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j-chim

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[ "Roc Carmichael\n\nRashad Bernard \"Roc\" Carmichael (born September 9, 1988) is a former American football cornerback. ", "He was drafted by the Houston Texans in the fourth round of the 2011 NFL Draft. ", "He played college football at Virginia Tech.", "\n\nEarly years\nCarmichael played high school football at Gwynn Park High School in Brandywine, Maryland.", "\n\nCollege career\nDuring his college career at Virginia Tech, Carmichael recorded 115 tackles (75 solos), 10 interceptions, 16 pass breakups, and 26 passes defended.", "\n\nProfessional career\nCarmichael was selected in the fourth round as the 127th overall draft pick by the Houston Texans in the 2011 NFL Draft.", "\n\nCarmichael was signed off of the Texans' practice squad by the Philadelphia Eagles on September 18, 2013. ", "He was released by the Eagles on August 30, 2014, but re-signed in November of the same year. ", "He was again released on December 9, 2014. ", "On May 5, 2015, he was released by the Cardinals.", "\n\nOn May 11, 2017, Carmichael signed with the Winnipeg Blue Bombers of the Canadian Football League. ", "He was moved to the suspended list on September 7, 2017, and his contract expired after the season.", "\n\nReferences\n\nExternal links\nHouston Texans bio\nVirginia Tech Hokies football bio\n\nCategory:1988 births\nCategory:Living people\nCategory:Players of American football from North Carolina\nCategory:American football cornerbacks\nCategory:Virginia Tech Hokies football players\nCategory:Houston Texans players\nCategory:Philadelphia Eagles players\nCategory:Arizona Cardinals players\nCategory:People from Laurinburg, North Carolina\nCategory:People from Brandywine, Maryland\nCategory:Winnipeg Blue Bombers players" ]

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[ "Ashwell Quarry and Quarry Springs\n\nAshwell Quarry and Quarry Springs is a three hectare nature reserve managed by the Herts and Middlesex Wildlife Trust near Ashwell in Hertfordshire. ", "Ashwell Quarry is owned by a local farmer, and Quarry Springs by Hertfordshire County Council. ", "It is a Regionally Important Geological Site.", "\n\nThe quarry may date to Roman times and its Totternhoe stone was probably used to build Ashwell's fourteenth-century church. ", "In the nineteenth century it was grazed by sheep, adding the nutrients required for wild flowers which need soils which are dry and chalky. ", "In 1970 it became a nature reserve. ", "Plants include pyramidal orchid, clustered bellflower and glaucous sedge, and there are rare mosses in shaded hollows. ", "Quarry Springs has rare wildlife such as flatworms which need water which is clean and at a constant temperature around 10 degrees Celsius.", "\n\nA permit is required from the local warden of the Wildlife Trust for entry to Ashwell Quarry, which is a mile west of Ashwell, on the Hinxworth Road opposite Loves Lane. ", "Quarry Springs is on the opposite side of the road to the quarry.", "\n\nReferences\n\nCategory:Herts and Middlesex Wildlife Trust reserves\nCategory:North Hertfordshire District" ]

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[ "1995-1998 Dodge Van B2500 Timing Chain Cover with Gasket for V8 5.9L\n\nThis part replaces:\n\nITEM CONDITION\n\nThis timing cover is a new, aftermarket replacement part! ", "It is built to replace the cracked or damaged original cover exactly!", "\n\nSpecifications:\n\nEngine Timing Cover\n\nIncludes Gasket & Seal\n\nReplaces dealer part number: 4897723AA\n\nDirect bolt on replacement\n\nInstalls & fits just like the original\n\nBuilt to strict quality control standards\n\nThis inner timing cover is a great replacement and offers good cost savings over the dealer unit!", "\n\nLifetime Warranty\n\nThis item is backed by a Limited Lifetime Warranty. ", "In the event this item should fail due to manufacturing defects during intended use, we will exchange the part free of charge (excludes shipping charges) for the original purchaser. ", "Please keep your invoice for proof of this warranty." ]

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[ "There have been several forms of antiperspirant products, such as sticks, soft solids, roll-ons, and aerosols. ", "The antiperspirant products may additionally contain deodorant actives. ", "The different forms deliver antiperspirant actives, and optionally deodorant actives, to axillary areas. ", "There can be disadvantages when formulating these types of products.", "\nOne disadvantage is that when an antiperspirant active is included, steps need to be taken to stabilize the antiperspirant from hydrolyzing and polymerizing during storage. ", "When an antiperspirant polymerizes into larger species, the efficacy is reduced.", "\nAnother disadvantage is that materials used for delivery, such as in the sticks or soft solids, can leave a white residue on the skin. ", "This can be aesthetically unpleasing when seen on skin or when transferred to clothing during wearing.", "\nIt would be advantageous to develop a new form of delivery of antiperspirant and/or deodorant actives." ]

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[ "KillerLocker Ransomware Removal Guide\n\nDo you know what KillerLocker Ransomware is?", "\n\nKillerLocker Ransomware is a Portuguese malware threat that seems to be unfinished yet. ", "There is a chance that the authors will finish this malicious program in the near future and it will become “deadly” as its name suggests; however, since it has been discovered by researchers, including our team, it may also become an abandoned project. ", "If this was a fully finished program, it could strike a major blow to your computer as it can encrypt all your most important files, including executables. ", "The only chance to recover your files after such a dangerous attack would be to risk paying the demanded ransom fee or use a recent backup you probably saved on a removable drive. ", "But since this ransomware is not a fully-working one and we have not yet found it spreading on the web, you can actually decrypt your files and remove KillerLocker Ransomware from your system.", "\n\nAlthough our researchers have not found this ransomware being distributed massively, we can still assume how it will be spread once it reaches the finished status; if at all. ", "We consider it essential for you to know how such a threat can infiltrate your system in order for you to be more prepared and able to avoid the next attack. ", "The mostly used method is most probably spamming campaigns. ", "This means that you may get a spam e-mail that looks totally legitimate and refers to an unpaid invoice, an issue with wrong credit card details, an undelivered parcel, and so on. ", "This mail will have a file attachment that can show up as an image or text file; although, in reality, it is a malicious executable file, most often a Trojan infection.", "KillerLocker Ransomware screenshotScroll down for full removal instructions\n\nThe trick is to convince you that you must see this attachment because the moment you save it onto your hard drive and run it to see the content, you actually infect your system with this ransomware. ", "This is why it is so important that you understand that even if you have a spam filter, such spam mails might end up in your inbox or other folders. ", "You need to become more cautious about which mails you open to be able to protect your computer.", "\n\nAnother method that could be used is called Exploit Kits. ", "This simply means that cyber criminals can take advantage of your browsers and drivers (Java and Flash) when these are not updated regularly. ", "Older bugs could be used to drop infections like KillerLocker Ransomware onto your computer. ", "We recommend that you keep all your programs and drivers up-to-date all the time to avoid such malicious attacks. ", "Because if a working version of this ransomware lands on your system, it will be too late to realize its presence and act upon it by deleting KillerLocker Ransomware because all your files will have been encrypted by then.", "\n\nMost unfinished ransomware programs we have seen lately do not even get to the point of encrypting your files. ", "This infection however actually does what it claims. ", "It uses the well-known AES-256 encryption algorithm to encrypt every file in your %ProgramFiles%, %APPDATA%, %USERPROFILE%\\Desktop, %USERPROFILE%\\MyPictures, and %LOCALAPPDATA% directories. ", "The encrypted files get a \".rip\" extension and become unusable until decrypted. ", "After finishing with your files, this infection drops a text file on your desktop called \"key.txt\" that contains the hardcoded decryption key, which was \"chavekey12345678910\" in our case.", "\n\nThe whole encryption may not take more than half a minute, which does not give you enough time from launch till accomplishment to react to this damage. ", "As a matter of fact, in this particular case, it would be a big mistake to delete KillerLocker Ransomware and soon you will understand why. ", "The ransom note window comes up on top of all your active windows but this one you can easily close or change with the Alt+Tab combination. ", "You can see a weird clown in the middle of this window, which is rather scary. ", "All you learn from this note though that your files have been encrypted with the AES-256 algorithm and you have 48 hours to pay the ransom fee; and all this in Portuguese. ", "This means that this ransomware will most likely target Portuguese users once it is finished. ", "However, there is no information about the amount of money you should transfer, no Bitcoin wallet address given, and neither are you given a contact e-mail or website. ", "Instead, you can simply enter the decryption code into the field called “Key” and press the “Decrypt files” button to recover all your files. ", "This is why it is not worth closing this window or removing this ransomware. ", "Once you manage to recover your files, you can simply remove KillerLocker Ransomware from your computer without further ado.", "\n\nIf you are ready to act, please follow our instructions below that contain all the necessary steps to delete this unfinished version of KillerLocker Ransomware. ", "It is really not too complicated, so even if you are not an experienced user, you can simply do it. ", "Nonetheless, it should be clear by now that if you want to keep malicious programs away from your system, you need to become a more cautious computer user and web surfer. ", "If you are looking for an automated solution, we suggest that you use a malware removal application that can automatically safeguard your computer from all possible malware threats.", "\n\nRemove KillerLocker Ransomware from Windows\n\nOpen the “key.txt” file on your desktop.", "\n\nCopy the decryption password and paste it in the field provided at the bottom of the ransom note screen.", "\n\nPress the Decrypt files button.", "\n\nAfter the decryption is done, close the ransom note window.", "\n\nPress Win+E to launch File Explorer.", "\n\nLocate the downloaded malicious file and delete it.", "\n\nBin the “key.txt” file from your desktop.", "\n\nEmpty your Recycle Bin.", "\n\nRestart your PC.", "\n\nIn non-techie terms:\n\nKillerLocker Ransomware is an unfinished malicious program that has not hit the web yet, but it has the potential to become your next nightmare. ", "The version our researchers tested in our internal lab actually drops a text file on the desktop that contains the hardcoded decryption password. ", "This version encrypts your most important files targeting certain directories and then displays its ransom note with a scary clown image right in the middle of this window. ", "However, there is no information about the demanded ransom fee or any ways to contact these criminals to transfer the fee for the decryption key. ", "Instead, you can simply paste the key you find in the text file and decrypt the files yourself before you set out to remove KillerLocker Ransomware from your system. ", "If you want to keep your computer safe from similar but more dangerous attacks, you should install a reliable anti-malware application that will automatically take care of all your security issues." ]

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[ "Q:\n\nString Array length is showing 1 even the array is empty after call split by comma (,)\n\nHere is my code:\nserialNumbers = \"\";\n\nString[] serialArray = serialNumbers.split(\",\");\n\nint arrayLength = serialArray.length;\n\narrayLength is showing 1 even there have no value in serialArray. ", "I was expecting that length should return 0 in this case.", "\n\nA:\n\nFrom the doc:\n\nIf the expression does not match any part of the input then the\n resulting array has just one element, namely this string.", "\n\nNote that this doc is from the String.split(String, int) method, which is invoked from String.split(String)\n\nA:\n\nSplit always returns at least one element.", "\nIn the case that a separator is not found, the entire input is returned in a single-element array.", "\n\n" ]

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[ "Endovascular recanalization of the thrombosed filter-bearing inferior vena cava.", "\nTo evaluate the authors' preliminary experience with use of endovascular methods to treat inferior vena cava (IVC) thrombosis in patients with IVC filters. ", "Catheter-directed thrombolysis, balloon maceration, mechanical thrombectomy, and stent placement were used to treat 10 patients with thrombosis of filter-bearing IVCs causing symptoms in 18 limbs. ", "Procedural challenges, technical and clinical success, complications, postprocedural filter status, and postprocedural pulmonary embolism (PE) prophylaxis were monitored. ", "Technical and clinical success were achieved in 15 of 18 (83%) and 14 of 18 symptomatic limbs (78%), respectively. ", "Major bleeding (muscular hematoma) occurred in one patient (10%). ", "Postprocedural PE prophylaxis included anticoagulation (n = 8) and placement of a new filter into a newly placed Wallstent (n = 1). ", "During clinical follow-up, no clinically detectable PE was observed. ", "Data pertaining to late limb status were available at a median of 19 months (range 1-46 months) follow-up in seven patients: three patients were asymptomatic, two patients had ambulatory edema only, one patient had constant mild edema, and one patient had constant severe edema. ", "Postprocedural filter stability was radiographically documented at a median of 255 days (range, 4-1021 d) of follow-up. ", "Endovascular recanalization of the occluded IVC is feasible even in the presence of an IVC filter." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Evolve\n\nIt's the age-old story.", "\n\nHumanity attempt colonisation of a planet and fall victim to aggressive wildlife, fauna and hulking predators with insatiable appetites. ", "Cue the rescue mission to evacuate the colony and minimise losses, and all within five days. ", "Here's where you, and friends, come in.", "\n\nYou'll play as one of four members of a specialist team (there's another perspective which we'll get to shortly), dropped at strategic points on the world, and tasked with protecting colonists during evacuation and hunting down whatever huge beast is going at the survivors like a Nandos platter.", "\n\nEach specialist has their own particular weapons and abilities. ", "The Trapper must track down the beast and use an energy field to contain it in the immediate area, thereby blocking its escape. ", "The Assault must bring the armoured creature down with heavy weaponry, while the Medic and Support characters need to use their futuristic equipment to keep the team alive. ", "The hunt itself, tracking down the beast that lurks somewhere on each map, is reminiscent of the Raids you'll see in MMORPGs, with smaller creatures and dangers to contend against before even encountering what effectively is the map's boss. ", "The twist, and that other perspective, is that the hulking creature can be controlled by another player.", "\n\nUnlike the first-person perspective of the hunters, the monster handler plays in third-person, and the beast - there are three types available - dwarfs the humans in size and shear strength. ", "However, at each round's start it's relatively weak and easy prey for a well-trained squad of hunters. ", "The odds quickly decrease if the creature is given the chance to eat the local wildlife, digestion letting the beast armour up and eventually evolve, which unlocks new abilities and makes it a much tougher predator.", "\n\nIt becomes a formidable opponent, and the only chance of success is for the hunters to work as a team. ", "Coordination of each skill is absolutely vital to survival. ", "So the broad strokes of the gameplay are defined: the alien fleeing its attackers, feeding, trying to catch its pursuers off-guard, then fleeing again to repeat the evolution and unlock yet more abilities. ", "The hunters trying to track, capture and kill their target. ", "Who is predator and who is prey flickers back and forth between the factions repeatedly over the course of the round. ", "There are different conditions for both factions depending on the game mode played, but the main thrust of this asymmetric multiplayer duel is simple and ingenious.", "\n\nThe big question though is how fast would the experience wear thin. ", "While there is a single player mode with bots filling out the rest of the roles, it's really only there to test out the different characters and grab some easy XP. ", "This is mainly a multiplayer title that demands five players who know what they're doing to enjoy, while there's a handful of modes that use the same maps but under different conditions and only three monsters available at launch.", "\n\nAs a features list, it mightn't seem much. ", "But variety is soon apparent through the synergy of the different specialist classes (and the trio of different character builds in each class) stacked against three very different monsters, and how each and every one is controlled.", "\n\nWe've experienced a range of experiences already: aggressive monster players who target hunters through skilful exploitation of the terrain the early stages of the match, leading us into dead ends then confounding us by appearing out of nowhere, scoring a kill then ghosting back into the foliage. ", "Or those that lay false trails and stalking around the maps, with our first encounter being the gigantic stage three mutations that are a terrifying foe.", "\n\nThere's a great difference between the trio of monsters, and a genuine sinking feeling in the stomach occurs come the match's start when you realise your opponent is one you personally hate (that'd be the Wraith for us), or as the match progresses and you feel the creature is all-too easily giving you the slip.", "\n\nFiltered through this experience is a perk system a dozen strong for both sides that can improve certain skills, plus the bonuses of elite creatures do make every match unique - and somehow there is really something here for every type of player. ", "Lone wolves will love the role of the monster, while real team players are allowed to use Medic and Support to care for their colleagues. ", "Trappers and Assault can be more aggressive with their tasks and so care less about the team dynamic.", "\n\nWe've sat through many, many hours of the alpha and beta, and poured a week and change so far into the final version of the game, and are amazed at the lack of wear on the gameplay. ", "Each match is different and always exciting. ", "You never know how good the competition is and must always assume the worst. ", "There's a lot to learn and refine, in terms of both tactics and strategies. ", "There's no grind, with perks and characters unlocked quickly and higher player levels awarded with mostly cosmetic additions. ", "It means that knowledge and strategy become key to winning, rather than an unlocked top-tier weapon or ability.", "\n\nEvolve is certainly not a game for everyone, but fans of ground-breaking, strategic action will not be disappointed. ", "It feels innovative and extremely exciting. ", "It's new, fresh and gives an urgently-needed shot in the arm to the stagnating throng of triple-A shooters. ", "It's a great idea for a title that's masterly crafted in the final product." ]

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[ "// CodeContracts\n// \n// Copyright (c) Microsoft Corporation\n// \n// All rights reserved. ", "\n// \n// MIT License\n// \n// Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the \"Software\"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:\n// \n// The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.", "\n// \n// THE SOFTWARE IS PROVIDED *AS IS*, WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. ", "IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.", "\n\n// File System.Runtime.CompilerServices.IsJitIntrinsic.cs\n// Automatically generated contract file.", "\nusing System.", "Collections.", "Generic;\nusing System.", "IO;\nusing System.", "Text;\nusing System.", "Diagnostics.", "Contracts;\nusing System;\n\n// Disable the \"this variable is not used\" warning as every field would imply it.", "\n#pragma warning disable 0414\n// Disable the \"this variable is never assigned to\".", "\n#pragma warning disable 0067\n// Disable the \"this event is never assigned to\".", "\n#pragma warning disable 0649\n// Disable the \"this variable is never used\".", "\n#pragma warning disable 0169\n// Disable the \"new keyword not required\" warning.", "\n#pragma warning disable 0109\n// Disable the \"extern without DllImport\" warning.", "\n#pragma warning disable 0626\n// Disable the \"could hide other member\" warning, can happen on certain properties.", "\n#pragma warning disable 0108\n\n\nnamespace System.", "Runtime.", "CompilerServices\n{\n static public partial class IsJitIntrinsic\n {\n }\n}\n" ]

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[ "Q:\n\nДва одновременных действия при нажатии на ссылку\n\nЕсть код:\n<script type=\"text/javascript\">\nfunction doRequest0(){\n$.get('api.php?order_id=<?php echo $data_id_var; ?", ">&data_client_tel1=<?php echo $data_client_tel_var; ?", ">&count_call', {\n action: 'doFunctionOnServer'\n}, function(data){\n });\n}\n</script>\n\nЕсть ссылка при нажатии которой выполняется код:\n<a href=\"tel:<?php echo $data_client_tel_var; ?", ">\" id=\"doRequest0\"><?php echo $data_client_tel_var; ?", "></a> Кол.: ", "<?", "php echo $count_call_var1; ?", ">\n\nТо есть, если кратко:\nПри нажатии на ссылку tel:0000000, должно открываться уведомление о том, через какую программу открыть префикс tel (либо сразу должна открываться звонилка, если нажали на ссылку в телефоне). ", "Все так работает.", "\nВторое действие, которое должно быть: Это отправка данных через ajax скрипту, который допишет в базу информацию о номере, на который пытались позвонить.", "\nЕсли с первым действием все получается, то второе уже не выполняется.", "\nПодскажите, как сделать так, чтобы выполнялось два действия при нажатии на ссылку?", "\n1. ", "Чтобы открывалась стандартная звонила на телефоне либо на компьютере, когда нажали на ссылку-номер.", "\n2. ", "В этот же момент должна отправится информация на сервер о том, что на эту ссылку нажали.", "\nУ меня не получается сделать так, чтобы сразу два действия выполнялись. ", "Получается сделать либо первое либо второе действие.", "\n\nA:\n\nА где собственно происходит привязка этой функции к обработчику событий? ", "У Вас название функции doRequest0 находится в атрибуте id\nВам нужно эту функцию привязать к атрибуту onclick\n<a href=\"tel:<?php echo $data_client_tel_var; ?", ">\" onclick=\"doRequest0()\"><?php echo $data_client_tel_var; ?", "></a> Кол.: ", "<?", "php echo $count_call_var1; ?", ">\n\n" ]

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[ "using System;\nusing System.", "Linq;\n\nnamespace Blazor.", "Sdk\n{\n class Program\n {\n static int Main(string[] args)\n {\n if (args.", "Length == 0)\n {\n Console.", "WriteLine(\"Usage: dotnet blazor <command>\");\n return 1;\n }\n\n var command = args[0];\n var remainingArgs = args.", "Skip(1).ToArray();\n\n switch (command.", "ToLowerInvariant())\n {\n case \"serve\":\n Host.", "Program.", "Main(remainingArgs);\n return 0;\n default:\n throw new InvalidOperationException($\"Unknown command: {command}\");\n }\n }\n }\n}\n" ]

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[ "545 F.2d 1300\n93 L.R.R.M. (BNA) 2870, 79 Lab.", "Cas. ", " P 11,740\nWilliam J. USERY, Secretary of Labor, Plaintiff, Appellant,v.LOCAL DIVISION 1205, AMALGAMATED TRANSIT UNION, Defendant, Appellee.", "\nNo. ", "76-1235.", "\nUnited States Court of Appeals,First Circuit.", "\nArgued Sept. 10, 1976.Decided Nov. 17, 1976.", "\n\nEloise E. Davies, Atty., ", "Appellate Section, Civ. ", "Div., ", "Dept. ", "of Justice, Washington, D.C., with whom Rex E. Lee, Asst. ", "Atty. ", "Gen., Washington, D.C., James N. Gabriel, U.S. Atty., ", "Boston, Mass., William J. Kilberg, Sol. ", "of Labor, Beate Bloch, Associate Sol., ", "Jerome J. Davis, Atty., ", "Dept. ", "of Labor, and Robert E. Kopp, Atty., ", "Appellate Section, Civ. ", "Div., ", "Dept. ", "of Justice, Washington, D.C., were on brief, for appellant.", "\nLawrence E. Katz, Cambridge, Mass., with whom Arthur J. Flamm, and Flamm, Mason, Paven & Feinberg, Boston, Mass., were on brief, for appellee.", "\nBefore CLARK, Associate Justice, U.S. Supreme Court (Ret.),* ", "McENTEE and CAMPBELL, Circuit Judges.", "\nLEVIN H. CAMPBELL, Circuit Judge.", "\n\n\n1\nThis suit to set aside an election of officers held in June of 1973 by Local 1205 of the Amalgamated Transit Union was brought by the Secretary of Labor under section 402(b) of the Labor-Management Reporting and Disclosure Act of 1959 (LMRDA), 29 U.S.C. § 482(b).1 The Secretary charges the Local with violations of section 401(e) of the LMRDA, first by imposing \"an unreasonable meeting attendance qualification for candidacy\", and second by unreasonably refusing to accept certain nominations.", "\n\n\n2\nAfter the Secretary's complaint was filed in the district court, both parties conducted discovery, and Local 1205 moved for summary judgment, filing an affidavit and brief. ", " Although the Secretary had ample time to do so, he apparently neglected to file a brief in advance of the hearing on the motion; and after argument the court directed entry of judgment for the Local.", "\n\n\n3\nThe Secretary's failure to file a timely brief in the district court cannot be condoned. ", " The district court was entitled to the cooperation of both parties, and especially of the Secretary, who instituted the suit. ", " The court was under no obligation to perform unaided legal research, nor to accept a brief out of time.", "\n\n\n4\nThe Local, however, has not asked us to affirm on the ground of the Secretary's non-cooperation with the district court, nor did the court itself indicate this factor as a reason for its judgment; both sides have briefed and argued the substantive legal issues, and it would now seem to be in the interest of the Local and its members for us to decide these matters even as it turns out adversely. ", " We proceed, therefore, to the merits.", "\n\n\n5\nThe undisputed facts relating to the two claimed violations of the LMRDA are as follows.", "\n\n\n6\n1. ", "Disqualification of Klayton for non-attendance.", "\n\n\n7\nIn May, 1973, Local 1205 had 338 members made up of 268 active and 70 retired employees of the Greyhound Lines (Eastern Division) and the Bangor and Aroostook Railroad. ", " Most active members worked out of Boston (212). ", " Others held positions based in Bangor (17), Portland (6), Providence (15), Hartford (18) and New Haven (2). ", " Meetings were held monthly in both Boston and Portland; members located elsewhere could bus to the meetings if they desired using free Greyhound pass privileges.", "\n\n\n8\nLocal 1205 held regular biennial elections. ", " In September, 1971, the Local adopted a bylaw requiring that candidates for office must have attended not less than six regular meetings each year during the twenty-four months prior to an election, such a rule being optional with each local under the International's constitution. ", " The bylaw included a liberal excuse provision by which a member, absent for a legitimate reason, could obtain attendance credit simply by sending a postcard to the recording secretary within ten days after the meeting.", "\n\n\n9\nIn December, 1972, Local 1205 conducted a special election for financial secretary and member Ronald Klayton was elected. ", " Klayton had not attended six meetings a year for the preceding twenty-four months, but being the sole nominee was allowed to stand and serve. ", " Six months later, however, when the Local conducted its regular elections, Klayton was not permitted to run for the office because of the attendance requirement. ", " Although he had attended ten meetings in the 1972-73 year, he had gone to only five meetings in 1971-72.2\n\n\n10\n2. ", "Refusal of Willie Higgins' nomination.", "\n\n\n11\nUnder the Local's bylaws, nominations of officers take place at the regular May meeting. ", " Nominations may be made by mail if they are received by the recording secretary on or before the day of the nominating meeting. ", " In May, 1973, Willie Higgins and two other members of the Local attended the meeting in Boston with the intention of nominating themselves for office. ", " When the meeting was cancelled for lack of a quorum, Higgins and his companions vainly attempted to submit their nominations in writing to the recording secretary. ", " By letter, Higgins protested to the Local the rejection of these nominations, but his protest was unavailing. ", " He thereupon appealed to the International prior to the election, but the appeal was denied. ", " The election took place in June, 1973, and four days later Higgins challenged it under a provision in the constitution of the International allowing voting members to challenge the conduct or results of an election within 10 days afterwards. ", " Higgins maintained that the refusal to accept the proffered written nominations had been improper. ", " The executive board of the Local denied his appeal as did the International vice president. ", " The general executive board of the International informed Higgins that it would hear his appeal; however, the record is silent on whether or not the issue was ever taken up by that body. ", " On October 2, 1973, Higgins filed a complaint with the Secretary of Labor challenging the June, 1973, election. ", " That complaint led to this proceeding.", "\n\n\n12\n* We first consider the bylaw which caused Klayton to be disqualified as a candidate for office for failure to attend six meetings each year during the twenty-four month period prior to elections. ", " Section 401(e) of the LMRDA provides, in part, that in elections subject to the Act,\n\n\n13\n\". . . ", " (A) reasonable opportunity shall be given for the nomination of candidates and every member in good standing shall be eligible to be a candidate and to hold office (subject to . . . ", " reasonable qualifications uniformly imposed) and shall have the right to vote for or otherwise support the candidate or candidates of his choice . . ..\"", "\n\n\n14\nThe question here is thus whether the candidacy restriction was a \"reasonable qualification\". ", " The legislative history and wording of section 401(e) reveal a congressional purpose to ensure open and democratic union elections and to limit candidacy restrictions to those that do not invite abuse, especially by entrenched incumbents. ", " See Wirtz v. Hotel Employees, Local 6, 391 U.S. 492, 499, 88 S.Ct. ", "1743, 20 L.Ed.2d 763 (1968); Wirtz v. Local 153, Glass Bottle Blowers, 389 U.S. 463, 470-71, 88 S.Ct. ", "643, 19 L.Ed.2d 705 (1968); Aaron, The Labor-Management Reporting and Disclosure Act of 1959, 73 Harv.", "L.Rev. ", "851 (1960). ", " With respect to attendance, a requirement that candidates must have attended 75 percent of all meetings within the preceding two years has been held invalid, Wirtz v. Local 153, Glass Bottle Blowers, 405 F.2d 176, 178 (3d Cir.), ", "on remand from 389 U.S. 463, 88 S.Ct. ", "643, 19 L.Ed.2d 705 (1968). ", " But lesser requirements covering, for example, 25 percent of meetings in one year, have been upheld, e.g., Shultz v. Local 420, Aluminum Workers, 74 L.R.R.M. 2281 (N.D.N.Y.1970). ", " See Martin v. Boilermakers, Local 636, 245 F.Supp. ", "375 (W.D.Pa.1963) (one meeting per quarter for each of five quarters). ", " There is presently a split between circuits over a requirement of attendance at 50 percent of meetings over a thirty-six month period. ", " Brennan v. Local 5724, Steelworkers, 489 F.2d 884, 888 (6th Cir. ", "1973) (upholding such a requirement as a \"reasonable qualification\"); Brennan v. Local 3489, Steelworkers, 520 F.2d 516, 520 (7th Cir. ", "1975), cert. ", "granted, 424 U.S. 907, 96 S.Ct. ", "1100, 47 L.Ed.2d 311 (1976) (disapproving such a requirement). ", " See also Brennan v. Local 639, Teamsters, 161 U.S.App.", "D.C. 173, 494 F.2d 1092, 1098-99 (1974).", "\n\n\n15\nThe Secretary makes much of the fact that the 50 percent a year, twenty-four month requirement here in issue, disqualifies almost 94 percent of the membership from running, and he compares this figure with the 93 percent disqualified under a different candidacy limitation struck down in Wirtz v. Hotel Employees, Local 6, 391 U.S. 492, 88 S.Ct. ", "1743, 20 L.Ed.2d 763 (1968). ", " The Local responds that the present requirement is ameliorated by the liberal excuse provision and free bus privileges and points out that Klayton, the candidate disqualified by the rule, was himself an incumbent, albeit a very recent, and certainly not an \"entrenched\" one. ", " Apathy rather than the stringency of the requirement is said to be the reason for the high percentage of disqualification. ", " See Brennan v. Local 5724, supra, 489 F.2d at 888-89.", "\n\n\n16\nWe do not give conclusive weight here to the fact that nearly 94 percent of the membership did not meet the requirement although this is certainly of importance; the question is not only how many were disqualified but how burdensome was the qualification. ", " We do conclude, however, that a bylaw which has the effect of requiring attendance for a period that must begin no later than eighteen months before a biennial election cannot be squared with Congress' aim to open up union elections and make them democratic thereby combating the likelihood of an entrenched leadership. ", " See Wirtz v. Local 153, Glass Bottle Blowers, supra, 405 F.2d at 176 (invalidating a 75 percent requirement that had much the same practical effect); Brennan v. Local 3489, Steelworkers, supra, 520 F.2d at 520 (invalidating 50 percent, thirty-six month requirement that had same effect). ", " At least, such a prolonged attendance requirement places a heavy burden of justification upon the union, a burden that has not been met here.3\n\n\n17\nThis is not to say that a union may not restrict candidacy to members who have demonstrated some interest in union affairs and who have had some exposure to the union's problems; but these aims can be satisfied by qualifications capable of being met in a shorter period. ", " By requiring a candidate to, in effect, project his candidacy eighteen months or more in advance, the challenged requirement seems to us to erect too high a barrier under a statute whose purpose is to guarantee union democracy.", "\n\n\n18\nIt is significant, also, that the bylaw goes well beyond the attendance requirement sanctioned in the Secretary's interpretative regulations that were in effect in June of 1973. ", " Section 422.206 of the LMRDA Interpretative Manual then provided that a provision requiring a member \"to have attended at least one-half of the regular meetings of his local union for 24 months previous to the election before he may be eligible to hold office, is not unreasonable if it is applied fairly and uniformly to all members.", "\"4 Klayton would have qualified under such a provision (he attended a total of fifteen meetings in the twenty-four months prior to the election). ", " What disqualified him here was the requirement that six of the twelve required meetings be attended in each of the two years. ", " While the Secretary's interpretative regulations are not binding on courts, they gave currency to the then views of the official charged by Congress with enforcement of the LMRDA, and we think they are entitled to some weight when ascertaining what qualifications are reasonable in gray areas of the Act. ", " Cf. ", "Stockman v. Clark, 539 F.2d 264, 269 (1st Cir. ", "1976). ", " See generally 4 Davis, Administrative Law Treatise § 30.09 et seq.", "\n\n\n19\nWe hold that the attendance requirement in question was excessive and unreasonable and that it violated the Act.", "\n\nII\n\n20\nSection 402(a) of the LMRDA states that a prerequisite to the filing of a civil action by the Secretary is that he receive a complaint from a union member \"who has exhausted the remedies available under the (union's) constitution and bylaws\". ", " 29 U.S.C. § 482(a)(1). ", " The statute provides that a union member wishing to contest a union election must file his complaint either within one month of a final adverse decision by the union or within four months of his initial invocation of internal remedies. ", " 29 U.S.C. § 482(a)(2).5\n\n\n21\nHiggins filed his complaint on October 2, 1973. ", " The Local contends that he had exhausted his internal remedies for the purposes of section 402(a) on June 1, 1973, prior to the election and at the end of his first round of appeals. ", " Alternatively, the union suggests that even if one were to take the view that there had been no final disposition of Higgins' complaint prior to the elections, he was confined to the four month time period beginning with the original invocation of internal remedies on May 11, 1973. ", " This would have required filing of the complaint by September 11, 1973 at the latest. ", " The Local rejects the Secretary's contention that Higgins' post-election round of challenges should provide the measure by which to determine the timeliness of the complaint to the Secretary. ", " We disagree.", "\n\n\n22\nThe LMRDA provides that \"(e)xisting rights and remedies to enforce the constitution and bylaws of a labor organization with respect to the elections prior to the conduct thereof shall not be affected by (Title IV). ", " The remedy provided by (Title IV) for challenging an election already conducted shall be exclusive,\" 29 U.S.C. § 483. ", " The Supreme Court has said that the LMRDA provides for an expeditious, exclusive post-election remedy, see Calhoon v. Harvey, 379 U.S. 134, 140, 85 S.Ct. ", "292, 13 L.Ed.2d 190 (1964); and several district courts have concluded on the basis of the Supreme Court's language in Harvey that invocation of pre-election remedies does not place in motion the statutory timetable. ", " See Wirtz v. H. H. Guy Lodge, No. ", "873, Railroad Trainmen, 279 F.Supp. ", "873, 874 (W.D.Pa.1967); Wirtz v. Local 30, Operating Engineers, 242 F.Supp. ", "631 (S.D.N.Y.1963), vacated as moot, 366 F.2d 438 (2d Cir. ", "1966).", "\n\n\n23\nIn contending that the pre-election remedy was decisive here, the Local relies upon Hodgson v. United Steelworkers, 459 F.2d 348 (3d Cir. ", "1972). ", " In that case a union member protested the absence of his name on the ballot for an International election. ", " This appeal, filed with the union prior to the election as required by the International's constitution, was denied. ", " Following the election, the member again protested his exclusion from the ballot. ", " Almost simultaneously, he was advised by the Department of Labor that his union remedies would not be exhausted until he filed a protest to the union after the publication of the tellers report. ", " The union responded to this first post-election protest by informing the member that his challenge to the nomination procedure had already been decided against him. ", " After the issuance of the tellers report, two months after the election, the member protested once more. ", " The union replied by letter that he had \" 'invoked and exhausted the remedies available under the International Constitution many months ago.' \" ", " A complaint to the Secretary was filed within one month of receipt of this letter.", "\n\n\n24\nThe third circuit held that the complaint was not timely filed under section 402(a), reasoning that the statute speaks of a member \"who has exhausted the remedies available under the (union's) constitution and bylaws\". ", " The union constitution's provision for contesting nominating procedures required that an appeal be instituted not later than forty-five days before an election. ", " There was no post-election recourse for challenging nominations. ", " Despite the Secretary's assertion that Congress had not intended the operation of section 402(a) to interfere with internal union election procedures prior to an election, the court stated that the delay in filing which resulted from the member's second round of appeals \"could serve no purpose other than to lengthen unnecessarily the time required to resolve any conflict between union procedure and the federal law.\" ", " Id. at 352.", "\n\n\n25\nBut Hodgson, even if we were to assume that it was correctly decided, does not help the Local here. ", " Neither Local 1205's bylaws nor the International's constitution designate a pre-election procedure, much less an exclusive one, for challenging nominations. ", " Higgins made his first round of protests under a general procedure available to any member who feels he has been dealt with \"unfairly\". ", " His second round of protests, which immediately preceded his complaint to the Secretary, invoked the only procedure in the union constitution that relates specifically to elections; and that procedure is available only after an election has been held. ", " Had Higgins not invoked the latter, it might well have been said that he had not exhausted the pertinent \"remedies available under the constitution and bylaws\" of the union, as section 402 commands must be done. ", " While judicial resolution of union election conflicts should not be needlessly delayed, the statute requires a full scale effort to resolve disputes within the union itself, and permits resort to the statutory remedy only when internal procedures have failed. ", " See Wirtz v. Local 153, Glass Bottle Blowers, supra, 389 U.S. at 471-72, 88 S.Ct. ", "643; Wirtz v. H. H. Guy Lodge, No. ", "873, Railroad Trainmen, supra, 279 F.Supp. ", "at 874. ", " We conclude that the complaint was timely filed within the meaning of section 402(a). ", " It follows that the district court should have decided whether the Local's refusal to accept the nominations was in violation of the LMRDA, and this question is now open for consideration upon remand.", "\n\n\n26\nThe judgment of the district court dismissing the Secretary's complaint is vacated, and the case remanded to the district court for further proceedings not inconsistent with this opinion. ", " No costs.", "\n\n\n27\nSo ordered.", "\n\n\n\n*\n Sitting by designation\n\n\n1\n Section 402(b) provides:\n\"The Secretary shall investigate such complaint and, if he finds probable cause to believe that a violation of this subchapter (Title IV) has occurred and has not been remedied, he shall, within sixty days after the filing of such complaint, bring a civil action against the labor organization as an entity in the district court of the United States in which such labor organization maintains its principal office to set aside the invalid election, if any, and to direct the conduct of an election or hearing and vote upon the removal of officers under the supervision of the Secretary and in accordance with the provisions of this subchapter and such rules and regulations as the Secretary may prescribe. ", " The court shall have power to take such action as it deems proper to preserve the assets of the labor organization.\"", "\n\n\n2\n Klayton was eventually elected financial secretary at the 1975 election, held after commencement of this suit. ", " It is not now contended that Klayton's success in 1975 has rendered moot the question of the legality of Klayton's 1973 disqualification for non-attendance. ", " Seemingly it has not. ", " See Wirtz v. Local 153, Glass Bottle Blowers, 389 U.S. 463, 475, 88 S.Ct. ", "643, 19 L.Ed.2d 705 (1968); Brennan v. Local 3489, Steelworkers, 520 F.2d 516, 518 n. 3 (7th Cir. ", "1975), cert. ", "granted, 424 U.S. 907, 96 S.Ct. ", "1100, 47 L.Ed.2d 311 (1976)\n\n\n3\n While the Local's liberal postcard \"excuse\" rule makes the requirement less burdensome, it also tends to undermine the justification for it: if prospective candidates can so easily avoid coming to meetings the bylaw would seem to serve little purpose other than to screen out those who did not make up their minds to run at least a year and a half early\n\n\n4\n The regulation went on to indicate that such an attendance requirement could \"well be unreasonable\" in circumstances in which attendance presented an unusual degree of difficulty for a significant proportion of the membership. ", " We need not decide if that was so here, since by requiring attendance at six meetings each year the challenged bylaw was significantly more burdensome than that sanctioned by the Secretary\nThe Secretary's regulations have since been altered so as to further qualify the per se validity of a 50 percent, twenty-four month rule. ", " See 29 C.F.R. 452.38(a).", "\n\n\n5\n Section 402(a) reads as follows:\n\"(a) A member of a labor organization\n(1) who has exhausted the remedies available under the constitution and bylaws of such organization and of any parent body, or\n(2) who has invoked such available remedies without obtaining a final decision within three calendar months after their invocation,\nmay file a complaint with the Secretary within one calendar month thereafter alleging the violation of any provision of section 481 of this title (including violation of the constitution and bylaws of the labor organization pertaining to the election and removal of officers). ", " The challenged election shall be presumed valid pending a final decision thereon (as hereinafter provided) and in the interim the affairs of the organization shall be conducted by the officers elected or in such other manner as its constitution and bylaws may provide.\"", "\n\n\n" ]

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[ "Q:\n\nSecond segue from TableViewController creating SIGABRT error relating to the first\n\nI have created a NoteBook application within a larger app. ", "I have all the functionality working including a segue to an Add Note page which triggers programatically from clicking a note (to edit it) or a + barButtonItem. ", "\nI need a second segue to send the user back to the home page of the app, but every way I seem to try it conflicts with the existing segue I have in place. ", "\nCan anyone suggest a way to get the second segue to work. ", "They both have different identifiers which I am referencing in the methods. ", "Its just the goHome segue that will not work...\nclass NoteBookViewController: UITableViewController, NoteViewDelegate {\nfunc didUpdateNoteWithTitle(newTitle: String, andBody newBody: String) {\n self.noteBookEntries[self.selectedIndex] [\"title\"] = newTitle\n self.noteBookEntries[self.selectedIndex] [\"body\"] = newBody\n\n self.tableView.reloadData()\n\n saveNotesArray()\n}\n\nvar noteBookEntries = [[String:String]] ()\n\n@IBAction func newNote() {\n\n var newNote = [\"title\" : \"\", \"body\" : \"\"]\n noteBookEntries.insert(newNote, at: 0)\n\n self.selectedIndex = 0\n\n self.tableView.reloadData()\n\n saveNotesArray()\n\n performSegue(withIdentifier: \"editNoteBookSegue\", sender: nil)\n}\n\nvar selectedIndex = -1\n\nfunc saveNotesArray() {\n\n UserDefaults.standard.set(noteBookEntries, forKey: \"notes\")\n UserDefaults.standard.synchronize()\n}\n\noverride func viewDidLoad() {\n super.viewDidLoad()\n\n if let newNote = UserDefaults.standard.array(forKey: \"notes\") as? [[", "String:String]] {\n noteBookEntries = newNote\n }\n\n self.navigationItem.leftBarButtonItem = UIBarButtonItem(barButtonSystemItem: UIBarButtonSystemItem.reply, target: self, action: #selector(NoteBookViewController.navigateToNextViewController))\n\n}\n\nfunc navigateToNextViewController(){\n self.performSegue(withIdentifier: \"goHome\", sender: self)\n}\n\noverride func didReceiveMemoryWarning() {\n super.didReceiveMemoryWarning()\n}\n\n override func tableView(_ tableView: UITableView, numberOfRowsInSection section: Int) -> Int {\n return noteBookEntries.count\n}\n\noverride func tableView(_ tableView: UITableView, cellForRowAt indexPath: IndexPath) -> UITableViewCell {\n let cell = tableView.dequeueReusableCell (withIdentifier: \"CELL\")! ", "as UITableViewCell\n cell.textLabel?.text = noteBookEntries[indexPath.row][\"title\"]\n return cell\n}\n\noverride func tableView(_ tableView: UITableView, commit editingStyle: UITableViewCellEditingStyle, forRowAt indexPath: IndexPath) {\n if editingStyle == UITableViewCellEditingStyle.delete {\n noteBookEntries.remove(at: indexPath.row)\n UserDefaults.standard.set(noteBookEntries, forKey: \"notes\")\n self.tableView.reloadData()\n }\n}\n\noverride func tableView(_ tableView: UITableView, didSelectRowAt indexPath: IndexPath) {\n\n self.selectedIndex = indexPath.row\n\n performSegue(withIdentifier: \"editNoteBookSegue\", sender: nil)\n}\n\n override func prepare(for segue: UIStoryboardSegue, sender: AnyObject?) {", "\n let notesEditorVC = segue.destination as! ", "NewNoteBookEntryViewController\n\n notesEditorVC.navigationItem.title = noteBookEntries[self.selectedIndex] [\"title\"]\n notesEditorVC.noteBodyText = noteBookEntries[self.selectedIndex] [\"body\"]\n notesEditorVC.delegate = self\n\n}\n\n}\nerror message relating to original segue - this segue works until the second is added\n\nA:\n\nIn your prepareForSegue method first line is:\nlet notesEditorVC = segue.destination as! ", "NewNoteBookEntryViewController\n\nThis method is called for each of your segues. ", "When it is called for your first segue it works totally fine because the destination view controller is, in fact, of type NewNoteBookEntryViewController.", "\nHowever, when this method is called for your second segue, the destination controller is of different type. ", "So, you get a crash when you force downcast it.", "\nYou should add some logic to your prepareForSegue method so that you distinguish between segues. ", "For example:\nif segue.identifier == \"addNote\" {\n let notesEditorVC = segue.destination as! ", "NewNoteBookEntryViewController\n //some other code\n}\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "2005 Asia-Pacific Rally Championship\n\nThe 2005 Asia-Pacific Rally Championship season (APRC) was an international rally championship organized by the FIA. ", "The champion was Finnish driver Jussi Valimaki.", "\n\nCalendar\n\nPoints\n\nReferences\n\nExternal links\nOfficial website\nResults on FIA website\n\nCategory:Asia-Pacific Rally Championship seasons\nAsia-Pacific Rally\nRally\nRally" ]

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[ "Boris Johnson has told Sky News there is \"cash available\" for his growing list of spending pledges if he becomes the next prime minister.", "\n\nThe race favourite was challenged over his funding commitments in an interview with the Sophy Ridge on Sunday programme as he outlined plans to reverse education cuts and pour billions of pounds into schools.", "\n\nThe former foreign secretary has raised eyebrows at Westminster in making a string of financial promises from extra police on the streets and more transport cash through to big tax cuts and faster broadband for all.", "\n\nMr Johnson is the acknowledged frontrunner in the fight for Downing Street with rival Foreign Secretary Jeremy Hunt.", "\n\nBoth men are currently on the campaign trail, speaking at a series of hustings with party members, who will decide which candidate takes the Tory crown.", "\n\n\nSpeaking to Ridge on Sunday, Mr Johnson stressed the importance of education and said a top priority would be to ensure schools got the funding they need.", "\n\nHe has committed to pump an extra £4.6bn a year into the system by 2022-23 if he gets the keys to Number 10.", "\n\n'Survive Sophy Ridge and you can survive anything'\n\nMr Johnson said: \"I think education is the single most important thing that we Conservatives believe in.", "\n\n\"In the sense that it is the tool that every kid should have to make the most of their talents and their opportunities, and a great education is the job of the state to provide to absolutely everybody.", "\n\n\"What's been happening in the UK over the last few years is that too many schools have been falling behind in their per capita provision.", "\n\n\"So what I want to do, day one, is level up and make sure that everybody, primary schools and secondary schools, get the funding they need.\"", "\n\nHe also promised extra support for special educational needs.", "\n\nBut tackled by Ridge over his burgeoning list of spending commitments and that he was \"having his cake and eating it\", Mr Johnson insisted there was \"headroom available\" in the Treasury coffers and argued \"sensible tax cuts\" would generate growth and so increase revenue.", "\n\nHe said: \"Well actually, of course, as the great Tunisian scholar and sage Ibn Khaldun pointed out as early as the 14th century, there are plenty of taxes that you can cut which will actually increase your revenues and there are ways of making sure that you stimulate growth, you stimulate enterprise and you get more in.", "\n\n\"But what is certainly true is at the moment there is cash available.\"", "\n\nHe added: \"I think at the moment there is the headroom available and we intend to use it.", "\n\n\"I also think you can do some great things to stimulate economic growth with tax cuts.\"", "\n\n:: The full interview with Boris Johnson - discussing education, Brexit and much more - will be on Sophy Ridge on Sunday at 9am." ]

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[ "Washington D.C. [USA], Nov 6 (ANI): The Khorasan group of the ISIS or the ISIS-K, which specifically operates in south Asia, attempted a suicide attack in India 2018, a top American official has informed lawmakers.", "\n\n\"Of all of the branches and networks of ISIS, ISIS-K is certainly one of those of most concern-probably in the neighbourhood of 4000 individuals or so. ", "We certainly share the concerns of both the US military and embassy. ", "They have attempted to certainly inspire attacks outside of Afghanistan,\" Russel Travers, Acting Director of the US National Counter-terrorism Center, Office of Director of National Intelligence, said on Tuesday.", "\n\n\"They attempted last year to conduct a suicide attack in India--it failed,\" Travers said in response to Senator Maggie Hassan over the group's ability to carry out terrorist attacks in the region.", "\n\n\"I heard clearly that ISIS-K threatens not only US forces in Afghanistan, but also has designs on striking the US homeland,\" she said in a video posted on her official Twitter page while mentioning about her travel to Afghanistan and Pakistan last month.", "\n\nLast week, Hassan said, there were more than 20 ISIS branches globally, some of which are using sophisticated technology, such as drones, to conduct operations.", "\n\n\"We know that ISIS-K and other affiliates of ISIS want to strike the US homeland,\" the Senator added.", "\n\nDespite, the United States' key victories against ISIS in Syria and Iraq, the terror outfit remains a threat to America.", "\n\nMeanwhile, Travers, in his response emphasized that the ISIS-K had a couple of years ago tried to inspire an attack in New York which the FBI interrupted. ", "Then there was an attack in Stockholm in 2017 that killed five people, he added.", "\n\n\"So they certainly have got a desire and the propaganda would indicate that they want to conduct attacks outside of Afghanistan. ", "I would say that we saw attack claims by ISIS-K ramping up throughout '16, '17, '18. ", "Somewhat lower at the beginning of this year, although now I think we're looking at about an attack a day or so,\" the counter-terrorism official said. (", "ANI)" ]

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[ "Swiftboating\n\nThe term swiftboating (also swift-boating or swift boating) is a pejorative American neologism used to describe an unfair or untrue political attack. ", "The term is derived from the name of the organization \"Swift Boat Veterans for Truth\" (SBVT, later the Swift Vets and POWs for Truth) because of their widely publicized—and later discredited—campaign against 2004 U.S. presidential candidate John Kerry.", "\n\nSince the political smear campaign that the group conducted against Kerry, the term has come into common use to refer to a harsh attack by a political opponent that is dishonest, personal, and unfair. ", "The Swift Boat Veterans and media pundits objected to this use of the term to define a smear campaign.", "\n\nOrigin\nThe term \"Swift Boat\" itself refers to a class of United States Navy vessel used during the Vietnam War. ", "During the 2004 presidential campaign, John Kerry's heroism under fire as a Swift Boat commander in Vietnam was a centerpiece of his campaign. ", "A number of Vietnam veterans who had served on Swift Boats formed a 527 organization called Swift Boat Veterans for Truth (later renamed Swift Vets and POWs for Truth or SVPT) with the intent of discrediting his military record and attacking his subsequent antiwar activities as a member of Vietnam Veterans Against the War. ", "The group produced a series of television ads and a bestselling book, Unfit for Command. ", "The unsubstantiated charges against Kerry by the SVPT gave rise to the term \"swiftboating\" as a synonym for \"the nastiest of campaign smears\", \"a slimy political attack\", and, for many, \"ugly, unprincipled slander\". ", "As the purpose of a tax-exempt 527 organization is \"to focus on the issues\" rather than \"attack or defend a specific candidate\", the SBVT was fined by the Federal Election Commission in 2004 for specifically attacking Kerry instead of focusing on political issues.", "\n\nLater use\nCharges of \"swiftboating\" were made by supporters of both major candidates in the 2012 presidential election. ", "Republican Party strategists compared attacks on Mitt Romney's tenure at Bain Capital to swiftboating: \"It's very clear they are trying to re-create and take a page out for the 2004 Bush campaign.\" ", "The term was also used by a representative of Barack Obama's re-election campaign to describe the documentary film Dishonorable Disclosures and an associated ad campaign released by the Special Operations OPSEC Education Fund on the topic of the death of Osama bin Laden.", "\n\nThe feminist Gloria Steinem has accused Donald Trump of swiftboating his rival Hillary Clinton during the 2016 presidential race, calling her 'Crooked Hillary', despite his record of much more frequent and severe lying.", "\n\nHillary Clinton compared Republicans' statements about Christine Blasey Ford during the Kavanaugh confirmation process to the \"swift-boating of John Kerry\".", "\n\nThe New York Times reported in 2008 that many Swift Boat veterans, \"especially those who had nothing to do with the group that attacked Senator John Kerry's military record in the 2004 election—want their good name back, and the good names of the men not lucky enough to come home alive\", expressed regret and dismay that the term \"swift boat\" has come to represent a political attack and \"political chicanery\" against a member of a different party.", "\n\nConservative objections and use\nThe use of this term as a pejorative has resulted in objections from some conservatives who object to the implied criticism of the tactics used by Swift Vets and POWs for Truth.", "\n\nIn 2006, conservative commentator Emmett Tyrrell denounced its repeated negative usage, saying it \"is about to join such terms as McCarthyism and McCarthyite\" as a \"hate term\". ", "In a 2006 interview, John O'Neill, spokesman for Swift Vets and POWs for Truth, called the term's usage a \"baseless smear against somebody's personal character\".", "\n\nRepublican Newt Gingrich, putting his own twist on the neologism at a presidential campaign stop on January 1, 2012, said he felt he was being \"Romney-boated\" by the barrage of negative ads run against him. ", "Fox News Radio host John Gibson has written a book titled How the Left Swiftboated America, in which he defines swiftboating as \"the political trick of claiming to expose truth while in fact lying\".", "\n\nSee also\n John Kerry military service controversy\n Borking, another political neologism\n Astroturfing\n\nReferences\n\nCategory:Political terminology of the United States\nCategory:Political campaign techniques" ]

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[ "Scharner's Benefited By Hodgson's Arrival\n\nKeith Downing believes that Paul Scharner has benefited from the arrival of Roy Hodgson as he now has a defined role to excel in.", "\n\nSpeaking to wba.co.uk Downing believes that we are seeing the best of Scharner now he's being used as a foil for Mulumbu in midfield, and the stability of his positioning is helping to improve his match day form.", "\n\n'There is a massive focus to Paul's game, he does extra training and his professionalism is noticeable. ", "Hodgson sees Scharner as a foil with Mulumbu, those two midfield players are very important for us and have both done very well.'", "\n\nOne of the things that pleases Downing is that he says Scharner is one of the first into training and one of the last out, and that he is still very driven to improve as a player despite his age.", "\n\nNot only is that a brilliant asset and mentality whilst on the pitch, but it also makes him a brilliant influence off the pitch." ]

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[ "Now for the icing on the cake. ", "There's one last thing that sets me apart from control, and that's the knowledge that I know my life has happened, is happening, and will happen exactly as it was intended to, and there isn't a fucking thing any of you can do to alter that.", "\n\nStrange, I haven't figured out what my first name is yet, but I'm starting to think everyone should just call me sue..... Sue all your pants off. ", "It's not pleasant being immortal and unable to die..... You're all sick and you need help\n\nAll I would have to do is wink at a lawyer and they would take my case in a heartbeat because I could literally sue any person in the universe.... Where's my cash settlement so I can retire and spend more time with my family and friends?", "\n\nLife isn't a video game, just stop it, control the video game world, and stay the hell out of my life.... Pay the people who have been robbed, this fundraiser crap is all bull, so is the lottery.... It's all a big lie and pyramid scheme.... Leave the shemes for wall street and video games, people's lives have had enough of being traded, you do NOT trade human beings, and if you're going to eat animals, make them free range and leave the genetically engineered cows on the moon\n\nJust talk to me in person, I'm not a monster, I'm a man who's cup is overflowing and I have too many dinner plates in front of me.... I can't do this for all of you... I have a family of my own that needs me.... I can't be everything to every living soul on the planet\n\nI still quit, I won't help a world that lives like this. ", "Ask me in person after I get my cheque.... Blizzard can fork it out, they owe me lots of cash... After all, you were all watching me play to make better games.... I bet you wish I would play the new games and figure them out for you... They must be too hard, hahahaha" ]

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[ "Q:\n\nHow to learn a new library/framework in Haskell?", "\n\nI would like to delve into the Yesod web framework but I am not really sure how to do it. ", "It would be perfect if I could test each method individually and interactively in GHCi. ", "So I really want to know how it works internally. ", "It is not just about how to use Yesod or any other library. ", "Is this a reasonable way to do it? ", "How deal others with learning a new library in Haskell?", "\n\nA:\n\nYesod heavily relies on Template Haskell, quasiquotes and compilation, even for templates. ", " You could test it to some extent on the command line, but this is going to be very inconvenient. ", " However, the Yesod Book is very comprehensive and gives a beginner-friendly introduction.", "\n\nA:\n\nWeb frameworks aren't exactly the easiest thing to test on a method by method basis because they need a lot of context. ", " Since they are primarily dealing with network communication they invariably have to run in some monad (IO at the very least). ", " The three most popular Haskell web frameworks today all define their own monad to make things more convenient. ", " Typically this will include a good bit of state under the covers to keep track of things like headers, parsed query string and post parameters, etc. ", " This means that if you want to test at least some of the web server API you'll have to have a complete HTTP request and/or the underlying data needed derived from the request by the web server monad.", "\nNow it's certainly possible to create an API that makes all of the above easier to do. ", " Yesod's version of this is in the wai-test package. ", " Snap's version is in the Snap.", "Test module in snap-core.", "\nYesod also relies a lot on Template Haskell (TH), which is Haskell's meta-programming library (like Lisp macros). ", " All three web frameworks use TH in places, but Yesod uses it more heavily with its custom quasiquoted DSLs. ", " TH requires two passes. ", " First you have to compile the TH code, then that code is executed, generating new code. ", " Then the new code gets compiled into your program along with everything else. ", " This two-pass system means that in general code requiring TH will be harder to play with by hand in GHCi than code without it.", "\nTypically in my web applications I don't just run GHCi from scratch. ", " I usually am loading another code file that I've written. ", " That allows us to work around the Template Haskell problem because the Template Haskell parts are specified in the file and the code gets generated when I start up GHCi. ", " From then on out you can play with whatever functions were generated.", "\n\n" ]

