1) { /* it is an error */ printf("Failed to set number of child processes\n"); return -1; } } // open /dev/urandom for reading frandom = fopen("/dev/urandom", "r"); if ( frandom == NULL ) { printf("I can't open /dev/urandom, giving up\n"); return -1; } fread(&buf, block, 1, frandom); if ( ferror(frandom) ) { // we read less than 1 byte, get out of the loop printf("Error reading from urandom\n"); return -1; } fclose (frandom); // pID=0 => child pID <0 => error, pID > 0 => parent for (i=1; i<nbproc; i++){ pID = fork(); // break out of the loop if a child if (pID == 0) break; // exit if fork fails if (pID < 0) { printf("fork() failed, dying \n"); return -1; } } pstart = (struct testlink*)malloc(sizeof(struct testlink)); pstart->ram=NULL; pstart->next=NULL; pcurr = pstart; while ( 1==1 ) { ram = (void *)malloc(block); if (ram == NULL) { printf("can't allocate memory\n"); return -1; } memcpy(ram, &buf, block); // store allocated blocks of ram in a linked list // so no one think we are not using them pcurr->ram = ram; pnew = (struct testlink*)malloc(sizeof(struct testlink)); pnew->ram=NULL; pnew->next=NULL; pcurr->next=pnew; pcurr=pnew; } return 0; } So far i tried setting the following tuneables: vm.overcommit_memory vm.overcommit_ratio vm.swappiness vm.dirty_ratio vm.dirty_background_ratio vm.vfs_cache_pressure None of these sysctl settings seemed to have any effect. The server will start swapping after my code above go above the 16GB barrier even if swappiness is set to 0, overcommit is disabled, etc. I even tried to turn swap off to no avail. Even with no swap, kswapd is still triggered and performance decreases. Finally, the relevant content of cgconfig.conf file mount { cpuset = /cgroup/computenodes; cpu = /cgroup/computenodes; memory = /cgroup/computenodes; } #limit = 120G group computenodes { # set memory.memsw the same so users can't use swap memory { memory.limit_in_bytes = 120G; memory.memsw.limit_in_bytes = 120G; memory.swappiness = 0; # memory.use_hierarchy = 1; } # No alternate memory nodes if the system is not NUMA # On computenodes use all available cores cpuset { cpuset.mems="0"; cpuset.cpus="0-47"; } } Finally, we use Centos 6, kernel 2.6.32. Thanks A: **Note: Undeleting for posterity ** Your problem is here # No alternate memory nodes if the system is not NUMA # On computenodes use all available cores cpuset { cpuset.mems="0"; cpuset.cpus="0-47"; } } You are only ever using one node of memory. You need to set this to use all nodes of memory. I also think the below applies too, and you'll see the problem still unless you know about the below. So leaving in for posterity. This issue basically boils down to the hardware being used. The kernel has a heuristic to determine the value of this switch. This alters how the kernel determines memory pressure on a NUMA system. zone_reclaim_mode: Zone_reclaim_mode allows someone to set more or less aggressive approaches to reclaim memory when a zone runs out of memory. If it is set to zero then no zone reclaim occurs. Allocations will be satisfied from other zones / nodes in the system. This is value ORed together of 1 = Zone reclaim on 2 = Zone reclaim writes dirty pages out 4 = Zone reclaim swaps pages zone_reclaim_mode is set during bootup to 1 if it is determined that pages from remote zones will cause a measurable performance reduction. The page allocator will then reclaim easily reusable pages (those page cache pages that are currently not used) before allocating off node pages. It may be beneficial to switch off zone reclaim if the system is used for a file server and all of memory should be used for caching files from disk. In that case the caching effect is more important than data locality. Allowing zone reclaim to write out pages stops processes that are writing large amounts of data from dirtying pages on other nodes. Zone reclaim will write out dirty pages if a zone fills up and so effectively throttle the process. This may decrease the performance of a single process since it cannot use all of system memory to buffer the outgoing writes anymore but it preserve the memory on other nodes so that the performance of other processes running on other nodes will not be affected. Allowing regular swap effectively restricts allocations to the local node unless explicitly overridden by memory policies or cpuset configurations. To give you some idea here of what is going on, memory is broken up into zones, this is specifically useful on NUMA systems which RAM is tied to specific CPUs. In these hosts memory locality can be an important factor in performance. If for example memory banks 1 and 2 are assigned to physical CPU 0, CPU 1 can access this but at the cost of locking that RAM from CPU 0, which causes a performance degradation. On linux, the zoning reflects the NUMA layout of the physical machine. Each zone is 16GB in size. What is happening at the moment with zone reclaim on is the kernel is opting to reclaim (write dirty pages to disk, evict file cache, swap out memory) in a full zone (16 GB) rather than permit the process to allocate memory in another zone (which will impact performance on that CPU. This is why you notice swapping after 16GB. If you switch off this value this should alter the behaviour of the kernel not aggressively reclaim zone data and instead allocate from another node. Try switching off zone_reclaim_mode by running sysctl -w vm.zone_reclaim_mode=0 on your system and then re-running your test. Note, long running high memory processes running on a configuration like this with zone_reclaim_mode off will become increasingly expensive over time. If you allow lots of disparate processes running on many different CPUs all using lots of memory to use any node with free pages, you can effectively render the performance of the host to something akin to it only having 1 physical CPU.
2023-08-07T01:27:15.642919
https://example.com/article/6150
Tag: M255 Module materials for Developing concurrent distributed systems (M362) just arrived and I’m a little daunted. I completed the now discontinued Object-oriented programming with Java (M255) in 2008 so I think it would be wise to read over the module notes – thankfully I still have them as PDF. With ten years remaining in my contract and the government’s intentions unclear, I’ve decided to get my finger out and focus on completing the BSc (Honours) Computing and IT (B62). It can use 120 points from four completed modules – M150, T175, MST121 and M255 as well as 30 points from MS221, which I have already started. At level two I’m taking two courses on top of MS221 which I intend to study concurrently, so as to be half way through by the end of next year:
2023-11-08T01:27:15.642919
https://example.com/article/6748
David Cho (director) Cho Sung-kyu (born March 3, 1969), also known as David Cho, is a South Korean film producer, executive producer, director and screenwriter. Apart from producing and investing in numerous films as CEO of Sponge Entertainment, Cho wrote and directed Second Half (2010), The Heaven Is Only Open to the Single! (2012), The Winter of the Year Was Warm (2012), Santa Barbara (2014), and Planck Constant (2015). Career Born in 1969, David Cho first studied History at Yonsei University, then changed his major and graduated with a degree in Mass Communication. He published the film magazine Nega in 1997, then founded the production/distribution company Sponge Entertainment in 2000. As owner and president of Sponge Entertainment, he produced and invested in numerous Korean arthouse films, such as Jang Hoon's Rough Cut, Lee Yoon-ki's My Dear Enemy, Kim Ki-duk's Dream, and E J-yong's Actresses. In 2010, Cho made his directorial debut with Second Half starring Ryu Seung-soo and Esom, about a beleaguered film producer who meets a waitress in a seaside town and suspects she may be his daughter from a long-ago one-night stand. Cho's second film The Heaven Is Only Open to the Single! (2012) is about a famous actress (played by Choi Yoon-so) who's just been publicly dumped by a comedian and banned by her agency from dating, and an unknown indie musician rejected by a matchmaking service who falls for her onscreen while composing the soundtrack for her film. With a cast of real-life Hongdae musicians led by Lee Neung-ryong of the band Sister's Barbershop, Cho interspersed live musical performances into the film. Also released in 2012, Cho's third film The Winter of the Year Was Warm focuses on a Seoul-based film producer/director who's fond of the laidback atmosphere in the coastal city of Gangneung, and a nurse who lives in Gangneung but yearns for the cultural life of Seoul; after meeting through a common friend, they each agree to set aside one room in their respective apartments for the other to stay at on weekends, but in sharing their homes with each other, they eventually start to develop a strange sort of in absentia intimacy. The film drew critical acclaim when it premiered at the 17th Busan International Film Festival and as it traveled the international film festival circuit, with particular praise for Cho's nuanced script and use of lighting, as well as Kim Tae-woo and Ye Ji-won's naturalistic acting. In 2014, Cho cast Lee Sang-yoon and Yoon Jin-seo in his fourth film Santa Barbara (2014). They played, respectively, a music director and a creative director at an advertising agency who fall in love while collaborating on a commercial; after their break-up, they are forced to work together again on a project in Santa Barbara, California, the location of their dream winery tour when they were still a couple. In a departure from his previous films which blended finely-observed realism and light romance, Cho's Planck Constant (2015) contained more surrealistic and fantasy elements, with Kim Jae-wook playing a man who gets his hair cut 1 millimeter a day, while writing a screenplay in his head. Filmography As director Second Half (2010) (also credited as voice cameo) The Heaven Is Only Open to the Single! (2012) (also credited in bit part) The Winter of the Year Was Warm (2012) Santa Barbara (2014) Planck Constant (2015) (also credited as music director) Life Is but an Empty Dream (2015) Two Rooms, Two Nights (2015) As screenwriter Second Half (2010) The Heaven Is Only Open to the Single! (2012) The Winter of the Year Was Warm (2012) Santa Barbara (2014) Planck Constant (2015) As producer Geochilmaru: The Showdown (2005) Tokyo! (2008) Planck Constant (2015) As executive producer Public Toilet (2002) Last Scene (2005) On the Road, Two (documentary, 2006) The Wonder Years (2007) For Eternal Hearts (2007) Beautiful (2008) Rough Cut (2008) My Dear Enemy (2008) Dream (2008) Iri (2008) Oishii Man (2009) A Million (2009) (also credited with original idea) The Executioner (2009) Looking for My Wife (2010) Second Half (2010) The Winter of the Year Was Warm (2012) As investor April Snow (2005) Ad-lib Night (2006) Chongqing (2008) Antique (2008) Portrait of a Beauty (2008) Hello, Schoolgirl (2008) Romantic Island (2008) A Frozen Flower (2008) The Naked Kitchen (2009) The Scam (2009) My Girlfriend Is an Agent (2009) Running Turtle (2009) The Case of Itaewon Homicide (2009) City of Fathers (2009) The Executioner (2009) Actresses (2009) Vegetarian (2010) Looking for My Wife (2010) No Doubt (2010) Super Monkey Returns (2011) Head (2011) Venus in Furs (2012) Tumbleweed (2013) References External links Category:1969 births Category:Living people Category:South Korean film producers Category:South Korean film directors Category:South Korean screenwriters Category:Yonsei University alumni
2024-06-03T01:27:15.642919
https://example.com/article/6958
import { useBackend } from '../../backend'; import { Button, Flex, NoticeBox } from '../../components'; /** * This component by expects the following fields to be returned * from ui_data: * * - siliconUser: boolean * - locked: boolean * - normallyLocked: boolean * * And expects the following ui_act action to be implemented: * * - lock - for toggling the lock as a silicon user. * * All props can be redefined if you want custom behavior, but * it's preferred to stick to defaults. */ export const InterfaceLockNoticeBox = (props, context) => { const { act, data } = useBackend(context); const { siliconUser = data.siliconUser, locked = data.locked, normallyLocked = data.normallyLocked, onLockStatusChange = () => act('lock'), accessText = 'an ID card', } = props; // For silicon users if (siliconUser) { return ( <NoticeBox color={siliconUser && 'grey'}> <Flex align="center"> <Flex.Item> Interface lock status: </Flex.Item> <Flex.Item grow="1" /> <Flex.Item> <Button m="0" color={normallyLocked ? 'red' : 'green'} icon={normallyLocked ? 'lock' : 'unlock'} content={normallyLocked ? 'Locked' : 'Unlocked'} onClick={() => { if (onLockStatusChange) { onLockStatusChange(!locked); } }} /> </Flex.Item> </Flex> </NoticeBox> ); } // For everyone else return ( <NoticeBox> Swipe {accessText}{' '} to {locked ? 'unlock' : 'lock'} this interface. </NoticeBox> ); };
2024-07-20T01:27:15.642919
https://example.com/article/6561
Safety and efficacy of vaginal hysterectomy in the large uterus with the LigaSure bipolar diathermy system. This study was undertaken to assess safety and efficacy of vaginal hysterectomy in case of large uterine size (> or = 250 g) using the LigaSure bipolar diathermy (Valleylab, Boulder, CO). In a retrospective study, medical records of 102 patients who underwent vaginal hysterectomy and who had uterine weight (evaluated after surgery) 250 g or greater were reviewed. All hysterectomies were performed by using the LigaSure vessel sealing system to secure vascular pedicles (uterosacral-cardinal, uterine and ovarian and round ligaments). Of the 102 vaginal hysterectomies, 99 were successfully performed (97.1%; 95% confidence interval, 91.6-99.4%), whereas a conversion from the vaginal to the abdominal route was required in 3 cases. The median uterine weight was 455 g (range, 241-1913 g). The weight of the largest uterus successfully removed vaginally was 1600 g, without intraoperative and postoperative complications. The median operative time was 50 minutes (range, 25-50 minutes). The current study confirms that very large uterine volume does not represent a real obstacle to perform vaginal hysterectomy and that results in a safe and effective technique in cases of uterine weight 250 g or greater.
2023-09-19T01:27:15.642919
https://example.com/article/3368
Q: Filter using IndexOf() returning blank results I'm running a filter on a list that looks like this. if (!(this.state.filter && c.lastName && c.lastName.toLowerCase().indexOf(this.state.filter) == -1)) { return true } else if (!(this.state.filter && c.firstName && c.firstName.toLowerCase().indexOf(this.state.filter) == -1)){ return true } else if (!(this.state.filter && name && name.toLowerCase().indexOf(this.state.filter) == -1)){ return true } else if (!(this.state.filter && c.email && c.email.toLowerCase().indexOf(this.state.filter) == -1)){ return true } else { return false } But, because null, 0, and '' all match that query, every filter returns everyone who doesn't have either a first name, last name, or email. I know I could separate this by having separate filter fields for each item, but it seems like there must be a better way to not match the empty string? A: You need to check that your property is of type string, so instead of ... && c.lastName && ... it would need: ... && typeof c.lastName === 'string' && ... To condense it all a bit, you could do: return !this.state.filter || [c.lastName, c.firstName, name, c.email].some( value => typeof value === 'string' && value.toLowerCase().includes(this.state.filter) ); var test = { state: {}, test: function(c, name) { return !this.state.filter || [c.lastName, c.firstName, name, c.email].some( value => typeof value === 'string' && value.toLowerCase().includes(this.state.filter) ); } } test.state.filter = 'abcd'; var res = test.test({ lastName: 'Mr abc', firstName: 'Helen' }, ''); console.log(res); res = test.test({ lastName: 'Mr abcd', firstName: 'Helen' }, 'John'); console.log(res); res = test.test({ lastName: 0, firstName: null }, NaN); console.log(res);
2023-09-15T01:27:15.642919
https://example.com/article/7709
Q: Reference column with assigned variable in data.table I want to convert a column in my data table from factor to numeric values, but the catch is I am using a "dictionary" (a list) so I want to be able to refer to the column variable via the "dictionary": #my "dictionary" outcomes <- list("heart attack"="Hospital 30-Day Death (Mortality) Rates from Heart Attack", "heart failure"="Number of Patients - Hospital 30-Day Death (Mortality) Rates from Heart Failure", "pneumonia"="Number of Patients - Hospital 30-Day Death (Mortality) Rates from Pneumonia") #named variable outcome <- outcomes[["heart attack"]] #conversion function as.numeric.factor <- function(x) {as.numeric(levels(x))[x]} #convert my data table column from factor to numeric DT[, outcome := as.numeric.factor(outcome)] DT[, outcome := as.numeric.factor(outcome)] is ideally what I want to do, but I know I can't just stick a named variable outcome in there and hope data table will know I am referring to the column that has the value of outcome. Sorry I'm quite new to data table and I am a bit confused about how to deal with named variables in general when referencing columns. A: Using tidyverse approach: library(tidyverse) Your_df_mod <- Your_df %>% mutate_at(.vars=outcome,.funs=funs(as.numeric(.)))
2023-09-07T01:27:15.642919
https://example.com/article/1048
![Hasan Minto](jceh_32_105_001_f01){#F1} ![Priya Morjaria](jceh_32_105_001_f02){#F2} ![Kovin Naidoo](jceh_32_105_001_f03){#F3} **Myopia is a growing epidemic that will affect half the global population by 2050, and its complications can cause irreversible visual loss.** ![Although a simple pair of spectacles will correct visual loss, they cannot prevent the blinding consequences of high myopia. CAMBODIA](jceh_32_105_001_f04){#F4} People with myopia -- or short-sightedness -- are unable to see objects that are far away, but can see near objects clearly. This affects every aspect of their life, including education, employment and safety. Over 2 billion people worldwide are estimated to have myopia, defined as ≤ −0.5 dioptres (D). Of these, around 10% have high myopia, defined as ≤ −5 D.[@B1],[@B2] People with high myopia are at increased risk of potentially blinding eye conditions such as macular degeneration, retinal detachment, open-angle glaucoma and cataract. Myopia is already a major public health challenge. In 2015, an estimated 480 million people worldwide were considered blind or visually impaired because they did not have access to spectacles,[@B3] making myopia the leading cause of visual impairment and blindness worldwide. By 2050,[@B2] myopia is expected to affect 5 billion people, which is half of the projected global population at that time. This will place an even greater burden on health services to provide spectacles and to prevent and manage the conditions associated with high myopia. Uncorrected myopia, together with macular degeneration, were estimated to be responsible for a US \$250 billion loss in global productivity in 2015.[@B4] As myopia becomes more common, this is set to rise. Making a difference {#s1} =================== Meeting the need for myopia correction, and slowing down or reversing the global increase in myopia, requires that we address service delivery, access to affordable correction, health promotion, advocacy and policy change at both national and global level. Collaboration between government, civil society, researchers, innovators and the private sector -- rather than competition -- is essential. The International Myopia Institute (**[www.myopiainstitute.org](http://www.myopiainstitute.org)**) is one example of a collaboration that is bringing about consensus on key issues such as definitions, clinical guidelines, clinical trials, and how to involve industry. We need more coalitions around education, service delivery, health promotion, advocacy, and research. Coalitions and partnerships will allow us to scale up efforts and make the impact that is needed. **Governments** must take the lead in addressing the increase in myopia. National policies must address child eye health specifically; e.g., by making eye examinations compulsory for children at school entry and making it easier to import (or manufacture) products and drugs that can help to control myopia progression. Healthy school initiatives should include spending time outdoors as this has been shown to delay the onset of myopia (which means that children would be less likely to develop high myopia). Schools provide an ideal point of contact between health and refractive error services for children and their parents; e.g., by hosting health promotion activities that encourage parents to take children for an eye examination and to get the appropriate correction for them. **The private sector** must support all components of a comprehensive approach, be it service delivery, human resource development, advocacy, policy change, research or health promotion. Industry should drive the agenda to create advanced, yet affordable, myopia control products, whether contact lenses or spectacle lenses, and make them accessible for all. **Non-governmental organisations** (NGOs) involved in eye health are key to supporting the comprehensive approach by prioritising advocacy and policy change. NGOs must support the scaling up of services rather than see themselves as a replacement for either government or practitioners. They play a crucial role and can adopt a more active approach to influencing change. It is vital that myopia is included in World Health Organization, UNICEF, and other broader development agendas, as myopia has the potential to slow the education of our children and thus hamper efforts to achieve the United Nations\' Sustainable Development Goals (**[www.un.org/sustainabledevelopment](http://www.un.org/sustainabledevelopment)**). ![Myopia and high myopia are rapidly increasing worldwide](jceh_32_105_001_f05){#F5} **Optometrists, ophthalmologists and allied eye health professionals** can all play a role in reducing the detrimental impact on quality of life due to myopia. Health promotion and education need to become a critical component of patient management. Eye care professionals will also need to support efforts to change government policy and use their connection in the community to become advocates for these changes. This issue discusses evidence for the myopia epidemic and the risks of high myopia along with the interventions available to reduce the risk of myopia and slow down its progression. While there are clinical and optical interventions to slow down the progression of myopia, lifestyle and environmental changes (less near work and more time outside) are arguably of greater importance as it protects children against the onset of myopia. We have included practical tips on how to detect, refer, diagnose and manage myopia. A list of data that are required for monitoring myopia management are described to encourage clinicians to begin monitoring myopia progression in patients. ###### School eye health ![School eye health programmes form an integral part of the global effort to address myopia. Read our 2017 issue on School Eye Health here: **[www.cehjournal.org/school-eye-health](https://www.cehjournal.org/school-eye-health)**](jceh_32_105_001_f06){#F6}
2023-10-22T01:27:15.642919
https://example.com/article/6969
I do believe most of the commentary here on this thread is getting it wrong. We do not believe that anybody is entitled to success in this country. But we do believe in opportunity. We believe in a country where hard work pays off and responsibilities are rewarded and everybody is getting a fair shot and everybody’s doing their fair share. As a matter of fact, Obama is right here. The problem lies not with what he said, but what he believes. He actually espoused what most conservatives believe. However, his actions are the opposite of what words come out of his mouth. "Everybody's doing their fair share?" What about the huge expansion of welfare rolls since he took office? "Everybody is getting a fair shot?" How do you explain affirmative action policies and the biases of your justice department? It's not what he said that is offensive here, it's how contrary what he said is from what he believes. This country succeeds because there is no system of self serving avarice that seeks to stack the system so only winners excel. NO, this country succeeds because of the American spirit fiercely Independence and the “Ambition” that brings out the best work ethic in the world and enables any person to move from being dirt poor to the middle class or with unbelievable goals to become among the richest. There is nothing that gets in the way of the American Spirit to Achieve. 63 posted on 10/05/2012 10:58:01 AM PDT by Vendome (Don't take life so seriously, you won't live through it anyway) I have always believed that Obama’s world view is that of a sophomore university student who has taken a few sociology classes and think they have the answers to all the world's problems. Of course, in his case, he came to that point probably already having had a fair amount of indoctrination into the philosophy of his liberal parents, and uncle ‘Frank’. The bottom line is that in the America that most of us remember and love, it is possible for anyone to become one of those ‘few at the top’. The reality is that when people reaching for the top don't make it all the way, they wind up populating the middle class. That's a good thing, but Obama doesn't understand it. His world view is, like so many on the left, one in which there are only Tiny Tims and Scrooges. “....And his completely, brain-dead supporters go along with this jackass without even realizing the stupidity of the argument they’ve bought into....” Right on!! Just another classic example of just how debilitating the disease of liberalism is on the human mind. It rots out the ability to think objectively and logically. Basically turning them into zombies, mentally speaking. It has no known cure. The sooner this is realized, the sooner the solution will be realized. There are not enough padded celss for all of em though. That just reads like a weird comment.No one is entitled to a job. Check. No one is entitled to handouts. Check. No one is entitled to this or that freebie. Check. But "success" is something that someone achieves. Something they achieve by inspiration, or perspiration, or some times just by good fortune. It is nothing that is thrust into their hands... Now the Pres wants to be overseer of what he perceives to be acceptable measures of a person's 'success'. Marxists are all the same. Useless, covetous, haters and dividers. A pox on all of them. I don’t care what he says he believes, the only people he’s helping are the people who support him. What has he done that’s helped the middle class? There are fewer middle class jobs, higher taxes, and rising costs. These are not helping the middle class, which pays the taxes so that Obama has money to hand out to his supporters. 72 posted on 10/05/2012 11:42:32 AM PDT by popdonnelly (The first priority is get Obama out of the White House.) Who the bleep is this “WE “ doing all the “ believing “—————show of hands please. Sounds like a tent meeting of a bunch of retread marxists. Do the Obamaphonies realise he expects them to “share” some effort to pay up for their phones? It wouldn’t make a difference. They are more concerned that their “messiah” is being attacked and maligned than they are in seeing reason and fact. This is one case where they’ll have to “find out the stove is hot” all by themselves. so it grows from the middle class, built not the top down, last time I checked it was the top rich guys who made the jobs. Obama is so far out there radical that he has no clue about life, the real world, the economy or even how to create jobs, hell he has no idea about the constitution due ot his radical teachings and brainwashing. And we have this radical left wing man because of the media lying all the time Everyone “is entitled to success,” IF they earn it. NOBODY is guaranteed success. But, in Obamaworld, IF you earn success, and begin to reap the rewards of that success, you ARE NOT “entitled” to those rewards; that wouldn’t be “fair,” because “You didn’t build that.” In Obamaworld, you can latch onto all the opportunities you can find, take all the risks you can stand, put out all of the effort you can muster, and reap all the rewards you’re due, EXCEPT that WHEN you do so, there’ll be Uncle Sam at your door with his hand out intent on keeping things “fair.” Obama has NO problem with people building things; he has HUGE issues with those same people KEEPING very much of the reward they earned in the process. Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.
