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tomekkorbak

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[ "Student Programs\n\nShare\n\nDonations made toward Student Programs help to enrich all related activities and enhance scholarship/award programs which include career development, education and training, and leadership development opportunities for the future leaders of our profession.", "\n\nThanks to our 2011-2012 ScaleUp program sponsors for helping to enrich the next generation of chemical engineers. ", "AIChE acknowledges the following generous sponsors whose support has made ScaleUp a continued success.", "\n\nThe AIChE Leadership Challenge: Volunteer Leaders for the Future is an exciting, new initiative, led by Institute Leaders, to support a three-year subsidized membership program for young professionals. ", "Learn more.", "\n\nTranslate this page\n\nShare This Post:\n\nThe AIChE Foundation and the Minority Affairs Committee are working together to bolster fundraising efforts in support of the Minority Affairs Committee Scholarship Fund. ", "Learn more about how you can help." ]

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[ "// Copyright 2015 CoreOS, Inc.\n//\n// Licensed under the Apache License, Version 2.0 (the \"License\");\n// you may not use this file except in compliance with the License.", "\n// You may obtain a copy of the License at\n//\n// http://www.apache.org/licenses/LICENSE-2.0\n//\n// Unless required by applicable law or agreed to in writing, software\n// distributed under the License is distributed on an \"AS IS\" BASIS,\n// WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n// See the License for the specific language governing permissions and\n// limitations under the License.", "\n\npackage iptables\n\nimport (\n\t\"os\"\n\t\"sync\"\n\t\"syscall\"\n)\n\nconst (\n\t// In earlier versions of iptables, the xtables lock was implemented\n\t// via a Unix socket, but now flock is used via this lockfile:\n\t// http://git.netfilter.org/iptables/commit/?id=aa562a660d1555b13cffbac1e744033e91f82707\n\t// Note the LSB-conforming \"/run\" directory does not exist on old\n\t// distributions, so assume \"/var\" is symlinked\n\txtablesLockFilePath = \"/var/run/xtables.lock\"\n\n\tdefaultFilePerm = 0600\n)\n\ntype Unlocker interface {\n\tUnlock() error\n}\n\ntype nopUnlocker struct{}\n\nfunc (_ nopUnlocker) Unlock() error { return nil }\n\ntype fileLock struct {\n\t// mu is used to protect against concurrent invocations from within this process\n\tmu sync.", "Mutex\n\tfd int\n}\n\n// tryLock takes an exclusive lock on the xtables lock file without blocking.", "\n// This is best-effort only: if the exclusive lock would block (i.e. because\n// another process already holds it), no error is returned. ", "Otherwise, any\n// error encountered during the locking operation is returned.", "\n// The returned Unlocker should be used to release the lock when the caller is\n// done invoking iptables commands.", "\nfunc (l *fileLock) tryLock() (Unlocker, error) {\n\tl.mu.", "Lock()\n\terr := syscall.", "Flock(l.fd, syscall.", "LOCK_EX|syscall.", "LOCK_NB)\n\tswitch err {\n\tcase syscall.", "EWOULDBLOCK:\n\t\tl.mu.", "Unlock()\n\t\treturn nopUnlocker{}, nil\n\tcase nil:\n\t\treturn l, nil\n\tdefault:\n\t\tl.mu.", "Unlock()\n\t\treturn nil, err\n\t}\n}\n\n// Unlock closes the underlying file, which implicitly unlocks it as well. ", "It\n// also unlocks the associated mutex.", "\nfunc (l *fileLock) Unlock() error {\n\tdefer l.mu.", "Unlock()\n\treturn syscall.", "Close(l.fd)\n}\n\n// newXtablesFileLock opens a new lock on the xtables lockfile without\n// acquiring the lock\nfunc newXtablesFileLock() (*fileLock, error) {\n\tfd, err := syscall.", "Open(xtablesLockFilePath, os.", "O_CREATE, defaultFilePerm)\n\tif err !", "= nil {\n\t\treturn nil, err\n\t}\n\treturn &fileLock{fd: fd}, nil\n}\n" ]

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[ "ALEXANDRIA, Va. (AP) — The government’s watchlist of more than 1 million people identified as “known or suspected terrorists” violates the constitutional rights of those placed on it, a federal judge ruled Wednesday.", "\n\nThe ruling from U.S. District Judge Anthony Trenga grants summary judgment to nearly two dozen Muslim U.S. citizens who challenged the watchlist with the help of the Council on American-Islamic Relations.", "\n\nThe judge is seeking additional legal briefs before deciding what remedy to impose.", "\n\nThe plaintiffs said they were wrongly placed on the list and that the government’s process for adding names is overbroad and riddled with errors.", "\n\nThe watchlist is disseminated to a variety of governmental departments, foreign governments and police agencies.", "\n\nThe FBI declined comment on the ruling Wednesday. ", "In court, FBI lawyers argued that the difficulties suffered by the plaintiffs pale in comparison to the government’s interests in combating terrorism.", "\n\nGadeir Abbas, an attorney for the plaintiffs, called the ruling a victory. ", "He said he will ask the judge to severely curtail how the government compiles and uses its list.", "\n\n“Innocent people should be beyond the reach of the watchlist system,” Abbas said. “", "We think that’s what the Constitution requires.”", "\n\nAbbas said that while there has been significant litigation over the no-fly list, which forced the government to improve the process for people seeking to clear their name from the list, Trenga’s ruling is the first to broadly attack the government’s use of the watchlist. ", "Trenga wrote in his 31-page ruling that the case “presents unsettled issues.”", "\n\nUltimately, Trenga ruled that the travel difficulties faced by plaintiffs — who say they were handcuffed at border crossings and frequently subjected to invasive secondary searches at airports — are significant, and that they have a right to due process when their constitutional rights are infringed.", "\n\nHe said the concerns about erroneous placement on the list are legitimate.", "\n\n“There is no evidence, or contention, that any of these plaintiffs satisfy the definition of a ‘known terrorist,’” Trenga wrote. ", "And the alternate standard for placement — that of a “suspected terrorist” — can easily be triggered by innocent conduct that is misconstrued, he said.", "\n\nThe watchlist, also known as the Terrorist Screening Database, is maintained by the FBI and shared with a variety of federal agencies. ", "Customs officers have access to the list to check people coming into the country at border crossings, and aviation officials use the database to help form the no-fly list, which is a much smaller subset of the broader watchlist.", "\n\nThe watchlist has grown significantly over the years. ", "As of June 2017, approximately 1.16 million people were included on it, according to government documents filed in the lawsuit. ", "In 2013, the number was only 680,000. ", "The vast majority are foreigners, but according to the government, there were roughly 4,600 U.S. citizens and lawful permanent residents on the watchlist as of 2017.", "\n\nAbbas argued at a court hearing this year that the intrusions imposed on those listed are all for naught and that the list is worthless in terms of preventing terrorism. ", "He noted that Omar Mateen, the man who shot and killed 49 people at an Orlando nightclub in 2016, was at one time on the list but was removed from it. ", "Others who have committed terrorist acts have never been included on the watchlist.", "\n\nThe lawsuit was filed in 2016, and has exposed previously unknown details about the list and how it is disseminated. ", "In particular, government lawyers acknowledged after years of denials that more than 500 private entities are given access to the list.", "\n\nGovernment lawyers describe those private agencies as “law enforcement adjacent” and include university police forces, and security forces and hospitals, railroads and even animal-welfare organizations.", "\n\nAbbas said the revelations about the government’s actions have come after years of dismissive responses from government officials who accused the Council on American-Islamic Relations and others of paranoia, and that people are now paying more attention to the civil-rights implications of watchlisting.", "\n\nThe House of Representatives this year adopted a proposal from Democratic Minnesota Rep. Ilhan Omar that would force President Trump’s administration to disclose details about how it shares the watchlist with foreign countries." ]

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[ "Q:\n\nHow many animals is the King of Zion to ride according to Zechariah?", "\n\nI've read that Zechariah prophesied that the King of Zion would enter the city on a donkey with another donkey in tow. ", " But the passage seems to indicate just one animal to me:\n\nRejoice greatly, O daughter of Zion!", "\n Shout aloud, O daughter of Jerusalem!", "\nBehold, your king is coming to you;\n righteous and having salvation is he,\nhumble and mounted on a donkey,\n on a colt, the foal of a donkey.", "\n\n—Zechariah 9:9 (ESV)\n\nIt seems that the author of Matthew assumed it was a donkey and a colt:\n\nNow when they drew near to Jerusalem and came to Bethphage, to the Mount of Olives, then Jesus sent two disciples, saying to them, “Go into the village in front of you, and immediately you will find a donkey tied, and a colt with her. ", "Untie them and bring them to me. ", "If anyone says anything to you, you shall say, ‘The Lord needs them,’ and he will send them at once.” ", "This took place to fulfill what was spoken by the prophet, saying, [paraphrase of Zechariah 9:9]—Matthew 21:1-4 (ESV)\n\nIn the English at least, I can't see how either the original passage in Zechariah or its paraphrase in Matthew require there to be two animals. ", " Am I missing something?", "\n\nA:\n\nDavid Instone-Brewer posits that Matthew was following a rabbinic tradition that rejected the notion that synonymous (poetic) parallelism was intended in the Hebrew Bible:\n\nIt is very unlikely that a well-read Jew would misunderstand parallelism. ", "This type of poetic construction was still being used as late as Baruch and 4 Esdras. ", " However, as I have shown elsewhere, the rabbinic authorities before 70 CE totally rejected the concept of synonymous parallelism in Scripture. ", "They regarded Scripture, including the Writings, as a perfect law. ", "One of the characteristics which they assumed to be part of a perfect law was the lack of redundancy. ", "Any unnecessary repetition involved redundancy, and implied sloppy writing by the divine legislator. ", "This did not mean that they only rejected parallelism which was exactly synonymous, if this ever exits. ", "They also rejected parallelism which adds details which were not present in the first line. ", "They do so because a perfect legislator would have used one line or the other—either a general phrase which would imply the more specific or a specific phrase which would be an example of the general.—\"The Two Asses of Zechariah 9:9 in Matthew 21\", Tyndale Bulletin 54.1 (2003) 87-97. [", "PDF]\n\n(Hat tip to H3br3wHamm3r81.)", "\nAccording to this theory Matthew would have:\n\nSeen or received a report of Jesus' entry into Jerusalem.", "\nConnected the detail of Jesus riding a donkey to Zechariah 9:9.", "\nAgreed that the apparent parallel structure implied two animals.", "\nWrote his account to include two animals:\n\nThey brought the donkey and the colt and put on them their cloaks, and he sat on them.—Matthew 21:7 (ESV)\n\nBy implication, either the report Matthew had of the historical event or his version of that report are confused about the number of animals present. ", " The strength of the case seems to rest on the weight given to the tradition which rejects parallelism compared to the weight given to recording a historical event accurately.", "\nOn the other hand, if Matthew's recollection or source of the event was fuzzy on the number of animals, it's not out of the realm of possibility that he interpolated that detail from the prophet's book.", "\n\nA:\n\nAdmittedly this passage is very difficult, but there are some parallels in the gospels that we must compare with similar passages in the Hebrew Bible. ", "In other words, our fundamental hermeneutic is to interpret Scripture with Scripture.", "\nFirst, when we find Jesus on the Mount of Olives, he is in the company of a crowd of people according to the gospel of Matthew. ", "That is, all three synoptic gospel accounts indicate that Jesus migrated to the Mount of Olives from Jerusalem, but Matthew is the only gospel to emphasize that there was a \"crowd\" with him on the Mount of Olives (Matthew 21:8).", "\nWhen King David was on the Mount of Olives (when he was in exile because of rebellious Absalom), there were two donkeys that arrived on the Mount of Olives that were carrying bread, raisins, fruit and wine destined for Jerusalem (2 Sam 16:1-2). ", "This passage indicates that these donkeys were intended to be mounted by the King (Absalom) for whom the provisions and foodstuffs on the donkeys were refreshment for his companions. ", "There is no mention of whether or not David confiscated the load of goods (or the donkeys), but the amount of foodstuffs is almost exactly parallel to what Abigail provided to David's 600 men (1 Sam 25:13), when she loaded donkeys with the same foodstuffs for David and his companions (1 Sam 25:18).", "\nIn other words, Jesus mounted the single colt to enter the East Gate of Jerusalem as the deliverer of Israel (the Messiah) in parallel to both Zechariah 9:9 (complete fulfillment) and Ezekiel 43:1-4 (partial fulfillment). ", "But this story starts with two animals and ends with one. ", "That is, the colt and her mother were already loaded with foodstuffs (when they were retrieved by the two disciples) so that (a) Jesus could feed and refresh the crowd that was with him on the Mount of Olives; and (b) to take and ride the single colt into Jerusalem. ", "To put it another way, if Jesus is on the Mount of Olives as the rejected king (like David), then the two asses (donkey and colt) carried the foodstuffs and refreshment for the crowd of several hundred people who were with Jesus on the Mount of Olives in the very same form and fashion as had occurred when King David and his men were on the Mount of Olives.", "\nFinally, both Mark and Luke focus on the triumphal entry into Jerusalem (and thus the emphasis on one animal that was mounted by Jesus), but Matthew is the only gospel that expands the sight picture of the triumphal entry, and includes an emphasis and therefore mentions the \"crowd\" with Jesus on the Mount of Olives. (", "The other gospels simply mention the unidentified \"they\" who were with Jesus, and Luke uses the word \"crowd\" only after Jesus had begun to leave the Mount of Olives.) ", "My own personal view is that the two animals (donkey and colt) were retrieved by the two disciples fully provisioned with foodstuffs and refreshment for a time of preparatory celebration, but only one of them (the colt) was mounted by Jesus into Jerusalem. ", "The key parallel in the Hebrew Bible again is therefore 2 Sam 16:1-2.", "\nThere are therefore no contradictions in the gospel accounts, but simply an amplified view from the perspective of Matthew, who captures the very details of prophecy and the very nuance of David the rejected king on the Mount of Olives. ", "Such an emphasis is not a surprise, since Matthew is the \"regal\" gospel and therefore has placed an emphasis on Jesus as the Son of David.", "\n\n" ]

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[ "Yeovil Town can confirm that James Tilley’s loan has been terminated by Brighton and Hove Albion.", "\n\nThe midfielder now heads northbound to Blundell Park, joining up with Ian Holloway’s Grimsby Town in League Two.", "\n\nThe technically gifted midfielder was originally supposed to stay until the end of the season, but Tilley will now move on ahead of schedule after making 21 appearances for the green and white.", "\n\nDespite not scoring, Tilley made a number of goal contributions for the Glovers, linking up well with Rhys Murphy providing vital assists, most notably away to Chorley.", "\n\nWe thank Tilley for his contribution this season and wish him well for the future." ]

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[ "Nuclear divisions with reduced numbers of microtubules in Tetrahymena.", "\nUltrastructural observations on micronuclei of Tetrahymena thermophila, WH-6 dividing in the presence of colchicine suggest that the microtubules present at the time of drug addition persist, but no new microtubules are formed. ", "It is suggested that the great amount of elongation seen in these drug-treated micronuclei may not be due to the persisting microtubules alone. ", "On the basis of ultrastructural and light-microscopic observations, it is proposed that at least part of the motive force responsible for the elongation which occurs in colchicine may be due to an active sliding of the micronuclear membrane on some element of the cell cortex. ", "In addition, the macronucleus of this species of Tetrahymena was found to be capable of dividing in colchicine in the absence of internal nuclear microtubules." ]

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[ "_Nation4Nation\n\nLadies and gentlemen, it’s a pleasure for me to announce you that another Nation4Nation is coming!", "\n\nOur amazing and really brave Belgium girl, Eva, gonna introduce you her country and national meal as well. ", "Also guys from Lithuania has decided to show you the best from themselves. ", "So don’t hesitate and come to explore Belgium and Lithuania together!" ]

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[ "Indian tax evaders subjected to a 'load of rubbish' By Amarnath Tewary\n\nPatna, Bihar Published duration 11 January 2012\n\nimage caption The garbage was removed after a public outcry (Photo: Prashant Ravi)\n\nCivic authorities in India's Bihar state have dumped heaps of stinking garbage outside a shopping complex to penalise its owner for evading taxes.", "\n\nThree truckloads of rubbish were emptied outside the centre in the state capital Patna's Kankerbagh locality.", "\n\nOfficials said they were forced to take the extreme step as the complex owner had not paid taxes for 12 years.", "\n\nAfter a public outcry, the civic authority removed the garbage from the area where it had been deposited.", "\n\nIt says it will no longer use \"such unusual ways\" to collect tax dues.", "\n\nPatna is one of India's filthiest cities with stinking piles of rubbish literally found in every nook and cranny.", "\n\nThe Municipal Corporation officials often express their inability to clean the city because of staff shortages and poor resources.", "\n\n'No option'\n\nHarishankar Prasad, senior deputy tax collector of Kankerbagh area, told the BBC that he had repeatedly asked Avinash Kumar, the proprietor of the JP Market complex, to clear his dues of 164,000 rupees ($3,175; £2,052)\n\nOn Tuesday, civic officials dumped the rubbish in front of the market gate, ignoring protests from local shopkeepers.", "\n\n\"We had no option left after several reminders to him to pay the tax dues had went unheeded,\" Mr Prasad said.", "\n\nHe said it was done to put pressure on Mr Kumar to clear his dues.", "\n\nUpset by the stench, residents of the nearby area protested by blocking roads against the \"unusual way of embarrassing people into paying their tax dues\".", "\n\n\"Why should people, who pay their taxes regularly, have to suffer the stench of garbage on the road?\" ", "asked Rajesh Kumar.", "\n\n\"The stinking filth is unbearable and it forced us to remain indoors for the whole day on Tuesday.\"", "\n\nMr Prasad said the civic authority was not planning to repeat the \"unusual\" punishment.", "\n\n\"We've abandoned the exercise for the time being,\" he said.", "\n\n\"But please ask those defaulters where in the law is it written that they can live in the city, do their business and not pay municipal taxes?\" ", "he asked.", "\n\nIt is not the first time Patna civic officials have opted for unusual ways to humiliate tax defaulters.", "\n\nIn 2006, municipal corporation officials hired a group of eunuchs to shame tax defaulters into paying their dues.", "\n\nEunuchs - who are feared and reviled in many parts of India - gathered outside the shops or homes of suspected tax defaulters and sang \"to embarrass\" them into paying their dues." ]

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[ "// RUN: %clang_cc1 -fsyntax-only -verify %s\n\n#define nil (void *)0;\n\nextern void foo();\n\n@protocol MyProtocolA\n- (void) methodA;\n@end\n\n@protocol MyProtocolB\n- (void) methodB;\n@end\n\n@protocol MyProtocolAB <MyProtocolA, MyProtocolB>\n@end\n\n@protocol MyProtocolAC <MyProtocolA>\n- (void) methodC;\n@end\n\nint main()\n{\n id<MyProtocolA> obj_a = nil;\n id<MyProtocolB> obj_b = nil;\n id<MyProtocolAB> obj_ab = nil;\n id<MyProtocolAC> obj_ac = nil;\n\n obj_a = obj_b; // expected-warning {{assigning to 'id<MyProtocolA>' from incompatible type 'id<MyProtocolB>'}}\n obj_a = obj_ab; /* Ok */\n obj_a = obj_ac; /* Ok */\n \n obj_b = obj_a; // expected-warning {{assigning to 'id<MyProtocolB>' from incompatible type 'id<MyProtocolA>'}}\n obj_b = obj_ab; /* Ok */\n obj_b = obj_ac; // expected-warning {{assigning to 'id<MyProtocolB>' from incompatible type 'id<MyProtocolAC>'}}\n \n obj_ab = obj_a; // expected-warning {{assigning to 'id<MyProtocolAB>' from incompatible type 'id<MyProtocolA>'}}\n obj_ab = obj_b; // expected-warning {{assigning to 'id<MyProtocolAB>' from incompatible type 'id<MyProtocolB>'}}\n obj_ab = obj_ac; // expected-warning {{assigning to 'id<MyProtocolAB>' from incompatible type 'id<MyProtocolAC>'}}\n \n obj_ac = obj_a; // expected-warning {{assigning to 'id<MyProtocolAC>' from incompatible type 'id<MyProtocolA>'}}\n obj_ac = obj_b; // expected-warning {{assigning to 'id<MyProtocolAC>' from incompatible type 'id<MyProtocolB>'}}\n obj_ac = obj_ab; // expected-warning {{assigning to 'id<MyProtocolAC>' from incompatible type 'id<MyProtocolAB>'}}\n\n if (obj_a == obj_b) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolA>' and 'id<MyProtocolB>')}}\n if (obj_b == obj_a) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolB>' and 'id<MyProtocolA>')}}\n\n if (obj_a == obj_ab) foo (); /* Ok */\n if (obj_ab == obj_a) foo (); /* Ok */ \n\n if (obj_a == obj_ac) foo (); /* Ok */ \n if (obj_ac == obj_a) foo (); /* Ok */ \n\n if (obj_b == obj_ab) foo (); /* Ok */ \n if (obj_ab == obj_b) foo (); /* Ok */ \n\n if (obj_b == obj_ac) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolB>' and 'id<MyProtocolAC>')}} \n if (obj_ac == obj_b) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolAC>' and 'id<MyProtocolB>')}} \n\n if (obj_ab == obj_ac) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolAB>' and 'id<MyProtocolAC>')}} \n if (obj_ac == obj_ab) foo (); // expected-warning {{comparison of distinct pointer types ('id<MyProtocolAC>' and 'id<MyProtocolAB>')}} \n\n return 0;\n}\n" ]