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[ "Introduction {#Sec1}\n============\n\nCalcium homeostasis modulator 1 (CALHM1) and its homolog, CALHM3, hetero-hexamerize to form a non-selective fast-activating voltage-gated channel, CALHM1/CALHM3, which is permeable to large molecules including ATP^[@CR1]^. CALHM1, which can form a slowly-activating voltage-gated channel by itself ^[@CR2]--[@CR7]^, has been reported to be expressed in various polarized cells including taste bud cells (TBCs)^[@CR8],[@CR9]^, nasal^[@CR10]^ and bladder^[@CR11]^ epithelia, and cortical neurons^[@CR6],[@CR7],[@CR12]^, and to mediate taste perception^[@CR8],[@CR13]^ and memory formation^[@CR14]^. Currently, CALHM1 is best characterized in TBCs. ", "Taste buds face the oral cavity and underlying tissue, and detect taste compounds in foods and drinks. ", "TBCs are polarized, with their apical and basolateral surfaces divided by tight junctions. ", "Among distinct cell types, CALHM1 is expressed selectively in type II TBCs, which detect sweet, umami, or bitter compounds. ", "In response to taste stimuli applied to the apical membrane, type II TBCs generate action potentials in the basolateral membrane, which lead to the release of ATP as the neurotransmitter towards gustatory nerves expressing the ATP-gated ion channel P2X2/3R^[@CR15]^. The chemical synapse in type II TBCs, which lack conventional synaptic features including synaptic vesicles and expression of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, is unique in employing voltage-gated ion channels as conduits for neurotransmitter release. ", "CALHM1 was identified as an essential, but not the sole, component of the neurotransmitter-release channel in type II TBCs^[@CR2]^. Recently, a CALHM1/CALHM3 hetero-hexamer composed of CALHM1 and CALHM3 was identified as the ATP channel complex of type II TBC^[@CR1]^. Another study reported CALHM1 localization in the basolateral membrane of type II TBCs at points of contact with P2X2R-expressing nerve fibers for the focal release of purinergic signals^[@CR16]^. Although, mechanisms underlying CALHM1/CALHM3 localization in polarized cells such as taste cells remain unexplored.", "\n\nFully-matured membrane proteins that have undergone post-translational processing in the endoplasmic reticulum and Golgi are sorted to transporting vesicles and exported. ", "In polarized epithelial cells, plasma membrane proteins are delivered into the apical or basolateral membrane, or both. ", "For basolateral sorting, intrinsic basolateral transport signal sequences in intracellular domains are generally involved in recognition by adaptor proteins and subsequent sorting to clathrin-coated transporting vesicles^[@CR17]^. Several canonical targeting sequences exist^[@CR18]^. The most common types are tyrosine-based and dileucine motifs. ", "Tyrosine-based motifs include YxxΦ (Y, tyrosine; x, any amino acid; and Φ, an amino acid with a bulky hydrophobic side chain)^[@CR19],[@CR20]^ and NPxY (N, asparagine; and P, proline)^[@CR21]^. Dileucine motifs consist of diverse hydrophobic amino acids (LL, IL, LEL, and ML)^[@CR19],[@CR22]^. Rarer motifs include those with a single leucine^[@CR23]--[@CR25]^ and one with a polyproline core^[@CR22]^.\n\nHerein, we generated an antibody against a short peptide sequence corresponding to the carboxyl terminal end of mouse CALHM1, and data from immunohistological analyses using it supported punctate localization near nerve fibers in the basolateral membrane of type II TBCs^[@CR16]^. As plasma membrane proteins cannot diffuse over the tight junction, CALHM1/CALHM3 must initially be delivered to the basolateral membrane, and subsequently accumulate at points of contact with nerve fibers. ", "Here, using an epithelial model of MDCKII cells, we explored the mechanisms of the polarized sorting of CALHM1/CALHM3 to further understanding of the structural basis behind the regulation of CALHM channel localization in polarized cells.", "\n\nResults {#Sec2}\n=======\n\nCALHM1 localization in taste bud cells {#Sec3}\n--------------------------------------\n\nImmunofluorescence staining of tongue sections containing circumvallate papillae using an antibody targeting the Cter end of mouse CALHM1 (Fig.", " [1A,B](#Fig1){ref-type=\"fig\"}) revealed small punctate signals within the wild-type taste buds (Fig.", " [1C,D](#Fig1){ref-type=\"fig\"}). ", "The immunoreactivities are specific to CALHM1 because they were absent in *Calhm1* knockout mice (Fig.", " [1D](#Fig1){ref-type=\"fig\"}), with the immunizing peptide-preabsorbed antibody, and in the absence of the primary antibody (Fig.", " [1C](#Fig1){ref-type=\"fig\"}). ", "Almost all CALHM1 signal puncta were associated with type II TBC marker proteins PLCβ2 and TRPM5, confirming CALHM1's selective expression in type II TBCs (Fig.", " [2A](#Fig2){ref-type=\"fig\"}). ", "To examine the relationship between CALHM1 and the basolateral membrane, we performed high-resolution imaging of TBCs immunostained with antibodies against CALHM1 and TRPM5. ", "TRPM5 is distributed throughout the basolateral membrane but not in apical microvilli^[@CR26]^. CALHM1 signals were observed in the basolateral membrane lined by TRPM5 immunoreactivity (Fig.", " [2B](#Fig2){ref-type=\"fig\"}). ", "Similar results were obtained in TBCs double-stained with antibodies against CALHM1 and KCNQ1, a basolateral membrane marker for all TBCs (Supplementary Fig.", " [S1](#MOESM1){ref-type=\"media\"}). ", "CALHM1 signals were absent on the apical surface of TBCs. ", "Together with the fact that CALHM1/3 channel currents have been recorded by whole-cell voltage-clamp recordings^[@CR1],[@CR2]^, these observations indicate that CALHM1 is present in the basolateral membrane. ", "Furthermore, each CALHM1 punctum was localized close to P2X2R-expressing afferent gustatory nerve fibers (Fig.", " [2A](#Fig2){ref-type=\"fig\"}), as recently reported by Romanov *et al*.^[@CR16]^. These results strongly support the punctate CALHM1 localization in the basolateral membrane of type II TBCs at points of contact with nerve fibers. ", "Notably, high-resolution imaging revealed that immunoreactivities for TRPM5 and KCNQ1 reduced or disappeared in plasma membrane patches with CALHM1 immunoreactivity (Fig.", " [2C](#Fig2){ref-type=\"fig\"} and Supplementary Fig.", " [S1](#MOESM1){ref-type=\"media\"}).Figure 1The specificity of the CALHM1 antibody. (**", "A**) The specificity of the obtained CALHM1 antibody was verified by Western blotting using 40 µg of whole-cell lysates obtained from N2a cells transfected with empty vector (Mock), mouse CALHM1 (mCALHM1), mouse CALHM3 (mCALHM3), or human CALHM1 (hCALHM1). (**", "B**) Immunofluorescence confocal images of N2a cells transiently transfected with CALHM1 and 3. ", "CALHM1 and DAPI are labeled green and blue, respectively. ", "Scale bar, 10 µm. (**", "C**) Confocal images (green) of the circumvallate papilla immunostained with the CALHM1 antibody, immunizing peptide-preabsorbed CALHM1 antibody, or no primary antibody. (**", "D**) Immunofluorescence confocal images (green) of the circumvallate papilla of wild-type (*Calhm1*^+/+^) and CALHM1 knockout (*Calhm1*^−/−^) mice with the CALHM1 antibody. ", "Punctate intragemmal signals were observed in *Calhm1*^+/+^ but not *Calhm1*^−/−^ mice, supporting the specificity of the antibody and revealing punctate CALHM1 localization in the taste buds. ", "Scale bar, 50 µm. ", "Data are representative of circumvallate papillae in more than three animals.", "Figure 2Localization of CALHM1 in the basolateral membrane of type II TBCs close to afferent nerve fibers. (**", "A**) Confocal images of double-staining of CALHM1 (green) and PLCβ2, TRPM5, or P2X2R (red) in the circumvallate taste buds. ", "Scale bar, 20 µm. ", "Data are representative of multiple taste buds from each circumvallate papilla in three animals. (**", "B**) Airyscan images of TBCs in the circumvallate taste buds double-stained for CALHM1 (green) and TRPM5 (red). ", "Scale bar, 2 µm. ", "Data are representative of five images. (**", "C**) Line plots of basolateral membrane areas carrying a single CALHM1 punctum shown in (**C**) (i--iii). ", "CALHM1 signal, green line; TRPM5 signal, red line; A.U., arbitrary units.", "\n\nBasolateral sorting of CALHM1/CALHM3 in epithelial cells {#Sec4}\n--------------------------------------------------------\n\nWe examined the direction of CALHM1/CALHM3 sorting in the apical-basolateral axis in polarized MDCKII cells, a well-established platform for the analysis of epithelial protein sorting^[@CR27]^, in which neither CALHM1 nor CALHM3 are endogenously expressed. ", "Transient transfection of CALHM1-GFP and untagged CALHM3 was performed because the generation of cells stably expressing CALHM1 was unsuccessful due to the cytotoxicity of CALHM channel expression^[@CR2],[@CR3]^. We subsequently immunostained CALHM1-GFP and Na^+^/K^+^ ATPase, a basolateral membrane marker protein, and acquired z-stack images of the stained cells. ", "CALHM1 was primarily observed within the cytoplasm with a granular appearance, while a small fraction was noted in the Na^+^/K^+^ ATPase-positive basolateral membrane (Fig.", " [3A](#Fig3){ref-type=\"fig\"}). ", "CHX treatment decreased the number of intracellular granular signals over time, and signals only remained in the basolateral membrane at 4 h, with none in the putative apical membrane region between the apical ends of Na^+^/K^+^ ATPase signals (Fig.", " [3B--E](#Fig3){ref-type=\"fig\"}). ", "As expected from the heteromer formation between CALHM1 and 3^[@CR1]^, when untagged CALHM1 and CALHM3-GFP were expressed, CALHM3 signals were also observed only in the basolateral membrane (Fig.", " [3F](#Fig3){ref-type=\"fig\"}). ", "These observations suggest that the cytoplasmic granular signals were transporting vesicles containing newly synthesized CALHM1/CALHM3 complexes that were being trafficked to the basolateral membrane. ", "Therefore, only in subsequent immunostaining experiments, we used 2-h CHX-treatment to facilitate the detection of CALHM1 in the plasma membrane. ", "Any reduction in CALHM1 protein levels caused by longer treatment would impair analysis. ", "When CALHM1 was expressed in the absence of CALHM3, its plasma membrane localization was indistinguishable from cytoplasmic signals even after prolonged CHX treatment (data not shown), possibly due to the slow forward trafficking^[@CR1]^.Figure 3Localization of CALHM1/CALHM3 in the basolateral membrane of MDCKII epithelia. (**", "A--E**) Fluorescence double-labeling of GFP (green) and Na^+^/K^+^ ATPase (red) in polarized MDCKII cells that were transiently transfected with CALHM1-GFP and untagged CALHM3 and treated with 100 µg/mL cycloheximide (CHX) for the indicated time. (**", "F**) Double-staining of GFP (green) and Na^+^/K^+^ ATPase (red) in MDCKII epithelia transfected with untagged CALHM1 and CALHM3-GFP and treated with CHX for 2 h. Na^+^/K^+^ ATPase signals were used as a marker for the basolateral membranes. ", "Upper panel, XY image. ", "Lower panel, XZ image reconstructed at the blue line in the upper image. ", "Note that Transwell filter membranes exhibit autofluorescence in the green channel and generate straight signals at the bottom of the cells in the XZ images throughout the manuscript. ", "Api, apical membrane; Baso, basolateral membrane; Scale bars, 10 µm. ", "Data are representative of two experiments.", "\n\nFurthermore, the apical membrane was labeled by biotinylation. ", "Figure [4A,B](#Fig4){ref-type=\"fig\"} clearly demonstrate that CALHM1 signals are co-localized with Na^+^/K^+^ ATPase but not with apical biotin signals, confirming the absence of CALHM1/CALHM3 in the apical membrane. ", "This suggests that either CALHM1 or 3, or both, possess signal sequences responsible for basolateral sorting of the CALHM1/CALHM3 complex. ", "In contrast, the pannexin 1 channel, sharing functional and structural similarities with CALHM^[@CR4],[@CR8]^ but functions in the apical membrane of various epithelia^[@CR28],[@CR29]^, was selectively localized in the apical membrane of MDCKII epithelia, suggesting distinct sorting mechanisms between these channels (Fig.", " [4C](#Fig4){ref-type=\"fig\"}).Figure 4Distinct membrane localization of CALHM and pannexin channels. (**", "A--B)** Fluorescence double-labeling of polarized MDCKII cells transfected with CALHM1-GFP and untagged CALHM3. ", "GFP (green) and apical membrane-bound biotin (**A**) or Na^+^/K^+^ ATPase (**B**) (red) were double-stained. ", "Biotin and Na^+^/K^+^ ATPase signals were respectively used as markers for the apical and basolateral membranes. (**", "C**) Double-staining of GFP (green) and Na^+^/K^+^ ATPase (red) in MDCKII epithelia transfected with pannexin 1-GFP. ", "Upper panel, XY image. ", "Lower panel, XZ image reconstructed at the blue line in its upper image. ", "Api, apical membrane; Baso, basolateral membrane; Scale bars, 10 µm. ", "Data are representative of four experiments.", "\n\nBasolateral sorting signals in CALHM1 and CALHM3 {#Sec5}\n------------------------------------------------\n\nBoth CALHM1 and 3 are four-transmembrane proteins with cytoplasmic Nter, Cter and Loop. ", "To identify intracellular domains containing basolateral sorting signals, we utilized two single membrane-spanning proteins, CD4 and Ii, which have opposite membrane topologies with their Cter and Nter in the cytoplasm, respectively (Fig.", " [5A](#Fig5){ref-type=\"fig\"}). ", "We created a series of FLAG-tagged chimeric constructs of a recipient protein (Ii or CD4) and an intracellular region of CALHM1 or 3 (Fig.", " [5A](#Fig5){ref-type=\"fig\"}), and established MDCKII clones stably expressing one of those chimeras. ", "Ii Nter was replaced with Nter or Loop of CALHM1 or 3, and CD4 Cter with Cter or Loop of CALHM1 or 3, while IiΔN and CD4ΔC were used as controls. ", "Loop was fused with both IiΔN and CD4ΔC because the direction and/or distance from the plasma membrane of certain sorting signal sequences is critical^[@CR25]^. Apical and basolateral sorting of the eight chimeras were quantified in polarized epithelia of the stable clones by the domain-specific surface biotinylation assay. ", "Because protein levels of CD4ΔC-CALHM1 Cter and CD4ΔC-CALHM3 Cter were too low for quantitative analysis but were rescued by treatment with MG132, a proteasome inhibitor (Fig.", " [5B](#Fig5){ref-type=\"fig\"}), only Cter chimeras were analyzed after 4-h treatment with MG132. ", "Representative Western blots and quantitative results of the domain-specific surface biotinylation assay are shown in Fig.", " [5C,D](#Fig5){ref-type=\"fig\"}. ", "The amounts of each chimera detected in the apical and basolateral membranes are expressed as percentages of the total amount in the entire plasma membrane. ", "The control proteins lacking intracellular domains, IiΔN and CD4ΔC, did not show selective sorting, as demonstrated by equal distribution between the apical and basolateral membranes. ", "Regarding chimeras, none of Nter and Loop of CALHM1 and 3 promoted basolateral delivery of IiΔN, and CALHM1 Nter increased apical delivery of IiΔN. ", "In contrast, Cter and Loop of CALHM1 and 3 markedly promoted basolateral sorting of CD4ΔC. ", "These results demonstrate that Cter and Loop of CALHM1 and 3 contain intrinsic basolateral sorting signals.", "Figure 5Loop and Cter of CALHM1 and 3 contain basolateral sorting signals. (**", "A**) Illustration of chimeric constructs of the intracellular domain-truncated invariant chain (IiΔN) or CD4ΔC and an intracellular domain of mouse CALHM1 or 3. ", "All chimeras were FLAG-tagged on their Cter. (**", "B**) Effects of MG132 (20 µg/mL) on expression levels of the chimeric proteins. ", "Upper panels display representative Western blots of CD4ΔC-CALHM1Cter and CD4ΔC-CALHM3Cter, and the lower panel shows a quantitative summary of expression levels of each chimera 0, 4, and 8 h after MG132 treatment. ", "N = 3. ", "Uncropped blots are shown in Supplementary Fig.", " [S2](#MOESM1){ref-type=\"media\"}. (**", "C**) Representative Western blots of the domain-specific biotinylation assays in stable MDCKII clones expressing each chimera. ", "Whole-cell lysates (Input) of apically (Ap)- or basolaterally (Bl)-biotinylated cells and their avidin pull-down eluates (Surface) were analyzed by SDS-PAGE/Western blotting. ", "FLAG-tagged chimeric proteins were detected by anti-FLAG antibody. ", "Na^+^/K^+^ ATPase and β-tubulin were detected as markers of the basolateral membrane and cytosol, respectively. ", "IiΔN and CD4ΔC alone were tested as controls. ", "CD4ΔC-CALHM1Cter and CD4ΔC-CALHM3Cter were analyzed after 4-h MG132 treatment (+MG). ", "Images taken from the same gel but at different exposures are separated by dashed black lines. ", "Uncropped blots are shown in Supplementary Fig.", " [S3](#MOESM1){ref-type=\"media\"}. (**", "D**) The amounts of each chimera detected in the apical and basolateral membranes are expressed as percentages of the total amount in the entire plasma membrane. ", "N = 4\\~5. ", "^*NS*^*p* \\> 0.05, \\**p* \\< 0.05 and \\*\\**p* \\< 0.01 (vs. control, Bonferroni post-hoc test).", "\n\nConserved canonical basolateral sorting signals in CALHM1 {#Sec6}\n---------------------------------------------------------\n\nWe identified conserved canonical basolateral sorting motifs in the intracellular domains of CALHM1 and 3 (Fig.", " [6](#Fig6){ref-type=\"fig\"}): CALHM1 motifs: one tyrosine-based, four dileucine, and one proline-based in Loop and Cter but none in Nter; CALHM3 motifs: dileucine in Loop and tyrosine-based and one dileucine (LL) in Cter.", "Figure 6Alignment of primary sequences of mouse CALHM3 and CALHM1 from different vertebrates. ", "Putative transmembrane domains of mouse CALHM1 and 3 are indicated by gray shades and conserved canonical basolateral sorting motifs are highlighted by red letters. ", "\\*Represents a fully conserved residue, and ':' and '.' ", "indicate strong and weak similarities, respectively.", "\n\nTo identify functional signals, alanine mutations were introduced to those canonical motifs in CALHM1 and chimeric constructs of CD4ΔC, creating mutant Loop or Cter. ", "After establishing MDCKII clones stably expressing the mutant chimeras, we quantified their polarized sorting by the domain-specific surface biotinylation assay (Fig.", " [7A,B](#Fig7){ref-type=\"fig\"}). ", "Disruption of the dileucine motif (ML/AA) in Loop and tyrosine-based motif (YI/AA) in Cter significantly decreased basolateral sorting of CD4ΔC-Loop and CD4ΔC-Cter, respectively. ", "Mutation of a dileucine motif in Cter (LL/AA) also slightly reduced basolateral sorting of CD4ΔC-Cterm (non-significant). ", "In contrast, disruption of other motifs in Cter (LEL, LM, and PP) had no effect. ", "These results identify the dileucine motif in Loop (ML), the tyrosine-based motif in Cter (YIDI), and potentially one dileucine motif in Cter (LL) as functional signals for basolateral sorting of CALHM1. ", "CALHM3 also conserves the three motifs in Loop and Cter, and no other unique canonical motifs exist (Fig.", " [6](#Fig6){ref-type=\"fig\"}), suggesting that these conserved motifs in CALHM3 are also functional.", "Figure 7Identification of functional basolateral sorting signals. (**", "A**) Representative Western blots of the domain-specific biotinylation assays in stable clones of MDCKII cells expressing CD4ΔC, CD4ΔC-CALHM1Loop, CD4ΔC-CALHM1Cter, or either one of the mutant chimeras in which one of the candidate basolateral sorting signals was disrupted by alanine substitution. ", "Whole-cell lysates (Input) of apically (Ap)- or basolaterally (Bl)-biotinylated cells and their avidin pull-down eluates (Surface) were analyzed by Western blotting. ", "CD4ΔC fusion proteins were detected by anti-FLAG antibody. ", "Na^+^/K^+^ ATPase and β-tubulin signals serve as markers for the basolateral membrane and cytosol, respectively. ", "CD4ΔC-CALHM1Cter proteins were analyzed after 4-h MG132 treatment (+MG). ", "Uncropped blots are shown in Supplementary Fig.", " [S4](#MOESM1){ref-type=\"media\"}. (**", "B**) The amounts of each chimera detected in the apical and basolateral membranes are expressed as percentages of the total amount in the entire plasma membrane. ", "N = 4\\~7. ", "^*NS*^*p* \\> 0.05 \\*\\**p* \\< 0.01 and \\*\\*\\**p* \\< 0.001 (Bonferroni post-hoc test).", "\n\nCanonical signal motifs are not necessary for basolateral sorting of CALHM1/CALHM3 {#Sec7}\n----------------------------------------------------------------------------------\n\nFinally, the Loop dileucine and Cter tyrosine-based motifs in CALHM1 and 3 were substituted with alanines, the resulting mutants CALHM1 (MLYI/4A) and CALHM3 (LMYL/4A) were used to transiently co-transfect polarized MDCKII cells, and CALHM1's distribution was evaluated by immunostaining. ", "The domain-specific surface biotinylation assay was infeasible because generation of stable cell lines expressing full-length CALHM1 proteins was unsuccessful due to their cytotoxicity^[@CR2],[@CR3]^. Disruption of these motifs did not alter basolateral sorting of the channel (Fig.", " [8A,B](#Fig8){ref-type=\"fig\"}). ", "Additional mutations of the conserved dileucine motifs (LL) in Cter were introduced into CALHM1 and 3, and the resulting mutant CALHM1/3 channel composed of CALHM1 (MLYILL/6A) and CALHM3 (LMYLLL/6A) still maintained basolateral sorting (Fig.", " [8C,D](#Fig8){ref-type=\"fig\"}), suggesting that the canonical basolateral sorting signals identified by the chimeric approach are dispensable for basolateral delivery of the actual CALHM1/CALHM3 channel complex.", "Figure 8Canonical signals are non-essential for basolateral sorting of CALHM1/CALHM3 channel. (**", "A--B)** Fluorescence double-labeling of polarized MDCKII cells expressing GFP-fused CALHM1 MLYI/4A and untagged CALHM3 LMYL/4A with GFP (green) and Na^+^/K^+^ ATPase (**A**) or apical membrane-bound biotin (**B**) (red). (**", "C--D**) MDCKII epithelia expressing GFP-fused CALHM1 MLYILL/6A and untagged CALHM3 LMYLLL/6A were double-stained with GFP (green) and Na^+^/K^+^ ATPase (**C**) or apical membrane-bound biotin (**D**) (red). ", "Upper panel, XY image. ", "Lower panel, XZ image reconstructed at the blue line in the upper image. ", "Api, apical membrane; Baso, basolateral membrane; Scale bars, 10 µm. ", "Data are representative of three experiments.", "\n\nDiscussion {#Sec8}\n==========\n\nRecently, in type II TBCs, CALHM1 (*i.e*., ", "CALHM1/CALHM3 channel^[@CR1]^) was located in the basolateral membrane in discrete puncta, localized close to P2X2/3 receptor-expressing afferent nerve fibers^[@CR16]^. Furthermore, large mitochondria are consistently juxtaposed closely to membrane areas accumulating CALHM1 to provide ATP^[@CR16]^. The close apposition of the ATP source, ATP-release channel, and ATP receptors is thought to enable regulated, spatially-localized ATP release without synapses. ", "That study^[@CR16]^ employed monoclonal antibody mapping to residues 318 to 328 (EEPPLMGNGWA) on Cter of human CALHM1, corresponding to 321--330 (EAPLMSNGWA) of mouse CALHM1. ", "Our independent immunohistological data using a polyclonal antibody against the Cter end (residues 338--348) of mouse CALHM1 generated in this study support the punctate localization of CALHM1 in the basolateral membrane of type II TBCs specialized for focal neurotransmitter release. ", "Our data also suggest that membrane patches carrying CALHM1, which are sites for neurotransmission, are distinct in terms of the local protein repertoire from the remaining basolateral membrane, which expresses TRPM5 and KCNQ1 and contributes to general cellular signaling. ", "This is a novel insight into functional membrane micro-domains within type II TBCs.", "\n\nHow is the localization of CALHM1/CALHM3 regulated? ", "We hypothesized two processes: As it cannot cross the tight junction, it needs to be delivered to the basolateral membrane first, and then accumulates at points of contact with nerve fibers. ", "This work addressed the initial polarized sorting of the channel in an epithelial model. ", "In polarized MDCKII cells, CALHM1/CALHM3 was distributed throughout the basolateral membrane, suggesting intrinsic basolateral sorting of the channel in epithelial cells. ", "TBCs must contain additional machinery to further accumulate CALHM1/CALHM3 in localized spots.", "\n\nIn chimeric experiments, Loop and Cter of both subunits induced basolateral sorting of the recipient membrane proteins. ", "We identified a dileucine motif in Loop and a tyrosine-based motif in Cter that are responsible among conserved basolateral sorting motifs, while a conserved dileucine motif in Cter may also play a role. ", "Of note, the dileucine motif in Loop was functional only when Loop was fused with CD4ΔC but not IiΔN, suggesting that the direction and/or distance of the motif from the membrane surface is critical for functionality. ", "Furthermore, CALHM1 is degraded by the ubiquitin-proteasome system^[@CR3]^. The MG132 sensitivity of CD4ΔC-CALHM1 Cter and CD4ΔC-CALHM3 Cter but not the other chimeras suggests that ubiquitination sites reside in Cter of these subunits.", "\n\nSorting mechanisms in multipass membrane proteins are less clear and more complex compared with those in single membrane-spanning proteins. ", "CALHM1/CALHM3 is a hetero-hexamer with unknown subunit stoichiometry, and each subunit has four transmembrane domains. ", "Surprisingly, the disruption of all intracellular signal motifs in CALHM1 and 3 found in the chimeric protein experiments failed to alter the basolateral delivery of the CALHM1/3 channel complex, suggesting that those canonical signals are partly responsible but additional signals are also involved. ", "As reported in Kir2.1, which forms a homo-tetrameric channel with each subunit exhibiting two transmembrane domains^[@CR30]^, the tertiary and quaternary structures of CALHM1/CALHM3 may form a \"signal patch\" within its intra- or inter-subunit assembly. ", "Intracellular Nter and Cter of Kir2.1 together form a Golgi export signal interacting with AP1, which is also engaged in basolateral sorting^[@CR18]^. The structure and subunit stoichiometry of the CALHM1/CALHM3 complex would thus provide further insight into its sorting mechanisms. ", "Alternatively, the CALHM1/3 channel may bind with an unknown protein that transports it to the basolateral membrane.", "\n\nCALHM1 has been reported to be expressed in brain neurons and involved in memory formation^[@CR14]^ and the pathogenesis of Alzheimer's disease^[@CR7]^. However, it remains unclear where CALHM1 is localized in neurons and whether CALHM3 is involved. ", "Like epithelial cells, cortical neurons have a highly polarized structure with an axon at one end and dendrites at the other. ", "Epithelial cells and neurons utilize common machineries to sort proteins^[@CR31]^. Basolateral membrane proteins in epithelial cells are localized in the cell body and dendrites in neurons, whereas apical proteins are in axons. ", "Therefore, CALHM channels may be localized in the cell body and/or dendrites in neurons. ", "A recent study^[@CR11]^ reported that CALHM1 is expressed in the urothelium as well as suburothelium and detrusor muscle of the porcine bladder, and that it mediates hypotonic stretch-induced ATP release from those cells in culture. ", "Both the apical and basolateral membranes of urothelial cells exhibited marked immunoreactivity in response to a commercially available CALHM1 antibody (HPA018317, Sigma), whose specificity for CALHM1 has not been validated using *Calhm1* knockout tissues. ", "However, our specificity-validated CALHM1 antibody did not generate signals in mouse urothelial cells (data not shown). ", "This may reflect species differences or a lack of specificity for CALHM1 of the commercial antibody. ", "Another recent study^[@CR10]^ reported that CALHM1 is involved in mechanical stress-induced ATP release from the apical membrane of cultured mouse nasal epithelium. ", "Although that study provides compelling functional evidence using *Calhm1* knockout mice, CALHM1 localization was not tested. ", "Reliable histological analyses are indispensable.", "\n\nOverall, the present results, revealing intrinsic basolateral targeting of the CALHM1/CALHM3 channel, provide a basis for future research on molecular mechanisms leading to spatial confinement of the CALHM channel function not only in TBCs but also other polarized cells, including neurons.", "\n\nMaterials and Methods {#Sec9}\n=====================\n\nEthics {#Sec10}\n------\n\nAll experiments were conducted using protocols approved by the Institutional Animal Care and Use Committee of Kyoto Prefectural University of Medicine.", "\n\nCALHM1 antibody {#Sec11}\n---------------\n\nGuinea pig polyclonal anti-mouse CALHM1 antibody was raised against a peptide corresponding to the carboxyl terminal end of mouse CALHM1 (residues 338 to 348: RKEVATYFSKV) and affinity-purified with the peptide. ", "N2a cells transfected with CALHMs^[@CR3]^ were used to assess antibody specificity. ", "In Western blots, this antibody reacted with mouse and human CALHM1 but not mouse CALHM3 (Fig.", " [1A](#Fig1){ref-type=\"fig\"}), and it generated immunofluorescence signals in CALHM1-transfected (Fig.", " [1B](#Fig1){ref-type=\"fig\"}) but not mock-transfected (data not shown) cells, supporting its specificity for CALHM1.", "\n\nImmunohistochemistry {#Sec12}\n--------------------\n\nNine micrometer-thick fixed sections of tongue epithelia containing circumvallate papillae were prepared from wild-type or *Calhm1* knockout mice, as previously described^[@CR2],[@CR3]^. Sections were treated in a preheated target retrieval solution (Agilent Technologies) at 80 °C for 20 min and blocked in PBS containing 5% normal donkey serum and 0.1% Triton X-100. ", "As primary antibodies, guinea pig anti-CALHM1 (1:10,000), rabbit anti-TRPM5 (Alomone), rabbit anti-PLCβ2 (Santa Cruz), rabbit anti-P2X2R (Sigma), goat anti-KCNQ1 (Santa Cruz) antibodies were used. ", "For fluorescent labeling of CALHM1, signals were developed using biotin-conjugated donkey anti-guinea pig IgG antibody (Millipore) followed by an avidin-biotin complex (Vector Laboratories), a tyramide signal amplification biotin system (Tyramide SuperBoost Kit, Thermo Fisher), and Alexa fluor 488-conjugated streptavidin (Thermo Fisher). ", "Other proteins were simultaneously labeled using Alexa fluor 546-conjugated donkey anti-rabbit IgG or Alexa fluor 647-conjugated donkey anti-goat IgG (Thermo Fisher). ", "Images were acquired using a LSM510 confocal scanning microscope (Carl Zeiss) with an EC Plan-Neofluar 20×/0.50 NA objective or an EC Plan-Neofluar 40×/1.30 NA oil objective with the pinhole set to 2 Airy Units for the green channel and adjusted to yield the same optical slice thickness in the red channel. ", "Images show single optical sections. ", "DAPI was excited with 2 photons using the MaiTai titanium-sapphire laser tuned at 780 nm (Spectra-Physics). ", "Some of the images shown in Fig.", " [2B](#Fig2){ref-type=\"fig\"} and Supplementary Fig.", " [S1](#MOESM1){ref-type=\"media\"} were acquired using a Zeiss Axio Observer Z1 with Plan Apochoromat 63×/1.40 NA oil DIC M27 and an LSM 800 confocal unit with Airyscan module (Carl Zeiss). ", "The fluorescence was excited using laser lines of 640, 561, and 488 nm and each detection wavelength was 643--700, 563--640, and 491--575 nm through main beam splitters of 640 (T10/R90), 561, and 488, respectively. ", "The images were Airyscan processed automatically with an additional manual adjustment of plus 0.5 per channel using the Zeiss Zen Blue 2.3 software package.", "\n\nPlasmid vectors {#Sec13}\n---------------\n\nMouse CALHM1 (Accession\\# NM_001081271) and CALHM3 (Accession\\# XM_140729) cDNAs were gifts from Dr. J. Kevin Foskett (University of Pennsylvania). ", "Human CD4 (Accession\\# M12807.1)^[@CR32]^ and human invariant chain (Ii, Accession\\# NM_004355.3) with the tetramerization motif mutated (Q63A/T56A/T66A)^[@CR33]^ were provided by Dr. Gerald W. Zamponi (University of Calgary) and Dr. Gergely Lukacs (McGill University), respectively. ", "The membrane topology of CALHM1 with four transmembrane domains and intracellular carboxyl terminus (Cter) and amino terminus (Nter) was experimentally determined^[@CR4]^. A similar topology of CALHM3 was predicted using TMHMM v.2.0. ", "Nter, intracellular loop (Loop), and Cter of CALHM1 and 3 are: in CALHM1, M1-E16 (Nter), N72-A107 (Loop), S203-V349 (Cter); in CALHM3, M1-E16 (Nter), R72-D91 (Loop), P203-V348 (Cter). ", "Chimeras of Nter-truncated Ii (IiΔN, G34-M233) or Cter-truncated CD4 (CD4ΔC, M1-C422) and intracellular domains of CALHM1 or 3 with an additional start methionine as necessary (Fig.", " [4A](#Fig4){ref-type=\"fig\"}) were created by InFusion HD PCR cloning technology (Clontech). ", "For untagged protein expression, coding sequences were cloned in pcDNA3.1(−) (Thermo Fisher). ", "For carboxyl-terminal fusion of a protein to EGFP or 3 × FLAG, its coding sequence without a stop codon was cloned in-frame into pEGFP-N1 (Clontech) or p3 × FLAG^[@CR3]^. Point mutations involved site-directed mutagenesis.", "\n\nCell culture {#Sec14}\n------------\n\nThe Madin-Darby canine kidney II (MDCKII) epithelial cell line was a gift from Dr. Masayuki Murata (Tokyo University). ", "Cells were maintained in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1× Antibiotic-Antimycotic (Gibco) at 37 °C in a humidified incubator with 5% CO~2~-in-air. ", "To produce polarized monolayers, cells were seeded on Transwell filter inserts (Corster) at 3 × 10^5^ cells per 3.2-mm filter for immunostaining, or 5 × 10^5^ cells per 24-mm filter for the domain-specific biotinylation assay, and cultured for 3 or 7 days, respectively.", "\n\nTransient transfection of polarized MDCKII cells {#Sec15}\n------------------------------------------------\n\nCulture medium was replaced with DMEM with reduced CaCl~2~ (5 µM) and cells were cultured for another 2 days. ", "They were then washed once and incubated for 15 min in PBS containing 1 mM MgCl~2~, before being incubated with a transfection mixture of expression vectors and Lipofectamine 3000 in OPTI-MEM (Invitrogen) on both apical (80 µL) and basolateral (20 µL) sides at 37 °C. ", "Expression vectors of CALHM1 fused with EGFP (CALHM1-GFP, 0.5 µg) and/or untagged CALHM3 (1.5 µg) were transfected except that 1.5 µg of untagged CALHM1 and 0.5 µg of CALHM3 fused to EGFP (CALHM3-GFP) were transfected (Fig.", " [2F](#Fig2){ref-type=\"fig\"}). ", "Normal DMEM was added to both sides 5--7 h later (80 and 400 µL to apical and basolateral sides, respectively). ", "Cells underwent immunostaining within 15\\~20 h post-transfection.", "\n\nImmunostaining {#Sec16}\n--------------\n\nCells were treated with 100 µg/mL cycloheximide (CHX) at 37 °C for 2 h to inhibit protein synthesis and promote visualization of the cell-surface localization of CALHM proteins^[@CR1],[@CR3]^, unless otherwise stated. ", "Cells were washed with ice-cold PBS twice. ", "They were then fixed immediately or subjected to surface biotinylation of the apical membrane before fixation. ", "For apical biotinylation, cells were incubated for 30 min at 4 °C with 0.5 mg/mL EZ-Link sulfo-NHS-SS-biotin (Thermo Scientific) in PBS containing 0.1 mM CaCl~2~ and 1 mM MgCl~2~ (PBS-Ca) on the apical side and PBS-Ca on the basolateral side. ", "The apical biotin solution was refreshed 15 min after the start of incubation. ", "The biotinylation reaction was stopped by adding glycine to the final concentration of 100 mM and two washes with ice-cold PBS containing 100 mM glycine. ", "After the final wash, cells were fixed with 4% paraformaldehyde in PBS for 20 min, permeabilized with 0.25% Triton X-100 in PBS for 30 min, and blocked in PBS containing 5% normal goat serum (PBS-NGS) for 1 h (all at room temperature). ", "They were then incubated at 4 °C overnight with primary antibodies diluted in PBS-NGS: mouse anti-GFP (Clontech), rabbit anti-Na^+^/K^+^ ATPase (Abcam), and rabbit anti-biotin (Abcam) antibodies. ", "The following day, cells were incubated at room temperature for 1 h with Alexa Fluor-conjugated secondary antibodies (Thermo Fisher Scientific) in PBS-NGS, before mounting in Vectashield (Vector Laboratories). ", "Confocal images were acquired using a LSM510 microscope with an EC Plan-Neofluar 100×/1.30 NA Oil objective and the pinhole set to 1 Airy Unit for the red channel and adjusted to yield the same optical slice thickness in the green channel. ", "Images show single optical XY planes or XZ planes reconstructed from Z-stack images, which were taken from the apical to basal ends of cells at depth intervals of half the optical slice thickness and deconvoluted and reconstructed using Image J software (NIH).", "\n\nGeneration of stable cell lines {#Sec17}\n-------------------------------\n\nMDCKII cells in a 3.5-cm dish were transfected at 50\\~70% confluency with 2.5 µg of an expression vector using Lipofectamine 3000. ", "The next day, cells were collected by trypsinization and plated in ten 10-cm dishes. ", "Isolated colonies of stably-transfected clones formed in the presence of 800 µg/mL of G418 (Cosmobio) were collected after 10\\~14 days. ", "Protein expression of transfected genes was confirmed by Western blotting.", "\n\nDomain-specific surface biotinylation {#Sec18}\n-------------------------------------\n\nSurface biotinylation specific to the apical or basolateral membrane domain of MDCKII epithelia was performed using the same procedure as described in the Immunostaining section above, but the biotin solution was applied to either the apical or basolateral side. ", "After stopping biotinylation by washing with PBS containing 100 mM glycine, cells were washed with ice-cold PBS twice, harvested in 70 µL of lysis buffer (PBS containing 1% Triton X-100, 1 mM phenylmethylsulfonyl fluoride, and 1× protease inhibitor cocktail (Sigma-Aldrich)), and centrifuged at 15,000 × g and 4 °C for 10 min. ", "Supernatants were collected as whole-cell lysates. ", "Biotinylated proteins in 300 µg of the whole-cell lysates were pulled down by 50 µL of NeutrAvidin agarose resin (Thermo Fisher Scientific) and eluted by incubating the resin in 50 µL of Laemmli sample buffer at 37 °C for 1 h. The whole-cell lysates (100 µg) were denatured in Laemmli sample buffer (Total), and the total amount of the eluate samples (Surface) was subjected to SDS-PAGE/Western blotting^[@CR3]^. Primary antibodies were mouse anti-FLAG (Sigma), rabbit anti-Na^+^/K^+^ ATPase (Abcam), and mouse anti-β-tubulin (Thermo Fisher). ", "The apical membrane distribution of a 3 × FLAG-tagged protein expressed in the entire plasma membrane is presented as a percentage: 100 × (I~Api.", "Surf~/I~Api.", "Tot~)/\\[(I~Api.", "Surf~/I~Api.", "Tot~) + (I~Baso.", "Surf~/I~Baso.", "Tot~)\\] (%), where I~Api.", "Surf~ and I~Api.", "Tot~ are band intensities of a target protein in the eluate and whole-cell lysate of apically-biotinylated cells, respectively, and I~Baso.", "Surf~ and I~Baso.", "Tot~ are those of basolaterally-biotinylated cells. ", "The Na^+^/K^+^ ATPase localization restricted to the basolateral membrane (\\>90%) was used as a criterion for successful polarization of the epithelia.", "\n\nStatistical analyses {#Sec19}\n--------------------\n\nData are means ± SEM. ", "Comparison involved one-way analysis of variance followed by Bonferroni post-hoc tests. *", "P*-values \\< 0.05 were significant. ", "N = number of experiments.", "\n\nSupplementary information\n=========================\n\n {#Sec20}\n\nSupplementary Information\n\n**Publisher's note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "\n\nElectronic supplementary material\n=================================\n\n**Supplementary information** accompanies this paper at 10.1038/s41598-019-39593-5.", "\n\nWe thank Dr. Yasunobu Okada for critical reading of the manuscript. ", "This work was supported by JSPS KAKENHI \\[15K18974 and 17K08543 to M.K., 26713008 and 16K15181 to A.T.\\]; Salt Science Research Foundation \\[1542 and 18C2 to A.T.\\]; Society for Research on Umami Taste to A.T.\n\nM.K. and A.T. conceived and designed the study; M.K., G.W., M.A.K., and A.T. performed experiments; Y.O. and M.A.K. generated the CALHM1 antibody; M.K., M.A.K. and A.T. analyzed data; M.K. and A.T. wrote the manuscript.", "\n\nThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.", "\n\nCompeting Interests {#FPar1}\n===================\n\nThe authors declare no competing interests.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nJava Application Window not recognized as java window in C# InterOp\n\nI am using Java Access Bridge API with interop in C#. ", "When trying to create a new AccessibleWindow with the hwnd obtained from the user32.dll method GetForegroundWindow(), it does not recognize the window as a java window, returning null. ", "IsJavaWindow() returns false, but calling it a second time returns true. ", "I tested this out with the example \"SwingSet2\" application. ", "\n public void Initialize()\n {\n if(!Initialized)\n {\n accessBridge = new AccessBridge();\n var hwnd = WindowsNativeMethods.", "GetForegroundWindow();\n var window = accessBridge.", "CreateAccessibleWindow(hwnd);\n window.", "AccessBridge.", "Initialize();\n window.", "AccessBridge.", "Functions.", "GetAccessibleContextFromHWND(hwnd, out vmId, out mainContext);\n Initialized = true; \n }\n }\n\nI am also using code from this repo: Google Access Bridge\n\nA:\n\nInitialize() or the initialization code in general needs to called in a UI thread or a message pumping thread.", "\nUsing the IntPtr from GetForegroundWindow() or GetActiveWindow() always returns false in IsJavaWindow(), but using FindWindow() works from user32.dll's methods.", "\n\n" ]

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[ "The show, called Finding Prince Charming, will see 13 \"charming and gorgeous suitors\" all live in one house while they \"compete to win the heart of one of the nation's most eligible gay heartthrobs,\" Logo said in a press release.", "\n\n\"One by one, the suitors are eliminated until the heartthrob chooses one ideal man to sweep him off of his feet and commit to an exclusive relationship,\" Logo said.", "\n\nWhile the show does sound like a gay spin-off of The Bachelor, Finding Prince Charming is not affiliated with that ABC show.", "\n\nThe show will be hosted by Lance Bass, the former NSYNC member who married Michael Turchin in 2014." ]

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[ "The Documentation Center of Cambodia (DC-Cam) is set to launch a new interactive multimedia website later this month hosting more than 1 million publicly accessible documents related to the Khmer Rouge regime.", "\n\nPheng Pong-Rasy of DC-Cam’s genocide education project, said the new website will launch next week and is intended to be a free resource that Cambodians will be able to access from their smartphones to learn about their collective past.", "\n\nWhile in the past the group has tried to reach people through printed written materials, Pong-Rasy believes the now-widespread use of smartphone technology means that people in remote areas of the country will easily be able to access the documents directly.", "\n\n“We came up with this idea of creating a permanent website where students and youngsters of all generations could access them with their phone whenever they want. ", "This is our main purpose,” he said.", "\n\n“We created this [website] not only to target youngsters, but anyone who could see it… especially those who are living far away from town and those who have never been educated at all about Khmer Rouge history,” he added.", "\n\nAs well as being able to access the documents, visitors to the website can use an interactive timeline of events, from the earliest days of the party formation to the present-day Khmer Rouge tribunal hearings. ", "The website will also feature profiles of key individuals and audio-visual materials, including rare photographs and interviews with survivors.", "\n\nIt will be accessible in both the Khmer and English languages and have spaces for users to leave comments and ask questions, which will be answered by DC-Cam staff.", "\n\nEstimates suggest as many as 1.7 million Cambodians died under the reign of the totalitarian Khmer Rouge, which ruled the country between 1975 and 1979.", "\n\nHang Chuon Naron, education minister, said resources such as the new DC-Cam website could be valuable supplements to education in school about the history of the Khmer Rouge.", "\n\n“There’s a saying, ‘if we don’t know about the history, that history will repeat itself.’ ", "So we have to know and learn both bad and good lessons. ", "So to be able to analyze, where do we want to go? ", "Where are we from? ", "To know where we should go, we need to be prepared to build the nation. ", "So to build a nation, [we] need to know the history too,” he said.", "\n\nHe added that the ministry had worked with DC-Cam in the past to publish schoolbooks and conducted training for teachers and had added questions on the Khmer Rouge to national examination papers.", "\n\nLatt Ky, Khmer Rouge tribunal coordinator with local rights group Adhoc, said the website would especially benefit members of the public previously unexposed to their modern history, and also civil parties to the ongoing trials of former regime officials, who would “be able to learn about their story from the relevant documents.”", "\n\nThe new DC-Cam website will be available at www.thekhmerrougehistory.com." ]

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[ "Retrograde tubal transfer of human embryos.", "\nThis preliminary study was designed to evaluate retrograde cannulation of the Fallopian tubes up to the isthmo-interstitial junction using the new technique of tubal embryo stage transfer (TEST). ", "Follicular aspiration was performed under the guidance of a vaginal ultrasound probe in 51 women treated with GnRH + HMG. ", "The oocytes retrieved were inseminated in vitro with 50,000 motile spermatozoa and kept in Menezo B2 medium without serum, at 37 degrees C, in an atmosphere of air + 5% CO2. ", "The eggs were checked 24 and 36 h after insemination. ", "No fertilization occurred in 23 patients. ", "Cleaved embryos were obtained in the 28 other patients. ", "One to seven embryos at the 2-4-cell stage were transferred with the 'Baudelocque Black Catheter' (BBC) into one tube and spare embryos were frozen. ", "Five pregnancies occurred after retrograde TEST, for a pregnancy rate of 9.8% per cycle and 17.9% per transfer. ", "One patient has given birth to a normal full-term baby. ", "One singleton and one twin pregnancy are ongoing (8 months in June 1989). ", "The other two pregnancies were ectopic." ]

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[ "The effectiveness of power Doppler vocal fremitus imaging in the diagnosis of breast hamartoma.", "\nTo evaluate the usefulness of power Doppler vocal fremitus (PDVF) breast sonography for differentiation of hamartomas from other breast (malign or benign) masses. ", "Two hundred and six breast masses in 180 women were evaluated. ", "The breast lesions were scanned first by mammography (MG), then by ultrasonography (US) with PDVF imaging. ", "Finally, biopsy was performed on lesions suspicious for malignancy (n=172). ", "We used PDVF imaging to evaluate whether the Power acoustic Doppler artifact existed in all breast lesions. ", "Pathology results of 172 biopsied lesions showed that 83 were malign and 89 masses were benign. ", "Totally 39 breast hamartomas were diagnosed radiologically (n=25) or histopathologically (n=14). ", "All hamartomas (n=39) produced the power acoustic Doppler artifact as the surrounding tissue at the same depth in PDVF imaging. ", "On the other hand, none of the malign or benign lesions, apart from hamartomas, evidenced a similar vibrational artifact as the surrounding tissue at the same depth in the PDVF imaging. ", "PDVF imaging during breast sonography is an invaluable technique in the identification of breast hamartomas from other benign or malign breast masses." ]

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[ "Differential roles of JNK and Smad2 signaling pathways in the inhibition of c-Myc-induced cell death by TGF-beta.", "\nThe transforming growth factor beta (TGF-beta) plays an important role in constraining cellular proliferation, but it is also a potent inducer of programmed cell death or apoptosis. ", "Here, we demonstrate that TGF-beta can have an opposite effect, acting as a survival factor to prevent c-Myc-induced cell death in Rat-1 fibroblasts. ", "However, in marked contrast to TGF-beta, Smad2, which is a critical intracellular mediator of the TGF-beta signaling pathway, functions as an antagonist to induce increased cell death. ", "The protective activity of TGF-beta was associated with the activation of c-Jun N-terminal Kinase (JNK) and was not linked to the ability of TGF-beta to promote cell cycle progression. ", "Expression of dominant-interfering forms of various components of the JNK signaling pathway, including Rac1, Cdc42, mitogen-activated protein kinase kinase 4 (MKK4), and c-Jun, abolished TGF-beta-mediated cell survival. ", "Furthermore, overexpression of the constitutively activated mutant RacL61F37A, which selectively stimulates JNK cascade but not G1 cell cycle progression or actin polymerization, was sufficient to prevent apoptosis induced by c-Myc. ", "These findings describe a differential effect of two separated signaling pathways of TGF-beta and indicate for the first time that Smad2 can act as antagonist to suppress TGF-beta-dependent cell survival. ", "Oncogene (2000) 19, 1277 - 1287." ]

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[ "[Immunologic aspects of migraine headaches and autonomic prosopalgias].", "\nThe paper presents the results of an immunological screening of patients with facial vegetative neuralgia, Horton's syndrome, and migraines prior to and following therapy. ", "The patients with migraines were found to have an activated local humoral immunity. ", "Those from all the groups showed lower serum immunoglobulin A concentrations after therapeutic interventions." ]