2023-10-13T01:27:15.642919
https://example.com/article/9347
8 - 12. Solve -2*n + 9 = -5*o, z*o = k*n - 3*n - 10 for o. -1 Suppose 0 = 24*u - 8 - 64. Solve u*k + 4*f - 25 - 1 = 0, 2*k + 5*f = 29 for k. 2 Let p(v) = v - 8. Let j be p(11). Let k(i) = -i**2 - 12*i - 14. Let m be k(-10). Solve 0*n + 2 = -r + 5*n, 3*n = -j*r - m for r. -2 Let o(g) = g**3 + 6*g**2 - 8*g + 5. Let n be o(-7). Suppose b - 1 = 4. Suppose b*f - 5*s - 40 = 0, 3*f + 2*s + 0 = 9. Solve 4*i = w + i + n, w + f*i = 12 for w. -3 Let q be (-1 + 6/4)/((-1)/(-2)). Solve 2*i + 3*l = 1 + q, 5*i = -4*l + 5 for i. 1 Suppose q - 26 = -14. Suppose q = 6*x - 2*x. Solve -4*n + 13 = 5*d, -4*n + 18 = x*d - 5*n for d. 5 Suppose 15*k = 18*k + 120. Let t be -9*(3 + (k/12)/1). Solve r = -v, 4*v + 1 = -0*r - t*r for v. -1 Let r = 556 - 551. Solve 4*n + r = l, 7*l - 2*l = -2*n + 25 for l. 5 Suppose 2*j + j + 4 = 2*w, j = -4*w + 8. Let g(k) = k**3 - 2*k**2 + 2*k - 1. Let v be g(w). Solve -4*a - 10 = 3*c, -5*a = -6*a - v*c + 2 for a. -4 Suppose 0*a = a - 4. Suppose -4*x - r = -27, -a*x + 2*r + 12 = -6. Suppose x*i = i. Solve i = 4*q - 3*c + 8, 2*q - 7*q = -5*c + 5 for q. -5 Suppose -13*c + 14*c - 11 = 0. Solve 4*j = 2*f - 12, 3*f + 6*j - c = 5*j for f. 4 Suppose 0 = 7*f - 197 + 71. Solve 3*m = -v - 4, 4*v = 4*m + 50 - f for m. -3 Let s(b) = 4*b**2 + 5*b + 6. Let p be s(-2). Suppose 2*x - 8 = -4*w - 0*x, x - p = -4*w. Solve -n - 20 = 2*k + w*n, 0 = -2*k - 3*n - 16 for k. -5 Let d be (1*(4 - 4))/(-2). Let u be 7*(d/4 + 1). Solve u*p - 16 = 4*i + 2*p, 0 = -2*i - 2*p - 8 for i. -4 Let i(d) = 2*d - 10. Let a be i(7). Suppose a*b = -2*k + 28, -5*k - 2*b = -2*k - 22. Solve -k*c = -5*c + h + 2, -2*c - 2*h = -12 for c. 4 Let t = -473 + 477. Solve -t*r + 3*m = -1, -2*m - 1 = 3*r + 11 for r. -2 Suppose -5*z - 23 = -3*m - 93, 2*z - 54 = -4*m. Let n = -12 + z. Solve -2*o - 2*f + n = 1, 2*f = o - 5 for o. 3 Suppose -10 = 2*o, 5*b + 97 = 2*o + 537. Let l = b + -81. Solve 13 = -5*c - 7, 0 = -5*n - l*c for n. 4 Let x = -31 - -33. Suppose -7*c = -5*c - 2, 2*f = x*c + 4. Solve -q + 6 = -2*s, f*q + 4*s = -16 - 6 for q. -2 Let k(g) = g**3 - 6*g**2 + 7*g - 7. Suppose 2*l + 20 = 6*l. Let u be k(l). Solve u*j = 2*x, 0 = 2*x - j + 6*j for x. 0 Suppose 4*i = 2*a - 11 - 7, -3*a + 23 = -2*i. Let j be -1*a/(-3 - -2). Solve -3*p - 8 - j = 0, -3*b = 4*p + 8 for b. 4 Let y(j) = -j**2 + 5*j + 6. Let i be y(-3). Let l = i - -25. Suppose 6*u + 3 = l*u. Solve -5*a + 3*h = -22, -4*a - 3*h - 1 = u for a. 2 Suppose -71 = -2*o + w - 6, 2*w = -4*o + 150. Suppose -133*l + 1165 = -940 + 243. Solve -4*k = 2*a + o - 9, -4*k = -2*a + l for k. -5 Let h be 2/((-16)/(-7) + -2) - 3. Let b = 11 - 7. Suppose 4*s - 4 + 0 = -b*o, -4*s = 2*o - h. Solve 3*m - 5*l + 15 + s = 0, m = 4*l - 17 for m. 3 Let j(h) = -2*h - 21. Let g be j(-9). Let n be 1 + g + 7 - 3. Solve -3*c = n*l + l + 3, -7 = 4*c + l for c. -2 Let p be 2/((8/(-14))/(90/(-105))). Solve -b + 3*r = -0*b - p, 4*b = r - 10 for b. -3 Suppose -2*s = -32 + 4. Let a = s - 11. Solve 0 = c + 2*c + w - 3, 3*w - 3 = -a*c for c. 1 Suppose 0 = m + 5, -2*p = 4*m - 8*m - 28. Let y be (-3)/(396/(-60) - -6). Solve y*u - 2*w = 11 + 2, 0 = -p*u + w + 11 for u. 3 Suppose 14 + 41 = 5*s - r, 0 = -4*s - 2*r + 44. Solve 0 = 3*u + 5*y - s, -u - 4*u + 1 = 4*y for u. -3 Suppose -33*j + 32*j - 3 = -5*c, 3*c - 6 = 0. Solve 3*x - 4*z = j, -4*x - z - 18 = -8*x for x. 5 Suppose 0 - 13 = 2*g - 5*l, 4*g - l - 19 = 0. Suppose 0 = -3*f - m + 1 + g, -2*f - 5*m = 4. Solve 3*o + c = 7*o - 24, -3*o + f = 3*c for o. 5 Let j(x) = x**2 + 2*x - 4. Let q be j(-4). Suppose -q*v - v = -4*u - 17, -4*v + 16 = -2*u. Solve -5*z + 3*z - u*l + 4 = 0, -4*z + 15 = -3*l for z. 3 Let r be (9 + -6 - -9) + -7. Solve -2*p = -5*s + 17, r*s = 2*p - 5*p + 37 for p. 4 Let j = -633 - -655. Let d(w) = -w**2 - 8*w + 7. Let s be d(-5). Let b = j - s. Solve b = 2*r + 3*p - 15, 4*p - 3 = 2*r + 3 for r. 3 Let u be (-5 + 4)*4*5/(-4). Solve -4*y - u*d + 21 = 0, -y + 13 = y + 5*d for y. 4 Suppose 4*c - 4*o - 21 = 3*c, 0 = -c - 4*o - 11. Suppose t - 4*t = c*q - 21, 3*q - 33 = 5*t. Solve -2*n = -4*a + 20, -4*n + a - q - 13 = 0 for n. -4 Let r(y) = -2*y**2 + 6*y + 5. Let g be r(3). Solve -n = -g*q, 2*q - 13 = 3*n - 0*q for n. -5 Let t = 24 + -22. Suppose t*w - 2*r = 8, 0 = -w + 2*r + 3*r + 12. Solve 4*u + 4*j = -32 - 8, 2*u - w*j = 0 for u. -5 Suppose -2*m = -5*z + 25, 8*m + 5 = z + 4*m. Solve -4*p + z*t - 19 = -3*p, 5*p + 5*t = -5 for p. -4 Let k = -6 - -9. Let g be -5*(k - 88/20). Let v = g - 6. Solve -2*b - v = -3*w + 9, 15 = 2*w - 3*b for w. 0 Let l(n) = n**3 + 8*n**2 + 6*n - 5. Let b be l(-7). Let y(d) = -8*d - 13. Let o be y(-2). Solve 5*a - 4 = b*k + 7, o = -2*k - 3*a for k. -3 Suppose -4*x + 3 = -9. Suppose -x*p = -0*p - 144. Suppose j - p = 3*l - 5*l, l = j + 30. Solve u + l = -4*s - 2*u, 9 = -s - 2*u for s. -5 Let n(q) = -q**3 + 11*q**2 - 3*q + 7. Let c be n(11). Suppose -12*w = -15*w + 132. Let z = w + c. Solve 2*p + 18 = -4*u, -p + z = p - 5*u for p. -1 Suppose -5*g = 2 + 3. Let m = 1 - g. Suppose -2*l + 24 = m. Solve 3*p - l = -t, 2*t + 0 = 3*p - 14 for t. -1 Let r(o) = o**3 + 6*o**2 - 6*o + 11. Suppose 2*h = 2*q - 8 - 8, 5*h = q - 36. Let u be r(h). Solve 2*l - u*z - 16 = -l, -5*z - 5 = 0 for l. 4 Suppose -21*n + 18*n + 9 = 0. Suppose 45 = n*u + 3*c, 3*u = 2*c + 3*c + 29. Solve -3 + 10 = -5*v + p, -5*v = -4*p + u for v. -1 Let k be (-1 + (14 - 4))*(-6)/(-27). Solve -4*n + s - 17 = 0, 4*s - 1 = -3*n + k*s for n. -3 Let t = 721 - 718. Solve -2*z - h + 4 = 0, -5*h = -2*z - t*z - 5 for z. 1 Let p(c) = -4*c - 24. Let d be p(-13). Suppose -2*a = -4*u + d, u - 4*a - 26 = -5. Solve -4*i + 2 + 20 = -2*o, u = -3*o - i for o. -3 Let k be -9*8/(-792) - (-228)/33. Solve -k*n + 3*n + 2*f = 12, -2*f + 7 = n for n. -1 Let t(r) = 3*r - 11 + 0*r - 16. Let z be t(13). Solve -h = h + x + z, -5*h = -4*x + 17 for h. -5 Let g = 9 - 7. Suppose 0*r + 5*r - 3*a = 34, g*a + 6 = 0. Solve -3*p + 1 = j + 2, -r*j + 2*p + 29 = 0 for j. 5 Suppose -37 = -5*z - 4*t, -7*z + 3*z - 4*t + 32 = 0. Suppose -z*r = -4 - 96. Solve b = -4*c - b + 10, 0 = -4*c - 4*b + r for c. 0 Suppose -4*o = -s - 21, 102 - 92 = 4*o - 2*s. Suppose -1 = -3*y - 4*g - 150, 4*y + 178 = 5*g. Let m = -19 - y. Solve 4*t + 5*l + o = -28, -m = 3*t + 4*l for t. -4 Let g(p) = 25*p + 53. Let t be g(-2). Solve 3*y - 9 = -t*s, 5*s - 3*y - 1 = 6 for s. 2 Let k be -69*5/(-15)*(2 - 1). Solve b + k = -5*j, 0*j + j + 13 = -3*b for j. -4 Let o be (0 - 0) + (1 - (-4 - -1)). Let y(l) = -l**3 + 6*l**2 - 11*l + 12. Let r be y(o). Solve 3*w + 0*w + m + 5 = r, -2*m + 11 = -w for w. -3 Suppose -3*f + 31 = 43. Let g be 1 - 3 - 12/(f + 1). Solve 5*l - 5 = -w - 30, -10 = 2*l - g*w for l. -5 Let y be (0 - 1) + 2/6*3. Let u(w) = 23*w + 166. Let a be u(-7). Solve 0*z + z = -2*i - 1, 5*i + z - a = y for i. 2 Let s = -44 + 48. Let z be 26/7 - ((-8)/7)/s. Solve -5*i + 20 = z*c - c, 2*c - 6 = 4*i for c. 5 Suppose 0 = -2*o - 4 + 4. Solve -2*v - 2*s = -1 + 5, o = 5*s for v. -2 Let n = 19 + -18. Suppose -3*h + n = -p - 2, -2*p = -3*h. Suppose -z = 4*x - 10, -4*z + h*x = -x - 2. Solve -2*a - z*q - 3*q - 31 = 0, -5*q - 34 = 3*a for a. -3 Suppose 0 = 2*o - 2*r + 12, 5*o + 0*r + 36 = -r. Let l be 12/(-10)*(o/3 + -1). Solve f = -4*v - 4, 0 = l*f + f - v + 20 for f. -4 Let r = -32 + 34. Suppose -4*v - 16 = 2*x, -4*x + 14 + r = -4*v. Solve 2*t - 5*o + 18 = x, -t - o + 7 = 2*t for t. 1 Let n(t) = -4*t - 21. Let w be n(-7). Suppose 39 = 6*o + w*o. Let h = 0 + 5. Solve 30 = -2*l - h*q, -l = -0*l - o*q - 7 for l. -5 Let q = -39 - -59. Let g(y) = y**3 - 7*y**2 - 15*y - 24. Let f be g(9). Solve 6*n - 2*n + q = 4*h, 0 = 3*n + f for h. 4 Let x(g) = g**3 + 5*g**2 + 3*g + 2. Let k be x(-4). Let b be (-2 - (-10)/(-5))/(-2). Suppose 18 + b = 5*i. Solve i*n = f + 2 + k, 21 = n - 5*f for n. 1 Suppose -7*x - 49 = -133. Let f be x/(3/(-6) + -1). Let h be (2 - 3)*(3 + f). Solve -5*r - 13 = -4*q + h*q, r - q - 1 = 0 for r. -2 Let g(s) = s**2 + 4*s + 6. Let b be g(-4). Suppose -4*f = -7*f + b. Let t be f/4 - (-5)/2. Solve -5*p + t = -2*x, p + 5 = 2*p + 4*x for p. 1 Let z be 0*(16/(-6))/(-8). Solve 5*u + z*u = -i - 11, -4*u - 10 = 2*i for i. -1 Let l(q) = -q**3 + 4*q**2 + 7*q - 7. Let o be l(5). Suppose 23*n - 532 = -348. Solve -d = x + n, -3 + 23 = -2*d - o*x for d. -4 Let a(f) = -2*f**2 + 43*f + 23. Let j be a(22). Let m be (-5 + 1)
2023-11-01T01:27:15.642919
https://example.com/article/8955
renewable energy We’re no strangers to green thinking or renewable energy, and this week, the latest addition to our array of eco-friendly infrastructure was installed: a cluster of Telsa Powerpacks. A sort of souped-up version of the Powerwall residential batteries announced in 2015, the Powerpacks are purpose-built to commercial and utility-grade specifications. They’re meant to endure harsh conditions—Chicago winters, for…
2024-07-30T01:27:15.642919
https://example.com/article/9655
Frequently Asked Questions Do you have a question? Maybe this will help: How do I order? Calling is always best so we can discuss what you want, availability and pricing. We can also set up a face to face free consultation. Our number is 210-688-9550 We get pretty busy on weekends, so if we don’t answer, please leave a message – Include your name and contact information, and what you would like to talk about(child’s party, cakes, etc.) & we will call you back as soon as possible. How much do your cakes cost? Our cakes start at $45 Prices will vary based on your custom design, so give us a call to discuss your cake today.
2024-07-10T01:27:15.642919
https://example.com/article/3197
“Audit of Disbursement Vouchers (DVs) with corresponding bank debit memo, showed that on various days in December 2017 SEAGI and ERA in the amount of P4,457,500.00 and P5,998,800.00, respectively, or a total of P10,456,300.00 were granted to PTNI officials and employees, including personnel hired under as Contract of Service (COS) without approval of the President,” the COA said.
2023-12-07T01:27:15.642919
https://example.com/article/7540
Q: Website suddenly not available on chromium I use a trading platform called cTrader, from IC Markets. They have a web platform that ran fine (a bit slow) on chromium, and all of the sudden, it's not working anymore. The site says my browser is not supported. Any ideas on how could I fix this? I am using a raspberry Pi 3 B+, so full chrome is not an option, and already tried Firefox ESR. A: At the moment, Chromium in Raspbian Buster is version 74. Not far behind the latest Chrome 77. But some websites do not recognize the browser because Chromium announces itself as 'chromium' instead of 'chrome'. So those sites assume it's some incapable browser and prevents the user from using it. Very annoying. Fortunately there is an easy fix. I installed User Agent Switcher on chromium, and then created a custom User Agent string, Mozilla/5.0 (Windows NT 10.0; Win64; x64) AppleWebKit/537.36 (KHTML, like Gecko) Chrome/74.0.3729.169 Safari/537.36 and set it to be applied as default for all sites. That way websites will think you are running Chrome, not Chromium.
2023-10-02T01:27:15.642919
https://example.com/article/6307
The Port of Yantai lies on the shores the Shandong Peninsula off the Yellow sea in Shandong Province in northeast-central People’s Republic of China. It is a major harbor and seaport with far-reaching road and rail connections to the cities of the province. The Port of Yantai is Shandong’s largest fishing port with a vibrant economy. The city received its name from the 1398 AD watchtowers on Mount Qi that were used to raise alarms on the appearance of Japanese pirates. In 2007, over 2.1 million people lived in the metropolitan area. Port History The Port of Yantai was known in the West as Zhifu, actually the name of an island in the natural deep-water harbor that has long been home to a seaport. Anglo-French forces occupied the port in 1860, forcing its opening to foreign trade as it became by treaty an international port in 1861. The Port of Yantai was the site for negotiations in 1876 between Britain and China that ended with the opening of more treaty ports and to a Chinese minister at London’s Court of St. James. Despite its status as a treat port, the no foreign settlements or concessions were located in the Port of Yantai. However, many foreign traders lived in the city, leading to active trade in the late 19th Century. Exports at the time included beans, silk, and local produce. Steamships took goods to junks that served smaller coastal ports. Through the late 19th Century, the Port of Yantai was little more than a fishing village. In the last decade of the 19th Century, the Port of Yantai’s population doubled, but its commerce was all but ruined after 1898 when the Germans developed the Port of Qingdao on the peninsula’s southern coast. Like other ports in northern Shandong, the Port of Yantai stagnated for the first half of the 20th Century. Its revival came in 1956 when the railways linked it to Lancun. In 1914, the Jiaodong Circuit of the new Republic of China was located in the Port of Yantai, and the city was part of the anti-Japanese revolutionary committee in 1938. After the birth of the People’s Republic of China in 1950, Yantai received city status, and several municipalities were merged with Yantai City to create the Yantai Region. In 1984, the Port of Yantai was designated as an open city, and foreign investment was invited, simulating considerable growth. New industries have grown up producing machinery, processed foods, textiles, electronics, auto parts, construction equipment, instruments and meters, and metallurgical products. Gold trading and working have become important to the Port of Yantai economy, and traditional products like wines, wooden clocks, locks, and tinned foods continue to be stable exports. The Port of Yantai is an important strategic location for China’s defense. Together with the Port of Dalian (about 160 kilometers north across the bay), the Port of Yantai is the main point for coastal guards for Beijing. Since it became a prefecture-level city in 1983, the Port of Yantai has focused on modernizing and developing as an economic center for the province.
2024-04-29T01:27:15.642919
https://example.com/article/6353
Hi! I’m David. Please help me #keepmoving outdoors with an #Alinker Walking Bike. I'm a single Dad and would love to be able to enjoy the outdoors again with my daughter and friends. Diagnosed with Rheumatoid Arthritis at age 2, I spent most of my youth in and out of a wheelchair and in and out of hospitals. After many years and total joint replacements in both hips and knees, I became more mobile and began participating in outdoor activities with the assistance of several local non-profit groups that assist the disabled in the participation of sports such as hiking, kayaking, sailing and more. However, in early 2018, I had to have a second knee replacement (on the same knee) and later that year, I fell and since then, I have not been able to walk without assistance. I currently use crutches outside and a walker in the home. I have not participated in any outdoor activities for over a year. I no longer go for walks, regular grocery shopping, go to malls or other public venues. Walking with crutches while having Rheumatoid Arthritis causes added pain in my back, neck and shoulders. This pain along with an overall fear of falling prevents me from going out, enjoying the great outdoors in New England and being socially active as I had been before the knee replacement and subsequent fall. I attend Physical Therapy several days a week and am trying to get some strength back. The #Alinker is a three-wheeled walking bike designed to help people stay active and live life to the fullest allowing users experience chronic aches and pains, chronic illnesses and recovering from an injury, they can all still be active! Currently, Health Insurance plans do not cover a very broad range of mobility devices and that’s why campaigns like this are so important. I'd be able to rebuild and maintain muscle tone in my legs, be able to walk upright instead of using all my energy focusing on trying not to fall and once again enjoy my time outdoors and with family and friends without the feeling like I'm slowing everyone down. It may even allow me to return to scuba diving as I'd be able to use the #Alinker to walk the trail down to the water's edge at Ft. Wetherill park in Jamestown, RI. to It really would give me so much freedom back, open up my world again, and change my life. To learn more about my life’s journey, please visit me at davidstmartin.com. Thank you for your consideration and support. The campaigns are about sharing. Most people have no idea what life is like when you live with MS or what happens after you have a stroke. Isolation is often a bigger problem than the symptoms of the disease itself. With the campaigns we can share and educate people, because it can happen to all of us. When we create a movement where people simply show up for each other, it might get a bit ‘safer’ and less ‘scary’ to engage with each other. Some people share their experiences on their campaign, others share their funds to support the campaigns. It is not about asking for money, it is creating an opportunity for people to learn and show up with #generosity. Being generous resonates with who we are as humans. We understand generosity deeply and when you practice it, you feel so much better PLEASE NOTE The campaigns are in Canadian $ (back end requirement on our side), the $2800 CAD includes the Alinker, shipping, process and campaign fees and our support. The campaigns are all or nothing, no credit cards are charged unless the campaign reaches its goal. As soon as the campaign reaches its goal, we ship an Alinker. Campaigners do not handle money. On disability or welfare, you cannot handle money without being penalized, but you can receive an Alinker ! When the campaign raises more than the goal, the campaigner can chose another campaign where we then make the donation to, paying it forward, or get the balanced paid out, the choice is the campaigner's. If you want to start a campaign and are outside Canada or the USA, write an email to molly@thealinker.com. We can get a shipping quote to where you live, and include that in the campaign goal. Together we build a movement of kindness and generosity, because we all need it Why do we facilitate crowdfunding on our site? We believe that the Alinkers should be available for everybody, regardless of income and people who start a crowdfunding campaign here, will have access to a life changing Alinker. Did you see how happy Selma Blair is using her Alinker? Her anxiety dropped from level 10 to 2 after she got back on her new Alinker. She is so happy and so on with this new invention, that she wants to create a fund to get people access to Alinkers. These crowdfunding campaigns are the first step to make Alinkers available for everybody. Selma and BE are now putting their energy together to build a generous community around all the campaigners! The campaigners are people who allow others to show up generously, give them love! Why an Alinker? Generally, medical devices are a technical solution for a body with a problem.The Alinker is designed for who we are, a whole human being, who wants to live an active and engaged life. We are a human, we have a body. Whether we miss a leg of have MS, it does not change us as a person. Yet the world we live in, treats us as a body with a problem, which creates a social divide between people based on their body, based on what we have, not on who we are. Isolation and loneliness are more devastating than the disease itself. So we need to show up for each other, acknowledge each other and be present to who we are. These campaigns are here to bridge the gap between a high quality custom Alinker, and the people who live at the receiving end of a 'sickcare' system that drives people into poverty. So, show up, be radically generous, it is something we humans really understand.When you read each story in each campaign, pause and imagine who that person is, and why they started the campaign, reach out to them, let them know they are surrounded and seen, heard and not alone. When we do that, we feel better and create a safer community where we know we can show up for each other. It connects us with our essence, we are radically generous creatures, we just got a little lost in systems that are not designed for our wellness. Who is the Alinker for? The Alinker is for people who want to stay active, regardless of mobility challenges. To operate and use the Alinker you must have the ability to: walk to some degree flex and extend your legs bear weight on one leg briefly while getting on and off the Alinker be consciously aware of your surroundings be aware of your ability and limitations What is the Alinker? The Alinker is an exceptionally cool, three-wheeled walking bike for humans with mobility constraints. It’s not a medical device, it’s a lifestyle tool, designed to enable users to lead active and socially engaged lives — at eye level. On the Alinker, users sit upright -- at eye level with standing companions. Weight is supported by the seat with no stress on the lower body, while handle bars provide additional support. Feet remain on the ground, keeping users stable and safe. Delete update Delete milestone Share this post Edit your message Report campaign Report submitted Thank you. We take reports like yours very seriously. Our goal is to keep the community safe. Please know that we may contact you for more information, but that we won't notify you personally of our decision. If the campaign remains available within a few days, it's likely that we determined it not to be in violation of our policies. Thank you. We've already received your previous report. If the campaign remains available within a few days, it's likely that we determined it not to be in violation of our policies. Record a video Upload a video Nothing grabs attention for your cause like a personal video. Take a minute or two to record one now. Record a short video message of support. Or upload one from your device. You can preview or redo your video before you post it. Nothing grabs attention for your cause like a personal video. Upload a short video message of support. Upload a short video message of support. Or record one right now.
2024-02-21T01:27:15.642919
https://example.com/article/8551
[The role of endothelial nitric oxide in neurogenic contractions of the carotid artery in rabbits during cooling]. The role of endothelial nitric oxide in contractions induced by endogenous noradrenaline released by transmural nerve stimulation (TNS) and by exogenous noradrenaline (NA) was studied in isolated rings of rabbit carotid artery during cooling. At 37 degrees C, TNS produced frequency-dependent contractions of artery. Endothelium removal or inhibition of nitric oxide synthase by NG-nitro-L-arginine methyl ester (L-NAME) significantly enhanced TNS-induced contractions. The magnitude of maximal contraction to exogenous NA was increased in L-NAME-treated intact rings. Cooling the incubation bath from 37 degrees C to 26 degrees C increased the magnitude of neurogenic contractions in intact rings. L-NAME increased further the magnitude of neurogenic contractions at 26 degrees C in intact, but not in denuded arterial rings. Similarly, L-NAME increased contractions induced by exogenous NA during cooling. The results suggest that the response of the carotid artery to noradrenergic stimulation is modulated by nitric oxide originating from endothelial cells at normal as well as reduced temperature. (Tab. 1, Fig. 6, Ref. 19.)