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[ "Q:\n\nSyntax Question: @Html.", "LabelFor(m => m.UserName)\n\nGoing from ASP.NET 2.0 (VB) to MVC 3 (C#), I'm very confused about the syntax being used for the View.", "\n@Html.", "LabelFor(m => m.UserName)\n\nWhere did that m come from? ", " My only guess is that it represents the model that is being passed into the view. ", " I tried changing the m to c and it still works fine.", "\nIs the part of the syntax that involves the \"=>\" more of a MVC, C#, or Razor element?", "\n\nA:\n\nWhere did that m come from?", "\n\nIt's the parameter in a lambda expression.", "\n\nMy only guess is that it represents the model that is being passed into the view. ", "I tried changing the m to c and it still works fine.", "\n\nThat's because the name doesn't matter. ", "It's just a parameter name, it doesn't actually refer to any existing variable.", "\n\nIs the part of the syntax that involves the \"=>\" more of a MVC, C#, or Razor element?", "\n\nIt's C#, but LabelFor uses what the compiler translates m => m.UserName into to extract what it needs to build up the label.", "\nThis is a very deep an intricate subject. ", "I suggest that you find a book that you're comfortable with (e.g., C# in Depth is very good on this subject) to understand more. ", "You want to read about lambda expressions and expression trees.", "\n\nA:\n\nIt's a syntax trick that has been present since C# 3.0 (I think; maybe 3.5).", "\nIf you were to write this in code (and your Razor view does get translated to a C# code file before compiling, so it really is in code), there are two possible ways the compiler can compile it depending on the context.", "\nIf the method LabelFor() expects a delegate, it's compiled to an anonymous method. ", "Alternatively, if the method expects an System.", "Linq.", "Expressions.", "Expression<Func> type, an expression tree is constructed. ", "This is what is happening in your case.", "\nThe reason for this convulted syntax is that the expression tree contains enough information, that (combined with Reflection) the LabelFor() method can extract the actual property to which you are referring. ", "If you were to pass it simply as LabelFor(Model.", "UserName), there wouldn't be enough information for the LabelFor() to do this. ", "It would just get the value from the UserName property. ", "But now it knows where it came from, and can use more Reflection to have a glance at the attributes of the property. ", "Attributes such as DisplayFormat, Required, and others.", "\nThe m (or c or whatever) is actually your model. ", "LabelFor is an extension method and it simply passes your model back to your Lambda expression, so that the whole expression tree trick can work. ", "You could also write it like LabelFor(x=>Model.", "UserName), but I don't think it would work (I haven't tried though, maybe it does).", "\n\nA:\n\nThat's a Lambda Expression, link.", "\nThe deal is this: the m is a variable that receives the instance of the model in the given circunstance.", "\nInside the labelFor, it will call a compile-time created class, which has a method that does what you have passed as an argument to the LabelFor.", "\nA lambda expression can be switched by a delegate, with the exact same results, excepting a minor, really minor performance boost, once.", "\nThe general idea is that you are passing a method to be execute somewhere in the LabelFor method.", "\nex:\nthe method: \npublic void Dummy(Action<string> action)\n{\n if(iFeelLikeIt) {action(\"I feel Like it\");}\n}\n\nShould be used as:\nDummy(msg => MessageBox.", "Show(msg));\n\n" ]

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[ "Background\n==========\n\nMammary gland neoplasms are the most prevalent tumors in dogs, and their treatment is still challenging. ", "A crucial problem in the handling of this type of neoplasm is to obtain primary mammary epithelial cell cultures from the original tumors. ", "The aim of this study was to determine the best conditions to culture primary mammary epithelial cells from several histological types of canine breast tumors.", "\n\nMaterials and methods\n=====================\n\nSeveral culturing conditions have been tested including enzymes such as collagenases types III and IV, trypsin and hyaluronidase, differential centrifugation and trypsinization. ", "Four tumor samples were processed to obtain organoids, stromal and epithelial cells. ", "The histological tumor types studied were mixed carcinoma and simple adenoma. ", "The cells were phenotypically characterized according to an immunocytochemical panel, including cytokeratins, alpha smooth muscle actin and vimentin.", "\n\nResults\n=======\n\nResults have shown that the best method of obtaining primary epithelial cell lines comprises the use of collagenase type I, hyaloronidase and trypsin followed by serial differential trypsinization.", "\n\nConclusions\n===========\n\nStandardization of such methodological tools in the canine model for the study of cancer will allow a more detailed analysis of the action of new antineoplastic agents, which could be applied to animals and, eventually, to humans.", "\n\nFinancial support\n=================\n\nFAPESP and CNPq.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nNinject Factory: Create the appropriate class based on a parameter\n\nI have 3 classes:\n\nclass SqlQueryService : IQueryService\nclass FileQueryService : IQueryService\nclass NCRFileQueryService : FileQueryService\n\nI have create an interface factory:\npublic interface IQueryServiceFactory\n{\n IQueryService Create(string connection);\n}\n\nIn the application module:\nBind(typeof(IQueryService)).To(typeof(SqlQueryService)).Named(\"Data Source\"); \nBind(typeof(IQueryService)).To(typeof(NCRFileQueryService)).Named(\"NCR File Source\");\nBind(typeof(IQueryService)).To(typeof(FileQueryService)).Named(\"File Source\");\n\nBind<IQueryServiceFactory>().ToFactory();\n\nIn my app I want to create an instance of one of three classes based on a parameter like the following:\nIQueryService queryService =\n _queryServiceFactory.", "Create(_configuration.", "SelectedTPV.Connection);\n\nIf the string parameter starts with \"Data Source\" create a SqlQueryService\nIf the string parameter starts with \"File Source\" create a FileQueryService\nIf the string parameter starts with \"NCR File Source\" create a NCRFileQueryService\n\nIt's possible to do that? ", "\n*Note: My app is a winforms app with .NET Framework 3.5 because is for and OLD windows\nThe Ninject version that I use is 3.2.2.0 and the version of the Ninject Extensions Factory is 3.2.1.0\n\nA:\n\nYou can do this by creating a custom instance provider and then binding your factory like:\nthis.", "Bind<IQueryServiceFactory>()\n .ToFactory(() => new UseFirstArgumentAsNameInstanceProvider());\n\nSee Treating the first factory method parameter as a name specifier in the documentation.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Patterns of synonymous codon usage bias in the model grass Brachypodium distachyon.", "\nBrachypodium distachyon has been proposed as a new model for the temperate grass because it is related to the major cereal grain species (such as wheat, barley, oat, maize, rice, and sorghum) and many forage and turf species. ", "In this study, a multivariate statistical analysis was performed to investigate the characteristics of codon bias and the main factors affecting synonymous codon usage in Brachypodium. ", "We found that low- and high-GC content genes with different codon usage occur frequently in the genome. ", "The results of neutrality, correspondence, and correlation analyses indicated that mutational pressure and selective constraint were the main factors in shaping codon usage. ", "Coding sequence length and the hydrophobicity of each protein were also identified as influences on codon usage bias, although their effect was minor. ", "In addition, 27 codons, defined as \"optimal codons\", might provide useful information for gene engineering, gene prediction, and molecular evolution studies." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nhow to list all the email subject in GMail?", "\n\nI want to list all the email subject in my gmail account.", "\nimport imaplib\nimport email\nuser=\"xxxx\"\npassword=\"yyyy\"\ncon=imaplib.", "IMAP4_SSL('imap.gmail.com')\ncon.login(user,password)\nnum=int(con.select(\"[Gmail]/&YkBnCZCuTvY-\")[1][0])\n\nThe num is 1200,there are 1200 emails in my gmail account.", "\nI want to list all the email subject.", "If i want to get the first email subject ,\nresult,data=con.fetch(b'1', '(RFC822)')\nprint email.message_from_string(data[0][1])[\"Subject\"]\n\nThe two lines can get it.", "\nBut i can't list all the email subject as the following,how to fix it?", "\nfor item in range(num+1):\n result,data=con.fetch(str(item), '(RFC822)')\n print email.message_from_string(data[0][1])[\"Subject\"]\n\nA:\n\nTry modifying your range in your for loop. ", " I believe the message ids in fetch() are '1 based'\nfor item in range(1,num+1):\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Hyperparathyroidism: the overlooked disorder.", "\nHyperparathyroidism often goes undiagnosed because the early symptoms are very subtle and, if they are noticed, are attributed to old age, depression, or anxiety. ", "The serum calcium level is crucial to the diagnosis. ", "Some of the symptoms of the disorder suggest anxiety or depression, but the overall cluster does not fit DSM-III R or nursing diagnosis criteria. ", "Because hyperparathyroidism requires surgical intervention, nurses can offer assistance by providing emotional support and recommending strategies that will help elderly persons maintain function until the treatment is completed." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "[Activity and stability of glucoamylase preparations in different methods of immobilization].", "\nCatalytic activity and stability of glucoamylases immobilized by different methods (adsorption, covalent binding) are studied comparatively. ", "The highest stability is shown to be obtained under covalent binding. ", "The binding efficiency and immobilized glucoamylase properties depend on the nature of insoluble carrier and a purification degree of the enzyme preparations. ", "The choice of the cross-linking agent promoting a binding between the enzyme and the carrier is very significant. ", "The activity and stability of immobilized glucoamylases obtained when using different cross-linking agents rise in such a sequence: 2,4-toluylenediisocyanate, cyanurochloride, glutaric dialdehyde, gossypol. ", "Catalytic properties and stability are determined for soluble and immobilized glucoamylase forms from different sources." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Category Archives: Connecticut\n\nDrop the defense of DOMA and you will lose conservative support -- support which can prove critical, come election day:\n\nPeter Wolfgang, director of the conservative Family Institute of Connecticut, has taken back his endorsement of Republican U.S. Senate candidate Linda McMahon, although he is still voting for her “because her victory could mean the end of Roe v. Wade.”", "\n\nThe announcement, first reported by the Hartford Courant, was on the institute’s Facebook page Monday.", "\n\nWolfgang had endorsed McMahon in September, but pulled back when she said after a political debate Sunday that she now backs repeal of the Defense of Marriage Act.", "\n\n“I’m still voting for Linda because her victory could mean the end of Roe v. Wade. ", "But because Linda McMahon flip-flopped and now supports a repeal of DOMA — the one federal law that stops Connecticut’s judicially imposed re-definition of marriage from being imposed on the rest of the nation — my September 18th endorsement of her is no longer accurate,” he wrote on Facebook. -- ", "New Haven Register\n\nWe are sure the majority of gay men are appalled by this kind of behavior. ", "How can it be stopped?", "\n\nA Connecticut homosexual pled guilty on Tuesday to sending 300 threatening messages, including death threats, to the leader of a state pro-life, pro-marriage organization.", "\n\n53-year-old Daniel Sarno of Enfield, Connecticut, admitted intimidating Peter Wolfgang, the executive director of the Family Institute of Connecticut, over a six-month period from last November until May.\n\nWolfgang said Sarno identified himself as a homosexual in the letters, which came addressed “Attention: Peter Wolfgang.”", "\n\n“Unfortunately, this is not an isolated incident,” Wolfgang said in a statement e-mailed to LifeSiteNews.com. “", "In fact it is part of a growing and disturbing intimidation campaign among some proponents of same-sex ‘marriage.’ ", "It is clear that their pretense of ‘tolerance’ is over.” -- ", "LifeSiteNews\n\nAn Enfield man admitted in court Tuesday that he sent hundreds of threatening letters to the director of the socially conservative Family Institute of Connecticut, which is at the forefront of political opposition in Hartford to gay marriage.", "\n\nThe guilty plea in U.S. District Court by Daniel Sarno comes a week after an apparently similarly motivated event in which an armed man espousing opposition to social conservatism shot a security guard while trying to enter the offices of the Family Research Council in Washington, D.C., on Aug. 15.", "\n\nThe Family Institute and the Family Research Council are affiliated organizations created to press agendas that include opposition to abortion and to marriage other than that between a man and a woman.", "\n\nSarno, 53, admitted orchestrating a letter-writing campaign that began in November and ended in May when U.S. postal inspectors tracked the letters to his house, an official familiar with the matter said. ", "All the letters were addressed to Family Institute Executive Director Peter Wolfgang.", "\n\n\"No mercy for homophobes,\" said one letter, obtained by The Courant. \"", "I suggest you make your funeral arrangements real soon, Mr. Wolfgang. (", "Trust me. ", "I know.)\"", "\n\nAssistant U.S. Attorney John Durham said, \"Some of the letters contained threats separate and apart from the generally obnoxious nature of the letters.\"", "\n\nSarno, in many of the letters, referred to people who shared the beliefs of the Family Institute as \"Bible thumping,\" \"fear mongering\" and \"sanctimonious,\" Durham said.", "\n\n... Wolfgang, who was in court, issued a statement through his organization thanking authorities for protecting him, his family and his professional colleagues.", "\n\n\"Unfortunately, this is not an isolated incident,\" Wolfgang said. \"", "In fact, it is part of a growing and disturbing intimidation campaign among some proponents of same-sex 'marriage.' ", "It is clear that their pretense of 'tolerance' is over.", "\n\n\"Using death threats to stifle debate is un-American. ", "These types of tactics won't work. ", "The Family Institute of Connecticut will continue its work to strengthen and protect marriage, life and religious freedom.\"", "\n\nThe statement from the Family Institute said that in the letters, Sarno \"identified himself as homosexual and made it clear that he was threatening Peter's life because of Peter's beliefs and public advocacy.\"", "\n\nSeveral students at a Hartford high school expressed horror and left the auditorium when two male members of a city-funded school play shared a passionate kiss onstage on Friday. ", "School officials said they opted against informing parents about the event ahead of time, saying that the students needed exposure to homosexuality, and hailed the “chaotic” reaction as a victory for raising the gay issue.", "\n\n... School officials had told students that homosexual displays of affection would be featured in the play, and many asked to be excused. ", "One school official cited by The Courant, nursing academy principal David Chambers, said that he had considered sending an opt-out letter to parents before changing his mind. ", "The school reportedly received a number of phone calls from parents following the incident.", "\n\nThis is clearly a coordinated strategy now. ", "We've seen it in Connecticticut, California, and now Great Britain.", "\n\nIt is not impossible to provide practical benefits for same-sex couples without endangering your state's marriage laws, but the laws have to be drawn carefully if the goal is to provide some compassionate help for those ineligible for marriage, while retaining your marriage laws.", "\n\nBut it's much harder:\n\n\"Peter Tatchell, who is fronting the 'Equal Love' campaign, . . . ", ".said: \"Since there is no difference in the rights and responsibilities involved in gay civil marriages and heterosexual civil partnerships, there is no justification for having two mutually exclusive and discriminatory systems.", "\n\n\"Banning black couples from getting married would provoke uproar. ", "The prohibition on gay marriages should arouse similar outrage.", "\n\n\"The ban on same-sex civil marriages and opposite-sex civil partnerships is a form of legal sexual apartheid - one law for gay couples and another law for heterosexual partners. ", "Two wrongs don't make a right.\"", "\n\nThe campaign's legal advisor, Robert Wintemute, expressed confidence that the court would strike down the ban.", "\n\nHe said of the current laws: \"It's discriminatory and obnoxious, like having separate drinking fountains or beaches for different racial groups, even though the water is the same.", "\n\n\"The only function of the twin bans is to mark lesbian and gay people as socially and legally inferior to heterosexual people.", "\n\n\"I am confident that we have a good chance of persuading the European Court of Human Rights that the UK's system of segregating couples into two 'separate but equal' legal institutions violates the European Convention. ", "I predict that same-sex couples will be granted access to marriage in the UK.\"", "\n\nThe application to the ECHR will be filed by all eight couples simultaneously today. ", "Should the court find that the law contradicts European conventions, then the UK will be obliged to make changes.\"", "\n\nThe Lawlor-and-McDonald-controlled Judiciary Committee in Connecticut just passed a same-sex marriage bill -- without religious liberty protections! ", "For the second time in a month, Lawlor and McDonald have used their Judiciary Committee roles to attack religious liberty and people of faith in Connecticut.", "\n\nLast month, they failed in their efforts to involve the state in matters of internal church governance -- but only after an historic uprising from the people of Connecticut. ", "But now they're back at it again with a bill to enshrine last year's CT Supreme Court ruling into statute, without any substantive protections for churches, religious organizations or people of faith. ", "In the process, they fought off amendments that would have given conscience protections to Justices of the Peace, limited teaching on homosexuality in the schools, and protected religious liberty rights of churches and religious organizations (like Catholic Charities!).", "\n\nSB899 was approved by the Judiciary Committee this past Monday evening, and now goes to the full Senate, where there will be efforts to add a religious liberty amendment to the bill. ", "NOM has just launched a radio ad campaign in Connecticut focused on protecting our religious liberties. (", "\n\n2. ", "Then make plans to attend the Rally for Religious Liberty in Hartford at 10:00am next Tuesday, April 7th. ", "The rally is being sponsored by the Family Institute of Connecticut, and will meet on the North Steps of the Capitol (overlooking Bushnell Park). ", "Help us have a great turnout on Tuesday!" ]

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[ "1. ", "Field of the Invention\nThe present invention relates to a discharge volume control method, a discharge pressure control method, an injecting apparatus, a microbody forming method, a discharge volume control device, and a discharge volume control program.", "\n2. ", "Description of the Related Art\nA microinjection, which is a method of injecting a specific substance (DNA, a drug, or the like) into a cell under a microscope, has been known in the fields of regenerative medicine, new drug designing, and the like. ", "Microinjection is a method of pressurizing a capillary filled with a solution containing a predetermined substance in advance, thereby discharging the solution into a cell penetrated by the capillary to inject the substance into the cell. ", "This method allows, for example, to examine effects of the injected substance on the cell. ", "A quantitative discharge of a solution into a cell is critically important for microinjection. ", "Therefore, liquid discharge volume control methods for regulating a discharge volume conveniently and accurately with high repeatability have been developed.", "\nFor example, Japanese Patent Application Laid-open No. ", "H3-119989 (Paragraphs 0010 to 0014, FIG. ", "1, and FIG. ", "2) discloses a microinjection apparatus in which a male screw is rotated to move a plunger, thereby pressurizing a capillary to discharge liquid. ", "Specifically, when an operator presses a button provided on a control box included in the microinjection apparatus, an electric signal is generated, and the generated electric signal causes a piezoelectric element to produce a drive force to rotate the female screw so that the plunger is moved to discharge liquid filled in the capillary. ", "Accordingly, the operator of the microinjection apparatus achieves the discharge of the liquid out of the capillary penetrated into a cell conveniently at the simple push of the button.", "\nWhile the conventional technology described above achieves discharge of liquid conveniently by moving a plunger with the push of a button, a discharge volume is regulated by an operator of the microinjection apparatus who observes a cell penetrated by the capillary under a microscope and estimates the discharge volume based on a degree of expansion of the cell to determine whether a predetermined liquid volume has been discharged. ", "Therefore, the conventional technology still has a problem of not attaining a quantitative discharge of the liquid." ]