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[ "Introduction\n============\n\nOne of the most studied classes of skin-targeted compounds is retinoids. ", "All-trans retinoic acid (RA) also referred to as tretinoin, and its synthetic or natural derivatives (retinoids) affect epidermal growth and differentiation [@b1]. ", "Synthetic retinoids are today used widely in the treatment of psoriasis and other disorders of keratinization [@b2]. ", "Also, acne has been widely treated with various forms of natural and synthetic retinoids for more than 40 years [@b3].", "\n\nLater, retinoids has been used in the treatment for hyperpigmentation disorders such as post-inflammatory hyperpigmentation and melasma [@b4].", "\n\nSeparate from the effect of retinoids in skin disease, Kligman and Willis were the first to introduce retinoids for use as antiphotoaging agents [@b5]. ", "After its application, the authors noticed improvement in skin depigmentation and rejuvenation [@b6]. ", "Today, retinoids are extensively used for this indication [@b7],[@b8].", "\n\nFurther studies have shown that RA\\'s clinical effects include improvement in wrinkles, surface roughness, mottled pigmentation and skin appearance as a whole when used on photo-damaged skin [@b9]--[@b11]. ", "However, topical use of RA has also shown to develop erythema, scaling and burning/pruritus [@b12]. ", "Therefore, there is a constant thrive within the cosmetic industry to develop retinoid-like anti-ageing ingredients with significantly reduced side effects.", "\n\nAt a cellular level, retinoids are known to modulate the proliferation and differentiation of epidermal keratinocytes [@b13],[@b14],[@b14],[@b15] by binding to nuclear retinoic acid receptors (RARs) and 9-*cis*-retinoic acid receptors (RXRs), which results in upregulation or downregulation of the transcription of target genes [@b16].", "\n\nRA is the biologically active form of vitamin A (retinol). ", "Endogenous production of RA by epidermal keratinocytes involves the uptake of preformed vitamin A from the surroundings followed by a series of metabolic activation steps involving retinol dehydrogenases (RDH1, RDH4, RDH10, RDH12 and DHRS9) and retinal dehydrogenases (RALDH1, RALDH2 and RALDH3) [@b17]--[@b19]. ", "DHRS9 specifically is encoding an enzyme that mediates conversion of retinol into RA.", "\n\nWhilst endogenously produced or exogenously applied, RA is transported through the cytoplasm by specific intracellular retinoic-binding proteins (CRABP2) [@b8].", "\n\nOnce synthesized, the cellular levels of RA are controlled by several cytochrome P450-dependent enzymes (CYPs) -- CYP26 A1, B1 and C1 -- which metabolize RA into 4-hydroxy-RA, 4-oxo-RA and 18-OH-RA [@b20],[@b21]. ", "CYP26B1 is known to be higher expressed than both CYP26A1 and CYP26C1 in human keratinocytes [@b19],[@b22].", "\n\nOver the last quarter century, 532 genes have been validated to be regulated by RA [@b23]. ", "In some cases, this control is direct, driven by a liganded RAR:RXR heterodimer bound to a DNA response element; in others, it is indirect, reflecting the actions of intermediate transcription factors, non-classical associations of receptors with other proteins or even more distant mechanisms.", "\n\nCell cultures have been studied extensively to characterize and prophesy the effect of retinoids on epidermal differentiation and growth [@b13],[@b15],[@b24]--[@b27].", "\n\nIn addition, a selection of genes using RT-PCR has been studied in full-thickness skin treated with retinoids [@b28],[@b29].", "\n\nToday, recent gene array techniques allow the characterization of the mRNA expression status of a large number of genes in cells or tissues after retinoid treatments with more than 170 studies conducted.", "\n\nSome studies using gene arrays have also been carried out on reconstructed epidermis and human epidermis *in vivo* [@b30].", "\n\nHowever, to our knowledge, gene array analysis following the treatment of RA on organoculture of full-thickness skin has not been investigated earlier.", "\n\nThe aim of the present study was to determine whether it is possible to use an organoculture of full-thickness skin as a preclinical model to evaluate modulation of gene expression profile following topical application of a commercially available retinoid cream.", "\n\nMaterials and methods\n=====================\n\n*Ex vivo* study -- skin explant model\n-------------------------------------\n\nSkin from surgical waste material from breast reductions was collected and immediately put in DMEM at 8°C. ", "All subcutaneous fat was removed with a scalpel to ensure full diffusion nutrification of the tissue. ", "8-mm punch biopsies were taken from the skin and referred to as full-thickness skin explants. ", "Thereafter, the explants were put on Millipore Millicell Culture Plate Inserts (12 mm Ø) (Millipore Corporation, Stockholm, Sweden). ", "Inserts containing skin explants were put in 6-well plates (1 insert/well), and 1 mL of supplemented keratinocyte medium (M154) (Life Technologies, Stockholm, Sweden) was added to each well to allow survival of the explants.", "\n\nThree donors were used for this study. ", "They were all healthy Caucasian females of 23, 41 and 60 years of age. ", "The collection of skin samples was approved by the local Ethics Committee of Stockholm. ", "All participants gave written informed consent for the skin sample collections, and the studies followed the guidelines of the World Medical Association\\'s Declaration of Helsinki (2000) concerning biomedical research involving human subjects.", "\n\nExhibiting an enhanced functional barrier function compared with reconstructed skin [@b31] (ref), the use of viable skin explant allows topical application of finished product to study cosmetic effects on a molecular level. ", "In this study, 5 mg cm^−2^ of cream containing RA (tretinoin) (0.05%) (Aberela®, Jannsen-Cilag) was applied topically on each explant, using positive displacement pipette. ", "5 mg cm^−2^ is a typical finite dose applied on skin penetration test and considered as a non-occlusive dose [@b32],[@b33].", "\n\nThe study was vehicle controlled with a cream containing all ingredients except for RA, referred to as placebo. ", "The placebo cream was applied in the same conditions as the test cream.", "\n\nThe explants were incubated with the RA cream for 24 h at 37°C in 5% CO~2~ humidified air. ", "In the end of the incubation period, two Ø 3 mm biopsies were taken from each explants following RNA extraction.", "\n\nSkin explant viability\n----------------------\n\nAlamar blue® (Invitrogen, Stockholm, Sweden) was used as reagent for measuring skin viability. ", "Ø 3 mm biopsies were used for corresponding Alamar blue tests according to manufacturer\\'s protocol. ", "Briefly, Ø 3 mm biopsy was taken from each organoculture and put in 200 μL of Alamar blue dye and media at 1 : 10 ratio for 15 h at 37°C. ", "Absorbance was measured at wavelengths of 570 nm and 600 nm to calculate Alamar Blue reduction, which is a measure of reduction reactants of cellular metabolism.", "\n\nRNA isolation\n-------------\n\nTotal RNAs were extracted from skin samples using QIAzol Lysis Reagent (Qiagen). ", "Isolation begins with immersion of skin explants into QIAzol Lysis Reagent (Qiagen) followed by mechanical homogenization of the explants with a rotator--stator homogenizer (TissueRuptor, Qiagen) on ice for 20 s. RNA isolation was performed using the RNeasy mini kit (Qiagen), and DNase I digestion was performed following the manufacturer\\'s instruction.", "\n\nMicroarray expression analysis\n------------------------------\n\nRNA concentration was measured with ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE), and RNA quality was evaluated using the Agilent 2100 Bioanalyzer system (Agilent Technologies Inc, Palo Alto, CA).", "\n\nThe 250 nanograms of total RNA from each sample were used to prepare biotinylated fragmented cRNA according to the GeneChip® 3′ IVT Express Kit Manual (Affymetrix Inc., Santa Clara, CA). ", "Affymetrix GeneChip® expression arrays (Human Genome U133 Plus 2.0) were hybridized for 16 h in a 45°C incubator, rotated at 60 rpm. ", "The arrays were washed and stained using the Fluidics Station 450 and finally scanned using the GeneChip® Scanner 3000 7G (Affymetrix).", "\n\nMicroarray data analysis\n------------------------\n\nSubsequent analysis of the gene expression data was carried out in the freely available statistical computing language R (<http://www.r-project.org>) using packages available from the Bioconductor project ([www.bioconductor.org](www.bioconductor.org)) [@b34]. ", "The raw data were normalized using the robust multi-array average (RMA) method [@b35],[@b36]. ", "To search for the differentially expressed genes between the **X** samples and the **Y** samples group, an empirical Bayes moderated *t*-test was then applied using the 'limma' package [@b37]. ", "To address the problem with multiple testing, the *P*-values were adjusted using the method of Benjamini and Hochberg [@b38].", "\n\nRegulation of individual probe sets in gene ontology categories using gene-set enrichment analysis\n--------------------------------------------------------------------------------------------------\n\nThe enrichment analysis [@b39] was performed to determine the probability that gene ontology groups are specifically overexpressed in RA-treated skin as compared to vehicle-treated skin. ", "For this analysis, we used the public DAVID Bioinformatics database; <http://david.abcc.ncifcrf.gov/> [@b40]. ", "The enrichment score of each gene was determined by calculating the relative expression in the RA-treated skin compared with placebo-treated skin.", "\n\nGenes that were significantly upregulated or downregulated more than twofold were included in this analysis to evaluate enriched functional gene ontology groups.", "\n\nTo determine the overrepresented categories, a GO category-specific list for each category of interest was compiled containing those probe sets identified as differentially expressed. ", "A GO enrichment score of \\>1 was set as a limit to be discussed as a finding.", "\n\nAs a further step, genes that were more than 10-fold differentially expressed were analysed manually to investigate which genes were affected most predominantly by RA.", "\n\nReal-time reverse-transcriptase polymerase chain reaction (RT-PCR)\n------------------------------------------------------------------\n\nTo validate the mRNA microarray results, three significantly upregulated genes were selected and their expression was analysed with real-time quantitative polymerase chain reaction (RT-qPCR) (Bio-Rad, Stockholm, Sweden). ", "Skin explants from facial or breast skin from nine patients with a median age of 37 years were used for this conformational study. ", "It is noteworthy that these donors differ from the donors used for the micro-array study. ", "Total RNA from these skin explants treated with RA, as described above, were prepared with RNeasy mini kit (Qiagen) and treated with DNase I (Qiagen) to remove contaminating genomic DNA. ", "Reverse transcription was performed with iScript cDNA synthesis kit (Bio-Rad). ", "SsoFast EvaGreen supermix (Bio-Rad) was used in the RT-qPCR together with specific primers (from Qiagen) for the genes of interest, that is, DHRS9, CYP26B1 and HBEGF. ", "Hot-start two-step PCR, consisting of 95°C for 3 min, followed by 40 cycles of 95°C for 10 s, 57°C for 30 s was performed using CFX96 Real-Time PCR Detection System (Bio-Rad). ", "Relative quantification of gene expression in the different explants was calculated using the delta-delta-C~T~ method using the TATA box-binding protein (TBP) as a reference gene.", "\n\nResults\n=======\n\nAlamar blue assay\n-----------------\n\nExplants from the three donors tested for the gene array were also tested for viability using Alamar blue assay. ", "The viability of explants was investigated after topical application of RA for 24 h. The results showed that RA was not affecting the viability of the explants during a 24-h application (Fig.[1](#fig01){ref-type=\"fig\"}).", "\n\n{#fig01}\n\nIdentification of RA-responsive genes by 24 h stimulation *ex vivo* (Step 1)\n----------------------------------------------------------------------------\n\nWe compared the transcriptional profiles of RA-treated and placebo-treated skin explants (*n* = 3) using Affymetrix oligonucleotide microarrays. ", "The microarrays simultaneously measure the levels of 22 000 mRNAs. ", "Among them were 93 significantly regulated by RA, within the limits of our selection criteria (less than twofold differentially expressed, *P* \\< 0.05). ", "Of these 93 genes, 60 genes were upregulated and 33 downregulated.", "\n\nTo understand the biological meaning behind such a large list of genes, functional annotation clustering analysis was performed using DAVID Bioinformatics resources. ", "The clusters with the smallest *P*-value (*P* \\< 0.05 adjusted using the method of Benjamini and Hochberg [@b38]) which were retrieved after 24-h stimulation with RA are presented in Fig.[2](#fig02){ref-type=\"fig\"}. ", "When we summarized the functional categories of the genes upregulated by RA, we found that more than 30% of them fall into one of the following ontological categories: clusters (lipid, hormone and retinoid metabolism) and in development (organ, tissue and epithelial development) (Table[1](#tbl1){ref-type=\"table\"}).", "\n\n###### \n\nSummary of the corresponding genes to the clusters within Fig.[2](#fig02){ref-type=\"fig\"}\n\n Gene name Gene symbol Gene ID Fold change\n ----------------------------------------------------------------------------- ------------- --------------- -------------\n Cluster 1a: Metabolism \n   Cytochrome P450, family 26, subfamily A, polypeptide 1 CYP26A1 206424_at 22.61\n   Dehydrogenase/reductase (SDR family) member 9 DHRS9 224009\\_×\\_at 11.96\n   Cytochrome P450, family 26, subfamily B, polypeptide 1 CYP26B1 219825_at 5.26\n   Acyl-CoA synthetase long-chain family member 3 ACSL3 201662_s\\_at 3.66\n   Proprotein convertase subtilisin/kexin type 5 PCSK5 213652_at 2.69\n   Nuclear receptor subfamily 3, group C, member 1 NR3C1 201866_s\\_at 2.36\n   Mitogen-activated protein kinase 14 MAPK14 211561\\_×\\_at −2.13\n   Retinol dehydrogenase 12 (all-trans/9-cis/11-cis) RDH12 242998_at −2.42\n   Diacylglycerol O-acyltransferase homologue 2 (mouse) DGAT2 226064_s\\_at −4.58\n   Arachidonate 12-lipoxygenase ALOX12 207206_s\\_at −4.73\n   Serine carboxypeptidase 1 SCPEP1 218217_at −6.41\n Cluster 1 b; Retinoic acid metabolism \n   Cytochrome P450, family 26, subfamily A, polypeptide 1 CYP26A1 206424_at 22.61\n   Dehydrogenase/reductase (SDR family) member 9 DHRS9 224009\\_×\\_at 11.96\n   Cytochrome P450, family 26, subfamily B, polypeptide 1 CYP26B1 219825_at 5.26\n   Retinol dehydrogenase 12 (all-trans/9-cis/11-cis) RDH12 242998_at −2.42\n   Serine carboxypeptidase 1 SCPEP1 218217_at −6.41\n Cluster 2: Development \n   Keratin 4 KRT4 213240_s\\_at 26.97\n   Cytochrome P450, family 26, subfamily A, polypeptide 1 CYP26A1 206424_at 22.61\n   Dehydrogenase/reductase (SDR family) member 9 DHRS9 224009\\_×\\_at 11.96\n   Epithelial membrane protein 1 EMP1 213895_at 7.31\n   F-box protein 32 FBXO32 241762_at 6.39\n   Paired-like homeodomain 1 PITX1 209587_at 4.54\n   Sciellin SCEL 1554921_a\\_at 4.06\n   Nuclear-receptor-interacting protein 1 NRIP1 202600_s\\_at 3.70\n   Heparin-binding EGF-like growth factor HBEGF 38037_at 10.8\n   Ephrin-B2 EFNB2 202669_s\\_at 3.18\n   Proprotein convertase subtilisin/kexin type 5 PCSK5 213652_at 2.69\n   Nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) NR3C1 201865\\_×\\_at 2.11\n   Sprouty homologue 1, antagonist of FGF signalling (Drosophila) SPRY1 212558_at −2.12\n   Mitogen-activated protein kinase 14 MAPK14 211561\\_×\\_at −2.13\n   Dystroglycan 1 (dystrophin-associated glycoprotein 1) DAG1 205417_s\\_at −2.28\n   Crystallin, alpha B CRYAB 209283_at −2.66\n   Prolactin receptor PRLR 227629_at −3.28\n   Nebulin NEB 205054_at −4.53\n   Chromosome 1 open-reading frame 68 C1orf68 217087_at −5.92\n\nTable includes gene name, gene symbol, gene ID and fold change compared with placebo. ", "Explain more the redundancy.", "\n\n![", "Heat map of hierarchical clustering of 93 genes in RA-treated explants compared with placebo. ", "Hierarchical clustering was performed using the [genesis]{.smallcaps} software [@b67], with default settings (e.g. Euclidian distance, average linkage) of genes differentially expressed more than less than twofold, that is, 93 genes. ", "Green indicates reduced expression, black indicates the unaltered expression, and red indicates increased expression in RA-treated as compared to placebo-treated explants (*n* = 3). ", "The colour scale bar is shown at the top of each figure.", "Cluster analyses of altered genes involved in metabolism genes and development genes. ", "Hierarchal clustering analysis was performed in both the gene (row) and experiment (column) dimension. ", "Yellow arrows indicate genes enriched in gene annotation clustering (David Bioinformatics) which resulted in cluster 1 representing genes involved in metabolism (Enrichment score 3.6). ", "5 genes of 10 genes in the metabolism cluster were defining genes involved in metabolism of RA. ", "Blue arrows indicate genes enriched in cluster 2 which were defined as involved in development (Enrichment score 2.0) by David Bioinformatics.](ics0036-0253-f2){#fig02}\n\nCluster 1: Metabolic process (including RA metabolic genes) (enrichment score 3.6)\n----------------------------------------------------------------------------------\n\nAs shown by the functional annotation clustering analysis, metabolic process was the top cluster identified in our study (enrichment score 3.6) highlighting RA metabolism pathways with totally 11 genes included (Table[1](#tbl1){ref-type=\"table\"}). ", "Two main enzymes were identified, involved in the metabolism of RA metabolism, that is, cytochrome P450 26 A1 (CYP26A1), which was highly upregulated and to a lesser extend, and CYP26B1.", "\n\nAlso, the SDR family member dehydrogenase reductase 9 (DHRS9), acyl-CoA synthetase long-chain family member 3 (ACSL3), proprotein convertase subtilisin/kexin type 5 (PCSK5), and nuclear receptor subfamily 3 (NR3C1) was found to be upregulated in our study.", "\n\nGenes that shown to be downregulated in this cluster were the inflammatory gene arachidonate 12-lipoxygenase (ALOX12), diacylglycerol O-acyltransferase (DGAT2), mitogen-activated protein kinase 14 (MAPK14), serine carboxypeptidase 1 (SCPEP1) and retinol dehydrogenase 12 (RDH12).", "\n\nCluster 2: Development genes (enrichment score 2.0)\n---------------------------------------------------\n\nThe second cluster was identified as the development genes including tissue development and epithelial development (Table[1](#tbl1){ref-type=\"table\"} and Fig.[2](#fig02){ref-type=\"fig\"}). ", "In total, 19 genes were identified in this cluster. ", "Keratin 4 (KRT4) was found to be highly upregulated. ", "Within the same cluster, heparin-binding EGF-like growth factor (HBEGF), CYP26A1, DHRS9, epithelial membrane protein 1 (EMP1), F-box protein 32 (FBX032), paired-like homeodomain 1 (PITX1), sciellin (SCEL), nuclear-receptor-interacting protein 1 (NRIP1), ephrin-B2 (EFNB2), proprotein convertase subtilisin/kexin type 5 (PCSK5) and NR3C1 were identified as genes induced by RA.", "\n\nDownregulated genes within the development cluster were as follows: sprouty homologue 1 (SPRY1), MAPK14, dystroglycan (DAG1), crystallin, alpha B (CRYAB), prolactin receptor (PRLR), nebulin (NEB), and chromosome 1 open-reading frame 68 (C1orf68), CYP26A1, DHRS9, NR3C1 and MAPK14 were identified in both cluster 1 and 2.", "\n\nValidation of microarray data with qRT-PCR\n------------------------------------------\n\nTo confirm independently the microarray results obtained, we performed quantitative RT-PCR analysis of three representative genes, that is, CYP26B1, DHRS9 and HBEGF (Fig.[3](#fig03){ref-type=\"fig\"}). ", "These three genes were chosen based on following criteria; they were significantly upregulated by RA and included in the gene ontology groups that were detected via functional annotation clustering using DAVID Bioinformatics resources. ", "These genes are also known to be regulated by RA and expressed in the two top 2 clusters of genes in our explant study: vitamin A metabolism (CYP26B1, DHRS9) and development (HBEGF). ", "Results showed upregulation of CYP26B1 (1.52-fold), HBEGF (3.22-fold) and DHRS9 (3.53-fold) by topical application of RA.", "\n\n{#fig03}\n\nStep 2: Analysis of genes affected more than 10-fold by RA\n----------------------------------------------------------\n\nUpon analysing the gene array manually for genes affected more than 10-fold, RA was shown to affect 8 genes more than 10-fold (Table[2](#tbl2){ref-type=\"table\"}).", "\n\n###### \n\nThe 8 genes that were stimulated more than 10-fold by topical application of RA\n\n Gene title Gene symbol Probe Set ID Fold change\n ----------------------------------------------------------- ------------- -------------- -------------\n Flavin-containing monooxygenase 2 (non-functional) FMO2 228268_at 50.17\n Sterile alpha motif domain containing 9 SAMD9 228531_at 40.02\n Carcinoembryonic antigen-related cell adhesion molecule 6 CEACAM6 211657_at 33.64\n Keratin 4 KRT4 213240_s\\_at 26.97\n Cytochrome P450, family 26, subfamily A CYP26A1 206424_at 22.61\n Chromosome 10 open-reading frame 54 C10orf54 225372_at 14.42\n Dehydrogenase/reductase (SDR family) member 9 DHRS9 224009_x\\_at 11.96\n Lipocalin 2 LCN2 212531_at 10.73\n\n*P* \\< 0.05.", "\n\nFlavin-containing monooxygenase (FMO) was in our study stimulated 50-fold by topical application of RA. ", "Next, sterile alpha motif domain containing 9 (SAMD9) was upregulated 40-fold in our study.", "\n\nFurthermore, carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6/cd66c) was induced 34-fold.", "\n\nKeratin 4 (KRT4) was also highly upregulated (27-fold) and was linked to the cluster of development genes by analysis using DAVID Bioinformatics. ", "Same accounts for cytochrome P450, family 26, subfamily A (CYP26A) which was already identified in the metabolism cluster.", "\n\nChromosome 10 open-reading frame 54 (c10orf54) was upregulated 14-fold. ", "This gene encodes for platelet receptor Gi24. ", "As already described, dehydrogenase/reductase (SDR family) member 9 (DHRS9) was highly upregulated (12-fold). ", "Finally, lipocalin 2 (LCN2) was upregulated 11-fold.", "\n\nDiscussion\n==========\n\nSeveral previous reports describe the genetic targets of retinoids using gene array techniques [@b41]. ", "However, the genetic profile of RA has not earlier been studied in explants of full-thickness skin. ", "In this study, we developed an *ex vivo* skin explant organoculture model to study the complete gene expression following RA treatment, adopting cDNA micro-array analysis.", "\n\nConcomitantly, we described an approach for recovering RNA of full-thickness skin taken from the explant model skin. ", "This procedure permits a direct quantitative and qualitative assessment of topical treatment with dermatological active ingredients, such as RA.", "\n\nWe found that 93 genes were significantly more than two-fold regulated by RA in three organocultures of human skin. ", "The marked alterations of the expressions of 93 genes were found to be involved in mainly two clusters, that is, lipid and retinoid metabolism and in development, that is, organ, tissue and epithelial development. ", "Comparing to previous studies in monocultures of keratinocytes, Lee *et al*. ", "showed that these cells responded to RA very fast with 315 genes affected already at 1 h. Please note that these authors used a threshold of 1.62-fold change to show effect of RA [@b41].", "\n\nLipid and retinoid metabolism\n-----------------------------\n\nAs shown by the functional annotation clustering analysis, metabolic process was the top cluster identified in our study, highlighting lipid and RA metabolism pathways. ", "Two main enzymes were identified with regard to retinoic acid metabolism, that is, CYP26A1, which was highly upregulated (22.6-fold) and to a lesser extend, and CYP26B1 (5.3). ", "The importance of these enzymes with regard to retinoid metabolism in the human skin has been confirmed by other authors [@b22],[@b42]. ", "For example, Lee *et al*. ", "showed induction of CYP26B1 (12.8-fold) by RA in epidermal keratinocytes after 4-h stimulation [@b41]. ", "In contrast to our study, these authors have showed that CYP26B1 is the most abundant RA metabolizing CYP26 enzyme in unstimulated keratinocytes at the mRNA level [@b42],[@b22],[@b43]. ", "On the other hand, they suggested that CYP26A1 may play a role during situations of excess of RA in epidermis which is the situation in our study.", "\n\nThe expression of DHRS9 was also increased in our study (11.96-fold) and is in agreement with Lee *et al*.\\'s study on epidermal keratinocytes where DHRS9 was induced 3.5-fold after 24 h [@b41].", "\n\nOther genes affected involved in metabolism were ACSL3 which was upregulated in our study which is concomitant with reports on the effect of RA on rat hepatoma cells [@b44]. ", "However, to our knowledge, such an effect of RA has not been reported in human skin to date.", "\n\nThe lipoxygenase, ALOX12, involved in fatty acid oxidation, was reduced after RA treatment. ", "These results are compatible with Lee *et al*.\\'s study in human keratinocytes where ALOX12B was reduced after RA treatment [@b41].", "\n\nMoreover, we found DGAT2 to be reduced (4.58-fold). ", "Same accounts for the expression of RDH12, which was also reduced (2.42-fold) in response to exogenous RA in our study. ", "To our knowledge, RDH12 has not been described in human skin previously.", "\n\nIn addition, MAP kinase 14, which is essential for embryonic development and regulates different cellular functions such as proliferation, differentiation, cell death, adhesion, migration, as well as the response to stress, and many metabolic pathways were found to be downregulated in our study. ", "A similar enzyme, MAPK13, was downregulated in human keratinocytes by RA treatment^.^ The inhibitory effect of RA on MAPK is documented by other authors and has been hypothesized to have a role in the inhibitory action of RA on UV-induced skin damage [@b45].", "\n\nRegulation of development genes by RA\n-------------------------------------\n\nRetinoid signalling is known to be important in the development of the eye [@b46], lungs [@b47], heart [@b48] and skin [@b49],[@b50]. ", "Adult skin continues to grow throughout the life of humans, and therefore, it is not surprising that genes involved in epidermal development are stimulated after RA application.", "\n\nIn our study, development genes were identified as the second cluster of importance by gene ontology analysis. ", "In this cluster, KRT4 was found to be highly upregulated which is also well known in human keratinocytes [@b41]. ", "It has even been suggested as a future marker for retinoid bioactivity in epidermis *in vivo* [@b41]. ", "Within the same cluster, HBEGF was increased which also is consistent with literature data on the proliferative effect of RA in human keratinocytes [@b41] and in reconstituted human epidermis [@b30].", "\n\nHBEGF was confirmed to be regulated by RA by qPCR in skin explants (Fig.[3](#fig03){ref-type=\"fig\"}). ", "The discrepancy in fold change (10.8 in the microarray study and 3.22 by qPCR) could be due to the difference in donors as well as skin site (facial and breast). ", "In fact, Cyp26a1, Cyp26b1, Rbp1, Crabp1, Hbegf and Krt4 are all known marker for retinoid activity ([@b65]).", "\n\nInterestingly, EMP1 was found to be highly upregulated (7.31-fold), which is consistent with reports in F9 teratocarcinoma stem cells [@b51]. ", "EMP1 has been prominently found in the gastrointestinal tract, skin, lung and brain but not in liver. ", "The proteins of this family are likely to serve similar functions possibly related to cell proliferation and differentiation in a variety of cell types [@b52].", "\n\nAnother gene in the development cluster, sciellin (SCEL), a precursor of the cornified envelope [@b53], was highly upregulated. ", "The specific function of this gene in human skin is not known to date, but deletion of this gene in mice did not affect normal barrier function [@b54].", "\n\nNRIP1 was also highlighted in the gene ontology analysis for development of genes, and interestingly, this biomarker has not been found in skin to date. ", "However, it has been described in context of regulation of mesenchymal stem cell differentiation by retinoids as NRIP1 is induced by RA in stem cells [@b55].", "\n\nThe upregulation of EfnB2 seen by retinoic acid in our study could implicate the regulation angiogenesis and blood vessel development as this has been reported in the literature [@b56]. ", "However, the role of EfnB2 has not been investigated to date in human skin.", "\n\nIt is noteworthy that NR3C1 also known as glucocorticoid receptor is upregulated in human skin by topical application of RA in our study. ", "To our knowledge, this mechanism has not been reported in human skin. ", "However, a study in cultured chick embryonic skin showed that the addition of 2 *μ*M retinol resulted in a threefold increase in specific dexamethasone binding to the glucocorticoid receptor [@b57]. ", "Whether the same mechanism applies to our model remains to be elucidated.", "\n\nProlactin receptor (PRLR) was profoundly downregulated which is in line with a study in patients with acne where isotretinoin caused suppression of several pituitary hormones such as prolactin in patients\\' sera [@b58].", "\n\nUpon analysing the gene array manually for genes affected more than 10-fold by RA without RA was found to upregulate 8 genes more than 10-fold. ", "One of these was FMO, which was upregulated 50.17-fold after 24-h stimulation with RA. ", "FMO has been found to be present in human skin [@b59]. ", "It is known to metabolize xenobiotics, but to our knowledge, not known to metabolize retinoids.", "\n\nSAMD9 was upregulated 40.02-fold by topical application of RA for 24 h. The function of SAMD9 in human skin is to date unknown, but it has been suggested to have a role in regulation of cell death in malignant glioma [@b60].", "\n\nFurthermore, CEACAM6/cd66c was induced 34.64-fold. ", "CEACAM6 is found on epithelial and other cells. ", "It has to our knowledge not been described to be expressed in human skin. ", "Other genes from the same family, for example CEACAM1, have shown to be important for the wound healing process in human skin [@b61].", "\n\nKRT4 was also highly upregulated (26.97-fold) and was linked to the cluster of development genes by analysis using DAVID Bioinformatics. ", "Same accounts for cytochrome P450, family 26, subfamily A (CYP26A), which was already identified in the metabolism cluster. ", "C10orf54 was upregulated 14.42-fold. ", "This gene encodes for platelet receptor Gi24. ", "The function of this receptor in human skin is to our knowledge unknown. ", "As already described, DHRS9 was highly upregulated (11.96-fold). ", "LCN2 was upregulated 10.73-fold. ", "The induction of LCN by RA has also been confirmed by other authors. ", "The confirming studies were investigating the effect of oral application of isotretinoin in patients with acne [@b62],[@b63] but also of RA in monocultures of keratinocytes [@b41].", "\n\nIn conclusion, we have in the current study shown that a full-thickness organoculture of human skin is an efficient non-invasive model to study the effects of topically applied compounds at the gene expression level.", "\n\nWe have in this study confirmed several genes affected by RA, which has been previously found by other authors in monocultures of keratinocytes [@b41], reconstructed epidermis [@b30] and in skin biopsies after oral application of isotretinoin [@b64], for example, CYP26A1/B1, DHRS9, ALOX12, KRT4, HBEGF and LCN2. ", "In fact, KRT4, HBEGF and CYP26A1/B1 are considered to be retinoid target genes [@b65] (Gericke *et al*., ", "2013) where KRT 4 is a marker for keratinocyte differentiation [@b66] (Wanner *et al*. ", "1996), CYP26 for retinoid metabolism and HBEGF for increased keratinocyte proliferation and epidermal thickness [@b8].", "\n\nWe have also disclosed several genes that have never been identified in human skin before, for example SCEL, EfnB2, SAMD9 and CEACAM6. ", "Consequently, the roles of these genes in skin have yet to be discovered.", "\n\nOverall, we believe that this organoculture model possessing a physiological complexity such as a fully functioning barrier function compared with cell cultures and reconstructed skin models could serve as a model to evaluate the effect of topical application of cosmetic ingredients. ", "The model has been shown in this study to be suitable for assessing short-term stimulation with RA. ", "Therefore, this model can be used as a first screen to identify more effective therapeutic strategies by testing functional connections between drugs and genes using databases such as connectivity map (Cmap, Broad Institute). ", "However, further evaluation will be needed including a larger sample group to confirm this hypothesis.", "\n\nThe authors wish to thank Hanna Göransson-Kultima and Maria Rydåker at the gene array platform, University of Uppsala, for gene array data analysis and Hans Törmä for knowledgeable and insightful discussions on retinoid metabolism. ", "This work was funded solely by Oriflame Cosmetics AB.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nChecking if an int is prime more efficiently\n\nI recently was part of a small java programming competition at my school. ", "My partner and I have just finished our first pure oop class and most of the questions were out of our league so we settled on this one (and I am paraphrasing somewhat): \"given an input integer n return the next int that is prime and its reverse is also prime for example if n = 18 your program should print 31\" because 31 and 13 are both prime. ", "Your .class file would then have a test case of all the possible numbers from 1-2,000,000,000 passed to it and it had to return the correct answer within 10 seconds to be considered valid. ", "\nWe found a solution but with larger test cases it would take longer than 10 seconds. ", "I am fairly certain there is a way to move the range of looping from n,..2,000,000,000 down as the likely hood of needing to loop that far when n is a low number is small, but either way we broke the loop when a number is prime under both conditions is found. ", "At first we were looping from 2,..n no matter how large it was then i remembered the rule about only looping to the square root of n. Any suggestions on how to make my program more efficient? ", "I have had no classes dealing with complexity analysis of algorithms. ", "Here is our attempt. ", "\npublic class P3\n{\n\n public static void main(String[] args){\n\n long loop = 2000000000;\n long n = Integer.parseInt(args[0]);\n for(long i = n; i<loop; i++)\n {\n String s = i +\"\";\n String r = \"\";\n for(int j = s.length()-1; j>=0; j--)\n r = r + s.charAt(j);\n if(prime(i) && prime(Long.parseLong(r)))\n {\n System.out.println(i);\n break;\n }\n }\n System.out.println(\"#\");\n }\n\n public static boolean prime(long p){\n\nfor(int i = 2; i<(int)Math.sqrt(p); i++)\n {\n if(p%i==0)\n return false;\n }\n return true;\n }\n}\n\nps sorry if i did the formatting for code wrong this is my first time posting here. ", "Also the output had to have a '#' after each line thats what the line after the loop is about Thanks for any help you guys offer!!!", "\n\nA:\n\nFirst you should precompute all prime numbers up to 2,000,000,000 using something like the Sieve of Eratosthenes. ", "You can store whether each number is prime in a bit array.", "\nThis is pretty fast, and then checking each individual number for primality is a simple lookup.", "\nIf you can't do this because you need to run a new instance of your program for each test case, use a fast primality testing algorithm like Miller-Rabin.", "\n\nA:\n\nYour prime check is very inefficient. ", "In fact, you don't need to re-check multiples of already checked numbers. ", "So when you check for %2, you don't need to check for %4.", "\nTo find out whether a number is a prime, you only have to try to divide it by all known primes until you reach the square root of the number to be checked. ", "Doing this reduces the number of divisions vastly: if your app has a list of the primes from 2..~44721 (for instance computed as preparation step), you can check all numbers until 2000000000 pretty quickly.", "\nAlso, you should make sure to check the smaller of the two permutations first (e.g. in your sample first check 13, then 31).", "\nEdit:\nHere's a sample I quickly put together in C# (you'll need to do some minor syntactic changes to have it run on Java, but I just had a C# compiler at hand):\npublic static long reverse(long value) {\n long result = 0;\n while (value > 0) {\n result = result*10+(value%10);\n value /= 10;\n }\n return result;\n}\n\npublic static long[] knownPrimes = new long[1000000];\npublic static int knownPrimeCount = 0;\n\npublic static bool isPrime(long value) {\n // we loop through all already known primes and try to divide by those (sieve sort of)\n for (int primeIndex = 0; primeIndex < knownPrimeCount; primeIndex++) {\n long primeToCheck = knownPrimes[primeIndex];\n if (value % knownPrimes[primeIndex] == 0) {\n // can be divided by the given prime -> not a prime\n return false;\n }\n if ((primeToCheck * primeToCheck) > value) {\n // square exceeds the value -> is a prime, no more checks needed\n return true;\n }\n }\n // if we come here, we've run out of primes to check against, and therefore we should indicate this as error\n throw new ArgumentException(string.", "Format(\"{0} is too large to be checked against known primes\", value), \"value\");\n}\n\npublic static void Main(String[] args){\n long loop = 2000000000;\n long n = 1999990000;\n\n // first we initialize all the primes we may be needing for the final computation\n knownPrimes[knownPrimeCount++] = 2;\n for (long i = 3; true; i++) {\n if (isPrime(i)) {\n // store the new prime\n knownPrimes[knownPrimeCount++] = i;\n if ((i * i) > loop) {\n break; // we have all the primes we need now\n }\n }\n }\n\n // now we try to find matches\n for (long i = n; i <= loop; i++) {\n long reversed = reverse(i);\n if ((reversed <= i) && isPrime(reversed) && isPrime(i)) {\n Console.", "WriteLine(\"{0} <-> {1}\", i, reversed);\n }\n }\n Console.", "WriteLine(\"#\");\n Console.", "ReadKey(true);\n}\n\nOn my computer and with the given loop and n in the source the result shows up instantaneous.", "\n\nA:\n\nUsing BigInteger.isProbablePrime(certainty) and BigInteger.nextProbablePrime() can significantly cut down the number of cases you need to check quite efficiently \n\n" ]

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[ "Cell populations enriched for stem cells are often desired for use in research or therapy. ", "Typical sources of stem cells include bone marrow, whole peripheral blood, leukopheresis or apheresis products, especially from “mobilized” donors, or other less common sources, such as umbilical cord blood and tissue or organ suspensions. ", "Enrichment of stem cells has been done in several ways. ", "Typical methods include density step gradients (e.g., FICOLL-HYPAQUE®, colloidal silica, and the like), elutriation, centrifugation, lysis of erythrocytes by hypotonic shock, and various combinations of these methods. ", "As an example, the purification of stem cells from bone marrow requires removal of erythrocytes and granulocytes, which is often accomplished by FICOLL-HYPAQUE® density gradient centrifugation. ", "There are disadvantages to each of these methods, one of which is the need for laborious washing steps after the enrichment step is performed, e.g., to remove the density gradient centrifugation medium.", "\nFollowing enrichment, the cells are typically washed by a repetitive process. ", "The steps generally include placing the enriched cell suspension into a centrifuge tube and pelleting the cells to the bottom of the tube by use of a centrifuge. ", "The tube is removed from the centrifuge, and the supernatant is decanted from the pelleted cells. ", "A wash liquid is added to the tube, and the cell pellet is resuspended. ", "These steps are typically repeated 2 to 4 times.", "\nOne disadvantage of this washing process is that sequential resuspension and centrifugation can decrease cell viability and increase cell lysis. ", "Another disadvantage of washing by centrifugation is the opportunity for bacteria or other infectious agents to contaminate the cells. ", "Even if all the materials are kept sterile, the repeated opening of the centrifuge tubes, and the exposure of pipettes and bottles of wash solution to the air can result in contamination. ", "The risk of contamination is sufficiently significant that some medical regulatory agencies have demanded that only “closed” systems are used for cell handling.", "\nFiltration methods have also been used to remove cells from blood while retaining other blood constituents for later use. ", "Such methods generally trap the cells on a filter in a non-recoverable form, while allowing other blood constituents to pass through the filter and into a collection vessel. ", "For example, filters are available to remove leukocytes from blood so that the incidence of alloimmune reactions is minimized following blood transfusions. ", "Leukocyte removal is typically done using filters which are made of matted plastic fiber mesh. ", "The mesh is usually arranged to trap the leukocytes in a reticulated matrix having enough depth so that the cells are trapped throughout the depth of the filter, thereby keeping the filter from clogging, as would occur if the leukocytes were trapped on a planar surface.", "\nIn addition to the physical trapping of the cells, the materials and large surface area of the filter allow leukocytes to adhere irreversibly to the surface. ", "Many of these adherent cells are the very ones desired for some medical procedures. ", "The resulting combination of trapping and adherence to the filter creates a highly efficient means of removing the leukocytes for disposal prior to blood infusion therapy. ", "However, when leukocytes are the desired cells, this method of filtration is not advantageous.", "\nA method that has been useful in the fractionation of various particles is tangential flow filtration (TFF) or “cross-flow” filtration. ", "TFF relies on the movement of a fluid parallel to the surface of a porous membrane filter. ", "The pores of the membrane allow passage of the fluid and of particles within the fluid that are typically smaller than the pores. ", "In addition, the cross-flow (or “tangential” flow) of fluid parallel to the filter prevents a build-up of particles larger than the pores on the filter surface.", "\nTFF has been used for the gross separation of various materials. ", "The use of tangential flow filtration in the pharmaceutical field has been reviewed by Genovesi (J. Parenter. ", "Aci. ", "Technol., ", "37:81, 1983), including the filtration of sterile water for injection, clarification of a solvent system, and filtration of enzymes from broths and bacterial cultures. ", "Marinaccio et al. (", "WO 85/03011) report a process for use in the removal of particulate blood components from blood for plasmapheresis, and Robinson et al. (", "U.S. Pat. ", "No. ", "5,423,738) describe the use of TFF for the removal of plasma from blood, allowing the reinfusion of blood cells and platelets into patients.", "\nIn another use, TFF has been reported for the filtration of beer (EP 0 208 450), specifically for the removal of particulates such as yeast cells and other suspended solids. ", "Kothe et al. (", "U.S. Pat. ", "No. ", "4,644,056) disclose the use of TFF in the purification of immunoglobulins from milk or colostrurn, and Castino (U.S. Pat. ", "No. ", "4,420,398) describes its use in the separation of antiviral substances, such as interferons, from broths containing these substances as well as viral particles and cells. ", "Similarly, TFF has been used in the separation of bacterial enzymes from cell debris. (", "Quirk et al., ", "Enzyme Microb. ", "Technol., ", "6:201, 1984). ", "In addition, tangential flow filtration units have been employed in the concentration of cells suspended in culture media. (", "See, e.g., Radlett, J. Appl. ", "Chem. ", "Biotechnol., ", "22:495, 1972).", "\nTFF has also been reported to separate liposomes and lipid particles according to size. (", "Lenk et al., ", "U.S. Pat. ", "No. ", "5,948,441). ", "TFF allows for the formation and isolation of liposomes and lipid particles having a defined size range from heterogeneous populations of such particles. (", "See Lenk et al., ", "supra).", "\nHowever, while TFF has been used for gross fractionation of biological liquids and the separation of, for example, liposomes, the use of TFF for separation of live cell populations differing in defined characteristics has not been appreciated in the art. ", "In particular, the unique problems associated with the selective separation of stem cells from other bone marrow cells or from blood cells and tissue or organ suspensions while maintaining sterility, cell viability and regenerative activity has not been addressed. ", "In addition, the removal of other cell populations such as, e.g., populations with overlapping size ranges, has not been solved by current approaches.", "\nTherefore, there remains a need in the art for additional devices and methods for selectively enriching stem cells from other bone marrow or blood constituents, including plasma, erythrocytes, and/or platelets, while preserving sterility, cell viability and regenerative and cellular activity. ", "The present invention satisfies these and other needs." ]

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[ "Alejandro Valverde admits his whole race schedule in 2016 is building towards winning the gold medal in the Olympic Games road race in Rio de Janeiro in August.", "\n\nThe 35-year-old Spaniard has won a lot of races in his career, but and Olympic medal has eluded him in his three attempts. ", "He finished 47th in Athens (2004), 13th in Beijing (08) and 18th in London four years ago, but in Rio he stands his best chance yet of winning.", "\n\n>> Save up to 31% with a magazine subscription. ", "Enjoy the luxury of home delivery and never miss an issue <<\n\nHe has already been named the lead rider of the Spanish national team for the race, where the hilly parcours will suit his style.", "\n\n“I can do well on the circuit they’ve designed in Rio,” Valverde told El Mundo. “", "I will do more one-day racing [in 2016] and I’ll see what I can do in the Giro d’Italia and I’ll help Nairo Quintana in the Tour de France, but I’ll be doing those races with Rio in the back of my mind. ", "I’ll be with him [Quintana in the Tour], but I will always be focused on how to be in best shape for the Games.", "\n\n“I feel very motivated for Rio. ", "It’s my fourth Olympics and it’s got a really good course for me. ", "Of course I’m motivated.”", "\n\nMany have questioned Valverde’s ability to be a true domestique to Quintana at the Tour and it sounds like the Spaniard himself isn’t willing to bury himself for the team leader if it means he will be out of shape for the Olympics.", "\n\nValverde returns to racing at Challenge Mallorca on January 28, where he was beaten last season by MTN-Qhubeka’s Steve Cummings, who triumphed in the Trofeo Adtratx-Mirador d’Es Colomer.", "\n\nThe Movistar rider bounced back the following day, however, to win the Trofeo Serra de Tramuntana by nearly 90 seconds from Lotto-Soudal’s Tim Wellens." ]

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[ "The acute effect of nicardipine on the renin-angiotensin-aldosterone system in salt-sensitive essential hypertension.", "\nTo determine the role of the renin-angiotensin-aldosterone (RAA) system in the acute effect of calcium channel blockers, we examined the acute effect of 40 mg nicardipine in 21 essential hypertensive patients. ", "Nine patients whose mean blood pressure (MBP) decreased more than 5% at 2 hours after 20 mg furosemide i.v. ", "were classified as salt-sensitive (SS); the remainder as salt-resistant (SR). ", "The percentage decrease of MBP with nicardipine was not different between the two subgroups (12.4 +/- 2.5% for SS, and 17.7 +/- 4.1% for SR). ", "The percentage decrease of MBP correlated with the pretreatment MBP (r = 0.67, p < 0.001), but not with the basal plasma renin activity (PRA), plasma aldosterone concentration (PAC), or natriuretic response. ", "A significant increase of heart rate was noted in SR (31.2%) but not in SS (6.5%), and was associated with a higher increase of PRA in SR (90.7%) than in SS (25.5%). ", "A correlation between the increase of PRA and the percentage increase of heart rate was noted (r = 0.77 p < 0.001). ", "Decrease of PAC was observed in SS but not in SR until the third hour. ", "The 3-hour sodium excretion was slightly greater in SR than in SS (59.9 +/- 9.1 vs. 35.1 +/- 3.0 mEq; p < 0.05). ", "In summary, the acute hypotensive effect of nicardipine is dependent upon the vascular tone regardless of the status of the RAA system. ", "An increase in PRA by nicardipine resulting from a baroreflex mechanism may counteract the inhibitory effect of aldosterone secretion by nicardipine. ", "The unchanged PRA in SS is due to their blunted baroreflex control of heart rate. ", "Mechanisms other than the change in the RAA system by nicardipine may account for the acute natriuretic effect." ]

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[ "Q:\n\nSmoother grid in a plot\n\nI'm trying to plot a smoother grid in the background of this grid that's already plotted. ", "This is what I've done so far. ", "The grid follows my major ticks. ", "I'd like this smoother grid to follow the minor ticks. ", "Is this possible?", "\nMy code until now: \nfig, ax = plt.subplots(figsize = (20,10))\n\nax.set_xticks(np.arange(0,round(max(datax)+1)))\nax.set_yticks(np.arange(0,round(max(datay)+1),step = 0.1))\nax.minorticks_on()\nax.grid(True)\nplt.xlabel(\"Tensão (V)\", fontsize = 14)\nplt.ylabel(\"Corrente (mA)\", fontsize = 14)\nplt.title(\"Experimento 2\", fontsize = 20)\nax.errorbar(datax,datay,xerr = sigmax, yerr = sigmay, fmt = ',')\nax.set(xlim= -1, ylim = 0)\n\nP.S.: would you guys organize this code differently? ", "I think it's a complete mess. ", "\ni want my grids to look like this\nthis is how they are now\n\nA:\n\nWhat you want is the linestyle keyword argument for grid, along with the linewidth keyword argument.", "\nHere's how you can use dotted lines for your grid, with thinner lines for the minor ticks:\nax.grid(True, which='major', linestyle=':', linewidth=1, color=\"black\")\nax.grid(True, which='minor', linestyle=':', linewidth=0.5, color=\"black\")\n\nHere's the output (I used faked data since you did not provide a MWE):\n\nYou can fiddle with the linewidth parameter to have the lines appear thinner, or on the color to make them fainter.", "\nYou can also try other linestyles out, like dashed (linestyle='--').", "\n\n" ]

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[ "Q:\n\nHow to avoid reading old files from S3 when appending new data?", "\n\nOnce in 2 hours, spark job is running to convert some tgz files to parquet.", "\nThe job appends the new data into an existing parquet in s3:\ndf.write.mode(\"append\").partitionBy(\"id\",\"day\").parquet(\"s3://myBucket/foo.parquet\")\n\nIn spark-submit output I can see significant time is being spent on reading old parquet files, for example:\n\n16/11/27 14:06:15 INFO S3NativeFileSystem: Opening 's3://myBucket/foo.parquet/id=123/day=2016-11-26/part-r-00003-b20752e9-5d70-43f5-b8b4-50b5b4d0c7da.snappy.parquet' for reading\n16/11/27 14:06:15 INFO S3NativeFileSystem: Stream for key\n 'foo.parquet/id=123/day=2016-11-26/part-r-00003-e80419de-7019-4859-bbe7-dcd392f6fcd3.snappy.parquet'\n seeking to position '149195444'\n\nIt looks like this operation takes less than 1 second per file, but the amount of files increases with time (each append adds new files), which makes me think that my code will not be able to scale.", "\nAny ideas how to avoid reading old parquet files from s3 if I just need to append new data?", "\nI use EMR 4.8.2 and DirectParquetOutputCommitter:\nsc._jsc.hadoopConfiguration().set('spark.sql.parquet.output.committer.class', 'org.apache.spark.sql.parquet.", "DirectParquetOutputCommitter')\n\nA:\n\nI resolved this issue by writing the dataframe to EMR HDFS and then using s3-dist-cp uploading the parquets to S3\n\n" ]

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[ "A systematic investigation of the kinetics of rapid axonal transport is proposed. ", "Efforts will be made to answer three main questions: 1) What are the limits to the concentration of material that can be transported along an axon? ", "2) Are these limits determined by the number of axonal microtubules? ", "3) Is transport velocity a function of the concentration of material actually being transported? ", "The transport of the adrenergic enzyme dopamine-Beta-hydroxylase and of proteins labeled by incorporation of 3H-leucine in rabbit peroneal and frog sciatic nerve will be measured. ", "Nerves will be subjected to various small step-gradients of temperature in vitro in order to produce local increases or decreases in the concentration of transport overloaded and partially unloaded nerves will be compared with the effect of the same drugs in normal nerves. ", "Stop-flow techniques developed in this laboratory will be used to assess the effects of the experimental conditions on transport-velocity. ", "Correlative measurements will be made of microtubular numbers and density in electron micrographs of nerves fixed after exposure to such conditions. ", "It is anticipated that the results of this project will help define the fundamental kinetic properties of rapid axonal transport and provide a basis for developing improved models of the process." ]

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[ "Whatever misgivings I’ve had about some other reports by the Grattan Institute, the latest one demonstrates the value of the Melbourne-based think tank. ", "Game changers: economic reform priorities for Australia seeks to identify those workable economic reforms that would produce the greatest benefits for the nation by 2022. ", "It proposes three: Broaden the GST to […]" ]

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[ "Important Information\n\nThis page contains Important information about Factory Delivery in Gothenburg.", "\n\nIf you wish us to arrange for your free transportation - contact us minimum 1 week prior to your arrival. ", "Please notify us of your flight number, arrival time/date/place, how many persons will be travelling and which hotel you will be staying at. (", "We care for transport from Landvetter Airport or Gothenburg Ferry Terminal to the FDC.)", "\n\nChecklist\n\nPlease contact your retailer if you wish to change your date of delivery.", "\n\nBill of Sale\n\nProof of a US social security number, Canadian citizenship or a Canadian passport.", "\n\nPhoto ID\n\nMembers of the Armed Forces must present a copy of their movement order (PCS) to Drop off agent, to avoid paying Import Duty in the USA.", "\n\nOpening Hours\n\nThe Factory Delivery Center is open on weekdays (Mon-Fri) from 08.00 am to 4.30 pm.", "\n\nWinter Tires\n\nWinter tires or snow chains must be used between Dec 1 and March 31 when road conditions require it.", "The rules applies to automobiles, light trucks and buses with a maximum weight of 3,5 tons and for the trailer pulled by such a vehicle.", "\n\nExeptions to the rule:\n\nIf the vehicle is registered in a country outside of Sweden\n\nWhen a journey begins or ends in a country outside Sweden\n\nAn approved winter tire is one that is specifically manufactured for winter road conditions. ", "On the website below you can find a list of approved tires:" ]

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[ "Sizing Guide\n\nAs shoe sizing varies between brands and even within brands, it is important that you have your child's exact foot measurement for reference rather than using the size from an existing pair.", "\n\nIf you have any questions or are unsure about the sizing please feel free to contact us so that we can advise you.", "\n\nBaby and toddler shoes should be longer than the foot by approximately 5-10mm.", "\n\nWhilst walking, feet naturally move towards the front of the shoe, so if the shoe is too short then one or more toes will push against the end of the shoe, causing discomfort and inhibiting development.", "\n\nWhen choosing the correct size, please also bear in mind that children's feet grow by approximately 5mm every 6 months, so a shoe that is only just fitting now will soon be too short if you don't allow for wriggle / growth room.", "\n\nWe advise you check their shoes every 2 months during their first year and every 3 months from 1 to 3 years.", "\n\nHow to measure your child's feet:\n\nWe have two methods for you depending on whether or not you have the use of a printer.", "\n\nMethod 1 (with printer):\n\nIf you have a printer we would recommend measuring your child's foot on our Printable Size Chart.", "\n\nPlease click the image to the left then print at ACTUAL SIZE(not \"Print to Fit\", \"Fit to Page\" or similar).", "\n\nYou can ensure the scale is correct with either a ruler, bank card or UK £1 coin.", "\n\nThe Printable Size Chart also gives comparisons to UK, EU and US sizes.", "\n\nMethod 1 (without printer):\n\nThe simplest way to choose the correct size for your little one is to have them stand barefoot and upright on a piece of A4 paper allowing for the full spread of the foot in terms of width & length.", "\n\nWith a pencil, make a mark where the back of the heel and the tip of the big toe end and measure between the two marks using a centimetre / millimetre ruler (ensure that your child’s toes aren't scrunched up).", "\n\nThe distance between the Measured Foot Length and the Shoe Inner Length should be between 5mm to 10mm to account for growth and wiggle room (slightly more, 7mm to 12mm if socks are worn).", "\n\nThe relevant Size Guide table can be found on each of the product pages, on the Sizing (Click Me) tab below the product images. ", "For your convenience, for each brand, we have also placed the Size Guides below." ]

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[ "Introduction\n\nPixelPie is an open-source, cross-platform (works on regular Processing and Android) game framework built for Processing.", "\n\nYou can see an older version of the framework at work in this video.", "\n\nIt was originally written entirely in Processing 2.2.1, for what was supposed to be a \"simple\" game that grew grossly out of proportion. ", "I've since separated the framework from the game code and re-written the framework in Java to be used as a Processing library.", "\n\nDownloads\n\nSource: https://github.com/AliasBlack/pixelpie\n\nExample: https://github.com/AliasBlack/pixelpie-example\n\nRough idea of the framework\n\nUnfortunately, there's a severe lack of documentation, aside from the Javadoc annotations inside the code, and the example linked above. ", "This will hopefully be remedied eventually - in the meantime, here's a rough explanation that will help the more adventurous folks get started.", "\n\nPixelPie is an event driven framework centered around the GameObject class.", "\n\nNearly everything you can interact with in the game is an extension of the GameObject class: Characters, platforms, NPCs, traps, powerups, and so on.", "\n\nThe GameObject class works by having several functions that are triggered when certain conditions are met. ", "Overriding these functions, such as mousePressed() and collide() will allow your object to react to mouse clicks and collisions respectively.", "\n\nLevels are created using the Tiled open-source level editor.", "\n\nUse \"Tile\" layers to decorate the level. ", "Tiles placed in tile layers have no interactivity in the game and are purely for decoration.", "\n\nGameObjects can be placed in a level by creating an \"Object\" layer, name it the same name as your GameObject class, and place copies of the object in the level using the Rectangle tool (uses the top left corner coordinates) or the Ellipse tool (uses center coordinates).", "\n\nLastly, to add sprites and levels to the game, use the included pp_assets.ods in the \"tools\" folder, you'll need LibreOffice Calc to open it. ", "It should be self explanatory. ", "After you are done, head to the \"Master\" tab, key in the absolute filepath to your game's \"data\" folder, and click Export to generate the required .json files.", "\n\nContribute!", "\n\nEvidently, the framework badly needs some proper documentation. ", "If you would like to help out creating documentation and examples, please send me a PM, or reply to this thread, I would really appreciate the help. ", "Alternatively, if you'd like to contribute to the code, please do not hesitate to ask me about anything related to the framework - I'm not a particularly good coder, and the framework needs all the help it can get.", "\n\nAnd that's it, hope this helps someone out there. :)" ]

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[ "1. ", "Field of the Invention\nThe present invention generally relates to the field of digital content distribution to mobile devices.", "\n2. ", "Description of the Background Art\nA user purchasing digital content from a content provider for download to a mobile device conventionally engages in a prerequisite financial transaction using the mobile device. ", "Following the transactions, the user then downloads the digital content from the content provider directly to the mobile device. ", "In some instances, the purchased digital content is too large to be stored on the mobile device or is formatted for a display screen much larger than that provided by the mobile device. ", "In other instances, the purchased digital content is too large to be downloaded from the content provider to the mobile device in a reasonable period of time due to bandwidth limitations over a mobile network.", "\nPurchased digital content may also require a Digital Rights Management (DRM) enabled application not supported by or available at the mobile device. ", "The purchased digital content can thus only be downloaded to a computing device supported by the DRM enabled application such as a desktop or laptop personal computer. ", "Further, backing up the digital content from the mobile device to a computer readable storage medium or a computing device may be inconvenient or impractical. ", "Therefore, digital content that is purchased and downloaded directly to a mobile device may be lost if the mobile device becomes damaged or lost." ]

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[ "One way of thinking about the wealthy and inequality in our cities is to consider how they circulate and engage with public spaces, to what extent are the super-rich really engaged with the city and why does this matter? ", "Themes of privacy, security, status and London’s relative safety emerge as key to these flows, writes Rowland Atkinson.", "\n\nThe Daily Telegraph recently gave coverage to a £4.5m home for sale in Hampstead. ", "The house, notable for its price tag alone perhaps, was deemed distinctive because it was largely underground, sporting, in iceberg fashion, a barely noticeable street level presence that concealed an extensive and airy home and gardens below. ", "Such homes are not a new phenomenon but they are increasingly prevalent and connect to the growth of a group of the very wealthy now living in London.", "\n\nAs a sociologist, one way of thinking through the implications of gated communities and fortress homes is to consider what these spaces say about and do to urban social practices and patterns of sociability – why are such homes created; what fears and aspirations do they respond to; how do such spaces reinforce and help to reproduce the existing inequalities of the city?", "\n\nOf course this is now a world of pronounced inequality and one in which the public realm and social investment are increasingly at stake in a political vision of the world in which trickle-down economics and naked personal ambition are feted by politicians and think-tanks. ", "The result of these inequalities and social conditions is the production of urban anxieties that translate into bunker style homes as well as the opulent display of defensive measures like remotely accessed gated developments, as affluent residents of the street in Lanchester’s novel Capital learn ‘we want what you’ve got’.", "\n\nTo say that such anxiety is new is of course untrue, there are certainly continuities here, but there are subtle and qualitative differences with earlier concerns about a culture of fear as the gap between the very wealthy and others becomes ever more marked – domestic space is increasingly private and inaccessible as though wealth grants a permit to invisibility. ", "Is this because of a fear of crime, a fear of intrusion, perhaps even a worry about public visibility, envy and a celebrity culture? ", "In many ways it is a complex combination of all of these factors, but it also relates to changes in income, wealth and urban society generative of changes in the built environment of the city.", "\n\nMuch has happened to make London it a rather different city from even a decade ago. ", "Part of the story of these changes is certainly about the moving frontier of gentrification and displacement that now takes in the destruction of good public housing in return for private and ‘affordable’ apartments. ", "The changes are also linked to the increasingly compositional character of households in the city, many of whom are largely absent, international investors as well as those who appear at key moments in the social and sporting calendar. ", "In the background changes in housing affordability, austerity and critical changes to the conditions under which welfare support is offered have also had massive impacts.", "\n\nThe changes we have seen in London and the appropriation of positional homes by international capital say something about the desirability of this particular city for those looking to invest and make further gains (the argument of economics), but they also say something about the nature of London’s urban culture and built environment which facilitates a lifestyle conducive to a group whose steps into public space are often timid, or at least wary of where and who is safe (an argument of the role of culture). ", "As many wealthy people suggest, when one has money the character of the world around becomes more pushy and potentially threatening.", "\n\nDomesticated public spaces linked to a fortified home spaces\n\nIn this context debates about cosmopolitanism, inequality and territory have ensued – who is London for and who do its political class really serve? ", "How do the wealthy move around and through these spaces and what, more importantly, do these mobilities say about their own social politics and connection to the wider citizenry of the capital? ", "Of course insights into these patterns are hard to discern yet are important to a broader evaluation of the value of the wealthy to the city, in both social and economic terms. ", "In fact much of the narrative around London for the rich is that the city is a safe place, in both social and economic terms. ", "For one thing, having money confers the ability to occupy a home that is a fundamental base from which forays into public and other private spaces can be made.", "\n\nElaborate security systems, a supporting cast of staffers and other services enable a seamless engagement with space are all in place and emanate from the domestic realm. ", "The ultimate goal of many buyers is a space that allows drive-in car parks with internal exits (common in many of the newly planned skyscrapers for the city to come in the next decade). ", "The poor doors of apartments alongside Versace interiors at the Battersea power station (Nine Elms) development are but one example of the ways in which the wealthy flow around the city almost in tandem with its wider population yet are impermeably separated – tinted glass, locked taxi doors or in lifts that piggyback on those used by lesser residents among other strategies of distance and control.", "\n\nIn this sense the wealthy are not an extra-territorial presence in cities like London but enjoy the sense of being threaded through the fabric of the city while being able to negotiate what are seen to be more risky groups and spaces. ", "Co-ordinated forays using personal drivers are an essential element of these networks and allow the conspicuous trappings of wealth, relatively unremarkable in such an affluent capital, to slip from view via communication by phone. ", "Yet, for them, the city appears as a delightful and open system whose emissaries welcome them in the form of ushering estate agents and no less entrepreneurial politicians.", "\n\nA politics of invisibility\n\nDespite the privatisation of public spaces and ongoing debates about the forced expulsion of the homeless, those on welfare and modestly paid workers, London feels as though it embraces the wealthy. ", "The renewed politics and legitimacy of austerity is not so much ignored, rather it is simply not part of this world, indeed it has helped to protect it. ", "Yet the mood of the city can only remain bullish to the extent that it denies an interest in those struggling with a straining infrastructure of over-priced homes and crowded transportation.", "\n\nThe search for a space that is safe leads to London for many international buyers and those with money more generally, the sense of danger found in many other national capitals fades from view even if the instinct for safety never dies. ", "London works because exposure can be limited and because districts and schools can be found that match needs which will not be compromised on. ", "The implication, to return to the example of the iceberg home, is the existence of a fortress archipelago of gated and fortress homes linked by sealed mobilities and encounters with safe zones. ", "Whether we care about the qualities and feel of this increasingly securitised form of urbanism is one thing, whether the excesses upon which it is built will be challenged is perhaps quite another.", "\n\nNote: The work underpinning this blog was funded by the ESRC and is based upon Limited exposure: Social concealment, mobility and engagement with public space by the super-rich in London by Rowland Atkinson in the Environment and Planning journal.", "\n\nAbout the Author\n\nRowland Atkinson is Professor and Research Chair in Inclusive Society at the University of Sheffield. ", "He tweets from @qurbanist." ]

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[ "Q:\n\nHow can I make NetworkManager assign specific addresses and names to machines that connect via \"Shared to other computers\"?", "\n\nIt appears as if, in Ubuntu 10.10, NetworkManger uses dnsmasq to implement the \"Shared to other computers\" method. ", " This is work fairly well for me, but I want the machines that connect to get specific IPs and names. ", " I would have thought this would be as simple as creating the /etc/dnsmasq.conf file with a bunch of dhcp-host lines in it, but NetworkManager seems to be using a custom configuration (/tmp/randomfilename.conf) instead of the one in /etc. ", " Is there some way to edit the config file NetworkManger uses, or is there some way in the GUI to do what I want?", "\n\nA:\n\nThere is no way unfortunately. ", "The settings are currently hard-coded in NetworkManager; since they need to match at multiple different levels (the dnsmasq configuration needs to match with the generated iptables rules for connection sharing to work, since it relies on NAT and IP forwarding).", "\nNote that the file generated in /tmp/ has never contained any data, and won't; it's an empty file that used to be passed to avoid using other configuration files for dnsmasq, since they'd interfere with setting up connection sharing.", "\n\n" ]

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[ "Q:\n\nWhy does using the identity $e^x=1/e^{-x}$ work better in evaluating negative numbers in the finite taylor series expansion of $e^(x)$\n\nWas in class where we look at both and notice that there is a difference in the error, but we didn't go into why. ", "The other method used the taylor expansion\n$$e^x=1+x+\\frac{x^2}{2!}+\\frac{x^3}{3!}+...$$\nWhy does using the identity $$e^x=\\frac{1}{e^{-x}}$$ work better for negative numbers?", "\nTo try and clear up what I'm asking, we coded a program to graph the error of the taylor series expansion of $e^x$ to n terms. ", "We then coded another one to use the identity mentioned above in the expansion and noticed that it worked better for negative numbers, why is that the case?", "\nFor comparison, we were comparing the the absolute fractional error of the sums $$\\frac{T(x,N)-e^x}{e^x}$$\nfor each method (with the identity and without). ", "Where $T(x,N)$ is the N-th order taylor series expansion of $e^x$. We plotted the error against the order of expansion (number of terms considered in the sum). ", "We evaluated various numbers, and saw that without using the identity, the error was higher for negative numbers. ", "\n\nA:\n\nIntuitive answer: when we sum the series for positive up to $x^n/n!$, the order of absolute error margin is roughly the module of the next term $|x^{n+1}/(n+1)!|$ of the series, because each next term is much less then the previous for large enough $n$. So for $e^{-x}$ and $e^x$ the absolute error margin is roughly the same if we add up to the $n$th term, because these modules coincide for opposite numbers. ", "However, for $x<0$ $e^x<e^{-x}$, and so the relative error margin is much higher for $e^x$, than for $e^{-x}$. However, if we calculate $e^x$ as $1/e^{-x}$ than the relative margin is the same as of $e^{-x}$, and thus is better.", "\n\n" ]

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[ "A parent has cancer: needs and responses of children.", "\nChildren who have a parent with cancer experience many changes, threats, and challenges that may engender many different thoughts, feelings, and responses. ", "Sometimes the needs and reactions of these children may go unrecognized by their overstressed family members and they may feel alone and unsupported. ", "Pediatric nurses in primary care settings are often in key positions to identify and assist well children in dealing with the stresses of having a seriously ill parent and to assist the parents in helping their children. ", "Primary and secondary prevention and intervention strategies may be used by the nurse in working with families prior to and during major life events such as a parent's diagnosis of and treatment for cancer." ]