2024-02-26T01:27:15.642919
https://example.com/article/9782
In the present research, the semiconductor clusters have been prepared in nanospace of cancrinite, which is a zeolite compound, and the resulting materials have been characterized. Furthermore, the synthetic conditions for other zeolite compounds available to hosts have been examined.In the former, lead and manganese ions were loaded in the nanospace of sulfide cancrinite and thiosulfate cancrinite hydrothermally synthesized, using the ion-exchange reaction, and the structures, optical properties and photocatalytic properties of the resulting materials were examined. Consequently, the following are found. (1) There existed cations and anions in the same nanospace of lead-exchanged cancrinite, and the plains at the foot of absorption peak assigned as corresponding to electron transition between cation and anion reached to visible light region. (2) The new absorption peak of manganese-exchanged cancrinite appeared in visible light region. (3) All the resulting materials showed the photoc … Moreatalytic activities for hydrogen evolution from a methanol aqueous solution under visible light irradiation, although amounts of hydrogen evolution were small. Especially, manganese-exchanged thiosulfate cancrite showed higher photocatalytic activity than the others.In the latter, sulfide sodalite, which has larger nanospace than sulfide cancrinite, was synthesized, and the photocatalytic activity of lead-exchanged sulfide sodalite was compared with that of lead-exchanged sulfide cancrinite. The results revealed that lead-exchanged sulfide sodalite showed higher photocatalytic activity than lead-exchanged sulfide cancrinte under visible light irradiation. Furthermore, the synthetic conditions for transition metal-doped gallophosphate molecular sieve, which has much larger nanospace than cancrinite and sodalite, were investigated. From the results, it was found that zinc-doped gallophosphate molecular sieve with good crystallinity was successfully produced by adding a small amount of zinc oxide to the starting gel. Less
2023-11-17T01:27:15.642919
https://example.com/article/1888
Q: Can an ASP.Net page implement an interface without using a codebehind page? I have an ASP.Net page that needs to implement an interface class I've created, but since the code in this page is inline, there's no class declaration, and therefore no place to put the "Implements IMyInterface" line. I also tried using the @interface page directive but it appears this only works for built in .Net framework classes. Are there any options other than using a codebehind page just to edit the class declaration line? A: You can do it with an Implements directive: <%@ Implements Interface="MyNamespace.IMyInterface" %>
2023-11-12T01:27:15.642919
https://example.com/article/8908
Scottish universities This is a list of universities in Scotland. There are fifteen universities based in Scotland, the Open University, and three other institutions of higher education. The first university in Scotland was St John's College, St Andrews, founded in 1418. St Salvator's College was added to St. Andrews in 1450. The other great bishoprics ...
2023-11-19T01:27:15.642919
https://example.com/article/5521
BIRMINGHAM, Ala. -- Bill Clark leans back in his chair and reflects on yet another milestone in his quest to bring back UAB football. Two-and-a-half years after the program was shuttered by the university and two years after a contingent of alumni and businessmen fought to have it restored, its head coach sits in a brand-new office inside a brand-new 46,000 square-foot, $22 million facility. Just outside his balcony is a brand-new covered practice field. It's 7 o'clock on a recent Friday morning, the sun is rising and football is almost here. Twenty-nine practices until kickoff against Alabama A&M on Sept. 2. "It's a big deal," Clark says on the eve of preseason camp. "It really is." The 49-year-old coach is grinning from ear to ear as he speaks. But he does that a lot these days. You get the sense he has to pinch himself every now and then to remember this is all real, that they really did hold it all together for so long and are about to come out on the other side not just ready to play a game for the first time since 2014, but to compete and win. Players have started reporting to campus, Clark says, and everyone is accounted for. Well, almost everyone. There are a few names on the way, but one who will never arrive, one he can't forget. It's in that instant when the conversation turns. Clark's face darkens. He would gladly give back this new office and all of his new toys just to change one decision he and so many others have come to regret. Because for all the joy and optimism that exists today, the reality is that UAB football isn't coming back this season in one piece. It's missing the very player who once made its return not just feel real, but exciting. It's missing his infectious smile and his incessant dancing. It's missing his enthusiasm to work even when the nearest game was more than a year away. Greg Bryant needed a second chance just as much as UAB did. But almost as soon as he felt his life starting to turn around, it was over, as he was shot and killed while in South Florida for Mother's Day. In the beginning, before anyone knew what the return of UAB football would look like, Clark huddled in an old, musty single-story office with his staff. The countdown to kickoff clock was shut down near the vacated receptionist desk. Some of the halogen lights overhead flickered as they attempted to construct a roster that had lost more than half its players. Where to begin? Clark had big plans, but no road map. He needed an infusion of talent, but he also knew his players couldn't be too young and compete. A team full of recent high school graduates would get manhandled, he thought. So it was off to the world of junior college football. After starting at Notre Dame, Greg Bryant was the crown jewel of UAB's first recruiting class after its program was shut down. Rich Barnes/USA TODAY Sports The names he heard his staff pitch felt vaguely familiar. Some he'd recruited prior to the shutdown at UAB, some he'd known since his days coaching high school, and some he'd seen only on TV. Greg Bryant was the latter. A coach called another coach who called another coach and suddenly Bryant's name was on Clark's desk. It took awhile for Clark to place him, but he got the picture soon enough: South Florida product who was a top-25 recruit coming out of high school. A rare mix of power and speed. ESPN's No. 2 tailback in the 2013 class, who played as a freshman at Notre Dame and rushed for 258 yards and three touchdowns as a sophomore. Grades, Clark soon found out, ultimately did Bryant in, landing him at a junior college near his home in Miami. This kid, Clark thought, was in another league. He watched his film and said, "Wow, he's unbelievable!" He'd heard Florida State, Auburn and several other Power 5 schools were heavily interested in him. Then, out of the blue, Clark's phone rang. It was Bryant, who told him, "Coach, I'm interested in y'all." "It was a long shot, a long shot" Clark said. "If it was a Birmingham guy, you get it. But for a guy from Miami to get the whole process of who we are, where we're headed, what we're going to do ..." He stopped himself, and added: "Guys will tell you they're coming and then, is it real?" No one knew. The advantage UAB had over other schools was time. With no games that year, players were able to enroll, spend the year rehabbing and training and not lose any eligibility. In the case of Bryant, he could work on his grades. "It was the perfect scenario," Clark said. Still, they waited. Clark had a coaches getaway at a hunting lodge in Mississippi that January before the semester began. There were a lot of new faces on staff, and he wanted to get everyone on the same page. With a fire roaring in the background, they answered the big questions facing the program: "Who are we? Where are we headed?" And on the side, they made calls. Lots and lots of calls. It was there, drawing the blueprint for the future of UAB football, that the final call came in. Bryant's paperwork was completed. "It was a big deal," Clark said. "He was the bell cow of that class." If there is truly a silver lining to every gray cloud, UAB's was this: In the midst of all the headlines about the program being shut down, it became a household name. When football was reinstated, Clark rarely had to explain the situation, whether he was talking to a recruit in South Florida or Southern California. Then Bryant's commitment happened and it created momentum. All the time, Clark said he'd have people ask, "Y'all got Greg Bryant?" Even coaches on his staff couldn't believe it, saying, "He's coming here?" "It validated us," Clark said. "I'm not a star guy, but UAB has never had a four-star and this is a five-star. My son knew him better than I did. These kids had watched him in the Under Armour Game. They knew." Safety Chris Morgan, who hosted Bryant on his official visit, was the first to know that his commitment was coming and watched as the floodgates opened afterward. "To have a big-name player, it made other guys say, 'OK, they're building something special,'" Morgan said. "Him coming here did a lot for that class." As Bill Clark prepares for the renaissance of UAB football, he does it without one of its most important pieces, Greg Bryant, who was shot and killed in May of 2016. Shanna Lockwood/USA TODAY Sports Marc Jonassaint, a safety from South Florida, made no bones about it: He doesn't come to UAB if Bryant isn't on board. He wouldn't even have known who they were, he said. "When UAB offered me, I looked at the class and went, 'Wow, you got Greg? You got all these other recruits? Sign me up. I need it.'" Jonassaint said. More than any new facility or fancy billboard, the signing of Bryant -- and his prospective teammates -- showed the world that UAB football was real. A boy wanted to see his mom, and no one could tell him no. Not his dad. Not his coach. No one. They tried to convince him that going home was a bad idea. Dad talked to Coach and they agreed: He has worked so hard to get his GPA up to a 2.75 and things were going great in Birmingham, so why risk it by returning to Miami? But it was Mother's Day and Bryant had some time off between semesters. And even though he'd made a deal with Morgan that he'd stay on campus, relax and get ready for workouts, he found a flight home anyway. Morgan shook his head when he saw a Snapchat Bryant posted of him kissing his mother a few days later. That was the GB he knew, always trying to make people happy. Hours later, Bryant was shot. His body was found by police in a car on Interstate 95. At the hospital, he was declared brain-dead and later passed away. He was 21 years old. "That was an awful day," Clark said, searching for and understandably failing to find the right words. Bryant wasn't at UAB long -- a little more than a semester, in fact -- but even a year after his death, his presence lingers. His jacket continues to hang on the same chair where he left it at Morgan's apartment. His jeans are still at Jonassaint's place, too. Neither can bear to get rid of them. "I've never met someone as happy as him," Jonassaint said. "He's smiling all the time, goofy. I can't see him doing anything wrong." Players reflexively talk about Bryant in the present tense, laughing about how funny he could be and then turning serious when describing what a talent he was. When veteran linebacker Shaq Jones first went head-to-head with him in the Oklahoma drill, he wanted to give the star from Notre Dame a good lick. Only he whiffed completely and Bryant scored a touchdown. "He said, 'Yeah, that's going to be all year long!'" Jones said, smiling. "It was just the competition that we had with him. He made everyone raise their level." With a fresh start and a more mature approach to the classroom, teammates saw a player destined for stardom. Jonassaint believed Bryant was going to be a one-and-done, heading straight for the NFL after one season. Together, Jonassaint said they'd talk about how they would be "the new UAB." "He wanted to break all the records, he wanted to be the best to ever come out of here," Morgan said. "We talked about it all the time: Put UAB on the map. Be the ones who bring UAB to places it had never been before." But now, Morgan, Jonassaint and the rest of the team have to move forward without him. They have to put UAB on the map without him. After Bryant's death, Morgan got a tattoo on his right forearm that has angel wings surrounding big block letters that spell out, "GB4E." "Every time I come up here, I never take it for granted," Morgan said. "Even the days I'm tired, you don't feel like getting up and going to class or getting up and going to workouts and you stop feeling, I just think about Greg. I got this tattoo. It's a reminder how quickly it can be taken away."
2024-07-03T01:27:15.642919
https://example.com/article/4759
/* -*- Mode: C++; tab-width: 4; indent-tabs-mode: nil; c-basic-offset: 4 -*- */ /* * This file is part of the LibreOffice project. * * This Source Code Form is subject to the terms of the Mozilla Public * License, v. 2.0. If a copy of the MPL was not distributed with this * file, You can obtain one at http://mozilla.org/MPL/2.0/. * * This file incorporates work covered by the following license notice: * * Licensed to the Apache Software Foundation (ASF) under one or more * contributor license agreements. See the NOTICE file distributed * with this work for additional information regarding copyright * ownership. The ASF licenses this file to you under the Apache * License, Version 2.0 (the "License"); you may not use this file * except in compliance with the License. You may obtain a copy of * the License at http://www.apache.org/licenses/LICENSE-2.0 . */ #include <node.hxx> #include <doc.hxx> #include <IDocumentFieldsAccess.hxx> #include <ndtxt.hxx> #include <fldbas.hxx> #include <osl/diagnose.h> bool CompareSwOutlineNodes::operator()( SwNode* const& lhs, SwNode* const& rhs) const { return lhs->GetIndex() < rhs->GetIndex(); } bool SwOutlineNodes::Seek_Entry(SwNode* rP, size_type* pnPos) const { const_iterator it = lower_bound(rP); *pnPos = it - begin(); return it != end() && rP->GetIndex() == (*it)->GetIndex(); } void SwNodes::UpdateOutlineNode(SwNode & rNd) { SwTextNode * pTextNd = rNd.GetTextNode(); if (!(pTextNd && pTextNd->IsOutlineStateChanged())) return; bool bFound = m_pOutlineNodes->find(pTextNd) != m_pOutlineNodes->end(); if (pTextNd->IsOutline()) { if (! bFound) { // assure that text is in the correct nodes array if ( &(pTextNd->GetNodes()) == this ) { m_pOutlineNodes->insert(pTextNd); } else { OSL_FAIL( "<SwNodes::UpdateOutlineNode(..)> - given text node isn't in the correct nodes array. This is a serious defect" ); } } } else { if (bFound) m_pOutlineNodes->erase(pTextNd); } pTextNd->UpdateOutlineState(); // update the structure fields GetDoc()->getIDocumentFieldsAccess().GetSysFieldType( SwFieldIds::Chapter )->UpdateFields(); } void SwNodes::UpdateOutlineIdx( const SwNode& rNd ) { if( m_pOutlineNodes->empty() ) // no OutlineNodes present ? return; const SwNodePtr pSrch = const_cast<SwNodePtr>(&rNd); SwOutlineNodes::size_type nPos; if (!m_pOutlineNodes->Seek_Entry(pSrch, &nPos)) return; if( nPos == m_pOutlineNodes->size() ) // none present for updating ? return; if( nPos ) --nPos; if( !GetDoc()->IsInDtor() && IsDocNodes() ) UpdateOutlineNode( *(*m_pOutlineNodes)[ nPos ]); } /* vim:set shiftwidth=4 softtabstop=4 expandtab: */
2024-04-05T01:27:15.642919
https://example.com/article/7049
Q: ASP.net This is a marker file generated by the precompilation tool, and should not be deleted I am currently getting this when visiting my http:// websitehere.com/excelData.aspx page: This is a marker file generated by the precompilation tool, and should not be deleted! The file system directory on the server looks like this: --mainDir |--excelData.aspx |--PrecompiledApp.config |--Web.config |--bin |--App_Web_cuydkh1j.dll |--exceldata.aspx.cdcab7d2.compiled Not sure what I need to add/remove in order for it to display my page without that precompilation tool text on it. The IIS server is version 6.1 A: One of the reasons for this problem is the file PrecompiledApp.config is missing from the root of your site (this file is generated by the publishing wizard). Hope this help others. A: Problem: When you upload the web application, sometimes the most important files in the bin folder (e.g., the .dll files) will not upload correctly. Solution: Re-upload the bin folder. Remember to overwrite.
2024-01-10T01:27:15.642919
https://example.com/article/6513
Based on Jay Anson’s book of the same name which was itself an account of a supposedly “true story” which was itself made into a film in 1979 which went on to spawn countless sequels…. (yes, I’m going for the longest sentence ever written by man) …has a family move into a gloomy house to then realize that its haunted and attempting some good old fashion possession. THE LOWDOWN I won’t even go into the “true story” moniker glued to this 2005 update. Either way, the Lutz' were kept away from this remake by the Studio; hence they had no input into the film whatsoever. This sucker was all fiction to me daddy-o! You want to hear my thoughts on that whole “did it happen” spiel? Read my reviews of the Amityville Horror and Amityville 2 and call it a life. For better and for worse Amityville Horror 2005 was your quintessential modern, razzle-dazzle horror flick. It moved at a lightning speed, went through its plot turns faster than you can say “A.D.D”, machine gunned every “wow”, “slick” and “elliptic seizure inducing” directing trick in the MTV book and boo scared the shite out of me until my butt was sore from all that seat hopping. It of course didn’t waste any time in getting its bowling horror ball rolling either, where I was assaulted by macabre goodies mucho early on up until the final frame. The film’s zippy demeanor and dread heavy feel definitely made way for an effortless watch, one that demanded next to nothing from what’s left of my grey matter. Tag to that, engaging performances all around with the highlight being “serious actor since he grew a fine looking beard” Ryan Reynolds and you a trouble-free lay that had me smiling throughout. A note on King Canuck Reynolds! Was that dude likeable... scratch that... LOVEABLE...or what? He stole every damn scene he was in (and even stoles scenes he wasn’t in) and I couldn’t help but adore the lad to severed limbs! His natural "endearing" quality, mixed in with a genuine sense of "menace" and awesome lines, made way for a very compelling character to follow around. As Reynolds' Lutz got crueler and crueler, I cheered for him louder and louder. You know that a-hole that cackles out loud from the back row of the theatre when the mean spirit-ness or/and atrocities hits the screen? Well that was me throughout this film! I haven’t rooted for a psycho to do the doo this much since The Stepfather "Spring Cleaned" his humble abode. According to this movie, George Lutz knows a thing or two about wrangling kids that’s for freaking sure! Parents take notes of "The Lutz Method" as to how to keep your brats in check (the holding the log bit was hands down hilarious...what a great scene). Good show Mr. Reynolds! Unfortunately, the rush-rush nature of the affair did lessen its overall impact. Don’t get me wrong, it was always fun times in a 1$ dollar wine bottle but it could’ve been so much more that just that! The story was hurried, build-up/tension were non existent, character development was waif-ish (Who were these people again?) while the “fear scenarios” didn't punch me as hard as they should’ve had since they kicked in hardcore too early in the game (i was numb to them at the half way point). And what was up with that priest subplot? It came and was dropped faster than a good habit! Talk about pointless! Furthermore, the film’s over-urgency made the age old “haunted house movie” question ring so much louder. “What will it take for these suburban imbeciles to leave that EVIL house already?” Screw looking for background on the house 1 hour and 20 minutes into the movie…YOU KNOW ITS HAUNTED! GET THE F*CK OUT! You thought they didn’t book swiftly enough in the 1979 version? Get ready for a "suspension of disbelief" castration with this remake! Overall, Amityville Horror 2005 was a sleek, quick and highly entertaining horror snack! With more padding and less "rush-rush"; it could’ve also have been a weighty horror film. Buy hey…I STILL HAD A BLAST! Reynolds owned the movie! I am now officially a HUGE fan! HAUNT THIS! GORE The film was brutal but lots of it was communicated via quick-cuts…so don’t blink! We get some nasty shot gun wounds, demonic faces, a finger inserted in a bullet hole, blood and some “Hellraiser” like human/creature oddities. Enough to please the gore fiends but again…DON’T BLINK! ACTING Ryan Reynolds (George) has left the baby faced Van Wilder behind to embrace the “bearded” Reynolds, one that tackles serious roles while still managing to be as fun loving as Michael Jackson burning in hell GREAT SHOW…specially when the axe kicked in! Melissa George (Kathy) hit all the right notes and was a cutie to boot! Philip Baker Hall (Father McNamara) wasn’t in the film long enough to leave much of an impression. He’ll always be the “Library Police” to me! T & A Its ladies night tonight with a shirtless Ryan Reynolds showing off his leftover muscles from Blade 3 like the champ that he is! Dig in girls! DIRECTING Andrew Douglas heavily dipped the nachos in the sour cream with audio/video tricks up the wazoo! On the upside, the flick was a deliciously somber and flashy piece of eye candy. On the downside, at times, I wished a chill on the quick cuts to digest what I had seen, before moving on to the next thing. SOUNDTRACK Was there one? Like really? Although varied sounds were efficiently used; I can’t say I picked up on the score much. BOTTOM LINE Amityville Horror 2005 was 95 percent BBQ Sauce and 5 percent meat. The banquet was well cooked, spicy in all the right places and it looked yummy to boot! The countless “will keep you awake” boo scares and Ryan Reynolds AMAZING performance made sure to tickle my fancy as well (did I just write tickle my fancy…wow I suck). Having said that, this was no T Bone…it was a McRibs at best. I personally preferred the original by an inch but this jacked up Fast Food version hit the spot as well…in a different way. It was just so damn entertaining! Now are you going to place an order or just read my lousy “food analogies” all day…see the movie and judge for yourselves amigos! ARROW OUT! BULL'S EYE The film was shot for an estimated 20 Million $ budget Andrew Douglas only directed one feature before this in 2003 named: "Searching for the Wrong-Eyed Jesus". Ryan Reynolds first lead in a feature credit was in Ordinary Magic in 1993
2023-09-15T01:27:15.642919
https://example.com/article/2188
Q: Issue with npm after reinstalling node.js I recently reinstalled node.js (latest version, 9.8.0) on my computer (running windows 10) as it started to glitch out. The problem is, now npm doesn't work. For example, upon entering npm in cmd, I get the error: Error: EPERM: operation not permitted, mkdir 'C:\Program Files (x86)\Nodist' TypeError: Cannot read property 'get' of undefined at errorHandler (C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205:18) at C:\Program Files\nodejs\node_modules\npm\bin\npm-cli.js:83:20 at cb (C:\Program Files\nodejs\node_modules\npm\lib\npm.js:224:22) at C:\Program Files\nodejs\node_modules\npm\lib\npm.js:262:24 at C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:81:7 at Array.forEach (<anonymous>) at C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:80:13 at f (C:\Program Files\nodejs\node_modules\npm\node_modules\once\once.js:25:25) at afterExtras (C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:178:20) at C:\Program Files\nodejs\node_modules\npm\node_modules\mkdirp\index.js:35:29 at C:\Program Files\nodejs\node_modules\npm\node_modules\mkdirp\index.js:47:53 at C:\Program Files\nodejs\node_modules\npm\node_modules\graceful-fs\polyfills.js:284:29 at FSReqWrap.oncomplete (fs.js:170:21) C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205 if (npm.config.get('json')) { ^ TypeError: Cannot read property 'get' of undefined at process.errorHandler (C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205:18) at process.emit (events.js:180:13) at process._fatalException (bootstrap_node.js:431:27) Error: EPERM: operation not permitted, mkdir 'C:\Program Files (x86)\Nodist' TypeError: Cannot read property 'get' of undefined at errorHandler (C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205:18) at C:\Program Files\nodejs\node_modules\npm\bin\npm-cli.js:83:20 at cb (C:\Program Files\nodejs\node_modules\npm\lib\npm.js:224:22) at C:\Program Files\nodejs\node_modules\npm\lib\npm.js:262:24 at C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:81:7 at Array.forEach (<anonymous>) at C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:80:13 at f (C:\Program Files\nodejs\node_modules\npm\node_modules\once\once.js:25:25) at afterExtras (C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:178:20) at Conf.<anonymous> (C:\Program Files\nodejs\node_modules\npm\lib\config\core.js:234:20) at C:\Program Files\nodejs\node_modules\npm\lib\config\set-user.js:23:20 at C:\Program Files\nodejs\node_modules\npm\node_modules\mkdirp\index.js:35:29 at C:\Program Files\nodejs\node_modules\npm\node_modules\mkdirp\index.js:47:53 at C:\Program Files\nodejs\node_modules\npm\node_modules\graceful-fs\polyfills.js:284:29 at FSReqWrap.oncomplete (fs.js:170:21) C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205 if (npm.config.get('json')) { ^ TypeError: Cannot read property 'get' of undefined at process.errorHandler (C:\Program Files\nodejs\node_modules\npm\lib\utils\error-handler.js:205:18) at process.emit (events.js:180:13) at process._fatalException (bootstrap_node.js:431:27) The node command works fine, though. Why would this happen? Edit: I have tried reverting to the recommended Node.js version (8.10.0), but I am getting the same issues. A: I had a similar problem a while ago. Try navigating to the file named .npmrc, in C:\Users\%UserName%, and deleting it.