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[ "---\nabstract: 'An asymmetry between the probabilities $P(\\nu_{\\mu}\\rightarrow\\nu_{e})$ and $P(\\bar{\\nu_{\\mu}}\\rightarrow\\bar{\\nu_{e}})$ would be direct indication of CP violation at the fundamental level. ", "Planck scale effects on neutrino mixing, we have derived the mixing angles of neutrino flavour due to Planck scale effects. ", "It has been shown that Jarlskog determinant remains nearly invariant due to Planck scale effects.'", "\nauthor:\n- Bipin Singh Koranga\ntitle: Nearly Invariance of Jarlskog Determinant due to Planck Scale Effects \n---\n\nKirori Mal college (University of Delhi,) Delhi-110007, India\n\nINTRODUCTION\n============\n\nThe evidence of a deficit of detected solar neutrinos [\\[]{}1\\] indicates that electron neutrinos must also participate in lepton mixing. ", "The participation of all three neutrinos in lepton mixing raises the possibility of CP and T violation in neutrino oscillations. ", "The emergence of large mixing parameter in lepton sector indicate the potentially large CP and T violation are maximal for neutrinos in vacuum. ", "A number of auther [\\[]{}2-6\\] have explored the phenomenology of CP and T violation in neutrino oscillations for several different scenarios of lepton masses and mixing parameters. ", "In both solar and atmospheric neutrino experiments can traverse a significant of the earth. ", "Long baseline accelerator and reactor experiment still longer baseline. ", "CP violation arise as three or more generation [\\[]{}7, 8\\]. ", "CP violation in neutrino oscillation is interesting because it relates directly to CP phase parameter in the mixing for $n>3$ degenerate neutrino. ", "We can write down the compact formula for the difference of transition probability between conjugate channel.", "\n\n$$\\Delta P(\\alpha,\\beta)=P(\\nu_{\\mu}\\rightarrow\\nu_{e})-P(\\bar{\\nu_{\\mu}}\\rightarrow\\bar{\\nu_{e}}),$$\n\nwhere $$(\\alpha,\\beta)=(e,\\mu),(\\mu,\\tau),(\\tau,e).$$\n\nThe main physical goal in future experiment are the determination of the unknown parameter $\\theta_{13}$ and upper bound $sin^{2}2\\theta_{13}<0.01$ is obtained for the ref [\\[]{}9\\]. ", "In particular, the observation of $\\delta$ is quites interesting for the point of view that $\\delta$ related to the origin of the matter in the universe. ", "The determination of $\\delta$ is the final goal of the future experiments. ", "We get the analytical expression for $\\Delta P(\\alpha,\\beta)$ using the usual form of the MNS matrix parametrization [\\[]{}10\\].", "\n\n$$U=\\left(\\begin{array}{ccc}\nc_{12}c_{13} & s_{12}c_{13} & s_{13}e^{-i\\delta}\\\\\n-s_{12}c_{23}-c_{12}s_{23}s_{13}e^{i\\delta} & c_{12}c_{23}-s_{12}s_{23}s_{13}e^{i\\delta} & s_{23}c_{13}\\\\\ns_{12}s_{23}-c_{12}c_{23}s_{13}e^{i\\delta} & -c_{12}s_{23-}s_{12}s_{13}s_{23}e^{i\\delta} & c_{23}s_{13}\\end{array}\\right),$$\n\nwhere c and s denoted the cosine and sine of the respective notation, thus $\\Delta P(\\alpha,\\beta)$ in vacuum can be written as$$\\Delta P(\\alpha,\\beta)=16J\\left(sin\\Delta_{21}sin\\Delta_{32}sin\\Delta_{31}\\right).$$\n\nHere $\\alpha$ and $\\beta$ denote different neutrino or anti-neutrino flavour\n\nwhere\n\n$$\\Delta_{ij}=1.27\\left(\\frac{\\Delta_{ij}}{eV^{2}}\\right)\\left(\\frac{L}{Km}\\right)\\left(\\frac{1GeV}{E}\\right),$$\n\n$\\Delta_{ij}=(m_{i}^{2}-m_{j}^{2})$is the difference of $i^{th}$ and $j^{th}$ vacuum mass square eigen value, E is the neutrino energy and L is the travel distance and the well known Jarlskog determinant [\\[]{}11\\], J is the standard mixing parametrization is given by\n\n$$J=Im\\left(U_{e1}U_{e2}^{*}U_{\\mu1}^{*}U_{\\mu2}\\right)$$\n\n$$=\\frac{1}{8}sin2\\theta_{12}sin2\\theta_{23}sin2\\theta_{13}cos\\theta_{13}sin\\delta,$$\n\nand the asymmetry parameter suggested by Cabibbo [\\[]{}12\\], as an alternative to measure CP violation in the lepton sector\n\n$$A_{cp}=\\frac{\\Delta P}{P(\\nu_{\\mu}\\rightarrow\\nu_{e})-P(\\bar{\\nu_{\\mu}}\\rightarrow\\bar{\\nu_{e}}),}$$\n\nThe purpose of this paper is to study the Planck scale effects on Jarlskog Determinant. ", "In Sec-2, we discuss the neutrino mixing angle due to Planck scale effects. ", "In Sec-3, we give the conclusions.", "\n\nNEUTRINO MIXING ANGLE DUE TO PLANCK SCALE EFFECTS\n=================================================\n\nTo calculate the effects of perturbation on neutrino observables. ", "The calculation developed in an earlier paper [\\[]{}13\\]. ", "A natural assumption is that unperturbed ($0^{th}$ order mass matrix $M$ is given by\n\n$$\\mathbf{M}=U^{*}diag(M_{i})U^{\\dagger},$$\n\nwhere, $U_{\\alpha i}$ is the usual mixing matrix and $M_{i}$ , the neutrino masses is generated by Grand unified theory. ", "Most of the parameter related to neutrino oscillation are known, the major expectation is given by the mixing elements $U_{e3}.$ We adopt the usual parametrization.", "\n\n$$\\frac{|U_{e2}|}{|U_{e1}|}=tan\\theta_{12}$$\n\n$$\\frac{|U_{\\mu3}|}{|U_{\\tau3}|}=tan\\theta_{23}$$\n\n$$|U_{e3}|=sin\\theta_{13}$$\n\nIn term of the above mixing angles, the mixing matrix is\n\n$$U=diag(e^{if1},e^{if2},e^{if3})R(\\theta_{23})\\Delta R(\\theta_{13})\\Delta^{*}R(\\theta_{12})diag(e^{ia1},e^{ia2},1).$$\n\nThe matrix $\\Delta=diag(e^{\\frac{1\\delta}{2}},1,e^{\\frac{-i\\delta}{2}}$) contains the Dirac phase. ", "This leads to CP violation in neutrino oscillation $a1$ and $a2$ are the so called Majoring phase, which effects the neutrinoless double beta decay. ", "$f1,$ $f2$ and $f3$ are usually absorbed as a part of the definition of the charge lepton field. ", "Planck scale effects will add other contribution to the mass matrix that gives the new mixing matrix can be written as [\\[]{}13\\]\n\n$$U^{'}=U(1+i\\delta\\theta),$$\n\n$$=\\left(\\begin{array}{ccc}\nU_{e1} & U_{e2} & U_{e3}\\\\\nU_{\\mu1} & U_{\\mu2} & U_{\\mu3}\\\\\nU_{\\tau1} & U_{\\tau2} & U_{\\tau3}\\end{array}\\right)+i\\left(\\begin{array}{ccc}\nU_{e2}\\delta\\theta_{12}^{*}+U_{e3}\\delta\\theta_{23,}^{*} & U_{e1}\\delta\\theta_{12}+U_{e3}\\delta\\theta_{23}^{*}, & U_{e1}\\delta\\theta_{13}+U_{e3}\\delta\\theta_{23}^{*}\\\\\nU_{\\mu2}\\delta\\theta_{12}^{*}+U_{\\mu3}\\delta\\theta_{23,}^{*} & U_{\\mu1}\\delta\\theta_{12}+U_{\\mu3}\\delta\\theta_{23}^{*}, & U_{\\mu1}\\delta\\theta_{13}+U_{\\mu3}\\delta\\theta_{23}^{*}\\\\\nU_{\\tau2}\\delta\\theta_{12}^{*}+U_{\\tau3}\\delta\\theta_{23}^{*}, & U_{\\tau1}\\delta\\theta_{12}+U_{\\tau3}\\delta\\theta_{23}^{*}, & U_{\\tau1}\\delta\\theta_{13}+U_{\\tau3}\\delta\\theta_{23}^{*}\\end{array}\\right).$$\n\nWhere $\\delta\\theta$ is a hermition matrix that is first order in $\\mu$[\\[]{}13,14\\]. ", "The first order mass square difference $\\Delta M_{ij}^{2}=M_{i}^{2}-M_{j}^{2},$get modified [\\[]{}13,14\\] as\n\n$$\\Delta M_{ij}^{'^{2}}=\\Delta M_{ij}^{2}+2(M_{i}Re(m_{ii})-M_{j}Re(m_{jj})).$$\n\nThe change in the elements of the mixing matrix, which we parametrized by $\\delta\\theta$[\\[]{}13\\], is given by\n\n$$\\delta\\theta_{ij}=\\frac{iRe(m_{jj})(M_{i}+M_{j})-Im(m_{jj})(M_{i}-M_{j})}{\\Delta M_{ij}^{'^{2}}}.$$\n\nThe above equation determine only the off diagonal elements of matrix $\\delta\\theta_{ij}$. The diagonal element of $\\delta\\theta_{ij}$ can be set to zero by phase invariance. ", "Using Eq(12), we can calculate neutrino mixing angle due to Planck scale effects,\n\n$$\\frac{|U_{e2}^{'}|}{|U_{e1}^{'}|}=tan\\theta_{12}^{'}$$\n\n$$\\frac{|U_{\\mu3}^{'}|}{|U_{\\tau3}^{'}|}=tan\\theta_{23}^{'}$$\n\n$$|U_{e3}^{'}|=sin\\theta_{13}^{'}$$\n\nAs one can see from the above expression of mixing angle due to Planck scale effects, depends on new contribution of mixing $U^{'}=U(1+i\\delta\\theta).$ To see the mixing angle due to Planck scale effects [\\[]{}13,15\\] only $\\theta_{13}$and $\\theta_{12}$ mixing angle have small deviation due to Planck scale effects.", "\n\nJARLSKOG DETERMINANT DUE TO PLANCK SCALE EFFECTS \n=================================================\n\nLet us compute Jarlskog determinant due to new mixing due to Planck scale effects\n\n$$J^{'}=Im\\left(U_{e1}^{'}U_{e2}^{'*}U_{\\mu1}^{'*}U_{\\mu2}^{'}\\right)$$\n\n$$=Im((U_{e1}+i(U_{e2}\\delta\\theta_{12}^{*}+U_{e3}\\delta\\theta_{13}))((U_{e2}-i(U_{e1}^{*}\\delta\\theta_{12}^{*}+U_{e3}^{*}\\delta\\theta_{13}))$$\n\n$$((U_{\\mu1}^{*}-i(U_{\\mu2}\\delta\\theta_{12}+U_{\\mu3}\\delta\\theta_{13}))((U_{\\mu2}+i(U_{\\mu1}\\delta\\theta_{12}+U_{\\mu3}\\delta\\theta_{23}^{*})$$\n\nWe simplified Jarlskog determinant due to new mixing matrix\n\n$$J^{'}=Im\\left(U_{e1}U_{e2}^{*}U_{\\mu1}^{*}U_{\\mu2}\\right)+Im(i(U_{\\mu1}U_{\\mu2})(|U_{e2}|^{2}\\delta\\theta_{12}^{*}+U_{e2}U_{e3}\\delta\\theta_{13}-|U_{e1}|^{2}\\delta\\theta_{12}^{*}-U_{e1}U_{e3}^{*}\\delta\\theta_{23}^{*})$$\n\n$$+Im(i(U_{e1}^{*}U_{e2})(|U_{\\mu1}|^{2}\\delta\\theta_{12}+U_{\\mu1}^{*}U_{\\mu3}\\delta\\theta_{23}^{*}-|U_{\\mu2}|^{2}\\delta\\theta_{12}-U_{\\mu2}U_{\\mu3}^{*}\\delta\\theta_{13}^{})$$\n\n$$=J+\\Delta J$$\n\nIn term of mixing angle, we can write Jarlskog determinant in term of mixing parameter due to Planck scale effects\n\n$$J^{'}=\\frac{1}{8}sin2(\\theta_{12}+\\epsilon_{12})sin2(\\theta_{23}+\\epsilon_{23})sin2(\\theta_{13}+\\epsilon_{13})cos(\\theta_{13}+\\epsilon_{13})sin\\delta,$$\n\nNumerically % change of Jarlskog determinant is very small [\\[]{}17\\], due to small change of mixing angle $\\theta_{12}$ and $\\theta_{13}.$ In reminder of this paper, we explore the neutrino mixing and jarlskog determinant due to Planck scale effects. ", "In order to ensure that our discussion is relevant to theoretical, we will restrict our considerations to neutrino mixing parameter due to Planck scale effects, which are not experimental. ", "Finally, we can wish one comment, if future experiment find the non zero value of CP phase so we can say there is small possible CP asymmetry due to Planck scale effects.", "\n\n[10]{} Supper-Kamiokande Collaboration, Y. Fukuda $et\\, al.", ",$Phys.", "Lett B **436**, 33, (1998).", "\n\nG. C. Branco, M.N Rebelo, Acta Phys.", "Polon.**B**38:3819-3850,2007.", "\n\nHiroshi Nunokawa, Stephen J. Parke, Jose W.F. Valle, Prog.", "Part.", "Nucl.", "Phys.**60**:338-402,2008.", "\n\nFrans R. Klinkhamer, Phys.", "Rev.**D**73:057301,2006.", "\n\nM.C. Gonzalez $et\\, al.", ",$Phys.", "Rev.**D**64:096006,2001\n\nZhi-zhong Xing, Phys.", "Lett.**B**487:327-333,2000.", "\n\nM. Kobayashi and T. Maskawa, Prog. ", "Theor. ", "Phys. ", "Rev. Lett. **", "45**, 652 (1973).", "\n\nV. Varger $et\\, al.", ",$Phys.", "Rev.Lett **45**, 2084 (1980).", "\n\nCHOOZ Collaboration, M. Apollonio, Phy. ", "Lett B **420**, 397 (1998).", "\n\nReview of Particle Physics, J. of Physics. **", "G** 33, 156 (2006).", "\n\nC. Jarlskog, Phys. ", "Rev. Lett.55, 1039 (1985).", "\n\nN. Cabibbo, Phys.", "Lett **B** 72,333 (1978).", "\n\nF. Vissani $et\\, al.", ",$Phys.", "Lett. ", "B571, 209, (2003).", "\n\nBipin Singh koranga, Mohan Narayan and S. Uma Sankar, arXiv:hep-ph/0607274,(Accepted in Phys.", "Lett **B**)\n\nBipin Singh koranga, Mohan Narayan and S. Uma Sankar, arXiv:hep-ph/0611186..\n\nBipin Singh koranga arXiv:0707.2045.", "\n\nBipin Singh koranga and S. Uma Sankar, arXiv:0704.1788\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Station Creek Cemetery\n\nStation Creek Cemetery is a heritage-listed cemetery at Normanton Road, Croydon, Shire of Croydon, Queensland, Australia. ", "It was opened . ", "It is also known as Golden Gate Cemetery. ", "It was added to the Queensland Heritage Register on 25 October 2002.", "\n\nHistory \nStation Creek cemetery is one of at least 10 cemeteries which served the Croydon area after it was declared a goldfield in 1886, although it is no longer in use. ", "It appears to have been gazetted as the Golden Gate cemetery in 1900 after a survey completed by Charles McGowan in 1899. ", "It comprises 1 hectare of land, south east of the Golden Gate town site, and east of the Croydon to Normanton railway line. ", "However, this cemetery is commonly known as the Station Creek cemetery, while an earlier burial ground west of the Croydon to Normanton railway line, adjacent to the Golden Gate township, is commonly known as the Golden Gate cemetery. ", "The Croydon goldfield was the last of the North Queensland gold rushes of the nineteenth century. ", "After a peak in gold production in 1900, mining declined over the next two decades. ", "There was a small revival during the 1930s Depression and again from 1988 to 1991 in the Tabletop and Golden Gate areas. ", "The present population of the district is approximately 300, and only the main Croydon Cemetery is still in use.", "\n\nCroydon is situated approximately west of Georgetown and south east of the port of Normanton on the Gulf of Carpentaria. ", "This area was first explored by Europeans in the 1860s. ", "John McKinlay searched for lost explorers Burke and Wills in 1862. ", "James Graham MacDonald explored a route from Carpentaria Downs to the Gulf in 1864. ", "H.E. Young investigated routes for an overland telegraph line between Cardwell and Normanton, which was built between 1869 and 1872, and later became a lifeline for the northern mining fields. ", "Pastoralists followed these early explorers, bringing sheep in 1865, but by 1867 many had retreated because of fever, drought, low wool prices and distance from markets\n\nGold was first discovered on Croydon Downs Station which had been taken up by W.C. Brown in 1881. ", "In the latter part of 1883, two of his employees James and Walter Alldridge found a leader of quartz carrying gold. ", "However it was not until 1885 that Richard and Walter Alldridge, acting under instructions from W.C. Brown, prospected the area and discovered twenty payable reefs. ", "The finds were reported in October 1885, and the Croydon area was proclaimed a goldfield on 18 January 1886, thus coming under administration of the Mines Department. ", "W.C. Brown and the Alldridge brothers shared a £1000 reward for the discovery, and the reward claim, Lady Mary, was taken up by 6 partners including W.C. Brown and Richard Alldridge.", "\n\nBy 1887, total population of the district had peaked at 7000, and by 1897 it still had the third highest population in north Queensland after Charters Towers and Townsville. ", "From 1890 to 1910, gold output from the Croydon reefs were second only to Charters Towers. ", "Total production from inception until 1947 was 772,374 ounces. ", "By 1909 however, production began to decline and by 1914, the population at the turn of the century had halved. ", "There was a small revival around Tabletop and Golden Gate between 1988 and 1991.", "\n\nResidents at Croydon goldfields faced many hardships from inadequate supplies of water, pasture grasses and timber for fuel and construction purposes. ", "Isolation was also a major problem until the Croydon to Normanton railway was completed in 1891. ", "The area was subject to droughts and floods, and even a cyclone in 1906. ", "Industrial action in 1888 resulted in the formation of a branch of the Amalgamated Miners' Association, and a strike occurred in 1889 when mining companies again tried to lower wages. ", "Some mines close to Croydon township failed around 1890 when the ore was cut by a wall of granite. ", "However rich discoveries at Golden Gate to the north west compensated a little for this. ", "A financial setback occurred in the \"crash\" of 1893, when most banks closed doors and gold buying ceased, throwing many miners out of work.", "\n\nAs on many other Queensland goldfields, Croydon had a Chinese community which developed on the north west fringe of the town. ", "The community constructed a temple, houses and other facilities such as pig ovens. ", "By the end of 1888 Mining Warden L.E.D. Towner reported that Croydon had a population of approximately 3500 of whom 300 were Chinese, Cingalese, Malays and African. ", "It appears that a shifting population of around 300 Asians was maintained. ", "This figure is surprising given that the Queensland Goldfields Amendment Act of 1878 excluded Chinese people from new fields for three years unless they had made the discovery. ", "However it appears that their involvement at Croydon was primarily as gardeners, carriers and cooks. ", "There was some racial tension at times. ", "A race riot occurred in 1886 when a Chinese residence was pulled down. ", "Also, in May 1888, William Hodgkinson, Minister for Mines, ejected all Chinese from the Croydon and Etheridge goldfields. ", "However, they were soon allowed to return because their market gardens were essential to the well-being of the community.", "\n\nDespite all difficulties, the 1890s were productive years for Croydon. ", "Pugh's Almanac of 1900 listed 3 banks, 6 blacksmiths, 5 bakers, 6 commission agents, 4 newsagents, 6 carriers, 2 chemists, 6 drapers, 11 sharebrokers, 4 newsagents, 18 hotels and 4 watchmakers, among many other assorted businesses. ", "Croydon became a municipality in 1892 under the control of the Croydon Divisional Board, and in 1907 administration was under the Croydon Shire Council.", "\n\nThe fields developed with Croydon as the main administrative and commercial centre surrounded by \"satellite\" communities established at outlying reefs. ", "Members of the outlying communities would visit Croydon on Saturday nights to shop, conduct their business and socialise. ", "There were townships at Golden Gate, Tabletop, Gorge Creek, Golden Valley, Goldstone, Carron, Twelve Mile, and campsites at Homeward Bound, Croydon King, Mark Twain, Lower Twelve Miles, Mulligan's, Flanagan's, Morning Light, Moonstone and Alluvial Springs. ", "This resulted in the establishment of at least 10 cemeteries throughout the district.", "\n\nThe township of Golden Gate was surveyed in December 1892 by W.A. Irwin, although there were buildings constructed well before this. ", "The survey was late in the history of the field considering that the first reward claim, Golden Gate PC, was taken up by Joseph Hardy and James Fulton on 12 April 1886. ", "However, yields from the Golden Gate fields were meagre until 1891, when a rich ore chute was discovered in Roger's No. ", "1 mine. ", "It went on to become the most productive field in the Croydon area. ", "By 1900, Golden Gate had a population of 600, 11 hotels, 8 stores, 3 churches and 3 butchers. ", "A school operated from 1896 to 1921, and a post office from 1891 to 1919. ", "Production declined during the years leading up to World War I, and the township virtually disappeared after the closure of Forsythe's Pioneer Mill in 1922.", "\n\nStation Creek cemetery appears to have been originally gazetted as the Golden Gate cemetery in 1900, after a survey completed by Charles McGowan in 1899. ", "Another and earlier burial ground commonly known as the \"Golden Gate Cemetery\" lies west of the Croydon to Normanton railway line adjacent to the Golden Gate township. ", "This earlier cemetery was never gazetted. ", "It was possibly in use until gazettal of the later cemetery at Station Creek. ", "Gordon Grimwade, who prepared a Conservation Plan for the Croydon cemeteries in January 2000, has recommended that this matter needs resolution by a \"location and ident\" survey.", "\n\nIt is not known why a new cemetery was gazetted for the area in a different location. ", "However the new site is midway between the Golden Gate group of mines and the Sunset group of mines, so it was possibly moved to facilitate common use by both of these communities.", "\n\nMines in the Golden Gate group included Golden Gate Nos 1 to 10, Golden Gate United, Golden Gate Consols, Tracey's Block, Morgan's Block, Rogers no. ", "1, and Plants Block, the deepest mine on the Croydon goldfields. ", "Mines in the Sunset group included True Blue, Content, Blue Peter, Sunset and Lady Isabelle.", "\n\nDescription \nStation Creek cemetery covers 1 hectare of land, north west of Croydon on the north east side of the Normanton Road, and south east of the Golden Gate town site. ", "The site is just west of Belmore Creek.", "\n\nThere are two clearly marked graves, although evidence of a further 34 has been noted. ", "One of the marked graves is that of a young girl, Charlotte Brown. ", "This grave is marked by a metal railing with higher rails towards the head.", "\n\nThe cemetery is bounded by natural vegetation and a Department of Main Roads gravel stockpile on the eastern boundary. ", "Access is from the Normanton Road about west of the Belmore Creek bridge crossing. ", "There is minor difficulty with access due to construction of the Belmore Creek bridge which has substantial side drains to the approaches. ", "A roughly defined track crosses a drainage gully on the north side of the road. ", "The track terminates near the corner of a post and wire fence which encloses the present cemetery boundary. ", "The fence was recently constructed and may not reflect the original boundary. ", "A single gate provides entry.", "\n\nThe terrain is gently sloping with fine grained, sandy soil. ", "Vegetation is predominantly natural although introduced weed species have been noted. ", "Eucalypts and other endemic tree species are scattered through the site. ", "Tussocky native grasses provide a dense cover during most of the year. ", "Native birds and animals utilise this habitat.", "\n\nHeritage listing \nStation Creek Cemetery was listed on the Queensland Heritage Register on 25 October 2002 having satisfied the following criteria.", "\n\nThe place is important in demonstrating the evolution or pattern of Queensland's history.", "\n\nThe Station Creek Cemetery, first surveyed in 1899, reflects the early development of the region. ", "The cemetery is an important record of the cultural development of the area, showing the ethnicity, occupations and social status of the inhabitants of early Croydon since settlement.", "\n\nThe place has potential to yield information that will contribute to an understanding of Queensland's history.", "\n\nThe cemetery has the potential to yield information in regards to the early history of the inhabitants of Croydon, their ethnic, social and religious backgrounds and standing within the community.", "\n\nThe place has a strong or special association with a particular community or cultural group for social, cultural or spiritual reasons.", "\n\nThe cemetery is significant for its high spiritual and symbolic value to the community because of the burials that took place there and the evidence of hardship experienced by the first inhabitants of Croydon.", "\n\nReferences\n\nAttribution\n\nExternal links \n\nCategory:Queensland Heritage Register\nCategory:Croydon, Queensland\nCategory:Cemeteries in Queensland\nCategory:Articles incorporating text from the Queensland Heritage Register" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "<?", "php\n/**\n * CodeIgniter\n *\n * An open source application development framework for PHP\n *\n * This content is released under the MIT License (MIT)\n *\n * Copyright (c) 2014 - 2017, British Columbia Institute of Technology\n *\n * Permission is hereby granted, free of charge, to any person obtaining a copy\n * of this software and associated documentation files (the \"Software\"), to deal\n * in the Software without restriction, including without limitation the rights\n * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell\n * copies of the Software, and to permit persons to whom the Software is\n * furnished to do so, subject to the following conditions:\n *\n * The above copyright notice and this permission notice shall be included in\n * all copies or substantial portions of the Software.", "\n *\n * THE SOFTWARE IS PROVIDED \"AS IS\", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR\n * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,\n * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. ", "IN NO EVENT SHALL THE\n * AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER\n * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,\n * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN\n * THE SOFTWARE.", "\n *\n * @package\tCodeIgniter\n * @author\tEllisLab Dev Team\n * @copyright\tCopyright (c) 2008 - 2014, EllisLab, Inc. (https://ellislab.com/)\n * @copyright\tCopyright (c) 2014 - 2017, British Columbia Institute of Technology (http://bcit.ca/)\n * @license\thttp://opensource.org/licenses/MIT\tMIT License\n * @link\thttps://codeigniter.com\n * @since\tVersion 1.0.0\n * @filesource\n */\ndefined('BASEPATH') OR exit('No direct script access allowed');\n\n/**\n * CodeIgniter Driver Library Class\n *\n * This class enables you to create \"Driver\" libraries that add runtime ability\n * to extend the capabilities of a class via additional driver objects\n *\n * @package\t\tCodeIgniter\n * @subpackage\tLibraries\n * @category\tLibraries\n * @author\t\tEllisLab Dev Team\n * @link\n */\nclass CI_Driver_Library {\n\n\t/**\n\t * Array of drivers that are available to use with the driver class\n\t *\n\t * @var array\n\t */\n\tprotected $valid_drivers = array();\n\n\t/**\n\t * Name of the current class - usually the driver class\n\t *\n\t * @var string\n\t */\n\tprotected $lib_name;\n\n\t/**\n\t * Get magic method\n\t *\n\t * The first time a child is used it won't exist, so we instantiate it\n\t * subsequents calls will go straight to the proper child.", "\n\t *\n\t * @param\tstring\tChild class name\n\t * @return\tobject\tChild class\n\t */\n\tpublic function __get($child)\n\t{\n\t\t// Try to load the driver\n\t\treturn $this->load_driver($child);\n\t}\n\n\t/**\n\t * Load driver\n\t *\n\t * Separate load_driver call to support explicit driver load by library or user\n\t *\n\t * @param\tstring\tDriver name (w/o parent prefix)\n\t * @return\tobject\tChild class\n\t */\n\tpublic function load_driver($child)\n\t{\n\t\t// Get CodeIgniter instance and subclass prefix\n\t\t$prefix = config_item('subclass_prefix');\n\n\t\tif ( ! 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", "$found)\n\t\t{\n\t\t\t// Check for subclass file\n\t\t\tforeach ($paths as $path)\n\t\t\t{\n\t\t\t\t// Does the file exist?", "\n\t\t\t\t$file = $path.", "'libraries/'.$this->lib_name.", "'/drivers/'.$prefix.$child_name.", "'.php';\n\t\t\t\tif (file_exists($file))\n\t\t\t\t{\n\t\t\t\t\t// Yes - require base class from BASEPATH\n\t\t\t\t\t$basepath = BASEPATH.'libraries/'.$this->lib_name.", "'/drivers/'.$child_name.", "'.php';\n\t\t\t\t\tif ( ! ", "file_exists($basepath))\n\t\t\t\t\t{\n\t\t\t\t\t\t$msg = 'Unable to load the requested class: CI_'.$child_name;\n\t\t\t\t\t\tlog_message('error', $msg);\n\t\t\t\t\t\tshow_error($msg);\n\t\t\t\t\t}\n\n\t\t\t\t\t// Include both sources and mark found\n\t\t\t\t\tinclude_once($basepath);\n\t\t\t\t\tinclude_once($file);\n\t\t\t\t\t$found = TRUE;\n\t\t\t\t\tbreak;\n\t\t\t\t}\n\t\t\t}\n\t\t}\n\n\t\t// Do we need to search for the class?", "\n\t\tif ( ! 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", "class_exists($class_name, FALSE))\n\t\t{\n\t\t\tif (class_exists($child_name, FALSE))\n\t\t\t{\n\t\t\t\t$class_name = $child_name;\n\t\t\t}\n\t\t\telse\n\t\t\t{\n\t\t\t\t$msg = 'Unable to load the requested driver: '.$class_name;\n\t\t\t\tlog_message('error', $msg);\n\t\t\t\tshow_error($msg);\n\t\t\t}\n\t\t}\n\n\t\t// Instantiate, decorate and add child\n\t\t$obj = new $class_name();\n\t\t$obj->decorate($this);\n\t\t$this->$child = $obj;\n\t\treturn $this->$child;\n\t}\n\n}\n\n// --------------------------------------------------------------------------\n\n/**\n * CodeIgniter Driver Class\n *\n * This class enables you to create drivers for a Library based on the Driver Library.", "\n * It handles the drivers' access to the parent library\n *\n * @package\t\tCodeIgniter\n * @subpackage\tLibraries\n * @category\tLibraries\n * @author\t\tEllisLab Dev Team\n * @link\n */\nclass CI_Driver {\n\n\t/**\n\t * Instance of the parent class\n\t *\n\t * @var object\n\t */\n\tprotected $_parent;\n\n\t/**\n\t * List of methods in the parent class\n\t *\n\t * @var array\n\t */\n\tprotected $_methods = array();\n\n\t/**\n\t * List of properties in the parent class\n\t *\n\t * @var array\n\t */\n\tprotected $_properties = array();\n\n\t/**\n\t * Array of methods and properties for the parent class(es)\n\t *\n\t * @static\n\t * @var\tarray\n\t */\n\tprotected static $_reflections = array();\n\n\t/**\n\t * Decorate\n\t *\n\t * Decorates the child with the parent driver lib's methods and properties\n\t *\n\t * @param\tobject\n\t * @return\tvoid\n\t */\n\tpublic function decorate($parent)\n\t{\n\t\t$this->_parent = $parent;\n\n\t\t// Lock down attributes to what is defined in the class\n\t\t// and speed up references in magic methods\n\n\t\t$class_name = get_class($parent);\n\n\t\tif ( ! ", "isset(self::$_reflections[$class_name]))\n\t\t{\n\t\t\t$r = new ReflectionObject($parent);\n\n\t\t\tforeach ($r->getMethods() as $method)\n\t\t\t{\n\t\t\t\tif ($method->isPublic())\n\t\t\t\t{\n\t\t\t\t\t$this->_methods[] = $method->getName();\n\t\t\t\t}\n\t\t\t}\n\n\t\t\tforeach ($r->getProperties() as $prop)\n\t\t\t{\n\t\t\t\tif ($prop->isPublic())\n\t\t\t\t{\n\t\t\t\t\t$this->_properties[] = $prop->getName();\n\t\t\t\t}\n\t\t\t}\n\n\t\t\tself::$_reflections[$class_name] = array($this->_methods, $this->_properties);\n\t\t}\n\t\telse\n\t\t{\n\t\t\tlist($this->_methods, $this->_properties) = self::$_reflections[$class_name];\n\t\t}\n\t}\n\n\t// --------------------------------------------------------------------\n\n\t/**\n\t * __call magic method\n\t *\n\t * Handles access to the parent driver library's methods\n\t *\n\t * @param\tstring\n\t * @param\tarray\n\t * @return\tmixed\n\t */\n\tpublic function __call($method, $args = array())\n\t{\n\t\tif (in_array($method, $this->_methods))\n\t\t{\n\t\t\treturn call_user_func_array(array($this->_parent, $method), $args);\n\t\t}\n\n\t\tthrow new BadMethodCallException('No such method: '.$method.'()');", "\n\t}\n\n\t// --------------------------------------------------------------------\n\n\t/**\n\t * __get magic method\n\t *\n\t * Handles reading of the parent driver library's properties\n\t *\n\t * @param\tstring\n\t * @return\tmixed\n\t */\n\tpublic function __get($var)\n\t{\n\t\tif (in_array($var, $this->_properties))\n\t\t{\n\t\t\treturn $this->_parent->$var;\n\t\t}\n\t}\n\n\t// --------------------------------------------------------------------\n\n\t/**\n\t * __set magic method\n\t *\n\t * Handles writing to the parent driver library's properties\n\t *\n\t * @param\tstring\n\t * @param\tarray\n\t * @return\tmixed\n\t */\n\tpublic function __set($var, $val)\n\t{\n\t\tif (in_array($var, $this->_properties))\n\t\t{\n\t\t\t$this->_parent->$var = $val;\n\t\t}\n\t}\n\n}\n" ]