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[ "Citation {#SECID0EUDAC}\n========\n\nBernardes M, Le MD, Nguyen TQ, Pham CT, Pham AV, Nguyen TT, Rödder D, Bonkowski M, Ziegler T (2020) Integrative taxonomy reveals three new taxa within the *Tylototriton asperrimus* complex (Caudata, Salamandridae) from Vietnam. ", "ZooKeys 935: 121--164. [", "https://doi.org/10.3897/zookeys.935.37138](10.3897/zookeys.935.37138)\n\nIntroduction {#SECID0EUEAC}\n============\n\n*Tylototriton asperrimus* Unterstein, 1930 was the second salamander species within the genus described after *T. verrucosus*. ", "It was considered a common species due to its relatively wide distribution from central and southern China to northern Vietnam (Bain and Nguyen 2004; [@B61]; [@B56]; [@B30]; [@B53]; [@B41]). ", "The increasing amount of field work conducted in these regions, combined with the incorporation of new technologies in taxonomic analyses (e.g., molecular studies, X-ray scans), has since resulted in a vast increase of knowledge on the taxonomy of this genus, turning it into the most speciose genus within the Salamandridae (Fig. [", "1](#F1){ref-type=\"fig\"}).", "\n\n![", "Current distribution map of the genus *Tylototriton*, from South and Central China, to northern Vietnam, Laos, Thailand, Myanmar, India, Bhutan and Nepal ([@B14]; [@B40]; [@B12]; [@B60]; [@B13]; [@B17]; [@B65]). ", "In red the distribution areas belonging to the subgenus Tylototriton, and in blue the distribution areas belonging to the sub--genus *Yaotriton* ([@B8]). ", "The numerical identification corresponds to the different species and undescribed taxa as follow: **1***T. himalayanus***2**T. cf. ", "himalayanus (Bhutan) **3**T. cf. ", "verrucosus (Manipur) **4***T. kachinorum***5***T. verrucosus***6***T. ngarsuensis***7***T. shanorum***8***T. shanjing***9***T. pseudoverrucosus***10***T. taliangensis***11***T. kweichowensis***12***T. yangi***13***T. pulcherrimus***14***T. anguliceps***15***T. uyenoi***16***T. podichthys***17***T. panhai***18***T. notialis***19***Tylototriton* taxon 2, this study **20***Tylototriton* taxon 3, this study **21***T. ziegleri***22***T. vietnamensis***23***T. hainanensis***24**T. cf. ", "hainanensis (Baise) **25**T. cf. ", "wenxianensis (Libo) **26**T. cf. ", "wenxianensis (Guizhou) **27***T. asperrimus***28**T. cf. ", "asperrimus (Guangdong) **29***T. lizhengchangi***30***T. liuyangensis***31***T. broadoridgus***32**T. cf. ", "wenxianensis (Chongquing and Hubei) **33***T. wenxianensis***34***T. dabienicus***35***T. anhuiensis* and **36***T. panwaensis*.](zookeys-935-121-g001){#F1}\n\nThe widely distributed taxon has been revealed to consist of several different species with smaller ranges, and accordingly with a more critical conservation status. ", "For example *T. vietnamensis*, recorded from Bac Giang, Quang Ninh, and Lang Son provinces, Vietnam ([@B2]), currently listed as Endangered (IUCN SSC ASG 2016), *T. ziegleri* from Ha Giang and Cao Bang provinces, Vietnam ([@B32]) and Yunnan Province, China ([@B22]), listed as Vulnerable (IUCN SSC ASG 2017), *T. broadoridgus*, known from Hunan, China ([@B47]) and *T. anhuiensis*, known from Anhui, China ([@B40]), both not yet assessed were some of the species recently described within the *T. asperrimus* species complex.", "\n\nHowever, the taxonomic assignments of some populations of *T. asperrimus* have not been completely resolved. ", "The population from Thuong Tien District, Hoa Binh Province, Vietnam, was identified as *T. asperrimus* due to low genetic differences in partial mitochondrial ([@B63]; [@B32]) and partial nuclear genes ([@B60]) compared with the Chinese population. ", "Nonetheless, other authors regarded this population as an undescribed species, T. cf. ", "asperrimus, based on genetic differentiation, including complete mitochondrial sequence data ([@B37]; [@B14]). ", "Taxonomic decisions, however, should at best not be based on genetic variation alone, but also be accompanied by other evidence, such as morphological and/or ecological differences. ", "Given the high degree of morphological conservatism within the genus *Tylototriton*, identifying phenotypic divergence can be especially challenging ([@B52]; [@B32]), but nonetheless crucial due to its repercussions on species delimitations.", "\n\nIn order to further understand the taxonomy of species within the *T. asperrimus* complex in Vietnam, we examined specimens of the population from Hoa Binh Province and other newly collected specimens from the region, and compared them with the holotype of *T. asperrimus* from Guangxi, China. ", "We combined molecular and detailed morphological analyses to infer the taxonomic status and phylogenetic relationships among these populations. ", "As a consequence, we herein describe three new taxa of the *T. asperrimus* complex from northern Vietnam.", "\n\nMaterials and methods {#SECID0EENAE}\n=====================\n\nSampling {#SECID0EINAE}\n--------\n\nField surveys were conducted in northern Vietnam by: 1) A. V. Pham and M. A. Vang in Sa De Phin Commune, Sin Ho District, Lai Chau Province in May 2015, and in Xuan Nha Nature Reserve, Van Ho District, Son La Province on 15 June 2016; 2) H. N. Ngo et al. ", "in Phu Canh Nature Reserve, Da Bac District, Hoa Binh Province on 11 June 2016; 3) T. D. Le et al. ", "in Xuan Son National Park, Du Village, Xuan Son Commune, Tan Son District, Phu Tho Province on 7 July 2016; and 4) T. S. Nguyen in Xuan Lien Nature Reserve, Bat Mot Commune, Thuong Xuan District, Thanh Hoa Province in July 2015 (Fig. [", "2](#F2){ref-type=\"fig\"}).", "\n\n![", "Distribution map of the new populations of *Tylototriton* from North Vietnam, based on the following symbols: **square** (taxon 3, this study) the population from Sin Ho District, Lai Chau Province; **diamond** (taxon 1, this study) the upper one identifies the population from Van Ho District, Son La Province, and the lower one identifies the population from Thuong Xuan District, Thanh Hoa Province; **triangle** (taxon 2, this study) the upper one identifies the population from Tan Son District, Phu Tho Province, the middle one identifies the population from Da Bac District, Hoa Binh Province, and the lower one identifies the population from Lac Son District, Hoa Binh Province. ", "The two populations identified by the **circles** represent *T. asperrimus* sensu stricto from China. ", "High resolution remote sensing land cover information was extracted from \"GLAD-UMD and SERVIR-Mekong, Natural annual tree canopy structure and surface water dynamics products, 2017\" (lower left panel). ", "Bioclimatic variables (right side) were extracted from remote sensing data provided by [@B5].](zookeys-935-121-g002){#F2}\n\nSpecimens were anaesthetized and euthanized in a closed vessel with a piece of cotton wool containing ethyl acetate ([@B48]), fixed in 80% ethanol for five hours, and subsequently transferred to 70% ethanol for permanent storage. ", "Tissue samples were preserved separately in 70% ethanol prior to fixation. ", "Specimens were subsequently deposited in the collections of the Institute of Ecology and Biological Research (**IEBR**), Hanoi, the Tay Bac University (**TBU**), Son La Province, Vietnam, and the Zoologisches Forschungsmuseum Alexander Koenig (**ZFMK**), Bonn Germany.", "\n\nMolecular analyses {#SECID0EBQAE}\n------------------\n\nTissue samples from muscle of preserved specimens were extracted using the DNeasy blood and tissue kit, Qiagen (California, USA). ", "A fragment of a mitochondrial gene, the NADH dehydrogenase subunit 2 (ND2), was amplified by PCR mastermix (Fermentas, Burlington, ON, Canada) using the primer pair, Sal_Nd2_F1 (5'- AAGCTTTTGGGCCCATACC-3') ([@B32]) and a newly design primer TyloR1 (5'- GGTCTTTGGTCTYATTATCCTAA -3'). ", "The PCR volume consisted of 21 μl (10 μl of mastermix, 5 μl of water, 2 μl of each primer at 10 pmol/μl and 2 μl of DNA or higher depending on the quantity of DNA in the final extraction solution). ", "The following temperature profile for PCR was used: 95 °C for 5 minutes to activate the taq; with 40 cycles at 95 °C for 30 s, 58 °C for 45 s, 72 °C for 60 s; and the final extension at 72 °C for 6 minutes. ", "PCR products were subjected to electrophoresis through a 1 % agarose gel (UltraPure™, Invitrogen, La Jolla, CA). ", "Gels were stained for 10 min in 1 X TBE buffer with 2 pg/ml ethidium-bromide and visualized under UV light. ", "Successful amplifications were purified to eliminate PCR components using a GeneJET™ PCR Purification kit (Fermentas). ", "Purified PCR products were sent to FirstBase Malaysia for sequencing. ", "We included 12 new samples from five populations distributed in north and north central Vietnam to another 21 known species' samples of *Tylototriton* (Table [1](#T1){ref-type=\"table\"}). ", "Additionally, five species were selected as outgroups: *Echinotriton andersoni*, *E. chinhaiensis*, *Lyciasalamandra atifi*, *Notophthalmus viridescens*, and *Pleurodeles waltl*, to root the tree ([@B40]; [@B60]).", "\n\n###### \n\nSamples of *Tylototriton* species used in the molecular analyses of this study. ", "Country label key: CH = China; L = Laos; VN = Vietnam.", "\n\n ---- ----------------------------- ---------------------------- ---------------------------------- ---------------------- ------------\n ID Species Voucher Locality Genbank no. ", " Source\n 1 *T. anhuiensis* AHU-16-EE-001 Yuexi, Anhui, CH [KY321388](KY321388) [@B40]\n 2 *T. asperrimus* lineage 1 CIB 70063 Longsheng, Guangxi, CH [KC147816](KC147816) [@B47]\n 3 *T. asperrimus* lineage 1 CIB 200807055 Jinxiu, Guangxi, CH [KC147815](KC147815) [@B47]\n 4 *T. asperrimus* lineage 2 CIB XZ20091201 Xinyi, Guangdong, CH [KY800876](KY800876) [@B60]\n 5 *T. broadoridgus* CIB 200085 Sangzhi, Hunan, CH [KC147814](KC147814) [@B47]\n 6 taxon 1 IEBR 4471 Van Ho, Son La, VN [MT210168](MT210168) This study\n 7 taxon 1 IEBR 4473 Van Ho, Son La, VN [MT210169](MT210169) This study\n 8 taxon 1 IEBR 4474 Van Ho, Son La, VN [MT210170](MT210170) This study\n 9 taxon 1 IEBR 4318 Thuong Xuan, Thanh Hoa, VN [MT210171](MT210171) This study\n 10 taxon 1 IEBR 4319 Thuong Xuan, Thanh Hoa, VN [MT210172](MT210172) This study\n 11 taxon 2 IEBR 4320 Tan Son, Phu Tho, VN [MT210164](MT210164) This study\n 12 taxon 2 IEBR 4321 Tan Son, Phu Tho, VN [MT210165](MT210165) This study\n 13 taxon 2 IEBR 4466 Da Bac, Hoa Binh VN [MT201166](MT201166) This study\n 14 taxon 2 IEBR 4467 Da Bac, Hoa Binh VN [MT210167](MT210167) This study\n 15 taxon 2 VNMN TAO1214 / VFUA.2009.8 Xuan Lien, Lac Son, Hoa Binh, VN [AB769531](AB769531) [@B32]\n 16 *T. dabienicus* lineage 1 HNNU10042015 Shangcheng, Anhui, CH [KC147811](KC147811) [@B32]\n 17 *T. dabienicus* lineage 2 CIB 08042905-2 Yuexi, Anhui, CH [KY800853](KY800853) [@B60]\n 18 *T. hainanensis* CIB 20081048 Diaoluoshan, Hainan, CH [KC147817](KC147817) [@B32]\n 19 *T. liuyangensis* CSUFT20100108 Liuyang, Hunan, CH [KJ205598](KJ205598) [@B62]\n 20 *T. lizhengchangi* KUHE 42317 Yizhang, Hunan, CH [AB769533](AB769533) [@B32]\n 21 *T. notialis* VNMN TAO1235 Pu Hoat, Nghe An, VN [AB769536](AB769536) [@B32]\n 22 *T. panhai* NUOL 00437 Botene, Xaignabouli, L [KT304306](KT304306) [@B37]\n 23 taxon 3 IEBR 4477 Sin Ho, Lai Chau, VN [MT210167](MT210167) This study\n 24 taxon 3 IEBR 4476 Sin Ho, Lai Chau, VN [MT210162](MT210162) This study\n 25 *T. taliangensis* KUHE 43361 Pet Trade [AB769543](AB769543) [@B32]\n 26 *T. verrucosus* KIZ 201306058 Husa, Yunnan, CH [AB922820](AB922820) [@B33]\n 27 *T. vietnamensis* KUHE 55172 Yen Tu, Bac Giang, VN [AB769538](AB769538) [@B32]\n 28 *T. vietnamensis* IEBR A.2014.43 Hoanh Bo, Quang Ninh, VN [KX609961](KX609961) [@B2]\n 29 *T. vietnamensis* IEBR A.2014.45 Loc Binh, Lang Son, VN [KX609963](KX609963) [@B2]\n 30 *T. wenxianensis* lineage 1 CIB 20090527 Wenxian, Gansu, CH [KC147813](KC147813) [@B32]\n 31 *T. wenxianensis* lineage 2 CIB Wg20090730001 Libo, Guizhou, CH [KY800842](KY800842) [@B60]\n 32 *T. wenxianensis* lineage 3 CIB WH10003 Wufeng, Hubei, CH [KY800865](KY800865) [@B60]\n 33 *T. ziegleri* VNMN 3390 Quan Ba, Ha Giang, VN [AB769539](AB769539) [@B32]\n ---- ----------------------------- ---------------------------- ---------------------------------- ---------------------- ------------\n\nThe sequences were aligned in Clustal X v2 ([@B55]) with default settings. ", "Data were analyzed using maximum parsimony (MP) and maximum likelihood (ML) as implemented in PAUP 4.0b10 (Swofford 2001), and Bayesian analysis in MrBayes 3.2 ([@B43]). ", "For MP analysis, heuristic analysis was conducted with 100 random taxon addition replicates using tree-bisection and reconnection (TBR) branch swapping algorithm, with no upper limit set for the maximum number of trees saved. ", "Bootstrap support (BP) ([@B10]) was calculated using 1,000 pseudo-replicates and 100 random taxon addition replicates. ", "All characters were equally weighted and unordered. ", "For ML analysis, we used the optimal evolution model as selected by ModelTest v3.7 ([@B39]). ", "To estimate BP in the ML analysis, a simple taxon addition option and 100 pseudo-replicates were employed. ", "We considered BP values of ≥ 70 % to represent strong support ([@B18]).", "\n\nFor Bayesian analyses, we used the optimal model, GTR+I+G as selected by Modeltest v3.7, for ML and combined Bayesian analyses. ", "Two simultaneous analyses with four Markov chains (one cold and three heated) were run for 10 million generations with a random starting tree and sampled every 1,000 generations. ", "Log-likelihood scores of sample points were plotted against generation time to determine stationarity of Markov chains. ", "The cutoff point for the burn-in function was set to 21, equivalent to 21,000 generations, in the Bayesian analysis, as -lnL scores reached stationarity after 21,000 generations in both runs. ", "Nodal support was evaluated using Bootstrap in PAUP and posterior probability in MrBayes v3.2. ", "Uncorrected pairwise divergences were calculated in PAUP\\*4.0b10.", "\n\nWe selected the relaxed-clock method ([@B6]) to estimate divergence times. ", "The obtained dataset was used as input for the computer program BEAST v1.8.0 ([@B7]). *", "A priori* criteria for the analysis were set in the program BEAUti v1.8.0. ", "One calibration point, the split between the clade containing *Tylototriton vietnamensis* + *T. panhai* and the clade consisting of *T. asperrimus* and other related species, estimated for 12.4 ± 2.3 million years ago (MYA) ([@B60]), was used to calibrate the phylogeny. ", "A general time-reversible (GTR) model using gamma + invariant sites with four gamma categories was employed along with the assumption of a relaxed molecular clock. ", "As for the priors, we used all default settings, except for the Tree Prior category that was set to Yule Process, as recommended for species-level analyses. ", "The codon-partitioned dataset was used for a single run. ", "In addition, a random tree was employed as a starting tree. ", "The length chain was set to 10^7^, and the Markov chain was sampled every 1,000 generations. ", "After the dataset with the above settings was analyzed in BEAST, the resulting likelihood profile was then examined by the program Tracer v1.6 to determine the burn-in cutoff point. ", "The final tree with calibration estimates was computed using the program TreeAnnotator v1.8.0 as recommended in the BEAST program manual.", "\n\nMorphological examination {#SECID0ELZAG}\n-------------------------\n\nAll specimens were sexed by evaluating the size of the opening of the cloacal fissure: females show a puncture-like opening and males a wider slit-like opening. ", "The holotype of *T. asperrimus* (ZMB 34089), collected from Guangxi Province, China, was loaned from the Zoologisches Museum Berlin (Museum für Naturkunde Berlin) and evaluated as a female (Fig. [", "3](#F3){ref-type=\"fig\"}). ", "In addition we investigated two other Vietnamese female specimens, one from IEBR: JJLR01195 from Pu Hoat Nature Reserve, Nghe An Province (*T. notialis*) and another from the Vietnam Forestry University (VFU) in Hanoi: VFUA.2009.8 (also known as voucher Tao1214 in [@B32]) from Thuong Tien Nature Reserve, Hoa Binh Province (T. cf. ", "asperrimus). ", "Morphological comparisons were only performed among animals of the same sex, and only males had a sufficiently large number of specimens (*N*) to perform statistical analysis.", "\n\n{#F3}\n\nA total of 23 morphological characters were measured following [@B2] to the nearest 0.01 mm with a digital caliper as follows: snout-vent length (**SVL**); head length (**HL**); head width (**HW**) measured behind the eyes and before the beginning of the parotoids; maximum head width (**MHW**); parotoid width (**PW**); maximum parotoid height (**PH**); eye length (**EL**); inter-eye distance (**IE**); inter-narial distance (**IN**); eye-narial distance (**EN**); lower jaw length (**LJL**) from tip of lower jaw to jaw angle; maximum upper eyelid length (**UEL**); humerus length (**HUM**); radius length (**RAD**); femur length (**FEM**); tibia length (**TIB**); axilla to groin (**AG**); trunk length (**TkL**) from wrinkle of throat to anterior tip of vent; length of the 5^th^ anterior dorsal nodule (**L5N**); width of vertebral cord (**WVr**) measured at the height of the 5^th^ nodule; cloaca length (**ClL**) length of cloaca muscle; tail length (**TL**); tail height (**TH**). ", "The following ratios were calculated based on the measures above: total forelimb length (**FORE**); total hindlimb length (**HIND**); hind-limb to forelimb lengths (**HIND/FORE**); the relative length of radius to humerus (**RAD/HUM**); tibia to femur (**TIB/FEM**); and tail length to tail height (**TL/TH**).", "\n\nThe morphological comparison between the new taxa and their congeners were based on the specimen examination and the following literature: [@B9], [@B4], [@B52], [@B47], [@B31], [@B32], and [@B62]. ", "When measurements were involved, only the ones taken in similar ways were found suitable for comparison and used as reference.", "\n\nStatistical analysis {#SECID0E5BBG}\n--------------------\n\nWe first compared the morphological characters of males between the two clades originating on both sides of the Da River: the western clade from Son La and Thanh Hoa provinces (referred to as taxon 1) and the eastern clade from Hoa Binh and Phu Tho provinces (referred to as taxon 2; for reference see Fig. [", "2](#F2){ref-type=\"fig\"}). ", "Subsequently we compared the above-mentioned males (jointly referred to as T. cf. ", "asperrimus) and the males originating from Lai Chau Province (referred to as taxon 3).", "\n\nThe statistical analyses had to be conducted on different subsets of morphological characters according to data availability. ", "Morphological characters that could not be obtained for all the species had to be excluded from the overall analysis. ", "These included: PW, PH, EL, IE, UEL, AG, and ClL. Whether the measured morphological characters showed a linear increase with body size was analyzed through correlation analyses (see Suppl. ", "material [1](#S1){ref-type=\"supplementary-material\"}). ", "Accordingly, measurements of morphological characters and character ratios were standardized by SVL (R\\[character\\]: % SVL) to exclude the effect of body size, and log-transformed. ", "A Principal Component Analysis (PCA) was tested by a one-way Analysis of Variance (ANOVA) between populations. ", "Because morphological traits within individuals are not independent of each other, comparisons between different morphological traits of species were based on Multivariate Analysis of Variance (MANOVA) and proceeding to ANOVA and Tukey HSD test only if the MANOVA yielded a significant result (i.e., 'protected ANOVA' ([@B58]). ", "Roy's Greatest Root was chosen as test of significant differences among groups in the MANOVA procedure.", "\n\nSignificance levels were set to 95 %. ", "All statistical analyses were performed in R v 3.1.2, the vegan package was used to calculate PCA ([@B35]).", "\n\nMacroclimatic information {#SECID0EJEBG}\n-------------------------\n\nClimatic information at the sample sites were extracted from remote sensing data ([@B5]). ", "Representing averages across last decades with a spatial resolution of 0.1°, the following bioclimatic variables were available: Annual Mean Temperature BIO1, Mean Diurnal Range BIO2, Isothermality BIO3, Temperature Seasonality BIO4, Max Temperature of Warmest Month BIO5, Min Temperature of Coldest Month BIO6, Temperature Annual Range BIO7, Mean Temperature of Wettest Quarter BIO8, Mean Temperature of Driest Quarter BIO9, Mean Temperature of Warmest Quarter BIO10, Mean Temperature of Coldest Quarter BIO11, Annual Precipitation BIO12, Precipitation of Wettest Month BIO13, Precipitation of Driest Month BIO14, Precipitation Seasonality BIO15, Precipitation of Wettest Quarter BIO16, Precipitation of Driest Quarter BIO17, Precipitation of Warmest Quarter BIO18, and Precipitation of Coldest Quarter BIO19.", "\n\nResults {#SECID0ETEBG}\n=======\n\nMolecular analyses {#SECID0EXEBG}\n------------------\n\nThe combined matrix contained 1036 aligned characters. ", "Of those, 370 were parsimony informative. ", "MP analysis of the dataset recovered 2 most parsimonious trees with 1400 steps (CI = 0.54; RI = 0.65). ", "Our phylogenetic analyses recovered the Vietnamese T. cf. ", "asperrimus as a sister taxon to *T. asperrimus* from China with strong support values from all analyses (MP~BP~ = 90, ML~BP~ = 88, PP = 100) (Fig. [", "4](#F4){ref-type=\"fig\"}). ", "The genetic differences between Vietnamese populations and the Chinese lineage were 3.3 to 3.6 % for the population from Son La Province; 3.2 to 3.4 % for the population from Thanh Hoa Province; 3.3 to 3.6 % for the population from Phu Tho Province; 3.2 to 3.6 % for the population from Da Bac District, Hoa Binh Province; and 3.4 to 3.5 % for the population from Lac Son District, Hoa Binh Province, respectively (Table [2](#T2){ref-type=\"table\"}).", "\n\n is from [@B32].](zookeys-935-121-g004){#F4}\n\n###### \n\nUncorrected p-distances of the mitochondrial DNA sequences used in this study for members of the *Tylototriton asperrimus* species complex.", "\n\n ---- ------------------------ ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ----\n ID Taxon--Locality 1 2 3 4 5 6 7 8 9 10 11 12 13 14\n 1 *T. asperrimus*--China -- \n 2 *T. asperrimus*--China 0.001 -- \n 3 taxon 1--Son La 0.034 0.034 -- \n 4 taxon 1--Son La 0.036 0.035 0.001 -- \n 5 taxon 1--Thanh Hoa 0.034 0.033 0.005 0.006 -- \n 6 taxon 1--Son La 0.034 0.033 0.004 0.005 0.005 -- \n 7 taxon 1--Thanh Hoa 0.033 0.032 0.005 0.006 0.000 0.005 -- \n 8 taxon 2--Phu Tho 0.034 0.033 0.029 0.030 0.028 0.029 0.028 -- \n 9 taxon 2--Phu Tho 0.036 0.035 0.030 0.031 0.029 0.030 0.029 0.001 -- \n 10 taxon 2--Hoa Binh 0.036 0.034 0.030 0.030 0.028 0.029 0.028 0.002 0.003 -- \n 11 taxon 2--Hoa Binh 0.033 0.032 0.026 0.027 0.025 0.026 0.025 0.005 0.006 0.005 -- \n 12 taxon 2--Hoa Binh 0.035 0.034 0.029 0.031 0.029 0.029 0.028 0.007 0.008 0.007 0.002 -- \n 13 taxon 3--Lai Chau 0.042 0.041 0.039 0.040 0.038 0.039 0.038 0.044 0.045 0.044 0.041 0.044 -- \n 14 taxon 3--Lai Chau 0.041 0.041 0.039 0.040 0.036 0.039 0.036 0.044 0.045 0.044 0.041 0.044 0.002 --\n ---- ------------------------ ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ------- ----\n\nFurthermore, our genetic analyses identified different lineages within the Vietnamese clade of T. cf. ", "asperrimus. ", "The genetic variation between taxon 1 and taxon 2 varied between 2.5 % (between Thanh Hoa and Hoa Binh populations) and 3.1 % (between Son La and Phu Tho populations). ", "In contrast, within-population differences were only 0.0 to 0.6 % in taxon 1 and 0.1 to 0.9 % in taxon 2.", "\n\nThe population from Lai Chau Province turned out to be a distinct and basal lineage within a weakly supported clade, including *T. notialis*, *T. asperrimus* from China, and taxon 1 and taxon 2 from Vietnam (Fig. [", "4](#F4){ref-type=\"fig\"}). ", "In this case the genetic differences of taxon 3 to the topotypical population of *T. asperrimus* ranged between 4.1 to 4.2 % to taxon 1 between 3.6 to 4.0 %, and to taxon 2 between 4.1 to 4.5 % (see Table [2](#T2){ref-type=\"table\"} for genetic distances). ", "Our time estimates are very similar to those generated by [@B60], and the results show that *T. asperrimus* from China split from taxon 1 about 2.5 MYA (95% highest posterior densities -- 95% HPD = 1.4--3.7), while taxon 3 diverged from the two taxa approximately 3.4 MYA (95% HPD = 2.3--4.8) (see Suppl. ", "material [2](#S2){ref-type=\"supplementary-material\"}).", "\n\nMorphological examination {#SECID0EPCAI}\n-------------------------\n\nVietnamese species compared to the Chinese holotype\n\nThis comparison was only based on three female specimens: the holotype of *T. asperrimus*, one from Hoa Binh Province (taxon 2), and one from Nghe An Province (*T. notialis*) (Table [3](#T3){ref-type=\"table\"}). ", "Due to the lack of replicates it was not possible to perform statistical analyses between the Chinese and the Vietnamese clades. ", "After correcting the absolute measures to ratios of snout-vent length, the most prominent differences between the female of taxon 2 and the female holotype of *T. asperrimus* from China were: a wider and longer head (MHW = 28.99, HL = 29.15 in taxon 2 vs. MHW = 25.35, HL = 26.60 in *T. asperrimus*), a longer lower jaw (LJL = 17.40 in taxon 2 vs. 14.85 in *T. asperrimus*), and higher values for most of the measured head features (including the distance between the eyes) for taxon 2. ", "The exceptions were found in the distance between eye and nostril (EN = 6.37 in *T. asperrimus* vs. 4.86 in taxon 2) and head width (HW = 18.54 in *T. asperrimus* vs. 13.67 in taxon 2) which in these cases the values were higher in *T. asperrimus*. ", "The female from taxon 2 also had higher values for tail length (TL = 85.62 in taxon 2 vs. 77.28 in *T. asperrimus*), cloacal muscles (ClL = 11.39, ClW = 7.63 in taxon 2 vs. ClL = 7.01, ClW = 3.65 in *T. asperrimus*), and vertebra width (WVr = 4.46 in taxon 2 vs. 2.80 in *T. asperrimus*). ", "The female from China had a longer trunk length (TkL = 74.58 in *T. asperrimus* vs. 69.67 in taxon 2). ", "The female from Nghe An Province differed by having the smallest eye length, the shortest distance between both eyes, the smallest glandular warts and by having the longest limbs, while other measurements did not separate it from other lineages.", "\n\n###### \n\nMorphological comparisons between the available females. ", "Measures as absolute values (in mm) and ratios of characters to snout vent length (% SVL) between *Tylototriton asperrimus* holotype from China (ZMB 34089), T. cf. ", "asperrimus from Thuong Tien Nature Reserve, Hoa Binh Province, Vietnam (taxon 2) (VFUA.2009.8), and *T. notialis* (JJLR01195) from Pu Hoat Nature Reserve, Nghe An Province, Vietnam. ", "For abbreviations see Materials and methods.", "\n\n --------------- ------------------- --------------- --------------- ----------------- --------- ---------------\n Character Absolute measures Ratios to SVL \n *T. asperrimus* taxon 2 *T. notialis* *T. asperrimus* taxon 2 *T. notialis*\n **SVL** 73.45 76.82 76.16 -- -- --\n **MHW** 18.62 22.27 19.64 25.35 28.99 25.79\n **HW** 13.62 10.50 -- 18.54 13.67 --\n **HL** 19.54 22.39 20.86 26.60 29.15 27.39\n **PL** 10.74 13.03 12.78 14.62 16.96 16.78\n **PH** 5.78 7.45 7.54 7.87 9.70 9.90\n **EL** 3.17 3.86 2.94 4.32 5.02 3.86\n **EN** 4.68 3.73 3.79 6.37 4.86 4.98\n **IN** 5.78 7.37 6.46 7.87 9.59 8.48\n **IE** 9.40 10.13 9.11 12.80 13.19 11.96\n **LJL** 10.91 13.37 -- 14.85 17.40 --\n **UEL** 4.27 5.06 -- 5.81 6.59 --\n **HUM** 8.98 7.91 8.63 12.23 10.30 11.33\n **RAD** 16.04 16.88 18.11 21.84 21.97 23.78\n **FEM** 7.17 7.69 9.89 9.76 10.01 12.99\n **TIB** 17.07 18.29 18.37 23.24 23.81 24.12\n **FORE** 25.02 24.79 26.74 34.06 32.27 35.11\n **HIND** 24.24 25.98 28.26 33.00 33.82 37.11\n **HIND.FORE** 0.97 1.05 1.06 1.32 1.36 1.39\n **RAD.HUM** 1.79 2.13 2.10 2.43 2.78 2.76\n **TIB.FEM** 2.38 2.38 1.86 3.24 3.10 2.44\n **TL** 56.76 65.77 65.14 77.28 85.62 85.53\n **TH** 7.87 9.44 9.39 10.71 12.29 12.33\n **TL.TH** 7.21 6.97 6.94 9.82 9.07 9.11\n **ClL** 5.15 8.75 5.87 7.01 11.39 7.71\n **ClW** 2.68 5.86 5.25 3.65 7.63 6.89\n **WVr** 2.06 3.43 2.49 2.80 4.46 3.27\n **L5W** 2.39 2.66 2.29 3.25 3.46 3.01\n **AG** 37.12 37.56 -- 50.54 48.89 --\n **TkL** 54.78 53.52 -- 74.58 69.67 --\n --------------- ------------------- --------------- --------------- ----------------- --------- ---------------\n\nComparisons within T. cf. ", "asperrimus from Vietnam\n\nThe comparison between taxon 1 and taxon 2 included only males. ", "Absolute measures and ratios of species' morphological traits corrected by snout vent length are shown in Table [4](#T4){ref-type=\"table\"}. ", "Taxon 1 and taxon 2 did not differ in their respective SVL (*t*-test = -1.55, DF = 18, *p* = 0.14). ", "Taxon 1 presented wider head than taxon 2 (MHW = 27.37 ± 1.67, HW = 19.86 ± 0.95 for taxon 1 vs. MHW = 25.11 ± 0.81, HW = 18.75 ± 0.99 taxon 2). ", "The ratios of EN and IN also differed between lineages, with taxon 1 having a relatively longer snout (EN = 6.16 ± 0.68) than taxon 2 (5.50 ± 0.37) and taxon 2 having a wider snout (IN = 8.58 ± 0.57) than taxon 1 (7.94 ± 0.85). ", "Taxon 2 showed the highest variation range in limb data. ", "The ratio of FEM was longer in taxon 2 (12.59 ± 0.78) than in taxon 1 (10.99 ± 0.67), as well as the ratio of TIB (23.69 ± 2.35 in taxon 2 vs. 22.41 ± 0.61 in taxon 1), which together also resulted in longer hind limbs (HIND = 36.28 ± 2.89 in taxon 2 vs. 33.40 ± 0.99 in taxon 1). ", "The ratio of the fore-limbs on the other hand was alike between lineages. ", "Although taxon 2 presented lower minimum values for both RAD (18.80) and HUM (9.30) than in taxon 1 (RAD = 20.08 and HUM = 11.04). ", "The tail in taxon 1 was longer (87.06 ± 5.25) and less high (11.79 ± 1.14) than in taxon 2 (TL = 84.61 ± 5.20, TH = 12.43 ± 2.46). ", "Taxon 1 showed longer trunk (70.28 ± 3.41) than taxon 2 (68.78 ± 1.24).", "\n\n###### \n\nMorphological measurements between the *Tylototriton* males from Son La and Thanh Hoa provinces (taxon 1), from Phu Tho and Hoa Binh provinces (taxon 2), and from Lai Chau Province (taxon 3). ", "Measures as absolute values (in mm) and ratios of characters to snout vent length (% SVL). ", "Values are presented as mean ± standard deviation above minimum and maximum ranges, and for abbreviations see Materials and methods.", "\n\n --------------- --------------- ------------------- --------------- --------------- --------------- -------------- -------------- -------------- --------------\n Character *N* Absolute measures Ratios to SVL \n taxon 1 taxon 2 taxon 3 taxon 1 taxon 2 taxon 3 \n **SVL** 10 11 5 64.98 ± 1.87 66.59 ± 2.81 65.14 ± 2.12 \n 62.00 --67.95 61.57 --70.69 63.20--68.71 \n **MHW** 10 11 5 17.78 ± 1.11 16.71 ± 0.64 17.12 ± 0.43 27.37 ± 1.67 25.11 ± 0.81 26.30 ± 0.86\n 16.00 --19.63 15.66 --17.90 16.68 --17.60 24.71 --29.91 24.11 --26.31 25.61 --27.75 \n **HW** 10 11 3 12.89 ± 0.48 12.47 ± 0.63 10.00 ± 0.53 19.86 ± 0.95 18.75 ± 0.99 15.29 ± 1.04\n 12.10 --13.70 10.98 --13.13 9.56 --10.59 18.44 --21.29 16.98 --20.45 14.34 --16.40 \n **HL** 10 11 5 18.67 ± 0.71 18.79 ± 0.89 18.71 ± 0.93 28.75 ± 1.16 28.23 ± 1.23 28.72 ± 0.75\n 17.24 --19.54 17.64 --20.39 17.42 --19.95 26.63 --30.32 25.41 --29.80 27.56 --29.62 \n **PL** 10 5 5 9.74 ± 0.80 9.64 ± 0.58 10.34 ± 0.43 14.99 ± 1.31 14.80 ± 0.46 15.88 ± 0.79\n 8.52 --10.92 8.79 --10.27 9.92 --11.02 13.02 --16.64 14.28 --15.48 14.82 --16.92 \n **PH** 10 5 5 5.70 ± 0.68 5.28 ± 0.73 5.77 ± 0.21 8.78 ± 1.10 8.10 ± 0.97 8.87 ± 0.18\n 4.77 --6.98 4.50 --6.11 5.58 --6.12 7.13 --10.81 7.01 --9.52 8.64 --9.15 \n **EL** 10 5 5 3.14 ± 0.24 3.24 ± 0.12 3.26 ± 0.23 4.84 ± 0.41 4.99 ± 0.32 5.01 ± 0.31\n 2.60 --3.40 3.06 --3.40 3.02 --3.49 3.89 --5.24 4.54 --5.31 4.68 --5.45 \n **EN** 10 11 5 4.00 ± 0.41 3.66 ± 0.25 4.40 ± 0.46 6.16 ± 0.68 5.50 ± 0.37 6.77 ± 0.78\n 3.43 --4.75 3.24 --4.11 3.74 --5.05 5.23 --7.19 4.75 --6.03 5.74 --7.88 \n **IN** 10 11 5 5.16 ± 0.60 5.71 ± 0.40 5.67 ± 0.54 7.94 ± 0.85 8.58 ± 0.57 8.70 ± 0.63\n 4.03 --5.97 5.17 --6.43 5.01 --6.26 6.13 --9.18 7.79 --9.88 7.93 --9.35 \n **IE** 10 5 5 8.56 ± 0.17 8.61 ± 0.48 8.78 ± 0.56 13.18 ± 0.37 13.22 ± 0.45 13.48 ± 0.73\n 8.24 --8.82 8.11 --9.17 8.00 --9.50 12.53 --13.67 12.64 --13.85 12.66 --14.58 \n **LJL** 10 11 3 11.20 ± 0.61 12.59 ± 1.76 10.66 ± 0.62 17.25 ± 1.05 18.88 ± 2.30 16.29 ± 0.98\n 10.20 --12.11 10.05 --14.73 10.00 --11.24 15.54 --18.88 14.22 --21.33 15.63 --17.41 \n **UEL** 10 5 3 4.59 ± 0.36 4.42 ± 0.33 4.80 ± 0.15 7.07 ± 0.65 6.79 ± 0.64 7.35 ± 0.49\n 4.00 --5.07 3.92 --4.83 4.70 --4.97 5.98 --7.95 6.11 --7.42 6.90--7.86 \n **HUM** 10 11 5 7.86 ± 0.40 7.98 ± 0.99 9.03 ± 0.98 12.11 ± 0.74 11.96 ± 1.15 13.89 ± 1.69\n 7.15 --8.61 5.97 --9.22 7.81 --10.47 11.04 --13.89 9.30 --13.54 11.99--16.57 \n **RAD** 10 11 5 14.01 ± 0.61 14.46 ± 1.13 14.20 ± 1.12 21.56 ± 0.72 21.72 ± 1.52 21.78 ± 1.21\n 13.21 --14.96 12.50 --15.96 12.71 --15.86 20.08 --22.42 18.80 --23.60 19.84--23.08 \n **FEM** 10 11 4 7.14 ± 0.39 8.40 ± 0.81 8.17 ± 0.79 10.99 ± 0.67 12.59 ± 0.78 12.44 ± 0.99\n 6.31 --7.54 7.08 --9.59 7.46 --8.93 9.67 --11.83 11.50 --13.97 11.65--13.71 \n **TIB** 10 11 4 14.57 ± 0.60 15.78 ± 1.77 15.29 ± 0.82 22.41 ± 0.61 23.69 ± 2.35 23.30 ± 0.86\n 13.73 --15.75 13.14 --17.91 14.25 --16.03 21.27 --23.19 18.59 --26.67 22.24--24.34 \n **FORE** 10 11 5 21.87 ± 0.62 22.44 ± 1.86 23.23 ± 1.54 33.67 ± 0.89 33.68 ± 2.11 35.67 ± 2.13\n 21.11 --23.08 19.48 --25.18 21.75 --25.13 32.43 --35.35 30.36 --36.97 33.88--38.94 \n **HIND** 10 11 4 21.70 ± 0.78 24.18 ± 2.41 23.46 ± 1.58 33.40 ± 0.99 36.28 ± 2.89 35.74 ± 1.78\n 20.34 --22.80 21.14 --27.06 21.71 --24.80 31.51 --34.96 30.98 --39.90 33.89--38.05 \n **HIND/FORE** 10 11 4 0.99 ± 0.03 1.08 ± 0.05 1.03 ± 0.06 1.53 ± 0.06 1.62 ± 0.09 1.57 ± 0.12\n 0.95 --1.03 0.99 --1.15 0.99 --1.12 1.44 --1.65 1.40 --1.71 1.44--1.72 \n **RAD/HUM** 10 11 5 1.79 ± 0.13 1.34 ± 0.54 1.59 ± 0.20 2.75 ± 0.20 2.03 ± 0.89 2.43 ± 0.27\n 1.55 --2.02 0.86 --2.26 1.35 --1.83 2.47 --3.12 1.26 --3.53 2.14--2.80 \n **TIB/FEM** 10 11 4 2.05 ± 0.13 1.88 ± 0.15 1.88 ± 0.10 3.15 ± 0.18 2.83 ± 0.30 2.87 ± 0.21\n 1.91 --2.32 1.50 --2.09 1.78 --2.00 2.90 --3.56 2.12 --3.40 2.66--3.10 \n **TL** 10 11 4 54.94 ± 3.02 57.96 ± 4.12 55.97 ± 2.81 84.61 ± 5.20 87.06 ± 5.25 85.92 ± 2.47\n 50.47 --60.71 53.64 --64.13 53.16 --59.70 77.37 --93.13 76.88 --94.16 82.34--88.00 \n **TH** 9 10 5 8.06 ± 1.67 7.87 ± 0.71 8.00 ± 0.64 12.43 ± 2.46 11.79 ± 1.14 12.28 ± 0.90\n 6.13 --11.34 6.69 --8.83 7.03 --8.57 9.47 --17.28 9.82 --13.76 10.97--13.10 \n **TL/TH** 9 10 4 7.06 ± 1.35 7.49 ± 1.04 6.97 ± 0.75 10.93 ± 2.22 11.22 ± 1.51 10.72 ± 1.23\n 4.80 --8.82 6.21 --9.59 6.31 --8.02 7.31 --13.62 8.79 --14.07 9.78--12.52 \n **ClL** 10 5 4 8.98 ± 0.96 9.41 ± 1.70 8.34 ± 0.93 13.82 ± 1.43 14.39 ± 1.91 12.78 ± 0.98\n 8.02 --10.96 8.13 --12.12 7.54 --9.66 12.39 --16.98 12.67 --17.15 11.68--14.06 \n **ClW** 10 5 0 5.06 ± 0.67 4.63 ± 0.66 7.79 ± 1.03 7.08 ± 0.61 \n 4.16 --5.91 4.09 --5.77 6.38 --9.06 6.64 --8.16 \n **WVr** 10 10 5 1.99 ± 0.23 1.93 ± 0.27 2.30 ± 0.17 3.06 ± 0.37 2.90 ± 0.37 3.53 ± 0.25\n 1.58 --2.30 1.43 --2.37 2.10 --2.52 2.44 --3.53 2.23 --3.43 3.32--3.90 \n **L5N** 10 11 5 1.73 ± 0.26 1.93 ± 0.24 2.17 ± 0.63 2.67 ± 0.39 2.91 ± 0.41 3.31 ± 0.87\n 1.41 --2.12 1.39 --2.31 1.44 --3.04 2.12 --3.21 2.02 --3.60 2.25--4.42 \n **AG** 10 5 5 30.28 ± 2.41 30.26 ± 4.05 30.56 ± 1.80 46.59 ± 3.42 46.31 ± 3.91 46.92 ± 2.47\n 26.26 --35.45 27.36 --37.20 27.97 --32.66 40.68 --54.01 42.64 --52.62 44.26--50.13 \n **TkL** 10 10 3 45.66 ± 2.43 45.81 ± 2.16 43.31 ± 1.58 70.28 ± 3.41 68.78 ± 1.24 66.22 ± 3.86\n 41.48 --50.25 42.19 --50.20 42.10 --45.10 64.26 --76.57 67.35 --71.01 62.17--69.86 \n --------------- --------------- ------------------- --------------- --------------- --------------- -------------- -------------- -------------- --------------\n\nThe statistical analysis was based on nine males of taxon 1 and ten males of taxon 2. ", "A PCA analysis resulted in six principal components (PC) explaining 87 % of the total variation. ", "The first two PCs accounted for 52 % of the variation. ", "The scatterplot between PC1 and PC2 showed a clear separation of the two clades, with only a small overlap area (Fig. [", "5A](#F5){ref-type=\"fig\"}).", "\n\nThe head related data (MANOVA: *F*~1,\\ 17~ = 11.75, DF = 6, *p* \\< 0.001), and the limb related data (MANOVA: *F*~1,\\ 17~ = 5.10, DF = 9, *p* = 0.01) were significantly different between the two lineages. ", "Tail and dorsal morphological traits were not significantly different (MANOVA: *F*~1,\\ 17~ = 1.42, DF = 6, *p* = 0.3). ", "Our results identified MHW, HW, EN, IN, RAD/HUM, FEM, TIB/FEM, HIND, and HIND/FORE as important traits separating both lineages (Table [5](#T5){ref-type=\"table\"}). ", "Taxon 1 has a wider head (both as MHW +8.3 %; and as HW +5.6 %) and a longer snout (EN +10.7 %). ", "Taxon 2 has a wider snout (IN +7.5 %) (Fig. [", "6](#F6){ref-type=\"fig\"}).", "\n\nRegarding the limb data, FEM was 12.7 % longer on taxon 2, as well as the overall hind-limb length (HIND +7.9 %) and the ratio of HIND to FORE (+5.6 %). ", "On the contrary, the ratios of tibia to femur (TIB/FEM +10.2 %) and radius to humerus (RAD/HUM +26.2 %) were larger in taxon 1 (Fig. [", "7](#F7){ref-type=\"fig\"}).", "\n\n{#F5}\n\n{#F6}\n\n{#F7}\n\n###### \n\nResults from the MANOVA of the log--transformed ratio of characters to SVL of males. ", "The variation was analyzed between the populations from Son La and Thanh Hoa provinces (taxon 1; *N* = 9) and the populations from Phu Tho and Hoa Binh provinces (taxon 2; *N* = 10), and between these (jointly referred to as Tylototriton cf. ", "asperrimus) and the population from Lai Chau Province (taxon 3; in the comparison based on head and dorsum related data: *N~T.~*~cf.~*~asperrimus~* = 19 and *N*~taxon3~ = 3; and in the comparison of limb related data, *N~T.~*~cf.~*~asperrimus~* = 21 and *N*~taxon3~ = 4). *", "F*: *F*--test; DF: degrees of freedom; *P*: *p*--value. ", "For abbreviations of characters see Materials and methods. ", "In **Bold** significant results.", "\n\n ----------- ------------------- ----------------------------- -------------- --------- ----- --------------\n taxon 1 × taxon 2 T. cf. ", "asperrimus × taxon 3 \n *F* DF *P* *F* DF *P* \n MHW 17.62 17 **\\< 0.001** 0.08 20 0.79\n HW 7.48 17 **0.01** 52.48 20 **\\< 0.001**\n EN 4.85 17 **0.04** 7.52 20 **0.01**\n HL 0.76 17 0.4 0.09 20 0.77\n IN 4.56 17 **0.05** 0.09 20 0.77\n LJL 2.51 17 0.13 2.22 20 0.15\n RAD/HUM 5.92 17 **0.03** 0.34 23 0.56\n FEM 21.13 17 **\\< 0.001** 1.10 23 0.30\n TIB/FEM 7.07 17 **0.02** 0.42 23 0.52\n HIND 7.47 17 **0.01** 0.43 23 0.52\n HIND/FORE 4.95 17 **0.04** 0.03 23 0.87\n HUM 0.14 17 0.72 4.66 23 **0.04**\n RAD 0.17 17 0.7 \\<0.001 23 0.98\n TIB 1.99 17 0.18 0.83 23 0.78\n FORE 0.01 17 0.91 1.87 23 0.19\n TL 1.10 17 0.31 0.07 20 0.79\n TH 0.35 17 0.56 0.71 20 0.41\n TL.TH 0.25 17 0.63 0.56 20 0.46\n L5N 0.84 17 0.37 12.43 20 **\\< 0.01**\n WVr 1.61 17 0.22 5.02 20 **0.04**\n TkL 0.90 17 0.36 3.74 20 0.07\n ----------- ------------------- ----------------------------- -------------- --------- ----- --------------\n\nComparison of taxon 3 from Lai Chau Province with taxon 1 and taxon 2\n\nThis analysis is only based on males. ", "Absolute measures and ratios of species' morphological traits corrected by snout vent length are shown in Table [4](#T4){ref-type=\"table\"}. ", "All three taxa had similar measures for SVL, TL, and TH. ", "The narrowest head was recorded in taxon 3 (HW 15.29 ± 1.04; 19.86 ± 0.95 in taxon 1; 18.75 ± 0.99 in taxon 2) and its maximum values were still below the minima recorded for taxon 1 and taxon 2 (max HW = 16.40 in taxon 3; min HW = 18.44 in taxon 1 and = 16.98 in taxon 2). ", "The snout length was longer in taxon 3 (EN 6.77 ± 0.78), than in taxon 1 (6.16 ± 0.68) or taxon 2 (5.50 ± 0.37). ", "HUM was longer in taxon 3 (13.89 ± 1.69) and showed a maximum range (11.99 to 16.57) not repeated in taxon 1 (11.04 to 13.89) nor in taxon 2 (9.30 to 13.54). ", "Consequently, the sizes of the fore-limbs were also longer in taxon 3 (35.67 ± 2.13, range = 33.88 - 38.9) than in taxon 1 (33.67 ± 0.89, range = 32.43--35.35) and in taxon 2 (33.68 ± 2.11, range = 30.36 - 36.97). ", "In taxon 3 the width of the vertebral cord (WVr 3.53 ± 0.25) and the length of the rib nodules (L5N 3.31 ± 0.87) were wider than in taxon 1 (3.06 ± 0.37, and 2.67 ±0.39, respectively) and taxon 2 (2.90 ± 0.37, and 2.91 ±0.41, respectively). ", "Trunk length, on the other hand was shorter in taxon 3 (TkL 66.22 ± 3.86), than in taxon 1 (70.28 ± 3.41) or taxon 2 (68.78 ± 1.24) (Table [4](#T4){ref-type=\"table\"}).", "\n\nThe data set of head and dorsal morphological traits was based on 19 observations of taxon 1 and taxon 2 together and three observations of taxon 3 from Lai Chau. ", "A PCA identified five principal components (PCs) which together explained 84 % of the morphological variation (cumulative explanation of the first 3 PCs = 66 %; of the first 4 PCAs = 75 %). ", "The first two PCs accounted for 48 % of the variation graphically showing a clear separation of the two clades (Fig. [", "5B](#F5){ref-type=\"fig\"}). ", "HW, EN, WVr, and L5N were identified as the characters differentiating between the species (MANOVA: *F*~1,\\ 20~ = 20.52, *p* \\< 0.001) (Table [5](#T5){ref-type=\"table\"}). ", "Head width (HW) was 21 % smaller in taxon 3 than in taxon 1 and taxon 2 (*F*~2,\\ 19~ = 36.79, *p* \\< 0.001), and the size of the rib nodules (L5N) was 15 % longer in taxon 3 than in taxon 1 and taxon 2 (*F*~2,\\ 19~ = 6.59, *p* \\< 0.01). ", "The two remaining characters were only different between taxon 3 and taxon 2. ", "Both the snout length (EN) and the width of the vertebral cord (WVr) were longer in taxon 3 than in taxon 2, by 17 % (*F*~2,\\ 19~ = 7.21, *p* \\< 0.01) and 16 % (*F*~2,\\ 19~ = 3.45, *p* \\< 0.05), respectively (Fig. [", "6](#F6){ref-type=\"fig\"}).", "\n\nThe limb data included 21 observations of taxon 1 and taxon 2 together and four of taxon 3 and resulted in a PCA with three PCs explaining 88 % of the variation. ", "The overall MANOVA (*F*~1,\\ 23~ = 1.92, *p* = 0.13) was not significantly different between both lineages (Fig. [", "5C](#F5){ref-type=\"fig\"}).", "\n\nMacroclimatic comparison\n\nOur data show that *T. asperrimus* in Guangxi, China experiences the lowest temperatures during the coldest months (3--6 °C) than any of the remaining three taxa in North Vietnam (12 °C). ", "This species also shows the highest amount of precipitation during the coldest (169--233 mm vs. 38--80 mm for the remaining three taxa) and driest (170--180 mm vs. 38--80 mm for the three remaining taxa) quarter of the year, as well as in the driest month (26--44 mm vs. 4--10 mm for the three remaining taxa) (Table [6](#T6){ref-type=\"table\"}).", "\n\n###### \n\nBioclimatic conditions at the species records. ", "Abbreviations: Annual Mean Temperature BIO1, Mean Diurnal Range BIO2, Isothermality BIO3, Temperature Seasonality BIO4, Max Temperature of Warmest Month BIO5, Min Temperature of Coldest Month BIO6, Temperature Annual Range BIO7, Mean Temperature of Wettest Quarter BIO8, Mean Temperature of Driest Quarter BIO9, Mean Temperature of Warmest Quarter BIO10, Mean Temperature of Coldest Quarter BIO11, Annual Precipitation BIO12, Precipitation of Wettest Month BIO13, Precipitation of Driest Month BIO14, Precipitation Seasonality BIO15, Precipitation of Wettest Quarter BIO16, Precipitation of Driest Quarter BIO17, Precipitation of Warmest Quarter BIO18, and Precipitation of Coldest Quarter BIO19.", "\n\n ----------- ------ --------- --------- --------- --------- --------- ----------------- -----------------\n Variables Unit taxon 1 taxon 1 taxon 2 taxon 2 taxon 3 *T. asperrimus* *T. asperrimus*\n BIO1 °C 20.7 20.4 20.4 19.9 19.3 16.8 16.9\n BIO2 °C 5.3 5.5 6.1 6.0 6.6 7.4 5.9\n BIO3 °C 37.4 38.1 39.7 42.0 45.7 32.0 32.5\n BIO4 °C 1.0 1.0 1.0 0.9 0.8 2.0 1.5\n BIO5 °C 26.3 26.1 27.1 26.1 26.1 26.0 23.9\n BIO6 °C 12.1 11.5 11.7 11.7 11.6 3.0 5.7\n BIO7 °C 14.2 14.6 15.4 14.4 14.5 23.0 18.2\n BIO8 °C 23.6 23.0 22.8 22.2 20.4 22.1 20.9\n BIO9 °C 16.6 16.3 16.5 16.0 15.9 9.5 10.8\n BIO10 °C 23.5 23.2 22.3 22.4 21.4 22.7 21.2\n BIO11 °C 16.6 16.3 16.3 16.0 15.9 8.5 10.8\n BIO12 mm 1884.2 1624.6 1648.3 1603.5 1843.7 1703.7 1558.2\n BIO13 mm 379.8 351.2 324.4 373.0 421.6 316.5 335.5\n BIO14 mm 7.3 8.2 4.3 6.8 9.6 43.5 25.5\n BIO15 mm 92.2 88.6 89.0 93.9 85.8 59.2 74.1\n BIO16 mm 984.9 888.1 821.4 910.9 1041.8 784.6 813.5\n BIO17 mm 42.6 56.4 45.8 37.8 80.4 189.2 169.6\n BIO18 mm 986.2 843.3 403.8 856.8 424.9 390.7 738.1\n BIO19 mm 42.6 56.4 43.7 37.8 80.4 233.0 169.6\n ----------- ------ --------- --------- --------- --------- --------- ----------------- -----------------\n\nIntegrative taxonomy {#SECID0ECVAK}\n--------------------\n\nGenetic and morphological differences found in this study support the taxonomic separation between T. cf. ", "asperrimus from Vietnam and *T. asperrimussensu stricto* (from China), thus confirming the distinctness of the Vietnamese clade. ", "Furthermore, we uncovered genetic and morphological variations within the Vietnamese T. cf. ", "asperrimus clade. ", "However, based on our current knowledge these should be evaluated with caution regarding taxon 1 and taxon 2. ", "Therefore these taxa are treated herein at the subspecies level until further evidence is presented. ", "In addition, due to distinct morphological and molecular divergence, the population from Lai Chau Province was revealed to be distinct at the species level.", "\n\nTaxonomic accounts {#SECID0EPWAK}\n==================\n\nTylototriton pasmansi\n---------------------\n\nAnimalia\n\nM. Bernardes, M. D. Le, T. Q. Nguyen, C. T. Pham, A. V. Pham, T.T. Nguyen & T. Ziegler sp. ", "nov.", "\n\nA6ADDF55-CA52-51B4-B0D3-52F4FA5FEE8A\n\nhttp://zoobank.org/3B901B94-4741-40BD-BDC1-75086A06A8FA\n\n[Figures 8](#F8){ref-type=\"fig\"} [, 9](#F10){ref-type=\"fig\"}\n\n1. ", " Tylototritontaxon 2 (this study).", "\n\n2. ", " T. vietnamensis(referring to the population from Phu Tho Province): [@B30], page 327.", "\n\n3. ", " T. asperrimus(referring to the population from Hoa Binh Province): [@B63], page 583; [@B32], page 39; [@B28], page 55.", "\n\n4. ", " T. cf. ", "asperrimus(1) (referring to the population from Hoa Binh Province): [@B37], page 293.", "\n\n5. ", " T. cf. ", "asperrimus\"Lao Cai/Hoa Binh\" (referring to the populations from Lac Son, Hoa Binh): [@B14], page 254.", "\n\n6. ", " T. cf. ", "asperrimus\"northern Vietnam\" (referring to the populations from Lai Chau, Lao Cai, Hoa Binh, and Phu Tho) [@B15], page 80.", "\n\n### Holotype.", "\n\nIEBR 4466, adult male, collected in Phu Canh Nature Reserve, Da Bac District, Hoa Binh Province, on 11 June 2016 by H. N. Ngo et al.", "\n\n### Paratypes.", "\n\nFour adult males, same data as the holotype: IEBR 4467--IEBR 4470; two adult males collected from Xuan Son National Park, Tan Son District, Phu Tho Province, unknown collector: IEBR 4322 and IEBR 4323; four adult males collected from Xuan Son National Park, Tan Son District, Phu Tho Province, on 7 July 2016 by T. D. Le: IEBR 4320, IEBR 4321, IEBR 4500 and IEBR 4501. ", "One adult female collected from Thuong Tien Nature Reserve (Cot Ca forest, Quy Hoa Commune), Lac Son District, Hoa Binh Province at 720 m elevation on 24 July 2009 by V. Q. Luu: VFU A.2009.8.", "\n\n{#F8}\n\n### Etymology.", "\n\nThe species is named after Prof. Dr. Frank Pasmans, Ghent University (Belgium), who has made considerable and path-breaking contributions in the field of infectious diseases driven amphibian declines.", "\n\n### Diagnosis.", "\n\nThe new species is diagnosed by the following combination of characters: head slightly longer than wide; snout truncate in dorsal view and slightly angular in profile; relative wide distance between the eyes; distinct mid-dorsal ridge on head; tips of fingers reaching the eye when foreleg adpressed along head; labial and gular folds present; rib nodules distinct and varying from pointy to more rounded; glandular vertebral ridge high, slightly rough and segmented; dorsal skin more granulose than ventral skin; and skin in middle of abdomen with smooth tubercles shaped like transverse wrinkles.", "\n\n### Description of holotype.", "\n\nHabitus moderately slender; head broader than body, slightly longer than wide, depressed and slightly oblique in profile; snout wider than long (IN \\> EN), truncate in dorsal view, slightly angular shaped in profile and protruding beyond lower jaw; nostrils close to snout tip and slightly visible from above; labial fold slightly evident; dorsolateral bony ridges on head prominent, moderately protruding, from above eye to above anterior end of parotoid, posterior ends relatively thick and scrolled inside; mid-dorsal ridge on head distinct and thin; parotoids enlarged, projecting backwards; ventral skin with tubercles shaped like transverse wrinkles; gular fold weak; glandular vertebral ridge high, slightly rough and segmented, anteriorly thinner, extending from top of head to base of tail, separated from mid-dorsal ridge, with slight scoliosis at height of anterior limbs; number of trunk vertebras around 13; rib nodules distinct, rounded and small, with slightly bigger sizes reached at mid-trunk; tips of fore- and hind limbs touch when adpressed along body; tips of fingers reaching eye when foreleg laid forward; one toe missing on right hind-limb; and tail laterally compressed, thin and tip acuminated.", "\n\n### Color of holotype.", "\n\nIn preservative, the overall dorsal coloration faded dark grayish green, the ventral coloration dark brown, with faded yellow markings on vent, ventral margin of tail, tip of fingers and toes, and part of palms. ", "For color in life see Fig. [", "9](#F10){ref-type=\"fig\"}.", "\n\n{#F10}\n\n### Measurements of holotype (in mm).", "\n\nSVL 64.16; MHW 16.07; HW 11.87; HL 17.67; PL 9.61; PH 4.50; EL 3.06; EN 3.69; IN 5.55; IE 8.11; LJL 10.8; UEL 4.52; HUM 5.97; RAD 13.51; FEM 7.44; TIB 13.70; FORE 19.48; HIND 21.14; TL 53.91; TH 7.78; ClL 8.13; ClW 4.37; WVr 2.18; L5W 2.31; AG 27.36; and TkL 44.00.", "\n\n### Variation.", "\n\nParatypes from Hoa Binh Province are very similar to the holotype. ", "Paratypes from Phu Tho seem to present a stouter habitus, more distinct middorsal ridge but slightly less protruding dorsolateral ridges on head and slightly enlarged round rib nodules. ", "The variation of the morphological characters in males is summarized in Table [4](#T4){ref-type=\"table\"} and the additional measurements of one female can be found in Table [3](#T3){ref-type=\"table\"}.", "\n\n### Comparisons.", "\n\n*Tylototriton pasmansi* sp. ", "nov. ", "differs from other related species of *Tylototriton* as follows: from *T. anhuiensis* by distinctly separated rib nodules (versus continuous nodule-like warts in *T. anhuiensis*); from *T. asperrimus* by a wider (versus shorter) distance between the eyes, tips of fingers reaching eye (versus nostril) when foreleg laid forward, and head slightly longer than wide (versus wider than long in *T. asperrimus* according to [@B32]; [@B50]; [@B14]), however, the female holotype shows similar head proportions--see Discussion); from *T. broadoridgus* by a head longer than wide (versus equally long and wide), wider (versus shorter) distance between eyes, presence (versus absence) of gular fold, smoother (versus extremely rough) skin on ventral side shaped like transverse wrinkles (versus rounded shaped, uniform to dorsal side), distinctly separated rib nodules (versus continuous nodule-like warts), and narrower vertebral ridge (versus broader in *T. broadoridgus*); from *T. hainanensis* by the head being slightly longer than wide (versus much wider than long), and a snout truncate in dorsal view (versus rounded in *T. hainanensis*); from *T. liuyangensis* by a wider (versus shorter) distance between eyes, distinctly separated rib nodules (versus continuous nodule-like warts), and ventral side skin shaped like transverse wrinkles (versus covered by warts in *T. liuyangensis*); from *T. notialis* by a broader (versus narrower) head, a slightly angular (versus rounded) shaped snout in profile, longer (versus shorter) hind-limbs, and higher tail (versus thinner tail in *T. notialis*); from *T. panhai* by wider (versus shorter) distance between the eyes, presence (versus absence) of labial fold, distinct (versus absent) middorsal ridge on head, and dorsal color uniformly dark (versus dorsal color with characteristic colorful markings in *T. panhai*); from *T. vietnamensis* by round to pointy (versus slightly flattened) rib nodules, presence (versus absence) of gular fold, and high vertebral ridge (versus low vertebral ridge in *T. vietnamensis*); from *T. wenxianensis* by a truncate snout in dorsal view (versus round), wider (versus shorter) distance between the eyes, distinctly separated rib nodules (versus continuous nodule-like warts), presence (versus absence) of gular fold, smoother (versus extremely rough) skin on ventral side shaped like transverse wrinkles (versus rounded shaped and uniform to dorsal side), and colored marking on ventral slit (versus black colored ventral slit in *T. wenxianensis*); and from *T. ziegleri* by head slightly longer than wide (versus wider than long), smaller (versus enlarged knob-like) rib nodules, dispersed granules (versus more granulose) on dorsal skin and vertebral ridge slightly less (versus more) segmented and glandular.", "\n\nThe morphological comparison resulting from the measurements performed on the two females of *T. pasmansi* and *T. asperrimussensu stricto* (Table [3](#T3){ref-type=\"table\"}) showed that the first one presents: wider (versus narrower) and longer (versus less long) head, longer (versus shorter) lower jaw length, wider (versus shorter) distance between the eyes, as well as higher values for all of the remaining head features, with the exception of snout length and head width, which were, in these cases, higher in *T. asperrimus*. *", "T. pasmansi* additionally presents longer and higher (versus shorter and thinner) tail, bigger (versus smaller) cloacal muscles, wider (versus narrower) vertebral ridge, slightly bigger (versus smaller) rib nodules and shorter trunk length (versus longer trunk length in *T. asperrimus*).", "\n\n### Distribution.", "\n\nPhu Canh Nature Reserve, Da Bac District and Thuong Tien Nature Reserve, Lac Son District in Hoa Binh Province, and Xuan Son National Park, Tan Son District, Phu Tho Province, Vietnam (Fig. [", "2](#F2){ref-type=\"fig\"}).", "\n\n### Natural history.", "\n\nBased on remote sensing information the species is known from sites with an annual mean temperature of 20.4 to 20.7 °C, ranging from 11.5 to 26.3 °C during the year. ", "Annual precipitation is about 1624 to 1884 mm ranging throughout the year from 7.3 to 379.8 mm. ", "Further bioclimatic information is provided in Table [6](#T6){ref-type=\"table\"}.", "\n\nTylototriton pasmansi obsti\n---------------------------\n\nAnimalia\n\nM. Bernardes, M. D. Le, T. Q. Nguyen, C.T. Pham, A. V. Pham, T.T. Nguyen & T. Ziegler ssp. ", "nov.", "\n\n59184B47-F6BD-51F7-A6E6-21356C91016A\n\nhttp://zoobank.org/7A124E44-4F79-499F-AFD3-5B429D1AB4FB\n\n[Figures 9](#F10){ref-type=\"fig\"} [, 10](#F11){ref-type=\"fig\"}\n\n1. ", " Tylototritontaxon 1 (this study).", "\n\n### Holotype.", "\n\nIEBR 4471, adult male, collected in Xuan Nha Nature Reserve, Van Ho District, Son La Province, at an elevation of 1090 m a.s.l., ", "on 15 June 2016 by A. V. Pham and N. B. Sung.", "\n\n### Paratypes.", "\n\nEight adult males, the same data as the holotype: IEBR 4472--4475, TBU 11--14; two adult males collected at elevation of 950 m a.s.l. ", "in Xuan Lien Nature Reserve, Vin Village, Bat Mot Commune, Thuong Xuan District, Thanh Hoa Province, and in July 2015 by T. S. Nguyen: IEBR 4318 and IEBR 4319.", "\n\n### Etymology.", "\n\nThe new subspecies is named after Prof. Fritz-Jürgen Obst, the former herpetologist and director of the Museum für Tierkunde Dresden, Germany, as well as passionate *Tylototriton* keeper, who passed away on the 10 June 2018.", "\n\n### Diagnosis.", "\n\nThe new subspecies is diagnosed from the nominotypic subspecies *Tylototriton pasmansi pasmansi* by the following combination of characters: a wider head (both as head width and maximum head width), versus narrower head; a longer and narrower snout, versus shorter and wider snout; a shorter femur and associated hind-limb lengths, versus longer femur and longer hind-limbs length; less overall concentration of warts and small granules on skin, versus overall skin more granulose; and skin on lateral body with apparently same concentration of warts than dorsal side, versus higher concentration of warts on ventral side of the body than on dorsum in *T. p. pasmansi*.", "\n\n### Description of holotype.", "\n\nHabitus moderately stout; head broader than body, slightly longer than wide, depressed and slightly oblique in profile; snout wider than long (IN \\> EN), truncate in dorsal view, slightly angular shaped in profile and protruding beyond lower jaw; nostrils close to snout tip and not visible from above; labial fold slightly evident; dorsolateral bony ridges on head prominent, moderately protruding, from above eye to above anterior end of parotoid, posterior ends thin and scrolled inside; distinct middorsal ridge on head; parotoids enlarged, projecting backwards; dorsal skin granulose; skin on lateral body and between axilla-groin smooth, with no obvious presence of small glands; throat skin visibly more rough than in between axilla-groin region; gular fold present; glandular vertebral ridge high, slightly rough and segmented, anteriorly thinner, extending from top of head to base of tail, separated from middorsal ridge; number of trunk vertebrae 12; rib nodules distinct, rounded and pointy, with similar sizes throughout their length; fingers from fore- and hind limbs overlap when adpressed along body; tips of fingers reaching eye when adpressed along head; and tail laterally compressed, thin and tip acuminated.", "\n\n{#F11}\n\n### Color of holotype.", "\n\nIn preservative, with overall dark brown to blackish with faded yellow markings in vent margin, ventral tail fin, and tips of fingers and toes. ", "For color in life see Fig. [", "9](#F10){ref-type=\"fig\"}.", "\n\n### Measurements of holotype (in mm).", "\n\nSVL 67.95; MHW 18.1; HW 12.53; HL 19.44; PL 10.4; PH 5.5; EL 3.4; EN 3.99; IN 5.44; IE 8.64; LJL 12.11; UEL 5.07; HUM 8.12; RAD 14.43; FEM 7.05; TIB 15.75; FORE 22.55; HIND 22.80; TL 60.71; TH 8.46; ClL 8.86; ClW 5.88; WVr 2.18; L5W 2.12; AG 30.57; and TkL 46.48.", "\n\n### Variation (based on preserved paratypes).", "\n\nSome paratypes also show slightly bigger and rounded rib nodules, an overall more granulose skin, and faded yellow coloration on: anterior upper arms (like mating pads), posterior end of parotoids and first rib nodules. ", "The remaining characters were similar to the holotype. ", "Further measurements are summarized in Table [4](#T4){ref-type=\"table\"}.", "\n\n### Comparisons.", "\n\nIn addition to the diagnostic characteristics already mentioned above, *Tylototriton pasmansi obsti* ssp. ", "nov. ", "differs from *T. p. pasmansi* by having a moderately stout habitus (versus moderately slender, when excluding the population from Phu Tho), nostrils usually not visible (versus usually visible) from dorsal view, usually thinner (versus usually thicker) posterior end of the dorsolateral bony ridges on head, gular fold more evident (versus weaker), rib nodules with similar sizes throughout their length (versus with slightly bigger sizes at mid-trunk), and rib nodules sometimes pointy (versus rounded in *T. p. pasmansi*).", "\n\n### Distribution.", "\n\nXuan Nha Nature Reserve, Van Ho District, Son La Province and Xuan Lien Nature Reserve, Thuong Xuan District, Thanh Hoa Province, Vietnam (Fig. [", "2](#F2){ref-type=\"fig\"}).", "\n\n### Natural history.", "\n\nSpecimens were found between 14:00 and 16:00 h inside breeding ponds. ", "The surrounding habitat was characterized by secondary forest of large, medium and small hardwoods mixed with shrubs and vines. ", "Air temperature at the collection time was about 25 to 30 ^o^C and relative humidity was about 75 to 80 %. ", "Based on remote sensing information the species occurs at sites with an annual mean temperature of 19.9 to 20.4 °C, ranging from 11.7 to 27.1 °C during the year. ", "Annual precipitation is about 1603.5 to 1648.3 mm with yearly variations from 4.3 to 373.0 mm monthly. ", "Further bioclimatic information is provided in Table [6](#T6){ref-type=\"table\"}.", "\n\nTylototriton sparreboomi\n------------------------\n\nAnimalia\n\nM. Bernardes, M. D. Le, T. Q. Nguyen, C. T. Pham, A. V. Pham, T.T. Nguyen & T. Ziegler sp. ", "nov.", "\n\n37553400-6E3E-558F-B0B7-515FC0FE43A0\n\nhttp://zoobank.org/4599D131-7C89-4D62-B43A-15E24C6473B9\n\n[Figures 9](#F10){ref-type=\"fig\"} [, 11](#F13){ref-type=\"fig\"}\n\n1. ", " Tylototritontaxon 3 (this study).", "\n\n2. ", " T.sp.: [", "@B25], page 2.", "\n\n3. ", " T. verrucosus: [@B36], page 101; [@B57], page 1; [@B30], page 329.", "\n\n4. ", " T. cf. ", "asperrimus\"North Vietnam\": [@B15], page 80.", "\n\n### Holotype.", "\n\nIEBR 4476, adult male, collected in Sa De Phin Commune, Sin Ho District, Lai Chau Province, Vietnam, at an elevation of 1670 m a.s.l., ", "in May 2015 by A. V. Pham and M. A. Vang.", "\n\n### Paratypes.", "\n\nTwo adult males, same data as the holotype: IEBR 4477 and TBU 10; two adult males, collector unknown: IEBR 4478 and IEBR 4479.", "\n\n### Etymology.", "\n\nThe specific epithet is dedicated to late Prof. Dr. Max Sparreboom, who has made great contributions to the understanding of Urodela.", "\n\n### Diagnosis.", "\n\nThe new species is distinguished from other species of the genus by the following combination of characters: head longer than wide; snout truncate in dorsal view; tips of fingers reaching nostril when foreleg is laid forward; skin tubercles on ventral side shaped like transverse wrinkles; rib nodules distinct and round; vertebral ridge segmented, high and relatively wide; relatively wide distance between the eyes; and gular and labial folds present.", "\n\n### Description of holotype.", "\n\nHabitus stout; head broader than body, longer than wide, depressed and slightly oblique in profile; snout wider than long (IN \\> EN), truncate in dorsal view, rounded in profile and protruding beyond lower jaw; nostrils close to snout tip and not visible from above; labial fold slightly evident; dorsolateral bony ridges on head prominent, wide, moderately protruding, from above eye to above anterior end of parotoid, posterior ends slightly scrolled inside; middorsal ridge on head almost indistinct; parotoids enlarged, projecting backwards; ventral skin smoother than dorsal skin, with tubercles shaped like transverse wrinkles; gular fold weak; glandular vertebral ridge high, wide, smooth and segmented extending from top of head to base of tail, separated from middorsal ridge; number of trunk vertebrae 13; rib nodules distinct and roundish, the third anterior rib nodule on right side is located below the second nodule and the fourth nodule seems to not be associated with the fourth vertebra, nodules appear knob-like anteriorly, becoming smaller posteriorly; tips of fore- and hind limbs overlap when adpressed along body; tips of fingers reaching nostril when foreleg laid forward; and tail laterally compressed, thin and tip acuminated.", "\n\n### Color of holotype.", "\n\nIn preservative, with an overall faded dark brown coloration, with faded yellow markings on vent, ventral margin of tail, tips of fingers and toes, and part of palms. ", "For color in life see Fig. [", "9](#F10){ref-type=\"fig\"}.", "\n\n### Measurements of holotype (in mm).", "\n\nSVL 68.71; MHW 17.60; HW 9.85; HL 19.95; PL 10.18; PH 6.12; EL 3.43; EN 4.43; IN 6.26; IE 9.04; LJL 10.74; UEL 4.74; HUM 9.27; RAD 15.86; FEM 8.77; TIB 16.03; TL 59.70; TH 8.57; ClL 9.66; WVr 2.37; L5W 3.04; AG 30.99; and TkL 42.72.", "\n\n### Variation.", "\n\nTBU 10 (in worse preserved condition) presents rib-nodules thinner than holotype, glandular vertebral ridge more tubercular, and tail tip slightly rounded. ", "The remaining characters were similar to the holotype in morphology. ", "For detailed measurements see Table [4](#T4){ref-type=\"table\"}.", "\n\n### Comparisons.", "\n\n*Tylototriton sparreboomi* sp. ", "nov. ", "differs from other related species of *Tylototriton* as follows: from *T. anhuiensis* by distinctly separated rib nodules (versus continuous nodule-like warts in *T. anhuiensis*); from *T. asperrimus* by a head longer than wide (versus wider than long in *T. asperrimus* according to [@B32]; [@B50]; [@B14]), however the female holotype shows similar head proportions--see Discussion); from *T. broadoridgus* by head slightly longer than wide (versus equally long and wide), presence of skin on ventral side shaped like transverse wrinkles (versus covered with round shaped tubercles, like the dorsal side), distinctly separated rib nodules (versus continuous nodule-like warts), and narrower vertebral ridge (versus wider vertebral ridge in *T. broadoridgus*); from *T. hainanensis* by a head longer than wide (versus much wider than long), tips of fingers reaching nostril (versus eyes) when foreleg is laid forward, and a snout truncate in dorsal view (versus rounded in *T. hainanensis*); from *T. liuyangensis* by a wider (versus shorter) distance between eyes, distinctly separated rib nodules (versus continuous nodule-like warts), and lateral skin shaped like transverse wrinkles (versus covered by warts in *T. liuyangensis*); from *T. notialis* by a broader (versus narrower) head, longer (versus shorter) hind-limbs, and higher tail (versus thinner tail in *T. notialis*); from *T. panhai* by wider (versus shorter) distance between the eyes, presence (versus absence) of labial fold, and overall dorsal coloration mostly dark (versus with presence of characteristic dorsal colorful markings in *T. panhai*); from *T. pasmansi* sensu lato by a narrower (versus wider) head, slightly wider (versus slightly narrower) distance between the eyes, tips of fingers reaching nostril (versus eye) when foreleg laid forward, longer (versus shorter) humerus length, and slightly enlarged round-like rib nodules (versus slightly smaller, pointy to rounded rib nodules in *T. pasmansi* sensu lato); from *T. p. pasmansi* by a longer (versus shorter) length between eye and nostril and wider (versus narrower) vertebral ridge in *T. p. pasmansi*; from *T. pasmansi obsti* by a longer (versus shorter) femur length; from *T. vietnamensis* by a moderately stout (versus slender) habitus, presence (versus absence) of gular fold, and round (versus slightly flattened) rib nodules and high vertebral ridge (versus low vertebral ridge in *T. vietnamensis*); from *T. wenxianensis* by a truncate (versus more rounded) snout in dorsal view, wider (versus narrower) distance between the eyes, distinctly separated rib nodules (versus continuous nodule-like warts), smoother (versus extremely rough) skin on ventral side shaped like transverse wrinkles (versus rounded shaped and uniform to dorsal side), and colored marking on ventral slit (versus black colored ventral slit in *T. wenxianensis*); from *T. ziegleri* by a head longer than wide (versus wider than long), rounded but smaller (versus enlarged knob-like) rib nodules, and distinctly segmented vertebral ridge (versus even more segmented vertebral ridge in *T. ziegleri*).", "\n\n{#F13}\n\n### Distribution.", "\n\nKnown only from the type locality in Lai Chau Province, northern Vietnam (Fig. [", "2](#F2){ref-type=\"fig\"}).", "\n\n### Natural history.", "\n\nSpecimens were found in water between 9:00 and 16:30 h in ponds. ", "The surrounding habitat was secondary forest of large, medium and small hardwoods mixed with shrubs and vines. ", "Air temperature at the sites was 23 to 27 °C and relative humidity was 80 to 85%. ", "Based on remote sensing information, the species occurs at sites with an annual mean temperature of 19.3 °C, ranging from 11.6 to 26.1 °C during the year. ", "Annual precipitation is about 1843.7 mm with yearly variations from 9.6 to 421.6 mm. ", "Further bioclimatic information is provided in Table [6](#T6){ref-type=\"table\"}.", "\n\nDiscussion {#SECID0EESCK}\n==========\n\nBased on examples listed in Table [7](#T7){ref-type=\"table\"}, we argue that clear genetic and morphological differences help clarify the taxonomic status of the taxa in question. ", "The genetic differences between *T. pasmansi* and its closest relative *T. asperrimus* (from 3.2 to 3.6 %), between *T. sparreboomi* and *T. asperrimus* (from 4.1 to 4.2 %), and between *T. pasmansi* and *T. sparreboomi* (from 3.6 to 4.5 %) are higher than other minimum genetic distances between species of the genus *Tylototriton* (see *T. shanjing* × *T. verrucosus* × *T. pulcherrimus* × *T. podichthys*, *T. anguliceps* × *T. pulcherrimus*, *T. broadoridgus* × *T. dabienicus*, *T. anhuiensis* × *T. broadoridgus*, and *T. ngarsuensis* × *T. shanorum*).", "\n\n###### \n\nExamples of integrative taxonomy in other species of the genus *Tylototriton*. ", "\\*partial 16S rRNA and COI, and complete tRNA Leu, ND1, ND2, tRNA Ile, tRNA Gln, tRNA Met, tRNA Trp, tRNA Ala, tRNA Asn, tRNA Cys, and tRNA Tyr.", "\n\n -------- ------------------------------ ---------------------------------------------------------------------------- -------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n Source Gene used Species at stake Genetic var. (%) ", " Morphological variation and conclusions\n [@B66] partial cyt b *T. shanjing* × *T. verrucosus* mean 1.2; range 0.4--2.6 Morphology not discussed. ", "Conspecificity. [", "@B52], [@B31] and [@B34] point out that only a single, unvouchered sample of *T. verrucosus* was included, and cautiously defended the need for further examinations before taxonomic conclusions.", "\n [@B23] complete ND2 & partial cyt b *T. shanjing* × *T. verrucosus* 1.9 Size; head proportions; grooves on tail base; coloration. \"", "The topotypic *T. verrucosus* were deeply nested within *T. shanjing*.\"", "\n [@B23] complete ND2 & partial cyt b *T. pulcherrimus* × *T. verrucosus; T. pulcherrimus* × *T. shanjing* 2.1; 2.8 Not further discussed. ", "Treated as separated species.", "\n [@B31] partial ND2, POMC & Rag 1 *T. shanjing* (Jingdong and Nu Jiang, Yunnan, China) mean 1.4; range 0.2--2.1 Morphology not discussed. ", "Treated as intraspecific variation.", "\n [@B31] partial ND2, POMC & Rag 1 *T. shanjing* (from above) × *T. pulcherrimus* mean 2.6; range 2.5--2.8 Morphology not discussed. ", "Considered conspecific due to small genetic differences.", "\n [@B34] partial ND2 *T. yangi* × *T. daweishanensis* mean 0.4; range 0.2--0.5 Coloration. ", "Considered conspecific due to small genetic differences.", "\n [@B23] complete ND2 & partial cyt b *T. yangi* × *T. daweishanensis* mean 0.7 Not discussed. ", "Treated as separate species.", "\n [@B37] \\* *T. anguliceps* × *T. pulcherrimus* mean 3.1; range 2.8--3.4 Morphology not discussed. ", "Treated as separate species and used as example for low genetic divergence within species of the genus.", "\n [@B37] \\* *T. podichthys* (description) × *T. pulcherrimus* mean 2.9; range 2.5--3.4 Morphology not discussed. ", "The new species formed a unique clade within an unresolved polytomy containing *T. verrucosus*, *T. shanjing*, and *T. pulcherrimus*.", "\n [@B37] \\* *T. podichthys* (description) × *T. shanjing* mean 3.4; range 2.1--4.6 Ridge on midline of crown; coloration. ", "Treated as separate species.", "\n [@B27] partial ND2 *T. podichthys* (Xam Neua, Laos) × *T. shanjing* 0.4 When the paper was published, *T. podichthys* was not yet described. ", "The authors referred to this population as *T. verrucosus* from Laos, which formed a clade with *T. shanjing*, *T. pulcherrimus*, and *T. verrucosus* from the type locality.", "\n [@B37] \\* *T. podichthys* (description) × *T. verrucosus* mean 3.1; range 2.1--4.4 Ridge on midline of crown; coloration; skin on cranial crest; orientation of parotoids. ", "Separate species.", "\n [@B47] complete ND2 *T. broadoridgus* (description) × *T. wenxianensis* mean 3.9; range 3.8--4 Dorsal ridge; height of tail; presence of genital papillae; form of rib warts. ", "Treated as separate species.", "\n [@B47] complete ND2 *T. broadoridgus* (description) × *T. dabienicus* mean 3.5; range 3.4--3.5 Inferred morphological differences. ", "Separate species.", "\n [@B32] partial ND2 *T. broadoridgus* × *T. dabienicus* mean 3.3; range 3.3--3.4 Morphology not examined. ", "Treated as separate species and used as example for low genetic divergence within species of the genus.", "\n [@B31] partial ND2 *T. broadoridgus* × *T. dabienicus* 3.3 Morphology not examined. ", "The authors suspect conspecificity.", "\n [@B23] complete ND2 & partial cyt b *T. broadoridgus* × *T. dabienicus* 3.4 Not discussed. ", "Treated as separate species.", "\n [@B52] \\* (except COI) *T. notialis* (description) × *T. hainanensis* range 3.7--3.8 Form of rib warts. ", "Treated as separate species.", "\n [@B32] partial ND2 *T. notialis* (type from Laos) × *T. notialis* (Nghe An, Vietnam) 2.8 Coloration. ", "Considered conspecific.", "\n [@B32] partial ND2 *T. ziegleri* (description) mean 1.7; range 0.1--2.8 Treated as intraspecific variation.", "\n [@B32] partial ND2 *T. asperrimus* (China) × *T. asperrimus* (Thuong Tien, Hoa Binh, Vietnam) mean 2.7; range 0.1--3.4 Morphology not examined. ", "Considered conspecific by [@B32]; separate species, Tylototriton pasmansi, this study.", "\n [@B40] ND1, ND2 & cyt b *T. ziegleri* x *T. vietnamensis* 2.3 Known morphological differences based on [@B32]: ridges on head; skin; vertebral ridge; form of rib warts; tail size and height. ", "Treated as separate species.", "\n [@B40] ND1, ND2 & cyt b *T. anhuiensis* (description) × *T. broadoridgus* 3.2 Dorsal ridge width; head proportions. ", "Treated as separate species.", "\n [@B12] ND2 *T. ngarsuensis* (description) × *T. shanorum* range 3.0--3.4 Size; head length; rib nodules; dorsal ridge; parotoid position; coloration. ", "Treated as separate species.", "\n -------- ------------------------------ ---------------------------------------------------------------------------- -------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\nIt becomes apparent that these genetic differences, accompanied by clear morphological disparities, warrant taxonomic revision. ", "The shape of the head of the holotype of *T. asperrimus* (a female) is slightly longer than wide, but evidence from literature, likely based on males, supports a head morphology being (slightly) wider than long in this species ([@B32]; [@B50]; [@B14]). ", "In the diagnostic comparisons above, we followed the major consensus found in literature and used head shape as a diagnostic characteristic to separate *T. asperrimus*, *T. pasmansi*, and *T. sparreboomi*. [", "@B46] found differences between the head shape of males and females in *T. himalayanus*. ", "In *T. asperrimus* it is currently not clear if this change of head proportions is an exceptional occurrence or a feature related to sexual dimorphism. ", "Until this issue is clarified, the diagnostic feature should be employed with reservations. ", "The dorsal coloration described herein (as it is usually the case within this subgenus) should also be used cautiously as a diagnostic characteristic. ", "Additional work might uncover intra-specific color variations, as in *T. notialis* ([@B32]), and *T. ziegleri* ([@B14]).", "\n\nTwo taxa, *T. p. pasmansi* and *T. pasmansi obsti*, are herein cautiously described as subspecies, since their genetic divergences are lower (from 2.5 to 3.1 %) and morphological differences are more subtle. ", "In this case, additional surveys and genetic study (e.g., microsatellites, nuclear DNA analysis) should follow to provide a more complete taxonomic evaluation of these taxa. ", "These two subspecies appear to be separated by the Da River \\[Black River\\] (see Fig. [", "2](#F2){ref-type=\"fig\"}). ", "Since the Da River is the largest river in northwestern Vietnam, it may serve as a physical barrier restricting the gene flow between populations. ", "Recently, [@B16] assessed the patterns of macro-ecological niche differentiation in Asian crocodile newts. ", "The authors suggested that both niche conservatism as well as niche differentiation can be detected. ", "Many species occupy forested habitats at higher elevations, which are characterized by cooler and moister micro-habitats compared to lowland and open areas. ", "Although our low sample size prevents detailed niche assessments for the new taxa, the overall niche structure within the genus suggests that the taxa are restricted to micro-climatic pockets in mountainous areas. ", "Hence, not only the river systems represent likely barriers for gene flow, but also unsuitable micro-climatic conditions might limit dispersals in the region.", "\n\n[@B60] hypothesized that *Tylototritonsensu lato* originated from the ancestral area consisting of northern Indochina Peninsula and southern Yunnan Province during the middle Miocene, approximately 15 MYA. ", "This period coincided with the warming Miocene climate optimum ([@B64]; [@B3]). ", "It is also evident that the speciation rates of the group have slowed down significantly from the beginning of the Pleistocene, probably due to the global cooling during this epoch ([@B60]). ", "However, an important period between just before the Pliocene, around 6 MYA, and the Pleistocene, approximately 2.5 MYA, when a majority of speciation events within the group occurred (see Fig. [", "4](#F4){ref-type=\"fig\"} in [@B60]), has not been discussed in previous studies. ", "During the Pliocene, the global temperature was about 2--5 °C higher than that of the pre-industrial time ([@B64]; [@B42]; [@B45]). ", "Warmer climates, which have been shown to promote diversification rates in different animal groups, including ants, mammals, plethodontid salamanders, and softshell turtles, possibly through increased dispersal rates ([@B29]; [@B49]; [@B59]; [@B26]), are also likely to influence the evolution of the Knobby Salamanders in Asia. ", "Our study also suggests that the two new species emerged during this period, further supporting the higher rate of diversification of *Tylototriton* in the Pliocene.", "\n\n[@B60] and also [@B65] did not find support for the monophyly of *T. asperrimus*. ", "Their phylogeny placed the population from Thuong Tien, Hoa Binh (*T. p. pasmansi*) as conspecific to the *T. asperrimus* form from China (identified together as *T. asperrimus* lineage 1 in both studies). ", "These studies also misidentified the population from Xinyi County, Guangdong Province, China as *T. asperrimus* lineage 2, although this population forms a sister clade to the topotypic *T. hainanensis* from Hainan Island. ", "The population from Baise, which according to [@B15] is distributed in Napo and Jingxi counties, China, was also recovered as a sister taxon to *T. hainanensis* in previous studies ([@B63]; [@B37]; [@B14]). ", "Moreover, the studies by [@B60] and [@B65] did not support the monophyly of both, *T. wenxianensis* and *T. dabienicus* species complexes. ", "The *T. wenxianensis* complex appears to consist of at least two undescribed lineages, one in Libo county, Guizhou Province and the other in Wufeng county, Hubei Province, while in the *T. dabienicus* complex both studies apparently missed the description of *T. anhuiensis* by [@B40], and as a result, continue to identify the population from Yuexi, Anhui as an unknown lineage sister to *T. dabienicus*.", "\n\nThe so far undescribed population from Lao Cai Province, Vietnam has been successively attributed to a number of species: T. cf. ", "vietnamensis ([@B4]), *T. asperrimus* ([@B30]), purportedly *T. ziegleri* ([@B32]), and T. cf. ", "asperrimus \"northern Vietnam\" ([@B15]). [", "@B37], using a comprehensive phylogenetic sample, defended the conspecificity of the population from Lao Cai with the population from Lac Son, Hoa Binh Province, which we herein describe as *T. p. pasmansi*.", "\n\nBased on these new developments we suspect *T. asperrimus* (type) to be endemic to Guangxi Province, in China. ", "It is distributed in Jinxiu Yao Autonomous County in Mt. Dayao (including Dayaoshan Nature Reserve \\[[@B14]\\] and in Bainiu locality \\[[@B15]\\]) and in Mt. Xianglu (also Xianglushan) ([@B62]); in Longsheng County ([@B47]); Ziyuan County in Mt. Miao'er ([@B15]); in Huanjiang County including the Mulun Nature Reserve ([@B41]); and in Tian'e County ([@B15]). ", "According to [@B14] and 2018) the species has a wide distribution in fragmented mountain areas from northern through central and southern Guangxi. ", "The population from E'huangzhang Mts., ", "Yangchun County, Guangdong is shown as a sister to topotypic *T. asperrimus* ([@B14] and [@B15]), but still awaits proper taxonomic allocation.", "\n\nGiven the high demand of *Tylototriton* species in the international trade, and the persistent evidence of a high poaching rate ([@B11]; [@B33]; [@B38]; [@B44]; [@B2]; [@B12]) we decided to follow [@B19] and cautiously omit the exact locations in this manuscript.", "\n\nOutlook {#SECID0E2UEK}\n=======\n\nThis study increases the currently known number of *Tylototriton* species from northern Vietnam, from four (*T. anguliceps*, *T. notialis*, *T. vietnamensis*, and *T. ziegleri*) to six and one subspecies, by discovering *T. sparreboomi*, *T. p. pasmansi* and *T. pasmansi obsti*. ", "It also further affirms that this region supports the highest diversity within this genus ([@B32]).", "\n\nThe taxonomic separation of a single widespread species into multiple small-ranged taxa in turn has important implications for the conservation status of the original species ([@B24]; [@B51]). ", "We therefore recommend a re-assessment of the outdated Near Threatened status of *T. asperrimussensu lato* ([@B56]) to reflect taxonomic revisions and increasingly severe threats from international trade and habitat loss, which have taken place over the last decade.", "\n\nSupplementary Material\n======================\n\n###### XML Treatment for Tylototriton pasmansi\n\n###### XML Treatment for Tylototriton pasmansi obsti\n\n###### XML Treatment for Tylototriton sparreboomi\n\nWe thank the directorates of the Forest Protection Departments of Lai Chau, Lao Cai, Son La, Hoa Binh, Bac Giang, Quang Ninh, and Thanh Hoa provinces as well as Xuan Son National Park, Xuan Nha, Phu Canh, Thuong Tien, Tay Yen Tu, and Xuan Lien nature reserves for support of our field work and issuing relevant permits. ", "We are grateful to D. T. Le, H. N. Ngo, T. S. Nguyen (Hanoi), N. B. Sung (Son La), and M. A. Vang (Lai Chau) for their assistance in the field and providing specimens. ", "We thank H. T. Ngo (Hanoi) and A. Rauhaus (Cologne) for their laboratory assistance. ", "We would like to thank the loans from the Museum für Naturkunde, Berlin and the Vietnam Forestry University in Hanoi. ", "For the fruitful cooperation within joint amphibian projects we cordially thank S.V. Nguyen (IEBR, Hanoi) as well as T. Pagel and C. Landsberg (Cologne). ", "Cologne Zoo is partner of the World Association of Zoos and Aquariums (WAZA): Conservation Project 07011 (Herpetodiversity Research). ", "This research was partially funded by Cologne Zoo, the Vietnam Academy of Science and Technology (Grant No. ", "VAST04.09/19-20) to C. T. Pham and by the Ministry of Education and Training to (Grant No. ", "B2019-TTB-562-13) to A. V. Pham.", "\n\nSupplementary materials\n=======================\n\n10.3897/zookeys.935.37138.suppl1\n\n72C8136A-E4FC-5BA4-8A30-4FFBC9D2C833\n\n###### \n\nRegression of each morphological character to its respective snout-vent length value for taxon 1 and taxon 2\n\nmeasurement\n\nhttps://binary.pensoft.net/file/412509\n\nThis dataset is made available under the Open Database License (http://opendatacommons.org/licenses/odbl/1.0/). ", "The Open Database License (ODbL) is a license agreement intended to allow users to freely share, modify, and use this Dataset while maintaining this same freedom for others, provided that the original source and author(s) are credited.", "\n\nMarta Bernardes, Minh Duc Le, Truong Quang Nguyen, Cuong The Pham, Anh Van Pham, Tao Thien Nguyen, Dennis Rödder, Michael Bonkowski, Thomas Ziegler\n\n10.3897/zookeys.935.37138.suppl2\n\n3834BDD1-A252-5B29-A532-084AA335D065\n\n###### \n\nTime-calibrated tree of *Tylototriton* based on ND2 sequences. ", "The values indicate the split time (in million years ago) calculated by BEAST 1.8.0.", "\n\nmeasurement\n\nhttps://binary.pensoft.net/file/412510\n\nThis dataset is made available under the Open Database License (http://opendatacommons.org/licenses/odbl/1.0/). ", "The Open Database License (ODbL) is a license agreement intended to allow users to freely share, modify, and use this Dataset while maintaining this same freedom for others, provided that the original source and author(s) are credited.", "\n\nMarta Bernardes, Minh Duc Le, Truong Quang Nguyen, Cuong The Pham, Anh Van Pham, Tao Thien Nguyen, Dennis Rödder, Michael Bonkowski, Thomas Ziegler\n\n[^1]: Academic editor: A. Crottini\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nrequirejs require text! ", "with relative path cause unnormalized error on iphone, bet works on emulator\n\nI am using requirejs with phonegap, and load some text file in module definition like this\ndefine(['text!../configuration/systemcore.cfg', //config files\n 'text!../language/cn.systemcore.lang', //languagefiles\n 'Configuration', 'DatabaseHandler', 'Language', //framework js \n 'FileHandler', 'NotificationHandler', \n 'BaseModule' //base classes\n ], \n function(cfg, lang,\n Configuration, DatabaseHandler, Language, FileHandler, NotificationHandler,\n BaseModule) {\n\nEverything works fine in the ios emulator, but once loaded into ios device, it causes\nunnormalized error on text file which leads to load module timeout, why...\n\nA:\n\nOk, I added text : 'path/to/text.js' in the requirejs.config({ patch : {...}}) and it solved the problem. ", "It is still weird how can it work before in the emulator when I dont specifically point to the text.js\n\n" ]