2024-07-21T01:27:15.642919
https://example.com/article/1720
The field of taste perception has made significant advances in the past 15 y. Sweet, umami and bitter taste recognition occurs when corresponding molecules engage specific homo- or hetero-dimeric G-protein coupled receptors (T1Rs or T2Rs), followed by activation of the heterotrimeric G-protein subunit α-gustducin (G~αi~) (Salty and sour tastes are recognized by a different system).[@R1] While sweet and umami tastes each have a single receptor, humans harbor 25 receptors (mice have 35) for sensing bitter compounds, consistent with the notion that the ability to taste diverse bitter compounds prevents the consumption of potentially toxic substances. T1R and T2R receptors, however, are widely distributed in the body, and have been implicated in various non-gustatory roles.[@R2] The bitter taste sensor T2R38 is a receptor for the molecule phenylthiocarbamide (PTC), and genetic polymorphisms in the corresponding chromosomal locus segregates the population into \"tasters\" and "non-tasters."[@R3] Tasters have a functional allele that includes a proline-valine-alanine (PAV) sequence, while the corresponding sequence in non-tasters is alanine-valine-isoleucine (AVI). A new study implicates T2R38 in a non-gustatory role, that of sensing bacterial quorum-sensing (QS) molecules and stimulating innate immune responses [(Fig. 1)](#F1){ref-type="fig"}. ![**Figure 1.** Epithelial cells co-opt the T2R38 receptor to eavesdrop on *P. aeruginosa* conversations. Consequent innate immune responses help clear the bacteria.](gmic-4-91-g1){#F1} Bacteria use QS systems to coordinate gene expression in a population-dependent manner.[@R4] At threshold population densities, small molecules produced by the bacteria ("autoinducers") interact with specific proteins and activate signaling pathways that eventually alter bacterial gene expression. *Pseudomonas aeruginosa* produces two quorum-sensing molecules, C12HSL and C4HSL, that belong to the broad class of autoinducers known as acylated homoserine lactones (HSLs). In this new study,[@R3] Lee et al. confirmed T2R38 receptor expression in the apical membrane and cilia of upper airway sino-nasal respiratory epithelial cells from surgical explants, and demonstrated PTC- and *P. aeruginosa* acyl-HSL-dependent calcium signaling, but only in cells harboring the functional receptor (PAV/PAV). Elevated calcium levels were also observed in response to conditioned *P. aeruginosa* culture medium. T2R38 signaling was dependent on PLCβ2 and TRPM5 (as in gustation responses), but was independent of TLR signaling. Acyl HSL-stimulation of T2R38 resulted in nitric oxide (NO) production and increased ciliary beat frequency, processes that play a key role in mucociliary clearance of pathogens. Both responses were abrogated by inhibitors of PLCβ2 and nitric oxide synthase. Significantly, *P. aeruginosa* exposed to PAV/PAV cell cultures, but not to PAV/AVI or AVI/AVI cell cultures, were killed in high numbers in a NO-dependent fashion. To determine the relevance of T2R38-dependent innate immune responses in clinical settings, the investigators examined the correlation between patients' T2R38 alleles and the corresponding microbiological reports for bacterial growth, including *P. aeruginosa.* Gram-negative bacteria, including *P. aeruginosa,* were present in sino-nasal swabs from patients harboring the non-functional T2R38 alleles (PAV/AVI or AVI/AVI), but not in those encoding the functional allele (PAV/PAV). Despite the relatively small numbers of patient samples tested, and the limited information about normal flora, this result is of considerable interest. As suggested by the authors, T2R38 polymorphism-related innate immune defects in people could be tested and correlated with a simple T2R38-dependent taste test. PTC itself may not be useful for this test since heterozygotes (PAV/AVI) display varying abilities to taste this compound, whereas the sino-nasal cells from these individuals do not display acyl HSL-dependent innate immune responses, and are more similar to the non-functional homozygotes (AVI/AVI) in this respect. The study does not indicate if the QS molecules C12HSL or C4HSL themselves have a bitter taste, and if there is an allele-dependent heterogeneity in perception of this taste. The observation that bacterial HSLs stimulate host responses, in itself, is not novel. Numerous studies have demonstrated responses to acyl HSLs, including apoptotic and inflammatory signaling, in a range of host cells.[@R4] *P. aeruginosa* acyl HSLs have even been demonstrated to directly bind to the lipid-sensing PPAR (peroxisome proliferator activated receptor) transcription factors and impair their activity. More recently, *P. aeruginosa* acyl HSLs were shown to interact with IQ-motif containing GTPase-activating protein (IQGAP), and impact Rac1 and Cdc42-dependent cell migration.[@R5] The T2R38-acyl HSL interaction, however, suggests that the host is specifically tuning in to a conversation between bacteria. Notably, no endogenous ligands of T2R38 have been identified to date. Is it possible that acyl HSLs are the "natural" ligands for these receptors? Could T2R38-dependent innate immune responses play a similar role in the inside passage? T2R38 is expressed on intestinal enteroendocrine cells, as well as in Caco-2 cell lines, and is responsive to PTC-dependent signaling.[@R6]^,^[@R7] The presence and prevalence of acyl-HSLs in the gut, however, is unclear. In a recent review, Swearingen et al. comprehensively analyze published studies and state that "there has been no direct detection of acyl-HSLs within the normal mammalian intestinal tract" to date, except during *Yersinia enterocolitica* infections.[@R8] Yet, they emphasize the caveats to *all* the negative results, including the lack of sensitivity of the biosensors used to detect acyl-HSLs. It is, therefore, conceivable that T2R38 plays a role in intestinal innate immunity, at least in the context of specific infections. More broadly, the effects of T2R38 polymorphisms on the endogenous microbiota in the gut, and elsewhere, remains an open question. A relatively better established system of inter-kingdom signaling relates to the AI-3 quorum sensing system in various strains of *E. coli* and *S.* Typhimurium.[@R9] In this instance, the bacteria not only respond to AI-3 in a density dependent manner, but also to host epinephrine and norepinephrine (E/NE), and this signaling can be blocked by α-adrenergic antagonists. It is likely that AI-3, which remains to be structurally characterized, also modulates host adrenergic signaling. Inter-kingdom signaling appears to have a long evolutionary history, and the main point of novelty here is that we human beings are finally privy to some of these conversations. Previously published online: [www.landesbioscience.com/journals/gutmicrobes/article/23776](http://www.landesbioscience.com/journals/gutmicrobes/article/23776/)
2024-06-06T01:27:15.642919
https://example.com/article/8035
How to examine patients using the Abnormal Involuntary Movement Scale. The Abnormal Involuntary Movement Scale (AIMS) examination has been widely recommended for periodic screening for tardive dyskinesia and follow-up of patients diagnosed with the disorder. However, few guidelines exist about how to use the examination in clinical practice. The authors discuss for whom, when, and how the AIMS examination can be used in a multidisciplinary setting; amplify the original instructions for the examination; and propose conventions to clarify scoring. Noting that the AIMS examination is not specific for tardive dyskinesia, they discuss a clinical approach to the patient who is found to have abnormal movements. The AIMS examination is best conducted within the context of an ongoing treatment program, the authors say, and should be part of the informed consent process necessary with patients treated with neuroleptic drugs.
2023-11-24T01:27:15.642919
https://example.com/article/6738
Post the Padmavati protests, Shabana Azmi asks for boycott of IFFI Never one to mince words, Shabana Azmi is vocal about her distaste for the baseless Padmavati protests. She feels it’s time for the film industry to take a collective stand against the ugly controversies and protests surrounding the release of Padmavati. Says Shabana, “The entire film industry should boycott the IFFI next month in Goa in protest against the threats issued to Padmavati,Sanjay Leela Bhansali and Deepika Padukone. If Smriti Irani is preparing for such an impressive turn-out at IFFI this year that is possible only because the Indian Film Industry brings such acclaim to it. But the film industry keeps quiet about Padmavati! This is exactly like HKL Bhagat and Congress celebrating IFFI in Delhi after the murder of Safdar Hashmi.” Shabana wonders why so little action has been taken against the perpetrators of violence against the Padmavati team. “The CM of Rajasthan is sitting pretty. The first FIR lodged is under the Arms Act because there was open firing. Beyond that no action is taken against the criminals threatening naked violence.” She also cannot get over the irony of the UP government asking for the postponement of the release of Padmavati. “The UP government is asking for a delay in Padmavati’s release as they foresee a law and order problem! But the first vow the CM took was to firmly clear the State of its criminal elements. Aur film ki release hone pey ghutne tek diye?!!.” Shabana Azmi also lashes out at the censor board for delaying the certification of Padmavati. “The CBFC sends the film back because some paperwork is not complete! Only after 63 days will the film be screened for CBFC when Gujarat election is over and done with! Are we fools to not see through the design of fomenting unrest and polarizing votes?” The formidable actress-activist doesn’t hide her resentment at what she sees as a victimization of the entertainment industry for political purposes. “I am very angry. Film Industry needs to take a strong unified action and refuse to be sitting ducks anymore. If such threats had been made against any member of the political class would the reaction have been the same? Are the people in the film industry not equal citizens of this country?”
2024-07-26T01:27:15.642919
https://example.com/article/3468
package de.undercouch.bson4jackson.serializers; import com.fasterxml.jackson.databind.module.SimpleSerializers; import de.undercouch.bson4jackson.types.JavaScript; import de.undercouch.bson4jackson.types.ObjectId; import de.undercouch.bson4jackson.types.Symbol; import de.undercouch.bson4jackson.types.Timestamp; import java.util.Calendar; import java.util.Date; import java.util.UUID; import java.util.regex.Pattern; /** * BSON serializers * @author James Roper * @since 2.0 */ public class BsonSerializers extends SimpleSerializers { private static final long serialVersionUID = -1327629614239143170L; /** * Default constructor */ public BsonSerializers() { addSerializer(Date.class, new BsonDateSerializer()); addSerializer(Calendar.class, new BsonCalendarSerializer()); addSerializer(JavaScript.class, new BsonJavaScriptSerializer()); addSerializer(ObjectId.class, new BsonObjectIdSerializer()); addSerializer(Pattern.class, new BsonRegexSerializer()); addSerializer(Symbol.class, new BsonSymbolSerializer()); addSerializer(Timestamp.class, new BsonTimestampSerializer()); addSerializer(UUID.class, new BsonUuidSerializer()); } }
2023-10-27T01:27:15.642919
https://example.com/article/2134
The Indianapolis Colts have needs all over their roster, particularly on the defensive side of the football. New general manager Chris Ballard realizes that he has plenty of work to do on defense, and that will surely start with the front seven. The Colts desperately need pass rush help, and they also need starting inside linebackers. In all honesty, the Colts need four starting linebackers. They have needs other places, too, and one of those places you’ll see people talking about is at running back. With Frank Gore set to turn 34 this spring, the Colts need a young back to play with Gore and be the running back of the future. The Colts won’t be able to truly address every need this offseason in a satisfying way, but they’ll certainly do their best to fill as many as possible in free agency and the draft. Free agency is less than a month away, while the draft is still a little further away. The NFL Scouting Combine is just a couple of weeks away, however, so there will be a lot of draft talk coming in the next few weeks. Because of that, NFL Media’s Mike Mayock has released his initial position rankings for the 2017 NFL Draft, listing the top five players at each position. The Colts have a number of needs, but let’s take a look at his rankings for three Colts needs in particular: EDGE Rusher: 1. Myles Garrett, Texas A&M 2. Tim Williams, Alabama 3. Derek Barnett, Tennessee 4. Solomon Thomas, Stanford 5. Takkarist McKinley, UCLA This is easily the Colts’ biggest need, and the good news is that there are plenty of good players at the position in this year’s draft. While there’s absolutely zero chance that Myles Garrett will still be there when the Colts pick, the other guys on Mayock’s rankings could be, depending on how teams rank these guys and how the draft goes. The Colts have to be rooting for as many quarterbacks, running backs, wide receivers, etc. as possible to go before their pick, as that would push a lot of the defensive talent down the board. Linebacker: 1. Reuben Foster, Alabama 2. Haason Reddick, Temple 3. Zach Cunningham, Vanderbilt 4. Jarrad Davis, Florida 5. Alex Anzalone, Florida I think, just like most people would agree that Myles Garrett is the best overall prospect in the draft, most people would agree that Reuben Foster is the best inside linebacker in this draft. It was reported yesterday that he underwent shoulder surgery, however, which could push his draft stock down a bit - meaning he could possibly be there for the Colts’ pick. Running Back: 1. Dalvin Cook, Florida State 2. Leonard Fournette, LSU 3. Christian McCaffrey, Stanford 4. Alvin Kamara, Tennessee 5. Joe Mixon, Oklahoma It’s certainly worth noting that Mayock has Dalvin Cook as his top running back over Leonard Fournette, though that’s not a crazy opinion as others share it too. I think there are varying opinions about whether Cook or Fournette is the top back in this year’s draft, and it’s possible that both will be gone by the time the Colts pick. There are a number of mock drafts that have the Colts taking Cook, and while he would certainly be a big help, there are other running backs who will be available in later rounds that could also be interesting fits. The good news for the Colts is that there seem to be a number of good options at their positions of need who will be available when they pick in the first round. Chris Ballard will have some key decisions to make, and a big part of that will be the scouting process over the next several weeks. But if you want to get an idea of who the best players are at some of Indy’s top positions of need, Mayock’s rankings are a good place to start.
2024-03-08T01:27:15.642919
https://example.com/article/5995
Menu Conservative Grief at the End of Federalism Since the Supreme Court ruled 5-4 in favor of the constitutionality of the president’s health care plan, conservatives have been alternatively angry and despondent. To many observers, this reaction may appear to have its roots in hatred of the president, racism, an inability to understand the constitution, a lack of compassion, or excessive partisanship. None of those reasons explain the depth of the feelings of protest that exist and appear to be building. The United States constitution sets out a unique form of government. In the wake of revolution, the former British colonies became classic states with inherent power to govern with the consent of the people. The United States of America emerged in the form we know as a new and special type of entity. This national government would only have certain powers the states deemed necessary. Thus, this national government would be a limited government of delegated powers. This distinction helps explain why it has been uncontroversial for the states to require people to buy auto insurance, while it is a very big deal to see the national government attempting to act in the same way. The United States government is acting as though it is a government of inherent powers rather than one of delegated powers. Now, for many people this transformation of the national government from limited to omni-capable makes perfect sense. In the modern age, they believe, a central government must have wide authority to act. It must be able to tackle big problems. Conservatives, they charge, are attached to an antiquated system. But conservatives do not approve the federal system merely because it is old. There are older systems. Power under one head is older. Conservatives approve the system of states with broad power to govern and a central government with limited, delegated powers because it guarantees that most of the laws one lives under will be laws enacted close to home. Under a truly federal system, government is predominantly local. People who live in our states and in our communities should be the ones to work out the laws under which we live because of their familiarity with our local strengths, resources, traditions, threats, and challenges. People may be surprised to hear the news that Justice Kennedy worked unceasingly for a month to try to keep Justice Roberts from siding with the liberals, but his position on the case should not have been a surprise. Justice Kennedy has written clearly about his admiration for federalism as the great American contribution to governing. When he has gone against it, it has been to protect personal liberties he deemed of vital importance. In this case, the question was whether we would continue to have a truly federal system. It was perfectly in character for him to try to maintain our special contribution. For decades, conservatives have waited to see the Supreme Court cut back on the broad license of power granted to the central government as part of the New Deal (under the threat of court-packing). There have been signs that power was being cut back (such as the Lopez decision in 1995). We believed this case would finally end the ultra-expansive view of the commerce power and would restore a sense of limits to the central government’s power. Our hopes were sharply disappointed because the court ruled that we were correct about the commerce power, but then extended the power of the United States government through a broad construction of its power to tax. If this power to tax is as broad as the court says it is, then it is difficult to see where the reach of the central government ends. From the conservative viewpoint, we have lost federalism. Most people don’t know what federalism is and don’t care. But we do. The loss of government close to home is a great loss, indeed. It means the individual is more at the mercy of the mass than ever. It also means that the best means of limiting the power of the central government is gone. Every American student of civics is taught that the constitution has checks and balances in which the legislative, executive, and judicial branches rein each other in. What they have learned too rarely is that the best limit on the power of national governments is for some powers not to be granted to them at all. Article I, Section 8 of the constitution lists out the powers of the United States government. That was once a clear guide to what the government could and could not do. After the court’s ruling, one wonders why the framers of the document felt the need to include a list at all as it is apparently superfluous. Post navigation 4 thoughts on “Conservative Grief at the End of Federalism” Thank you for this carefully reasoned piece. It is one of the best things I have seen dealing with the healthcare legislation. It is nice to see someone talk about the serious constitutional and political issues at stake rather than just making appeals to emotion. I recommended this to my Facebook friends. P.S. — Are you aware of Os Guinness new book “A Free People’s Suicide: Sustainable Freedom and the American Future?” It deals, in part, with issues that tie in to this issue as well. Scott, many libertarians and conservatives fear the combination of distant governments and corporations the most. It is an unholy mixture. Comments are closed. Bestselling author Andrew Klavan on The End of Secularism: Anyone who works in the writing business will understand: I don’t have time to read books sent or lent to me unrequested. What with informational reading, professional reading and reading for my craft and spirit, even books I want to get to sometimes have to wait as long as a year. Plus I don’t remember ever having met Hunter Baker of [Union] University so I don’t know why he had his publisher send me his new book The End of Secularism. But I’m startled to report I glanced at it while laying it aside, then picked it up again, then read it through. This is a very well written, concise and learned primer on the secularization of the public square. It gives a fair recital of the arguments in favor of it, and a strong but sensible and moderate outline of the arguments against. It has a firm grasp of history and neither falls for the usual “This is a Christian country!” rhetoric that makes its way onto television nor accepts the “separation of church and state,” pieties that were rendered obsolete by the state’s aggressive intrustion into what Dr. Baker calls “the life-world,” ie. our values and private lives. It’s a book you’ll be glad you read the next time you get in an argument about religion’s role in politics. I wish I had time to write a full review of this book in a respectable venue (as opposed to this Blog of Ill Repute!). I just don’t. But if anyone from First Things or World Magazine or even the Weekly Standard or NRO is skulking through here and sees this, I think the book is well worth discovering.
2023-11-13T01:27:15.642919
https://example.com/article/1027
Film and Literature Reviews, Criticism, and Analysis. As well as personal artistic projects Menu Where do you begin, and I end?: Ingmar Bergman and Mixed Personality POTENTIAL SPOILERS: It’s also from 1966 so I don’t feel bad about this. There are very few films in my life that have made me gasp in shock from an editing technique. Ingmar Bergman’s Persona is one of these films. The editing means everything to Bergman’s 1966 horror thriller, it creates a taught meta film that plays with where reality actually is. The film begins in a projection room that begins to flash and burn through reels of footage, a video of the two main characters of the film is projected onto the wall of a small boy’s room. The main characters begin to flash between each other and the movie begins. Part way through the movie the celluloid film burns out and then continues on as if nothing happened. Bergman made sure that the editing within Persona was constantly making the viewer aware that they are watching a film. In this way, it’s an incredibly meta film but I digress from this point. The film’s editing is so stellar and mixes several realities, without the energetic editing of the film Persona would most likely be a mediocre film at best. Persona is also carried by its strong female leads and stunning framing. The movie often has Alma (Bibi Anderson) move over Elisabet Vogler’s (Liv Ullman) face, juxtaposing Alma’s head over Elisabet’s own to make it appear as if Alma is Elisabet. The real question of this movie is whether or not Alma is Elisabet, and if you look around you’ll find people are really torn on this. I personally thought that it was spelt out fairly clearly, however it is very much so open for each viewer’s interpretation, and I think that only adds to the malicious spirit of the movie. For all it’s worth, the setting of the film is rather sparse, the acting is really what makes this film a stand-out performance. Liv Ullman’s character has next to no lines, and Bibi Anderson has massive monologue after massive monologue. The fact that she could deliver all of these with increasing maliciousness throughout the film is astounding. She ratchets up the intensity from caring to hatred really quick, and it’s very believable. With next to no lines, Elisabet is a fascinating character, as she does all of her acting silently. We get to see her very expressive face fill with horror, deceit, compassion. Persona takes us through the full spectrum of human emotion with Elisabet’s face and takes us through both character’s struggles through Alma’s voice. The two are inseparable as one without the other makes the movie impossible, both are reliant on each other to tell the story. Without Elisabet’s facial expressions and actions we wouldn’t be able to interpret Alma’s own inner suffering, while without Alma’s monologues and probing speeches we would have no idea what was going on inside Elisabet’s head. It’s the fact that they’re perfect for each other that makes the viewer wonder if they are one in the same and if this is actually just a conversation with Alma’s own subconscious. Persona in its entirety is an absolutely gorgeous film filled with questions and mysteries to unlock. The lack of complete explanation of all of the imagery in the film makes it all the more intriguing to watch. It’s a film that has inspired the likes of David Lynch, David Cronenberg and David Fincher (I honestly didn’t expect those examples to all be David’s). Especially with Fincher’s Fight Club the inspiration is seen clearly. A movie that is as daring and provocative today as it was when it was first released, Persona is a classic that will continue to haunt viewers for years to come.
2023-08-21T01:27:15.642919
https://example.com/article/4781
Valgus stability of the elbow. The valgus stabilizers of the elbow have been identified anatomically, but their relative importance has not been quantified. The purpose of this study was to analyze the acute changes of the torque-displacement curve to valgus stress following (a) section of the posterior portion of the medial collateral ligament; (b) excision of the radial head; (c) prosthetic replacement of the radial head; and (d) excision of the anterior portion of the medical collateral ligament. Thirty cadaver specimens underwent load-displacement testing in three positions: 0 degrees, 45 degrees, and 90 degrees of flexion. The anterior portion of the medial collateral ligament was the primary stabilizer of the elbow to valgus stress. The relative contribution of the posterior ligament was minimal. After excision of the radial head alone, the slope of the load-displacement curve decreased an average of 30%. Silicone rubber radial head replacement did not significantly improve the stability to valgus stress after radial head excision.
2023-11-16T01:27:15.642919
https://example.com/article/5540
[Replacement therapy with subcutaneous immunoglobulin in primary immunodeficiency in children]. Primary antibody deficiency (PAD) is the most common form of primary immunodeficiency (PID), and presents up to 60-70% of PID. The hallmark of PAD are low antibody level and recurrent infections. Patients require life-long immunoglobulin replacement therapy. Now they can be treated either with intravenous (IVIG) or subcutaneous (SCIG) immunoglobulin. The last one is indicated in patients with unacceptable adverse reactions to the intravenous immunoglobulin preparations, with poor vein access or willing to improve the quality of their life. Several data and clinical trials proved that SCIG therapy is at least as safe and efficacious as IVIG to prevent infections in patients with PAD.
2024-04-02T01:27:15.642919
https://example.com/article/9355
Pink Empress Round Baby Bassinet A Beautiful Way to Start Off Her Life!This lovely and unique bassinet is the perfect sleeping space for your new arrival. With its pink graceful canopy to shield your little one from the light, and its lovely pink pleated skirt, your little one is all set for a delightful start. With a mesh storage shelf hidden behind the skirt for all your darling's diaper changing supplies, this bassinet is as practical as it is beautiful.
2024-06-19T01:27:15.642919
https://example.com/article/5367
Translocations of the MLL (Mixed Lineage Leukemia) gene are frequently found in human leukemias affecting both children and adults. Fusion of MLL to one of more than 60 genes results in generation of oncogenic proteins upregulating Hox genes that are vital to blood cell development. Patients harboring fusion of the MLL gene suffer from aggressive leukemias and poorly respond to available therapies. All of the oncogenic fusion proteins have a preserved N-terminal fragment of MLL that has been identified to interact with menin. It has been recently discovered that association with menin is critical to the leukemogenic activity of the MLL fusion oncoproteins. Selective targeting of the menin-MLL interaction has been emphasized as an effective therapeutic approach for the MLL-related leukemias. We propose to use HTS to develop small molecule inhibitors of the menin-MLL interaction as a potential therapeutic approach for acute leukemias related to MLL-translocations. No attempts to develop small molecule inhibitors of the menin-MLL interaction were reported to date. As a step in this direction, we have developed a fluorescence polarization (FP) assay for efficient screening of the MLPCN compound library at 10 5M concentration to identify inhibitors of this protein-protein interaction. To eliminate "false-positives" and identify ligands targeting menin we have optimized the secondary screenings by application of HTRF and NMR saturation transfer difference (STD) experiments. In this proposal we delineate an efficient strategy to combine HTS based on FP, HTRF and STD assays to develop inhibitors of the menin-MLL interaction, and then optimize their activities by medicinal chemistry approaches. Initial screening of small library of compounds resulted in identification of several weak ligands, demonstrating feasibility of such an approach. The most potent compounds developed and optimized within this proposal will be tested using appropriate leukemia cell- lines harboring MLL translocations. We believe that we will initiate a successful collaborative project to develop chemical compounds that may constitute a novel approach for treatment of acute leukemias related to genetic disorders of MLL gene. Furthermore, this work will facilitate the understanding of biological consequences of inhibiting the menin-MLL interaction and its impact on the disease development. PUBLIC HEALTH RELEVANCE: We propose to use high throughput screening (HTS) to develop chemical compounds that may reverse the oncogenic function of proteins causing acute leukemia. Ultimately, such compounds could be used as highly specific drugs for treatment of patients with aggressive forms of leukemia, which poorly respond to current therapies. [unreadable] [unreadable] [unreadable]
2023-09-24T01:27:15.642919
https://example.com/article/7514
This is an archived article and the information in the article may be outdated. Please look at the time stamp on the story to see when it was last updated. CLEVELAND — All of the teams in Cleveland’s Baseball Federation have new Indians jerseys to wear for their 2019 season. Saturday some of the players helped distribute them before their game. That includes Tribe outfielder Jake Bauers who was on hand to deliver the first 200 jerseys being donated. 10 teams received their jerseys at the Zelma George Recreation Center. In all, 2,500 jerseys will be donated to the city of Cleveland. Bauers said it’s special to be apart of this. More on the Cleveland Indians, here.