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[ "# Translation of Odoo Server.", "\n# This file contains the translation of the following modules:\n# \t* purchase_mrp\n# \n# Translators:\n# Martin Trigaux, 2019\n# \nmsgid \"\"\nmsgstr \"\"\n\"Project-Id-Version: Odoo Server saas~12.4\\n\"\n\"Report-Msgid-Bugs-To: \\n\"\n\"POT-Creation-Date: 2019-08-12 11:32+0000\\n\"\n\"PO-Revision-Date: 2019-08-26 09:13+0000\\n\"\n\"Last-Translator: Martin Trigaux, 2019\\n\"\n\"Language-Team: Dutch (https://www.transifex.com/odoo/teams/41243/nl/)\\n\"\n\"MIME-Version: 1.0\\n\"\n\"Content-Type: text/plain; charset=UTF-8\\n\"\n\"Content-Transfer-Encoding: \\n\"\n\"Language: nl\\n\"\n\"Plural-Forms: nplurals=2; plural=(n !", "= 1);\\n\"\n\n#. ", "module: purchase_mrp\n#: model:ir.model,name:purchase_mrp.model_mrp_production\nmsgid \"Production Order\"\nmsgstr \"Productieorder\"\n\n#. ", "module: purchase_mrp\n#: model:ir.model,name:purchase_mrp.model_purchase_order_line\nmsgid \"Purchase Order Line\"\nmsgstr \"Inkooporderregel\"\n\n#. ", "module: purchase_mrp\n#: model:ir.model,name:purchase_mrp.model_stock_move\nmsgid \"Stock Move\"\nmsgstr \"Voorraadmutatie\"\n" ]

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[ "It was the bride and groom’s wedding gift to each other — murder.", "\n\nTwo Pennsylvania newlyweds used a Craigslist escort ad to lure a married engineer to his bloody doom — just for the excitement of stabbing and strangling him, authorities charge.", "\n\nAfter the random killing, the couple allegedly celebrated at a Harrisburg strip club.", "\n\nIt was their dream to murder someone together — and it may not have been the first criminal caper for Elytte and Miranda Barbour, say cops in the sleepy town of Sunbury, some 150 miles northwest of Philadelphia.", "\n\n“This is the worst murder I’ve seen,” said Sunbury Police Chief Steve Mazzeo, who has headed the local force for six years.", "\n\nVictim Troy LaFerrara was stabbed some 20 times behind a garage, cops say.", "\n\n“The death may have circumstances that will lead the investigation of the Barbours to other states,” Mazzeo added.", "\n\nThe 18-year-old brunette bride has an 18-month-old daughter and works as an escort, according to her husband. ", "The groom, 22, is a dishwasher. ", "Both are from central North Carolina.", "\n\nThey had been married only three weeks when LaFerrara answered Miranda’s ad offering “companionship” for a price.", "\n\nPolice and court records say he agreed to meet Miranda at the Susquehanna Valley Mall at around 6:30 p.m. on Nov. 11.", "\n\n“Alright, I’m pretty close to the mall,” she allegedly texted the man, a more-than-250-pound environmental engineer whose wife, Colleen, was soon to be a widow.", "\n\n“Good,” LaFerrara answered.", "\n\n“I’m dropping my daughter off right now, then I’ll be at the mall in about 15,” Miranda answered, according to court records.", "\n\nWhen LaFerrara climbed into Miranda’s red Honda SUV, Elytte was allegedly hiding in the back seat — under a blanket.", "\n\nHere’s where the accounts of LaFerrara’s final moments ­diverge.", "\n\nMiranda has told cops that as she drove, the engineer “began groping her,” according to the criminal complaint.", "\n\n“She related he was touching her private areas and had his hand around her throat,” the complaint says.", "\n\nMiranda went for the knife “and started stabbing the victim,” the complaint continues.", "\n\n“She related [that] the first two or three times she stabbed him there wasn’t any reaction. ", "She then started blacking out and didn’t remember the rest of the time she was stabbing him.”", "\n\nBut cops say it was Elytte who struck first, pouncing from ­beneath the blanket and snapping a belt around LaFerrara’s neck so his wife could more easily swing her knife.", "\n\nThe engineer was “choking and gasping for air” as she drove around, looking for a secluded spot to dump the body and clean her car, Miranda allegedly told cops in a confession.", "\n\n“There was a lot of blood,” she allegedly said.", "\n\n“She then returned to her residence,” her confession continues, “where she and her husband departed for Harrisburg to celebrate his birthday” at a strip joint in the city.", "\n\nElytte was more forthcoming, telling investigators “that they committed the murder because they just wanted to murder someone together,” according to his own police affidavit.", "\n\nHe and Miranda had planned to kill before, but it just never worked out — until LaFerrara came along, he explained.", "\n\nAfter his wife’s arrest, but prior to his own, Elytte told The Daily Item of Sunbury that Miranda, whom he married on Oct. 22, regularly hired herself out as a “companion” to men she found online.", "\n\nElytte said his wife was paid $50 to $850 for meeting with men for such activities as dinner together or walks around a mall.", "\n\n“She is not a prostitute,” he said. “", "What she does is meet men who have broken marriages or have no one in their lives, and she meets with them and has delightful conversation.”", "\n\nLaFerrara, too, was a frequenter of strip joints, the paper reported. “", "He was just a big goofball,” one dancer told the paper." ]

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[ "Ankara refutes UN report claiming Turkey route for arms to al-Qaeda\n\nANKARA\n\nISIL militants (Rear) stand next to an ISIL flag atop a hill near Kobane as seen from the Turkish-Syrian border, with Turkish troops in foreground, in the southeastern town of Suruç, Şanlıurfa province. ", "AFP Photo / Aris Messinis\n\nTurkish Foreign Ministry refuted a United Nations report claiming that Turkey is being used as one of the primary routes for weapons smuggling to the Islamic State of Iraq and the Levant (ISIL) and al-Nusra.", "“Unfounded claims,” the ministry spokesperson Tanju Bilgiç told reporters on Dec. 30, elaborating on a report penned by the U.N. al-Qaida Sanctions Committee.", "Most of the weapons that are seized by the jihadist groups are from armies of Iraq and Syria and origins of those arms are members of the UN Security Council, he noted.", "“Most [arms] supplies have either been seized from the armed forces of Iraq or (to a lesser extent) the Syrian Arab Republic, or have been smuggled to ISIL and [al-Nusra], primarily by routes that run through Turkey,” said the report which was prepared by Analytical Support and Sanctions Monitoring Team to be presented to UN Security Council.", "“The arms and ammunition come from stored materials that date back to the 1980s and 1990s, along with more recent supplies,” the report dated to Nov. 14 has said.", "The foreign ministry official reaffirmed that al-Nusra and Islamic State of Iraq and the Levant (ISIL) have been designated as terrorists groups by Turkey. ", "Ankara has been “adamantly” fighting against the jihadist group and Turkey is part of anti-ISIL coalition.", "“Turkey is not merely fighting against the terrorist groups, but also in cooperation with international organizations especially with UN Analytic Support Group,” he said.", "Bilgiç noted that the group members visited Turkey in September and did not elaborate on “smuggling of arms”, though struggle with the ISIL was widely discussed during the visit.", "“Therefore, this allegation is new to us,” the spokesperson said noting that Turkey has asked the UN for an “explanation and strongly reacted as well.", "”Moreover, the United Nations Assistance Mission for Iraq (UNAMI) officials in Iraq has conveyed Turkey’s Embassy in Baghdad that they did not have any relevant data on the claims, Bilgiç said.", "The UNAMI officials also expressed unease over Analytical Support and Sanctions Monitoring Team’s reference to them for the claims, he noted.", "“We asked the UN officials on which grounds they raised those allegations,” the spokesperson stated.", "Turkey has been pressured by Western countries to beef up its measures at borders, which have been claimed to be a primary route for jihadists’ oil and weapons smuggling as well as foreign jihadists’ joining the war in Syria.", "Turkey, for its part, denies the accusations of negligence in its border policies and insists that it is maintaining a close and firm watch on its borders." ]

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[ "Residential Projects\n\nResidential customers have been and will continue to be the lifeblood of ADF Flooring. ", "Commercial projects are challenging and rewarding but Residential work is fulfilling to our staff as we watch our customers beam with happiness when their floors are completed. ", "It never gets old!", "\n\nWhether we are installing vinyl flooring, hard wood flooring, carpeting, laminate flooring or tile the smiles and joy that our customers experience is awesome. ", "The process of working with you is very straight forward and we make it as easy as possible for you. ", "One of our design consultants will work with you and discuss exactly what you are looking for.", "\n\nGive us a call at (603) 856-8040 and let us sit with you and discuss your needs!" ]

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[ "Q:\n\nHow to check if an alert is open using nodejs webdriver (wd)\n\nI am struggling writing a test; in which I want to check if an alert exists, check its text if it does and accept it.", "\nI checked How to wait for an alert in Selenium webdriver ?, ", "How to check if an alert exists using WebDriver? ", "and selenium 2.4.0, how to check for presence of an alert, but I fail to adapt it using https://github.com/admc/wd\nI have written something along\nbrowser.alertText(function (err, text) {\n if (text) {\n browser.acceptAlert(function () {\n // ...\n });\n }\n});\n\nIt works tremendously well when an alert is displayed, but alertText hangs when there is no alert window.", "\nHow can I check if the alert exists before issuing alertText?", "\nThanks for your help,\n\nA:\n\nThis may help - this is how I detect an alert using Selenium Webdriver for node.js:\nvar webdriver = require('selenium-webdriver');\n\nvar url = \"http://web-page-to-test-for-alert\";\n\ndriver = new webdriver.", "Builder().", "\n withCapabilities(webdriver.", "Capabilities.chrome()).", "\n build();\n\ndriver.get(url);\n\ndriver.switchTo().alert().then(\n function() {\n console.log(\"alert detected\");\n },\n function() {\n console.log(\"no alert detected\");\n }\n);\n\ndriver.quit(); \n\n'then' is related to promises: then(success, failure)\nand this may also help - it's how I ignore any alert that presents on a page:\nfunction ignoreAlert(driver) {\n // detect and accept any alert\n driver.switchTo().alert().then(function() {\n driver.switchTo().alert().accept();}, \n function(){});\n}\n\n" ]

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[ "PAUL McCartney has been named as a surprising addition to the cast of one of Hollywood’s most successful movie franchises.", "\n\nThe Sun reports that the former Beatle, 73, will star alongside Johnny Depp\n\nin the fifth instalment of the hit franchise, titled Dead Men Tell No Tales.", "\n\nFilm bosses are keeping his part a closely-guarded secret.", "\n\nBut insiders claim a huge set is being built around the singer, indicating the part is more than a cameo.", "\n\nIt is believed McCartney’s close friendship with Depp, who plays Captain Jack Sparrow, led to his involvement.", "\n\nA source close to the music legend said: “Macca’s a huge fan of the Pirates of the Caribbean movies and couldn’t turn down the chance to be involved.”", "\n\nDepp, 52, starred in Sir Paul’s video for his 2013 single Queenie Eye.", "\n\nRolling Stone Keith Richards, 72, played Sparrow’s dad in Pirates No 4, On Stranger Tides in 2011.", "\n\nMcCartney has tended to play himself in the past, including in A Hard Day’s Night and Help! ", "The movie Dead Men Tell No Tales is out next year.", "\n\nThis story originally appeared in The Sun" ]

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[ "[Blunted sleep-related blood pressure decline in diabetic patients].", "\nSleep-associated blood pressure decline (dipping) is decreased in diabetic patients. ", "The cause of this circadian abnormality is probably related to microvascular diabetic complications and the accompanying latent volume overload. ", "The blunting of blood pressure dipping is not a benign phenomenon, as exemplified by its link with augmented left ventricular mass. ", "Thus, blood pressure non-dipping may explain the increased incidence of left ventricular hypertrophy found in diabetic patients, irrespective of office blood pressure." ]