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[ "Saxeville, Wisconsin\n\nSaxeville is a town in Waushara County, Wisconsin, United States. ", "The population was 974 at the 2000 census. ", "The unincorporated community of Saxeville is located in the town.", "\n\nGeography\nAccording to the United States Census Bureau, the town has a total area of 36.5 square miles (94.7 km²), of which, 36.1 square miles (93.4 km²) of it is land and 0.5 square miles (1.3 km²) of it (1.34%) is water.", "\n\nDemographics\n\nAs of the census of 2000, there were 974 people, 393 households, and 312 families residing in the town. ", " The population density was 27.0 people per square mile (10.4/km²). ", " There were 610 housing units at an average density of 16.9 per square mile (6.5/km²). ", " The racial makeup of the town was 98.97% White, 0.31% from other races, and 0.72% from two or more races. ", "Hispanic or Latino of any race were 1.13% of the population.", "\n\nThere were 393 households out of which 28.5% had children under the age of 18 living with them, 70.7% were married couples living together, 5.1% had a female householder with no husband present, and 20.6% were non-families. ", "18.1% of all households were made up of individuals and 6.9% had someone living alone who was 65 years of age or older. ", " The average household size was 2.48 and the average family size was 2.78.", "\n\nIn the town, the population was spread out with 22.9% under the age of 18, 4.1% from 18 to 24, 27.0% from 25 to 44, 28.9% from 45 to 64, and 17.1% who were 65 years of age or older. ", " The median age was 43 years. ", "For every 100 females, there were 105.5 males. ", " For every 100 females age 18 and over, there were 104.1 males.", "\n\nThe median income for a household in the town was $39,688, and the median income for a family was $46,827. ", "Males had a median income of $33,438 versus $24,464 for females. ", "The per capita income for the town was $20,514. ", " About 5.4% of families and 9.2% of the population were below the poverty line, including 14.7% of those under age 18 and 4.8% of those age 65 or over.", "\n\nReferences\n\nCategory:Towns in Waushara County, Wisconsin\nCategory:Towns in Wisconsin" ]

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[ "Thomas Simson\n\nThomas Simson (1696–1764) was a Scottish medical academic at the University of St Andrews.", "\n\nLife\n\nHe was born in 1696. ", " He obtained the degree of MD from the University of Glasgow in 1720, and two years later, in 1722 was appointed as the first Chandos Professor of Medicine at St Salvator's College, University of St Andrews, the first specifically medical appointment at the university. ", " He was notable for lecturing predominantly in English, rather than the Latin which was at that time the normal language within the university.", "\n\nWorks\n\nHis publications included:\nConick sections. ", "Pitcarnii doctrina de circulatione sanguinii (1714)\nDe Re Medica (1726)\nA System of the Womb (1729)\nAn inquiry how far the vital and animal actions of the more perfect animals can be accounted for independent of the brain (1752)\n\nFamily\n\nHe married Margaret Preston on 20 January 1724, who bore him four children: Preston Simson (1728–1815); Robert Simson (1731–1817); Agnes Simson (1733–1780); and James Simson (1740–1770).", "\n\nHe died in 1764, and who succeeded by his son James Simson as Chandos Professor at the university.", "\n\nReferences\nDictionary of National Biography\n\nCategory:Academics of the University of St Andrews\nCategory:Alumni of the University of Glasgow\nCategory:1696 births\nCategory:1764 deaths" ]

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[ "Cold as the Clay\n\nCold as the Clay is the second solo album by Bad Religion's vocalist Greg Graffin released on July 10, 2006 in Europe, and the following day in the USA. ", "It was released on the label ANTI- (a sublabel of Epitaph Records). ", "It follows on from Graffin's 1997 release of American Lesion.", "\n\nGraffin has described the album as \"honor[ing] the legacy of American music. [...] ", "Traditional songs that helped form the 18th and 19th century American cultural landscape. ", "The modern songs are inspired by my love of country rock in vein of Gram Parsons, The Band, Neil Young\". ", "It was produced by fellow Bad Religion member, Brett Gurewitz (Mr. Brett), and features appearances by Jolie Holland, and members of The Weakerthans, in contrast to American Lesion, where Graffin recorded the entire album by himself. ", "A special Vinyl edition was released to celebrate Record Store Day 2017.", "\n\nTrack listing \nThe Epitaph records website gives the track listing as:\n\n \"Don't Be Afraid to Run\" – 4:12\n \"Omie Wise\" – 3:53\n \"Cold as the Clay\" – 3:19\n \"Little Sadie\" – 2:35\n \"Highway\" – 2:34\n \"Rebel's Goodbye\" – 3:52\n \"Talk about Suffering\" (with Jolie Holland) – 3:36\n \"Willie Moore\" – 3:56\n \"California Cotton Fields\" (with Jolie Holland) – 2:32\n \"The Watchmaker's Dial\" – 2:30\n \"One More Hill\" – 3:02\nTracks #1, 3, 5, 6, 10 written by Greg Graffin, tracks #2, 4, 7, 8, 11 are traditional songs with many versions and unknown writers, track #9 by Dallas Frazier & Earl Montgomery.", "\n\nAnother track, Footprints in the Snow, was originally announced as the 12th track of the album, but was removed during production.", "\n\nPersonnel \n Greg Graffin – vocals, acoustic guitar, harmonica, piano\n Jolie Holland – background vocals\n Brett Gurewitz – background vocals\n Stephen Carroll – guitar/slide guitar\n Joe Wack – guitar\n Chris Berry – guitar, banjo\n David Bragger – fiddle, banjo, mandolin\n Greg Smith – bass guitar\n Jason Tait – drums\n\nReferences \n\nCategory:Greg Graffin albums\nCategory:2006 albums\nCategory:Folk albums by American artists\nCategory:Anti- (record label) albums\nCategory:Alternative country albums by American artists\nCategory:Old-time music" ]

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[ "Partial nephrectomy versus radical nephrectomy for large (≥ 7 cm) renal tumors: A systematic review and meta-analysis.", "\nWe conducted a meta-analysis to evaluate the efficiency and safety of partial nephrectomy (PN) compared with radical nephrectomy (RN) for large (≥7 cm) renal tumors. ", "A comprehensive literature search with no restrictions on language or region was conducted from August up to October in 2018 in the electronic databases of PubMed, EMBASE, the Cochrane Library, and Scopus. ", "Studies meeting the inclusion criteria were subjected to a systematic review and cumulative meta-analysis to assess the oncological, functional, and perioperative outcomes of PN compared with RN for large renal tumors. ", "Sensitivity analyses were performed by repeating the original meta-analyses with exclusion of the lowest-weighted or lowest-scored study. ", "Thirteen retrospective studies including 2906 patients (PN: 1172; RN: 1734) were included in our analyses. ", "The pooled hazard ratio (HR) of overall survival (OS) indicated significant differences between the PN and RN groups (HR: 0.76; p = 0.001), although no significant difference was observed between the two groups in terms of cancer-specific survival (CSS; HR: 0.91; p = 0.51). ", "The pooled eGFR decrease was significantly lower in the PN group than that in the RN group (mean difference (MD): 11.59; p < 0.001). ", "PN was associated with longer operative time and more estimated blood loss (MD: 65.33 min, p < 0.001 and MD: 97.83 ml, p < 0.001, respectively). ", "Pooled odds ratios (ORs) revealed that, compared with RN, PN is associated with a significantly higher risk of low-grade and high-grade (OR: 1.59, p = 0.01 and OR: 7.35, p < 0.001, respectively) surgical complications. ", "No statistical significances were changed in sensitivity analyses on all outcome variables, except for that on the low-grade complication when excluding the lowest-scored study. ", "All results were pooled using the fixed-effects model due to the nil or low heterogeneity. ", "No obvious publication bias was screened about reporting OS. ", "In conclusion, while PN for large (≥7 cm) renal tumors is associated with better OS compared with RN, these methods show a similar CSS. ", "However, the advantages of PN, a more involved procedure than RN, in preserving renal function are accompanied by a higher risk of surgical complications. ", "Large-sample and well-designed randomized controlled trials with extensive follow up are needed to confirm and update our conclusions." ]

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[ "Adsorbent carbon, particularly activated carbon, is used extensively for a variety of purposes many of which depend to a considerable extent on the large surface area and surface activity of the carbon particles. ", "Carbon therefore is used in many filter applications. ", "For example, carbon filters are used in water filtration systems to remove dangerous organic compounds that are present in drinking water, as disclosed in U.S. Pat. ", "No. ", "4,561,976.", "\nWojcik and Karpinski described, in Chemia Stosowana XII, 2, 351 (1978) a process of modifying carbons by treating activated carbon with trimethylchlorosilane and dimethylsulfoxide. ", "The modified carbon displayed lower adsorption properties for water and ethanol vapour. ", "The reduction of adsorption properties with respect to water vapour was larger than with respect to ethanol.", "\nIn the present invention, chlorinated silanes are avoided. ", "If chlorinated silanes are used hydrogen chloride (HCl) will be produced during the silylating process. ", "It is thus possible that the silylated carbon produced also contains trapped HCl, that may then leach out of the treated charcoal and cause problems such as corrosion." ]

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[ "Gatineau Satellite Station\n\nThe Gatineau Satellite Station is a Canadian satellite station located in Cantley near Gatineau , in the province of Québec. ", " Like the Prince Albert Radar Laboratory, it was originally a military Radar station, operated by the Canadian Defence Research Telecommunications Establishment (DRTE), a division of the Canadian Defense Research Board. ", "With the two satellites / radar stations, it is possible to monitor the whole airspace over Canada, as well as parts from the USA and Alaska.", "\n\nTasks and equipment \nThe plant, which is still operated today, is primarily used as an earth station. ", "It has a large factory building and a 13-meter-diameter satellite antenna, replacing two old 10-meter-diameter antennas in June 2014.", "\n\nUsed as earth station for the following satellites:\nFormerly:\n ERS-2\n Envisat\n RADARSAT-1\nCurrent:\n Landsat 7\n RADARSAT-2\nFuture:\n RADARSAT Constellation\n\nExternal links \n Gatineau Satellite Station (English)\n\nExternal links \n\nCategory:Space program of Canada\nCategory:Outaouais" ]

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[ "Swimmers honored at Lake Mohawk Pool\n\nLong-time team members are off to college\n\nPhotos\n\nHigh school seniors and soon to be college freshmen, from left, Bridget Hilgendorff, Ryan Ryersen and Lizzie Wolfe enjoy their last home meet as Hawks swimming for Lake Mohawk Pool. ", "Not pictured, Samantha Russo.", "\nPhoto by Rose Sgarlato\n\nby Rose Sgarlato\n\nSPARTA— In a special poolside ceremony at Lake Mohawk Pool, four outgoing swimmers were honored on July 31 for their dedication to the team: Ryan Ryerson, Bridget Hilgendorff, Samantha Russo and Lizzie Wolfe.", "\n\nAll are 18, have recently graduated high school and are heading off to college.", "\n\nMost members of this gang have been a Lake Mohawk Hawk — the name of the Lake Mohawk Pool swim team — for more than half their lives, clocking in more than 10 years swimming in the summers for Lake Mohawk Pool, formerly known as The Cruiser Club. ", "During the school year, they swim for either their high school or NJ Club team and sometimes both.", "\n\nTheir coach, Tim Holovacs has been onboard for 10 years, but his legacy at Lake Mohawk Pool dates back almost 30 years ago to when he swam competitively at the pool and also coached in summers.", "\n\n“Tonight we honor our seniors, swimmers I have seen grow up over the years,\" Holovacs said. \" ", "I have too many fond memories of them all to recount here. ", "These are four swimmers who we could count on to be the core of the team.\"", "\n\nHilgendorff and Wolfe have been on the team since 8 years old. ", "They volunteered along the way to earn a coaching job.", "\n\n“Bridget and Lizzie stuck with us, eventually moving up to become full fledged coaches who have been instrumental in teaching our younger swimmers the skills and the fun that make our team great,” Holovacs said. “", "Filling two roles, coach and swimmer, can be tough sometimes but I can always count on them both to hop in to anything we need them to swim while corralling the younger swimmers so our practices and meets run smoothly.”", "\n\nHilgendorff will attend Connecticut College in the fall but is giving swimming a break. ", "Her favorite stroke is fly and best time is a 30.85.", "\n\n“I love the Lake Mohawk Hawks Swim Team because everyone cheers each other on whether they're 8 or 18,\" Hilgendorff said. \"", "When I'm racing and I see someone next to me I just know that I have to push myself to try and get the points for the team.”", "\n\nLizzie Wolfe will be attending Villanova University where she is entertaining joining the Club Team.", "\n\nSamantha Russo, a Hawk for 10 years, will be attending Bloomsburg University and, though swimming is not on her agenda, she said she will miss “ the nerve and adrenaline rush\" she gets right before diving in.", "\n\n“It has always been a fun experience, something I look forward to every summer. ", "Everyone is just so close. ", "We are more like family,” Russo said.", "\n\nHolovacs has fond memories of Russo.", "\n\n“Sam Russo, who is unfortunately away for tonight’s meet, always kept the mood light and kept me laughing,\" he said. \"", "Like the time when I was taking video of another swimmer's technique and Sam photo-bombed the video while passing by.”", "\n\nRyan Ryerson loves swimming because he enjoys seeing himself improve, especially in breaststroke, his favorite. ", "He has been on the team for six years and will be attending Syracuse University, where he intends to pursue club swimming.", "\n\n\"I’ve always enjoyed swimming on the Hawks’ swim team as it is a great way to stay in shape, make friends and have fun,\" Ryerson said. \"", "Helping the team win the meet drives me to beat the person in the lane next to me.”", "\n\n“Ryan Ryerson could always be called upon to swim whatever we needed,\" Coach Holovacs said. \"", "When he was, I think, 12 years old, we called him 'The Lady’s Man' because almost every meet we needed him to swim up with the 15-18 year old girls, so we could a field relay and keep competitive. ", "He was always willing to step up and swim up, sometimes as much as two age groups, and do whatever was needed to help the team.”", "\n\nCertainly these swimmers will be missed.", "\n\n\"These four swimmers have been great teammates and all of them will be sorely missed next year. ", "Thank you all for being such an important part of our team,” Holovacs said.", "\n\nThe Lake Mohawk Pool is a longstanding private pool club, located on Lake Mohawk in Byram Township, which has no residency requirements for membership." ]

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[ "Minimal in-person support as an adjunct to internet obesity treatment.", "\nInternet-based weight-loss programs appear promising in the short-term but, to date, have not been able to produce the level of weight loss seen in traditional in-person treatment; thus, novel approaches are necessary. ", "Using a combination of interactive technology and in-person support has been beneficial in other areas of medicine. ", "The aim of this study is to compare 12-month weight-loss outcomes of an Internet-only behavioral weight-loss treatment with the same program supplemented with monthly in-person meetings. ", "One hundred and twenty-three participants were randomized to an Internet-only (n = 62) or an Internet + in-person treatment (I+IPS; n = 61). ", "All participants then participated in a 12-month behavioral weight-loss program conducted over the Internet. ", "The groups met online weekly for the first 6 months and biweekly for the second half of the intervention. ", "The I+IPS group had access to the same Web site as the Internet-only group but, once a month, attended an in-person meeting in place of an online chat. ", "Assessments included body weight, program adherence, and social support measures. ", "An intent-to-treat analysis (n = 123) revealed there were no significant Group x Time differences (p = .15) in weight loss at either 6 (-6.8 +/- 7.8 vs. -5.1 +/- 4.8, p = .15) or 12 months (-5.1 +/- 7.1 kg vs. -3.5 +/- 5.1 kg, p = .17, for Internet-only and I+IPS, respectively). ", "Differences between groups for those completing all measures (n = 77) also revealed no significant differences at 6 months (-9.2 +/- 7.0 kg vs. -6.9 +/- 4.2 kg, p = .08) or 12 months (-8.0 +/- 7.5 kg vs. -5.6 +/- 5.5 kg, p = .10 for the Internet-only and I+IPS conditions, respectively). ", "Supplementation of an Internet weight-loss treatment with monthly in-person meetings did not result in greater weight losses over 12 months. ", "Dynamic, socially supportive, and interactive elements of the Web site may have obviated the need for further interpersonal behavioral counseling." ]

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[ "Social Inequality, Life Course Transitions, and Adolescent Development: Introduction to the Special Issue.", "\nConceptualizing adolescent development within a life course framework that links the perspectives on social inequality and early life course transitions has largely been absent from previous research. ", "Such a conceptual model is needed, however, in order to understand how the individual development of agentic capacities and the opportunities and constraints inherent in the social contexts of growing up interact and jointly affect young people's trajectories across the adolescent life stage. ", "We present the corner stones of the conceptual \"trident\" of social inequality, life course transitions, and adolescent development and identify three major themes the eleven contributions to this special issue address within this conceptual framework: social and individual prerequisites and consequences of coping with life course transitions; intergenerational transmission belts of social inequality; socialization of agency in and outside the family home. ", "These three themes exemplify the great analytical potential inherent in this framework." ]

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[ "Beer and wine producer Constellation Brands is seeing an uptick in the millennial generation's consumption of alcohol and, according to a company executive, that's in part thanks to one specific reason.", "\n\n\"When you said the millennials are drinking more, I'm like: That's because they have kids,\" Barclays analyst Lauren Lieberman said.", "\n\nLieberman made the comment somewhat jokingly during a discussion with Constellation Brands CFO David Klein, who was speaking with Lieberman at the Barclays Global Consumer Staples Conference on Wednesday.", "\n\n\"Well, I think that's exactly the answer,\" Klein responded.", "\n\nHe cited Constellation's research on millennials to back up his broader thesis: The company found that in 2013, millennials consumed about 24 alcoholic drinks per month. ", "By this year, that number has climbed to about 29 per month – with about 77% of all millennials in the U.S. consuming alcohol, according to Klein.", "\n\n\"What we don't know though is will we see that same thing with Gen Z as they age, will they — will life get more stressful for them and they drink a little more? ", "But it's too early to tell, but we definitely have seen that with millennials,\" Klein said.", "\n\nKlein added that Generation Z, ages 21 to 24, are consuming alcohol \"slightly more slowly\" than millennials did.", "\n\n\"I think what we have is people saying that they're drinking less or drinking better, but that's really driving people into trends like Corona Premier and seltzer and Mic Ultra, and brands like that,\" Klein saId.", "\n\nTwitter user @bluff_capital first noted the exchange on Thursday." ]

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[ "Adecco har sendt et propagandaskriv til sine arbeidere med et intervju av en mønsterarbeider som angivelig blir trigget av midlertidige arbeidsforhold. ", "Det spørs om hun hadde blitt like trigget hvis hun visste at hovedaksjonæren i Adecco er mangemilliardær.", "\n\n— Mange synes det er rart å gi slipp på det faste, men de ser ikke fordelene med å være midlertidig ansatt. ", "Noen ser usikkerhet – jeg ser frihet.", "\n\nOrdene kommer fra Anniken Edelsteen, som er ansatt og intervjuet av Adecco. ", "Intervjuet er distribuert til Adeccos ansatte med [email protected] som avsender. ", "Hensikten er trolig å få andre midlertidige ansatte til å innfinne seg meg usikkerheten som følger av et slikt ansettelsesforhold.", "\n\nLES OGSÅ: Dette tjener rikingene som vil kutte lønne til vanlige folk\n\nMidlertidig ansettelser er ikke gladstoffmateriale\n\nDet er sjeldent det publiseres gladsaker om midlertidige ansettelser og bemanningsbyråer. ", "Med god grunn. ", "I de fleste tilfeller ønsker ikke vanlig folk seg midlertidige ansettelser. ", "I en undersøkelse utført av Norstat i 2016 svarte 77 prosent av befolkningen at fast jobb er viktig, eller svært viktig for dem i fremtiden. ", "I aldersgruppen 19-29 er det 89 prosent som sier dette, ifølge Klassekampen. ", "Midlertidighet er altså ikke noe den overveldende majoriteten av lønnsarbeidere ønsker.", "\n\nBemanningsbyråenes effekt på norsk arbeidsliv assosieres først og fremst med økende grad av sosial dumping og en rasering av ordnede arbeidsforhold. ", "Når svært mange i fagbevegelsen tar til orde mot uvesenet er ikke det tilfeldig. ", "Selv den beste journalist kan ikke lage komedie av tragedie.", "\n\nLES OGSÅ: Den sosialdemokratiske lønnsadelen\n\nSelv ikke Dagens Næringsliv klarte å grave opp en gladsak\n\nDagens Næringsliv gjorde imidlertid et hederlig forsøk i fjor med utlysningen: Har du et vikariat og elsker det? ", "Dessverre for både Dagens Næringsliv og arbeidsgiverorganisasjonene fikk de ikke inn et tilstrekkelig godt eksempel, så det ble ingen sak.", "\n\nVi må anta at det er med dette som bakteppe at Adecco har bestemt seg for å ta saken i egne hender og lage sin egen gladsak om Anniken Edelsteen. ", "HR-konsulent i Adecco Trondheim, Wenke Eriksen, kan opplyse at Edelsteen ikke har mottatt honorar for intervjuet, men har stilt opp frivillig. ", "Leseren får selv vurdere om det taler til Adeccos fordel eller ei. ", "Det som er sikkert er at rent økonomisk lever ikke Edeelsteen noen lukrativ tilværelse. ", "I skattelistene for 2015 er hun registrert med en skattbar inntekt på 192 971 kroner.", "\n\nLangt mer lukrativt er det for lederne av bemanningsbyråene som leier ut mønsterarbeidere som Edelsteen. ", "Konsernsjef i Adecco, Torben Sneve, hadde en inntekt på 3,8 millioner kroner ifølge skattelistene for 2015. ", "Adecco er ikke i særklasse. ", "Inntekten til administrerende direktør i Jobzone, Espen Hem Jakobsen, var på 1,8 millioner kroner, mens administrerende direktør i Randstad Norge, Eivind Bøe, hadde en inntekt på 4,1 millioner kroner. ", "Øverst på pallen troner konsernsjef i Manpower, Maalfrid Brath, med en skatteregistrert inntekt i 2015 på 6,1 millioner kroner.", "\n\nLES OGSÅ: Når Kristin Clemet ber oss roe ned vet vi det er på tide å protestere\n\nTrigget av å øke formuen til en mangemilliardær?", "\n\nRiktig ille blir det først når vi går til aksjonærene. ", "Adecco Norge AS er 100 prosent eid av Olsten Norway AS som igjen er 100 prosent eid av Adecco Group. ", "En av hovedaksjonærene i Adecco Group er Philippe Foriel-Destezet med en formue på 2,6 milliarder dollar, omtrent 21,5 milliarder kroner. ", "Som Carl I. Hagen vil sagt det: Det er 21 500 millioner det. ", "Dersom Anniken sparer alt hun tjener og fortsetter å stå på i bemanningsbransjen kan også hun bli like rik som Philippe. ", "I år 113 432 etter Kristus.", "\n\nHvorfor har vi organisert oss selv slik?", "\n\nPolitikk blir ikke til av seg selv og nye lover og organisasjonsformer skaper nye vinnere og nye tapere. ", "Når Adecco forsøker å lure oss til å tro at midlertidighet er bra og noe arbeidstakerne ønsker er det naturligvis fordi de har interesse av økt midlertidighet. ", "Dette har arbeidsgiverorganisasjonene lobbet for lenge og de vinner stadig frem i den offentlige samtalen. ", "Ved fjorårets NHO-konferanse var det den offentlige ansatte Anita Krohn Traaseth (skatteregistrert inntekt på 2,4 millioner kroner) som feilaktig påstod at ungdom heller vil ha ”frihet” enn fast jobb.", "\n\nAt de rike forsvarer sine egne interesser kan vi ikke annet enn forvente. ", "Spørsmålet er om vi, vanlige folk, ikke burde begynne å kjempe litt bedre for våre egne interesser. ", "Et sted å begynne er høyere progressiv beskatning av folk med millioner i inntekter og milliarder i formue. ", "Det er valg i september." ]