2023-10-17T01:27:15.642919
https://example.com/article/1433
If you want a career as a mechanic, Surry Community College can send you on the road to a bright future with the Automotive Systems Technology program. Students learn how to apply technical knowledge and skills to repair, service, and maintain all types of automobiles. High school juniors and seniors can take Automotive Systems Technology classes tuition-free through the Career & College Promise dual enrollment program. Surry’s instructors are certified by the National Institute of Automotive Service Excellence. Night classes are offered. Hello, my name is David Weavil, and I am the Lead Automotive Instructor here for the Automotive Systems Technology at Surry Community College. Within this program, students learn to be successful automotive mechanics. This is a very hands-on program. The students do work in the classroom and learn the basics in the classroom through lecture, but the majority of work is done in the shop through hands-on learning in the lab setting here in the V-Building at Surry Community College. Students learn how to do the basic service items such as rotate tires, oil changes, changing cabin filters, transmission services and other routine car maintenance items. Then, they learn how to replace the brake pads, repair electrical systems, work on automatic and manual transmissions. Students will know how to troubleshoot engine performance and make repairs to their cars through the program. They will also deal with suspension, steering and drive train issues along with learning how to fix heating and air condition systems. In the lab we do a variety of work. One day we might be running a Power Balance Test on a car to determine what is making it misfire. Another day, we will be aligning cars. We may be working on heating and air conditioning systems. We may be working with electronics. We also teach students about alternative fuel vehicles, hybrids and the most modern automotive technology systems available. One topic we work on or talk about is car hacking. A modern car can be hacked – computer hacked, meaning that the car functions could be taken over by an outside source, and that is a real concern in automotive technology. And we do talk about that, deal with that and learn about that, as well as for instance self-driving cars and how we believe that will be really big in the future. We also take field trips to race shops, speedways, and some salvage yards to learn different aspects of the automotive technology field. Within the salvage yards, we do scavenger hunts to learn what different systems look like on the cars. They have to find certain items and how they differ from car to car. Degree and diploma seeking students can enroll in Work-Based Learning, which allows them to work for a company and earn college credit at the same time. These students enjoy networking in the industry while also gaining experience with the top of the line equipment right on campus. One of the great things about Surry Community College is the state-of-the-art equipment that we have here. The guys behind me right now are using the snap-on MODIS, which is a cutting edge technology for checking engine lights, scanning cars and things of that nature. We also have a new front end alignment machine, a great tire balancer – lot of good equipment here at Surry. Students also learn proper and safe work practices as defined by OSHA for clothing, eye protection and how to handle tools, power equipment, and the correct storage and disposal of chemicals. We teach them how to run their own garages how to be employed as an automotive technicians or shop foremen. They also leave the Automotive System Technology program knowing how to communicate with their employers and their customers about the repair and service needs. Mechanics make about about $37,000 per year on average and have the freedom to go into business for themselves or decide to work for someone. My plans after graduating from Surry Community College is to work for a dealership. I currently work right now, but I want to do a dealership after I graduate, and maybe 15 to 20 years from now build up enough money to own my own shop. I love working with my hands. That’s why I am in this program. As a kid, I have always told myself, man, I am good with my hands. What can I do to make with my hands? As I grew older, I started liking vehicles and fast cars, and I have always wanted to know what I can do to improve a vehicle or a car in general. I love a lot of things about this program. They teach us a lot, and I learn a lot from it too. One of the most interesting things is how to align a car. You go in a shop or you go to this dealership, and they work on your car, but you don’t know exactly how they do it. Until you are in it or experience it, it’s a total different world down there underneath the car, and it’s amazing how you learn from it and how every vehicle, trucks, muscle cars and sports cars are different. Part of the reason I chose Surry other than any other college is because they’re always on top of up-to-date new equipment. For an example, it could be for the AC machine, alignment racks and tools, and tools especially…Good thing I chose this college because they are up to date on tools. Student Cory Moxley decided to commute to Surry Community College from his home because he wanted the mechanics lab experience that wasn’t offered nearby. The 40-minute drive was hard at first, but I knew the instructors here are great, the equipment and stuff like that. It’s really good learning experience and learning environment as well. So that kept me going, coming to Surry. It’s a lot of hands-on work, you know, you will be in the room studying up on subjects whether it be brakes or engines, but three-quarters of the class is going to be out in the shop – hands work. That’s what I enjoy the most. This is my friend’s Allen’s car. Right now we are getting ready to rebuild the transmission. We took it out. It’s on a table in there in the transmission room, and next semester we have the manual transmission class, so we are going to try to rebuild it there. One of the coolest things we were doing…It was an engine repair class. Mr. Weavil actually picked up a 350 engine from a junk yard that had a bad engine knock with it. So, what we did is, we completely stripped it down, re-bored the cylinders inside the engine and got a full rebuild kit…So, it’s kind of cool to get to do stuff that is hands-on, and it will actually pay off in the long end by someone actually getting to use it. After I graduate, I probably am going to try to get in on a smaller shop. I live in Sparta, so there are a few shops around there I could go to, maybe here in Dobson even. But, eventually, I want to work in a dealership. Subaru is really what I am looking for. I am really into Subarus, so anything to do with that would be something I would be happy with. Students can earn a degree, a diploma, or certificate in Automotive Systems Technology at Surry Community College and can be prepared to take the National Institute of Automotive Service Excellence exam when they graduate. They will also be ready for full-time employment in dealerships and repair shops. For more information, go to www.surry.edu. You can also follow the program on Facebook @surryautomotive.
2023-10-21T01:27:15.642919
https://example.com/article/3941
Q: SelectListItem[] alternatives at non UI levels in ASP.net mvc I have seen usage of SelectListItem[] at BL, DAL etc. levels that are not in the aps.net MVC project. I am inclined to use anything that is IEnumerable<KeyValuePair<string, string>> instead e.g. Dictionary<string,string> c.f. Creating the IEnumerable<KeyValuePair<string, string>> Objects with C#? My reasons are not to add the extra dependency on Web.MVC when not needed and SelectListItem belongs to MVC context as it is heavier than IEnumerable<KeyValuePair<string, string>> Are these legitimate reasons or there are counter points to above that one should consider. Are there any well know principals that would prefer one over the other, e.g. is there a principal to reduce dependencies when not needed? A: Programming to an interface will help to decouple components and improve reusability in larger systems. Think about what it says to you when you see a method signature returning an IEnumerable<T> instead of an IList<T>. You know the designer expected you to enumerate the result, and you can reasonably assume that they did not intend for you to mutate the result in place. When designing a new component or library, I start by asking myself about the behavior I expect on either side of a method. Does the caller really need to supply an int[], or can I get by with an IEnumerable<int>? Further, if I require the array, does that mean I'm pushing an opinion onto the consumer? "You should always give me an array, because I think arrays are better." At the same time, if a method signature takes an IDictionary<TKey, TValue>, I can easily swap a Dictionary<TKey, TValue> for an ImmutableDictionary<TKey, TValue> if I decide that my code would benefit from some of the new(ish) immutable collections. As for whether or not you should reduce your dependencies, I think that's a question for your team to reflect on in the context of the project requirements. But on the question of replacing concrete types with interfaces where applicable and beneficial: go for it.
2024-05-15T01:27:15.642919
https://example.com/article/6994
Hall, whose acting credits include an early 80s stint on Saturday Night Live and a guest appearance on Curb Your Enthusiasm, will play Wreston Sarnoff, a well-dressed, talented and exceptionally gracious architect from neighboring town Eagleton who offers to design a new park for Pawnee. Of course, given Eagleton’s history of pranking Pawnee, Leslie is very suspicious.
2024-04-13T01:27:15.642919
https://example.com/article/6446
--- abstract: 'In this paper, we present a simple model of a three-dimensional insulating magnetic structure which represents a magnonic analog of the layered electronic system described in \[Phys. Rev. Lett. [**107**]{}, 127205 (2011)\]. In particular, our model realizes Weyl magnons as well as surface states with a Dirac spectrum. In this model, the Dzyaloshinskii-Moriya interaction is responsible for the separation of opposite Weyl points in momentum space. We calculate the intrinsic (due to the Berry curvature) transport properties of Weyl and so-called anomalous Hall effect (AHE) magnons. The results are compared with fermionic analogs.' author: - 'Vladimir A. Zyuzin' - 'Alexey A. Kovalev' bibliography: - 'MyBIB.bib' title: Spin Hall and Nernst effects of Weyl magnons --- Introduction ============ Recently, studies of intrinsic (topological) properties of fermionic systems have received tremendous interest from the research community. Some of these studies have concentrated on the quantum Hall effect,[@LaughlinPhysRevB.23.5632; @TKNN_PhysRevLett.49.405] Chern insulators,[@HaldanePhysRevLett.61.2015] topological insulators,[@VolkovPankratovJETPlett1985; @KaneMelePhysRevLett.95.146802; @HasanKaneRevModPhys.82.3045; @Bernevig.Hughes.ea:S2006] and Dirac (Weyl)[@Murakami2007NJP; @WanTurnerVishwanathSavrasovPhysRevB.83.205101; @BurkovBalentsPhysRevLett.107.127205] semimetals. Of particular interest are the transport properties and transitions between various topological phases. The Berry curvature[@Berry1984] plays an important role in descriptions of the intrinsic transport properties such as the Hall, Nernst, and axial or chiral current responses. [@RevModPhys.82.1959] In a phase transition that separates two insulating phases with different topological numbers, a semimetal phase necessarily occurs. This semimetal phase is characterized by a band touching and, in general is called the Dirac semimetal, a condensed-matter analog of relativistic fermions. Under breaking of either time-reversal or inversion symmetry, opposite chiralities separate either in momentum or energy, and in this way the so-called Weyl semimetal is stabilized. This scenario is realized in an analytical model presented in Ref. \[\]. The Weyl semimetal phase is of interest as it exhibits the anomalous Hall effect (AHE), surface Fermi arcs, and chiral anomaly driven responses. Similar topological effects are recognized in magnetic insulating systems. Due to a combination of the underlying lattice geometry and Dzyaloshinskii-Moriya interaction (DMI),[@Dzyaloshinsky:JoPaCoS1958; @Moriya:PR1960] the magnon bands can acquire a non-trivial Berry curvature and non-vanishing Chern numbers. [@Matsumoto.Murakami:PRL2011; @Shindou.Matsumoto.ea:PRB2013; @Zhang.Ren.ea:PRB2013; @Shindou.Ohe.ea:PRB2013; @Mook.Henk.ea:PRB2014; @Mook.Henk.ea:PRB2014a] As in the case of fermions, magnons can exhibit spin Nernst[@KovalevZyuzin2016; @RanOkamotoXiao2017; @ZyuzinKovalev2016] and thermal Hall responses,[@Katsura.Nagaosa.ea:PRL2010; @Matsumoto.Murakami:PRL2011; @Zhang.Ren.ea:PRB2013; @Matsumoto.Shindou.ea:PRB2014; @Lee.Han.ea:PRB2015; @Owerre2016JAP] and induce dissipative torques[@KovalevZyuzin2016] on the magnetic order. For example, the thermal Hall effect carried by magnons has been experimentally observed in insulating collinear ferromagnets with pyrochlore crystall structure.[@Onose.Ideue.ea:S2010; @Ideue.Onose.ea:PRB2012] The spin Nernst effect carried by magnons[@RanOkamotoXiao2017; @ZyuzinKovalev2016] was recently observed[@ShiomiTakashimaSaitoh2017] in an antiferromagnet. Different magnetic models have been proposed for realizations of the aforementioned intrinsic effects. These include two-dimensional kagome[@MishchenkoStarykhPhysRevB.90.035114; @Mook.Henk.ea:PRB2014a; @KovalevZyuzin2016] and honeycomb[@OwerreJPCM2016; @Owerre2016JAP; @PhysRevLett.117.227201; @Wang.Su.ea:PRB2017] magnets as well as pyrochlore[@Ideue.Onose.ea:PRB2012; @PhysRevLett.118.177201] and layered structures. By tuning exchange parameters some of the above magnetic systems reveal magnons described by a Weyl spectrum.[@WeylMagnons2016NatComm; @PhysRevLett.117.157204; @PhysRevB.95.224403; @0256-307X-34-7-077501; @Su.Wang:PRB2017; @2017arXiv170802948J; @OwerreArxiv2017a; @OwerreArxiv2017b] In this paper, we propose a new model that realizes Weyl magnons and the magnon analog of Fermi arcs. The model contains interchanging layers of honeycomb ferromagnets and antiferromagnets (see Fig. \[fig1\]). This is needed to establish the opposite chiralities of magnons. We show that in this model the magnon spectrum and topology qualitatively resemble those considered in Ref. \[\] and \[\] for fermions. For example, by varying inter-layer exchange parameters the nodal-line spectrum of magnons emerges (see Fig. \[fig\]). Furthermore, we observe a magnon surface states with the Dirac spectrum. These surface states might hybridize with the bulk states as they are shifted in energy. Our model can also be interpreted as a magnon analog of the 3D Shockley model.[@PhysRevB.86.075304; @Pershoguba.Banerjee.ea:PRX2018] When the DMI is switched on, either Weyl magnons or the magnon analog of stacked two-dimensional anomalous Hall effect layers (the so-called AHE magnons) are obtained. We study intrinsic (due to the Berry curvature) spin transport properties of the Weyl and AHE magnons. Magnon pumping due to magnetization dynamics was discussed in Ref. \[\]. Importantly for the present paper, one can draw an analogy between fermions responding to electric field and magnons responding to magnetization dynamics. As mentioned in Ref. \[\], in the case of a Weyl semimetal the AHE is semi-quantized, and it is proportional to the splitting of Weyl points in momentum space. In this paper, we show that the vicinity of the Weyl points leads to the magnon-driven spin current proportional to the splitting of Weyl points. However, other regions of the Brillouin zone also contribute to the response. For the AHE magnons, at small temperatures we recover the results of Ref. \[\]; that is, the response is proportional to the DMI strength, and it is a response of a number of stacked layers of two-dimensional Chern magnons. At higher temperatures, the response from the Weyl points acquires an extra logarithmic factor corresponding to the energy cutoff. In both cases the responses are temperature dependent, vanishing at zero temperature. This paper is organized as follows. In section \[section1\], we briefly review the Shockley model given in Ref. \[\]. Then, we construct a more general model that contains the Weyl and AHE magnons. We discuss how different phases emerge as the parameters of the model, such as DMI and exchange interactions, change. In section \[section2\], we study the intrinsic responses of the Weyl and AHE magnons, both analytically and numerically. For the analytical calculations, we adopt a simplified model that captures the contribution from the Weyl points. In the Appendix, we give details of the calculations. Topological magnons in layered systems {#section1} ====================================== 3D Shockley-like model ---------------------- Before we formulate our model of Weyl magnons, we give here a brief description of the 3D Shockley-like model introduced in Refs. \[\]. In such Shockley-like models one can obtain different topological phases with surface states. It is also known that a Weyl semimetal occurs at the phase transitions between the topological phases.[@Murakami2007NJP] Therefore, in the magnon version of the Shockley-like model one can expect magnon analogs of known topological phases including the Weyl phase, which is of particular interest to us. The Shockley-like model is described by the Hamiltonian $$\begin{aligned} \label{eq:Shockley} H &= \left( \begin{array}{cc} h({\bf k_{\parallel}}) & t(k_z,{\bf k_{\parallel}}) \\ t^{*}(k_z,{\bf k_{\parallel}}) & -h({\bf k_{\parallel}}) \\ \end{array} \right),\end{aligned}$$ where two types of interchanging layers are described by $\pm h({\bf k_{\parallel}})$ and the interlayer hopping amplitudes are described by $t(k_z,{\bf k_{\parallel}})$. Note that $h({\bf k_{\parallel}})$ could in principle correspond to a matrix, e.g., due to the spin or sublattice degrees of freedom. Taking $t(k_z,{\bf k_{\parallel}})=t_1({\bf k_{\parallel}})e^{-i k_z}+t_2({\bf k_{\parallel}}) e^{i k_z}$, one can obtain that such a model can describe surface states when $|t_1({\bf k_{\parallel}})|<|t_2({\bf k_{\parallel}})|$, where the layers have to be interrupted at the $t_2({\bf k_{\parallel}})$ bond. In $(k_x,k_y)$ regions where such a condition is satisfied the surface states are described by the spectrum $h({\bf k_{\parallel}})$, and can contain a Dirac cone. As we will show below, our model of Weyl magnons given by Eq. (\[eq:matrix\]) without the DMI corresponds to the model in Eq. (\[eq:Shockley\]). A realization with magnons -------------------------- We study spins located at the sites of a three dimensional lattice made of honeycomb layers stacked in the AA type. The unit cell of the system contains two honeycomb layers (see Fig. \[fig1\]A). For the bottom layer of the unit cell the first and second nearest neighbor exchange couplings are assumed to be ferromagnetic and antiferromagnetic, respectively. For the top layer the types of exchange couplings are switched (see Fig. \[fig1\]A). For simplicity, the exchange coupling between the layers, $J^{\prime}_{\mathrm{a}}$, within the unit cell is chosen to be ferromagnetic. We also include the Dzyaloshinskii-Moriya interaction (DMI) and an external magnetic field. A three dimensional system is obtained by translating the unit cell in the $z-$direction with the inter unit cell exchange coupling $J^{\prime}_{\mathrm{e}}$. The spin Hamiltonian is $$\begin{aligned} \label{ExchangeHamiltonian} H &= \sum_{m p \langle ij \rangle } (-1)^{p} J_{1} {\bf S}_{mpi}{\bf S}_{mpj} - (-1)^{p} J_{2} {\bf S}_{mpi}{\bf S}_{mpj} \\ & + \sum_{m p \langle\langle ij \rangle\rangle } {\bf D}_{(ij)}^{[\mathrm{z}]} \left[{\bf S}_{mpi} \times {\bf S}_{mpj} \right] - \mu_{\mathrm{B}} \sum_{mki} {\bf B}{\bf S}_{mpi} \nonumber \\ & + \sum_{m p \langle ij \rangle } (-1)^{p}{\bf D}_{(ij)}^{[\mathrm{R}]} \left[ {\bf S}_{mpi} \times {\bf S}_{mpj} \right] \nonumber \\ & - \sum_{m i} J^{\prime}_{\mathrm{a}} {\bf S}_{m 1 i}{\bf S}_{m 2 i} - \sum_{m i} J^{\prime}_{\mathrm{e}} {\bf S}_{m 2 i}{\bf S}_{m+1, 1 i} \,, \nonumber\end{aligned}$$ where the constants $J_{1}$, $J_{2}$, $J_{\mathrm{a}}^{\prime}$, and $J^{\prime}_{\mathrm{e}}$ denoting the exchange coupling are chosen to be positive and index $p=1,2$ denotes the bottom and top layers of the unit cell. The unit cell is translated in the $z-$direction, and $m = 1,2,3,\dots$ denotes the number of the unit cell. The vector ${\bf D}_{(ij)}^{[\mathrm{z}]} = D^{[\mathrm{z}]}{\bf e}_{z}\nu_{ij}$ is the out of plane second-nearest neighbor DMI with $\nu_{ij}=\pm$ signs for an $(ij)$ link shown in green in Fig. \[fig1\]B and the vector ${\bf D}_{(ij)}^{[\mathrm{R}]} = D^{[\mathrm{R}]} {\bf d}_{l}$ is the in-plane DMI of the Rashba type. Index $l=1,2,3$ denotes an $(ij)$ link on a lattice corresponding to a ${\bm \tau}_{l}$ vector (see Fig. \[fig1\]B) along which the spins interact. For a link $l$ the Rashba DMI vectors are ${\bf d}_{1} = \frac{1}{2}(\sqrt{3},-1)$, ${\bf d}_{2} = \frac{1}{2}(-\sqrt{3},-1)$, and ${\bf d}_{3} = (0,1)$, defined in red in Fig. \[fig1\]B. Note that the sign of the Rashba DMI for the same bond is opposite in the bottom and top layers. The reason for such a choice of DMI will be seen in the next section, where we study the responses of the system. Such DMI can be achieved by placing an extra non-magnetic charged layer between the top and bottom layers, such that the Rashba spin-orbit coupling is generated with opposite signs in the top and bottom layers. Note that there might also be a second-nearest neighbor in-plane DMI of the Rashba type. We omitted it as it does not lead to qualitatively different physical picture and is smaller than the first-neighbor Rashba DMI. All DMIs are small, such that $\frac{D^{[\mathrm{z}]}}{J_{1}} \ll 1$ and $\frac{D^{[\mathrm{R}]}}{J_{1}} \ll 1$. We assume that the magnetic field ${\bf B}$ is above the saturation value so that all spins align with the field. The direction of the field and hence of the magnetization is assumed to be general, namely $(m_{x},m_{y},m_{z})$, however, with the main component in the $z-$ direction, i.e. $m_{z} \gg m_{x},m_{y}$. Alternatively, the magnetic anisotropy in the $z-$ direction could also be used instead of the magnetic field to align spins in the $z-$ direction. We are now ready to study the magnons, fluctuations around the magnetization direction. The unit cell contains four elements, and a set of four boson operators is needed to describe the magnons. We perform the Holstein-Primakoff transformation, $S_{n}^{z}({\bf r}) = S - a_{n}^{\dag}({\bf r})a_{n}({\bf r})$ and $S^{+}_{n}({\bf r}) = S_{n}^{x}({\bf r}) + iS_{n}^{y}({\bf r}) = \sqrt{2S - a_{n}({\bf r})^{\dag}a_{n}({\bf r})} a_{n}({\bf r})$ with $a_{n}({\bf r})$ and $a_{n}^{\dag}({\bf r})$ for $n = 1,2,3,4$ denoting the four inequivalent sites of the unit cell, being the boson operators. Assuming $S \gg 1$, we obtain the Hamiltonian for non-interacting magnons written in Fourier space as $$\begin{aligned} \label{eq:matrix} H &= J_{1}S \left[ \begin{array}{cccc} \lambda_{\bf k}+ \Delta_{\bf k} & {\tilde \gamma}_{\bf k} & t_{k_{z}} & 0 \\ {\tilde \gamma}_{-\bf k} & \lambda_{\bf k} - \Delta_{\bf k} & 0 & t_{k_{z}} \\ t^{*}_{k_{z}} & 0 & -\lambda_{\bf k} + \Delta_{\bf k} & -{\tilde \gamma}_{\bf k} \\ 0 & t^{*}_{k_{z}} & - {\tilde \gamma}_{-\bf k} & -\lambda_{\bf k} - \Delta_{\bf k} \end{array} \right] \nonumber \\ & +\mu_{\mathrm{B}}BS+S (J_{\mathrm{a}}^{\prime} + J_{\mathrm{e}}^{\prime}),\end{aligned}$$ where ${\tilde \gamma}_{\bf k} = 2e^{i{\tilde k}_{x}\frac{1}{2\sqrt{3}}}\cos\left( \frac{{\tilde k}_{y}}{2}\right) + e^{-i{\tilde k}_{x}\frac{1}{\sqrt{3}}}$ with ${\tilde k}_{x} = k_{x} + \sqrt{3}\frac{D^{[\mathrm{R}]}}{J_{1}}m_{y}$ and ${\tilde k}_{y} = k_{y} - \sqrt{3}\frac{D^{[\mathrm{R}]}}{J_{1}}m_{x}$. We also introduced $\Delta_{\bf k} = 2\Delta \left[\sin(k_{y}) - 2\sin\left( \frac{k_{y}}{2}\right)\cos\left(\frac{\sqrt{3}k_{x}}{2} \right) \right]$ with $\Delta =\frac{ D^{[\mathrm{z}]}}{J_{1}}m_{z}$, and $t_{k_{z}}= t_{\mathrm{a}}e^{ik_{z}} + t_{\mathrm{e}}e^{-ik_{z}}$ with $ t_{\mathrm{a}/\mathrm{e}} = \frac{J^{\prime}_{\mathrm{a}/\mathrm{e}}}{J_{1}}$. For the diagonal elements we introduce $\lambda_{\bf k} = \lambda - \zeta_{\bf k}$ with $\zeta_{\bf k} = 2\delta\left[ \cos(k_{y})+ 2\cos\left(\frac{\sqrt{3}k_{x}}{2} \right)\cos\left(\frac{k_{y}}{2} \right) \right]$, where $\delta =\frac{ J_{2}}{J_{1}}$ and $\lambda = 3-6\delta$. The different signs in front of $\gamma_{\bf k}$ and $\lambda_{\bf k}$ for the top and bottom layers are due to the difference in the sign of the exchange interaction, i.e., ferromagnetic or antiferromagnetic. The space of the Hamiltonian is defined by the spinor $\Psi({\bf k}) = \left[ a_{1}({\bf k}),a_{2}({\bf k}),a_{3}({\bf k}),a_{4}({\bf k}) \right]^{\mathrm{T}}$. A straightforward diagonalization of the Hamiltonian gives the energy spectrum $$\begin{aligned} \label{spectrumweyl} (\epsilon_{\pm})^2/(SJ_{1})^2 &= \lambda_{\bf k}^2 + \Delta_{\bf k}^2 + \vert t_{k_{z}} \vert^{2} + \vert\tilde{\gamma}_{\bf k}\vert^2 \\ & \pm 2 \sqrt{ \lambda_{\bf k}^2\left( \Delta_{\bf k}^2 + \vert \gamma_{\bf k} \vert^2\right) + \vert t_{k_{z}} \vert^{2} \Delta_{\bf k}^2}\,, \nonumber\end{aligned}$$ where we define magnon energy by $E_{\pm}$ with $\epsilon_{\pm} \equiv E_{\pm} - \mu_{\mathrm{B}}BS - S (J_{\mathrm{a}}^{\prime} + J_{\mathrm{e}}^{\prime})$. In the following, we will search for the degeneracies (band touching) of the spectrum. We note that they can occur only for the $\epsilon_{-}^2$ spectrum branch. It is straightforward to see that the degeneracy occurs at the ${\bf K}^\prime = (0,\frac{4\pi}{3})$ and ${\bf K}= (0,-\frac{4\pi}{3})$ points of the two-dimensional Brillouin zone, and at values of the $k_{z}$ determined from the following considerations. Close to the ${\bf K}^\prime$ point, we approximate ${\tilde \gamma}_{\bf k} \approx -\frac{\sqrt{3}}{2}({\tilde k}_{y} + i{\tilde k}_{x})$, $\Delta_{\bf k} \approx -3\sqrt{3}\Delta$, $\zeta_{\bf k} \approx -3\delta$, and $\lambda_{\bf k} \approx 3(1-\delta)$. The points of possible degeneracy are defined by the equation $$\begin{aligned} \label{condition} \left( \Delta_{\bf k}^2 +\vert t_{k_{z}} \vert^2 + \vert {\tilde \gamma}_{\bf k}\vert^2 - \lambda_{\bf k}^2 \right)^2 = 4\vert t_{k_{z}}\vert^2 \left( \Delta_{\bf k}^2 - \lambda_{\bf k}^2 \right).