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[ "Q:\n\nWhy XML literals yield mutable objects in Scala?", "\n\nWhen declaring a node sequence in Scala as literals you yield a scala.xml.", "NodeBuffer which is mutable (it extends ArrayBuffer[scala.xml.", "Node] which in turn extends Seq[scala.xml.", "Node]):\nscala> val xml = <a /><b />\nxml: scala.xml.", "NodeBuffer = ArrayBuffer(<a></a>, <b></b>)\n\nscala> xml += <c />\nres46: xml.type = ArrayBuffer(<a></a>, <b></b>, <c></c>)\n\nscala> xml\nres47: scala.xml.", "NodeBuffer = ArrayBuffer(<a></a>, <b></b>, <c></c>)\n\nThis contradicts Scala's philosophy of using immutable objects and functional programming. ", "Why collections are immutable by default, but XML literals (which are first class citizens) are not in this case?", "\nHowever, is it possible to safely define an immutable node sequence by using XML literals?", "\n\nA:\n\nIt seems that immutable XML literals require a single root node (as does XML). ", "scala.xml.", "Group allows you to do this, using a \"pacifier\" root node of <xml:group />.", "\nThis is eloquently described in the API docs as \"A hack to group XML nodes in one node for output.\"", "\nscala> val xml = <xml:group><a /><b /></xml:group>\nxml: scala.xml.", "Group = <a></a><b></b>\n\nWhen you combine this fragment with other XML, the group node disappears:\nscala> <foo>{xml}</foo>\nres1: scala.xml.", "Elem = <foo><a></a><b></b></foo>\n\n" ]

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[ "Effective SEO Service\n\nSearch Engine Optimization is a process of increasing the visibility of your web page thorough organic or natural listing on search engine. ", "SEO is a planned strategy towards an organized implementation for accomplishing top and the best rankings in major Search engines like Google, Yahoo! ", "Search and Bing.", "\nIf you want your business to grow, sales to reach a new height, service to reach more and more people SEO is a must for you! ", "If you still think you doesn't need it, think again! ", "because 85% of the site traffic comes from search engines, so you can imagine how helpful it can be if you are placed in top search engine ranking, how much more beneficial it can be for your business, whether you are a big or a small business you need a good Search Engine Optimization strategy for your business, It can actually boost your bottom line.", "\nTo achieve a top ranking on search engines, a natural search engine optimization company needs to have a good knowledge of how search engine algorithms work and the keywords potential customers would search for in relation to an industry.", "\nWe have a widespread approach to search engine optimization which will help you develop and implement powerful and unbeaten SEO strategies to empower your online business prospective.", "\n\nHow Search Engine Optimization can be achieved:\n\nIt is not a one-time event or an instant gratification. ", "SEO requires a long-term outlook and commitment. ", "Search engine algorithms change regularly, so a related methods and tactics of SEO is needed.", "\nIt can be achieved by using certain services like keyword and competitive analysis with On page and Off page optimization factors.", "\n\nOn Page Optimization\n\nOn Page Optimization is one of the very important part of the Search Engine Optimization process. ", "On Page Optimization includes everything that the search engine finds on your page while visiting your page.", "\n\nTo achieve good page rank its important to:\n1) Make a user-friendly website. ", "Create great and unique content.", "\n2) Use a unique and relevant title and meta description on every page.", "\n\nOff Page Optimization\n\nOff Page Optimization is also a crucial part of the Search Engine Optimization process which involves using off-site factors to improve search engine page rank and increase the targeted visitor traffic to the website. ", "Off Page Optimization is critical to the long term authority of your website and combines with your on page optimization to establish a long term presence for the target keywords." ]

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[ "\nHow I Became a Knife Steel Metallurgist - AceyMan\nhttps://knifesteelnerds.com/2018/10/08/how-i-became-a-knife-steel-metallurgist/\n======\ncolinsidoti\nI love content like this. ", "I've found my knowledge becomes more specialized as\nI age, and content like this gives me an opportunity to grok other\nspecialities with relative ease.", "\n\nFor whatever reason (I'm a software engineer), I particularly enjoy content\nabout everyday physical goods. ", "Knife steel has just been added to my bookmark\nlist, but here are a couple more I think are worth sharing:\n\nMaking the ideal wool fabric for outerwear:\n[https://weatherwool.com/pages/the-weatherwool-\ndifference](https://weatherwool.com/pages/the-weatherwool-difference)\n\nChoosing the ideal card-holding material for leather wallets:\n[https://ashlandleather.com/blogs/inside-ashland/johnny-\nthe-f...](https://ashlandleather.com/blogs/inside-ashland/johnny-the-fox-\ninterior-leather-options)\n\nThe grades and quality of Panama Hats: [https://www.brentblack.com/panama-hat-\ngrades-explained.html](https://www.brentblack.com/panama-hat-grades-\nexplained.html)\n\n~~~\nkfk\nCould we stop calling it content and refer to it as “writing”?", "\n\n~~~\ndasil003\nI don't think that genie is going back in the bottle.", "\n\n------\nCPLX\nThis was really interesting. ", "It’s also the first time I’ve ever read anything\ndetailed about what kind of people go to Mines. ", "As a CC student we were always\nslightly in awe of this other strange and very small and unknown but highly\nregarded school, full of people studying rocks or something, on the other side\nof the hills. ", "Still underrated 25 years later it seems.", "\n\nIt’s also a great article that reminds me of what I actually like so much\nabout the internet. ", "A guy, who’s passions are almost incomprehensible to me in\nsome ways, who has this incredibly specialized knowledge that he wants to\nshare with the world. ", "So he makes a website and shares it. ", "And if I ever want\nto get deep into this topic there it is.", "\n\nIn the age of clickbait and awful social media it’s useful to remember why we\nwere excited about the thing in the first place. ", "I literally have no\ndemonstrated interest in knife steel but I still want to sign up for this\nguy’s Patreon just because I’m glad people like him exist.", "\n\n~~~\nribs\nHeh...I was excited when he mentioned the school. ", "I’m an amateur geologist and\nhave considered it with reverence for some time now. ", "Great mineral museum, if\nyou’re into that kind of thing.", "\n\n~~~\ntnorthcutt\n+1, really great museum with loads of samples (is that the right word?) ", "of\nmore minerals than you knew existed.", "\n\n------\nAceyMan\nI enjoyed this bio post by the site maintainer because it's demonstrative how\na person with seemingly few resources can take a meandering path to\nsignificant accomplishment and status (PhD). ", "Larrin's education arc mirrors\nmuch of the HN crowd mantra of late wrt the value of experience, degrees,\nelite schools, etc. ", "It's just a nice case study on all those fronts (and a\nnifty website, to boot).", "\n\n/Acey\n\n------\naxaxs\nThis is very fascinating, and I wish there were more resources or channels\navailable to here directly from scientists such as this. ", "Even the automotive\nsheetmetal advancements would be interesting to me, though no details given\nunfortunately.", "\n\nAs an aside, it is probably pretty hard being a metallurgist on the internet.", "\nThere are so many people who parrot blatantly wrong info, and present\nthemselves as authorities while having essentially zero training. ", "I learned\nthis the hard way by attempting to google comparisons of knife steels in\nparticular, only to realize nearly every single resource gave different\nanswers.", "\n\nAdditionally, I remember one very long thread in a gun debate, where several\nof these authorities were badmouthing Ruger for using cast vs forged parts,\nand how that seemed accepted as fact. ", "One person took the time to write to a\nmetallurgist at Ruger, who succinctly stated there was no inherent weakness to\nproperly cast steel, and that their formulas are designed to exceed\nperformance of plain forged steel(im leaving a lot of details out as im\nworking from memory). ", "It was a bit eye opening to me to realize these people\nwho work behind the scenes existed, but at the same time how frustrating it\nmust be to constantly be told you're wrong due to the nature of what you do.", "\nLuckily in CS we don't have quite the same issue. ", "Sure people get things\nincorrect, but the barrier to entry is higher(using a computer and the\ninternet vs using steel), and such a large amount of tech savvy people and CS\nprofressionals exist that these are often cleared up or refuted. ", "Metallurgists\nand other specialists don't have such a network to rely on.", "\n\n~~~\ndsfyu404ed\nIn the OEM part of the automotive world there's all sorts of dynamically\nadjusted shocks, sway bars, etc, etc. ", "None of that has made it into even the\nhighest levels (most $$$) of off road racing (where it would be very useful)\nor normal racing (where it would still be useful, but far less so) yet.", "\n\nMost recent tech is still under NDA and the people that do this stuff as their\nday job don't post on hobbyist boards and doing your own testing is\nprohibitively resource intensive compared to computer stuff. ", "That's why you\ndon't hear about recent tech until it's old. ", "If you keep up to date on\nacademic papers and industry press releases you can kind of get a fuzzy\npicture of what's going on.", "\n\n~~~\njusttopost\nThe truth isnt so simple.", "\n\nElectrically adjustible shocks were all over race cars in the late 80s to mid\n90s. ", "Sometime around the late 90s, we realized a good static setup is easier\nto setup, more reliable, cheaper and better understood in most cases. ", "While\nsome sports like drag racing still ocasionally use the tech (due to differing\nforces during launch vs run). ", "Aditionally, the bose system, in development\nsince the 80s, never really materialized in useable form, despite some neat\ndemos.", "\n\nTrue, most roadracing leagues ban it as 'active', and being outside the spirit\nof the race. ", "This was due to it potentially becoming an arms race of whose\nsponsor has the deeper pockets.", "\n\nI do wish there were still a few 'unlimited' style races. ", "Outside some hill-\nclimb racing it seems most innovation is explicitly forbidden. ", "Nascar has no\nrelation to stock cars, f1 are not as fun to watch and have become a bizarre\nweird sidenote, e-racing is finally coming of age, but regulations are making\nfor some monotonous designs.", "\n\nI am sure there would be some interest in a no-holds barred race. ", "Hell, there\nneeds be no rule that the craft even needs to touch the ground (or not be\nsucked down to it). ", "Lets open our collective transportation imagination...\n\n~~~\nggreer\n> I am sure there would be some interest in a no-holds barred race. ", "Hell,\n> there needs be no rule that the craft even needs to touch the ground (or not\n> be sucked down to it). ", "Lets open our collective transportation\n> imagination...\n\nI'd love to see this as well. ", "I think you'd end up with an interesting racing\nleague if you had the following rules:\n\n1\\. There are speed bumps at the entrance and exit of pit row. (", "This is to\nprevent designs that could never work on regular surface streets, such as side\nskirts for ground effect.)", "\n\n2\\. Losing teams can buy the winning vehicle for $100,000. (", "This is\neffectively a budget cap to prevent the best funded teams from dominating.)", "\n\nYou'd probably end up with all kinds of crazy designs: active aerodynamics, 6\nwheeled vehicles[1]… maybe even gas turbine electric drivetrains. ", "I'd\ndefinitely tune in.", "\n\n1\\.\n[https://en.wikipedia.org/wiki/Tyrrell_P34](https://en.wikipedia.org/wiki/Tyrrell_P34)\n\n------\ncreddit\nBoy did I enjoy that! ", "Beyond the enjoyable tale of his love of steel and how\nit has influenced his life, reading between the lines you can see just how\nbeing from certain backgrounds can really make a path like this challenging.", "\nHe had challenges from both an upbringing perspective (didn't know what the\nGRE was, sort of randomly chose colleges initially, etc.) ", "as well as from an\neducation perspective (the challenges of smaller/weaker schools, the value of\ngood teachers such as Mr. Bowler also see [http://www.equality-of-\nopportunity.org/assets/documents/teac...](http://www.equality-of-\nopportunity.org/assets/documents/teachers_wp.pdf))\n\n------\ntomrod\nThis is beautiful. ", "The passion that drives him to differentiate, rooted in his\npast and in his daydreams. ", "I recognize he succeeded where many in a similar\nsituation would have failed (myself included). ", "Kudos.", "\n\n------\n_emacsomancer_\nBlade steel and its study is really fascinating to me, though not at all\nrelated to my professional work. ", "But I became fascinated a couple of decades\nago by the manufacture of khukuris[1] in Nepal, which are often made of\nsalvaged leaf springs from German-made lorries. (", "Well, I end up working the\nNepali language professionally, if not khukuris.)", "\n\n[1] [https://en.wikipedia.org/wiki/Kukri](https://en.wikipedia.org/wiki/Kukri)\n\n------\nnoisy_boy\nIt was so satisfying to read about somebody's extremely specific passion which\nI can never understand but totally relate to. ", "I genuinely feel happy for the\nauthor and wish that he go on to do greater things in pursuit of his passion.", "\n\n------\nJenz\nI can’t stress how much my math teacher’s passion had to say about my math\nunderstanding.", "\n\n------\naasasd\nFinally someone who has actually studied the blade.", "\n\n------\ncodr4\nI've been practicing Ving Tsun for around 25 years. ", "Many aren't aware, but the\nmost of the system is based on blades. ", "The issue I've been having is finding\ngood enough knives to train with. ", "Most of the stuff out there is ornamental\ncrap that will teach you the wrong thing best case and break and hurt someone\nif you're unlucky. ", "I ended up getting two big, well balanced hunting knives\nthat I've blunted for training.", "\n\nI'm pretty sure I'll end up making my own sooner or later...\n\n------\nDrNuke\nTake a bow, Dr Knife Steel: inspirational, blessed and down-to-earth. ", "My\ncomparable obsession with austenitic steels has now gone fully virtual thanks\nto materials informatics.", "\n\n~~~\nAYBABTME\nAny pointers? ", "I have casually explored material sciences on Coursera, and I'm\nalways interested in computer-aided fields. ", "But I had never heard of material\ninformatics. ", "Is there anything CAD-like for the field?", "\n\n~~~\nDrNuke\nGeorgia Tech courses there are a nice intro\n[https://www.coursera.org/gatech](https://www.coursera.org/gatech) ... in\nparticular the one by Prof Kalidindi for materials informatics once you are\nfamiliar with the general, underlying physics\n[https://www.coursera.org/learn/material-\ninformatics](https://www.coursera.org/learn/material-informatics) and then\nthis for high-throughput experiments if you have your own lab\n[https://www.coursera.org/learn/high-\nthroughput](https://www.coursera.org/learn/high-throughput)\n\n------\ndm8\nThat was a great read. ", "I really admire people having passion as well as\nexpertise in these unique fields. ", "Once fortune 500 CEO had come to my school\nfor talk and he told us shortest path to rise up in corporate ladder is either\nhaving expertise in somewhat niche but valuable field or starting your own\nsuccessful company or having great amount of luck (which he said most C level\nfolks don't say out publicly)\n\n------\nChuckMcM\nThat is a great origin story, and his writing is awesome[1]. ", "I have always\nbeen interested in knives and swords but not to the extent to go full on nerd\non them!", "\n\n[1] [https://knifesteelnerds.com/2018/03/26/cru-forge-v-\ntoughness...](https://knifesteelnerds.com/2018/03/26/cru-forge-v-toughness-\ntesting-processing-and-background/)\n\n------\njaclaz\nOnly slightly off topic I recently get to know about a technique in\n(industrial) manufacturing, friction forging:\n\n[https://www.diamondbladeknives.com/Friction-\nForging](https://www.diamondbladeknives.com/Friction-Forging)\n\ncannot say if it actually delivers what it promises, but the video is\ninteresting.", "\n\n------\nlarrywright\nThis is fascinating, and I'm happy to see something like this here on HN. ", "It\nhits close to home too: I'm a nerd, but my cousin is a successful knifemaker.", "\nI've picked up some knowledge about the different kinds of steel from\nfollowing his work.", "\n\n------\nknown\nWhat are good alternatives to Gillette?", "\n\n" ]

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[ "Attend a Discussion Session\n\nMessage from the Director (January 30th, 2017)\n\nPage Image\n\nPage Content\n\nDear International\nStudents,\n\nPlease know that wherever you come from and whatever your\nbackground, we warmly welcome you to the University of Colorado Denver | Anschutz\nMedical Campus and consider you an integral part of our community. ", "Know too, that\nwe are here to help you navigate your immigration situation and offer the support that\nyou need to be successful. ", "Please find below the information that we are able to\nshare with you as of Tuesday, January 31, 2017 regarding the President’s\nExecutive Order on immigration.", "\n\nBan on nonimmigrant entries, for at least 90 days, for nationals of Iraq, Iran,\nLibya, Somalia, Sudan, Syria, and Yemen. ", "Other countries may be added.", "\nNonimmigrant statuses include anyone in B, F, J, H, or\nO status. ", "The term “national” is somewhat vague, but does include\ncitizens of the listed countries. ", "The ban does not apply to individuals with\ndual citizenship from one of the listed countries and the U.S. The travel ban\ndoes not include individuals who are citizens of a non-listed country who travelled\nto one of the listed countries.", "\n\nSuspension of the Visa Interview Waiver Program (VIWP), requiring all\nnonimmigrant visa applicants, regardless of where they are from, to attend a visa\ninterview at a U.S. Embassy or Consulate abroad.", "\n\nDirective to the Secretary of Homeland Security, Secretary of State, and the\nDirector of National Intelligence, to immediately conduct a review to determine the\ninformation needed from any country to adjudicate any visa, admission, or other\nbenefit under the INA (adjudications) in order to determine that the individual\nseeking the benefit is who the individual claims to be and is not a security or\npublic-safety threat.", "\n\n​​​Within 30 days, DHS must submit a report to the\nPresident of its conclusions and include a list of the countries that do not\nprovide adequate information for adjudications. ", "Identified countries will be\ngiven 60 days to start providing required information.", "\n\nAfter 60 days, DHS will submit a list of countries recommended to be\nincluded in a Presidential Proclamation prohibiting the “entry of foreign\nnationals” from countries that have not complied until compliance\noccurs.", "\n\nDirective to federal agencies to develop screening standards and procedures for\nall immigration benefits to identify fraud and detect whether a person intends to do\nharm. ", "Agencies are directed to create a process to evaluate the person’s\n“likelihood of becoming a positively contributing member of society” and\n“ability to make contributions to the national interest.”", "\n\nDirective to agencies to expedite the completion and implementation of a\nbiometric entry-exit system and includes reporting requirements.", "\n\nImmediate halt to all U.S. refugee admissions for four months and indefinite halt\nto all Syrian refugee admissions.", "\n\nSeveral legal actions were filed in federal court in\nresponse to the Executive Order and subsequent government actions. ", "The full\nconsequences of these lawsuits are not yet clear, but several press releases were\nissued on Sunday by the Department of Homeland Security.", "\n\nExecutive Orders Remain in Effect\n\nOn January 29, 2017, DHS issued a press release\nconfirming the agency “will continue to enforce all of President Trump’s\nExecutive Orders” and that “President Trump’s Executive Orders remain\nin place—prohibited travel will remain prohibited, and the US government retains\nits right to revoke visas at any time if required for national security or public\nsafety.”", "\n\nImpact on Permanent Residents\n\nSecretary Kelly of the Department of Homeland Security released a press statement Sunday evening clarifying how the Executive Order\napplies to Lawful Permanent Residents (LPRs): \"I hereby deem the entry of lawful\npermanent residents to be in the national interest.” ", "Although Permanent\nResidents will continue to be reviewed upon entry, “absent the\nreceipt of significant derogatory information indicating a serious threat to public\nsafety and welfare, lawful permanent resident status will be a dispositive factor in\nour case-by-case determinations.”", "\n\nA\nJanuary 29, 2017 DHS Fact Sheet describes Secretary Kelly's determination in\nfurther detail: “[L]awful permanent residents of the United States will be\nallowed to board U.S. bound aircraft and will be assessed for exceptions at arrival\nports of entry, as appropriate. ", "The entry of these individuals, subject to national\nsecurity checks, is in the national interest. ", "Therefore, we expect swift entry for\nthese individuals.\"", "\n\nInternational Travel\n\nThe U.S. Department of Homeland Security stated that they\nare working closely with airline partners to prevent travelers who would not be granted\nentry under the executive orders from boarding international flights to the\nU.S. To the extent possible, we would suggest that any member of our\ninternational community who must travel fly directly into Denver International Airport\n(DIA). ", "In the past, Customs and Border Protection officials at DIA have been\nwilling to work cooperatively with ISSS to resolve issues with entry.", "\n\nIf you are from Iran, Iraq, Libya, Somalia, Sudan, Syria,\nor Yemen, we strongly advise you not to travel outside of the U.S. until further\nnotice. ", "If you know of a colleague or fellow student from any of these countries\nwho is currently outside the U.S., please let an ISSS staff member know\nimmediately. ", "You can reach us by sending an e-mail to ISSS@ucdenver.edu or by calling (303)\n315-2230.", "\n\nOther Potential Impacts of the Executive\nOrder\n\nAs a result of this Executive Order, ISSS is anticipating\nlonger processing time for petitions and applications submitted to USCIS for\nadjudication. ", "Visa applications as U.S. Embassies and Consulates abroad are also\nlikely to take more time. ", "Finally, international students and scholars may\nexperience additional screening upon reentry to the U.S. after\ninternational travel.", "\n\nISSS staff is closely monitoring this very fluid\nsituation, and will do the best we can to get relevant and reliable information to you\nin a timely manner. ", "Please do not hesitate to contact ISSS with any questions,\nconcerns, comments, or suggestions. ", "You will find our current portfolio\nassignments on the ISSS website here.", "\nYou may also contact me directly at Michelle.larson-krieg@ucdenver.edu\nor 303.315.2235.", "\n\nWe understand that this Executive Order has the potential\nto cause significant stress and anxiety for anyone who is impacted, either directly or\nindirectly. ", "It is very important that you take care of both your physical and\nmental health. ", "Talking to a mental health professional about managing stress,\nstaying focused on your studies, and healthy interpersonal relationship can be very\nimportant." ]