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[ "3 responses to “1991 Flashback Friday Random 10”\n\n1. ", "Blue Canadian Rockies – The Byrds\n2. ", "It was a Very Good Year – The Sounds Like Us\n3. ", "Get Off Your Porch – Charlie Pickett\n4. ", "People Have the Power – Patti Smith\n5. ", "Respect – Aretha Franklin\n6. ", "Talk Me with You (When You Go) – The Jayhawks\n7. ", "Golden Slumbers – The Beatles\n8. ", "High Road – The Feelies\n9. ", "I Aint’ Ever Givin’ In – Fred Eaglesmith\n10. ", "So Fine – Chancellors\n\nBonus: What You Do to Me – Teenage Fanclub\n\nFour Decades for me two but 5 songs from the 60’s which is rare for me." ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nWPF triggering different Storyboard for the same Target multiple times\n\nCreating a card game and when the game starts, 5 cards are given to a hand. ", "Using the storyboard the card goes from the deck to the hand position 0-4 respectively. ", "There is 5 story, one for each 5 hand position.", "\nThe story are being called from a for loop which: \n\nget a new card from the Deck.", "\nRun the corresponding Story.", "\nDisplay the new card (the real one not the one coming from the Deck).", "\nReset the card coming from the Deck to its original position.", "\n\nThe problem is only the last story called from the for loop is being played. ", "If I change the loop number of occurrence, the stories are working for all the positions, but always only play the last one called . ", "\n<Page.", "Resources>\n\n <Storyboard x:Name=\"sDeckToHandPositionOne\" TargetName=\"HandPositionOne\"> \n <DoubleAnimation Storyboard.", "TargetProperty=\"(Image.", "RenderTransform).(TranslateTransform.", "X)\" To=\"0\" Duration=\"0:0:1\"/>\n <DoubleAnimation Storyboard.", "TargetProperty=\"(Image.", "RenderTransform).(TranslateTransform.", "Y)\" To=\"0\" Duration=\"0:0:1\"/>\n </Storyboard>\n\n <Storyboard x:Name=\"sDeckToHandOne\" TargetName=\"HandPositionOne\"> \n <DoubleAnimation Storyboard.", "TargetProperty=\"(Image.", "RenderTransform).(TranslateTransform.", "X)\" To=\"0\" Duration=\"0:0:1\"/>\n <DoubleAnimation Storyboard.", "TargetProperty=\"(Image.", "RenderTransform).(TranslateTransform.", "Y)\" To=\"0\" Duration=\"0:0:1\"/>\n </Storyboard>\n\n</Page.", "Resources>\n\nRunDeckToHandStory(string target) {\n\n string myStory = \"sDeckToHandPositionOne\";\n Storyboard story = (Storyboard)UI.Ctrl.", "Resources[myStory] as Storyboard;\n var moveX = (DoubleAnimation)story.", "Children[0];\n var moveY = (DoubleAnimation)story.", "Children[1];\n moveX.To = ImgHandCoordinates[Position][target] - ImgHandCoordinates[DeckOfCards][0];\n moveY.To = ImgHandCoordinates[Position][target] - ImgHandCoordinates[DeckOfCards][1];\n story.", "Begin();\n\n}\n\nFor (i=0; i<5; i++) {\n\n int targetHandPosition = i;\n newCard = GetNewCardFromDeck();\n RunDeckToHandStory(targetHandPosition);\n DisplayNewCard(targetHandPosition, newCard);\n ResetDeckCardPosition();\n\n}\n\nnote: This is an example, it might contain typo.", "\n\nA:\n\nIf I understand your problem correctly, you are trying to run a collection of Storyboard sequentially, that is, the next Storyboard needs to wait for the completion of the current Storyboard; however, your code is playing the collection of Storyboard in parallel, and the outcome is, only the last Storyboard is played, the others are simply ignored.", "\nI think you can line up the Storyboards in a queue, and only play the first Storyboard, and register a handler for the Storyboard's Completed event, in which you play the next Storyboard in the queue. ", "Like this\nvar storyboardQueue = new Queue<Storyboard>();\nstoryboardQueue.", "Enqueue((Resources[\"sDeckToHandPositionOne\"] as Storyboard));\nstoryboardQueue.", "Enqueue((Resources[\"sResetPosition\"] as Storyboard)); \nstoryboardQueue.", "Enqueue((Resources[\"sDeckToHandPositionTwo\"] as Storyboard));\nstoryboardQueue.", "Enqueue((Resources[\"sResetPosition\"] as Storyboard));\nstoryboardQueue.", "Enqueue((Resources[\"sDeckToHandPositionThree\"] as Storyboard));\nstoryboardQueue.", "Enqueue((Resources[\"sResetPosition\"] as Storyboard));\n//... other storyboards\n\nPlayNextStoryBoard(storyboardQueue);\n\nprivate void PlayNextStoryBoard(Queue<Storyboard> storyboardQueue)\n{\n if (storyboardQueue.", "Count > 0)\n {\n var sb = storyboardQueue.", "Dequeue();\n sb.", "Completed += (o, e) =>\n {\n PlayNextStoryBoard(storyboardQueue);\n };\n sb.", "Begin();\n }\n}\n\n" ]

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[ "Problem {#s1}\n=======\n\nIn 2015, National Health Service (NHS) England published the National Safety Standards for Invasive Procedures (NatSSIP)[@R1] based on recommendations in a report from the Surgical Never Events Taskforce.[@R2] This directed all healthcare providers that delivered NHS funded care to adhere to the safety standards contained within the NatSSIP when performing any invasive procedures on patients.", "\n\nThe NatSSIP provides a skeleton framework for any invasive procedure and as such some components of the NatSSIP are more or less applicable in different procedures or environments. ", "The intention is for the NatSSIP to be modified to a Local Safety Standard for Invasive Procedures (LocSSIP). ", "This LocSSIP is a set of safety standards drawn from the NatSSIP that apply to a particular clinical situation and are designed for a given hospital trust, taking into account human factors and working as teams.", "\n\nUniversity Hospitals Bristol NHS Foundation Trust (UHB) is a large teaching hospital. ", "Endoscopy is performed in three sites across the trust: the Bristol Royal Infirmary, Bristol Children's Hospital and South Bristol Community Hospital. ", "Endoscopies are also performed outside of the endoscopy departments, mainly in operating theatres and the intensive care unit. ", "Endoscopies are performed by a variety of clinicians including surgeons, gastroenterologists, respiratory physicians and nurse endoscopists. ", "UHB offers both routine endoscopic services widely available in secondary care institutions and more advanced, interventional endoscopy available only in tertiary centres, such as endoscopic mucosal resection and radiofrequency ablation for dysplastic Barrett's oesophagus and early oesophageal cancer.", "\n\nThe overall aim of this project was to develop and implement the LocSSIP in the endoscopy department at UHB. ", "Our SMART aim and the focus of this project was to ensure completion of the standard safety checklist (SSC) in 100% of patients, as directed by NHS England,[@R1] following development of the LocSSIP after a 12-month period. ", "To ensure quality was maintained, our aim was to ensure compliance scores of \\>80% after 12 months.", "\n\nAs this was new guidance, no baseline data was available for comparison. ", "Therefore, a plan was made to design and implement the LocSSIP over a 6-month period. ", "Following introduction of the checklist, baseline assessment of compliance was made; with repeat measurement after change, cycles had been implemented.", "\n\nBackground {#s2}\n==========\n\nEndoscopy allows direct visualisation of the lumen of the gastrointestinal and respiratory tract for diagnostic and therapeutic purposes. ", "As such, it is an invaluable tool for clinicians and patients. ", "It is an invasive procedure, often carried out under conscious sedation or general anaesthesia and as a consequence carries with it significant risk.", "\n\nThe National Confidential Enquiry into Patient Outcome and Death report 'Scoping our Practice' investigated over 1800 deaths within 30 days of therapeutic endoscopy and highlighted failings in practice across the UK.[@R3] It highlighted the shortcomings in procedure planning, safe administration of sedation and patient monitoring as opposed to technical competencies of the endoscopist. ", "The report made 21 recommendations to improve patient safety. ", "There are no large-scale evaluations available to assess whether these recommendations have been implemented and their effectiveness.", "\n\nThere is extremely limited published data specific to patient safety in endoscopy. ", "One single centre study found that a median of one adverse event occurred in each endoscopic procedure (n=140) carried out over a 4-month period of observation.[@R4] This study observed the whole patient pathway: preprocedure, intraprocedure and postprocedure.", "\n\nIn 2004, the National Patient Safety Agency (NPSA) published a report outlining the 'seven steps to patients safety' in response to the increasing complexity and risk associated with effective, modern healthcare.[@R5] In 2009, a modified version of the WHO surgical safety checklist became a requirement within the NHS.[@R6] The value of these developments was recognised and formed the basis of the NatSSIP published in 2015. ", "It has been recognised that clinical errors cause significant morbidity, mortality and expense across the NHS, and the NatSSIP is an effort to 'standardise, educate and harmonise' safety standards across invasive procedures in the NHS.", "\n\nMatharoo *et al* [@R7] published an excellent review into implementing SSCs in endoscopy.[@R7] The paper identified enablers and barriers to implementation of an endoscopy checklist. ", "Enablers included strong leadership skills from within the endoscopy team, alongside seeking support from 'external' respected sources and other departments familiar with surgical checklists. ", "Barriers included professional hierarchy, lack of evidence for its use within endoscopy, viewing it as a 'tick box' exercise, cumbersome duplication of documentation and lack of team engagement.", "\n\nMeasurement {#s3}\n===========\n\nThe WHO SSC has been in use in operating theatres for several years and is a well-embedded part of the culture in that environment. ", "This checklist forms a good exemplar on which to base LocSSIP guidance for endoscopy, with similar end results and targets. ", "Previous root cause analysis of two never events at UHB in 2014 had found 100% completion of the WHO SSC, but varying levels of attention from staff during its completion, identified as a possible contributor to the never events. ", "In response to this, a 'tick box' paper SSC was replaced by a verbal checklist that follows visual prompts on a wall-mounted poster. ", "NHS England recommended that organisations should develop scoring systems that allowed the quality of the performance of LocSSIPs to be assessed. ", "A 'compliance score' was therefore developed and implemented to assess the quality and attention levels of team members after its implementation.", "\n\nA 'completion score' documents that the SSC has been performed. ", "Points are then deducted from this initial score for not fully completing the checklist and for incorrect timing of the checklist, forming a 'full completion score'. ", "Inattention is measured at time out, and categorised as mild (any team members completing a small task), moderate (talking to a colleague) or severe (not present). ", "This inattention score is then deducted from the 'completion score' to give an overall 'compliance score'.", "\n\nData were collected prospectively for 'completion score', 'full completion score' and the 'compliance score' to gain baseline data following design of the checklist and to compare outcomes following our interventions. ", "To collect this data, we planned a period of independent observation within the endoscopy department at the Bristol Royal Infirmary over a 2-week period, 2 months after implementation of the safety checklist. ", "A medical student observed endoscopies and recorded data for each case on a standardised data collection pro forma. ", "Following implementation of change cycles, a further observational period was planned over 2 weeks, 12 months later. ", "Feedback from staff directly involved with the SSC was sought to establish the likelihood of the observed outcomes being due to our interventions.", "\n\nDesign {#s4}\n======\n\nThe 'perioperative never event working group' is a trust wide body at UHB drawing members from a wide variety of specialties and professions. ", "One of its roles is to facilitate the implementation of the NatSSIP across the trust. ", "The team implementing the NatSSIP in endoscopy was members of this group and had access to support from administrative and managerial staff through the group.", "\n\nThe initial development process was to carefully examine the NatSSIP and to identify points that were or were not applicable to endoscopy. ", "This allowed a draft LocSSIP to be written and circulated for review by the working group and lead nurse for endoscopy. ", "Concurrently, draft documentation was produced to support initial implementation of the LocSSIP.", "\n\nDraft LocSSIP guidance was based on the WHO surgical safety checklist. ", "The five steps of surgical safety consist of a 'team brief' at the beginning of a list to highlight any foreseeable problems before the list begins. ", "Each procedure has a 'sign in' when the patient arrives, 'time out' immediately prior to the procedure starting and a 'sign out' prior to the patient leaving the procedure room. ", "Finally, an end of list debrief is important to raise any learning points.", "\n\nA wall-mounted checklist was produced to provide a focus for all members of the clinical team and prompt of the information required for checklist completion. ", "A pro forma was produced to be included in a patient's notes to provide written documentation of completion of all stages of the checklist. ", "Staff were given education to promote a 'safety awareness' culture within the department.", "\n\nStrategy {#s5}\n========\n\nOur SMART aim and the focus of this project was to ensure completion of the SSC in 100% of patients, as directed by NHS England, following development of the LocSSIP after a 12-month period. ", "To ensure quality was maintained, our aim was to ensure compliance scores of \\>80% after 12 months. ", "In order to do this, the project was broken into several phases.", "\n\nDevelopment {#s5a}\n-----------\n\nAs discussed above, a draft of the LocSSIP was produced and circulated. ", "Draft documentation was also developed to support the LocSSIP.", "\n\nPDSA cycle 1: trial {#s5b}\n-------------------\n\nThis part of the process was designed to refine draft documentation and identify any obvious flaws in the early draft of the checklist.", "\n\nTo do this, the clinical lead attended an endoscopy list as an observer. ", "Several variations of the checklist and documentation were trialled alongside the existing patient pathway. ", "Between patients, comments were made by the endoscopy staff and further adaptations were made before the next patient's procedure. ", "The adapted format was then trialled on the next patient.", "\n\nThis was, effectively, multiple PDSA cycles carried out over the course of a few hours to develop the checklist and its supporting documents.", "\n\nPDSA cycle 2: development {#s5c}\n-------------------------\n\nInitial feedback from staff after a pilot of the developed documentation showed that there was significant repetition in the 'sign in' and 'time out' components of the checklist. ", "While this is essential in an operating theatre where the 'sign in' occurs before anaesthesia and the 'time out' immediately prior to the first incision. ", "Different staff are present for the two stages of the procedure and there is a significant time lapse between arrival in the anaesthetic area and first incision. ", "This is less applicable in endoscopy when the same staff are present for both steps and there is no significant delay between the steps. ", "This format was therefore felt to be cumbersome and disruptive to the endoscopy team, introducing significant delays to the high volume endoscopy lists.", "\n\nWe hypothesised that the negative feedback would equate to poor compliance when the checklist was implemented. ", "We decided, therefore, to combine the 'sign in' and 'time out' steps. ", "This format had been previously proposed by the NPSA when introducing safety checklists into interventional radiology.[@R8]\n\nPDSA 3: roll out {#s5d}\n----------------\n\nVersion 1 of the checklist and documentation was produced and approved following changes made through PDSA 2.", "\n\nA date was set to roll out the checklist, initially only at one of the endoscopy locations at UHB to enable full training of the team. ", "In the weeks leading up to the start date, educational sessions were carried out with endoscopy staff.", "\n\nThe checklist was introduced and embedded for 2 months before collecting baseline data on completion and compliance. ", "During this time, support was given to clinicians and support staff to maximise effectiveness.", "\n\nOur initial assessment of the data showed that completion of the checklist was carried out in all cases at 'time out', but only 91% at 'sign out'. ", "Reasons for failure to conduct 'sign out' includes changeover in staff and where the procedure did not go to plan (eg, unsuccessful gastroscopy due to stricturing from previous surgery). ", "In clinical situations that deviate from normal, the checklist potentially has an even more important role, and this was therefore, of some concern. ", "Qualitative measurements showed high levels of inattention from members of the team during the 'sign in' and 'sign out' stages, leading to poor compliance measurements.", "\n\nPDSA cycle 4: redesign and implementation {#s5e}\n-----------------------------------------\n\nPoor compliance measurements after completion of PDSA 3 led the LocSSIP implementation team to undertake a period of reflection and gain feedback from all team members to try to understand why compliance was poor.", "\n\nAn initial assumption had been made that staff were familiar with the WHO surgical safety checklist, having used this in theatres for a number of years, and therefore introducing a similar checklist in endoscopy would be an extension of this process. ", "However, a number of the endoscopy staff, both nursing and medical, had no prior theatre experience and therefore the process was entirely new to them. ", "On reflection, the team felt that more time needed to be spent with individuals, particularly those unfamiliar with the checklist in other contexts, to explain the purpose and value of the checklist, and therefore improve compliance. ", "Greater leadership within the endoscopy room and ownership of the checklist by one individual, who could be any member of the team, was also felt to have been useful.", "\n\nFeedback from a number of team members was the high level of repetition between some of the information sought within the checklist and information documented elsewhere within the existing care pathway documentation. ", "Analysis of results showed that when a question on the checklist had been answered in the pre-existing documentation, it was often glossed over or completely ignored.", "\n\nIn response to this, we felt that the best way to reduce repetition was to rewrite the patient care pathway documentation and thereby encourage all staff to engage more completely with the underlying principle of the LocSSIP: risk reduction. ", "The care plan was rewritten, minimising duplication and placing the checklist at the core of the document. ", "A full redesign of documentation required significant time and approval from a variety of committees across the trust. ", "This phase therefore took around 6 months to complete, before the new integrated checklist/patient care pathway could be introduced.", "\n\nWhen the revised documentation and version 2 of the checklist (online [Supplementary appendix 1](#SP1){ref-type=\"supplementary-material\"}) had been prepared, staff were given further educational sessions, and the clinical leads within each specialty were approached in an effort to further support its implementation. ", "Plans were made to perform observational reassessment of the data in July 2017, 12 months after baseline measurements had been made.", "\n\n10.1136/bmjoq-2017-000294.supp1\n\nThe number of adverse incidents reported in the department over the preceding 12 months was too small to allow statistical comparisons to be made to directly assess the efficacy of the checklist at reducing adverse incidents.", "\n\nResults {#s6}\n=======\n\n[Figure 1](#F1){ref-type=\"fig\"} summarises 'time out' and 'sign out' completion in the endoscopy department between assessments. ", "It shows improvement in performance on all measures except for 'time out' completion, where full compliance had been achieved in the initial assessment.", "\n\n{#F1}\n\nData from individual questions within the 'time out' and 'sign out' were also collected. [", "Table 1](#T1){ref-type=\"table\"} shows the proportion of times these questions were asked and answered during 'time out' between the two periods of assessment.", "\n\n###### \n\nPercentage of total 'time outs' that each checklist component was appropriatley completed\n\n Criteria 2016 (%) 2017 (%)\n ------------------- ---------- ----------\n Identity 100 100\n Consent 93 100\n Procedure 82 100\n Labels 100 100\n Allergies 84 96\n Coagulopathy 80 89\n Sedation plan 73 96\n Monitoring 73 96\n Equipment 73 93\n Diathermy 73 89\n Antibiotics 71 96\n Glycaemic control 82 89\n\n[Table 2](#T2){ref-type=\"table\"} shows the proportion of times individual questions were asked and answered during 'sign out' between the two periods of assessment.", "\n\n###### \n\nPercentage of total 'sign outs' that each checklist component was appropriatley completed\n\n Criteria 2016 (%) 2017 (%)\n --------------------------------- ---------- ----------\n Check patient details on report 76 89\n Equipment problems 71 82\n Follow-up arranged 73 96\n Recovery concerns 76 85\n Anticoagulation plan 76 85\n Specimen labelling 91 89\n\nThe composite score for compliance was 57% in 2016 and 90% in 2017.", "\n\nAfter the first audit, we identified that the lowest levels of compliance were seen in sections of the checklist where information was duplicated in the nursing care plan. ", "Following our interventions, there were significant improvements made, particularly in levels of attention and full completion of the checklist.", "\n\nThe poor compliance data seen at baseline assessment was unforeseen at the outset of the project. ", "The information sought during the 'sign in' and 'time out' was already being gathered within the nursing care plan prior to introduction of the formal checklist. ", "It was assumed that this would mean a smooth integration of the checklist in the endoscopy rooms.", "\n\nThe significant time involved in integrating the checklist with the nursing care plan documentation was an unforeseen part of the project and meant that less time than anticipated had passed before reassessment of the data was conducted.", "\n\nLessons and limitations {#s7}\n=======================\n\nA limitation of the study includes the 'Hawthorne effect', in which members of the team modify their behaviour due to their awareness of being observed. ", "The results may not therefore be a true reflection of everyday practice.", "\n\nSecond, the study may be limited by the sample size. ", "Baseline measurements observed 45 procedures, but on reassessment, this number was less at only 27 procedures during the 2 weeks of observation. ", "If performing this study again, it would be beneficial to gather similar numbers at both baseline and following interventions to increase the validity of results. ", "The 2-week period was needed to fit in with a special study module of the medical students involved as the independent observer and was therefore unable to be extended.", "\n\nA representative sample was attempted by rotating between different endoscopy rooms, and therefore covering different procedures performed by different teams. ", "However, use of the SSC in procedures such as bronchoscopy and endoscopic retrograde cholangiopancreatography were not observed. ", "Thus, conclusions from this audit may not be reliably drawn across the whole of endoscopy.", "\n\nThis project identified from previous adverse events within UHB that simply assessing completion of a checklist is not enough and that introducing a measurement of quality is essential to impact on safety. ", "This assessment of quality is a strength of the study. ", "However, the study makes the assumption that improving compliance with the checklist will go on to reduce adverse incidents. ", "Given that overall numbers of never events are very low, a much longer time frame is required to assess the impact of our changes on this and is outside the scope of the current project.", "\n\nConclusion {#s8}\n==========\n\nThe aim of our project was to introduce a LocSSIP and safety checklist to the endoscopy department at UHB. ", "Following its introduction, we aimed to achieve 100% completion of the SSC, with compliance levels \\>80% ensuring that this was performed in a high-quality manner, rather than simply a 'tick box' exercise. ", "Compliance rates over this 12-month time frame rose to 90% which is very encouraging, though there were still some aspects of the checklist that were incomplete.", "\n\nFeedback from all team members felt that the main contributions to the observed improvement were strong leadership within the endoscopy department, with a nominated individual taking ownership for the completion and being responsible to engage the whole multidisciplinary team at each 'time out' and 'sign in' checklist completion. ", "Broadening education on why the checklist was so important has helped to drive a wider cultural change that safety is the shared responsibility of all individual team members.", "\n\nEarly on in the development of the project, it became clear that simply adding in a checklist into the existing procedures of the endoscopy unit would lead to poor compliance. ", "We learnt that understanding the complete patient journey through the department and how the unit functioned meant that a tailored approach was required. ", "While this was a slight departure from the standard checklists seen in other parts of the hospital, it proved to be far more effective.", "\n\nThere was some concern from staff that patients would become anxious with repeated asking of a number of questions. ", "As part of the project, a small sample of eight patients were surveyed regarding their experience of being asked repeatedly to confirm details. ", "In all cases, the patients answered 'I would absolutely expect nothing less and I find it reassuring' and this is likely to have contributed to their answers of 'strongly agree' to being made to feel that their safety was the highest priority.", "\n\nThis project was an essential piece of work following the mandate from NHS England to implement LocSSIPs for all invasive procedures at a national level. ", "Use of the checklist is ongoing, and the trust is accountable for its use to Clinical Commissioning Groups and to the Care Quality Commission. ", "High completion and compliance rates after 12 months is very encouraging, but maintaining these high scores is essential in the longer term to maintain safety. ", "The development of LocSSIPs itself cannot guarantee the safety of patients, and it is essential that teams undergo regular, multidisciplinary training to promote teamwork and includes clinical human factor considerations.", "\n\nWhile ensuring patient safety is the primary incentive for the LocSSIP, Never Events are an enormous cost to an organisation. ", "Commissioners can withhold payment for the cost of the episode of care in which a Never Event has occurred and any subsequent costs involved in treating the consequences of a Never Event. ", "In addition, significant time and resources will be used in undertaking root cause analyses, leading to higher costs for the trust.", "\n\nThe project has succeeded in its initial goals, but there remains room for ongoing change and improvement. ", "Ongoing audit is essential, ideally with larger sample size to facilitate subgroup analysis and to highlight specific areas of weakness or specific procedures where compliance is poor. ", "This should allow more targeted interventions to reduce variation in standards.", "\n\nOur project demonstrates the initial development and implementation of LocSSIP within one department of our organisation. ", "The scoring systems developed to assess quality of its implementation are transferrable to other departments implementing LocSSIPs, and it is hoped that some of our experiences may help other departments who are at differing stages of implementation.", "\n\n**Contributors:** MCM is the main author of the manuscript and was the clinical lead in the QI project. ", "RKG is a significant contributor to the text of the article. ", "She made a significant contribution to the completion of the QI project. ", "EYX and CS collected and analysed the data for the results section of the paper. ", "RW redesigned and implemented the care plan as part of the QI team. ", "MKM was the supervisor of the project and significantly contributed to the writing of the manuscript.", "\n\n**Funding:** This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.", "\n\n**Competing interests:** None declared.", "\n\n**Patient consent:** Not required.", "\n\n**Provenance and peer review:** Not commissioned; externally peer reviewed.", "\n" ]

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[ "BRUSSELS -- The European Union's small antidisinformation team, Stratcom East, will get its own budget line, sources told RFE/RL on the sidelines of the Eastern Partnership summit in Brussels on November 24.", "\n\nStratcom East, comprising 14 people, was set up in 2015 by the EU, to fulfill three tasks: \"Effective communication and promotion of EU policies toward the Eastern Neighborhood,\" \"strengthening the overall media environment in the Eastern Neighborhood and in EU Member States,\" and, perhaps most significantly, \"to address and respond to disinformation activities by external actors.\"", "\n\nResponding to Russian propaganda and disinformation has been one of the main tasks.", "\n\nThe team has until now survived on around 200,000 euros taken from the EU's general strategic-communications budget.", "\n\nOfficials said now 1.1 million euros over the next three years will be directly dedicated to the unit to potentially hire more staff, to increase awareness in European Union member states, and to boost its media-monitoring work." ]

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[ "Alexandru Sătmăreanu\n\nAlexandru Ștefan Sătmăreanu (born 9 March 1952 in Oradea) is a Romanian former footballer whose teams included: Dinamo Bucureşti, VfB Stuttgart, and Fort Lauderdale Strikers.", "\n\nHonours\n\nClub\nDinamo Bucureşti\n Romanian League: 1972–73, 1974–75, 1976–77\n Trofeo Costa de Valencia: 1978\n\nNotes\n\nReferences\n\nExternal links\n\nFort Lauderdale Strikers stats\n\nCategory:1952 births\nCategory:Living people\nCategory:Romanian footballers\nCategory:Romania international footballers\nCategory:Association football defenders\nCategory:Liga I players\nCategory:FC Bihor Oradea players\nCategory:FC Dinamo București players\nCategory:VfB Stuttgart players\nCategory:Fort Lauderdale Strikers (1977–1983) players\nCategory:Expatriate footballers in Germany\nCategory:North American Soccer League (1968–1984) players\nCategory:North American Soccer League (1968–1984) indoor players\nCategory:Romanian expatriate sportspeople in Germany\nCategory:Romanian expatriate footballers\nCategory:Bundesliga players\nCategory:Expatriate soccer players in the United States\nCategory:Romanian expatriate sportspeople in the United States" ]

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[ "Fabulous! ", "Don't forget to share with your friends on Twitter and Facebook.", "\n\nHawaii House Committees Pass Marriage Equality Bill After Five Days Of Testimony\n\nAfter five days of public testimony in a joint House Judiciary & Finance Committee hearing, the 30-member panel voted Tuesday to pass Hawaii’s marriage equality legislation. ", "The bill will now go to the full House for a vote.", "\n\nHONOLULU — After more than 55 hours of testimony, the joint House committees voted Tuesday to pass Hawaii’s marriage equality bill, Senate Bill 1. ", "The House Judiciary Committee and Finance Committee voted 18 to 12. ", "The bill now goes to the full House for a final vote.", "\n\nBefore they voted, the House committees amended Senate Bill 1 to broaden a religious exemption that allows religious leaders to refuse service for same-sex marriage ceremonies and moved the effective date from Nov. 18 to Dec. 2.", "\n\nThe general public was allowed to register to testify until midnight on the first day of the House hearing Thursday, Oct. 31. ", "By the end of day, 5,184 people received registered numbers for testimony.", "\n\nTestifiers were allowed to speak for two minutes. ", "It was decided on Friday, Nov. 1, those who missed their numbers would be allowed another opportunity to testify after the more than 5,000 registered numbers had been called.", "\n\nThe line wraps around the corner to enter the hearing Monday. ", "Michelle Broder Van Dyke / Via BuzzFeed\n\nLawmakers in the House made it clear from the beginning they would listen to everyone, while conservative religious leaders encouraged testifiers to use up their allotted times and delay the hearing. ", "Conservatives attempted to stall the bill in hopes of defeating it.", "\n\nMonday morning lawmakers announced there would be tighter procedures for testifying at the hearing, including showing a photo ID, after allegations surfaced that people were testifying under registration numbers that did not match their names.", "\n\nIn this video a Honolulu police officer says “you would have to kill me” to enforce the bill:\n\nOn Tuesday afternoon, Chair of the House Finance Committee Sylvia Luke announced the end of testimony and Chairman of the House Judiciary Committee Karl Rhoads said while thanking staffers and the public that the joint committees hearing was “probably longest hearing ever in the history of Hawaii.”", "\n\nDuring the decision making process, the committees amended the bill to broaden a religious exemptions and moved the effective date to Dec. 2.", "\n\nThe House Judiciary Committee and Finance Committee voted to pass the bill.", "\n\nSB1 passed by a vote of 8-5 and 10-7 in the Judiciary and Finance Committees respectively. ", "Now goes to full House for second reading vote.", "\n\n— hihousedems (@HI House Democrats)\n\nHI House Democrats\n\n@hihousedems\n\nSB1 passed by a vote of 8-5 and 10-7 in the Judiciary and Finance Committees respectively. ", "Now goes to full House for second reading vote.", "\n\n/ Via\n\nThe bill will head to the full House Wednesday morning for a second reading. ", "Since the bill was amended, it will go back to the senate to be reconsidered, and will then be sent to Gov. Abercrombie for his signature.", "\n\n“The bill as amended is legally sound and is in accord with the Hawaii State Constitution. ", "We urge the Legislature to pass this bill, which will provide marriage equity and fully recognize religious beliefs in that context.”" ]

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[ "Q:\n\nWorking with Anonymous Types After Closing DB Connection\n\nI have code similar to the following.", "\nusing (MyEntities context = new MyEntities())\n{\n var activities = from act in context.", "Activities\n where act.", "ActTwittered == false\n select new { act.", "ActID, act.", "ActTitle, act.", "Category, act.", "ActDateTime, act.", "Location };\n\n foreach (var activity in activities)\n {\n /* ... */\n }\n}\n\nThis seems to work fine but my loop has a lot of processing. ", "I'm concerned that I'm leaving a database connection or other resources open during this processing.", "\nI tried declaring var activities before the using statement so I could process the data after the using statement, but this variable must be initialized where it is declared.", "\nCould someone who understands the inner workings of EF tell me if there are problems doing lengthy processing while an EF context is \"alive\", and how I make alleviate these problems.", "\nWhile I'm at it, perhaps you could also comment on the fact that I use act.", "Category.", "CatName within the loop. ", "This is a value from a related table. ", "Am I better to use a join in my EF query so I get the data all at once rather than forcing another (?) ", "database access to get the related data?", "\n\nA:\n\nYou can have the compiler infer the result type by calling a generic method on it:\n public static T CallFunc<T>( Func<T> theFunc )\n {\n return theFunc();\n }\n\n ... \n\n var activities = CallFunc( () =>\n {\n using( var context = new MyEntities() )\n {\n return \n (\n from act in context.", "Activities\n where act.", "ActTwittered == false\n select new { act.", "ActID, act.", "ActTitle, act.", "Category, act.", "ActDateTime, act.", "Location };\n )\n .ToList();\n }\n } );\n\n foreach( var a in activities ) ...\n\nDon't forget the .ToList() at the end, or your query won't be actually executed until you enumerate over it, which will happen after the context is closed.", "\n\nA:\n\nYour problem is in wanting the anonymous type to be accessible outside of its context. ", " You can use a specific type for your results and get the flexibility to access the values anywhere.", "\npublic class ActivitySummary\n{\n public int ActID { get; set; }\n public string ActTitle { get; set; }\n public string Category { get; set; }\n public DateTime ActDateTime { get; set; }\n public string Location { get; set; }\n}\n\n. . .", "\nList<ActivitySummary> activities;\n\nusing (MyEntities context = new MyEntities())\n{\n activities = from act in context.", "Activities\n where act.", "ActTwittered == false\n select new ActivitySummary { act.", "ActID, act.", "ActTitle, act.", "Category, act.", "ActDateTime, act.", "Location }.ToList();\n\n}\n\nforeach (var activity in activities)\n{\n /* ... */\n}\n\n" ]

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[ "Hollywood loves a Cinderella story, and Stella Meghie has a real one.", "\n\nIn 2009, Meghie quit her job as a publicist for fashion and beauty brands to go back to school and follow her dreams of being a writer/director. ", "In 2011, she completed her screenwriting degree at London’s University of Westminster; the years that followed have been a film student’s dream.", "\n\nShortly after graduating, she sold a number of TV projects. ", "Then she directed and found financing for her first film, “Jean of the Joneses,” which she originally wrote while in school. ", "In 2016, she managed to squeeze it into the South by Southwest Film Festival as a late entry. ", "The film premiered to rave reviews, with The Times calling it “a movie that is both fresh and refreshing, at once familiar and new.”", "\n\nThen her life changed in what looks like an instant.", "\n\n\nA month after “Jean’s” debut, Meghie signed with CAA. ", "The script, inspired by her family of Jamaican women, served as a calling card that led to deals with BET and VH1. ", "In just another month, a script by J. Mills Goodloe was in her mailbox.", "\n\nA little over a year after Meghie finished her first film, her second, Warner Bros. and MGM’s “Everything, Everything,” premieres in theaters everywhere.", "\n\n“Everything, Everything” director Stella Meghie. (", "Allen J. Schaben / Los Angeles Times)\n\nThat sort of movie-deal whirlwind doesn’t often happen to women, let alone black women. ", "But as the film industry roils with conversations about representation and diversity in front and behind the camera, Meghie’s long-gestating talent was perfectly positioned to rise.", "\n\n\n“There’s a conversation that’s happening right now that is helpful,” said Meghie. “", "But things are [only] going to change when projects like [‘Everything, Everything’] are made and they hire more women and minorities to direct and write. ", "Otherwise, it’ll be up to us, like I did with ‘Jean,’ to do it for ourselves.”", "\n\nAn adaptation of the bestselling YA novel by Nicola Yoon, “Everything, Everything” stars Amandla Stenberg (Rue of “The Hunger Games”) as a teen with a medical condition that requires her to stay inside her germ-free, super-antibacterial home. ", "But when a cute boy, played by “Jurassic World’s” Nick Robinson, moves in next door, she’s willing to risk her life just to swim in the ocean. ", "Anika Noni Rose and Ana de la Reguera also star.", "\n\nInitially, Meghie was more interested in making another indie than taking on a studio film, but after some nudging from her manager, she read Goodloe’s script and Yoon’s book.", "\n\nFrom left, Erica Ash, Sherri Shepherd, Michelle Hurst, Gloria Reuben and Taylour Paige in “Jean of the Joneses.” (", "courtesy of SXSW)\n\n\n“I basically did a New York walk-and-talk film with jazz music,” she said. “", "I didn’t think this would be my next film, but the book had so much humor and quirk to it. ", "Ten pages in I was like, ‘I’m supposed to do this.’”", "\n\nAfter meeting with Yoon, the two made a play for Stenberg, who they felt would best capture the essence of the book’s biracial main character. ", "Yoon, who is black and married to a Korean American, wrote a character in which her daughter, who is mixed, could see herself reflected. ", "Featuring, but not about, a biracial couple, and with four black women — Yoon, Meghie, Stenberg and Rose — at its core, “Everything, Everything” is an outlier in more ways than one. ", "Its singularity, however, positions the picture at once as progressive and sobering.", "\n\nIt certainly isn’t the sort of movie Hollywood typically produces.", "\n\nPerhaps this is why Meghie and Stenberg have made the Internet meme Joanne the Scammer the patron saint of the film, introducing the “the messy [chick] who lives for drama,” as the character played by Branden Miller describes herself on Twitter, to others on set. ", "Joanne achieved cyber fame by chronicling her scams online, like joking about switching the best picture cards at the 2017 Oscars or tweeting out inspirational tidbits such as, “Scam today before today scams you.”", "\n\n\nNeither Meghie or Stenberg could believe what was happening. ", "Plainly put, black women, unlike their white male counterparts, don’t get these types of opportunities at this level at such an early juncture in their careers — if ever. ", "A scam must be afoot.", "\n\n“Stella and I would just look at each other and there was this unspoken thing between us,” said Stenberg with a smile, “where we felt like, ‘We’re out here making this and they have no idea what it is. ", "They don’t know what they have their hands on. ", "They let us make this?’”", "\n\nAmandla Stenberg and Nick Robinson in “Everything, Everything,” (Warner Bros. Pictures)\n\nMeghie’s unique vantage point, Stenberg said, can be seen in the “black girl hair moments” her character has in the film or the shots of melanin peeking out of an unzipped top or the “sneaky game we’d play in terms of handheld camera shots.”", "\n\n\nRobinson added that Meghie was perfectly suited for the film because she “had a really good grasp on her audience and her voice.”", "\n\n“It was what I was hoping it would be,” he said about the filming process, noting it was Meghie who convinced him to take the role over a lunch.", "\n\nAs for what’s next for Meghie, she wants to continue telling “unique, honest stories.” ", "Whether that’s in the studio system or back on the indie streets, only time will tell.", "\n\n“Some stories don’t fit in the studio system, and I’m going to want to tell some of those,” she said. “", "And if there is something right in the studio system that I can bring something to, then that’s where you’ll find me.”", "\n\n\nContinuing to scam, in the best, most representative way possible.", "\n\nGet your life! ", "Follow me on Twitter (@TrevellAnderson) or email me: trevell.anderson@latimes.com." ]

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[ "Once the leading kitchen mixer-grinder brand, Sumeet had disappeared from the market, thanks to distribution problems and wrangles over succession. ", "Its management is now attempting a comeback, but will it succeed.", "\n\nTo build a successful brand and become the undisputed market leader is a tough job. ", "An even tougher one is to revive a once-formidable brand whose strongest presence now is in the memory of the previous generation. ", "Ajay Mathur should know this better than anyone else. ", "The 55-year-old is the director of Sumeet Appliances and has taken it upon himself to revive the brand his father founded and built. ", "The name Sumeet may not ring a bell now, but as an industry veteran succinctly puts it, what Dalda was to vanaspati ghee, Sumeet used to be to the mixer-grinder.", "\n\nSumeet has its origins in a challenge from a wife to her husband. “", "My mother had a Braun blender from Germany but the motor burnt out as it was not meant for the heavy-duty grinding Indian cooking calls for. ", "Since there were no Braun service centres in India then, she told my father that if he really was an engineer, he should be able to repair it,” Mathur says. ", "His father, Satya Prakash Mathur, did one better — he designed a mixie with a motor powerful enough to withstand the rigors of Indian grinding (a 500-600 watt motor, a unique L-shaped design, and a torque of 20,000 rpm that Mathur claims is comparable to an aircraft propeller were some of its attributes). ", "Bolstered by the positive feedback from his wife and friends, Mathur Senior took permission from his bosses at Siemens to float a company in 1963 to manufacture the mixies. ", "Power Company Appliances, registered in the name of his wife, Madhuri. ", "Contrary to popular perception, Sumeet (meaning good friend in Hindi) was a Mumbai brand, and not a South Indian one. ", "Armed with its USP, a motor that would not burn even with the toughest grinding, and complemented by after-sales service and a reputation for being able to last up to 20 years, Sumeet quickly became a household name.", "\n\nWhen Mathur says the brand ushered a revolution in the Indian kitchen, he is not far from the truth, something even rivals acknowledge. ", "Despite the entry of many me-too brands and the market being fragmented, Sumeet was able to hold on to its dominant position even up to the ’90s. ", "At its peak in the ’80s, Sumeet was selling around 60,000 machines a month, and enjoyed a market share of 43 per cent, says Mathur. ", "But then, the enviable success story began to unravel. ", "And this is where the narrative diverges.", "\n\n* * * * *\n\nAccording to Mathur, the primary reason we no longer see Sumeet on store shelves even in former strongholds such as Maharashtra and south India is the efforts of a distributor cartel in the South that refused to stock the machines. “", "If there is a villain in the Sumeet story, it’s the big distributors in the South who were also retailers. ", "If other dealers asked for 20 mixies, these distributors would give them five,” he says. ", "B A Srinivasa, the CEO of Viveks, one of the largest retailers in south India with 55 stores and a turnover of Rs 400 crore, flatly denies this. “", "We were always looking out for and nourishing the brand; that’s the kind of excellent relationship we had with its proprietors,” says Srinivasa who attributes the decline to conflicts within the family and the brand’s inability to adapt to an evolving market, the same reasons put forward by brand consultants and other industry players.", "\n\nMathur does not deny there was turmoil in the family. “", "There was no proper succession planning,” is how he puts it. ", "Two companies made Sumeet Appliances: Power Control Appliances and Sumeet Machines (now called Sumeet Appliances). ", "Mathur’s brother, Vivek, shifted base to Chennai in the mid-’80s and joined forces with their maternal uncle. ", "Power Control Appliances, the company registered in the name of Madhuri Mathur and controlled by her brother and younger son, took Maharashtra-based Sumeet Machines to court over the right to use the brand name Sumeet and, reportedly, even sent feelers to rivals to sell the company. ", "The courts, in the early ’90s, held that there could be only one proprietor of a trademark. ", "Mathur says Sumeet Appliances has now become the sole owner of the Sumeet trademark.", "\n\nBut while the Mathurs were busy wrangling in court and outside, the mixer-grinder market outside was changing. ", "Aggressive rivals, such as Maharaja and Bajaj in the North and West, and Preethi in the South, began offering similar and more advanced products, and soon started to gain traction.", "\n\nPreethi, the mixer-grinder brand of the Chennai-based Maya Appliances, started by a branch of the TTK family in 1978, was able to build on its strengths, and by the early 2000s, emerged as one of the highest-selling mixer-grinders. ", "It now claims to be the market leader with annual sales of 1.3 million units, in a heavily fragmented market estimated to be Rs 1,000 crore with sales between 8 and 10 million units. ", "In January last year, Maya Appliances was bought over by Philips. ", "This is likely to help Preethi enter new markets like the North and Philips gain dominance in the mid and lower-range price points as well as a significant presence in the southern markets. ", "Brands like Havells have also entered the fray, recently.", "\n\nSimultaneously, consumer preferences and lifestyles have changed. ", "While south Indian households might still need to grind chutneys for breakfast, they can now do it in sleek machines, available in an array of options. ", "And with customers constantly upgrading appliances, even Sumeet mixers’ ability to last 20 years is not as big an advantage now as it used to be two decades ago.", "\n\n* * * * *\n\nIt is to this difficult market that Mathur now plans to stage a comeback. ", "He acknowledges it is a daunting task (to put it mildly), considering Sumeet’s sales is now 10,000-12,000 a month (120,000 to 144,000 a year), including annual sales of 40,000 to army canteens, and restricted to the western Maharashtra market. ", "First up is scaling up production. “", "I have got control of our factory in Nashik now, the biggest appliance factory in India, which should help us reach an output of 150,000 units a month in 2014.” ", "Mathur says the disadvantage of Sumeet’s factory being located in Maharashtra, (most rivals have set up manufacturing plants in Uttarakhand and Himachal for the sizeable tax exemptions on offer) will be offset by the fact that the mixer will not be positioned at the lower end of the market (read cheaper). ", "Another challenge, which he himself points out, is the number of duplicates in the market.", "\n\nSumeet mixer-grinder, Mathur adds, has recently re-entered the Hyderabad and coastal Andhra markets, and Mathur plans to launch four models in Chennai in the next couple of months. ", "The company is also in talks with a major national consumer appliances retailer to expand its reach beyond distributors and standalone retailers, and a nation-wide ad campaign is planned for the middle of this year. ", "Mathur is also trying to register the brand in Sri Lanka, while his sister and son are setting up a company in Canada to establish the brand in the North American markets.", "\n\nBut despite its best efforts, can a brand that consumers may no longer be familiar with revive itself? “", "If C K Birla were to relaunch the Ambassador now, would customers be queueing up for it?” ", "is how a senior executive in a rival firm, who requests not to be named, views the strategy.", "\n\nPranesh Misra, chairman and managing director of Brandscapes Worldwide, puts it differently but is of a similar opinion. ", "Historically, hardly any brand has been able script a successful comeback of the sort Sumeet is aiming for and this is a category that’s driven by the latest technology, he says. “", "Also, it is saddled with an Indian name when the consumer goods market is dominated by multinational corporations, and is a brand that has been left behind.” ", "Misra even goes so far as to say it might be better to launch a new brand than revive the old one. (", "Incidentally, Misra too was once a Sumeet customer, and owned both a mixer-grinder and washing machine.)", "\n\nOthers are slightly more optimistic. “", "There’s always room for a strong brand like Sumeet, though the company will have to get many things right,” says Francis Xavier, CEO of the 25-year-old Chennai-based firm Francis Kanoi Market Research which tracks the kitchen appliances sector. “", "This is a market where the top three brands have sales of around 1.5 million, while the rest is split among an estimated 200 local brands. ", "It would be possible for a brand like Sumeet to corner a market share of up to 5 per cent but going beyond that would be very tough,” says Xavier.", "\n\nMathur, though, is determined to go ahead. “", "I may be 55 but I’m excited about our plans. ", "And I will not have lived if I don’t attempt this now — I feel responsible.”" ]

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[ "Referral Bucks - Referral Registration Survey\n\nReferral bucks are a credit of up to $100 to be used toward purchases of accessories or apparel from ElliptiGO. (", "Bikes excluded.) ", "Both the referrer and the new purchaser are eligible for the credit, but just ONE person needs to complete this form. ", "Once submitted and verified, you will receive an email confirmation from us.", "To redeem your credit you must call 858.876.8677 to place your order, as website orders cannot be credited.", "\n\nIf you have any questions about the program or credit, please email info@elliptigo.com\n\nThank you!", "\n\nTeam ElliptiGO\n\n*\n1.", "\nOriginal Owner's Name\n\n*\n2.", "\nOriginal Owner's Email\n\n*\n3.", "\nOriginal Owner's ElliptiGO Serial Number\n\n* Your serial number is an 8-digit number located under the bike on the round tube between the rear wheel and the kickstand.", "\n\nFor new/unassembled bikes, the serial # is also located on a white label on the outside of your shipping box and on a brown cardboard tag that hangs off the rear drive arm.", "\n\n*\n4.", "\nHow did the original owner first find out about the ElliptiGO?", "\n\n*\n5.", "\nReferred Owner's Name\n\n*\n6.", "\nReferred Owner's Email\n\n*\n7.", "\nReferred Owner's Date of Purchase\n\n*\n8.", "\nReferred Owner's ElliptiGO Serial Number\n\n* Your serial number is an 8-digit number located under the bike on the round tube between the rear wheel and the kickstand.", "\n\nFor new/unassembled bikes, the serial # is also located on a white label on the outside of your shipping box and on a brown cardboard tag that hangs off the rear drive arm.", "\n\n*\n9.", "\nHow did the referred owner first find out about the ElliptiGO?", "\n\n*\n10.", "\nWhere did the referred owner purchase their ElliptiGO?", "\n\nOnline\n\nRetail Store Location (Please type in store name below)\n\nIf you selected \"Retail Store\" above, please type in name of retail store here\n\n*\n11.", "\nWhat is your relationship to the other customer and how long have you known each other?" ]

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[ "Gentlemen, welcome to the work-life balance conversation\n\nMonday, August 18, 2014 11:12 AM\n\nIt's not just women who are discussing the challenge of work-life balance these days. ", "Max Schireson announced he is quitting his job as CEO of MongoDB to spend more time with his family. ", "Karin Agness writes about men entering the work-life balance conversation. ", "Read more" ]

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[ "A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes.", "\nConflicting evidence exists regarding the benefits of physical activity for long-term blood glucose control in adults with type 1 diabetes (T1D). ", "The object of this systematic review was to determine the effects of physical activity on long-term blood glucose control in T1D adults. ", "PubMed/Medline, Embase, CENTRAL, SPORTdiscus, Global Health and ICTRP were searched up to October 2013 for randomized trials of aerobic or resistance exercise training in T1D adults. ", "Exercises had to be performed at least twice weekly for a minimum of two months. ", "The primary outcome was glycated hemoglobin (HbA1c). ", "Secondary outcomes included cardiorespiratory fitness and insulin dose. ", "Six randomized trials were identified (323 adults); sample sizes ranged from n=6 to n=148 participants receiving the intervention. ", "Five trials had an unknown risk of bias; one trial was deemed to be at high risk of bias. ", "Exercise frequency varied from twice weekly to daily, with intensities (50-90% VO2peak), and session durations (20-120 min) varying widely. ", "Four trials reported HbA1c, which decreased with exercise training (mean difference [MD] -0.78% (-9 mmol/mol), 95% CI -1.14 (-13 mmol/mol) to -0.41 (-5 mmol/mol); p<0.0001; I(2) 0%) compared with controls. ", "Exercise training improved cardiorespiratory fitness by 3.45 ml/kg/min (95% CI 0.59 to 6.31, p=0.02, I(2) 0%) compared with controls. ", "One trial reported an effect on insulin dose (MD -0.4U/kg, 95% CI -0.53 to -0.27, p<0.00001) compared to controls. ", "There are currently insufficient well-designed studies to ascertain the true effect of exercise training on HbA1c in individuals with T1D, but current results are promising." ]

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[ "\n715 F.Supp. ", "1323 (1989)\nUNITED STATES of America\nv.\nPARCEL OF REAL PROPERTY KNOWN AS 708-710 WEST 9TH STREET, ERIE, PENNSYLVANIA and Buildings and Improvements Erected Thereon.", "\nCiv. ", "A. No. ", "88-106 Erie.", "\nUnited States District Court, W.D. Pennsylvania.", "\nJuly 14, 1989.", "\n*1324 James J. Ross, Asst. ", "U.S. Atty., ", "Erie, Pa., for U.S.\nJohn P. Garhart, Dunlavey, Nichols, Ward & Krill, Erie, Pa., for Richard A. & Jane M. DiLoreto.", "\nWill J. Schaaf, Marsh, Spaeder, Bauer, Spaeder & Schaaf, Erie, Pa., for Marquette Sav. ", "Ass'n.", "\n\nOPINION AND ORDER\nGERALD J. WEBER, District Judge.", "\nThe United States brought this action seeking to have the defendant property forfeited to the United States, on the theory that it was used by Richard DiLoreto, from the Spring of 1983 until 1986 or 1987, to store and sell cocaine. ", "See, 21 U.S.C. § 881(a)(7). ", "Title to the property is held by DiLoreto and his wife Jane as tenants by the entirety. ", "The property contains apartments, one of which the DiLoretos used as their home until approximately July, 1986. ", "Since that time the apartments have been rented out to others. ", "In an opinion and order dated March 14, 1989, we rejected Jane DiLoreto's assertion of innocent ownership and ordered her interest in the property, as well as Richard's, forfeited to the United States. ", "708 F.Supp. ", "698. ", "An appeal from that order of forfeiture is presently pending before the United States Court of Appeals for the Third Circuit.", "\nMarquette Savings Association holds a mortgage on the property. ", "The United States concedes that the mortgage is a valid lien on the property which preceded any alleged illegal use of the property. ", "At the time the property was seized in April, 1988, the mortgage payments were current. ", "Payments continued to be made by the DiLoretos, or on their behalf, through September, 1988. ", "Since that time, no further payments have been made. ", "The unpaid *1325 balance on the property as of October 1, 1988 was $29,120.03. ", "Since the time the property was seized, the United States, through an agent, has assumed the management and control of the property, and has collected the rents due and owing. ", "The monies collected by the United States are held in an account for the management and maintenance of the property.", "\nHaving conceded the validity and priority of Marquette's lien on the property, the United States agrees to give priority to the satisfaction of that lien, in the event of a forfeiture and sale of the property. ", "The United States, however, has indicated that it will refuse to pay any interest or costs which have accrued subsequent to the seizure in April, 1988. ", "Marquette has moved for summary judgment, seeking an order that it is entitled to post-seizure interest and costs from the United States in the event that the forfeiture is upheld on appeal. ", "Marquette also seeks to compel the United States to turn over to it all the rental monies currently being held, and for an order allowing Marquette to collect all further rent. ", "Finally, Marquette seeks to proceed with forclosure proceedings on the property.[1]\n\nI. Post-Seizure Interest\nIn support of its position that it is not obligated to pay post-seizure interest, the United States relies on United States v. One Piece of Real Estate, etc., ", "571 F.Supp. ", "723 (W.D.Tx.1983), and its progeny. ", "In One Piece, the court reasoned that requiring the United States to pay post-seizure interest to a lienholder would allow the lienholder's interest in the property to grow at the expense of the government. ", "The Court concluded that allowing such a diminution of the government's forfeited interest would be contrary to the holding in United States v. Stowell, 133 U.S. 1, 10 S.Ct. ", "244, 33 L.Ed. ", "555 (1890). ", "The Supreme Court there held that the interest of the government is fixed as of the date of the illegal act. ", "Therefore, the Texas District Court concluded that a lienholder is not entitled to interest or other charges that accrue after the date of seizure. ", "Accord, United States v. A Parcel of Real Property, 650 F.Supp. ", "1534 (E.D.La.1987); United States v. 8.4 Acres of Land, 648 F.Supp. ", "79 (D.S.C.1986); United States v. One Condominium Apartment, 636 F.Supp. ", "457 (S.D.Fla.1986); and United States v. All Interests of Severo E. Escobar, 600 F.Supp. ", "88 (S.D.Fla.1984).", "\nMarquette, however, does not come into court without its own case authorities. ", "It cites to the only circuit court case of which we are aware, which addresses the question of whether a lienholder is entitled to collect post-seizure interest from the United States. ", "In In re Metmor Financial, Inc., 819 F.2d 446 (4th Cir.1987), the court rejected the reasoning of One Piece, concluding that the court in One Piece had misconstrued Stowell.", "\nIn Stowell the Supreme Court had also held that:\nthe mortgage is valid as against the United States, and ... so far as concerns the real estate, the judgment of condemnation must be against the equity of redemption only.", "\nStowell, 133 U.S. at 20, 10 S.Ct. ", "at 248. ", "The Metmor court therefore notes that:\nIt is this aspect of Stowell, ignored by the government, that is critical for our purposes. ", "The case holds that, even though forfeiture occurred prior to the actual seizure, the government can succeed to no greater interest in the property than that which belonged to the wrongdoer whose actions have justified the seizure. ", "Ackley purchased the property encumbered by Metmor's secured note, with interest accruing. ", "His equity was subject to an obligation to repay the borrowed principal and to pay interest on the unpaid balance until all of the principal was repaid. ", "The government now attempts to transform that note into one that is unsecured and interest free. ", "Such a result would deprive Metmor of its stake in the forfeited property and *1326 would constitute a taking without due process.", "\n. ", " . ", " . ", " . ", " .", "\nThe government's legally cognizable interest in the forfeited property is not diminished by continuing payments to Metmor for the plain and simple reason that the government's \"interest\" in the property entails an obligation to make continuing \"interest\" payments on the preexisting mortgage. ", "The aspect of Stowell on which the Texas court relied relates only to when the government's interest attaches — not to the nature of that interest.", "\nMetmor, 819 F.2d at 448-449, and 450. ", "The Metmor court therefore, concluded that where a forfeited property is encumbered by a lien which encompasses a right to receive continuing interest payments, an innocent lienholder is entitled to collect from the government such interest as accrues until the principal is repaid. ", "Accord, United States v. Real Property in Sevier County, Tenn., 703 F.Supp. ", "1306 (E.D. Tenn.1988); United States v. Real Prop. ", "Titled in Name of Shashin, Ltd., 680 F.Supp. ", "332 (D. Hawaii 1987); and United States v. All That Tract & Parcel of Land, 602 F.Supp. ", "307, 313 (N.D.Ga.1985).", "\nWe have carefully reviewed all the relevant authorities and find ourself in agreement with that line of cases following the reasoning set out by the Fourth Circuit in Metmor. ", "To conclude otherwise would be to allow the United States the benefit of an interest-free loan at Marquette's expense. ", "That would be particularly disturbing in light of the fact that the United States has over the last few months, accumulated a substantial surplus of rent monies of several thousand dollars in its holding account for managing and maintaining the property. ", "Where the United States is generating income from the properties it is particularly disengenuous for it to argue that it should not be required to pay the interest on the mortgage.", "\nWhile we note that there is surplus income being generated from the property herein, we do not mean to intimate that our resolution of the post-seizure interest question necessarily depends on that fact. ", "The United States can certainly protect itself in forfeiture actions, from paying out any great deal of its own money for interest on liens against real property. ", "Where the property siezed is being used as a residence by the claimants or is otherwise being used by them, the United States can allow them to continue to occupy the premises (as we have often seen them do) on the condition that they keep the mortgage payments current, or at a minimum, keep the interest payments current. ", "The claimants certainly have an incentive to do so anyway, in order to protect their own interests in the property should they prevail in their attempt to thwart the forfeiture. ", "Where the payments are not being made by the claimants, the United States could rent the property, as is the case herein.", "\n\nII. ", "Post-Seizure Attorney's Fees and Costs\nIn addition to seeking post-seizure interest, Marquette seeks to collect from the United States, its attorney's fees and costs in this action. ", "Marquette relies on Metmor and its progeny as establishing that the United States is bound by all of the conditions and obligations of a mortgage. ", "We cannot agree. ", "Our holding herein as to post-seizure interest is based upon our conclusion that the right to continued interest payments is part and parcel of the lienholder's interest in the property. ", "Our review of the relevant authorities convinces us that the United States must compensate the lienholder for his entire interest in the property at the time of seizure. ", "Costs and fees do not enjoy the same status. ", "They are not an interest in the property, but are rather merely expenses required to protect an interest.", "\n\nIII. ", "Collection of Rental Payments\nMarquette also seeks to compel the United States to turn over to it all the surplus rental monies, and for an order allowing Marquette to collect all further rent. ", "In support of its position, Marquette points to a specific provision in the mortgage which assigns all rents for the property to Marquette, should the DiLoretos *1327 breach the terms of their mortgage. ", "Just as with the attorney's fees and costs, however, that provision is not part of Marquette's interest in the property. ", "It is simply a means of securing and protecting Marquette's interest should a default occur. ", "The United States is merely bound to make Marquette \"whole\" for its interest in the property. ", "The United States is not bound by the mortgage agreement to any particular manner of doing so. ", "In any event, to compel the United States to turn over the rent monies would interfere with the right of the United States to possess and control the property pending a final determination by the court of appeals as to the forfeitability of the property. ", "See, 21 U.S.C. § 881; 28 U.S.C. §§ 2409 & 2409a; United States v. Real Property in Sevier County, Tenn., 703 F.Supp. ", "1306 (E.D. Tenn.1988); and United States v. Real Prop. ", "Titled in Name of Shashin, Ltd., 680 F.Supp. ", "332 (D.Hawaii 1987). ", "If the property is ultimately deemed forfeited to the United States, any excess of rents over management and maintenance expenses would then become available to Marquette should the United States be unable, through a sale of the property or otherwise, to compensate Marquette fully for its interest in the property.", "\n\nIV. ", "Institution of Foreclosure Proceedings\nSimilarly, the United States is not bound by any provisions in the mortgage agreement providing for the institution of foreclosure proceedings by Marquette. ", "Such provisions provide only a remedy for Marquette and are not part of Marquette's interest in the property. ", "Also, the institution of any foreclosure proceedings by Marquette would obviously interfere with the United States' right to possess and control the property pending the outcome of the forfeiture action.", "\n\nORDER\nAND NOW, this 14th day of July, 1989, for the foregoing reasons, IT IS ORDERED that:\n1) Should this Court's order of forfeiture be upheld on appeal, Claimant Marquette shall be entitled to receive from the United States the unpaid balance of the mortgage at the time the DiLoretos defaulted, together with interest on that unpaid balance at the rate provided for in the mortgage note;\n2) Marquette shall not be entitled to collect from the United States any post-seizure attorney's fees or costs; and\n3) Marquette is not entitled during the pendency of the forfeiture action to collect any rent on the property, to institute any foreclosure proceedings, or to otherwise interefere in any manner with the United States' possession and control of the property.", "\nNOTES\n[1] While an appeal in this case is presently pending before the Court of Appeals, we conclude that we retain jurisdiction to consider Marquette's motion as an ancillary matter which will have no impact on the resolution of the pending appeal.", "\n" ]