\end{aligned}$$ Let us carefully analyze different cases of the parameters, in particular focusing on the strength of the DMI and inter-layer exchange interactions. \(i) When $\Delta_{\bf k}^2 > \lambda_{\bf k}^2$, this inequality can be rewritten as $3\Delta^2>(1-\delta)^2$ at the ${\bf K}^\prime$ point (the same consideration applies to the ${\bf K}$ point), and Eq. (\[condition\]) is reduced to $\vert {\tilde \gamma}_{\bf k} \vert^2 + \left( \sqrt{\Delta_{\bf k}^2 - \lambda_{\bf k}^2} - \vert t_{k_{z}}\vert \right)^2 = 0$. It is satisfied only when $\frac{1}{2\sqrt{ t_{\mathrm{a}}t_{\mathrm{e}} }} \sqrt{3\Delta^2 - (1-\delta)^2 - (t_{\mathrm{a}} - t_{\mathrm{e}} )^2 } < 1$, which sets in another condition for the DMI strength, namely $3\Delta^2 > (1-\delta)^2 + (t_{\mathrm{a}} - t_{\mathrm{e}} )^2 $. We derive the values of $k_{z}$ that nullify the bracket, and get $k_{z}^{\pm} = \pm \arccos\left( \frac{1}{2\sqrt{ t_{\mathrm{a}}t_{\mathrm{e}} }} \sqrt{3\Delta^2 - (1-\delta)^2 - (t_{\mathrm{a}} - t_{\mathrm{e}} )^2} \right)$. The condition ${\tilde \gamma_{\bf k}} = 0$ is easy to satisfy, and therefore we find two Weyl points at the ${\bf K}^\prime$ point, namely at $(0, \frac{4\pi}{3},k_{z}^{\pm})$ (for $D^{[\mathrm{R}]} = 0$). See Fig. (\[fig\]) for the magnon spectrum in the simplified case. When the condition $\frac{1}{2\sqrt{ t_{\mathrm{a}}t_{\mathrm{e}} }} \sqrt{3\Delta^2 - (1-\delta)^2 - (t_{\mathrm{a}} - t_{\mathrm{e}} )^2 } > 1$ is satisfied the system is gapped, and the system is an analog of the AHE phase for magnons (magnon AHE phase). This phase is discussed in Figs. (\[figPhaseD\]) and (\[fignew\]). \(ii) When $\Delta_{\bf k}^2 < \lambda_{\bf k}^2$, the degeneracy occurs at $\vert t_{k_{z}}\vert = 0$ and at the points defined by the equation $\vert {\tilde \gamma_{\bf k}}\vert^2 = \lambda_{\bf k}^2 - \Delta_{\bf k}^2$. The first condition is satisfied only when $t_{\mathrm{a}} = t_{\mathrm{e}}$. When both conditions are met, we obtain a nodal line touching of the spectrum close to the ${\bf K}^\prime$ point. The nodal line phase is unstable and it separates two distinct phases which are characterized by a surface state. Namely, when the DMI is absent, the surface Dirac state exists if the bulk is interrupted by breaking the largest of the two inter-layer exchange couplings, $J_{\mathrm{a}}^{\prime}$ and $J_{\mathrm{e}}^{\prime}$. This is consistent with the Shockley model discussed in Ref. \[\]. Since the same scenario occurs at both ${\bf K}$ and ${\bf K}^{\prime}$, we obtain two Dirac surface magnon states occurring at the ${\bf K}$ and ${\bf K}^{\prime}$ points. Finite values of the DMI will gap the surface Dirac state, and one obtains the AHE magnons. Such transitions are shown in Fig. (\[figPhaseD\]). We note that this behavior is expected as the above model is a honeycomb layer based magnon analog of a Weyl semimetal proposed in Ref. \[\] and with details elaborated in Ref. \[\]. \(iii) According to Fig. \[fignew\], there is a special point $(0,0,\pi/2)$ in the Brillouin zone at which an accidental degeneracy occurs. Exactly at this point, the DMI vanishes $\Delta_{\bf k} =0$, a small $k$ expansion around the point gives $\Delta_{\bf k} \approx \frac{1}{4}\Delta k_{y}(3k_{x}^2 - k_{y}^2)$ and $\mathrm{Re}\tilde{\gamma}_{\bf k} \approx 3-\frac{1}{4}\tilde{k}^2$, and given $\Delta \ll 1$ we can neglect the DMI in the spectrum (see Ref. \[\] for details). The spectrum (for $D^{\mathrm{R}}=0$) is then $(\epsilon_{\pm})^2 = (\vert \lambda_{\bf k}\vert \pm \vert \gamma_{\bf k}\vert )^{2} + \vert t_{k_{z}}\vert^2$, and there is a gap closing for $\epsilon_{-}$ at $k_{z}=\frac{\pi}{2}$ for the special case of $t_{\mathrm{a}}= t_{\mathrm{e}}$. According to Ref. \[\], the Berry curvature at this point is defined by the DMI and is $\propto \Delta k_{y}^2 k_{x}^2$, which is not of a monopole type. Therefore, this point is not topological. Spin current due to the Berry curvature {#section2} ======================================= In this section, we focus on the intrinsic transport properties of the Weyl and AHE magnons. Intrinsic transport properties are those defined by the Berry curvature and are non-dissipative in nature. Therefore, we study the contributions from the points in the magnon Brillouin zone where the Berry curvature is the most singular, i.e., from the degeneracies. We simplify the model so the integrals can be calculated analytically. The prime task of the simplified model is to highlight the characteristic dependences of the intrinsic response. Also we would like to identify differences in the response structures of the Weyl and AHE magnons. Numerical calculations for the full model are presented as well. Analytical results ------------------ We consider a small-angle magnetization precession about the dc magnetic field that points in the $z-$ direction. A small magnetic field rotating about the $z-$ axis can be used to induce such precession. As shown in Ref. \[\], the dynamic $x-y$ part of the magnetization will cause spin and heat currents carried by the magnons to flow. In the following, we focus on the currents that are due to non-trivial topology of the magnon band structure. For the magnon particle current we obtain (see the Appendix for details) $$\begin{aligned} \label{currentdynamics} J^{[\mathrm{M}]}_{x} = \frac{1}{V} \frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}} \sum_{\mu\nu}\sum_{\bf k} \Omega^{(\mu\nu)}_{xy}({\bf k})g(E_{\mu \nu} ) (\partial_{t} {\bf m})_{x},\end{aligned}$$ where $\Omega^{(\mu\nu)}_{xy}({\bf k})$ is the Berry curvature, and $g(\epsilon) =(e^{\beta \epsilon} - 1)^{-1} $ is the Bose-Einstein distribution function with $\beta = J_{1}/T$. One notices that a combination $\frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}}$ is an effective charge of the magnons, while $(\partial_{t}{\bf m})_{x}$ is a fictitious electric field. The opposite signs of $D^{[\mathrm{R}]}$ in the top and bottom layers of a unit cell, see Eq. (\[ExchangeHamiltonian\]), result in the same response of the magnons to the magnetization dynamics (the same sign would have resulted in a mutual compensation of the magnon response within a unit cell). Thus, the remaining part in Eq. (\[currentdynamics\]) has the meaning of the particle Hall conductivity of magnons, $$\begin{aligned} \label{sigma} \sigma_{xy} = \frac{1}{V} \sum_{\mu\nu}\sum_{\bf k} \Omega^{(\mu\nu)}_{xy}({\bf k})g(E_{\mu \nu} ) .\end{aligned}$$ Note that this response can also be associated with a spin Hall response defined by the spin Hall conductivity $\sigma_{xy}^s=-\hbar \sigma_{xy}$. In order to make a comparison with the known anomalous Hall responses of Weyl semimetals in the case of fermions, we analytically estimate contributions from the Weyl points, where the Berry curvature is singular (of monopole type). We adopt a simplified model of Weyl magnons for which the spectrum is $\epsilon_{\mu \nu}=E_{\mu\nu} - h = \mu v \sqrt{ k_{\parallel}^2 + ( \Delta_{\nu z} )^2}$, where $\mu = \pm$, $\nu = \pm$, $v \Delta_{\pm z} = \Delta \pm 2t\vert \cos(k_{z})\vert$ with $v=S$, $\Delta =3\sqrt{3} D^{[\mathrm{z}]}/J_{1}$, $h = \mu_{\mathrm{B}}B/J_{1}$, and $t = J^{\prime}/J_{1}$. This is a spectrum of the model Eq. (\[spectrumweyl\]) close to the ${\bf K}$ or ${\bf K}^{\prime}$ points in the hypothetical case with $\lambda_{\bf k} = 0$ and $t_{\mathrm{a}} = t_{\mathrm{e}} \equiv t = J^{\prime}/J_{1}$ (see Fig. \[fig\]). The Weyl points occur for the $\nu = -$ spectrum. For this model we derive the Berry curvature $$\begin{aligned} \Omega_{xy}^{(\pm ; \nu)}({\bf k}) = \mp \frac{1}{2} \frac{\Delta_{\nu z}}{( k_{\parallel}^2 + \Delta_{\nu z}^2 )^{3/2}},\label{Berry}\end{aligned}$$ which is also shown in Fig. \[fig\]. We calculate the current Eq. (\[currentdynamics\]) in the limit $\beta h > 1$ and $\beta v \vert \Delta_{\pm z} \vert < 1$ (temperature larger than either the DMI strength or the inter-layer exchange interaction) to be $$\begin{aligned} \label{resultcurrent1} J^{[\mathrm{M}]}_{x} \approx e^{- \frac{\mu_{\mathrm{B}}B}{T}} \frac{6\sqrt{3}D^{[\mathrm{z}]}}{\pi V T} \ln\left[ \frac{\Lambda}{P} \right] \left[ \frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}}(\partial_{t} {\bf m})_{x} \right].\end{aligned}$$ where $P = \mathrm{max}(3\sqrt{3}D^{[\mathrm{z}]},2J^{\prime}) $ and $\Lambda < \mu_{\mathrm{B}}B$ is a cutoff (see the Appendix for details). Parameter $P$ distinguishes the two phases: the Weyl magnons when $3\sqrt{3}D^{[\mathrm{z}]}<2J^{\prime}$, and the AHE magnons in the opposite case. We comment on the $\beta v \vert \Delta_{\pm z} \vert > 1$ case in the Appendix. We now comment on the special point $(0,0,\frac{\pi}{2})$ (see Fig. \[fignew\]). The Berry curvature expanded close to this point in small $k$ is $\propto k^4$ (see Ref. \[\] for details); therefore, the temperature behavior of the spin Hall response for small temperatures $T \ll J_{1}$ is $\propto \left(\frac{T}{J_{1}} \right)^7 e^{- \frac{\mu_{\mathrm{B}}B}{T}} $, and consequently, it is suppressed. We can now see a difference between fermions and bosons. Importantly, in the case of Weyl semimetals (fermions), the Hall conductivity is semi-quantized. This means that it is proportional to the splitting between the Weyl points in momentum space times the $\frac{e^2}{\hbar}$. In the case of bosons, as can be seen from Eq. (\[resultcurrent1\]), the calculated anomalous response is also proportional to the splitting between the Weyl points, which is proportional to $D^{[\mathrm{z}]}$. However, the response is temperature dependent, $\propto\frac{1}{T}e^{- \frac{\mu_{\mathrm{B}}B}{T}} $, and hence by no means quantized. Because the Berry curvature for the $E_{\pm, \nu}$ energy bands is opposite in sign, the integrand defining the current in Eq. (\[currentdynamics\]) is less singular at the Weyl points for bosons compared to fermions. Technically, it is due to the vanishing of the difference of the Bose-Einstein distribution functions for $E_{\pm \nu}$ energy bands at the Weyl points, where $E_{- -}=E_{+ -}$. In the case of fermions, the contribution to the anomalous Hall response comes only from fully filled bands, say, $E_{- - }$ when Fermi energy is larger than $h$, and the cancellation of the Fermi distribution functions does not occur. For the sake of generality, we also calculate the magnon spin Nernst current, $$\begin{aligned} \label{alpha} J_{x}^{[T]} = \alpha_{xy} ({\bm \nabla} T)_{y},\end{aligned}$$ where $\alpha_{xy}$ is the spin Nernst coefficient and the temperature gradient is applied to the system in the $y$ direction, namely, $({\bm \nabla} T)_{y}$. A generalization of the spin Nernst effect in fermion systems to boson systems, in particular to magnons in ferromagnets, was given in Ref. \[\]. The transverse to the temperature gradient response is again expressed via the Berry curvature, and it is given by $$\begin{aligned} \label{currentNernst} \alpha_{xy} = \frac{1}{TV} \sum_{\mu\nu}\sum_{\bf k} \Omega^{(\mu\nu)}_{xy}({\bf k})c_{1}\left(E_{\mu \nu} \right) ,\end{aligned}$$ where $c_{1}(x) = \int_{0}^{x} d\eta~\eta \frac{dg(\eta)}{d\eta}$. By studying the simplified model and after making the same approximations (see the Appendix for details), we obtain the expression for the spin density current, $$\begin{aligned} \label{resultcurrent2} J^{[\mathrm{T}]}_{x} \approx & \frac{\mu_{\mathrm{B}}B}{T} e^{-\frac{ \mu_{\mathrm{B}}B}{T}} \frac{6\sqrt{3} D^{[\mathrm{z}]}}{\pi V T} \ln\left[ \frac{\Lambda}{P}\right] \frac{({\bm \nabla} T)_{y}}{T}.\end{aligned}$$ Both currents, Eqs. (\[resultcurrent1\]) and (\[resultcurrent2\]), have similar features because of their dependence on the Berry curvature. The extra factor of $\frac{\mu_{\mathrm{B}}B}{T}$ in Eq. (\[resultcurrent2\]) is due to the energy dependence of $c_{1}(x)$. Numerical results ----------------- In Fig. \[fignew\], we explore the magnon bands by varying the strength of DMI. We observe that the Weyl points split by DMI and the splitting in the momentum space is proportional to the strength of DMI. We further observe annihilation of Weyl points when condition the $3\sqrt{3}D^{[\mathrm{z}]}= 2J^{\prime}$ is satisfied. Increasing DMI further leads to the formation of the AHE magnons. In Fig. \[fig2\], we plot numerical results for the temperature and the DMI strength dependence of the magnon Hall and Nernst conductivities, corresponding to Eqs. (\[sigma\]) and (\[currentNernst\]) for the model in Fig. \[fig1\]. Note that this calculation also accounts for the terms $\lambda_{\bf k}$ in Eq. (\[eq:matrix\]). We observe that the effect rapidly increases with temperature which reflects the exponential dependence on temperature in Eqs. (\[resultcurrent1\]) and (\[resultcurrent2\]). In addition, we observe a linear dependence on the DMI strength $D^{[\mathrm{z}]}$, again in agreement with Eqs. (\[resultcurrent1\]) and (\[resultcurrent2\]). Nevertheless, we note that there can also be contributions due to the Berry curvature of other regions in the Brillouin zone, in addition to the contributions of the Weyl points discussed in the previous subsection. Note also that Fig. \[fig2\] corresponds to the Weyl magnon phase as in all plots $3\sqrt{3}D^{[\mathrm{z}]}<2J^{\prime}$. Conclusions =========== To conclude, we have constructed a model of Weyl magnons, which is used to add new understanding of the structure and response functions of the Weyl magnons. Previous models utilized ferromagnets or antiferromagnets on pyrochlore, hyper-honeycomb, stacked honeycomb, and kagome lattices. [@WeylMagnons2016NatComm; @PhysRevLett.117.157204; @PhysRevB.95.224403; @0256-307X-34-7-077501; @Su.Wang:PRB2017; @2017arXiv170802948J; @OwerreArxiv2017a; @OwerreArxiv2017b] The honeycomb model in Ref. \[\] assumes anisotropic inter-layer exchange interaction which leads to the $\propto \sigma_{z}k_{z}$ term in the magnon Hamiltonian. This term is needed together with the dispersion linear in $k_{x}$ and $k_{y}$ space at the ${\bf K}$ and ${\bf K}^\prime$ points to fullfill the requirment of the Dirac Hamiltonian in three dimensions. Our model is different from the one introduced in Ref. \[\], and it is based on stacked ferromagnet and antiferromagnet honeycomb layers. At zero external magnetic field, in general, there might not be a magnetic order due to frustration of the exchange interactions. The external magnetic field above the saturation level aligns all spins, and one can discuss magnons in such a system. Different intra-layer exchange couplings (ferromagnetic/antiferromagnetic) create opposite magnon chiralities at the ${\bf K}$ or ${\bf K}^\prime$ points. The interlayer exchange coupling then hybridizes opposite chiralities of the magnons at the ${\bf K}$ and ${\bf K}^\prime$ points. Furthermore, the DMI separates the opposite chiralities in momentum, thus creating the Weyl points. In the absence of DMI, the model can also realize surface states with the Dirac spectrum. The model is a magnon analog of the fermion model given in Ref. \[\]. We have used the proposed model to calculate the intrinsic, due to the Berry curvature, responses of Weyl magnons. In particular, we have calculated responses to magnetization dynamics (magnon Hall effect) and temperature gradient (magnon Nernst effect) driven spin currents. The results are presented in the Eqs. (\[resultcurrent1\]) and (\[resultcurrent2\]). Using the similarity of our model to the fermion model given in Ref. \[\], we have compared the differences of the corresponding responses for magnons (bosons) and fermions (see the discussion after Eq. (\[resultcurrent1\])). Acknowledgments =============== We thank Bo Li for helpful discussions. This work was supported by the DOE Early Career Award DE-SC0014189. Calculation of the spin current =============================== In the following, we will be using the notations in the main text. We calculate a spin density current as a response first to the magnetization dynamics, and then to the temperature gradient. The latter is also called the magnon spin Nernst effect. Magnetization dynamics (magnon Hall effect) ------------------------------------------- We assume the magnetic orderis in the $z-$ direction. According to Ref. \[\], the spin current flowing in the $x-$ direction driven by magnetization dynamics in the $x-y$ plane is $$\begin{aligned} J^{[\mathrm{M}]}_{x} = \frac{1}{V} \frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}} \sum_{\mu\nu}\sum_{\bf k} \Omega^{(\mu\nu)}_{xy}({\bf k})g(E_{\mu \nu} ) (\partial_{t} {\bf m})_{x},\end{aligned}$$ where $\Omega^{(\mu\nu)}_{xy}({\bf k})$ is the Berry curvature, and $g(\epsilon) =(e^{\beta \epsilon} - 1)^{-1} $ is the Bose-Einstein distribution function with $\beta = J_{1}/T$. We assume a simplified model for which the dimensionless spectrum is $E_{\mu \nu} = h + \mu v \sqrt{ k_{\parallel}^2 + ( \Delta_{\nu z} )^2}$, where $\mu = \pm$ denotes the upper/lower Dirac cones with respect to the energy parameter $h$, $\nu = \pm$ is the gapped/ungapped case, again, with respect to the energy parameter $h$, $v \Delta_{\pm z} = \Delta \pm 2t\vert \cos(k_{z})\vert$, and the dimensionless velocity is $v=S$. Specifically, only the $\nu = -$ energy bands are degenerate at the Weyl points. We assume that momenta are bound such that $h \gg v \sqrt{ k_{\parallel}^2 + ( \Delta_{\nu z} )^2}$. This is a spectrum close to the ${\bf K}$ or ${\bf K}^{\prime}$ points in the case when $\lambda_{\bf k} = 0$ and $t_{\mathrm{a}} = t_{\mathrm{e}} \equiv t = J^{\prime}/J_{1}$ for the model discussed in the text. We chose such parameters to highlight the differences in calculations of the anomalous Hall effect between known fermion Weyl systems and the present Weyl boson model. The identity $$\begin{aligned} \frac{1}{e^{\beta E_{+\nu}} -1} - \frac{1}{e^{\beta E_{-\nu}} -1} = \frac{\sinh(\beta v \sqrt{ k_{\parallel}^2 + \Delta_{\nu z}^2 })}{\cosh(\beta v \sqrt{ k_{\parallel}^2 + \Delta_{\nu z}^2 }) - \cosh(\beta h)}\end{aligned}$$ is of use. We now calculate the current due to the Berry curvature in a case when analytic approximation is possible. The Berry curvature of the model for various bands is calculated as $$\begin{aligned} \Omega_{xy}^{(\pm ; \nu)}({\bf k}) = \mp \frac{1}{2} \frac{\Delta_{\nu z}}{( k_{\parallel}^2 + \Delta_{\nu z}^2 )^{3/2}}.\end{aligned}$$ We note that the Berry curvature is the same for both the ${\bf K}$ and ${\bf K}^\prime$ points. The expression defining the current is $$\begin{aligned} & 2\frac{1}{2(2\pi)^2} \sum_{\nu}\int_{-\pi/2}^{\pi/2} \Delta_{\nu z} dk_{z} \int_{0}^{\Lambda} k_{\parallel} dk_{\parallel} \frac{1}{(k_{\parallel}^2 + \Delta_{\nu z}^2)^{3/2}} \frac{\sinh(\beta v \sqrt{ k_{\parallel}^2 + \Delta_{\nu z}^2 })}{\cosh(\beta v \sqrt{ k_{\parallel}^2 + \Delta_{\nu z}^2 }) - \cosh(\beta h)} \\ & = \frac{\beta v}{(2\pi)^2} \sum_{\nu}\int_{-\pi/2}^{\pi/2} \Delta_{\nu z} dk_{z} \int_{ \beta v \vert \Delta_{\nu z} \vert }^{ \beta v\Lambda } \frac{dy}{y^2} \frac{\sinh(y)}{\cosh(y) - \cosh(\beta h)} \\ & \approx -\frac{2}{\cosh(\beta h)}\frac{\beta v}{(2\pi)^2} \sum_{\nu}\int_{-\pi/2}^{\pi/2} \Delta_{\nu z} dk_{z} \ln\left[ \frac{\Lambda}{ \vert \Delta_{\nu z}\vert} \right] \\ & \approx -2 e^{-\beta h}\frac{\beta \Delta}{\pi} \ln\left[\frac{\Lambda}{\mathrm{max}(\Delta,2t)} \right],\end{aligned}$$ where the factor of 2 in the first line is due to equal contributions from the ${\bf K}$ and ${\bf K}^\prime$ points. Here the cutoff is $\Lambda > \mu_{\mathrm{B}}B$. Going from the second line to third, we assumed that $\beta v \vert \Delta_{\nu z} \vert < 1$, and approximated the integral within logarithmic accuracy. Going from the third to fourth line, we again estimated the integral within logarithmic accuracy, and assumed $\beta h \gg 1$. The current, recalling $\Delta = 3\sqrt{3} D^{[\mathrm{z}]}/J_{1}$, $h \approx \mu_{\mathrm{B}}B/J_{1}$, and $t \approx J^{\prime}/J_{1}$, is then $$\begin{aligned} J^{[\mathrm{M}]}_{x} \approx e^{- \mu_{\mathrm{B}}B/T} \frac{6\sqrt{3}D^{[\mathrm{z}]}}{\pi V T} \ln\left[\frac{\Lambda}{ \mathrm{max}( 3\sqrt{3}D^{[\mathrm{z}]},2J^{\prime})} \right] \frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}}(\partial_{t} {\bf m})_{x}.\end{aligned}$$ We stress that the spin current of the magnetic system discussed in the main text, will contain contributions from all regions of the Brillouin zone. In the expression above, we have considered only the contribution from the ${\bf K}$ and ${\bf K}^\prime$ points for a very special case of $\lambda_{\bf k} = 0$ and $t_{\mathrm{a}} = t_{\mathrm{e}}$. In the $\Delta > 2t$ case, it is instructive to obtain a result for the spin current that is a sum of a number of stacked AHE Chern magnon layers. This regime happens at small temperatures, $\beta v \vert \Delta_{\nu z} \vert > 1$: $$\begin{aligned} & \frac{\beta v}{2(2\pi)^2} \sum_{\nu}\int_{-\pi/2}^{\pi/2} \Delta_{\nu z} dk_{z} \int_{ \beta v \vert \Delta_{\nu z} \vert }^{ \beta v\Lambda } \frac{dy}{y^2} \frac{\sinh(y)}{\cosh(y) - \cosh(\beta h)} \\ & \approx -\frac{1}{\cosh(\beta h)} \frac{\beta v}{2(2\pi)^2} \sinh\left(\beta \frac{3\sqrt{3} D^{[\mathrm{z}]}}{J_{1}}\right) \sum_{\nu}\int_{-\pi/2}^{\pi/2} \mathrm{sign}\left( \Delta_{\nu z}\right) dk_{z} \\ & = -\frac{1}{\cosh(\beta h)} \frac{\beta v}{4\pi} \sinh\left(\beta \frac{3\sqrt{3} D^{[\mathrm{z}]}}{J_{1}}\right).\end{aligned}$$ The response in this case is then $$\begin{aligned} J^{[\mathrm{M}]}_{x} \approx 2 e^{-\frac{\mu_{\mathrm{B}}B}{T}}\frac{SJ_{1}}{2\pi V T} \sinh\left(\frac{J_{1}}{T} \frac{3\sqrt{3} D^{[\mathrm{z}]}}{J_{1}}\right) \frac{\sqrt{3} D^{[\mathrm{R}]}}{J_{1}}(\partial_{t} {\bf m})_{x}.\end{aligned}$$ We stress that in all of the above calculations of the current we have focused primarily on the low $k$ contribution to the integrals. This is the only contribution that distinguishes the Weyl and AHE magnons. Temperature gradient (magnon spin Nernst effect) ------------------------------------------------ Spin current due to the Berry curvature driven by the temperature gradient $\frac{(\nabla T)_{y}}{T}$ is (magnon spin Nernst effect) $$\begin{aligned} J^{[\mathrm{T}]}_{x} = \frac{1}{V} \sum_{\mu\nu}\sum_{\bf k} \Omega^{(\mu\nu)}_{xy}({\bf k})c_{1}\left[g(E_{\mu \nu}) \right] \frac{(\nabla T)_{y}}{T}.\end{aligned}$$ To extract the analytic results, we approximate $$\begin{aligned} c_{1}\left[ g(\epsilon) \right] &= \left[ 1+g(\epsilon) \right] \ln\left[ 1+ g(\epsilon) \right] - g(\epsilon)\ln\left[ g(\epsilon) \right] \\ &= \ln\left[ g(\epsilon) \right] + \beta\epsilon\left[ 1+ g(\epsilon) \right] \\ &\approx e^{-\beta\epsilon}\left( 1+ \beta\epsilon \right).\end{aligned}$$ For our simplified model we approximate $$\begin{aligned} c_{1}\left[ g(E_{+\nu}) \right] - c_{1}\left[ g(E_{-\nu}) \right] \approx -2 \beta^2 h e^{-\beta h} v\sqrt{ k_{\parallel}^2 + ( \Delta_{\nu z} )^2}.\end{aligned}$$ We apply the same approximations as in the previous section, namely $\beta h \gg 1$ and $\beta v \vert \Delta_{\nu z} \vert < 1$. We then get for the integral defining the spin Nernst current the expression $$\begin{aligned} & 2\frac{1}{2(2\pi)^2} \sum_{\nu}\int_{-\pi/2}^{\pi/2} m_{\nu z} dk_{z} \int_{0}^{\Lambda} k_{\parallel} dk_{\parallel} \frac{1}{(k_{\parallel}^2 + \Delta_{\nu z}^2)^{3/2}} \left\{ c_{1}\left[ g(E_{+\nu}) \right] - c_{1}\left[ g(E_{-\nu}) \right] \right\} \\ & \approx 2 e^{-\beta h}\frac{\beta^2 h \Delta}{2\pi} \ln\left[\beta \mathrm{max}(\Delta,2t) \right].\end{aligned}$$ The spin Nernst current then reads $$\begin{aligned} J^{[\mathrm{T}]}_{x} \approx \frac{\mu_{\mathrm{B}}B}{T} e^{-\frac{ \mu_{\mathrm{B}}B}{T}} \frac{6\sqrt{3} D^{[\mathrm{z}]}}{\pi V T} \ln\left[\frac{\Lambda}{ \mathrm{max}(3\sqrt{3}D^{[\mathrm{z}]},2J^{\prime})} \right] \frac{(\nabla T)_{y}}{T}.\end{aligned}$$ In the $\Delta > 2t$ case, at small ($\beta v \vert \Delta_{\nu z} \vert < 1$) temperatures we get $$\begin{aligned} J^{[\mathrm{T}]}_{x} \approx 2\frac{\mu_{\mathrm{B}}B}{T} e^{-\frac{\mu_{\mathrm{B}}B}{T}}\frac{SJ_{1}}{2\pi V T} \sinh\left(\frac{J_{1}}{T} \frac{3\sqrt{3} D^{[\mathrm{z}]}}{J_{1}}\right) \frac{(\nabla T)_{y}}{T}.\end{aligned}$$ \#1
2024-03-04T01:27:15.642919
https://example.com/article/6958