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[ "Q:\n\nHow to eliminate delimiter during concatenation if a column is NULL/Has no Data\n\nI am concatenation two fields in my query:\nSELECT LASTNAME + ', ' + FIRSTNAME AS NAME FROM MyTable;\n\nJULIA ROBERTS = ROBERTS, JULIA\nNULL DONALD = NULL\nIn few rows, the firstname is missing, and my code concatenates with NULL to return NULL value for NAME.", "\nIf I use below query, it returns me comma along with the result which is not needed.", "\nSELECT LASTNAME + ',' + ISNULL(FIRSTNAME) AS NAME FROM MyTable;\n\nJULIA ROBERTS = ROBERTS, JULIA\nNULL DONALD = DONALD,\nIs there a way I can eliminate comma if firstname is NULL in DB ?", "\n\nA:\n\nSELECT LASTNAME + case when FIRSTNAME is null\n then ''\n else ',' + FIRSTNAME\n end AS NAME\n FROM MyTable;\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Technetium-99m isonitrile myocardial uptake at rest. ", "II. ", "Relation to clinical markers of potential viability.", "\nTo determine the utility of rest-injected technetium-99m methoxybutyl isonitrile (Tc-99m isonitrile) uptake as a marker of myocardial viability, the regional uptake of this agent was compared with regional wall motion by equilibrium gated blood pool scan in 26 patients with previous myocardial infarction and with postrevascularization uptake in 8 patients after coronary bypass surgery. ", "Rest left ventricular Tc-99m isonitrile uptake was assessed qualitatively in three coronary vascular territories as grade 0 (markedly reduced) to grade 2 (normal), and quantitatively by circumferential profile analysis. ", "Wall motion was scored qualitatively in corresponding vascular territories as normal, hypokinetic or akinetic/dyskinetic. ", "There was an overall relation between qualitative Tc-99m isonitrile uptake and wall motion. ", "Abnormal wall motion occurred in 74% of vascular territories with perfusion grade 0, in 61% of those with grade 1 and in 30% of those with grade 2; however, 26% of territories with grade 0 uptake had normal wall motion. ", "In the territories visually assigned perfusion grade 0, quantitative isonitrile uptake (mean value +/- SD) was higher when corresponding wall motion was normal or hypokinetic (62 +/- 15%) than when akinesia was detected by gated blood pool scan (39 +/- 16%, p less than 0.02). ", "Qualitative Tc-99m isonitrile uptake improved after coronary bypass surgery in 12 of 13 territories with reduced uptake preoperatively; this included all 5 territories with a preoperative Tc-99m isonitrile score of 0. ", "Quantitative uptake in these regions increased from 55 +/- 18% to 73 +/- 21% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)" ]

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[ "(1) Field of the Invention\nThe present invention relates to a process for preparing a 1-benzylimidazole compound by benzylation of a 1-unsubstituted imidazole, and also to a novel 1-benzylimidazole compound. ", "The 1-benzylimidazole compound is valuable as a curing agent and a curing promoter for a polyepoxy resin.", "\n(2) Description of the Related Art\nA process for reacting a 1-unsubstituted imidazole compound with benzyl chloride, cooperating with an HC acceptor in an appropriate solvent having no active hydrogen atom is known [see, for example, Recl. ", "Trev. ", "Chim. ", "Pays-Bas, Vol. ", "91, No. ", "12, 1383-1392 (1972)].", "\nThis benzylation process, however, involves the following problems. ", "Namely, the 1-imidazole compound formed by the reaction between the 1-unsubstituted imidazole compound and benzyl chloride is likely to react further with unreacted benzyl chloride to form a 1,3-dibenzyl imidazolium chloride compound, and therefore, the unnecessary imidazolium chloride is formed as a by-product in a large quantity. ", "Moreover, benzyl chloride is difficult to handle because of the lacrimatory property." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Q:\n\nHow to use a C# class library from an IronPython app in Visual Studio?", "\n\nI am a new user of Visual Studio, and I am trying to figure out how to load a C# class library built as part of a solution from an IronPython project in the same solution.", "\nBasically, I am trying to do the scenario in How to debug a class library in Visual Studio but using an IronPython script instead of the console application.", "\nNormally outside a solution I would use:\nimport clr\nclr.", "AddReferenceToFile(fname)\n\nWhat should I put in for fname?", "\n\nA:\n\nYou could configure the SearchPath directory\n\nand then:\nclr.", "AddReference(\"NameOfAssembly\")\n\nor you could also specify the full path:\nclr.", "AddReferenceToFileAndPath(@\"c:\\work\\someproject\\bin\\debug\\NameOfAssembly.dll\")\n\nHere's a blog post describing the different functions for loading assemblies in IronPython.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Myriad Genetics\n\nMyriad Genetics, Inc. is an American molecular diagnostic company based in Salt Lake City, Utah, United States. ", " Myriad employs a number of proprietary technologies that permit doctors and patients to understand the genetic basis of human disease and the role that genes play in the onset, progression and treatment of disease. ", "This information is used to guide the development of new molecular diagnostic products that assess an individual's risk for developing disease later in life (predictive medicine), identify a patient's likelihood of responding to a particular drug therapy (personalized medicine), assess a patient's risk of disease progression and disease recurrence (personalized medicine), and measure disease activity. ", "Following the discovery by Mary-Claire King that a gene on chromosome 17 is associated with an increased risk of breast cancer, Myriad attempted to patent this gene. ", "These patents were the subject of scrutiny after Myriad became involved in a lawsuit over its patenting practices, which led to the landmark Supreme Court decision Association for Molecular Pathology v. Myriad Genetics, Inc. which ruled these patents illegal. ", "\n\nIn August 2016, Myriad announced it would acquire Assurex Health for up to $410million, expanding the company's genetic testing for psychotropic medicine selection. ", "\n\nIn July 2018, Myriad completed an acquisition of reproductive genetic testing firm Counsyl for $375million, expanding the company's testing capabilities to carrier and prenatal screening.", "\n\nHistory\nThe global search for the genetic basis of breast and ovarian cancers began in earnest in 1988. ", "In 1990, at an American Society of Human Genetics Meeting, a team of scientists led by Mary-Claire King, Ph.D., from the University of California, Berkeley announced the localization through linkage analysis of a gene associated with increased risk for breast cancer (BRCA1) to the long arm of chromosome 17. ", " In August 1994, Mark Skolnick and researchers at Myriad, along with colleagues at the University of Utah, the U.S National Institutes of Health (NIH), and McGill University sequenced BRCA1.", "\n\nFounders\nThe founders of Myriad are Peter Meldrum (past President and CEO of Agridyne and past CEO and President of Myriad Genetics, Inc.), Kevin Kimberlin (Chairman of Spencer Trask & Co.), Dr. Walter Gilbert (Founder of Biogen) and Mark Skolnick (Adjunct Professor in the Department of Medical Informatics at the University of Utah).", "\n\nSubsidiaries\nSubsidiaries of Myriad Genetics include Myriad Genetic Laboratories, Inc., Myriad RBM, Crescendo Bioscience, Sividon Diagnostics, Assurex Health, and, most recently, Counsyl.", "\n\nProducts \nAmong the prognostic tests developed and marketed by Myriad is \"Prolaris\", which uses gene expression profiling to provide a 10-year prostate cancer-specific risk of death. ", "Another prognostic test, marketed as \"myRisk Hereditary Cancer\", reviews genetic markers correlated with elevated risk of developing any of eight hereditary cancers.", "\n\nControversies\n\nMyriad Genetics's intention to patent human genes led to intense controversy. ", "Because genes occur naturally in every human, in addition to raising moral questions, patenting them would constitute an obstacle to biomedical research worldwide. ", "Additionally, the company was selling its breast cancer diagnostic test for a price many described as \"outrageous\": $4000, the price of a whole genome sequencing (around 20,000 genes analyzed), when the test only looked at two genes. ", "Moreover, the discovery of their relevance to breast cancer was funded by the public.", "\n\nUSA: Association for Molecular Pathology v. Myriad Genetics (2013)\nMyriad Genetics was a defendant in the case Association for Molecular Pathology v. Myriad Genetics (formerly Association For Molecular Pathology et al. ", "v. United States Patent and Trademark Office).", "\nLawyers at the ACLU served as counsel for the plaintiffs. ", "In the suit, medical associations, doctors, and patients sued Myriad Genetics to challenge seven United States patents on genes related to breast cancer and ovarian cancer.", "\n\nTwo of the company's patents on the BRCA1 and BRCA2 genes were ruled invalid on March 29, 2010, by Judge Robert W. Sweet in the U.S. District Court for the Southern District of New York. ", "On appeal, the Court of Appeals for the Federal Circuit reversed the trial court in an opinion dated July 29, 2011 and held that the genes were eligible for patents.", "\n\nOn December 7, 2011, the ACLU filed a petition for a writ of certiorari to the Supreme Court. ", "On March 26, 2012, the Supreme Court vacated the Federal Circuit's judgment and remanded the case for further consideration in light of Mayo Collaborative Services v. Prometheus Laboratories, Inc., in which the Supreme Court had ruled, just six days earlier, that more restrictive rules were required to patent observations about natural phenomena.", "\n\nOn August 16, 2012, the Federal Circuit reaffirmed Myriad's right to patent the genes although they denied rights to patent comparisons of DNA sequences. ", "On November 30, 2012, the Supreme Court agreed to hear a second challenge to the two gene patents held by Myriad. ", "Oral argument took place on April 15, 2013. ", " On June 13, 2013, in Association for Molecular Pathology v. Myriad Genetics (No. ", "12-398), the US Supreme Court unanimously ruled that \"A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated\", invalidating Myriad's patents on the BRCA1 and BRCA2 genes. ", "However, the Court also held that manipulation of a gene to create something not found in naturesuch as a strand of synthetically-produced complementary DNA (cDNA)could still be eligible for patent protection.", "\n\nAustralia: D'Arcy v Myriad Genetics Inc (2015)\nMyriad Genetics has also been involved in litigation in Australia over the patentability of DNA sequences. ", " Regarding BRCA1, the company succeeded in the Federal Court, both at first instance and on appeal to the full court, but in October 2015 lost in a unanimous decision of the High Court, D'Arcy v Myriad Genetics Inc.\n\nIn Australia an invention is patentable if, to begin with, it is a \"manner of manufacture\". ", " The plurality in the High Court formulated the key question as: \"Whether the invention as claimed is for a product made, or a process producing an outcome as a result of human action\" (para [28]). ", " It held that the product in issue continued to consist basically of genetic information that occurs naturally, had not been altered as a result of human action, therefore had not been \"manufactured\" and consequently was not patentable. ", " The plurality reflected that a broader conception of patentability could, both by creating virtual monopolies and by blurring the boundaries of what might come to be patented, produce a chilling effect on research and application, contrary to the purposes of patent protection.", "\n\nThe appellant had cited the recent US Supreme Court decision for comparison. ", " The High Court was also aware that its decision could conflict with recent judicial decisions, as well as patents legislation, in other countries, and possibly with Australia's international obligations; however, it considered these to be issues for the legislature, as well as denying that its decision in this case was intended to set a precedent with regard to genetic patenting generally. ", " In addition, the rest of the court did not dissent from Gordon J's concluding observation: \"It is important to notice that the claims made in the patents in suit in the United States of America considered in Association for Molecular Pathology v Myriad Genetics Inc 186 L Ed 2d 124 (2013) were claims to the particular genetic sequences and therefore radically different from the disputed claims in this appeal\" (note 232).", "\n\nSee also\n Biological patents in the United States\n\nReferences\n\nExternal links\n Myriad Genetics home page\n Court documents for ACLU suit\n\nCategory:1991 establishments in Utah\nCategory:American companies established in 1991\nCategory:Biotechnology companies established in 1991\nCategory:Biotechnology companies of the United States\nCategory:Companies based in Salt Lake City\nCategory:Health care companies based in Utah\nCategory:Medical genetics\nCategory:Pharmaceutical companies of the United States" ]

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[ "Scotland is an old heartland of the Labour Right. ", "But if all was well in these heartlands, Corbyn would not now be Labour’s leader. ", "Nor would the Corbynista candidate Richard Leonard be within touching distance of the Scottish Labour leadership.", "\n\nIn 2014, as Scotland’s independence referendum began, Labour was still the biggest Westminster party in Scotland. ", "But it had been in trouble for some years, having been beaten into second place by the SNP in the Scottish parliament in a shocking 2011 landslide. ", "Its polling was weak, its leaders (Iain Gray; Johann Lamont) bland and gaffe-prone. ", "In 2012, for example, Lamont, then advised by deputy leader Anas Sarwar, tried to attacked the SNP from the right on welfare, denouncing the “something for nothing culture . ” ", "The SNP ran rings around her.", "\n\nThere were bigger problems, too. ", "Of course, Labour was always going to be Unionist. ", "Its strategy for implementing social democracy depended on the unity and power of the British state, its international competitiveness, and its role in NATO. ", "But campaigning alongside the hated Tories was a disaster waiting to happen.", "\n\nNonetheless, as the referendum campaign began, Scottish Labour threw everything at shoring up support for the Union. ", "Nominally, it had its own Unionist campaign, coordinated by Anas Sarwar, but its major efforts were organised through Better Together, a cross-party campaign chaired by Labour’s Alistair Darling, alongside campaign director Blair McDougall, and fronted by Blairite shadow development secretary Jim Murphy. ", "It was a conservative, status quo campaign, exemplified by the “no thanks” slogan. ", "Murphy addressed crowds from Irn-Bru crates in imitation of John Major’s soap box routine, but this was populist as it got.", "\n\nIn the end, a raucous independence campaign peeled off almost forty percent of Labour voters, especially in the poorest constituencies. ", "Scottish Labour responded by rewarding Murphy, a working-class boy made good who was fawned over by the media, with the leadership. ", "He was to ‘save’ the party. ", "In triumphalist mode, he pledged not to lose a single seat to the SNP in the general election.", "\n\nBut the idea that hard-line Blairism could ‘save Scottish Labour’ was ruthlessly tested and refuted. ", "In 2015, Labour was demolished in Scotland, left with only one MP—the same as the coalition-disgraced Liberals. ", "Murphy lost his East Renfrewshire seat. ", "It was as though Scottish Labour had been trailing along the abyssal plain hoping to be lifted by the currents, only to disappear down the Marianas trench.", "\n\nAnd subsequent polling showed that the result was not a one-off. ", "It wasn’t just that Labour’s image was affected by its Unionist alliance with the Tories in 2014. ", "The Referendum also indirectly pushed Miliband’s 2015 campaign to the right on Trident and spending cuts, as he ran scared of a Tory campaign linking him to the SNP. ", "It was as though Labour had set out to prove the SNP’s point: all the establishment parties in it together, on the side of militarism and the multinationals.", "\n\nWorse, Scottish Labour’s collapse contrasted with incremental gains made by Labour in England. ", "These losses, knocking out a string of leading right-wing Labour MPs, created such a profound existential crisis for Labour that for the first time in its history it elected a leader from the Bennite left. ", "The Labour Right had proved itself comprehensively inadequate to the new situation.", "\n\nAnd yet, Scottish Labour seemed determined to learn nothing. ", "In the 2017 snap election, it tried to fight the battles of 2014 again, emphasising Labour’s role as the main party of the Union. ", "Meanwhile, their constant attacks on Corbyn’s leadership gave the Tories ample attack material. ", "Labour’s record gains in England and Wales thanks to Corbyn’s national campaign were only mediocre in Scotland, where it went from holding one seat to a still-meagre seven.", "\n\nMurphy’s successor in East Renfrewshire, Blair McDougall, traded largely on his role as chair of Better Together, positioning himself as the slick, besuited candidate to “beat the SNP”—as though they were a bigger problem than the Tories. ", "He lost by more than Murphy, and the Conservatives took the seat for the first time since 1997.", "\n\nIn the current Scottish Labour leadership election, one can only wonder why anyone gives the continuity candidate, Sarwar, the time of day. ", "A leading author of Scottish Labour’s disaster, he predictably has the backing of Labour’s clapped out old establishment figures. ", "He is even using their cast-off lines, accusing his rivals of merely wanting a protest party, rather than power—as though the June election didn’t happen.", "\n\nEven if he could read the now-obvious appetite for real change, Sarwar would be a dismal choice. ", "A bland centrist millionaire who owned shares in a tax haven? ", "Just how lemming-like would one have to be?", "\n\nIf Scottish Labour ever wants to stand another chance of winning, it will pick Leonard, the trade unionist who has far-sightedly backed Corbyn and his policies through thick and thin. ", "Not the living embodiment of everything that has driven them to the brink of ruin.", "\n\nThis article has been amended to clarify that Blair McDougall was the campaign director of Better Together. ", "He was previously listed as chair." ]

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[ "Saturday, January 10, 2015\n\nRoger Simon doesn't mince words. ", "We are at war, whether we want to be or not. ", "And we're losing. ", "The leaders we have are ignoring it or desperate to change the subject. ", "Obama did that yesterday, like a magician creating a distraction. ", "while people were dying in Paris, his focus was on pandering to people who want free junior college.", "\n\nMeanwhile, under the watch of the man who masquerades under the moniker of president of the United States, someone who can barely muster a dopey three-minute speech filled with banalities about the killings in France, radical Islam has metastasized across the world in a manner only dreamed of on 9/11. ", "A map on Gretawire shows terror networks cutting a wide swathe across the planet, from South America through North Africa on to the Indian subcontinent and then into South-East Asia. ", "In a sense the map should already include Western Europe, the way things are going.", "\n\nAnd most likely things are going to get worse. ", "Al Qaeda (operating with impunity in Syria, Yemen and elsewhere) and ISIS (with a state of its own the size of Indiana) are in a pissing contest for terrorist maniacs of the year while Boko Haram is doing its best to exterminate everyone in Nigeria, andapparently succeeding – all in the name of Allah. ", "And our president never uses the word “Islamic” or acknowledges that we are at war — even though, quite obviously, the Islamists are at war with us and with Western civilization. ", "And they seem just to be getting started. ", "Only the morally narcissistic buffoons at the New York Times would think otherwise.", "\n\nWhich brings us to the 2016 presidential election. ", "I have written before, “We need a wartime consigliere.” (", "Yes, yes, I know the consigliere isn’t the boss — but you get the reference.) ", "We need a wartime president. ", "Hillary Clinton, obviously, is as far from that as you could get, except for Barack Obama. ", "So we have to look on the Republican side.", "\n\nI’m not prepared to comment on any of the candidates now. ", "I don’t know enough. ", "But I will say this: In this time of war, I will be looking, far above all things, for the best possible commander-in-chief, man or woman. ", "Put another way, how much does the person resemble Winston Churchill, the ultimate wartime leader, in my view? ", "That’s not an easy thing. ", "Churchill had a great verbal skill and certain unique charm that could inspire people. ", "I can’t immediately think of anyone who has that. ", "But Churchill was a figure of legend, someone even the oldest of us see from afar or on old news clips. ", "In his day, we know he was reviled by many.", "\n\nSo maybe someone will emerge. ", "We are in desperate need of that person after the last six, soon to be eight, years. ", "What has been lost domestically is certainly significant, but pales in comparison to the global situation and the religious war that we are in. ", "If America continues to lead from behind after 2016, it will cease to be America. ", "The world will shortly be in chaos and we will all be back in the Middle Ages. ", "Sound excessive? ", "I wish it did.", "\n\nSo I implore those of you reading to put aside your special interests for the moment, or at least soft-pedal them. ", "Most of them can wait and if we lose the war against Islamic terrorism, which, believe it or not, we are currently losing, they will all be irrelevant, the unread text of Obamacare buried in the sand like Shelley’s statue of Ozymandias. ", "Civilizations have died before. ", "Let’s not let it be ours. ", "Let’s overcome the reactionary leaders in our own country and in Europe, who suffer from such extreme cognitive disorders that even after #CharlieHebdo they insist on delinking Islam from terrorism. ", "Let’s find our Churchill — and now.", "\n\nNotwithstanding that Churchill (and Roosevelt) sold out millions of people to 50 years of communist tyranny. ", "Churchill was an inspirational leader. ", "Arguably, the British nation and perhaps the entire Anglosphere has him to thank for our freedom. ", "The Poles might have a different view." ]

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[ "The Villages might be a retirement mecca packed with seniors enjoying high-dollar pensions and investments that have paid off nicely, but it also owns the distinction of having the highest rate of full-time employees stuck in poverty.", "\n\nThat’s according to a recent study conducted by the financial website 24/7 Wall St., which claims Florida’s Friendliest Hometown has the highest rate of “working poor” – 4.4 percent – much higher than the national average of 3 percent.", "\n\nThe study defines “working poor” as those who have jobs but are not able to pay their bills, afford healthcare coverage or take care of many basic necessities. ", "This would include many of those workers who earn wages from local restaurants, golf courses and medical practices, to name a few. ", "Many of those employees are considered as living on the edge of irreversible poverty.", "\n\nThe study says that The Villages has an overall poverty rate of 9.2 percent. ", "Just 34.5 percent of the population between the ages of 16-64 works full-time, but that’s largely because 125,000-plus retirees call the sprawling community home. ", "But the mega-retirement community still has a 4.9 percent unemployment rate, which is quite a bit higher than the national average of 3.5 percent in September.", "\n\nAccording to the study, 25 percent of full-time workers – the average workweek is just 36.4 hours – are employed in education and health services jobs, with an average weekly salary of $835. ", "Another 9.5 percent earn their wages through leisure and hospitality, including many who are actually employees of The Villages. ", "Those workers get paid about $405 per week, which falls significantly under the nationwide average pay for all workers of $1,101, the study says.", "\n\nWorkers who currently struggle to make ends meet and happen to own homes in Sumter County also will soon be seeing more of their paychecks disappear, as the county commission voted last month to raise property taxes by 25 percent. ", "Those who rent homes or apartments also are likely to feel that pinch, as landlords are more than likely going to raise rental fees to cover the additional costs the county claims it needs to provide infrastructure and roadway needs in the newest section of The Villages south of State Road 44. ", "And it stands to reason that apparent use of food trucks in the newest part of the community instead of country clubs also could cut into the number of area jobs available to workers.", "\n\nThe only other Florida city to make the list was Sebring, which finished in the 11th spot with a poverty rate of 5.7 percent for its full-time workforce. ", "Also located in Central Florida, the typical Sebring household annual income is $36,374, which is the second lowest of any U.S. metro area. ", "About 5.1 percent of Sebring’s workforce is unemployed, while a whopping 18.7 percent live in poverty.", "\n\nThe top-10 cities/areas on the list, including their poverty rate of full-time workers and the official overall poverty rate are:" ]