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[ "Workers to get paid sick leave later this year under new law signed by governor\n\nPolitical columnist Charlie Stile and Statehouse reporter Dustin Racioppi discuss what Murphy has done in his first 100 days, and what they expect him to do in the next 100.", "\n\nExecutive Director of New Jersey Working Families Analilia Mejia, second from right, applauds Governor Phil Murphy during a roundtable discussion on minimum wage and paid sick leave in Newark, N.J. on Wednesday, January 17, 2018.(Photo11: Danielle Parhizkaran/Northjersey.com)\n\nNew Jersey became the 10th state Wednesday to require employers to provide paid sick leave for workers, putting into law a wage policy that has passed locally in about a dozen places around the state.", "\n\nDemocratic Gov. Phil Murphy signed the bill, A-1827, during a ceremony at Trenton's War Memorial, a week after signing equal pay legislation. ", "The bill-signing continues a streak of progressive achievements for Murphy, but he is seeking more on the economic front, including a $15 hourly minimum wage.", "\n\n\"This is not just about doing what's right for workers and their families,\" he said of paid sick leave. \"", "This is about doing the right thing for our economy and protecting more New Jerseyans' place in that economy.\"", "\n\nBill sponsors said an estimated 1.1 million New Jersey workers are unable to earn sick leave.", "\n\nThe law, which takes effect in six months, requires employers to give workers one hour of paid sick leave for every 30 hours worked, with an annual cap of 40 hours. ", "Workers may take off to care for their own mental or physical illness or injury, to care for family members, to address domestic or sexual violence or when their child's school or child care is closed due to an epidemic or public health emergency.", "\n\nMost workers in New Jersey will be eligible for paid sick leave, according to New Jersey Working Families, a political organization that helped drive the bill's passage. ", "Employers may not retaliate against workers who use their earned time off.", "\n\nMurphy and bill sponsors said the measure will help increase the value of doing business in New Jersey while also expressing the state's value of its workers. ", "Those affected by the bill \"will be able to lead a life that contributes to the life of New Jersey,\" said sponsor Sen. Loretta Weinberg, D-Teaneck.", "\n\nThe New Jersey Business Association, which had opposed the mandate, praised lawmakers for working with it the past several years to address a range of concerns it had over the potential effects on businesses. ", "After Murphy signed it, the association said the changes \"will mitigate impacts on well-intended employers.\"", "\n\nNEWSLETTERS\n\nGet the Breaking News newsletter delivered to your inbox\n\nWe're sorry, but something went wrong\n\nGet breaking news from all around North Jersey delivered to your inbox as soon as it happens.", "\n\nWhile lawmakers went back and forth over the years on the details, municipalities took it upon themselves to pass similar local paid sick leave laws. ", "Newark and Jersey City are the two major cities to have passed such measures. ", "The others include: Bloomfield, East Orange, Elizabeth, Irvington, New Brunswick, Montclair, Morristown, Passaic, Paterson, Plainfield, New Brunswick and Trenton." ]

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[ "Changes in ventilator settings and ventilation-induced lung injury in burn patients-A systematic review.", "\nVentilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (VT) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. ", "It is uncertain whether ventilation practices changed in a similar way in burn patients. ", "Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients. ", "Systematic search of the literature in PubMed and EMBASE using MeSH, EMTREE terms and keywords referring to burn or inhalation injury and mechanical ventilation. ", "Studies reporting ventilator settings in adult or pediatric burn or inhalation injury patients receiving mechanical ventilation during the ICU stay. ", "Two authors independently screened abstracts of identified studies for eligibility and performed data extraction. ", "The search identified 35 eligible studies. ", "VT declined from 14 ml/kg in studies performed before to around 8 ml/kg predicted body weight in studies performed after 2006. ", "Low-PEEP levels (<10 cmH2O) were reported in 70% of studies, with no changes over time. ", "Peak inspiratory pressure (PIP) values above 35 cmH2O were frequently reported. ", "Nevertheless, 75% of the studies conducted in the last decade used limited maximum airway pressures (≤35 cmH2O) compared to 45% of studies conducted prior to 2006. ", "Occurrence of barotrauma, reported in 45% of the studies, ranged from 0 to 29%, and was more frequent in patients ventilated with higher compared to lower airway pressures. ", "This systematic review shows noticeable trends of ventilatory management in burn patients that mirrors those in critically ill non-burn patients. ", "Variability in available ventilator data precluded us from drawing firm conclusions on the association between ventilator settings and the occurrence of VILI in burn patients." ]

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[ "A stable antibody-sensitized erythrocyte diagnostic preparation for detection of rhinovirus type 17 and its antibody.", "\nA diagnostic preparation was obtained by sensitization of formalinized sheep erythrocytes with antibody to rhinovirus type 17. ", "This preparation was agglutinated in the presence of relatively high concentrations of type 17 but not other types of rhinovirus. ", "It could also be used for detection of antibody to rhinovirus type 17 in the antigen neutralization test, the antibody levels determined in this way being similar to those found by conventional virus neutralization tests in cell cultures." ]

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[ "Q:\n\nDifferences between angular 2, Angular 2 universal\n\nwhich are the differences between angular 2, Angular 2 universal?", "\ni don't understand exactly the difference between angular 2 and angular 2 universal, which is the advantage to use angular 2 universal?", "\n\nA:\n\nI think Angular Universal is the library the awesome Angular team is working on to make building universal apps a smooth experience. ", "The library fixes a lot of nightmare we had working with Angular 1. ", "As a matter of fact, our worst nightmare in Angular 1 is what Angular Universal takes away in Angular 2.", "\nAnd then, the advantages to use angular 2 universal are \"better perceived performance\", \"optimized for search engine\", and \"site preview\".", "\nThanks.", "\n\n" ]

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[ "Slot machines free spins\n\nEnjoy Free Spins, Jackpot Slots and Bonus Rounds. ", "Top notch free online slots with impressive graphics and sounds will give you the best slot machine gaming. ", "List of Free Slots Games with Free Spins ☆ Play All Slot Games Instantly on Desktop or Mobile ☆ No Deposit ☆ No Registration ☆ Free Spins Explained!. ", "Play a huge selection of Vegas slots and other casino games online for free. ", "he or she can play the free online slot machines 24/7 with no strings attached. ", "all the thrills of real money slots for free and may even get additional bonus spins." ]

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[ "Data Is a Cost Problem\n\nOne of the major challenges that software developers and testers face on a daily basis stems from an inability to get realistic data. ", "Many times as a developer, you are interacting with a downstream service and you must use whatever data is available in that environment because the process for obtaining actual, usable data for your scenario is extremely time-consuming. ", "Often you cannot find the data that you need and it must be taken from production, which introduces a new host of challenges.", "\n\nTo complicate matters, personal data cannot be used from production because it increases an organization’s risk for theft, loss, or exposure. ", "Take the recent breach at Yahoo, where 500 million email accounts were breached, or the ~68 billion LinkedIn users whose data was recently compromised. ", "These breaches took place at the production level where security is high. ", "Production data used in development areas is not uncommon and security tends to be lower. ", "Operating in this way presents a significant risk to an organization’s brand reputation. ", "Thus, sensitive data must be scrubbed or masked, which is a time-consuming process requiring data expertise.", "\n\nUsing Service Virtualization to Overcome Data Costs\n\nNo matter what, data is a cost problem because it slows you down. ", "By using service virtualization, you can not only take control of a dependent application’s behavior and functionality for the purposes of stabilizing your test environments, but you can completely control those dependency’s data sources and supply whatever data you require that day for your effort. ", "At this point, the rules change because you are now not only in control of the data, but also the logic. ", "You can create services that behave the way you want them to, as opposed to strict adherence to their normal behavior patterns.", "\n\nIn a previous blog, I discussed defect virtualization, which has the same basic principles. ", "But there we were talking about service logic. ", "This blog will take the next step and talk about data control. ", "As we begin, let’s focus on the current data challenge that testers and developers face day-to-day.", "\n\nA Typical Day of Data in the Life of a Developer\n\nAt the beginning of an application's development process, the data required for testing is usually simple because the full functionality of the service has not yet been realized. ", "As development continues to add functionality, testing maturity increases, and so does the data complexity.", "\n\nFor example, let’s use the example from a previous blog post – let's say I am an airline, developing functionality on my tickets page. ", "I need to verify that users can get tickets for their flights, and depending on how far out in the future the flights are, the user will get one of several responses, which will change as the time gets closer. ", "At the beginning of the development process, I could simply generate a bunch of complex data with flights three months in the future, which would allow me to do all of the testing I need for the moment. ", "But of course, the problem is that I just lit the fuse on a time bomb. ", "In three months, this beautiful data will expire, and chances are I will have forgotten about it. ", "Suddenly all of my tests will start failing, at exactly the wrong time because the release will be coming up and I simply will not have time to regenerate the data... Sound familiar?", "\n\nForge a Sustainable Path\n\nBy introducing service virtualization early in the development process, you can lay the foundation to provide solutions to these data challenges. ", "A virtual service’s data can be derived from numerous locations, but at the beginning, simple virtual services start with fixed data. ", "You create these “fixed assets” or mocks to address the what-if scenario testing stages and keep things very simple. ", "The idea here being, “I just need a service that will respond with this particular payload.”", "\n\nAs virtual services mature, it becomes necessary to separate the data from the service so that if you want to add logic into the simulation, you don’t actually have to open up the virtual service to manipulate the data. ", "In fact, mature users create a virtual service in such a way that the data source handles the bulk of the logic. ", "They can then hand the data source off to a tester or test data management team to insert any data that this service might need in the future. ", "Adding new functionality to the service is as simple as adding a row to the data source. ", "This allows the virtualization effort to be shared and one virtual service can accommodate multiple teams. ", "Virtual services become living organisms that grow and change as needed.", "\n\nWhere Does This Data Come From?", "\n\nOnce development has created the initial simple service, it is time for the testing team to take over. ", "Testing teams will have more complex data requirements. ", "Where does this data come from? ", "Typically, you derive this data from record and playback. ", "This is often the first step when creating a virtual service. ", "You record the transactions between an application and the dependent backend systems and use this recording to create your virtual service. ", "This allows you to create a very usable baseline data source that can be extended whenever the need arises. ", "In my airline example, this would allow us to get realistic flight numbers and destinations. ", "The data would have all of the complexity necessary, including multi-segment and international flights. ", "The data source correlation handles all of the complex request/response relationships, and since subsequent changes to the “real” data can simply be re-recorded and merged into the existing virtual service, getting new data becomes trivial.", "\n\nThe data that we record does not come from production, and this protects us against a data breach in the lower environments. ", "The challenge with this data is that since it doesn't come from production, it’s not as complete or up-to-date. ", "This is where data generation and manipulation become a powerful function of service virtualization.", "\n\nNonexistent data can be supplemented with simple generated data to accomplish exactly what we need. ", "In my airline example, the flight dates in the responses can always be today’s date offset by three months. ", "By using data generation, this task becomes trivial.", "\n\nWe can continue to massage and manipulate the data by providing dynamic data to manage any “non-defined” request/response relationships. ", "These are the types of relationships that could never exist in a static dataset. ", "In the airline example, let’s say that when a request to the downstream component is made, it provides the user’s current location and this will be used in the response as the departure. ", "Since our test cases would be constantly changing, a real service would have to maintain all of the current locations so that they can be supplied in the response. ", "By using a virtual service, you don’t need to maintain all of the locations, you can simply dynamically return the user’s current location as the departure city.", "\n\nFinally, the use of negative data can be provided either statically or inserted into the datasource to ease negative or abnormal testing. ", "In my airline example, for instance, this would be inserting a random canceled or delayed flight to validate that the user is notified before they leave for the airport." ]

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[ "Q:\n\nCalculating moving average/stdev in SAS?", "\n\nHye guys,\nI included a screenshot to help clarify my problem:\nhttp://i40.tinypic.com/mcrnmv.jpg.", "\nI'm trying to calculate some kind of moving average and moving standard deviation. ", "The thing is I want to calculate the coefficients of variation (stdev/avg) for the actual value. ", "Normally this is done by calculating the stdev and avg for the past 5 years. ", "However sometimes there will be observations in my database for which I do not have the information of the past 5 years (maybe only 3, 2 etc). ", "That's why i want a code that will calculate the avg and stdev even if there is no information for the whole 5 years.", "\nAlso, as you see in the observations, sometimes I have information over more than 5 years, when this is the case I need some kind of moving average which allows me to calculate the avg and stdev for the past 5 year. ", "So if a company has information for 7 years I need some kind of code that will calculate the avg and stdev for, lets say, 1997 (by 1991-1996), 1998 (by 1992-1997) and 1999 (1993-1998).", "\nAs i'm not very familiar with sas commands it should look (very very roughly) like:\nset var\nif year = i then stdev=stdev(year(i-6) untill year(i-1)) and average = avg(year(i-6) untill year(i-1))\n\nOr something like this, I really have no clue, I'm gonna try and figure it out but it's worth posting it if I won't find it myself.", "\nThanks!", "\n\nA:\n\nThe correct way to do it is to use PROC EXPAND.", "\nThere are a lot of options you can use with it but you might want to do\nPROC EXPAND DATA=TESTTEST OUT=MOVINGAVERAGE;\nCONVERT VAL=AVG / TRANSFORMOUT=(MOVAVE 5);\nRUN;\n\nand likewise for MOVSTD. ", " It automatically ignores missing values but you can adjust that behavior as well\n\nA:\n\nI would advocate proc sql here for readability. ", "Using Chang Chung's data as an example you could try the following:\n/* test data */\ndata one;\n input symbol $ value date :date9.;", "\n format date date9.;", "\ncards;\nABP1 -0.025 18feb1997\nABP1 0.05 25feb1998\nABP1 -0.025 05mar1999\nABP1 0.06 20mar2000\nABP1 0.25 05mar2001\nABP1 0.455 07mar2002\nABP1 0.73 25feb2003\nABP1 1.01 19feb2004\nABP1 1.25 16feb2005\nABP1 1.65 09feb2006\nABP1 1.87 08feb2007\nABT 0.555 14jan1991\nABT 0.6375 14jan1992\nABT 0.73 16jan1993\n;\nrun;\n\nproc sql;\n create table two as\n select distinct\n a.symbol,\n b.value,\n year(a.date) as year,\n b.date as date5\n from\n one a,\n one b\n where\n a.symbol=b.symbol\n and intck('year',b.date,a.date) between 1 and 5\n order by\n a.symbol,\n year,\n date5;\nquit;\n\nproc sql;\n create table three as\n select distinct\n symbol,\n year,\n count(symbol) as n5,\n avg(value) as avg5,\n std(value) as std5\n from\n two\n group by\n symbol,\n year;\nquit;\n\n" ]

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[ "[vA3C](../../index.html ) &raquo;<br>[Viewer]( ../readme-reader.html ) &raquo;<br>[Cookbook]( ./index.html )\n=================================================================================================\n<br>\n<div id=rm >\n\t<a href=JavaScript:displayMD(\"#readme.md#rm\"); >Read Me</a>\n</div>\n\n<div class=menu id=jr >\n\t<a href=JavaScript:displayMD(\"#json-reader/readme.md#jr\"); >JSON Reader</a>\n</div>\n\n<div class=menu id=ed>\n\t<a href=JavaScript:displayMD(\"#export-data-json/readme.md#ed\"); >Export Data JSON</a>\n</div>\n\n***\n\n<div class=menu id=lcl >\n\t<a href=JavaScript:displayMD(\"#load-collada-load/readme.md#lcl\"); >Load Collada Load</a>\n</div>\n\n<div class=menu id=lcp >\n\t<a href=JavaScript:displayMD(\"#load-collada-parse/readme.md#lcp\"); >Load Collada Parse</a>\n</div>\n\n\n<div class=menu id=ljl >\n\t<a href=JavaScript:displayMD(\"#load-json-load/readme.md#ljl\"); >Load JSON Load</a>\n</div>\n\n\n<div class=menu id=ljo >\n\t<a href=JavaScript:displayMD(\"#load-json-object/readme.md#ljo\"); >Load JSON Object</a>\n</div>\n\n\n<div class=menu id=ljp >\n\t<a href=JavaScript:displayMD(\"#load-json-parse/readme.md#ljp\"); >Load JSON Parse</a>\n</div>\n\n\n\n\n\n<!--", "\nhttp://va3c.github.io/viewer/cookbook/json-reader/readme-reader.html\n\n<i class=\"fa fa-external-link\"></i> [Live Demo (latest)]( http://va3c.github.io/viewer/va3c-editor/latest/index.html ) \n-->\n\n<i class=\"fa fa-github\"></i> [Source code on GitHub]( https://github.com/va3c/viewer/tree/gh-pages/cookbook ) \n<br>\n<br>\n\n<i class=\"fa fa-copy\"></i> [Copyright and license]( https://github.com/va3c/va3c.github.io/blob/master/LICENSE )" ]

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[ "Europe Gets Austerity, But With Few Signs Of Growth\n\nA French man holds a flare during a protest against the government's austerity measures on Tuesday in Lille, northern France. ", "European governments are proposing austerity measures, but critics say there should also be a plan for economic growth.", "\n\nSo far, European markets have not been impressed by last week's EU plan designed to fix the current crisis. ", "Here, a trader is seen at the stock market in Frankfurt, Germany, on Monday.", "\n\nMichael Probst\n/ AP\n\nListen\n\nListening...\n\n/\n\nOriginally published on December 13, 2011 7:20 pm\n\nThe plan European leaders agreed on last week to save the euro doesn't seem to have reassured the markets.", "\n\nTwo ratings agencies said the plan worked out in Brussels, which calls for greater fiscal integration, failed to address the immediate crisis of rising debts and the crushing costs of borrowing.", "\n\nAnd some economists worry that the EU leaders are wrong to put so much emphasis on austerity without any real plans to stimulate economic growth.", "\n\nFor example, Portugal's growth rate last year was anemic, and the economies of Greece and Ireland shrank.", "\n\nBut the more urgent problem for these three countries was mounting debt. ", "And when it looked like they might default, the European Union stepped in with some bailout money and provided a reprieve.", "\n\nThe three countries swallowed the bitter medicine that was prescribed, and announced cuts in public payrolls and welfare costs — as well as tax hikes.", "\n\nAnd while Italy's new prime minister has talked about the need for growth, he too has come up with a tough austerity package. ", "Spain's incoming prime minister promises similar pain. ", "All this austerity has sparked fierce street protests across southern Europe.", "\n\n\"When you are in a hopeless situation of excessive debt, you can't escape a painful adjustment process,\" he said.", "\n\nToo Much Austerity?", "\n\nBut some economists are warning that the mono-focus on austerity is not only hurting the most vulnerable, it's making overall economic matters worse.", "\n\n\"Fiscal austerity in the eurozone has now become part of the crisis rather than a solution to it,\" says economist Simon Tilford.", "\n\nThe debt burden of troubled eurozone countries is growing faster than their economies.", "\n\n\"So this is the absolute worst of all worlds: fiscal austerity, contracting economies and a dramatic increase in the burden of the debt relative to the size of the economy,\" Tilford says. \"", "Because their economies are shrinking and the debt burdens are rising, it's a very difficult situation, and it's the reason why investors have taken fright because they cannot see, understandably, how various economies are going to grow.\"", "\n\nAnd unless they grow, Tilford says, these countries won't be able to service their debt.", "\n\nGerman economist Ferdinand Fichtner agrees and adds that the current austerity-only focus risks creating a downward spiral.", "\n\n\"Where the weak economy, which stems from the euro-area crisis, feeds into a weaker labor market situation, and that in turn affects consumption again, meaning that the production will drop again,\" he says. \"", "And then you have this negative feedback loop, and you are quickly in a real recession.\"", "\n\nStimulating Growth\n\nThere are ways debt-troubled countries might try to stimulate growth without spending lots of public money and adding to their debt woes.", "\n\nStrong eurozone nations like Germany and the Netherlands could launch stimulus programs and expand public-private partnership schemes, says former banker Sony Kapoor. ", "He says the EU has some funds it could direct to shovel-ready projects.", "\n\n\"For example, cross-border power transmission, transport infrastructure, green energy investments, broadband investments, which effectively the European Investment Bank could start tomorrow with this new capital increase,\" he says.", "\n\nBut it's hardly clear those efforts, even if implemented, would prove big enough to make a real difference.", "\n\nFor years, burdensome bureaucracy and corruption in some eurozone countries have stifled innovation. ", "Even in Germany, with the strongest economy in the eurozone, legendary red tape is an impediment to growth, especially for startups.", "\n\nSascha Kellert co-founded a high-tech firm called ezeep and applied for a no-collateral loan for startups through the Berlin Investment Bank.", "\n\n\"It was supposed to be a quick loan,\" Kellert says with a laugh. \"", "On the website, they advertise 'two weeks,' but it turned out to be four months.\"", "\n\nEconomist Gayle Allard says Spain and Italy are talking about cutting rules and regulations, and making it easier for companies to hire and fire people. ", "It's all part of an effort to boost competitiveness and productivity. ", "But so far, she says, it is mostly talk.", "\n\n\"There is talk of making it easier to do business, definitely talk of labor market reform, although they haven't said how they are going to do it, there isn't any very popular way to do it,\" Allard says. \"", "So unfortunately, there is a dearth of ideas.\"", "\n\nCopyright 2013 NPR. ", "To see more, visit http://www.npr.org/.\n\nTranscript\n\nMELISSA BLOCK, HOST:\n\nFrom NPR News, this is ALL THINGS CONSIDERED, I'm Melissa Block. ", "European leaders may have agreed on a deal last week to save the euro, but financial markets have been sending a clear message ever since. ", "They're still worried. ", "According to two rating agencies, the deal fails to address the immediate crisis of rising debt and the crushing costs of borrowing. ", "And looming over all of this is one more problem that has both the markets and economists spooked – growth, or a lack of it.", "\n\nAs NPR's Eric Westervelt reports, many experts worry that E.U. leaders are spending too much time belt-tightening and not enough trying to get their economies growing again.", "\n\nERIC WESTERVELT, BYLINE: Last year, Portugal's growth rate was anemic, and the economies of Greece and Ireland actually shrank. ", "But the more urgent problem for these countries was mounting debt. ", "And when it looked like they might default, the European Union stepped in with some bailout money and provided a reprieve. ", "The three countries swallowed the bitter medicine that was prescribed and announced cuts in public payrolls and welfare costs, as well as tax hikes.", "\n\nAnd while Italy's new prime minister has talked about the need for growth, he, too, has come up with a tough austerity package. ", "Spain's incoming prime minister promises similar pain. ", "All this austerity has sparked fierce street protests across southern Europe. ", "Yet, Germany's finance minister, Wolfgang Schaeuble, shows little sympathy.", "\n\nWOLFGANG SCHAEUBLE: (Speaking foreign language)\n\nWESTERVELT: When you are in a hopeless situation of excessive debt, you can't escape a painful adjustment process, he said. ", "But some economists are warning that the mono-focus on austerity is not only hurting the most vulnerable, it's making overall economic matters worse.", "\n\nSIMON TILFORD: I think fiscal austerity in the eurozone has now become part of the crisis rather than a solution to it.", "\n\nTILFORD: So this is the absolute worst of all worlds: fiscal austerity, contracting economies and a dramatic increase in the burden of the debt relative to the size of the economy because their economies are shrinking and the debt burdens are rising. ", "It's a very, very difficult situation. ", "It's the reason why investors have taken flight because they cannot see, understandably, how various economies are going to grow.", "\n\nWESTERVELT: And unless they grow, Tilford says, these countries won't be able to service their debt. ", "German economist Ferdinand Fichtner agrees and adds that the current austerity-only focus risks creating a downward spiral.", "\n\nFERDINAND FICHTNER: Where the weak economy, which stems from the euro-area crisis, feeds into a weaker labor market situation, and that in turn affects consumption again, meaning that the production will drop again. ", "And then you have this negative feedback loop, and you are quickly in a real recession.", "\n\nWESTERVELT: There are ways debt-troubled countries might try to stimulate growth without spending lots of public money and adding to their debt woes. ", "Strong eurozone nations like Germany and the Netherlands could launch stimulus programs and expand public-private partnership schemes, says former banker Sony Kapoor. ", "He says the E.U. has some funds it could direct to shovel-ready projects.", "\n\nSONY KAPOOR: For example, cross-border power transmission, transport infrastructure, green energy investments, broadband investments, which effectively the European Investment Bank can start tomorrow with this new capital increase that it could have.", "\n\nWESTERVELT: But it's hardly clear if those efforts, even if they were implemented, would prove big enough to make a real difference. ", "For years, burdensome bureaucracy and corruption in some eurozone countries have stifled innovation. ", "Even in Germany, with the strongest economy in the eurozone, legendary red tape is an impediment to growth, especially for startups.", "\n\nGerman efficiency is a diehard myth. ", "Like most of its eurozone partners, Germany is efficient at throwing up piles of paperwork, layers of approval and forms that need stamping. ", "Sascha Kellert co-founded a high-tech firm called ezeep and applied for a no-collateral loan for startups through the Berlin Investment Bank.", "\n\nSASCHA KELLERT: It was supposed to be a quick loan. ", "It took us to the total of exceeding four months. ", "That was supposed to be the quick loan. ", "So on the website, they advertise it as taking two weeks, and it turned out to be four months.", "\n\nWESTERVELT: Economist Gayle Allard says Spain and Italy are talking about cutting rules and regulations, and making it easier for companies to hire and fire people. ", "It's all part of an effort to boost competitiveness and productivity. ", "But so far, she says, it is mostly talk.", "\n\nGAYLE ALLARD: There is talk of making it easier to do business, definitely talk of labor market reform, although they haven't said exactly how they are going to do it. ", "So unfortunately, there really is a dearth of ideas.", "\n\nWESTERVELT: Eurozone leaders seem too overwhelmed by the day to day market attacks, she says, and the enormity of the crisis, that they've yet to really think through any serious approach to growth. ", "Eric Westervelt, NPR News, Berlin. ", "Transcript provided by NPR, Copyright NPR." ]

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[ "Q:\n\nMongoDB not working with PHP on WAMP\n\nI have been having trouble with getting MongoDB and php working together:\n( ! ) ", "Fatal error: Class 'Mongo' not found in C:\\wamp\\www\\mongoDBTest\\index.php on line 6\n\nHere are my details:\n\nsystem: Windows NT LAPBTN1894 6.1 build 7600 (Windows 7 Enterprise Edition) AMD64\nArchitecture: x64\nApache/PHP: Apache/2.4.4 (Win64) PHP/5.4.12 thread safe\nCompiler: MSVC9 (Visual C++ 2008)\nMongoDB: 2.4.5\n\nMongoDB works fine on it's own and I have created the data/db folder.", "\nI have tried adding php_mongo.dll to my php ext folder using the file \"php_mongo-1.3.1-5.4-vc9-x86_64.dll\" and then renaming it and adding the relevent extension in the php.ini file.", "\nI also know about this site and not found anything useful\n http://www.php.net/manual/en/mongo.installation.php#mongo.installation.windows\n\nA:\n\nI am supposing you have restarted WAMP after changing the php.ini extensions.", "\nAt first, try to add the MongoDB in your ENVIRONMENT PATH and restart computer (you would be surprised by the amount of problems the restart does solve).", "\nWhen changing the php.ini try either to do not change the DLL name, and add it the way you downloaded it.", "\nYou can check some of this tips in detail clicking here.", "\n\n" ]

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[ "Moderate hyperbilirubinemia induces a transient alteration of neonatal behavior.", "\nTo investigate the behavioral changes induced by moderate hyperbilirubinemia in the otherwise healthy, untreated newborn infant. ", "Fifty term neonates (23 boys) with untreated moderate hyperbilirubinemia (median: 14.3 mg/dL; range: 13.2-20 mg/dL) and 50 matched control subjects with lower bilirubin concentrations (median: 9.1 mg/dL; range: 5.3-12 mg/dL) were administered the Brazelton Neonatal Behavioral Scale at 87 hours of life (range: 72-110 hours). ", "A subgroup analysis was also performed at 104 hours of life (range: 96-134 hours) and at 3 weeks of age. ", "At the first examination, all behavioral clusters were significantly altered in the group with moderate hyperbilirubinemia. ", "The visual and auditory capabilities of the hyperbilirubinemic infant were especially compromised. ", "Although social-interactive cluster scores significantly correlated both with serum bilirubinemia and birth weight, the former accounted for 8.7% of the variance and the latter accounted for only 4.7%. ", "The moderate hyperbilirubinemia neonates' scores also showed a negative correlation with the autonomic system and more frequent presence of tremors. ", "After 24 hours, a decrease in serum bilirubin within the moderate hyperbilirubinemic group was associated with improved scores. ", "At 3 weeks of age, the behavioral assessment of the 2 groups did not show significant differences. ", "Untreated moderate hyperbilirubinemia is associated with a transient and apparently reversible alteration of neonatal behavior, particularly in the social-interactive area." ]

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[ "---\nabstract: 'The superfluid properties of a two-state Fermi mixture in an optical lattice are profoundly modified when an imbalance in the population of the two states is present.", "We present analytical solutions for the free energy, and for the gap and number equations in the saddle-point approximation describing resonant superfluidity in the quasi-two-dimensional gas. ", "Inhomogeneities due to the trapping potentials can be taken into account using the local density approximation. ", "Analyzing the free energy in this approximation, we find that phase separation occurs in the layers. ", "The phase diagram of the superfluid and normal phases is derived and analytical expressions for the phase lines are presented. ", "We complete the investigation by accounting for effects beyond mean-field in the BEC limit where the system is more properly described as a Bose-Fermi mixture of atoms and molecules.'", "\nauthor:\n- 'J. Tempere$^{\\ast}$, M. Wouters and J.T. Devreese'\ntitle: 'Imbalanced Fermi superfluid in a one-dimensional optical potential'\n---\n\nThe formation of pairing correlations in a mixture of two types of fermions is frustrated when the number of fermions in each state is unequal. ", "The effect of such “spin imbalance” on pairing has been investigated theoretically since Clogston’s seminal work [@Clogston] for conventional superconductors, and has led to the prediction of novel pairing states [@FFLO], i.a. ", "relevant for color superconductivity in dense quark matter [@quark] and for neutron-proton pairing in asymmetric nuclear matter [@nuclear]. ", "The experimental study of Fermi superfluids with imbalanced spin population has only recently become possible, in ultracold atomic gases [@MIT-imbal; @RICE-imbal], renewing theoretical interest in imbalanced superfluidity [@theory-imbal; @bedaque; @IskinPRL97].", "\n\nIn these experiments, the interaction strength between ultracold fermions can be precisely controlled through the use of Feshbach resonances. ", "These scattering resonances allow to tune the s-wave scattering length from a large negative value, giving rise to a Bardeen-Cooper-Schrieffer (BCS) superfluid [@FermiBCS], to a large positive value where a Bose-Einstein condensate (BEC) of weakly bound molecules is formed [@FermiBEC].", "\n\nAlso the trapping geometry confining the Fermi gas can be precisely controlled experimentally. ", "Of particular interest is the possibility to impose a crystalline potential through the use of optical lattices. ", "These allow to experimentally mimic theoretical lattice models such as the Hubbard model. ", "One-dimensional optical lattices allow to study stacked layers of superfluid and create a geometry analogous to layered (cuprate) high-temperature superconductors. ", "Optical lattices have been used to demonstrate superfluid behavior of condensates [@CataliottiSCI293], and to probe the Mott-superfluid transition [@GreinerNAT415]. ", "So far, fermionic superfluidity in an optical lattice has only been studied [@MIT-optilatt] with balanced Fermi gases.", "\n\nWe investigate the effect of spin imbalance on the superfluid properties of a Fermi gas in an optical lattice. ", "In particular, we will examine the case of a one-dimensional optical lattice generated by two counterpropagating laser beams (parallel to the $z$-axis) with wave length $\\lambda$. These laser beams generate a periodic potential $V_{0}\\sin^{2}\\left( 2\\pi z/\\lambda\\right)\n.$When loaded in this optical lattice, the gas forms a stack of typically a few hundred quasi-2D layers containing several thousands of atoms each. ", "The interaction between atoms within a given quasi-2D layer can be modelled by a 2D contact interaction whose strength $g$ depends on the model cutoff $K_{c}$ and on the energy of the scattering atoms through [@RanderiaPRB41]$$\\frac{1}{g}=\\frac{m}{4\\hbar^{2}}\\left[ i-\\frac{\\ln\\left( E/E_{b}\\right)\n}{\\pi}\\right] -\\int_{k<K_{c}}\\frac{d^{2}\\mathbf{k}}{(2\\pi)^{3}}\\frac\n{1}{(\\hbar k)^{2}/m-E+i\\varepsilon}.\\label{g}$$ Here, $m$ is the mass of the atoms and $E_{b}$ is the energy of the bound state that always exists in two dimensions, given by$$E_{b}=\\frac{C\\hbar\\omega_{L}}{\\pi}\\exp\\left( \\sqrt{2\\pi}\\frac{\\ell_{L}}{a_{s}}\\right) ,\\label{Eb}$$ with $a_{s}$ the (3D) s-wave scattering length of the fermionic atoms, $\\omega_{L}=\\sqrt{8\\pi^{2}V_{0}/\\left( m\\lambda^{2}\\right) }$ and $\\ell\n_{L}=\\sqrt{\\hbar/(m\\omega_{L})}$ and $C\\approx0.915$ (cf. ", "Ref. [", "@PetrovPRA64]).", "\n\nIn this letter we derive an *analytical* expression for the free energy of the gas with density $n$ in a layer in the optical potential. ", "Extremizing this free energy with respect to the superfluid gap allows to set up and solve the gap equation. ", "We derive analytical expression for both the gap and the chemical potential, for fixed imbalance. ", "However, we will argue that the imbalanced gas may be unstable with respect to phase separation into a balanced superfluid and a halo of excess carriers, similar to the three-dimensional case [@bedaque], and we derive the phase diagram for the gas, again retrieving analytic expressions for the phase boundaries.", "\n\nThe partition sum of the quasi-2D Fermi gas can be written as a path integral over the exponential of the action functional $S$ for the fermionic fields $\\bar{\\psi}_{k,\\sigma},\\psi_{k,\\sigma}$ where $\\sigma$ denotes the spin. ", "We write $k=\\{\\mathbf{k},\\omega_{n}\\}$ for the 2D wave number **k** and the Matsubara frequency $\\omega_{n}=(2n+1)\\pi/\\beta$ where $\\beta=1/(k_{B}T)$ is the inverse temperature:$$\\mathcal{Z}=\\int\\mathcal{D}\\psi\\mathcal{D}\\bar{\\psi}\\exp\\{-\\mathcal{S}\\},$$ with $$\\mathcal{S}=\\frac{1}{\\beta}\\sum_{\\omega_{n}}\\int_{\\mathcal{B}}\\frac\n{d\\mathbf{k}}{(2\\pi)^{2}}\\text{ }\\left\\{\n{\\textstyle\\sum\\limits_{\\sigma=\\uparrow,\\downarrow}}\n\\bar{\\psi}_{k,\\sigma}\\left[ -i\\omega_{n}+\\mathbf{k}^{2}-\\mu_{\\sigma}\\right]\n\\psi_{k,\\sigma}+g\\bar{\\psi}_{k,\\uparrow}\\bar{\\psi}_{-k,\\downarrow}\\psi_{-k,\\downarrow}\\psi_{k,\\uparrow}\\right\\} .\\label{S1}$$ Here, we use units such that $\\hbar=k_{F}=E_{F}=1$. The number of spin-up and spin-down fermions is controlled through the chemical potentials $\\mu_{\\uparrow}$ and $\\mu_{\\downarrow}$. The partition sum corresponding to the action functional (\\[S1\\]) can be calculated following the standard procedure of introducing the Hubbard-Stratonovic decomposition, integrating out the Grassman variables, and performing the saddle-point approximation [@MichielPRA70; @popov] with a constant gap $\\Delta$. We therefore neglect the possibility of two-dimensional FFLO type states with a modulated order parameter [@FFLO; @LOFF]. ", "It is useful to express the results as a function of $\\mu=(\\mu_{\\uparrow}+\\mu_{\\downarrow})/2$ determining the total number of fermions and $\\zeta=(\\mu_{\\uparrow}-\\mu_{\\downarrow})/2$ expressing the imbalance in chemical potentials. ", "We find $\\mathcal{Z}_{sp}=\\exp\\{-\\beta\n\\Omega_{sp}\\}$ with $$\\Omega_{sp}=-\\frac{\\Delta^{2}}{g}-\\frac{1}{\\beta}\\int\\frac{d^{2}\\mathbf{k}}{(2\\pi)^{2}}\\left\\{ \\log\\left[ 2\\cosh(\\beta\\zeta)+2\\cosh(\\beta\nE_{k})\\right] -\\beta\\xi_{k}\\right\\} .\\label{freeE}$$ Here the $k$-integration is convergent at large wave vectors so that the wave vector cutoff $K_{c}$ can be sent to infinity, $\\Delta$ represents the pairing gap, $\\xi_{k}=k^{2}-\\mu$ is the free particle spectrum, and $E_{k}=\\sqrt\n{\\xi_{k}^{2}+\\Delta^{2}}$ is the Bogoliubov spectrum. ", "The saddle-point free energy $\\Omega_{sp}$ allows to derive the gap and number equations. ", "A similar result was derived for the homogeneous 3D gas by Iskin and Sa de Melo [@IskinPRL97]. ", "For the 2D case however, we succeeded to perform the wave-number integrations analytically in the limit of temperature going to zero:$$\\begin{aligned}\n8\\pi\\Omega_{sp} & =-\\Delta^{2}\\ln\\left( E_{b}\\right) -\\mu\\left( \\sqrt\n{\\mu^{2}+\\Delta^{2}}+\\mu\\right) +\\Delta^{2}\\ln\\left( \\sqrt{\\mu^{2}+\\Delta^{2}}-\\mu\\right) -\\dfrac{\\Delta^{2}}{2}\\nonumber\\\\\n& -2\\zeta\\left( k_{b}^{2}-k_{a}^{2}\\right) +\\xi_{b}\\sqrt{\\xi_{b}^{2}+\\Delta^{2}}-\\xi_{a}\\sqrt{\\xi_{a}^{2}+\\Delta^{2}}+\\Delta^{2}\\ln\\left(\n\\dfrac{\\sqrt{\\xi_{b}^{2}+\\Delta^{2}}+\\xi_{b}}{\\sqrt{\\xi_{a}^{2}+\\Delta^{2}}+\\xi_{a}}\\right) \\label{fresult}$$ where $\\xi_{a,b}=k_{a,b}^{2}-\\mu$ and for $\\zeta>\\sqrt{\\Delta^{2}+(\\min\n[\\mu,0])^{2}}$ $$\\left\\{\n\\begin{array}\n[c]{l}k_{a}=\\sqrt{\\max[\\mu-\\sqrt{\\zeta^{2}-\\Delta^{2}},0]}\\\\\nk_{b}=\\sqrt{\\mu+\\sqrt{\\zeta^{2}-\\Delta^{2}}}\\end{array}\n\\right. ", " \\text{ }$$ For $\\zeta\\leqslant\\sqrt{\\Delta^{2}+(\\min[\\mu,0])^{2}}$ the terms containing $k_{a}$ and $k_{b}$ in (\\[fresult\\]) vanish. ", "The Bogoliubov energy $E_{k}$ for quasiparticle excitations with wave vector $k=k_{a},k_{b}$ becomes equal to the imbalance of the chemical potentials $\\zeta$. All quasiparticle states with $k\\in\\lbrack k_{a},k_{b}]$ have a Bogoliubov energy less than $\\zeta$, and contribute as normal state particles, rather than as superfluid excitations, to the free energy.", "\n\nIskin and Sa de Melo [@IskinPRL97] solve the gap and number equations for the imbalanced three-dimensional superfluid numerically with respect to $\\zeta,\\mu$ and $\\Delta$ for a given imbalance $\\delta n/n$ and a given interaction strength $g$. In the two-dimensional case, this procedure applied to (\\[freeE\\]), yields analytical results, summarized in Table \\[tab1\\]. ", "However, the question can be raised as to whether the state with fixed $\\delta\nn/n$ is stable with respect to phase separation into a phase with a balanced superfluid ($\\delta n/n=0$) in the center of the trap and an imbalanced halo of excess spin component surrounding it. ", "Indeed, in the experiment of Ketterle and co-workers [@MIT-shellimage] for a three-dimensional gas with a nonuniform trapping potential, the excess spin component is expelled in a shell surrounding a spin-balanced superfluid . ", "Will this be similar for a 2D gas within a layer of the optical potential ?", "\n\n$\\begin{tabular}\n[c]{l|cc}\\hline\\hline\n& $E\\_[b]{}/2&lt;( n/n) \\^[2]{}E\\_[F]{}$ & $( n/n) \\^[2]{}E\\_[F]{}&lt;E\\_[b]{}/2$\\\\\\hline\n$\\^[2]{}$ & $0$ & $2E\\_[b]{}E\\_[F]{}( 1-h( E\\_[F]{}/E\\_[b]{}) ) $\\\\\n$$ & $E\\_[F]{}$ & $E\\_[F]{}-( 1-h( E\\_[F]{}/E\\_[b]{}) ) $\\\\\\hline\\hline\n\\end{tabular}\n$\n\nIf we consider a 2D trapping potential $V\\left( \\mathbf{r}\\right) $ that varies slowly on the length scales set by the interparticle distance $\\ell=n^{-1/2}$ and the superfluid gap $\\ell_{\\Delta}=\\sqrt{\\hbar^{2}/m\\Delta\n}$, we can apply the procedure outlined by De Silva and Mueller [@DeSilvaPRA73] for the imbalanced gas in a regular three-dimensional trap. ", "That is, we calculate $n\\left( \\mathbf{r}\\right) $ and $\\delta\nn\\left( \\mathbf{r}\\right) $ in the local density approximation, where the local average chemical potential equals $\\mu=\\mu_{0}-V\\left( \\mathbf{r}\\right) $ and the difference between the chemical potentials $\\zeta=\\zeta\n_{0}$ is constant in space for a spin-independent trapping potential:$$\\begin{aligned}\nn\\left( \\mathbf{r}\\right) & =-\\left. ", " \\partial\\Omega_{sp}/\\partial\n\\mu\\right\\vert _{\\mu=\\mu_{0}-V\\left( r\\right) ,\\zeta=\\zeta_{0}}\\\\\n\\delta n\\left( \\mathbf{r}\\right) & =-\\left. ", " \\partial\\Omega_{sp}/\\partial\\zeta\\right\\vert _{\\mu=\\mu_{0}-V\\left( r\\right) ,\\zeta=\\zeta_{0}}.\\end{aligned}$$ The gap is then found by extremizing $\\Omega_{sp}$ with respect to $\\Delta,$ for $\\mu$ and $\\zeta$ fixed by the local density approximation, rather than for $\\delta n/n$ fixed. ", "The validity of this procedure depends on whether the local density approximation is justified; this need not be the case for all experimental setups [@RICE-imbal].", "\n\nFor $\\zeta=0$, we find that, the free energy $\\Omega_{sp}$ shows a single minimum at $\\Delta_{\\text{bal}}=\\sqrt{2E_{b}\\left( \\mu+E_{b}/2\\right) }$ [@RanderiaPRB41], where its value is $\\Omega_{\\text{bal}}=-\\left(\n\\mu+E_{b}/2\\right) ^{2}/(4\\pi)$. This minimum represents the superfluid state (since $\\Delta\\neq0$). ", "As the imbalance $\\zeta$ is increased, $\\Omega_{sp}$ develops a second minimum around $\\Delta=0,$ representing the normal state. ", "The free energy of the normal state is $\\Omega_{0}=-[(\\mu+\\zeta)^{2}\\Theta\n(\\mu+\\zeta>0)\\left. ", " +(\\mu-\\zeta)^{2}\\Theta(\\mu-\\zeta>0)\\right] /(8\\pi).$ We have verified numerically that no other minima of $\\Omega_{sp}$ except the ones at $\\Delta=\\Delta_{\\text{bal}}$ and $\\Delta=0$ occur.", "\n\nUpon increasing $\\zeta$ the free energy curves are only affected in the region $\\Delta<\\zeta$. The minimum at $\\Delta=\\Delta_{\\text{bal}}$, representing the superfluid state, is therefore not affected by changes in $\\zeta$ until it ceases to exist: $\\Omega_{\\text{bal}}$ is independent of $\\zeta$. From this it follows that the superfluid state does not sustain imbalance ($\\delta n=0$ since $\\partial\\Omega_{\\text{bal}}/\\partial\\zeta=0$). ", "The free energy of the normal state, $\\Omega_{0}$, does depend on $\\zeta$, so that the normal state supports imbalance, as expected. ", "This scenario is similar to that for a 3D imbalanced Fermi mixture [@bedaque].", "\n\nTo evaluate the phase boundary between the balanced superfluid and the imbalanced normal state, we should make a distinction between the cases $\\mu>\\zeta$ and $\\mu<\\zeta$. For $\\mu>\\zeta$ the thermodynamic potentials of the superfluid and normal state are equal for $\\mu E_{b}=\\zeta^{2}-(E_{b}/2)^{2},$ whereas for $\\zeta>\\mu>-\\zeta$, they are equal for $\\mu=(\\zeta-\\sqrt{2}E_{b})/(\\sqrt{2}-1)$. In the normal state, the chemical potential of at least one of the spin components (up or down) should be positive for there to be any particles at all. ", "This means that $\\mu+\\zeta>0$ or $\\mu-\\zeta>0.$ For $\\zeta>0,$ the first condition is easier to fulfill, so that it determines the boundary in the phase diagram with the “empty phase” (no particles).", "\n\nFigure \\[fig2\\] shows the phase diagram of the superfluid (SF), normal (N), fully polarized normal (NP) and empty phases as a function of $\\mu/E_{b}$ and $\\zeta/E_{b}.$ This phase diagram looks qualitatively similar to the one obtained in 3D by mean field theory in Ref. [", "@DeSilvaPRA73].", "\n\n\\[ptb\\]\n\n[phasdiag.eps]{}\n\nWithin this local density approximation, moving from the center of the trap towards the edge corresponds to moving down along the arrow in figure \\[fig2\\]. ", "From the center to the edge we encounter first the balanced superfluid (SF), then a shell of spin-imbalanced normal gas, and finally a shell of fully polarized normal gas, as illustrated in the inset. ", "The superfluid state in this treatment is balanced in the limit of temperature zero, but allows for imbalance for any $T>0$.\n\nIn a typical experiment with a 1D optical lattice, several hundreds of layers are present. ", "As long as the Fermi energy and the superfluid gap are much larger than the tunneling rate between the layers, the pairing is essentially a phenomenon that takes place within each layer individually [@giulianoPRL] and each layer can be treated in the local density approximation by setting $\\mu_{0}^{\\left( i\\right) }=\\mu_{0}-U^{\\left(\ni\\right) },$ where $U^{\\left( i\\right) }$ is the trapping potential at the center of the $i$th layer. ", "The tunneling between the different layers is between layers of zero imbalance, so that the results of Refs. [", "@MichielPRA70; @giulianoPRA71] can be used.", "\n\nThe preceding saddle point calculation implicitly makes the mean field assumption that the typical size of the paired state $\\ell_{\\Delta}$ is much larger than the distance between the fermionic atoms $\\ell$. Deep in the BEC limit, the system is in fact more suitably described as a Bose-Fermi mixture of strongly bound bosonic pairs and excess majority component atoms. ", "We again can treat the 2D Bose-Fermi mixtures in the $\\mu$-$\\zeta$ plane analytically. ", "The energy density of the Bose-Fermi mixture is given by $E=2\\pi n_{F}^{2}+g_{BB}n_{B}^{2}/2+g_{BF}n_{B}n_{F}$ where the density of bosonic molecules $n_{B}$ and of fermionic atoms $n_{F}$ are positive. ", "The coupling constant $g_{BB}$ for dimer-dimer scattering in 2D has been calculated by Petrov et al. [", "@petrov2D], but not that for dimer-atom scattering, $g_{BF}$. However in the limit of very low energy scattering, dimensional arguments show that to first order the dimer-dimer and dimer-atom scattering amplitudes are equal. ", "The chemical potentials are $\\mu_{F}=4\\pi n_{F}+g_{BF}n_{B}$ for the fermionic atoms and $\\mu_{B}=g_{BB}n_{B}+g_{BF}n_{F}$ for the bosonic molecules.", "\n\nA minimal energy state has a positive curvature as a function of the densities, i.e. the eigenvalues of $H_{ij}=\\partial^{2}E/\\partial\nn_{i}\\partial n_{j}\\ $have to be positive. ", "A necessary condition is that its determinant is positive: $4\\pi g_{BB}-g_{BF}^{2}>0.$ Inverting the expressions for the chemical potential gives$$\\begin{aligned}\nn_{F} & =\\frac{g_{BB}\\mu_{F}-g_{BF}\\mu_{B}}{4\\pi g_{BB}-g_{BF}^{2}}\\label{nf}\\\\\nn_{B} & =\\frac{4\\pi\\mu_{B}-g_{BF}\\mu_{F}}{4\\pi g_{BB}-g_{BF}^{2}} \\label{nb}$$ The expressions (\\[nf\\]), (\\[nb\\]) provide us with the information on the phase diagram for phase separation of the 2D Bose-Fermi mixture. ", "The condition for a finite number of fermions is $\\mu_{F}>g_{BF}\\mu_{B}/g_{BB}$ and for a finite number of bosons, it is $\\mu_{B}>g_{BF}\\mu_{F}/4\\pi$, where we have used $4\\pi g_{BB}>g_{BF}^{2}$, as required for the stability of the system. ", "To use the above results for the BEC side of the BEC/BCS crossover with imbalance, we substitute the bosonic chemical potential by $\\mu_{B}\\rightarrow\\mu_{\\uparrow}+\\mu_{\\downarrow}+E_{b}=2\\mu+E_{b}$ and the fermionic chemical potential by $\\mu_{F}\\rightarrow\\mu_{\\uparrow}=\\mu+\\zeta$. The condition for a finite molecule density is then $$\\mu>-\\frac{E_{b}}{2}\\left( 1-\\frac{g_{BF}}{2\\pi}\\right) +\\frac{g_{BF}}{4\\pi\n}\\zeta\\label{mmin}$$ while the condition for a finite fermion density reads$$\\mu<\\frac{\\zeta-E_{b}g_{BF}/g_{BB}}{2g_{BF}/g_{BB}-1} \\label{mmax}$$ In between these limits, a mixture of bosonic molecules and fermionic atoms may coexist. ", "Thus, we expect corrections beyond mean field to allow for an additional phase to appear in the phase diagram of Fig.\\[fig2\\]: the imbalanced superfluid, qualitatively indicated by the shaded region. ", "Moreover, Eq. (", "\\[mmax\\]) indicates that the line separating the spin-balanced superfluid (molecules only) from the imbalanced superfluid lies below the mean field SF-NP phase boundary of Fig.\\[fig2\\].", "\n\nIn conclusion, the experimental and theoretical investigation of resonance superfluidity in Fermi gases has been marked by two recent advances: the creation of a Fermi superfluid from a gas with unequal spin populations [@MIT-imbal; @RICE-imbal], and the detection of fermionic superfluidity in an optical lattice [@MIT-optilatt]. ", "We have combined both effects and studied the effect of unequal spin populations on the superfluidity in an optical lattice.", "\n\nWe derived an analytical expression for the free energy of the imbalanced 2D Fermi gas, eq. (", "\\[fresult\\]). ", "From this result, the BEC/BCS gap equation and saddle-point number equations can be solved analytically, and results are provided for fixed imbalance $\\delta n$ in table (\\[tab1\\]) However, analyzing the free energy as a function of the superfluid gap we found that phase separation occurs, and a (possibly imbalanced) normal and (always balanced) superfluid phase separate. ", "The phase boundaries are evaluated analytically. ", "The shell structure of the inhomogeneously trapped gas is revealed to successively be from the center to the edges a balanced superfluid, the spin-imbalanced normal state and the fully polarized normal state. ", "In the deep BEC limit a Bose-Fermi mixture offers a more suitable description than the mean-field picture. 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[ "The NCAA transfer portal is much like the Matrix—you can only see it if you’re inside of it, and information regarding the portal must be taken with a grain of salt.", "\n\nBut according to InsideMDSports’ Jeff Ermann, senior defensive lineman Adam McLean has entered the portal and could be transferring away from College Park to take his talents elsewhere.", "\n\nMcLean, a former four-star recruit, broke out last season with 36 tackles and a sack across 11 games. ", "The 305-pound roadblock on the interior defensive line played in the Red-White Game in April and looked to be in line for a sizable role this season, but it seems as though he is exploring options elsewhere.", "\n\nOn the other side of the football, the Terrapins could be losing a tight end. ", "While there’s no official word about him entering the portal just yet, Michael Cornwell appears to be leaving the program, according to a video posted by the graduate tight end on Twitter Wednesday morning.", "\n\n❤️ Maryland, it's been nothing short of extraordinary pic.twitter.com/SKaZB3rlSR — Michael Cornwell (@mikecorn5) May 29, 2019\n\nLast offseason, Cornwell transitioned to tight end after three years (five games) with the program at wide receiver, and he was utilized often as a result. ", "He played in 10 of the team’s 11 games, but didn’t catch a single ball all season long. ", "With Mike Locksley’s new regime, it seems as though the position will be running routes more often. ", "In the spring game, tight ends combined for 17 catches, 125 yards and four touchdowns. ", "To put that into perspective, Maryland tight ends have caught 15 passes combined over the last three seasons.", "\n\nIn that game, Cornwell himself caught five passes for 28 yards, including a seven-yard touchdown from MVP Tyler DeSue. ", "However, with First Team All-MAC tight end Tyler Mabry transferring from Buffalo and three-star freshmen Tyler Devera and Malik Jackson on the way, position coach Mike Miller’s group is a bit crowded. ", "After earning his degree last week, Cornwell will use his new graduate status to explore other options.", "\n\nIncredibly proud of these young men and all of the Terps graduating this week. ", "They MAXIMIZED their opportunities to earn a degree from this great university! ", "pic.twitter.com/LY5K3Fp8vm — Michael Locksley (@CoachLocks) May 22, 2019\n\nIn other news\n\nMen’s basketball point guard Anthony Cowan Jr. is officially returning to Maryland for his senior season, as Wednesday night was the deadline for players to withdraw from the NBA Draft.", "\n\nThat instantly makes the Terrapins a contender next season, even with the loss of Bruno Fernando to the association. ", "CBS Sports college basketball guru Jon Rothstein ranked them as the No. ", "6 team in the country in his post-withdrawal deadline rankings.", "\n\nPreseason Top 25:\n\n\n\n1. ", "Michigan St\n\n2. ", "Louisville\n\n3. ", "Duke\n\n4. ", "UK\n\n5. ", "KU\n\n6. ", "Maryland\n\n7. ", "UNC\n\n8. ", "UVA\n\n9. ", "Nova\n\n10. ", "Gonzaga\n\n11. ", "TT\n\n12. ", "SHU\n\n13. ", "Baylor\n\n14. ", "LSU\n\n15. ", "Memphis\n\n16. ", "FSU\n\n17. ", "Arizona\n\n18. ", "Florida\n\n19. ", "UW\n\n20. ", "Purdue\n\n21. ", "VCU\n\n22. ", "Georgetown\n\n23. ", "Harvard\n\n24. ", "Mississippi St\n\n25. ", "Utah St — Jon Rothstein (@JonRothstein) May 30, 2019\n\nAfter winning the national championship against Boston College Sunday, Maryland women’s lacrosse was awarded with seven All-American nominees.", "\n\nAllegra Rivas led Maryland volleyball’s defense as the libero last season, and following a 522-dig freshman campaign, she’ll be training with the U.S. National Team.", "\n\nALLEGRA RIVAS\n\n\n\nSO PROUD of @allegrarivas, who is one of 20 players in the country selected to the 2019 US Junior National Training Team! ", "pic.twitter.com/kwmUifhfw2 — Maryland Volleyball (@TerpsVolleyball) May 29, 2019\n\nAnd finally, Maryland men’s golf’s Peter Knade has been named to PING’s All-Northeast Region Team, as the junior led the Terrapins all season long." ]

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[ "Mandatory Credit: Rich Barnes-USA TODAY Sports\n\nOne only needs to watch this year’s NBA Finals to see that the league is getting smaller, but there will always be room for big men in the game of basketball.", "\n\nAnd after Ernie Grunfeld‘s unwise investments in the Washington Wizards frontcourt, (DeJuan Blair, anyone?) ", "the interior is one place the team need to retool.", "\n\nThis year is great for big men at the very top of the draft, but there are some nice finds to be had lower down on the board.", "\n\nHere are four such big men who might have a chance to end up as Wizards next year." ]