1. Introduction {#sec1-animals-09-00678} =============== Mucositis is a painful and debilitating condition arising in 40--60% of oncology patients treated with chemotherapeutic agents \[[@B1-animals-09-00678]\]. The condition results from a series of biological events initiated by the epithelial cell response to cytotoxic damage \[[@B2-animals-09-00678]\]. Pathological damage manifests as ulceration, inflammation and breakdown of the alimentary mucosal membranes. Mucositis affects the entire length of the gastrointestinal tract from mouth to the rectum \[[@B1-animals-09-00678]\]. Pain may arise directly due to the activation of nociceptors \[[@B3-animals-09-00678]\], or in response to other gastrointestinal events such as abdominal bloating and ulceration \[[@B4-animals-09-00678]\]. The frequency at which mucositis affects chemotherapy patients, and the serious nature of the symptoms it causes, render the mucositic condition to be the major dose-limiting factor in cancer treatment regimens \[[@B1-animals-09-00678]\]. Consequently, a range of research programs are directed at further elucidating the mechanisms of mucositis pathogenesis, and development of novel therapeutic agents for symptomatic relief of symptoms \[[@B5-animals-09-00678],[@B6-animals-09-00678]\]. Many of these programs of research utilize animal models. Legislation governing the use of animals in research frequently requires severity assessment of procedures performed on animals and amelioration of pain by analgesic administration \[[@B7-animals-09-00678]\]. However, objective, pain-specific parameters for severity assessment in rodents are lacking, and those that exist have not been widely validated. This has significant impacts on the ability to accurately apply humane endpoints and provide analgesic intervention. Further, since mucositis is a self-limiting condition, with symptoms self-resolving once cancer therapy ends, reduction of patient pain is a key goal of therapy \[[@B2-animals-09-00678]\]. Similarly, reduction of pain or other clinical signs is the primary aim in rodent models evaluating novel therapeutics. In clinical practice, patients are frequently prescribed potent opioid analgesics such as fentanyl and morphine to manage mucositis pain \[[@B8-animals-09-00678]\]. By extrapolation it might be assumed that rats with mucositis experience pain, and that this pain can be alleviated with opioid analgesics. Therefore, the use of opioid analgesics in this model may aid in validation of pain specific measures. The identification of a reliable measure of pain would considerably improve the translational validity of rodent models of mucositis. The rat grimace scale (RGS) is a measure of spontaneous pain that has been considered to evaluate the pain response \[[@B9-animals-09-00678]\]. The scale comprises four facial action units; orbital tightening, nose/cheek flattening, ear changes and whisker change. The RGS is well-studied, and validated, for the assessment of acute pain, such as that produced post-surgically \[[@B10-animals-09-00678],[@B11-animals-09-00678]\]. However, in the face of visceral pain, such as intestinal mucositis, the RGS is less studied and the literature available is generally conflicting as to the validity of this scoring method \[[@B12-animals-09-00678]\]. Instead, gastrointestinal models tend to employ typical clinical scoring schemes arguably more indicative of general health, rather than specific to pain \[[@B5-animals-09-00678],[@B13-animals-09-00678]\]. The disease activity index (DAI) evaluates disease severity based on general clinical observations; overall appearance of the animals, bodyweight loss, rectal bleeding and stool consistency. While an association between clinical signs and pain has been demonstrated in gastrointestinal disorders in human clinical practice, this has not been validated in rodent models of mucositis \[[@B3-animals-09-00678],[@B14-animals-09-00678]\]. The open field test is a well validated measure of anxiety in rodent models. Although it does not measure pain, previous studies have shown that visceral pain and anxiety are often interrelated \[[@B15-animals-09-00678]\]. Therefore, the open field test has the potential to be an adjunctive tool for measuring affective state and associated pain. The aim of the current study was to assess the utility of the RGS for pain assessment in female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats with chemotherapy-induced mucositis. The Dark Agouti rat mammary adenocarcinoma model (DAMA) was specifically chosen as it is extensively used in research investigating mucositis in rats \[[@B16-animals-09-00678]\]. The Opioid analgesics were administered to determine if the responses were pain-specific. A secondary aim was to examine whether changes in other measures of affective state, such as the DAI and the open field test, reflected the grimace responses recorded. 2. Materials and Methods {#sec2-animals-09-00678} ======================== 2.1. Animals and Experimental Design {#sec2dot1-animals-09-00678} ------------------------------------ Female Dark Agouti rats (DA/Arc; n = 60) were acquired from a Specific-Pathogen Free production facility, Animal Resources Centre (ARC) (Perth, Western Australia). The supply facility undertakes a quarterly health screening program, covering a range of bacterial, viral and parasitic organisms, for which the colony screened negative. Rats were group-housed in groups of 5 in standard open-top polycarbonate rat cages (50 cm × 31 cm; Tecniplast, NSW, Australia) with ad libitum access to potable reverse osmosis treated water, a standard rat chow (Specialty Feeds, Glenn Forest, WA, Australia), and provided shredded paper as enrichment. Lights were set to a 12-h light-dark cycle and animal facility room temperature was maintained between 21 °C and 23 °C. Rats were given a seven-day acclimatization period. During this period rats were handled daily and habituated to the grimace observation chamber and open field arena. Following baseline behavioral analysis, rats, weighing approximately 140 g, were anaesthetized with isoflurane (induction 4%, maintenance 1--2% to effect, in O~2~). Isoflurane was selected as it provides rapid induction and recovery. Once anaesthetized, animals were injected with 0.2 mL (2.0 × 10^7^ cells/mL) of breast cancer inoculum into the right flank as described by Gibson et al., 2002; day 0 \[[@B17-animals-09-00678]\]. Tumors were allowed to grow for seven days. Rats were given wet food and clinical scoring was performed daily. On day 8, a random number generator was used to assign rats to five groups (n = 12) into which the animals were allocated. The experimental groups were: (1) saline injection (ip) + saline (sc q 12 h); (2) 5-Fluourouracil (5-FU) (150 mg/kg; ip) + saline (sc q 12 h); (3) 5-FU (150 mg/kg; ip) + morphine (3.33 mg/kg; q 12 h sc); (4) 5-FU (150 mg/kg; ip) + fentanyl (10 μg/kg; q 12 h sc); and (5) 5-FU (150 mg/kg; ip) + oxycodone (3 mg/kg; q 12 h sc). When determined by group allocation, saline was administered in an equivalent volume to 5-FU. Opioid analgesics and equivalent volume of saline were administered by subcutaneous injection at 12 hourly intervals for the remainder of the study (a total of 6 doses) ([Figure 1](#animals-09-00678-f001){ref-type="fig"}). Dosages of all agents administered, and dosing schedule, were based on previous literature \[[@B18-animals-09-00678],[@B19-animals-09-00678]\]. Sample sizes were chosen using RGS data from a previous publication \[[@B20-animals-09-00678]\], with an alpha value of 0.05, power 0.8, and mean difference of 0.3, indicating a requirement for 12 animals per treatment group. The study was carried out in 6 balanced replications over a three-month time period. Rats were humanely euthanized via CO~2~ asphyxiation 72 h post chemotherapy and saline administration. Rats were placed individually in a CO~2~ chamber, with a gradual fill rate of 20% of chamber volume/min. Death was confirmed by lack of corneal reflex and cessation of heartbeat. Animal housing and experimental protocols were approved by the Animal Ethics Committee of The University of Adelaide and conducted in accordance with the provisions of the Australian Code for the Care and Use of Animals for Scientific Purposes \[[@B21-animals-09-00678]\]. This paper was written in accordance with Animal Research: Reporting in vivo experiments: The ARRIVE guidelines \[[@B22-animals-09-00678]\]. This study was conducted as part of a larger experiment evaluating the influence of chemotherapy-induced mucositis and opioid palliation on the development of chemotherapy-induced cognitive impairment. 2.2. Facial Image Analysis {#sec2dot2-animals-09-00678} -------------------------- Grimace scoring was performed at the same time of day for each animal during the light phase of the circadian cycle, at 5 time-points: 24 h prior to injection of tumor inoculum, 24 h prior to 5-FU or saline administration, and 24 h, 48 h and 72 h post-5-FU or saline injection. The latter three time points were selected to include an observation point 2 h following analgesic injection. Rats were removed from the home cage and placed in a 34 cm × 20 cm × 21 cm clear chamber. Two video cameras (Panasonic Video Camera HC-V180, Selangor, Malaysia) were placed perpendicularly on the outside sides of the chamber, with the two remaining sides and base being covered with white paper to enhance the clarity of the recordings. Rats were video recorded for a five minute-duration and then placed back into the home cage. All facial grimace recordings were performed in a quiet environment, in white light (150 lux) with no experimenter present. For image extraction, at each time-point a still image was selected and retrieved every 6 s using a video to JPG converter software (Free Studio v. 5.0.101 build: 201, United Kingdom). This occurred until a total of fifty images was obtained. Ten images of the rat's face were then randomly selected from the still images using a random number generator. Images were only selected when photos showed rats directly facing the camera, and were then cropped to show the face alone. In the scenario where an image did not show the rat directly facing the camera, a new random number was generated. Three final images for scoring were then selected using a random number generator. All images were selected by an operator who was blinded to the group and time-point. The images were placed into a pre-designed excel spreadsheet for scoring and assigned a random number code. Scoring was performed by a treatment-blinded experienced coder using the method described by Sotocinal et al. 2011 \[[@B9-animals-09-00678]\]. Each image was scored based on four action units: orbital tightening, nose/cheek flattening, ear changes and whisker change. A score from 0--2 (0 = not present, 1 = moderate, 2 = severe) was assigned to each facial unit. The four action unit scores were summed to produce the total score and a mean of the scores for all three images obtained. 2.3. Disease Activity Index {#sec2dot3-animals-09-00678} --------------------------- Disease activity index (DAI), \[[@B5-animals-09-00678]\] was recorded at 5 time-points; 24 h prior to tumor inoculum (baseline), 24 h prior to 5-FU and saline administration (tumor baseline), and 24 h, 48 h and 72 h post-injection. DAI scoring was conducted by a blinded observer, 2 h following analgesic injection prior to facial image analysis. DAI was measured on a scale of 0--3 severity (scored from 0 normal to 3 increasing in morbidity) per parameter based on overall appearance of the animals \[[@B23-animals-09-00678]\], bodyweight loss, rectal bleeding and stool consistency ([Table 1](#animals-09-00678-t001){ref-type="table"}). 2.4. Open Field Test {#sec2dot4-animals-09-00678} -------------------- Anxiety level and locomotor activity were measured using the open field test (OFT) 72 h post 5-FU or saline administration. The OFT was conducted 1 h following facial image analysis. The OFT consisted of an enclosed, open field arena (1000 cm × 1000 cm × 1000 cm) in a brightly lit room, with a video camera (Logitech HD Webcam C525, Lausanne, Switzerland) suspended above the arena. The test commenced when a rat was placed in the center of the arena. After five minutes the rat was removed and placed back into the home cage. Each test was video recorded for the five minute period. Between each test the arena was cleaned using 70% ethanol. Analysis was performed retrospectively by a blinded observer using ANY-maze™ software (Stoelting Co.,Wood Dale, IL, USA). Two zones, peripheral and center, were superimposed, and the time spent, distance travelled and number of zone crosses for each zone were analysed. 2.5. Statistical Analysis {#sec2dot5-animals-09-00678} ------------------------- Statistical analyses were conducted using Megastat Excel Add-In (version 10.3 Release 3.1.6 Mac, McGraw-Hill Higher Education, New York, NY, USA) and SPSS software (SPSS Inc., Chicago, IL, USA). Data were tested for normality and homogeneity of variance using the Shapiro--Wilk test. One animal was excluded from the study and subsequent analyses due to unrelated health issues, resulting in an n = 11 for the saline control group. RGS and DAI data between groups at each time point were analysed non-parametrically using a Kruskal-Wallis test with a *post-hoc* Mann Whitney U-test. The Friedman test with a *post-hoc* Mann Whitney U-test was applied to determine within group significances across time for both RGS and DAI data. Bonferroni correction was applied where appropriate to account for multiple comparisons. A repeated measures analysis of variance (ANOVA) with Tukey's post hoc test was used to analyze body weight and open field data. Significance was determined at *p* \< 0.05. 3. Results {#sec3-animals-09-00678} ========== 3.1. Facial Image Analysis {#sec3dot1-animals-09-00678} -------------------------- There were no significant differences in RGS between treatment groups at any individual time-points (baseline *p* = 0.98; tumor baseline *p* = 0.68; 24 h *p* = 0.20; 48 h *p* = 0.57; 72 h *p* = 0.58) ([Figure 2](#animals-09-00678-f002){ref-type="fig"}). Friedman analysis determined that the RGS scores were significantly higher post treatment (χ^2^(4) = 68.7, *p* \< 0.001). Post-hoc Mann Whitney U-test determined that grimace scores were significantly increased for rats in all treatment groups at the 72 h time-point compared to tumor baseline (*p* \< 0.05) ([Table 2](#animals-09-00678-t002){ref-type="table"}). 3.2. Disease Activity Index and Body Weight {#sec3dot2-animals-09-00678} ------------------------------------------- Disease activity index scores increased significantly over time (*p* \< 0.05). This increase was potentiated at 24 h, 48 h and 72 h compared to tumor baseline (*p* \< 0.001, [Table 2](#animals-09-00678-t002){ref-type="table"}). There were no significant differences in DAI between treatment groups prior to 5-FU administration (*p* \> 0.05). Administration of 5-FU significantly increased DAI within each time-point compared to saline control ([Figure 3](#animals-09-00678-f003){ref-type="fig"}). The analgesic agents morphine and oxycodone increased DAI compared to 5-FU alone at later time-points (refer to [Figure 3](#animals-09-00678-f003){ref-type="fig"}). There were no significant differences in body weight between groups prior to chemotherapy injection. After chemotherapy administration there was a significant reduction in body weight at 24, 48 and 72 h in comparison to tumor baseline (F (4, 270) = 414, *p* \< 0.001) ([Figure 4](#animals-09-00678-f004){ref-type="fig"}). Body weight was further decreased for animals that received 5-FU in combination with analgesics compared to saline-injected rats. Morphine and oxycodone potentiated this weight loss compared to the 5-FU control group (24 h oxycodone alone, *p* = 0.044, 48 h; *p* = 0.008, *p* \< 0.001, 72 h; *p* = 0.01, *p* \< 0.001, respectively). 3.3. Open Field Test {#sec3dot3-animals-09-00678} -------------------- There were no significant differences between treatment groups in the time spent in the centre or peripheral zones (*p* = 0.638, *p* = 0.650; respectively) ([Figure 5](#animals-09-00678-f005){ref-type="fig"}). However, all rats, irrespective of treatment group, spent more time in the peripheral zone compared to the center zone (*p* \< 0.05). No significant difference was detected between treatment groups in the distance travelled (centre, *p* = 0.415; peripheral, *p* = 0.494) and number of zone crosses (entries and exists) (centre, *p* = 0468, *p* = 0.470; peripheral, *p* = 0.540, *p* = 0.536; respectively), for both centre and peripheral zones. 4. Discussion {#sec4-animals-09-00678} ============= In the current study we aimed to determine, firstly, whether rats with implanted tumors and experiencing mucositis displayed pain as determined through expression of a 'pain face', and secondly, whether this pain could be ameliorated through the use of potent opioid analgesics, hence validating the RGS as a pain measure in this model. A further aim was to examine whether the condition of the rats and accompanying analgesic treatment led to a change in affective state as evaluated through a standard general clinical scoring protocol and an established test of anxiety. No difference in pain scores was demonstrated between groups at any individual time points. An important observation was that, while a significant increase in RGS was observed from baseline to 72 h post 5-FU and saline administration for all groups, the scores were consistently low, and frequently below the threshold able to be scored by an unbiased observer using a point system. Our study findings imply that either: (1) rats with tumors/mucositis experienced minimal pain; or (2) the RGS lacked the sensitivity to successfully discriminate pain in this model. In consideration of the DAI scores, it becomes clear, however, that animals were experiencing some adverse welfare impact as evidenced by the increased scores, which reached approximately 50% of the total score possible at the later time-point. This scoring method is not unique to assessment of pain. Given the current findings of weight loss and changes in appearance in these rats, and previous studies demonstrating that other behavioral indicators of pain were exhibited at the time points evaluated \[[@B12-animals-09-00678]\], it is probable that the RGS is not a valid indicator of pain in this model. These results may have more general application to other gastrointestinal models of disease such as IBD and colitis where an acute visceral pain insult is anticipated, although there is some evidence to the contrary \[[@B24-animals-09-00678]\]. It is feasible that in the current study there was a confounding effect of the analgesic agent on assessment of the RGS score. For example, opioid agents may have produced a sedative effect thus influencing the facial action units. This may explain the significant RGS score exhibited in the morphine group at the 24 h time-point compared to tumor baseline, although this was not observed with other opioid agents. However, no change in spontaneous locomotor activity was measured in the open field apparatus, and based on previous literature this renders a sedative effect unlikely \[[@B25-animals-09-00678]\]. Furthermore, previous studies have disputed an influence of opioids on grimace tests \[[@B11-animals-09-00678],[@B26-animals-09-00678]\]. The selected dosing regimens and time period for behavioral analysis may be factors in the minimal RGS response observed to the opioid treatments. Additionally, a significant increase in RGS score was observed from tumor baseline to 72 h in the saline control group. This elevation in RGS score may have been influenced by the pain caused by tumor burden, since this group had the largest tumors, being untreated. At 72 h there was also a trend towards significance in the DAI scores for these animals. However, we again urge caution in interpretation of these findings given the low scores, and the lack of sensitivity of the RGS over small changes, due to ordinal scoring. Alternatively, the minimal RGS change exhibited may have arisen as a result of the time points chosen for data analysis. The peak of histological damage in 5FU-induced mucositis typically occurs at 48--72 h following injection \[[@B5-animals-09-00678],[@B27-animals-09-00678]\], and thus pain was expected to be maximal at this point. However, it is feasible that histological damage and maximal pain experience may not be coincident. Alternatively, the 'pain face' may be inhibited by animals in longer term pain, due to the need to avoid predator attention \[[@B9-animals-09-00678]\]. The majority of studies to date have demonstrated declines in RGS following an initial peak in response to a painful insult by 6--8 h following the noxious stimulation \[[@B28-animals-09-00678],[@B29-animals-09-00678],[@B30-animals-09-00678]\]. However, previous studies involved a surgical stimulus \[[@B28-animals-09-00678],[@B29-animals-09-00678],[@B30-animals-09-00678]\], or inflammatory pain model \[[@B28-animals-09-00678]\], hence pain duration in the current study may have been reduced in comparison to the visceral pain sensation of mucositis. Contrarily, an assumed chronic pain insult caused by tooth movement caused a grimace response in rats for several days post-pain insult \[[@B31-animals-09-00678]\], as did the presence of colitis \[[@B14-animals-09-00678]\]. It is noteworthy that in the current study, grimace values were a small fraction of the maximum obtainable score (i.e., 8); often scoring under one. Therefore, while a statistically significant change may have been noted, the biological relevance is questionable in terms of practical usage, since an observer is only able to score whole numbers. It is plausible that the chosen observation period for grimace analysis and strain of rat used in the current study may have contributed to the RGS results obtained. Animals in this study were video recorded for a shorter duration compared to previous studies \[[@B9-animals-09-00678],[@B14-animals-09-00678]\]. Exploration of the relatively new environment may have masked grimace response, with animals not having time to habituate to the chamber. However, changes in rat grimace score following recovery from exposure to either isoflurane or air have been reported using an identical scoring period to that used in the current study (five minutes) \[[@B32-animals-09-00678]\]. Furthermore, the rat strain used may have impacted on the ability to accurately score facial features. Previous research has implied that detection of grimace facial features in dark-colored animals is impaired \[[@B33-animals-09-00678],[@B34-animals-09-00678]\]. This may however be as a result of poor achievement of background contrast, rather than the pigmentation of the animal per se. We tried to minimize this factor by using a white background when performing grimace scoring. Nonetheless, this could be a limitation of the study. Furthermore, our findings concur with previous results in a 5-FU induced mucositis model in white Sprague-Dawley rats, where mucositis did not elevate RGS in a longitudinal study design in which rats acted as their own controls \[[@B12-animals-09-00678]\]. The DAI has been widely used in models of mucositis to assess presence of the mucositic condition, in addition to severity, and is generally the sole assessment method utilized for making decisions on humane endpoint implementation, as prescribed by Animal Ethics Committees. The DAI findings in this study mirror those described in other mucositis studies with a progression in clinical signs until 72 h post-chemotherapy injection. However, the DAI is not specific to pain and therefore may not be useful in guiding when analgesic intervention is required. Further, it is apparent that the analgesic agents, morphine and oxycodone, actually increased the DAI score, thus challenging its interpretation. Closer inspection of the individual scores contributing to total DAI reveals that score is heavily influenced by weight loss, which increased over time in concert with histological disease progression, as described in previous studies. Since morphine and oxycodone potentiated weight loss, the DAI scores for these groups were relatively higher. If we assume that oxycodone is controlling pain, it is assumed that this exacerbation of bodyweight loss was brought about either through reduced appetite as a result of nausea, or as a result of a sedative effect rendering a larger proportion of the time budget being spent engaged in sleep. These are well recognized side effects of opioid administration \[[@B35-animals-09-00678],[@B36-animals-09-00678]\]. This observation is consistent with previous studies, which have shown that the opioid analgesic, buprenorphine, similarly exacerbated bodyweight loss \[[@B27-animals-09-00678],[@B35-animals-09-00678],[@B37-animals-09-00678]\]. This lack of sensitivity of the DAI poses an issue when implementing humane endpoints. If strict point-score cut-offs are applied without the input of clinical judgement, animals may be withdrawn from a study as a result of analgesic side-effects such as weight loss, which influenced DAI. These side effects may not in themselves negatively impact on affective state. This poses an ethical issue in terms of animal wastage. 5. Conclusions {#sec5-animals-09-00678} ============== There is a genuine need to develop and validate objective pain assessment tools in animal models of gastrointestinal disease such as the mucositis model described here. This will not only improve animal welfare and satisfy legislative requirements, but improve the translational validity of the models. Our data imply that the RGS fails to meet this need in a rat model of chemotherapy-induced mucositis and alternative pain assessment strategies are required. Alternative methods of emotional affect should be investigated, to include activities of daily living, such as burrowing and nest building, measures of affective biasing, or the use of running wheel activity. The conditioned place preference test might also be employed to examine preference for a substance assumed to provide an ameliorating effect \[[@B38-animals-09-00678]\]. Taking our findings, and those of others, into consideration, we also urge caution in conflating statistical significance with clinical significance when it comes to validating tools for practical implementation. Furthermore, given an apparent lack of sensitivity of traditional DAI scoring to side-effects of opioid analgesics, the comparative efficacy of opioid analgesics in these models cannot be established. Conceptualization, R.P.G. and A.L.W.; Data curation, R.P.G. and A.L.W.; Formal analysis, R.P.G. and A.L.W.; Funding acquisition, A.L.W.; Investigation, R.P.G. and A.L.W.; Methodology, R.P.G. and A.L.W.; Project administration, R.P.G., G.S.H. and A.L.W.; Resources, G.S.H. and A.L.W.; Supervision, G.S.H. and A.L.W.; Writing---original draft, R.P.G. and A.L.W.; Writing---review & editing, R.P.G., G.S.H. and A.L.W. This research was part funded by an Australian Federation of University Women grant to A.L.W. A.L.W. was supported by a NHMRC Peter Doherty Biomedical Research Fellowship. R.P.G was supported by an Australian Government Research Training Program Scholarship. The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. ![Overview of the experimental timeline for treatment and behavioral analyses. Abbreviations: RGS---rat grimace scale, DAI---disease activity index, OFT---open field test.](animals-09-00678-g001){#animals-09-00678-f001} ![Box plot of rat grimace score. Maximum obtainable score was 8. Statistical comparison within group across time not shown (refer to [Table 2](#animals-09-00678-t002){ref-type="table"}). Saline + Saline (n = 11), 5-FU + Saline (n = 12), 5-FU + Fentanyl (n = 12), 5-FU + Morphine (n =12) and 5-FU + Oxycodone (n = 12) at all time-points.](animals-09-00678-g002){#animals-09-00678-f002} ![Disease activity index scores. Data expressed as median with range. Symbols denote significance obtained using a Kruskal-Wallis test with a *post-hoc* Mann Whitney U-test, between groups, at each time point. \* *p* \< 0.05 compared to saline. \^ indicates *p* \< 0.05 compared to 5-FU alone. Statistical comparison within group across time not shown (refer to [Table 2](#animals-09-00678-t002){ref-type="table"}). Saline + Saline (n = 11), 5-FU + Saline (n = 12), 5-FU + Fentanyl (n = 12), 5-FU + Morphine (n = 12) and 5-FU + Oxycodone (n = 12) at all time-points.](animals-09-00678-g003){#animals-09-00678-f003} ![Body weight change. Data presented as mean % change in body weight ± standard error of the mean. \* *p* \< 0.05 compared to saline, \^ *p* \< 0.05 compared to 5-FU. Saline + Saline (n = 11), 5-FU + Saline (n = 12), 5-FU + Fentanyl (n = 12), 5-FU + Morphine (n = 12) and 5-FU + Oxycodone (n = 12) at all time-points.](animals-09-00678-g004){#animals-09-00678-f004} ![Time spent in center and peripheral zones of the open field test. Data presented as mean ± SEM. \* *p* \< 0.05 compared to center zone. Saline + Saline (n = 11), 5-FU + Saline (n = 12), 5-FU + Fentanyl (n = 12), 5-FU + Morphine (n = 12) and 5-FU + Oxycodone (n = 12).](animals-09-00678-g005){#animals-09-00678-f005} animals-09-00678-t001_Table 1 ###### Disease activity index scoring criteria. Overall Appearance \* Weight Loss (%) Stool Consistency Rectal Bleeding Score ----------------------- ----------------- ------------------- ----------------------------------- ------- Normal No weight loss Normal Stools No observable blood 0 Mild 0--5% Loose Blood spots in faeces 1 Moderate 5--10% Mild diarrhoea Clear evidence of blood in faeces 2 Severe \>10% Overt diarrhoea Gross bleeding 3 \* Overall appearance was determined based on criteria; dull or ruffled coat, hunched, pale or sunken eyes, change in behavior, reduced food or water intake, dehydration, squealing when handled, reluctant to move. animals-09-00678-t002_Table 2 ###### Statistical comparison within group across time for RGS and DAI. RGS DAI -------------------------- ---------- ------------ Tumour baseline vs. 24hr 0.28 0.54 Tumour baseline vs. 48hr 0.07 0.07 Tumour baseline vs. 72hr 0.03 \* 0.06 *5-FU + Saline* Tumour baseline vs. 24hr 0.06 \<0.001 \* Tumour baseline vs. 48hr 0.53 \<0.001 \* Tumour baseline vs. 72hr 0.03 \* \<0.001 \* *5-FU + Fentanyl* Tumour baseline vs. 24hr 0.91 \<0.001 \* Tumour baseline vs. 48hr 0.12 \<0.001 \* Tumour baseline vs. 72hr 0.001 \* \<0.001 \* *5-FU +Morphine* Tumour baseline vs. 24hr 0.03 \* \<0.001 \* Tumour baseline vs. 48hr 0.47 \<0.001 \* Tumour baseline vs. 72hr 0.01 \* \<0.001 \* *5-FU + Oxycodone* Tumour baseline vs. 24hr 0.11 \<0.001 \* Tumour baseline vs. 48hr 0.12 \<0.001 \* Tumour baseline vs. 72hr 0.001 \* \<0.001 \*
2024-05-21T01:27:15.642919
https://example.com/article/8408