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[ "Current medications for type 2 diabetes are insufficient, and, as such, new antidiabetic agents that ameliorate insulin resistance and hyperlipidemia are needed to combat this disease. ", "AMP-activated protein kinase (AMPK) serves as a \"fuel gauge\" in cells and represents an attractive target for treating metabolic disease ([@B1],[@B2]). ", "AMPK is activated under conditions that signify cellular stress, such as exercise, ischemia, and hypoxia, which induce an increment in the intracellular AMP-to-ATP ratio ([@B3]). ", "Once activated, it orchestrates a variety of metabolic processes including stimulation of glucose uptake in muscle, increases in fatty acid oxidation, and inhibition of hepatic cholesterol and triglyceride synthesis and lipogenesis ([@B4],[@B5]). ", "These metabolic responses are primarily mediated through phosphorylation of enzymes or transcription factors and co-activators that regulate gene expression ([@B3]).", "\n\nInterestingly, AMPK can also be activated by the antidiabetic drugs metformin and thiazolidinediones (TZDs) ([@B6],[@B7]) and other natural products with antiobesity and antidiabetes properties, such as berberine ([@B8]) and resveratrol ([@B9]). ", "The mechanism by which these agents exert their beneficial metabolic effects has been shown to be, at least in part, via modulating mitochondrial function ([@B10][@B11][@B12][@B13]--[@B14]). ", "These findings raised the possibility of discovering novel therapeutics for metabolic disease from compounds that perturb mitochondrial function and thus activate AMPK.", "\n\nIn this study, we set up a high-throughput screening assay based on mitochondrial membrane potential (Δψm) and identified a small-molecule compound C1 that depolarizes Δψm in a mild manner without causing cell toxicity. ", "C1 increases cellular AMP-to-ATP ratio and activates AMPK, resulting in beneficial metabolic effects in L6 myotubes and HepG2 cells and in *db*/*db* mice. ", "Interestingly, our studies indicate that C1 causes mild inhibition of mitochondrial respiration through a mechanism distinct from TZDs, metformin, or berberine ([@B13]). ", "These findings suggest that targeted identification of mild mitochondrial modulators may represent an effective approach for the discovery of new therapeutics for type 2 diabetes.", "\n\nRESEARCH DESIGN AND METHODS\n===========================\n\nMaterials.", "\n----------\n\nCompound C, 5-aminoimidazole-4-carboxamide-1-[d]{.smallcaps}-ribofuranoside (AICAR), 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1), carbonyl cyanide *m*-chlorophenylhydrazone (CCCP), wortmannin, metformin, rosiglitazone, troglitazone, and insulin were obtained from Sigma Aldrich (St. Louis, MO). ", "Radiochemical 2-deoxy-\\[^3^H\\]-[d]{.smallcaps}-glucose and Western blotting detection kits (enhanced chemiluminescence) and Hyperfilm were purchased from Amersham Biosciences (Uppsala, Sweden).", "\n\nCell culture.", "\n-------------\n\nL6 myoblasts were cultured in Dulbecco\\'s modified Eagle medium (DMEM) (Invitrogen, Carlsbad, CA) supplemented with 10% FBS, 4.5 g/l glucose, 100 units/ml penicillin, and 100 μg/ml streptomycin at 37°C in 5% CO~2~. For L6 myoblast differentiation, the concentration of FBS was decreased from 10 to 2%. ", "Myotubes were used for experiments 5--7 days after differentiation. ", "HepG2 cells were maintained in DMEM containing 10% FBS, 1 g/l glucose, 100 units/ml penicillin, and 100 μg/ml streptomycin at 37°C in 5% CO~2~.\n\nMitochondrial membrane potential assay.", "\n---------------------------------------\n\nThis assay was based on a previous report with modifications ([@B15]). ", "Briefly, 7,000 L6 myoblasts per well were seeded into black 96-well optical-bottom plates (Greiner Bio-One, Dusseldorf, Germany) at 100 μl per well. ", "On day 5 of differentiation, compounds were added and plates were incubated at 37°C for 10 min. ", "After incubation, 100 μl fresh medium containing 0.2 μg JC-1 was added to each well. ", "Plates were incubated for another 20 min at 37°C, and each well was washed three times with 100 μl Krebs-Ringer phosphate HEPES buffer. ", "Fluorescence was measured in a Flexstation II plate reader (Molecular Device, Union City, CA) with first at lengths of excitation and emission (ex/em) 530 nm/580 nm (\"red\") and then at ex/em 485 nm/530 nm (\"green\"). ", "The ratio of red to green reflects the Δψm. ", "The coefficient of variation (CV%) and *Z*′ factor for the quality control of high-throughput screening assay were estimated ([@B16]).", "\n\nAdenine nucleotide extraction and measurement.", "\n----------------------------------------------\n\nL6 myotubes cultured in 60-mm dishes treated with C1 were washed with PBS (140 mmol/l NaCl, 2.7 mmol/l KCl, 10 mmol/l Na~2~HPO~4~, 1.8 mmol/l KH~2~PO~4~) and trypsinized. ", "The samples for cellular adenine nucleotides measurement were prepared and analyzed as previously described ([@B17]).", "\n\nMeasurement of 2-deoxy-\\[^3^H\\]-[d]{.smallcaps}-glucose uptake.", "\n---------------------------------------------------------------\n\n2-Deoxyglucose uptake was measured as described ([@B17],[@B18]). ", "Briefly, after stimulation with C1 or insulin, cells were washed three times with HEPES-buffered saline solution (20 mmol/l HEPES \\[pH 7.4\\], 136 mmol/l NaCl, 4.7 mmol/l KCl, 1.25 mmol/l MgSO~4~, 1.2 mmol/l CaCl~2~) followed by incubation with 2-deoxy-\\[^3^H\\]-[d]{.smallcaps}-glucose for 10 min. ", "Cells were washed with ice-cold PBS, lysed using 0.1% Triton-X 100, and radioactivity counted.", "\n\nWestern blot analysis.", "\n----------------------\n\nCell lysates were subjected to electrophoresis through 8% SDS-PAGE and blotted with antibodies for AMPK, phospho-AMPK, acetyl-CoA carboxylase (ACC), phospho-ACC, Akt, and phospho-Akt purchased from Cell Signaling Technology (Beverly, MA) and β-actin from Upstate (Billerica, MA). ", "The immunoblots were visualized by chemiluminescence using the enhanced chemiluminescence Western Blotting System.", "\n\nDetermination of triglyceride and cholesterol contents.", "\n-------------------------------------------------------\n\nHepG2 cells cultured in 60-mm dishes were lysed in RIPA buffer (20 mmol/l Tris-HCl, pH 8.0, 1% Nonidet P-40, 1 mmol/l sodium orthovanadate, 1 mmol/l phenylmethylsulfonylfluoride, 1 mmol/l dithiothreitol, 1 mmol/l EDTA, 1 mmol/l EGTA, 2 μg/ml aprotinin, 2 μg/ml leupeptin, and 1 μg/ml pepstatin). ", "Triglyceride and total cholesterol contents were determined in cell lysates using a colorimetric assay and are expressed as milligram lipid per milligram of cellular protein as described ([@B19],[@B20]).", "\n\nMeasurement of respiration in L6 myotubes and isolated mitochondria.", "\n--------------------------------------------------------------------\n\nMitochondria were isolated from mouse quadriceps muscle using a method previously described ([@B13]). ", "Respiration measurements in L6 myotubes and isolated mitochondria were conducted at 37°C in a Clark type oxygen electrode (Strathkelvin Instruments, Motherwell, Scotland). ", "For L6 myotubes, respiration measurements were conducted using cell culture medium, while for mitochondria, a standard respiration medium was used ([@B13]). ", "Cells or mitochondria were transferred to the electrode chamber, and after attaining a steady rate of oxygen consumption, C1 was added dose-dependently, and its effect on oxygen consumption was recorded.", "\n\nDetermination of lactate content.", "\n---------------------------------\n\nThe cells were cultured in a 24-well plate and treated with C1 and positive control in serum-free cell culture medium for the indicated time. ", "Lactate in the medium was measured with a lactate assay kit from Nanjing Jiancheng Bioengineering Institute (Nanjing, China).", "\n\nAnimal experiments.", "\n-------------------\n\nAll animal experiments were approved by the Animal Ethics Committee of either the Shanghai Institute of Materia Medica or Garvan Institute of Medical Research/St. Vincent\\'s Hospital, where the experiments were conducted. ", "Male C57BL/6J *db*/*db* and lean C57BL/6J mice were housed in a temperature-controlled room (22 ± 2°C), with a light/dark cycle of 12 h. At 8--14 weeks of age, mice were randomly assigned to acute or chronic treatment. ", "The acute effects of C1 (50 mg/kg) on oxygen consumption rate (VO~2~) and respiratory exchange ratio were measured using an eight-chamber indirect calorimeter (Oxymax series; Columbus Instruments, Columbus, OH) as described previously ([@B21]). ", "To examine the acute effects of C1 on activation of AMPK, lean mice were given intraperitoneal injections of vehicle (0.9% NaCl), C1 (20 mg/kg), or AICAR (400 mg/kg) as a positive control. ", "Animals were killed after 2 h with the liver freeze clamped for the determination of phosphorylation of AMPK and ACC. ", "For chronic treatment, lean and *db*/*db* mice received oral administration of either vehicle (0.5% methylcellulose) or C1 (50 mg · kg^−1^ · day^−1^) or metformin (250 mg · kg^−1^ · day^−1^) for 4 weeks. ", "Body weight and food intake were recorded daily. ", "Fasting and random-fed blood glucose levels were measured every other week. ", "Glucose tolerance test (2 g/kg glucose i.p.) ", "was performed in overnight-fasted mice as described before ([@B13]). ", "Plasma concentrations of nonesterified fatty acids (NEFAs) and triglyceride were measured using kits from Wako Diagnostics (Richmond, VA) and Nanjing Jiancheng Bioengineering Institute (Nanjing, China), respectively. ", "Plasma insulin content was measured by using a rodent insulin enzyme-linked immunosorbent assay (ELISA) kit (Linco Research, St. Charles, MO). ", "After 4 weeks of treatment, animals were killed with the liver freeze clamped for the determination of gene expression.", "\n\nRNA isolation and real-time PCR.", "\n--------------------------------\n\nGene expression was analyzed by real-time PCR (RT-PCR). ", "Total RNA prepared from mouse livers was extracted with Trizol (Invitrogen). ", "Complementary DNA generated by M-MLV Reverse Transcriptase (Promega, Madison, WI) was analyzed by quantitative PCR using an SYBR Premix Ex *Taq* (TaKaRa, Dalian, China). ", "All samples were run in duplex with and normalized to tubulin expression. ", "The sequences of oligonucleotide primers used are described elsewhere ([@B22]).", "\n\nGlucose output assay.", "\n---------------------\n\nPrimary hepatocytes were prepared from Sprague-Dawley rats as previously described ([@B23],[@B24]) and were plated with DMEM containing 1 g/l glucose (Invitrogen) in 12-well plates (5 × 10^5^ cells in each well). ", "After 4-h attachment, cells were changed to serum-free medium and incubated with 5, 10, and 20 μmol/l C1 for 16 h. The medium was then replaced with 500 μl glucose production buffer consisting of glucose-free DMEM, without phenol red, supplemented with 20 mmol/l sodium lactate and 2 mmol/l sodium pyruvate. ", "After a 4.5-h incubation, 50 μl medium was collected and the glucose concentration was measured with a colorimetric glucose assay kit (Fudan-Zhangjiang, Shanghai, China).", "\n\nStatistical analysis.", "\n---------------------\n\nResults are presented as means ± SE. ", "Differences between groups were analyzed by Student\\'s *t* test. ", "For respiration measurements, the effect of C1 treatment is given as a percentage of intraindividual control values (100%), with *P* values calculated by paired *t* tests. *", "P* \\< 0.05 was regarded as statistically significant.", "\n\nRESULTS\n=======\n\nIdentification of C1 by Δψm and AMPK assays in L6 myotubes.", "\n-----------------------------------------------------------\n\nΔψm provides an index of mitochondrial function, and therefore to screen for novel compounds that can affect mitochondrial function, we developed a high-throughput screening assay in a 96-well format for Δψm in L6 myotubes using JC-1, a positively charged fluorescent compound. ", "Initially, we characterized this assay using the mitochondrial uncoupler CCCP as a control and observed a dose-dependent decrease in Δψm with CCCP ([Fig. ", "1](#F1){ref-type=\"fig\"}*A*). ", "The CV% and *Z*′ factor determined with CCCP were 8.5 and 0.6, respectively, which meet the criteria for quality control of a high-throughput screening assay.", "\n\n{#F1}\n\nNext, the effect of berberine, TZDs, and metformin on Δψm was examined, since we have previously reported that these agents exert their beneficial effects, in part, by perturbing mitochondrial function ([@B13]). ", "A decrease in Δψm of ∼20% was observed when L6 myotubes were treated with the above compounds for 30 min ([Fig. ", "1](#F1){ref-type=\"fig\"}*B*). ", "We also tested the AMPK activator AICAR ([@B25],[@B26]) and observed no effect on Δψm. ", "A recent study reported that AICAR (0.5 mmol/l) inhibits oxidative phosphorylation in primary mouse hepatocytes ([@B27]), and thus it would be expected to also decrease Δψm. ", "However, there is clearly a difference in sensitivity between cell types, as we have found that even at a concentration of 2 mmol/l, AICAR does not inhibit respiration in L6 myotubes (data not shown).", "\n\nWe then proceeded to randomly screen our compound library, which contains pure synthetic compounds and natural products collected from different sources, and from this screen, we identified a small molecule (449.14 Da), named C1 ([Fig. ", "1](#F1){ref-type=\"fig\"}*C*), as a compound able to depolarize Δψm in a dose-dependent manner within a 30-min treatment. ", "Compared with CCCP ([Fig. ", "1](#F1){ref-type=\"fig\"}*D*), which depolarized Δψm within a narrow dose range, C1 depolarized Δψm in a relatively mild manner, reaching \\<50% even at the highest test concentration (100 μmol/l). ", "For subsequent experiments, a concentration of 20 μmol/l was used, since this dose gave a decrease in the Δψm (∼20%) similar to the other antidiabetic agents tested ([Fig. ", "1](#F1){ref-type=\"fig\"}*B*).", "\n\nBecause AMPK acts as an energy sensor, we examined if treatment of L6 myotubes with C1 would lead to activation of AMPK. ", "We observed a dose- and time-dependent activation of AMPK by C1 as evidenced by the increase in Thr-172 phosphorylation of the α-catalytic subunit of AMPK and the increase in Ser-79 phosphorylation of its downstream target ACC ([Fig. ", "1](#F1){ref-type=\"fig\"}*E* and *F*).", "\n\nC1 stimulates glucose uptake via the AMPK pathway in L6 myotubes.", "\n-----------------------------------------------------------------\n\nSeveral studies have linked AMPK activation with the stimulation of glucose uptake and utilization by skeletal muscle ([@B28],[@B29]). ", "As shown in [Fig. ", "2](#F2){ref-type=\"fig\"}*A*, C1 stimulated glucose uptake dose-dependently, with 20 μmol/l C1 resulting in a nearly twofold increase compared with controls. ", "To further elucidate the mechanism of C1-stimulated glucose uptake, we measured the effects of 100 nmol/l insulin and 20 μmol/l C1, respectively, or together on glucose uptake. ", "As shown in [Fig. ", "2](#F2){ref-type=\"fig\"}*B*, when L6 myotubes were treated with insulin and C1 together, glucose uptake was stimulated to a higher extent compared with single treatment with insulin or C1. ", "This additive effect indicated that C1 stimulated glucose uptake in L6 myotubes through a pathway distinct from the insulin-signaling pathway. ", "Indeed, while the phosphatidylinositol 3′ kinase inhibitor wortmannin was able to block glucose uptake and Ser-473 phosphorylation of Akt by insulin, C1 did not activate Akt and wortmannin did not inhibit the stimulation of glucose uptake by C1 ([Fig. ", "2](#F2){ref-type=\"fig\"}*C* and *D*). ", "We next examined whether the effects of C1 were dependent on AMPK by using the AMPK inhibitor compound C. Compound C pretreatment abolished the ability of C1 to increase glucose uptake ([Fig. ", "2](#F2){ref-type=\"fig\"}*C*) and blocked the phosphorylation of AMPK and ACC by C1 ([Fig. ", "2](#F2){ref-type=\"fig\"}*D*).", "\n\n![", "Effect of C1 on glucose uptake in relation to the AMPK and phosphatidylinositol 3-kinase/Akt signaling pathways. *", "A*: Dose-dependent effects of C1 on glucose uptake. ", "L6 myotubes were treated for 1 h with a different dose of C1 as described in [research design and methods]{.smallcaps}. *", "B*: Additive effect of C1 on insulin-stimulated glucose uptake. ", "Cells were treated with 100 nmol/l insulin and 20 μmol/l C1 for 30 min and 1 h, respectively. *", "C*: Influences of wortmannin and compound C on C1-induced glucose uptake. ", "After serum deprivation for 2 h, 25 nmol/l wortmannin or 20 μmol/l compound C was added to the cells for 30 min before and during the incubation with 20 μmol/l C1 for 1 h. A total of 100 nmol/l insulin was added in the last 30 min. *", "D*: The effects of C1 on AMPK, ACC, and Akt phosphorylation. ", "\\*\\**P* \\< 0.01 compared with DMSO group; §*P* \\< 0.05. *", "n* = 3 independent experiments.](zdb0011059750002){#F2}\n\nC1 decreases lipid contents via the AMPK pathway in HepG2 cells.", "\n----------------------------------------------------------------\n\nTo investigate whether C1 also influences lipid metabolism, we tested its effects in human hepatoma HepG2 cells. ", "As shown in [Fig. ", "3](#F3){ref-type=\"fig\"}*A*, C1 decreased the contents of triglyceride and cholesterol dose-dependently, with 5 μmol/l C1 able to lower lipid contents with a similar potency to that of 2 mmol/l metformin. ", "Similar to the L6 myotubes, C1 dose-dependently activated the AMPK pathway in HepG2 cells, as evidenced by the increase in AMPK and ACC phosphorylation ([Fig. ", "3](#F3){ref-type=\"fig\"}*B*). ", "The effects of C1 and metformin on ACC phosphorylation and decreasing triglyceride content could be partially blocked by compound C pretreatment ([Fig. ", "3](#F3){ref-type=\"fig\"}*C* and *D*), suggesting that, like metformin ([@B19]), the lipid-lowering effect of C1 is largely mediated through AMPK.", "\n\n{#F3}\n\nC1 influences mitochondrial metabolism via a mechanism different from TZDs and metformin.", "\n-----------------------------------------------------------------------------------------\n\nATP generation occurs primarily in mitochondria, and a decrease in Δψm will lead to a reduced ATP production, an increase in the AMP-to-ATP ratio, and activation of AMPK ([@B30],[@B31]). ", "Because the activation of AMPK by TZDs and metformin involves inhibition of respiratory complex I, we wondered if C1 shares a similar mechanism. ", "C1 treatment for 1 h increased the AMP-to-ATP ratio in a dose-dependent manner, up to fourfold greater than basal levels at a concentration of 40 μmol/l ([Fig. ", "4](#F4){ref-type=\"fig\"}*A*). ", "We also observed a time-dependent increase in the AMP-to-ATP ratio with 20 μmol/l C1 ([Fig. ", "4](#F4){ref-type=\"fig\"}*B*). ", "To determine if the change in nucleotide ratio was due to an effect on cellular respiration, we examined oxygen consumption in L6 myotubes and observed a dose-dependent inhibition of respiration at similar concentrations of C1 ([Fig. ", "4](#F4){ref-type=\"fig\"}*C*). ", "To determine if this effect was due to a specific inhibition of mitochondrial function, we isolated muscle mitochondria and examined the effect of C1 on ADP-stimulated respiration in the presence of complex I (glutamate) or complex II (succinate) substrates. ", "Surprisingly, C1 did not inhibit mitochondrial respiration with either substrate ([Fig. ", "4](#F4){ref-type=\"fig\"}*D*). ", "C1 also had no effect on mitochondrial respiration in the absence of ADP (data not shown).", "\n\n![", "Effects of C1 on AMP-to-ATP ratio and respiration. ", "Cellular ATP and AMP content were measured by HPLC as mentioned in [research design and methods]{.smallcaps}. ", "Results are presented as fold over DMSO group. *", "A*: Dose-dependent effects of C1 on AMP-to-ATP ratio after incubation for 1 h in L6 myotubes (*n* = 3). *", "B*: Time course of C1 (20 μmol/l) induced changes in AMP-to-ATP ratio (*n* = 3). *", "C*: Effect of C1 to inhibit the respiration of intact L6 myotubes (*n* = 6). *", "D*: Effect of C1 on the respiration of isolated mitochondria from mouse quadriceps muscle (*n* = 4). *", "E* and *F*: Time-dependent effect of C1 (20 μmol/l) on lactate release from L6 myotubes and HepG2 cells, respectively (*n* = 3). ", "\\**P* \\< 0.05; \\*\\**P* \\< 0.01 compared with DMSO group; \\#\\#*P* \\< 0.01 between C1 and troglitazone or metformin. ", "Results are presented as percentage of DMSO group.](zdb0011059750004){#F4}\n\nBecause a decrease in aerobic respiration may lead to an elevation in anaerobic respiration to compensate, we tested whether C1 increased lactate release, a marker of anaerobic respiration. ", "C1 (20 μmol/l) acutely increased lactate production from L6 myotubes by 20 and 65% at 1 and 4 h, respectively ([Fig. ", "4](#F4){ref-type=\"fig\"}*E*). ", "A similar effect was observed for cells treated with 50 μmol/l troglitazone. ", "In HepG2 cells, both C1 and metformin also increased lactate release within 1--4 h ([Fig. ", "4](#F4){ref-type=\"fig\"}*F*).", "\n\nAcute effects of C1 in mice.", "\n----------------------------\n\nBased on the in vitro data, we examined whether C1 could acutely affect whole-body metabolism in C57BL/6J lean mice. ", "Animals were dosed with 50 mg/kg C1 and in the 6 h following, we observed no change in VO~2~ (data not shown), but a significant decrease in respiratory exchange ratio, indicating a shift to fatty acid utilization ([Fig. ", "5](#F5){ref-type=\"fig\"}*A* and *B*). ", "To investigate if AMPK might be involved, we measured the phosphorylation of AMPK and ACC in the liver, 2 h after C1 treatment, and observed a clear activation of this pathway ([Fig. ", "5](#F5){ref-type=\"fig\"}*C*), to a degree similar to that of the positive control AICAR ([Fig. ", "5](#F5){ref-type=\"fig\"}*D* and *E*) ([@B21]).", "\n\n![", "Acute effect of C1 on respiratory exchange ratio (RER) and the AMPK pathway. ", "For RER measurement, lean mice were placed in a metabolic chamber at 9:00 [a.m.,]{.smallcaps} and after 2 h of rest, C1 (50 mg/kg) or saline (vehicle) was administered by oral gavage. ", "For acute experiment, C57BL/6J lean mice were given either vehicle (0.9% NaCl) or C1 (20 mg/kg) or AICAR (400 mg/kg) by intraperitoneal injection. ", "After 2-h treatment, animals were killed, with liver freeze-clamped for the determination of phosphorylation of AMPK and ACC. *", "A*: Changes of RER throughout the period of monitoring. *", "B*: Comparison of the average RER results before and after drug administration. *", "C*: The phosphorylation state of liver AMPK and ACC. *", "D* and *E*: The ratio of phosphorylation level versus protein level of AMPK and ACC. ", "\\*\\**P* \\< 0.01; \\**P* \\< 0.05 compared with vehicle (*n* = 7--12).](zdb0011059750005){#F5}\n\nChronic effects of C1 in mice.", "\n------------------------------\n\nTo assess the antidiabetic potential of C1 in vivo, *db*/*db* mice and lean mice were administered 50 mg · kg^−1^ · day^−1^ for 4 weeks. ", "We compared the efficacy of C1 with the well-known antidiabetic agent metformin (250 mg · kg^−1^ · day^−1^). ", "Food intake and body weight gain were checked daily, and no significant differences were observed between the three groups ([Table 1](#T1){ref-type=\"table\"}). ", "In lean mice, plasma parameters were generally unchanged by C1 and metformin treatment, apart from a small increase (12%) in random-fed glucose levels in C1-treated animals. ", "In *db*/*db* mice, random-fed and fasting blood glucose levels were decreased 42 and 21%, respectively, by C1 treatment, while metformin decreased blood glucose levels by ∼20% ([Table 1](#T1){ref-type=\"table\"}). ", "Plasma levels of insulin and triglyceride were unchanged by C1 or metformin treatment, but NEFA levels were decreased by ∼20% in C1-treated *db*/*db* mice. ", "C1 and metformin did not alter glucose tolerance in lean mice ([Fig. ", "6](#F6){ref-type=\"fig\"}*A* and *B*); however, in *db*/*db* mice, both agents improved glucose clearance, as evidence by the ∼25% decrease in the AUC ([Fig. ", "6](#F6){ref-type=\"fig\"}*C* and *D*). ", "Liver gluconeogenesis plays an important role in regulating glucose levels; therefore, we assessed the expression of two key gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in response to C1 treatment. ", "The expression of G6Pase and PEPCK was approximately threefold higher in *db*/*db* mice compared with lean controls ([Fig. ", "6](#F6){ref-type=\"fig\"}*E* and *F*). ", "C1 treatment reduced the expression of G6Pase and PEPCK by 45 and 62%, respectively, in *db*/*db* mice. ", "Interestingly, in lean mice, C1 treatment did not affect PEPCK expression, but caused an almost twofold increase in G6Pase. ", "To more directly examine the effect of C1 on gluconeogenesis, we measured glucose output in primary hepatocytes. ", "As shown in [Fig. ", "6](#F6){ref-type=\"fig\"}*G*, overnight treatment of hepatocytes with C1 dose-dependently inhibited glucose output by 25--35%.", "\n\n###### \n\nChronic effects of C1 and metformin on metabolic parameters in mice\n\n Plasma parameters *db*/*db*-Veh *db*/*db*-C1 *db*/*db*-Met Ln-Veh Ln-C1 Ln-Met\n --------------------------------------- --------------- ---------------------------------------------- --------------------------------------------- ------------- --------------------------------------------- -------------\n Food intake (g · day^−1^ · mouse^−1^) 4.41 ± 0.09 4.39 ± 0.07 4.04 ± 0.09 2.94 ± 0.04 2.88 ± 0.15 2.89 ± 0.05\n Body weight gain (g) 4.5 ± 0.51 5.05 ± 0.40 4.32 ± 0.27 3.00 ± 0.77 2.51 ± 0.47 1.8 ± 0.21\n Fasting blood glucose (mmol/l) 21.9 ± 1.9 17.3 ± 1.5[\\*](#TF1-1){ref-type=\"table-fn\"} 17.0 ± 2.9[\\*](#TF1-1){ref-type=\"table-fn\"} 10.7 ± 0.5 11.2 ± 0.5 10.0 ± 0.6\n Random-fed blood glucose (mmol/l) 20.3 ± 1.8 11.8 ± 0.7[\\*](#TF1-1){ref-type=\"table-fn\"} 16.3 ± 1.8[\\*](#TF1-1){ref-type=\"table-fn\"} 11.0 ± 0.3 12.3 ± 0.6[\\*](#TF1-1){ref-type=\"table-fn\"} 10.8 ± 0.6\n Plasma insulin (ng/ml) 8.06 ± 1.37 10.99 ± 2.09 8.29 ± 1.13 0.48 ± 0.03 0.43 ± 0.03 0.48 ± 0.03\n Plasma NEFA (mEq/l) 1.18 ± 0.09 0.96 ± 0.05[\\*](#TF1-1){ref-type=\"table-fn\"} 1.12 ± 0.16 0.72 ± 0.05 0.80 ± 0.07 0.83 ± 0.07\n Plasma triglyceride (mmol/l) 0.85 ± 0.03 0.82 ± 0.04 0.91 ± 0.18 0.66 ± 0.06 0.63 ± 0.05 0.67 ± 0.03\n\nData are means ± SE (*n* = 7--10). ", "Daily food consumption and body weight gain were measured during the study. ", "Blood samples from mice were collected after oral administration of vehicle (Veh) (0.5% methylcellulose) or C1 (50 mg · kg^−1^ · day^−1^) or metformin (Met) (250 mg · kg^−1^ · day^−1^) for 4 weeks.", "\n\n\\**P* \\< 0.05 vs. vehicle.", "\n\n{#F6}\n\nDISCUSSION\n==========\n\nInterest in mitochondrial biology has undergone a resurgence in recent years, with the discovery that mitochondrial dysfunction is linked with several diseases, including obesity and type 2 diabetes ([@B32]). ", "Intriguingly, mild perturbation of mitochondrial function has been associated with beneficial effects for obesity and type 2 diabetes ([@B10][@B11][@B12][@B13]--[@B14],[@B28],[@B33]). ", "Metformin and TZDs, drugs widely prescribed for the treatment of type 2 diabetes, exert their antidiabetic effects partly through inhibition of respiratory complex I ([@B10][@B11]--[@B12]). ", "We have recently shown that berberine, a natural product with antidiabetic effects, also inhibits complex I of the respiratory chain ([@B13]). ", "A common finding of these reports is that inhibition of mitochondrial function leads to activation of AMPK in tissues such as muscle and liver, and the pleitropic actions of AMPK likely mediate most of the beneficial effects of these compounds. ", "Therefore, we hypothesized that small molecules, which depolarize Δψm, would activate AMPK and have beneficial effects on these metabolic diseases. ", "Herein, we set up a high-throughput screening assay based on Δψm and discovered a small molecule C1 as a novel modulator of mitochondrial function.", "\n\nC1 treatment caused depolarization of Δψm in L6 myotubes in a relatively mild fashion, and a consequence of this was activation of AMPK and improvements in metabolic parameters both in vitro and in vivo. ", "In principle, several factors may lead to a drop in Δψm, including inhibition of mitochondrial respiration, induction of proton leakage (uncoupling), or opening of the mitochondrial permeability transition pore. ", "Mitochondrial permeability transition pore opening is tightly correlated with initiation of apoptosis ([@B34]), and we excluded this pathway, since we observed no induction of markers of apoptosis after C1 treatment (data not shown). ", "We also ruled out C1 acting directly as an uncoupling agent, as it did not accelerate respiration rate in isolated mitochondria, as typical uncoupling agents do ([@B35]). ", "Similarly, uncoupling agents have been shown to induce cell death ([@B36]), and we observed no obvious toxicity on viability of a range of different cell types (L6, Hela, A549, and PC12), even at high doses of C1 (data not shown). ", "Collectively, our results suggested that the likely mode of action of C1 to decrease Δψm was through inhibition of mitochondrial respiration.", "\n\nSeveral antidiabetic agents, such as troglitazone, rosiglitazone, metformin, and berberine, have been shown to inhibit mitochondrial respiratory complex I ([@B10][@B11][@B12][@B13]--[@B14],[@B37]). ", "With our assay system, we confirmed that these agents, as expected, caused a decrease in Δψm. ", "Given that the effect of C1 on Δψm was of a comparable magnitude to the above compounds, it seemed possible that C1 might act via a similar mechanism. ", "C1 dose-dependently inhibited respiration in L6 myotubes, and this lead to an increase in the AMP-to-ATP ratio. ", "However, to our surprise, when we examined isolated mitochondria, C1 did not affect ADP-stimulated respiration with either glutamate or succinate as the substrate. ", "Therefore, C1 does not appear to inhibit respiration via a direct effect on mitochondrial respiratory complexes or the phosphorylation system (i.e., ATP synthase and adenine nucleotide exchanger) ([@B10]). ", "Another important factor regulating mitochondrial respiration is a constant supply of electron donors (e.g., NADH) ([@B30]). ", "There are several shuttle systems (e.g., malate-aspartate shuttle, α-glycerophosphate shuttle) that oxidize cytosolic NADH and transfer the reducing equivalents to the mitochondrial respiratory chain ([@B38]). ", "Inhibition of one of these shuttles could lead to impairment in respiration in intact cells, which would not be apparent using glutamate or succinate as substrates in isolated mitochondria. ", "For example, the anti-inflammatory drug indomethacin, which inhibits the α-glycerophosphate shuttle, inhibits glucose oxidation in intact kidney tubules, without affecting pyruvate oxidation in rat kidney mitochondria ([@B39],[@B40]). ", "Our similar results for C1 suggest that it may also inhibit one of these shuttle systems, and our finding of increased lactate release support this, as a rise in cytosolic NADH/NAD^+^ would favor the lactate dehydrogenase reaction ([@B41]).", "\n\nA consequence of reduced mitochondrial respiration and an elevated AMP-to-ATP ratio is activation of the AMPK pathway, which induces a rapid shutdown of anabolic processes and stimulation of catabolic processes to try and overcome metabolic stress ([@B26],[@B28]). ", "Given its effect on Δψm it was not unexpected that we observed robust stimulation of the AMPK pathway in L6 myotubes and HepG2 cells with C1. ", "The effects of C1 to stimulate glucose uptake in L6 myotubes and to inhibit lipid synthesis in HepG2 cells were also shown to be largely dependent on AMPK, as these effects could be mostly abrogated by treatment with the AMPK inhibitor compound C. In fact, the ability of AMPK to overcome a mild metabolic stress represents an important protective mechanism, and it has been shown that other agents that mildly inhibit or uncouple mitochondria also increase glucose transport and inhibit lipid synthesis ([@B8],[@B28],[@B42],[@B43]).", "\n\nBased on our in vitro findings, we sought to test the effect of C1 in vivo. ", "Pharmacokinetic studies in rats showed favorable bioavailability of C1 (43%) and plasma concentrations in the range that depolarized Δψm and activated AMPK in vitro (supplementary Fig. ", "1 in the online appendix, available at <http://diabetes.diabetesjournals.org/cgi/content/full/db09-0223/DC1>). ", "Initially, we administered a single dose of C1 to mice, and while this did not significantly affect whole-body energy expenditure, we did observe a reduction in the respiratory exchange ratio, suggesting a switch to whole-body fatty acid oxidation. ", "These findings of elevated fat utilization are consistent with activation of the AMPK pathway ([@B26]), which we observed in the liver of lean animals dosed with C1. ", "We next assessed the chronic effects of 4 weeks of treatment of C1 in *db*/*db* mice and lean mice. ", "Neither C1 nor the antidiabetic drug metformin had any major effect in lean mice. ", "In *db*/*db* mice, C1 improved glucose homeostasis to a degree similar to that of metformin, as evidenced by the reduction in blood glucose levels and improved glucose tolerance. ", "C1 also decreased plasma NEFA levels, which is potentially a consequence of the enhanced whole-body fat utilization we observed. ", "Liver gluconeogenesis is a critical component of glucose homeostasis, and we observed a dose-dependent reduction in glucose output from primary hepatocytes and a downregulation of hepatic PEPCK and G6Pase expression by C1 in *db*/*db* mice. ", "Interestingly, the expression of G6Pase, but not PEPCK, was significantly upregulated by C1 treatment in lean animals. ", "A number of studies have reported that AMPK activators decrease gluconeogenic gene expression ([@B44],[@B45]); however, similar to our findings, a recent study showed that AICAR treatment of *ob*/*ob* mice potently upregulated the expression of G6Pase in liver, while at the same time reducing the expression of PEPCK ([@B44]). ", "The reason for the disparity in findings regarding AMPK activators and G6Pase expression is unclear at present.", "\n\nOverall, we propose a scheme whereby C1 causes mild inhibition of mitochondrial respiration, through a mechanism distinct from TZDs, metformin, or berberine, ultimately leading to activation of AMPK, with beneficial metabolic outcomes ([Fig. ", "7](#F7){ref-type=\"fig\"}). ", "Despite the encouraging results with C1 and the fact that many prominent antidiabetic compounds are known to inhibit mitochondrial function, there are several potential concerns regarding the use of compounds that target mitochondria. ", "For example, in addition to their role in energy production, mitochondria play an important role in apoptotic signaling and calcium regulation ([@B46],[@B47]), and disruption of these pathways may compromise cellular homeostasis. ", "Furthermore, inhibiting ATP production in certain cells (e.g., pancreatic β-cells) will have deleterious functional consequences, as these cells rely on ATP as a key signaling intermediate ([@B30]). ", "We did not observe any obvious cytotoxic effects of C1 in our cell and animal studies, and the only potentially negative finding was an increase in lactate production in our cell studies. ", "Lactic acidosis is an undesirable side effect of metformin, and further studies are required to determine if increased lactate levels occur in vivo in response to all compounds that inhibit mitochondrial function, and whether this outweighs their beneficial effects on metabolism through AMPK activation.", "\n\n{#F7}\n\nIn summary, we have used a screen for Δψm to identify a novel small molecule C1 that activates the AMPK pathway and exerts beneficial metabolic effects in vitro and in vivo related to metabolic syndrome. ", "Unlike other antidiabetic agents that also work through the AMPK pathway, C1 does not appear to directly affect mitochondrial complex I, but indirectly inhibits mitochondrial function, potentially through impairing the supply of electron donors. ", "Our findings therefore suggest that high-throughput screening for compounds that mildly perturb mitochondrial function is a promising approach to discover novel therapeutics for the treatment of type 2 diabetes and other related metabolic diseases.", "\n\nSupplementary Material\n======================\n\n###### Online-Only Appendix\n\nThe costs of publication of this article were defrayed in part by the payment of page charges. ", "This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.", "\n\nThis work was supported by the National Natural Science Foundation of China (Grants U0633008, 30472045, and 30623008), Shanghai Commission of Science and Technology (Grant 09ZR1407100), the National Hi-Tech Research and Development Program Grant of China (Grants 2007AA09Z402 and 2008AA02Z105), the National Health and Medical Research Council (NHMRC) of Australia (Project Grant 535930 to J.M.Y.), the Rebecca Cooper Medical Research Foundation of Australia (to N.T.), and the China-Australia Special Fund (08400709300). ", "N.T. was supported by a Career Development Award from the NHMRC of Australia.", "\n\nNo potential conflicts of interest relevant to this article were reported.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "The particle system’s frame rate is fixed to a value. ", "For instance, changing the value to 2 will make the particles render at 2 frames per second. ", "Note this does not slow down the particle system itself." ]