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[ "Q:\n\nJSON parsing performance is slow\n\nMy JSON parser is very slow. ", "I wanted to ask, if I am missing something, or doing something wrong. ", "Is it wrong that I am calling a method in my doInBackground in my AsyncTask, should I put everything in my Asynctask? ", "Every help is appreciated. ", "Here is my relevant code:\nprivate class DownloadFilesTask extends AsyncTask<String, Integer, Long> {\n private ProgressDialog progress = null;\n\n @Override\n protected void onPreExecute() {\n progress = ProgressDialog.show(ArticleActivity.this, null,\n \"Artikel wird geladen...\");\n\n super.onPreExecute();\n }\n\n @Override\n protected Long doInBackground(String... params) {\n // TODO Auto-generated method stub\n String link = getIntent().getStringExtra(\"articleLink\");\n getJSONfromURL(\"my JSON Url\");\n return null;\n }\n\n protected void onPostExecute(Long result) {\n TextView txtArticle = (TextView) findViewById(R.id.txtViewArticle);\n txtArticle.setText(Html.fromHtml(item.getArticle()));\n progress.dismiss();\n }\n }\n\ngetJSONfromURL():\n public static void getJSONfromURL(String url) {\n\n // initialize\n InputStream is = null;\n String result = \"\";\n\n // http post\n try {\n HttpClient httpclient = new DefaultHttpClient();\n HttpPost httppost = new HttpPost(url);\n HttpResponse response = httpclient.execute(httppost);\n HttpEntity entity = response.getEntity();\n is = entity.getContent();\n\n } catch (Exception e) {\n Log.e(\"log_tag\", \"Error in http connection \" + e.toString());\n }\n\n // convert response to string\n try {\n BufferedReader reader = new BufferedReader(new InputStreamReader(\n is, \"UTF-8\"), 8);\n StringBuilder sb = new StringBuilder();\n String line = null;\n while ((line = reader.readLine()) !", "= null) {\n sb.append(line + \"\\n\");\n }\n is.close();\n result = sb.toString();\n } catch (Exception e) {\n Log.e(\"log_tag\", \"Error converting result \" + e.toString());\n }\n\n // try parse the string to a JSON object\n try {\n JSONObject jObject = new JSONObject(result);\n String myJSON = jObject.getString(\"content\");\n item = new Items();\n item.setArticle(myJSON);\n Log.i(\"json\", myJSON);\n } catch (JSONException e) {\n Log.e(\"log_tag\", \"Error parsing data \" + e.toString());\n }\n\n }\n\nThanks- \nEdit: \nthis is the JSON respnse. ", "It's not that big. ", "I always see these Apps, like google currents, that do not take even a second to load an article. ", "How do they do it?", "\n{\n \"domain\": \"www.spiegel.de\",\n \"next_page_id\": null,\n \"url\": \"http://www.spiegel.de/politik/ausland/bloomberg-empfiehlt-obama-als-us-praesident-a-864853.html\",\n \"short_url\": \"http://rdd.me/gfvpdlzr\",\n \"author\": null,\n \"excerpt\": \"Washington - Wenige Tage nach dem verheerenden Sturm \\\"Sandy\\\" hat der New Yorker Bürgermeister Michael Bloomberg die Wiederwahl von Präsident\",\n \"direction\": \"ltr\",\n \"word_count\": 772,\n \"total_pages\": 0,\n \"content\": \"<div id=\\\"spArticleColumn\\\" score=\\\"62.5\\\">\\n\\n\\t\\t\\t\\t\\t\\n\\n\\t\\t\\t<div id=\\\"spArticleTopAsset\\\" score=\\\"40.0\\\">\\n\\t\\t\\t\\t\\t\\n<div class=\\\"spArticleImageBox spAssetAligncenter\\\">\\n\\t\\t\\t\\t\\t\\t\\n\\t\\t\\t\\t\\t\\t<span href=\\\"http://www.spiegel.de/politik/ausland/bild-864853-420390.html\\\">\\n\\t\\t\\t\\t\\t\\t\\t\\t\\t\\t\\t<img src=\\\"http://cdn1.spiegel.de/images/image-420390-panoV9free-jmiw.jpg\\\" width=\\\"520\\\" border=\\\"0\\\" class=\\\"spPanoImageTeaserPic\\\" title='New Yorks Bürgermeister Bloomberg: \\\"Unser Klima ändert sich\\\"' alt='New Yorks Bürgermeister Bloomberg: \\\"Unser Klima ändert sich\\\"'></span>\\n\\t\\t\\t\\t\\t\\t\\t\\t\\t\\n\\t\\t\\t\\t\\t</div>\\n\\t\\t\\t\\t\\n</div>\\n\\t\\t\\t\\n\\t\\t\\t\\t\\n\\t\\t\\t\\t\\n<div id=\\\"spFbTwitterBarStd\\\" score=\\\"1.25\\\">\\n\\n\\t\\n\\t\\t\\n\\t\\n\\t\\n\\n\\t\\t\\t\\n\\t</div>\\n<div id=\\\"spArticleSection\\\" score=\\\"37.5\\\">\\n\\t\\n<p>Washington - Wenige Tage nach dem verheerenden Sturm \\\"Sandy\\\" hat der New Yorker Bürgermeister <a href=\\\"http://www.spiegel.de/thema/michael_bloomberg/\\\" title=\\\"Michael Bloomberg\\\" class=\\\"spTextlinkInt\\\">Michael Bloomberg</a> die Wiederwahl von Präsident <a href=\\\"http://www.spiegel.de/thema/barack_obama/\\\" title=\\\"Barack Obama\\\" class=\\\"spTextlinkInt\\\">Barack Obama</a> empfohlen. ", "Obama habe die Führerschaft beim Thema Klimawandel inne, schrieb das Stadtoberhaupt auf Bloomberg.com.</p>\\n\\n<p>\\n\\n\\t\\\"Unser Klima ändert sich. ", "Und während die Zunahme extremer Wetterlagen, die wir in New York und in der Welt erlebt haben, eine Folge davon sind oder nicht sein mögen, das Risiko, das es so sein könnte - angesichts der Zerstörung in dieser Woche - sollte alle gewählten Führer dazu zwingen, sofort zu Handeln\\\", so der frühere Republikaner Bloomberg. ", "</p>\\n\\n<p>Die Metropole und die einzelnen US-Staaten könnten solche Katastrophen nicht alleine stemmen: \\\"Wir brauchen Führung vom Weißen Haus\\\", schrieb der Bürgermeister. ", "Obama habe in den vergangenen Jahren wichtige Schritte für den Umweltschutz eingeleitet. ", "Romney habe dagegen in allen wichtigen Bereichen einschließlich dem Umweltschutz den Kurs gewechselt.</p>\\n\\n<p>New York und die gesamte US-Ostküste sind von der Sturmkatastrophe schwer getroffen worden. ", "Bis Donnerstag zählten die Behörden 56 Tote. ", "In Medien ist von über 80 Opfern die Rede. ", "Experten befürchten, dass sich der Schaden, den \\\"Sandy\\\" an der US-Ostküste angerichtet hat, auf bis zu 50 Milliarden Dollar summieren könnte. ", "Die Empfehlung für Obama und der Verweis auf extreme Wetterlagen kommen unmittelbar vor dem Urnengang. ", "Am kommenden Dienstag entscheiden die US-Wähler, ob erneut Obama oder sein republikanischer Herausforderer Mitt Romney ins Weiße Haus einzieht.</p>\\n\\n<div class=\\\"spPhotoGallery\\\" score=\\\"18.25\\\">\\n\\t\\n\\t\\t<ul><li class=\\\"spFirst\\\">\\n\\t\\t\\t\\t\\t\\t\\t\\t\\t<a href=\\\"http://www.spiegel.de/fotostrecke/us-praesident-obama-besucht-sandy-sturm-opfer-in-new-jersey-fotostrecke-89203.html\\\" title=\\\"Fotostrecke zeigen...\\\"><img src=\\\"http://cdn2.spiegel.de/images/image-419915-thumbbiga-sumg.jpg\\\" width=\\\"160\\\" border=\\\"0\\\"></a></li> \\n\\t\\t\\t\\t\\t\\t\\t<li>\\n\\t\\t\\t\\t\\t\\t\\t\\t\\t<a href=\\\"http://www.spiegel.de/fotostrecke/us-praesident-obama-besucht-sandy-sturm-opfer-in-new-jersey-fotostrecke-89203.html\\\" title=\\\"Fotostrecke zeigen...\\\"><img src=\\\"http://cdn2.spiegel.de/images/image-419909-thumbbiga-svrk.jpg\\\" width=\\\"160\\\" border=\\\"0\\\"></a></li> \\n\\t\\t\\t\\t\\t\\t\\t<li>\\n\\t\\t\\t\\t\\t\\t\\t\\t\\t<a href=\\\"http://www.spiegel.de/fotostrecke/us-praesident-obama-besucht-sandy-sturm-opfer-in-new-jersey-fotostrecke-89203.html\\\" title=\\\"Fotostrecke zeigen...\\\"><img src=\\\"http://cdn4.spiegel.de/images/image-419877-thumbbiga-dvih.jpg\\\" width=\\\"160\\\" border=\\\"0\\\"></a></li> \\n\\t\\t\\t\\t\\t\\t\\t</ul><br clear=\\\"all\\\">\\n\\t\\t\\t<a href=\\\"http://www.spiegel.de/fotostrecke/us-praesident-obama-besucht-sandy-sturm-opfer-in-new-jersey-fotostrecke-89203.html\\\" title=\\\"Fotostrecke zeigen...\\\"><strong>Obama im Katastrophengebiet:</strong>\\n\\t\\t\\t<span>Kümmerer-in-Chief</span></a></div>\\n\\t<br clear=\\\"all\\\">\\nDas Krisenmanagement im Nachgang von \\\"Sandy\\\" könnte Obama nun vielleicht genau jenen Vorsprung im Präsidentschaftsrennen bringen, den er braucht, um am 6. ", "November zu siegen. ", "Die Wahlempfehlung des beliebten Bloomberg folgt just einen Tag, nachdem der seinerseits beliebte Republikaner und Gouverneur Chris Christie den Präsidenten in seinem Staat New Jersey empfangen, ihn wieder und wieder für seinen Umgang mit der Katastrophe <a href=\\\"http://www.spiegel.de/politik/ausland/us-praesident-obama-besucht-sandy-sturm-opfer-in-new-jersey-a-864602.html\\\" title=\\\"gelobt\\\" class=\\\"spTextlinkInt\\\">gelobt</a> hat: Außerordentlich, exzellent, wunderbar - das waren die Worte Christies, der eigentlich als einer der entschiedensten Unterstützer von Mitt Romney galt. ", "\\n\\n<p>Dass nun ausgerechnet Regierungschef und Bürgermeister der vom Sturm am schwersten getroffenen Gebiete - New Jersey und New York City - so einhellig die Führungsqualitäten Obamas in der Krise loben, wird Eindruck machen auf viele unabhängige, unentschiedene Wähler. ", "Die zeigten sich in ihrer Mehrheit zunehmend genervt von der polarisierten Auseinandersetzung zwischen Demokraten und Republikanern. ", "Bloomberg selbst wurde zwischenzeitlich gehandelt als aussichtsreicher Dritte-Partei-Kandidat, der sowohl Romney als auch Obama Stimmen hätte nehmen können. ", "Doch er verzichtete. ", "Fortan bemühten sich beide Lager um seine Wahlempfehlung. ", "Obama hat gewonnen.</p>\\n\\n<p>Obama selbst hat die Hilfsbereitschaft für die Opfer des Hurrikans \\\"Sandy\\\" gelobt. ", "Die Nachbarschaftshilfe sei ebenso überragend gewesen wie die Hilfe über die Parteigrenzen hinweg, sagte Obama am Donnerstag bei einem Wahlkampfauftritt in Green Bay im Bundesstaat Wisconsin. ", "\\\"Während eines Sturms gibt es keine Demokraten und keine Republikaner\\\", erklärte der Präsident. ", "Er appellierte an die US-Bürger, die Sturmopfer weiter zu unterstützen. ", "\\\"Wir sind sprachlos und demütigt angesichts der zerstörerischen Kraft der Natur\\\", sagte Obama bei seinem ersten Wahlkampfauftritt nach einer Hurrikan-bedingten Zwangspause. ", "</p>\\n\\n<p>\\n<b>Obama setzt erneut auf \\\"Change\\\"-Slogan</b>\\n</p>\\n\\n<p>Unterdessen belebt Obama im Wahlkampf-Endspurt einen seiner erfolgreichen Slogans von 2008 wieder: \\\"Change\\\". ", "\\\"Ich weiß wie Wandel aussieht, denn ich habe dafür gekämpft\\\", sagte er vor etwa 2600 Zuhörern im Bundesstaat Wisconsin. ", "Sein Herausforderer Mitt Romney wolle die Wirtschaftskrise mit Mitteln lösen, die Ursache der ökonomischen Probleme seien, die er bei seinem Amtsantritt vorgefunden habe, sagte Obama. ", "</p>\\n\\n<p>\\\"Romney hat alle seine Talente als Verkäufer genutzt, um genau die Politik aufzuhübschen, die unserem Land so sehr geschadet hat. ", "Es ist dieselbe Politik, hinter der wir in den vergangenen vier Jahren hergeputzt haben - und das bietet er an als Wandel.\\\" So aber sehe Wandel - \\\"change\\\" - nicht aus.</p>\\n\\n<p>\\n\\n\\t\\\"Change\\\" war neben \\\"Hope\\\" - Hoffnung - einer der Schlüsselbegriffe, mit denen Obama 2008 das Weiße Haus eroberte. ", "Doch im laufenden Wahlkampf verzichtete er bislang weitgehend darauf, an diese griffigen Slogans anzuknüpfen - wohl auch, weil ihm viele Wähler vorwerfen, zu wenig in Washington bewegt und viele seiner Ankündigungen von vor vier Jahren nicht umgesetzt zu haben. ", "</p>\\n\\n<p>Statt dessen zog Romney mit dem Versprechen durchs Land, für \\\"wahren Wandel\\\" - \\\"real change\\\" zu sorgen, sollte er am kommenden Dienstag zum Präsidenten gewählt werden. ", "Fünf Tage vor der Wahl schien Obama nun entschlossen, den Begriff für sich zurückzuerobern. ", "\\\"Wisconsin, ich sage Euch: Wir wissen, wie Wandel aussieht. ", "Und was Romney anbietet, ist sicher kein Wandel.\\\" </p>\\n\\n<p>Wisconsin ist einer jener Handvoll Staaten, die die Wahl mitentscheiden könnten, denn hier ist noch nicht klar, wer von den beiden Bewerbern am Ende die Nase vorn haben wird. ", "Auch Nevada, Colorado und Ohio zählen zu den \\\"battleground states\\\", die zum Zünglein an der Waage werden könnten. ", "Auch sie standen auf dem Reiseplan des Präsidenten am Donnerstag. ", "Romney wird am Freitag in Wisconsin und Ohio erwartet.</p>\\n\\n</div>\\n<p><i>lei/dpa</i></p>\\n\\t\\n\\t\\t\\n\\n\\n<br class=\\\"spBreakNoHeight\\\" clear=\\\"all\\\"></div>\\n\\t\\t\\t\\t\\n\\t\\t\\t\\t\",\n \"date_published\": \"2012-11-01 20:02:00\",\n \"dek\": \"Barack Obama punktet mit seinem Krisenmanagement nach der \\\"Sandy\\\"-Katastrophe. ", "New Yorks Bürgermeister Bloomberg setzt sich für die Wiederwahl des US-Präsidenten ein - und verweist auf dessen Klimapolitik. ", "Zuvor hatte ihn bereits ein Top-Wahlhelfer von Mitt Romney gelobt.\",", "\n \"lead_image_url\": \"http://cdn1.spiegel.de/images/image-420390-thumb-jmiw.jpg\",\n \"title\": \"US-Wahlkampf: New Yorks Bürgermeister empfiehlt Obama\",\n \"rendered_pages\": 1\n}\n\nA:\n\nIf you do find that the JSON parser is taking a significant amount of time I would reccomend switching to the Jackson Streaming API. ", "It requires a bit more work to setup than other parsers, but I've found it to be extremely fast.", "\n\n" ]

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[ "Q:\n\nC#, calculate position of point by position and distance values of other points\n\nI have a struct with these values:\nstruct Point {\n public float x;\n public float y;\n}\n\nAnd I have three variables of this structure point1, point2 and point3. ", "\nI need to calculate position of point4 and only things that I have is the distances of point4 from each of these points.", "\nIs it possible to calculate position of point only by position of other three points with distances?", "\n\nA:\n\nOf course its possible. ", "This is simple geometry.", "\n\nTake point P1. ", "Somewhere at distance d is P4.", "\nWhat geometrical shape in 2D defines all points at a given distance from another point? ", "Yup, a circle. ", "Lets draw a circle centered in P1 with radius equal to the distance between P1 and P4.", "\nNow take P2 and do the same with the appropiate distance. ", "Now, what can happen? ", "Well, there are 2 possibilities:\n\nCircles around P1 and P2 don't intersect: the problem has no solution, you have finished.", "\nCircles around P1 and P2 have one (are tangent) or two intersection points.", "\n\nNow take the third point P3 and again draw a circle with the appropiate radius. ", "Two things can happen again:\n\nNew circle intersects with previous drawn circles in one of the intersection points previously identified; you found your solution, the common intersection point of all three circles is P4.", "\nNew circle does not intersect with previous drawn circles in any of the intersection points previsouly identified; problem has no solution.", "\n\nNow that the algorithm for solving the code is clear, you \"just\" need to implement it. ", "Consider creating types that represent points and circles and methods that intersect circles:\nclass Point\n{\n public double X { get; }\n public double Y { get; }\n ...\n}\n\nclass Circle\n{\n public Point Center { get; }\n public double Radius { get; }\n ....\n public static IEnumerable<Point> Interstect(Circle first, Circle second) { ... }\n}\n\nWhen you have coded something and stumbled upon unsurmountable odds you can post another question here asking for help solving more precisely defined problems you may be encountering. ", "No one is just going to code your (home)work for you.", "\nI do note that the solution is not mathematically trivial, but if you can't solve the mathematical problem to begin with then you have no business trying to code a solution.", "\n\n" ]

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[ "Asian blepharoplasty.", "\nAsian blepharoplasty requires an intimate knowledge of the anatomical subtleties distinct to the Asian patient. ", "With this knowledge and a thorough understanding of patients' expectations, the surgeon confidently can achieve predictable results and a preservation of Asian eyelid qualities in those patients who desire it." ]

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[ "Fair in Thousand Oaks aimed at helping seniors live well\n\nLive Well — Age Well, an information and technology fair featuring vendors and “ask the doctor” consultations, will take place May 18 at the Goebel Adult Community Center in Thousand Oaks.", "\n\nMore than 25 vendors will provide information on topics such as hearing and vision checks, free chair massages and assisted-living facilities, said Mike McAdam, recreation coordinator at the center.", "\n\nTeenagers with skills in electronics will work individually with people who need help with cellphones, cameras, laptop computer and other devices, he said.", "\n\nSponsored by the Conejo Recreation and Park District and UCLA Health, the event will feature doctor-led seminars and free tests of blood pressure, vital signs and body mass index. ", "Physicians also will staff an “ask the doctor” table.", "\n\n“There’s so much information and so many providers in the same place at the same time — a one-stop shop,” McAdam said. “", "Our goal is for seniors to gain ... information about living well and aging well to stay as active and healthy as possible.”", "\n\nThere will be talks on “What Every Senior Should Know” from 10-11 a.m., “Nutrition & Longevity” from 11 a.m. to noon, “What Screening Do You Need?” ", "from noon to 12:30 p.m. and “Take Action Stay Heart Healthy” from 1-2 p.m.\n\n“I will discuss the vaccines that are recommended, what diseases they prevent and what risks are involved with routine vaccinations. ", "I will also address some of the common myths surrounding vaccines,” said Ferrara, who works for UCLA Health System in the Thousand Oaks Multispecialty Group.", "\n\n“Many of the well-educated patients I see in my office are very hesitant about receiving vaccines, and when I delve into the reasons why, I often find that patients have been misinformed about the risks and benefits,” Ferrara said.", "\n\nShe thinks every patient has a right to choose whether to receive vaccines.", "\n\n“But I also believe that it is our duty as physicians to ensure that the choice is made based upon accurate information,” she said." ]

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[ "Dolichocephala arnaudi\n\nDolichocephala arnaudi is a species of dance flies, in the fly family Empididae.", "\n\nReferences\n\nCategory:Empididae\nCategory:Insects described in 2012\nCategory:Diptera of North America" ]

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[ "Q:\n\nElegantly mapping two objects based on id?", "\n\nI have two tables/lists of objects, which are connected by an ID (in SQL terms, a foreign key). ", "Is there some elegant way to perform a transformation on them so I end up with the \"child objects\" being referenced in a property in the \"parent\"?", "\nExample:\nTable1: Id, Name\nTable2: Id, Name, ForeignId (referencing Table1.Id)\n\nExpected result:\nTable2Object.", "Table1Object containing the correct object form Table1\n\nI know I can do it with first grouping the children by Id (purely for performance) and then going over the parents with a foreach, but that seems rather ... well ... unelegant to me.", "\n\nA:\n\nRelations with underscore? ", "Interesting =)\nYou can use _.map() & _.filter() for this:\nvar t = [\n {id: 1, Name: 't1'},\n {id: 2, Name: 't2'},\n {id: 3, Name: 't3'},\n {id: 4, Name: 't4'}\n];\nvar f = [\n {id: 1, Name: 'f1', ForeignId:1},\n {id: 2, Name: 'f2', ForeignId:1},\n {id: 3, Name: 'f3', ForeignId:2},\n {id: 4, Name: 'f4', ForeignId:3}\n];\n\nvar res = _.map(t, function(p){\n var j = _.filter(f, function(n){\n return p.id === n.ForeignId;\n });\n if(j && j.length) p.f = j;\n return p;\n});\n\nRes structure:\n\n" ]

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[ "1. ", "Introduction {#sec1-molecules-24-02170}\n===============\n\nExtraction is a key tool to supply the ever-increasing market requirement for bioactive compounds, and sustains and contributes to the rapid growth of the agro-food industry \\[[@B1-molecules-24-02170]\\]. ", "Existing extraction technologies are linked to several technological, environmental, and scientific barriers that are generally complex and difficult to overcome, for instance, minimizing energy and toxic solvent consumption, all the while reducing CO~2~ emission and guaranteeing safety and control for both the final product and the technical staff involved \\[[@B2-molecules-24-02170],[@B3-molecules-24-02170]\\]. ", "Consequently, green engineering and bio-refinery concepts gained a lot of attention worldwide by promoting environmentally friendly and efficient techniques that have the ability to substitute conventional processes \\[[@B4-molecules-24-02170]\\]. ", "Studies generally include the design of alternative extraction techniques using, for example, microwaves \\[[@B5-molecules-24-02170]\\], ultrasound \\[[@B6-molecules-24-02170]\\], or supercritical fluids \\[[@B7-molecules-24-02170]\\], but may also involve the search for alternative solvents to replace petrochemical solvents \\[[@B8-molecules-24-02170]\\]. ", "Within this context, it is important to state that solvents are widely used in academia for practical work; in analytical chemistry laboratories; as well as in industries to produce aromas, fats and oils, colors, antioxidants, or fine chemicals. ", "They are regarded as liquid medium used either for chemical product synthesis or for extraction, separation, and purification of bioactive compounds from various plant matrices. ", "Most extraction solvents used in academia or industry, like *n*-hexane, present undeniable advantages including a low boiling point leading to a highly efficient and simple removal, as well as an easy industrial implementation. ", "However, these low boiling point-solvents also generate substantial amounts of volatile organic compounds, explaining why they are universally considered as hazardous with associated environmental and health issues \\[[@B8-molecules-24-02170],[@B9-molecules-24-02170]\\]. ", "Furthermore, these solvents are often derived from petroleum, a fossil resource. ", "Acknowledging those concerns, many researchers have shifted their focus towards finding green alternatives to substitute petroleum-based solvents \\[[@B4-molecules-24-02170],[@B10-molecules-24-02170]\\]. ", "Within this context, green analytical chemistry (GAC) emerged to investigate clean practical alternatives to substitute polluting methods in order to lessen the ecological issues resulting from the side effects of conventional analytical methodologies that generate an important amount of chemical waste \\[[@B11-molecules-24-02170]\\]. ", "One of the solutions is to develop bio-based liquid phases produced from agricultural by-products \\[[@B4-molecules-24-02170],[@B12-molecules-24-02170],[@B13-molecules-24-02170]\\].", "\n\nTerpenes, ones of the major secondary metabolite families in plants, have been subjected to multiple investigations as a bio-replacement of conventional solvents \\[[@B8-molecules-24-02170]\\]. ", "The most common solvent derived from terpenes is undoubtedly [d]{.smallcaps}-limonene \\[[@B4-molecules-24-02170]\\], which is mainly present in *Citrus* peel essential oils, with levels exceeding 70%--95% \\[[@B13-molecules-24-02170],[@B14-molecules-24-02170],[@B15-molecules-24-02170]\\]. ", "It is responsible for the *Citrus* characteristic scent and could represent a valuable solution to the substitution of petrochemical solvent \\[[@B14-molecules-24-02170]\\]. ", "Indeed, the world market demand for *Citrus* fruits exceeds 100 million tons. ", "However, up to 40%--50% of the total mass that is treated is considered as peel waste \\[[@B16-molecules-24-02170],[@B17-molecules-24-02170]\\]. ", "Therefore, valorization of this by-product is of great economic and environmental importance for the industry. ", "Studies that investigated limonene include fats' and oils' determination in olive seeds using Soxhlet extraction \\[[@B18-molecules-24-02170]\\], extraction of oil from rapeseed and microalgae \\[[@B8-molecules-24-02170],[@B10-molecules-24-02170]\\], carotenoids from tomato \\[[@B14-molecules-24-02170]\\], aroma from caraway \\[[@B10-molecules-24-02170]\\], and moisture determination by Dean--Stark distillation \\[[@B19-molecules-24-02170]\\]. ", "The results obtained from those studies confirmed the potential of [d]{.smallcaps}-limonene as a green alternative to replace petroleum solvent in the extraction of secondary and primary metabolites from different plant matrices.", "\n\nWhile the use of [d]{.smallcaps}-limonene as a green solvent may sound like a valuable alternative, the fact that it is an unsaturated terpene that oxidizes easily under exposure to air makes it less attractive, especially as the formed oxidation products are labelled as allergens \\[[@B4-molecules-24-02170]\\]. ", "Logically, we considered that a total hydrogenation of [d]{.smallcaps}-limonene could produce *p*-menthane, a stable saturated terpene, which would not be oxidizable. ", "Such an approach seems particularly relevant if we consider the scarcity of saturated terpenes in natural essential oils compared with the abundance of [d]{.smallcaps}-limonene in *Citrus* by-products. ", "This study thus aims to synthesize *p*-menthane ([Figure 1](#molecules-24-02170-f001){ref-type=\"fig\"}) and evaluate its performances under the green analytical chemistry concept as a toluene replacement for moisture determination. ", "The green alternative performance was also compared to that of *n*-hexane for the extraction of natural substances such as carotenoids, aromas, and vegetable oils using Soxhlet or the conventional single step procedure. ", "The idea was to develop an ecological process that takes economical issues into consideration and presents itself as a competitive potential process for natural substance efficient extraction in cosmetic, food, or agrochemical applications. ", "This was completed with a theoretical solubility analysis of targeted secondary and primary metabolites in *p*-menthane and *n*-hexane using a computational predictive method (conductor-like combination of quantum chemistry (COSMO) coupled with statistical thermodynamics (RS)). ", "A comparison of *p*-menthane has also been done with toluene for moisture determination in Dean--Stark distillation apparatus.", "\n\n2. ", "Results and Discussion {#sec2-molecules-24-02170}\n=========================\n\n2.1. ", "Solubility Study: Experimentation and Modelisation {#sec2dot1-molecules-24-02170}\n-------------------------------------------------------\n\nA theoretical study was performed considering the technical parameters of the solvents for the extraction of the targeted compounds via a computational predictive method (COSMO-RS). ", "Solvent selectivity is a matter of polarity-based solubility parameters that involves both solutes and solvents. ", "The software screening model for solvents is a method used to determine and predict thermodynamic properties of the solvent without the need for any experimental data. ", "This is based on conductor-like combination of quantum chemistry (COSMO) coupled with statistical thermodynamics (RS) \\[[@B20-molecules-24-02170],[@B21-molecules-24-02170]\\].", "\n\n[Figure 2](#molecules-24-02170-f002){ref-type=\"fig\"} shows the COSMO-RS predicted solubilities of (i) β-carotene, (ii) three model triglycerides (LLL, OLL, and LOP; with L, O, and P for linoleoyl, oleoyl, and palmitoyl chains, respectively), and (iii) [d]{.smallcaps}-limonene and S-carvone aroma compounds in *n*-hexane and *p*-menthane. ", "These targeted solutes were chosen as they represent valuable compounds extractable from carrots, rapeseeds, and caraway, respectively. ", "The simulations were carried out by taking into consideration the solvent boiling points (b.p.) ", "and the operating laboratory conditions set at 25 °C. ", "The results expressed in log10 (x-soluble) show a high theoretical solubility of the compounds in both solvents. ", "In most cases, *p*-menthane has probability of solubility higher than, or similar to, *n*-hexane, which represents a significant first step to determine whether *p*-menthane can successfully replace *n*-hexane for the extraction of different natural products.", "\n\n\"x-soluble\": solute/solvent ratio expressed as a mole fraction. ", "Gray: reference. ", "Green: better or equivalent. ", "Red: slightly poorer than the reference. ", "Triglycerides abbreviated use L, O, and P for linoleoyl, oleoyl, and palmitoyl.", "\n\n2.2. ", "Extraction of Aromas from Caraway Seeds {#sec2dot2-molecules-24-02170}\n--------------------------------------------\n\nFood aromas are complex mixtures of volatile substances. ", "They are usually only present at very low concentrations. ", "Before using aromas, an extraction process from the targeted matrix is required.", "\n\nA study conducted by Filly et al. ", "\\[[@B22-molecules-24-02170]\\] compared the performance of eight alternative solvents (α-pinene, MeTHF, ethyl acetate, ethyl lactate, ethanol, dimethylcarbonate, and water) to n-hexane for extraction of aromas from caraway seeds. ", "The results showed that bio and green solvents have the potential to replace petroleum-based solvents. ", "Here, *p*-Menthane was evaluated as an alternative to *n*-hexane for the extraction of aromas from caraway seeds using solid--liquid extraction by ULTRA-TURRAX^®^ (Tube Drive P control for stirring, dispersing, grinding, and homogenization).", "\n\nThe chemical selectivity and performance comparison between the two solvents for two major compounds that are [d]{.smallcaps}-limonene and S-carvone were determined using GC-MS (gas chromatography coupled to mass spectrometry). ", "Several authors established that those two monoterpenes are the major compounds of caraway seeds in extractions carried out with different solvents \\[[@B4-molecules-24-02170],[@B23-molecules-24-02170]\\]. ", "As illustrated in [Table 1](#molecules-24-02170-t001){ref-type=\"table\"}, it is interesting to notice that both solvents showed a relatively similar profile of aroma compounds with no particular solvent selectivity detected. ", "The major compounds extracted from caraway seeds were S-carvone with approximately 60% for *p*-menthane and 64% for *n*-hexane, followed by [d]{.smallcaps}-limonene with 40% and 35% for *p*-menthane and *n*-hexane, respectively.", "\n\n2.3. ", "Carotenoids Extraction from Carrots {#sec2dot3-molecules-24-02170}\n----------------------------------------\n\nCarotenoids are largely used in the food industry as colorants or nutritional ingredients \\[[@B24-molecules-24-02170]\\]. ", "Several studies have indeed shown the beneficial role of carotenoids in decreasing the risk of diseases \\[[@B25-molecules-24-02170]\\] such as heart diseases, cardiovascular diseases, and cataracts \\[[@B22-molecules-24-02170],[@B26-molecules-24-02170],[@B27-molecules-24-02170]\\]. ", "Carrot is considered as an important dietary source of carotenoids, mainly carotenes, which impart their characteristic orange color to carrots. ", "As carotenes are one of the most hydrophobic compounds in the plant kingdom (logP around 15), they cannot be extracted with aqueous solutions of whatever organic solvent. ", "Existing methods of carotene extraction are thus mostly based on pure organic solvents such as *n*-hexane.", "\n\nGreen extraction techniques were developed according to the literature for carrots carotenoids extraction, such as ultrasound irradiation \\[[@B28-molecules-24-02170]\\] and supercritical CO~2~ extraction with ethanol \\[[@B29-molecules-24-02170]\\] or canola oil \\[[@B30-molecules-24-02170]\\] as co-solvent for the recovery of carotenoids. ", "The high achieved extraction yield for both processes may suggest the positive feasibility of the processes.", "\n\nHere, the objective was to investigate *p*-menthane as a bio-sourced alternative via solid--liquid extraction using an ULTRA-TURRAX^®^ device. ", "Extractions were performed in the same maceration conditions for both solvents for one hour at room temperature.", "\n\n[Table 1](#molecules-24-02170-t001){ref-type=\"table\"} shows that a slightly higher yield was obtained for the extraction of α- and β-carotene using *p*-menthane compared with *n*-hexane, although the differences were modest. ", "These results are somewhat in agreement with the COSMO-RS predicted solubilization properties of both solvents for β-carotene ([Figure 2](#molecules-24-02170-f002){ref-type=\"fig\"}). ", "Therefore, for this specific application, *p*-menthane could be considered as a promising alternative to *n*-hexane.", "\n\n2.4. ", "Rapeseed Oil Extraction {#sec2dot4-molecules-24-02170}\n----------------------------\n\nRapeseed oil is an internationally consumed commodity oil, ranked third worldwide and first in Europe \\[[@B4-molecules-24-02170]\\]. ", "Generally, the industrial processing of rapeseed involves pressing followed by extraction with hexane. ", "In fact, pressing as a single unit operation is relatively inefficient and does not ensure complete expulsion of oil. ", "Therefore, solvent extraction is an additional operation for an efficient extraction \\[[@B31-molecules-24-02170]\\]. ", "The outcome is two products: oil and low-valued meal. ", "This latter is either used for animal feed or fertilizer. ", "However, this method presents numerous industrial disadvantages as using hexane for rapeseed oil extraction raises many safety and environmental concerns as hexane is listed as a hazardous air pollutant \\[[@B32-molecules-24-02170]\\] and is known as a potential neurotoxic. ", "Considering those concerns, oil extraction of rapeseeds was carried out by solid--liquid extraction using ULTRA-TURRAX^®^ for *p*-menthane and *n*-hexane.", "\n\n[Table 1](#molecules-24-02170-t001){ref-type=\"table\"} shows the composition of rapeseeds oil determined by GC-FID (gas chromatography techniques coupled to flame ionization detector) and extracted using both solvents. ", "The lipid profiles of *p*-menthane and *n*-hexane extracts were similar in terms of fatty acid composition. ", "The percentage summations of saturated, as well as mono- and poly-unsaturated fatty acids, and yields were also compatible with those of rapeseed oils documented in literature for *n*-hexane, methyl tetrahydrofuran, ethyl acetate, *p*-cymene, *[d]{.smallcaps}*-limonene, and pinenes \\[[@B4-molecules-24-02170],[@B33-molecules-24-02170]\\].", "\n\n2.5. ", "Analytical Extraction: Soxhlet Extraction of Rapeseeds {#sec2dot5-molecules-24-02170}\n-----------------------------------------------------------\n\nSoxhlet is globally the most used lab-scale technique for fat and oil extraction. ", "However, it is time- and energy-consuming and also uses important amounts of petroleum-based solvents, mainly *n*-hexane \\[[@B18-molecules-24-02170]\\]. ", "As mentioned above, the latter is ranked high on the hazardous solvents list. ", "Consequently, many research groups over the years have investigated new alternatives \\[[@B4-molecules-24-02170]\\]. ", "In this context, bio-solvents such as terpenes have gained a great deal of attention as they can potentially offer a renewable alternative to these solvents \\[[@B34-molecules-24-02170]\\].", "\n\nThe extraction results on rapeseeds are shown in [Figure 3](#molecules-24-02170-f003){ref-type=\"fig\"}. ", "The mass yield of *p*-menthane extraction was compared with that of *n*-hexane (40.5% vs. 39.5%, respectively). ", "No significant difference was noted, which may be the result of the strong polar nature of both solvents that leads to a high dissolving power for triglycerides. ", "Additionally, *p*-menthane has a higher boiling point, inducing a decrease of oil viscosity and giving a better diffusion rate in the rapeseed matrix.", "\n\nFatty acid methyl ester's (FAME's) derivatives were identified and quantified by GC-FID. ", "Values of ∑SFAs (total saturated fatty acids) were 14.1% for *p*-menthane and 14.9% for *n*-hexane. ", "Amounts of ∑MUFAs (total mono-unsaturated fatty acids) were 61.1% for *p*-menthane and 58.1% for *n*-hexane, while those for ∑PUFAs (poly-unsaturated fatty acids) were 26.6% for *p*-menthane and 26.0% for *n*-hexane.", "\n\nThese results point out that for both solvents, the fatty acid profile of the resulting oils (the composition) and the mass yields of the extraction process are very similar. ", "The main fatty acids extracted using both solvents are oleic (C18:1), linoleic (C18:2), and linolenic (C18:3) acids. ", "These three unsaturated fatty acids represent more than 85% of the total extracted oil fatty acid composition. ", "Even though *n*-hexane is widely used for vegetable oil extraction using Soxhletin analytical laboratories because of its high extraction and selectivity abilities, *p*-menthane exhibited similar capacities, making it a competitive and efficient alternative.", "\n\n2.6. ", "Analytical Extraction: Dean--Stark Azeotropic Distillation of Carrots {#sec2dot6-molecules-24-02170}\n--------------------------------------------------------------------------\n\nInitially, Dean--Stark apparatus was developed to measure the water content present in petroleum products, which is feasible thanks to the azeotropic ability of numerous compounds \\[[@B35-molecules-24-02170]\\]. ", "Nowadays, Dean--Stark apparatus has become a tool associated with the separation of water from different matrices. ", "The latter has repeatedly been modified to cover a broader range of applications. ", "It is widely used for water determination in food products and is frequently cited for products with volatile compounds. ", "The azeotropic distillation occurs between water and petroleum solvents such as toluene \\[[@B4-molecules-24-02170]\\]. ", "While toluene gives satisfying results, it is labeled as hazardous and toxic \\[[@B19-molecules-24-02170],[@B36-molecules-24-02170]\\]. ", "To mitigate environmental and health concerns related to this solvent, new alternative were considered \\[[@B37-molecules-24-02170],[@B38-molecules-24-02170]\\]. ", "In this way, a range of terpenes were investigated including [d]{.smallcaps}-limonene \\[[@B19-molecules-24-02170]\\], and the results showed that there are no significant differences between toluene and [d]{.smallcaps}-limonene procedures, thus concluding that [d]{.smallcaps}-limonene could be considered as a possible alternative for petroleum-based solvents.", "\n\n[Figure 4](#molecules-24-02170-f004){ref-type=\"fig\"} shows water distillation kinetics of carrots for both toluene and *p*-menthane. ", "The azeotropic distillation of the mixture has different kinetics for water recovery for each solvent because of the boiling point difference. ", "Water distillation kinetics were somewhat similar for the two solvents. ", "When using *p*-menthane, the water recovery was delayed by 2 min. ", "However, once the distillation started, the alternative solvent gave a faster water recovery compared with toluene. ", "The boiling point of the azeotropic mix is very close to the water boiling point; the water is accordingly more volatile as to lower temperatures. ", "The distillation curve slope was higher when using *p*-menthane, whereas the time needed to attain 100% water recovery was 55% shorter than for toluene. ", "Thus, *p*-menthane will reduce not only the procedure duration, but also the energy consumption. ", "The percentage of carrot water content obtained through this process was 81.5% and 82.4% for toluene and *p*-menthane, respectively, which means that *p*-menthane could possibly replace toluene in a Dean--Stark procedure.", "\n\n3. ", "Materials and Methods {#sec3-molecules-24-02170}\n========================\n\n3.1. ", "Plant Material and Chemicals {#sec3dot1-molecules-24-02170}\n---------------------------------\n\nRapeseeds were provided by OLEAD. ", "They originated from France-Gironde and were cultivated in 2016. ", "Caraway seeds and carrots were purchased from a local market (Avignon, France). ", "For chemicals, *n*-hexane (HPLC grade) was supplied by VWR International (Darmstadt, Germany). ", "Standards such as β-Carotene (95%--99%) and [d]{.smallcaps}-limonene were provided by Sigma-Aldrich (Germany), and S-carvone was from Merck™ (Darmstadt, Germany). ", "Ruthenium on carbon (5 wt%) was purchased from Strem Chemicals.", "\n\n3.2. ", "Hydrogenation of [d]{.smallcaps}-Limonene {#sec3dot2-molecules-24-02170}\n----------------------------------------------\n\nHydrogenation of [d]{.smallcaps}-limonene to *p*-menthane at a low temperature (approximately 40--50 °C) was carried out using a ruthenium catalyst on activated charcoal, thus leaving a great margin to control the exothermicity of the reaction (boiling points of [d]{.smallcaps}-limonene and *p*-menthane are 177 and 170 °C, respectively). ", "A catalytic charge of 1.5 wt% ruthenium on charcoal (5 wt%) was sufficient to completely hydrogenate limonene under 25 bars of hydrogen pressure. ", "Those tests were conducted on a maximum batch of 56 g of *[d]{.smallcaps}*-limonene. ", "All reactions were conducted until complete conversion of [d]{.smallcaps}-limonene to *p*-menthane was achieved, the purity of which was determined by gas chromatography. ", "The products were all mixed and then filtered under vacuum on Clarcel (filter aid) to retain the catalyst and give a completely colorless liquid product. ", "The overall mass yield of the operation was 97%. ", "Losses could be attributed to transfers and the amount of material retained on the filter during the removal of the catalyst.", "\n\n3.3. ", "Computational Solubility Assessment {#sec3dot3-molecules-24-02170}\n----------------------------------------\n\nThe solubility of (i) *β*-carotene from carrots, (ii) S-carvone and [d]{.smallcaps}-limonene aromas from caraway seeds, and (iii) model triglycerides (glyceryltrilinolein, LLL; glyceryloleoyl--dilinoleoyl, OLL; and glyceryllinoleoyl--oleoyl--palmitoyl, LOP) from rapeseeds was evaluated for both *p*-menthane and *n*-hexane using the theoretical prediction model COSMO-RS (COSMO software). ", "Computation methods consider the technical properties of the solvents to assay and examine the solutes. ", "The chemical structures of the solvents and solutes were transformed by JChemPaint version 3.3 (GitHub Pages, San Francisco, CA, USA), while for the entry syntax, (SMILES) notation was followed. ", "They were then used for the solubility parameters calculation of solvents and targeted compounds. ", "Predictions of relative solubility were carried out at two temperatures: 25 °C and at the boiling point of each solvent (extraction temperature).", "\n\n3.4. ", "Solid--Liquid Extraction {#sec3dot4-molecules-24-02170}\n-----------------------------\n\nExtractions of the oil from rapeseed, carotenoids from carrots, and aromas from caraway seeds were performed using an ULTRA-TURRAX^®^ Tube Drive System (Paris, France) \\[[@B4-molecules-24-02170],[@B39-molecules-24-02170]\\]. ", "The dried vegetable materials were grounded prior to extraction. ", "One gram of each matrix, 20 g of ceramic balls, and 10 mL of solvent (*p*-menthane or *n*-hexane) were added into a tube with a stirring device. ", "The obtained mixture was mechanically stirred and macerated at 4000 rpm for 60 min at 25 °C. ", "The residue was removed by filtration and centrifuged at 9000 rpm for 10 min.", "\n\n3.5. ", "Dean--Stark Distillation {#sec3dot5-molecules-24-02170}\n-----------------------------\n\nAt first, moisture determination of carrots was carried out according to the American Oil Chemists' Society (AOCS) official method Ja 2a--46 \\[[@B40-molecules-24-02170]\\]. ", "The experimental apparatus was composed of three major parts: a 500 mL round-bottom flask coupled with an electrical heater, a graduated Dean--Stark receiver, and a condenser. ", "The sample weight was 10 ± 0.6 g for each experiment. ", "The weight amount was set according to Harel and Talmi \\[[@B41-molecules-24-02170]\\] to obtain an adequate water amount in the receiver that did not exceed 10 mL, which was the maximal countenance. ", "Toluene as a distillation solvent was compared to *p*-menthane. ", "One hundred milliliters of each were used.", "\n\nThe electrical heating was maximized in the beginning of the experiment until the first droplets in the Dean--Stark receiver were collected. ", "The heating was then adapted to a distillation rate of 100 drops/min. ", "When most of the water was distilled (approximately 80%), heating was then increased to a distillation rate of 200 drops/min and continued until the end of the distillation. ", "About 30 mL of either toluene or *p*-menthane was added at the top of the condenser to recover the water droplets that adhered to the condenser. ", "The Dean--Stark collector was then cooled to room temperature for a few minutes until the layer was clear.", "\n\nThe moisture content was calculated as follows:$$Moisture~\\left( \\% \\right) = \\frac{{{volume}~{of}~{water}~}\\left( {mL} \\right) \\times 0.997 \\times 100}{{{Weight}~{of}~{fresh}~{sample}~}\\left( g \\right)},$$ where 0.997 is the water density at 20°C.", "\n\n3.6. ", "Soxhlet Extraction and Procedure {#sec3dot6-molecules-24-02170}\n-------------------------------------\n\nThe extraction of oil from rapeseeds was carried out according to the standardized Soxhlet procedure \\[[@B18-molecules-24-02170]\\] using *n*-hexane and *p*-menthane as solvents. ", "For each extraction, 20 g of dried and ground rapeseeds was put in a 33 × 100 cellulose thimble and inserted into a 250 mL Soxhlet apparatus. ", "Experiments were carried out for eight hours with a solvent volume of 170 mL. After the extraction, the solvent was eliminated in a rotary evaporator. ", "The content was then dried for 2 h in an oven under a circulating air set at 65 °C. ", "After cooling in a desiccator for 1 h, the flask was precisely weighed up to constant value. ", "The results obtained were expressed as follows:$$\\%~Oil~content = \\frac{{weight}~{of}~{oil}~{obtained}~{after}~{extraction}}{{weight}~{of}~{dry}~{sample}} \\times 100.$$\n\n3.7. ", "Total Carotenoid Analysis {#sec3dot7-molecules-24-02170}\n------------------------------\n\nTotal carotenoids were quantified using UV/visible spectrophotometry (Biochrom Libra S22 UV/Vis spectrometer, Guibeville, France). ", "Absorbances were measured at 450 nm using *n*-hexane as a blank. ", "Carotene concentration in each extract was calculated via a calibration curve previously obtained using a pure standard of β-carotene (\\>98%). ", "The carotene yield was expressed as g (β-carotene) per 100 g of dry matter (%).", "\n\n3.8. ", "Specific Determination of Carotenoids by HPLC-DAD {#sec3dot8-molecules-24-02170}\n------------------------------------------------------\n\nThe identification and quantification of extracts was carried out using HPLC-DAD consisting of a HPLC Agilent 1200 equipped with a UV/vis detector (DAD). ", "Separation was attained at a temperature of 25 °C on a YMC C30 column (250 × 4.6 mm and 3 µm ID). ", "The mobile phase in this case consisted of a combination of A (methanol/MTBE/water, 81/15/4) and B (methanol/MTBE/water, 10/90/4). ", "The linear gradient was from 100% to 0% B (*v/v*) within 90 min. ", "The pumping flow rate was 1.0 mL/min. ", "The volume used for the sample volume was 5 µL, while the quantitative detection was measured at 450 nm. ", "To establish carotenoids calibration curves, standard carotenoids were used with concentrations ranging from 5, 10, 25, 50, to 100 mg/L. Identification of the main carotenoids in carrot extracts was carried out in triplicate by comparing the retention times and absorption spectra.", "\n\n3.9. ", "Rapeseed Oil Profiling by GC-FID Analysis {#sec3dot9-molecules-24-02170}\n----------------------------------------------\n\nRapeseed oil FAMEs were separated, identified, and quantified by GC-FID. ", "Preparation of samples from extracted rapeseeds oils was performed using acid-catalyzed trans-methylation \\[[@B4-molecules-24-02170]\\]. ", "Then, 1 mL of methanolic sulfuric acid (5% *v/v*) was added to a precise volume of extracted oils and the internal standard. ", "The mixture was then heated at 85 °C for 90 min and latter onset to cool until it reached room temperature. ", "Then, 1.5 mL sodium chloride (0.9%) solution and 1 mL *n*-hexane were added. ", "The mixture was shaken strongly for 30 s prior to centrifugation at 4000 rpm for 2 min. ", "An aliquot of the organic layer was moved into a vial for a GC analysis using a 7820A GC system (Agilent technologies, Santa Clara, CA, USA) equipped with a BD-EN14103 capillary column (30 m × 0.32 mm × 0.25 μm), as well as an FID and an auto-sampler. ", "The carrier gas was helium at 33 mL/s. The sample injection volume was 2 μL, while the split ratio was set at 1:20 at 250 °C. ", "The oven initial temperature was set at 50 °C for 1 min, and then increased to 20 °C/min until it reached 180 °C, then a rate of 2 °C/ min until 230 °C, and was then held isothermally at 230 °C for 10 min. ", "Data collection was carried out by Agilent EZChrom Elite software. ", "Identification of FAMEs was performed in comparison with purified FAME standards (Sigma Co., St Louis, MO, USA), while the quantification was achieved using internal calibration. ", "The internal standard used was glyceryl triheptadecanoate (Sigma Co., Cleveland, OH, USA).", "\n\n3.10. ", "Identification of Aroma by GC-MS {#sec3dot10-molecules-24-02170}\n--------------------------------------\n\nAroma identification was carried out using an Agilent 6890N GC coupled with an Agilent 5973 MS (Agilent, Massy, France). ", "The extracts were analyzed on a fused-silica capillary column HP-1MSTM (polydimethylsiloxane, 50 m × 0.25 mm i.d. ", "× 0.25 µm film thickness; Interchim, Montluçon, France) and INNOWAX (polyethyleneglycol, 50 m × 0.20 mm i.d. ", "× 0.4 µm film thickness; Interchim, Montluçon, France). ", "The carrier gas was helium pumped at a constant flow of 1 mL/min. ", "The injector temperature was set at 250 °C with split ratio of 1:150. ", "The initial temperature was set at 45 °C and increased by a rate of 2 °C/min until 250 °C, and was then held isothermal for 20 min at either 250 °C (apolar column) or 230 °C (polar column). ", "The temperature of 230 °C is the ion source temperature (apolar column) and 250 °C corresponds to the transfer line temperature (polar column). ", "The ionization energy was set at 70 eV.\n\n4. ", "Conclusions {#sec4-molecules-24-02170}\n==============\n\nIn this work, the potential of *p*-menthane as a green alternative to petroleum solvents such as *n*-hexane and toluene was investigated. ", "This bio-based solvent was prepared by hydrogenation of D- limonene, a by-product of deterpenation of essential oils obtained from orange peels. ", "The solubility of certain bioactive compounds in *p*-menthane was experimentally and theoretically compared with *n*-hexane using a simulation software COSMO-RS. ", "It was found that both solvents have relatively similar solvation efficacy. ", "Experimentally, it was observed that a slightly higher extraction yield can be obtained on carrots using the alternative solvent, while for caraway aromas and rapeseed oils, similar extraction potential was recorded for both solvents. *", "p*-Menthane was also used for water determination using Dean--Stark apparatus. ", "As the boiling point of *p*-menthane is higher than that of toluene, the azeotropic distillation is consequently higher for *p*-menthane, leading to a brief delay of the start of the distillation; but once the distillation started, the recovery was 55% shorter than for the toluene. ", "Thus, *p*-menthane could offer an interesting green and sustainable alternative solution to replace some hazardous petroleum-based solvents for a diverse set of applications ranging from practical work for students in academia, to analytical laboratories and industrial processes in the pharmaceutical, cosmetic, aroma, and food areas.", "\n\n**Sample Availability:** Samples of the compounds are not available from the authors.", "\n\nFor research articles with several authors, a short paragraph specifying their individual contributions must be provided. ", "The following statements should be used \"conceptualization, F.C., A.-S.F.-T., A.B. and M.L.; methodology, F.C., A.-S.F.-T., A.B. and M.L.; software, F.C., A.-S.F.-T.; validation, F.C., A.-S.F.-T., A.B. and M.L.; formal analysis, S.M., S.H., M.T.; investigation, A.-S.F.-T., S.M., S.H., M.T.; resources, F.C., A.-S.F.-T., A.B. and M.L.; data curation, S.M., S.H., M.T.; writing---original draft preparation, F.C., S.M., S.H., M.T., A.-S.F.-T., A.B. and M.L.; writing---review and editing, F.C., S.M., S.H., M.T., A.-S.F.-T., A.B. and M.L.; visualization, F.C., S.M., S.H., M.T., A.-S.F.-T., A.B. and M.L.; supervision, F.C., A.-S.F.-T., A.B. and M.L.; project administration, F.C., A.-S.F.-T., A.B. and M.L.; funding acquisition, F.C., A.-S.F.-T., A.B. and M.L.\n\nThis research received no external funding.", "\n\nThe authors declare no conflict of interest.", "\n\n{#molecules-24-02170-f001}\n\n{#molecules-24-02170-f002}\n\n{#molecules-24-02170-f003}\n\n{#molecules-24-02170-f004}\n\nmolecules-24-02170-t001_Table 1\n\n###### \n\nComparison of efficiency using *n*-hexane and *p*-methane for extraction of secondary and primary metabolites extracted from different plant matrices. ", "GC-MS---gas chromatography coupled to mass spectrometry; DM---dry matter; FID---flame ionization detector; SFAs---saturated fatty acids; MUFAs---mono-unsaturated fatty acids; PUFAs---poly-unsaturated fatty acids.", "\n\n Description *n*-Hexane *p*-Menthane\n ---------------------------------------- ------------------------------------------------- ---------------\n **Caraway Seeds** **Major Compounds Identified by GC-MS (µg/mL)** \n [d]{.smallcaps}-Limonene 622.3 ± 49 624.6 ± 32\n *S*-Carvone 1118 ± 33 934 ± 29\n Yield (g/100 g) 1.74 ± 0.08 1.56 ± 0.03\n **Carrots** **Carotenoids Identified by HPLC (µg/mL)** \n β-Carotene 28.17 ± 0.23 25.97 ± 1.96\n α-Carotene 11.01 ± 1.51 11.24 ± 0.23\n Yield (g/100 g DM) 32.5 ± 2 35.7 ± 1.5\n **Rapeseed Oil** **Compounds Identified by GC-FID (%)** \n                    saturated compounds \n Myristic acid C14:0 0.09 ± 0.0004 0.09 ± 0.0002\n Palmitic acid C16:0 5 ± 0.038 4.9 ± 0.063\n Stearic acidC18:0 1.5 ± 0.011 1.5 ± 0.018\n Arachidic acid C20:0 0.6 ± 0.003 0.6 ± 0.006\n Behenic acid C22:0 0.4 ± 0.002 0.4 ± 0.003\n Lignoceric acid C24:0 0.2 ± 0.001 0.2 ± 0.002\n                      mono-unsaturated \n Palmitoleic acid C16:1 0.2 ± 0.001 0.2 ± 0.003\n Oleic acid C18:1 62 ± 0.43 62.1 ± 0.8\n Gadoleic acid C20:1 1.2 ± 0.007 1.2 ± 0.01\n                     poly-unsaturated \n Linoleic acid C18:2n6c 19.5 ± 0.14 19.4 ± 0.25\n Linolenic acid C18:3n3 8.9 ± 0.06 8.8 ± 0.11\n ∑SFAs 7.9 8\n ∑MUFAs 63.5 63.6\n ∑PUFAs 28.5 28.3\n Yield (g/100 g) 38.38 ± 0.05 37.1 ± 0.07\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Cuesta Case – Triangular\n\n$9,950.00$9,450.00\n\nNo more leaning in or lifting out! ", "Featuring a lockable swinging door, the Triangular Cuesta Case provides curators the flexibility and access they need to stage, rotate, and secure artifacts with ease. ", "Includes steel-reinforced door frame and 1/4″ low-e tempered glass elements." ]

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[ "Q:\n\n\"Play Game\" tab on Facebook fanpage\n\nI have a fanpage and a game app. ", "The fanpage was created before the game, so I already have some likes, which I'd like to preserve. ", "I need to add some tab or button which takes the user to my app (www.apps.facebook.com/myapp). ", "There are no options about that on the fanpage's admin panel.", "\nThanks\n\nA:\n\nWelcome to SO!", "\nYou have to build an HTML/PHP page with the button linking to your game page.", "\nAlso have in mind that you can use the same application (your game) with the Timeline App by serving the content from a different directory. ", "You can setup this in the facebook developer app.", "\nSome helpful resources:\nPage Tab Tutorial\nhttps://developers.facebook.com/docs/appsonfacebook/pagetabs/\nPHP SDK\nhttps://developers.facebook.com/docs/reference/php/\nJavascript SDK\nhttps://developers.facebook.com/docs/reference/javascript/\n\n" ]

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[ "KOTA KINABALU – Kertam’s death leaves behind only one female Sumatran rhino, pushing the critically-endangered species closer to extinction.", "\n\nMalaysia’s last surviving male Sumatran rhino died of cardiopulmonary failure, according to an autopsy report.", "\n\n30 year old Kertam’s death leaves behind only one female Sumatran rhino, pushing the critically-endangered species closer to extinction.", "\n\nKertam also known as Tam, had been sick since April was under medications, among them were anti-inflammatories, intravenous infusion of vitamins and minerals, stomach acid reduction medications and tranquilisers.", "\n\n“The most obvious visible problem was his right kidney, which contained numerous abscesses and stones. ", "The abscesses were likely caused by a urinary tract infection, which was treated with intravenous antibiotics,” Sabah Deputy Minister Datuk Christina Liew said in a statement.", "\n\nTam, had lived in a nature reserve on Borneo island and had showed a decline in appetite and alertness.", "\n\nConservationists are hoping to use in-vitro fertilisation (IVF) techniques to create offspring from Malaysia’s last female Sumatran rhino, Iman, and an Indonesian male.", "\n\nIman’s is incapable of becoming pregnant due to problems with her uterus but was still able to produce eggs.", "\n\nThe Sumatran rhino once found throughout Malaysia and as far as eastern India is nearing extinction with only fewer than 80 left according to the World Wildlife Fund." ]

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[ " In the United States Court of Federal Claims\n OFFICE OF SPECIAL MASTERS\n No. ", "15-662V\n Filed: June 13, 2016\n Not for Publication\n\n*************************************\nSARAH DAVIS, *\n *\n Petitioner, *\n * Attorneys’ fees and costs decision;\n v. * respondent does not object\n *\nSECRETARY OF HEALTH *\nAND HUMAN SERVICES, *\n *\n Respondent. ", " *\n *\n*************************************\nAnne Carrión Toale, Sarasota, FL, for petitioner.", "\nAdriana R. Teitel, Washington, DC, for respondent.", "\n\nMILLMAN, Special Master\n\n DECISION AWARDING ATTORNEYS’ FEES AND COSTS 1\n\n On June 24, 2015, petitioner filed a petition under the National Childhood Vaccine Injury\nAct, 42 U.S.C. §§ 300aa-10–34 (2012) (“Vaccine Act”) alleging that her receipt of the Menactra\nvaccine on June 20, 2012 caused her to develop an altered mental state. ", "Pet. ", "at ¶ 3. ", "On April 28,\n2016, the undersigned issued an Order Concluding Proceedings.", "\n\n On June 13, 2016, petitioner filed an unopposed motion for attorneys’ fees and costs.", "\nPetitioner requests a total of $19,850.00 in attorneys’ fees and costs. ", "In compliance with General\nOrder #9, petitioner’s counsel filed a signed statement from petitioner saying that petitioner\nincurred $133.75 in costs in litigating this case.", "\n\n1\n Because this unpublished decision contains a reasoned explanation for the special master’s action in this\ncase, the special master intends to post this unpublished decision on the United States Court of Federal\nClaims’s website, in accordance with the E-Government Act of 2002, 44 U.S.C. § 3501 note (2012)\n(Federal Management and Promotion of Electronic Government Services). ", "Vaccine Rule 18(b) states that\nall decisions of the special masters will be made available to the public unless they contain trade secrets or\ncommercial or financial information that is privileged and confidential, or medical or similar information\nwhose disclosure would constitute a clearly unwarranted invasion of privacy. ", "When such a decision is\nfiled, petitioner has 14 days to identify and move to redact such information prior to the document=s\ndisclosure. ", "If the special master, upon review, agrees that the identified material fits within the banned\ncategories listed above, the special master shall redact such material from public access.", "\n\f The Vaccine Act permits an award of “reasonable attorneys’ fees” and “other costs.”", "\n42 U.S.C. § 300aa-15(e)(1). ", "It is not necessary for a petitioner to prevail in the case-in-chief in\norder to receive a fee award as long as petitioner brought the claim in “good faith and there was a\nreasonable basis for the claim.” ", "Id. Based on the reasonableness of petitioner’s request and the\nlack of opposition, the undersigned GRANTS petitioner’s application for attorneys’ fees and\ncosts.", "\n\n Accordingly, the undersigned awards $19,850.00, as a lump sum in the form of a check\npayable jointly to petitioner and Maglio Christopher & Toale, PA. ", "She also awards $133.75 as a\nlump sum in the form of a check payable solely to petitioner.", "\n\n In the absence of a motion for review filed pursuant to RCFC Appendix B, the clerk of the\ncourt is directed to enter judgment herewith. ", "2\n\n\nIT IS SO ORDERED.", "\n\n\nDated: June 13, 2016 s/ Laura D. Millman\n Laura D. Millman\n Special Master\n\n\n\n\n2\n Pursuant to Vaccine Rule 11(a), entry of judgment can be expedited by each party, either separately or\njointly, filing a notice renouncing the right to seek review.", "\n 2\n\f" ]

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[ "Only the Animals (film)\n\nOnly the Animals () is a 2019 French drama film directed by Dominik Moll.", "It is based on the novel Seules les bêtes by Colin Niel.", "\n\nCast \n Laure Calamy - Alice\n Denis Ménochet - Michel\n Valeria Bruni Tedeschi - Evelyne\n Damien Bonnard - Joseph\n Guy Roger N’Drin - Armand\n - Marion\n\nReferences\n\nExternal links \n \n \n\nCategory:French drama films" ]

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