Q: Remove and insert drop down list values I have a couple of dropdown lists like this <asp:DropDownList runat="server" OnSelectedIndexChanged="Update_ddls" AutoPostBack="true" ID="ddl1" /> <asp:DropDownList runat="server" ID="ddl2" /> Which are populated by a column in my db like this query.CommandText = "SELECT * FROM locations" DataTable = New DataTable() DataAdapter = New SqlDataAdapter(query) DataAdapter.Fill(DataTable) If Not Page.IsPostBack Then ddl1.DataSource = DataTable.DefaultView ddl1.DataTextField = "location" ddl1.DataValueField = "location" ddl1.DataBind() ddl1.Items.Insert(0, New ListItem("Select...", "Select...")) End If I also have a function called Update_ddls which runs OnSelectedIndexChanged that looks like this ddl2.Items.Remove(ddl2.Items.FindByValue(ddl1.SelectedValue.ToString())) Which removes the selected item in ddl1 from the second dropdown but if I keep changing the ddl1 item then ddl2 won't have any items left in it. Is there a way to re-add the previously deleted items in the Update_dlls function without re-databinding because if I re-databind I lose the selected item in the ddl? Thanks in advance A: Store SelectedValue in some variable before rebinding the dropdownlist and then simply remove the value from dropdownlist
2023-08-03T01:27:15.642919
https://example.com/article/6158
President also says we need to interrogate notion that EWC incompatible with growing, flourishing economy Reply by President Cyril Ramaphosa to the Debate on the State of the Nation Address, Parliament, Cape Town Speaker of the National Assembly, Chairperson of the National Council of Provinces, Honourable Members, I wish to extend my sincere gratitude and appreciation to all the Honourable Members who participated in the debate yesterday for asserting that a new era has dawned and embracing the call for a new partnership to build a new nation in which all may be free, secure and equal. I wish to thank all Members, and particularly those who participated in the debate, for their contributions and suggestions. It was a meaningful debate that engaged with the issues that most directly affect our people. The debate was conducted with decorum and respect – respect for each other, respect for the dignity of the House and respect for the people that we have all been sent here to represent. We should always remain mindful that this is the People’s Parliament. It was built by our people, for our people, and it belongs to our people. The dignified manner in which the debate was conducted was very much in accord with what our people expect from their representatives in this, their House. As Honourable Members met yesterday to debate the State of the Nation Address, ordinary South Africans have also been discussing it over the last few days. Many South Africans have been expressing their views on social media and in traditional media, many have commented on government communications platforms, and some have shared their views when we pass each other in the corridor or on the street. This morning I had occasion to take my early morning walk in Gugulethu, joined by people from the area, many of whom commented on the speech. Since delivering the State of the Nation Address on Friday night, I have been humbled and encouraged by the response of people from all walks of life to the call to work together to build a new, better South Africa. They are galvanised by a sense patriotism that elevates the interests of the country above narrow, selfish interests. They are moved by a conviction that tomorrow will be better than today. They have, to a man and a woman, all been saying they are ready to lend a hand to build a South Africa that benefits all its people. I have received messages from many people consisting of only two words: “Send Me”. What emerged clearly from the debate yesterday, is that all the members of this Parliament are committed to build a nation where progress is measured not by growth in gross domestic product or global competitiveness rankings, but by how the lives of the most vulnerable and marginalised are changed for the better. We are building a nation where our greatest concern must be those in society who have least. The poor. The unemployed. The most important people in this country are not those who walk the red carpet in Parliament, but those who spend their nights on the benches outside its gates. The most important people in this country are those whose shacks are flooded with every rainfall and whose taps run dry whether there is a drought or not. It is those who have been looking for work their entire adult lives, who have had to drop out of school, who are suffering from preventable diseases, who have been orphaned or abandoned, who rely on an old age pension to feed their families, who do not have the seed or the implements to work their small piece of land. In everything that we do, as government and as a society, these are the people whose interests and needs must come first. These are the people whose voices must be heard. They are the people we all collectively are being sent to – to improve their lives, to heal their wounds and to make their hope a reality. At the centre of our approach to improving the lives of our people is the Madiba way of getting our people involved in changing their lives for the better and making them, as Madiba urged, ‘their own liberators’. It is to advance their interests that we have called for a new social compact founded on the principles of social justice, solidarity and equality. It is only by bringing all social partners – and all South Africans – together in pursuit of a common national agenda that we will be able to defeat poverty and inequality. Collaboration, partnership and consensus building are essential features of our rich African past and will be central in determining our future. Throughout our history, we have used collaboration and partnership to overcome the greatest of difficulties and resolve the most intractable of problems. It is our intention, through initiatives like the Jobs Summit and Social Sector Summit, to bring together the skills, insights, experiences and capabilities of all South Africans to address critical challenges in our society. We want to build consensus. We want to invite all South Africans to participate, to lend a hand. This we have to do because our people want to be involved. They say: ‘Nothing about us without us.’ We should remember how the Freedom Charter was written, how volunteers spread out across the country to collect the demands of the people for discussion at the Congress of the People. We should remember how we wrote the Constitution, where we received around 1.7 million submissions from ordinary South Africans. Now, we need to mobilise all South Africans to achieve the vision of the Freedom Charter and the values of the Constitution. As leaders – whether in government, business, labour or civil society – we have a responsibility to work together. Encouraged by the response of our people – and by the views expressed in yesterday’s debate – I am confident that we can move with urgency and purpose to forge a new social compact to revive our economy, create jobs, reduce inequality and effect fundamental social and economic transformation. I am confident that – while there will necessarily be much contestation and vigorous debate – all parties represented in this Parliament are committed to work together to make this a reality. I concur with the sentiment expressed yesterday that we need to unite as political parties to support the pursuit of a developmental state and an inclusive economy. If we are to work together effectively, we should be prepared to engage each other on the matters of national importance on which we may disagree. On such fundamental matters as the redress of the injustices of the past, we should not simply agree to disagree. We must discuss and debate and persuade each other. Yesterday, there was a concern raised about black economic empowerment and affirmative action. There was a suggestion that young white people are excluded from jobs, bursaries and opportunities based on the colour of their skin. We must not ignore such concerns, nor must we dismiss them. Rather we must engage with them, for the statement that young white South Africans are unfairly disadvantaged by our affirmative action policies is not borne out by reality. Data from Statistics South Africa indicate that white young people still do better in development indicators such as education, employment, entrepreneurial opportunities and wellbeing. Unemployment among Africans stands at 30 percent and just under 7 percent among whites. Employment prospects still favour white young people as compared to their black counterparts. They are still more likely to complete matric and progress to tertiary education. They are more likely to complete tertiary education and proceed into the labour market with better prospects. White South Africans, particularly men, still dominate at the senior levels of the economy. We have made significant progress since 1994 in addressing these racial disparities, but we clearly have a long way to go. We have even further to go to address gender disparities. It is therefore critical that we accelerate black economic empowerment, employment equity and the transformation of our education system. We should emphasise that the task of building a united nation that belongs to all South Africans, black and white, does not suggest that we ignore the legacy of our apartheid and colonial past. On the contrary, the creation of a non-racial society requires the liberation of Africans in particular and black people in general from political and economic bondage. Let us remember the contract we all entered into as South Africans when we adopted our Constitution. It says: We, the people of South Africa, Recognise the injustices of our past; Honour those who suffered for justice and freedom in our land; Respect those who have worked to build and develop our country; and Believe that South Africa belongs to all who live in it, united in our diversity. We therefore, through our freely elected representatives, adopt this Constitution as the supreme law of the Republic so as to - - Heal the divisions of the past and establish a society based on democratic values, social justice and fundamental human rights; - Lay the foundations for a democratic and open society in which government is based on the will of the people and every citizen is equally protected by law; - Improve the quality of life of all citizens and free the potential of each person; and - Build a united and democratic South Africa able to take its rightful place as a sovereign state in the family of nations. May God protect our people. Nkosi Sikelel’ iAfrika. Morena boloka setjhaba sa heso. God seën Suid-Afrika. God bless South Africa. Mudzimu fhatutshedza Afurika. Hosi katekisa Afrika. This commitment we all made must inform the debate we need to have on all fundamental measures of redress that we need to undertake to heal the divisions of the past in order to establish a society based on democratic values, social justice and fundamental human rights. The return of the land to the people from whom it was taken speaks to precisely how we can heal the divisions of the past. We need to interrogate the statement that the expropriation of land without compensation is incompatible with a growing, flourishing economy. We need to respond to the view that what we propose represents a violation of the spirit and intent of our democratic Constitution. There are few in our country who would contest the fact that dispossession of black South Africans of their land contributed fundamentally to the impoverishment and disempowerment of the majority of our people. This morning, while walking in Gugulethu, I met Mr Cedric Alberts, who was forcibly removed from District Six in 1969. His family’s story illustrates in vivid terms the pain and damage caused by the former rulers of this land. The expropriation of land without compensation is envisaged as one of the measures that we will use to accelerate the redistribution of land to black South Africans. We will need to determine, collectively, how we can implement this measure in a way that promotes agricultural production, improves food security, advances rural development, reduces poverty and strengthens our economy. For it to serve this purpose, we will need to locate this measure within a broad and comprehensive land redistribution and agricultural development programme. This is a profound responsibility that has been given to our generation. We owe it to our ancestors and to our children to ensure that we fulfil it. In dealing with this complex matter, we will not make the mistakes that others have made. We will not allow smash and grab interventions. We will handle this matter in the same way we have handled all difficult issues our country has had to handle. We will always seek to do what is in the interests of our people. This includes, Honourable Buthelezi, how we will handle the Ingonyama Trust issue. No-one is saying that land must be taken away from our people. Rather it is how can we make sure that our people have equitable access to land and security of tenure. We must see this process of accelerated land redistribution as an opportunity and not as a threat. We must see it as an opportunity to free all of us from the bitterness and pain of the past. Another grave historical injustice that we need to correct is the economic inequality between men and women. It is a task that requires both a deliberate bias in economic policy towards the advancement of women and a fundamental shift in almost every aspect of social life. One of the programmes where we have sought to integrate various approaches is the ‘She Conquers’ initiative, which aims to empower adolescent girls and young women to reduce HIV infections, tackle gender-based violence, keep girls in school and increase economic opportunities. It recognises how patriarchal attitudes, poverty, social pressures, unemployment and lack of adequate health and other services conspire to reduce the prospects of young women – and then involves these women in overcoming these challenges. This is one of the ways we are working to build a nation that is prepared to confront the many different ways in which women are subjugated, marginalised and overlooked – a nation that wages a daily struggle against patriarchy, discrimination and intolerance. We must all work together to tackle the chauvinism experienced by women in the workplace and other social settings. We must confront the social and economic factors that prevent young women from completing school, entering higher education and graduating. Government has adopted an integrated programme of action to eliminate all forms violence against women and children. With the support of communities, we aim to prevent such violence by transforming attitudes, practices and behaviours. We are working to provide a comprehensive package of services to women and children affected by violence and to improve the provision of long-term care, support and empowerment of survivors of violence. These are crimes that often occur within the family and it is therefore critical that we do not make this a purely criminal justice issue. It is a social issue that must engage, involve and mobilise the whole of society. We must be prepared, as government, to acknowledge where we have failed our people. Where we have made mistakes, we will correct them. The Marikana tragedy stands out as the darkest moment in the life of our young democracy. Members will recall that the Commission of Inquiry headed by retired Judge Farlam investigated the direct and root causes of the tragedy. Three broad areas were identified for action: compensation to those injured and the families of those who lost their lives, examining the procedures of public order policing and preparing valid cases for prosecution according to applicable laws. Government is making progress in continuous engagement with the legal representatives of the victims, especially on the matter of reparations to families who lost their loved ones. This must be concluded in the coming months. The incident also brought into sharp focus the distress felt by people living in mining communities. As we engage with mining companies, unions and communities on the finalisation of the Mining Charter, we need to ensure that these measures receive priority attention. I would like to use this opportunity to address the role that I played in my capacity as a Lonmin director in the events of that tragic week. Notwithstanding the findings of the Farlam Commission on my responsibility for the events that unfolded, I am determined to play whatever role I can play in the process of healing and atonement. In this, I am guided by the needs and wishes of the families of the 44 workers who lost their lives. Alongside Marikana, the Life Esidemeni tragedy stands out as an instance of the most appalling dereliction by the state of its duty to the people. We welcome the arbitration process led by former Deputy Chief Justice Dikgang Moseneke and are determined that we should never allow anything like this to happen again in our country. Honourable Members, What has become clear over the last few days is that South Africans really want to contribute to making a difference. Let me cite just two examples, of Cape Town residents that I happened to meet yesterday morning. One of the people I met was a gentlemen who runs a factory manufacturing textiles that employs 65 people. He said that after listening to the State of the Nation Address, he was so enthusiastic about the prospects for our country and the need for everyone to lend a hand that he has decided to expand his business and employ 65 more people in his business. He said his confidence in the economy derives from the commitment of government to provide sound leadership, create certainty, root out corruption and end wastage. A young woman I met spoke enthusiastically about her plans to start a business. The only thing she asked was that government takes steps to bring down the cost of data, which was the greatest impediment to the success of her business. This shows that South Africans are not short of ideas and initiative and potential. It is our responsibility, as government and as Members of Parliament, to give them the means to unlock that potential. One of the ways we are responding to the particular need of this young women is to bring down the cost of data through the competition market inquiry into data services. At the same time, government is working to create a conducive environment for investment in efficient networks that enable the reduction of costs, enhance competition and remove barriers to entry by small businesses. As indicated in the State of the Nation address, we will therefore expedite our engagement with industry to conclude the allocation of radio frequency spectrum, creating regulatory certainty and predictability. The need for government to support entrepreneurs has emerged as a recurring theme in the broader debate on SONA. This morning as I walked with several people in Gugulethu and Athlone, I met a woman called Thulake, who runs a bag making business. She started her business with a partner in Gugulethu with R3,000. Today, it’s got a net asset value of R700,000. She needs to have a factory and looks to her government to build the infrastructure that can make her business grow. We have received numerous calls for government to pay suppliers timeously. A Mr Ismail Ebrahim wrote to us on Facebook. He said: “Mr President, I am a small businessman trying to start a business the honest way. I have been sent from piller to post for the last seven years between departments of water, energy and city of Tshwane. I have stood in queues for days and only get excuses or no response at all. My business will create jobs, but the government red tape is stifling our entrepreneurship. Please help.” The frustration that these entrepreneurs have to endure at the hands of the very state that is supposed to assist them is a matter of great concern. It is clear that the failure of some government departments to pay suppliers within 30 days has a devastating impact on small and medium-sized businesses. This is something that I want to see addressed as I visit government departments, because the culture of late payment has gone on for far too long and has caused far too much damage, particularly to emerging black businesses. Honourable Members, A number of speakers in the debate yesterday highlighted the urgent need to address the financial, operational and governance problems at state owned enterprises. I particularly welcome those Honourable Members who offered concrete suggestions on how we can do this. In addition to the steps announced in the State of the Nation Address to address governance and financial management at specific SOEs, we are developing an overarching SOE strategy to support a developmental growth trajectory. We will soon be completing work on a new, centralised ownership model that allows for better strategic alignment, improved coordination and more effective oversight. It is proposed that this include a State-Owned Company Coordinating Council, chaired by the President, which would be responsible for high level strategic direction. The new ownership model would incorporate new methods for funding SOEs, which could include a shift towards a greater mix of debt and equity finance. Where circumstances are suitable – and where the developmental function of an SOE is not compromised – there may be opportunities to involve strategic equity partners as minority investors. We are going to be meeting the Board Chairs, CEOs and CFOs of these companies to clarify their commercial and developmental mandates and discuss their plans for financial sustainability and the promotion of local manufacturing. On one of the matters raised by both Minister Patel and the Honourable Shivambu, government will continue its work on the establishment of a sovereign wealth fund in line with the resolutions of the 54th National Conference of the governing party. We have looked at the experiences of countries like Singapore, China and Norway, which have all successfully built up sovereign wealth funds which act as custodians of the resources of the nation for future generations. There are a number of industries that have an important role to play in growing our economy and creating jobs. We mentioned some of these in SONA, like agriculture, mining and tourism, but there are others that also need support and investment. We were reminded by Sipho Sithole, the founder of Native Rhythm Records, that the cultural industries make a significant contribution to our economy and employ many people. Cultural industries have great potential for growth, but require closer attention and backing from government. As we indicated in the State of the Nation Address, the work being done to grow the economy and create employment, needs to take place alongside decisive interventions to support people who are poor and vulnerable. We agree that the high levels of long term unemployment means that we must think differently about social grants. We are therefore engaging with our social partners through Nedlac on a comprehensive social security reform, which will, among other things, enable us to provide a longer and more comprehensive system of unemployment insurance alongside a system of mandatory death and disability social insurance benefits. A number of speakers commented favourably on our decision to institute a review of the configuration, number and size of national government departments. Changes of this nature need to be well considered, they should be evidence based and should not be made in haste. This review, which we expect to take several months, will be based on a thorough analysis of the suitability and cost of the existing configuration. It will involve broad consultation so that the views of a broad range of stakeholders are considered and so that South Africans understand the rationale for the decisions that will ultimately be made. I have noted during the course of the debate several comments about members of the Executive. Whatever views one might hold about members of Cabinet, this does not justify in any way the kind of character assassination and insults we have heard. On the matter of the composition of Cabinet, an announcement will be made by the President at the appropriate time. The work we must undertake to tackle corruption and state capture has, quite correctly, featured prominently in the debate. It is time that we implement our resolutions on the conduct of lifestyle audits of all people who occupy positions of responsibility, starting with members of the Executive. As we indicated in the State of the Nation Address, we are equally determined to tackle corruption and other economic crimes in the private sector. Institutions like SARS, the Reserve Bank, the Financial Intelligence Centre and our law enforcement agencies work together to detect and prosecute tax evasion. South Africa will continue to play a leading role in international efforts – through structures like the OECD and G20 – to tackle the various forms of tax avoidance. We were reminded in the House of the responsibility that we have as South Africans to those peoples on our continent and around the world who continue to suffer occupation, discrimination and oppression. At this moment, we wish to express our deepest concern at the continued imprisonment of Palestinian children in Israelii jails. We reiterate our call to the Israelii government to engage in meaningful dialogue with the Palestinian leaders to find a resolution that affirms the equal rights of both people to self-determination, freedom and security. On Friday last week, on the day that the State of the Nation Address was delivered, the South African training vessel ‘SA Agulhas’ returned from an Indian Ocean research voyage. Providing 20 young cadets with on the job exposure to being at sea, the voyage lasted 80 days. Two of these young people are present here today, Ms Ayanda Miya and Mr Mluleki Khwela. Ms Miya is from Empangeni and studied Maritime Studies at the Cape Peninsula University of Technology. Mr Kwhela is from Umlazi and studied Maritime Studies at Durban University of Technology. We invited them to join this joint sitting today because they are among the young people who have seized the opportunities available to them to develop their talents and pursue the careers of their dreams. They are among the new generation of South Africans who are at the forefront of our national effort to develop our Ocean Economy. We welcome you to this joint sitting and wish you all the best in developing your skills and furthering your careers. In conclusion, allow me to thank all the Honourable Members who participated in yesterday’s debate for ensuring a robust, quality discussion of the challenges that our people face. I also want to thank the people of South Africa for having responded so enthusiastically to the call that went out in the State of the Nation. There is a lot of hard work ahead of us, but I am certain that if we harness the energy, wisdom and talents of all South Africans, we will surely succeed. Let us all rise to the task that our people have given us and say, ‘Yes, send me. Thuma mina’. I thank you. Issued by The Presidency, 20 February 2018
2024-04-06T01:27:15.642919
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