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[ "Today’s guest is rising WTA tennis pro Sophie Chang. ", "At only 18 years of age, Sophie reached career high rankings of #569 in singles and #283 in doubles this week.", "\n\nSophie is very well-spoken, intelligent, and mature beyond her years. ", "We discussed how she went from not winning a match for an entire year when she first started competing to becoming a top-ranked junior and then a professional tennis player. ", "Sophie also talked to me about her training, diet, and how she deals with the ups and downs on the USTA Pro Circuit.", "\n\nI found out about Sophie when several of my friends shared clips of her playing and training on social media. ", "I also realized that Sophie is originally from Maryland, my home state, and immediately knew that I wanted her to be a guest on The Tennis Files Podcast!", "\n\nOn this episode, you will learn:\n\nHow Sophie’s support system helped her become an elite tennis player\n\nWhat obstacles Sophie has faced and how she has overcome them\n\nA typical day of training on the pro tour\n\nHow Sophie uses meditation to help her performance\n\nDifferences between the men’s and women’s game\n\nThe mindset that you need to have to succeed on the pro tour\n\nSophie’s favorite tennis drill\n\nHow to deal with the ups and downs on the pro tour\n\nWhy it is difficult to stay financially afloat as a pro\n\nHow Sophie prepares for her tennis matches\n\nand more.", "\n\nSophie is an amazing talent and I expect to see great things from her in the future! ", "There is a ton of great information in this episode that you can use to improve your mindset, training, and your tennis game.", "\n\nSubscribe to automatically download new episodes\n\nClick this icon, click the blue “View in iTunes” button, then hit “Subscribe.”", "\n\nOr hit the subscribe button in your favorite podcast app!", "\n\nLinks Mentioned in This Episode\n\nSophie’s Social Media Pages – Facebook, Twitter, Instagram\n\nResults Personal Training Harford County\n\nSofibella Wear\n\nDragon Promotions\n\nThe Building Blocks of Tennis Success eBook\n\nIf you enjoyed my interview with Sophie, help spread the word and share this episode with a friend!" ]

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[ "Search\n\nLloyds Banking Group is expected to reveal this week that it paid more than 20 of its staff £1 million or more last year, but over 4,000 low-paid workers at the bank got no pay increase at all.", "\n\nUnite national officer Dominic Hook said: “Last week the bank imposed a pay increase worth a measly 1.75 per cent which is to be shared amongst ordinary bank staff.", "\n\n“There are 4,000 staff at Lloyds who got no pay increase at all and large numbers have endured four pay freezes in a row. ", "It is one rule for the millionaires and another for hard-up staff on the front line in branches and call centres.", "\n\n” To make matters even worse Lloyds have sacked 35,000 staff and the majority of workers left are stressed, overworked and feel far from prosperous.", "\n\n“Unite is urging Lloyds to return to the negotiating table to recognise the contribution ordinary staff up and down the country are making to help the bank get back on its feet.”", "\n\nLast week Lloyds Banking Group imposed an additional 1.75% pay pot to be shared amongst staff working in branches, call centres and back office functions up and down the country. ", "Lloyds Banking also announced a further 550 job cuts this month. ", "This is on top of the 1,340 job losses announced in January." ]

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[ "Effect of inhalation injury on lung water accumulation.", "\nFourteen thermally injured patients with severe inhalation injury were sequentially studied with the thermal-green dye double indicator dilution technique of extravascular lung water (EVLW) measurement. ", "Eight females and six males (average age, 49 years, and average thermal burn, 37% body surface) were studied for 2-31 days postinjury. ", "All were burned in a closed space, had facial burns, soot in their sputum, and a mean carboxyhemoglobin level of 30%. ", "Nine patients died, six of sepsis, one each of acute renal failure, hepatorenal syndrome, and anoxic brain damage. ", "Mean EVLW on admission was 7.0 +/- 2.9 ml/kg and remained normal in the five survivors and in the patients dying of acute renal failure and anoxic brain damage. ", "Six patients had increases in EVLW, caused by altered pulmonary capillary permeability in five and by elevation of hydrostatic pressures in one patient (hepatorenal death). ", "Of the five patients with permeability edema, one appeared to result from a direct early effect of inhalation injury resulting in an EVLW of 13.3 ml/kg on admission. ", "The other four patients had EVLW increases after the onset of sepsis, resulting in a mean EVLW of 23.2 +/0- 7.2 ml/kg at death (p less than 0.01). ", "Seventy-one per cent of all patients developed pneumonia, which appears to have caused an EVLW increase in one patient; the other EVLW increases were caused by systemic sepsis. ", "In our present study of 14 patients with definite severe inhalation injury only one had an early increase in EVLW directly related to the inhalation injury, an early effect on capillary permeability presumably caused by direct chemical toxicity of inhaled gases. ", "The remaining four cases of permeability edema occurred 4-24 days postinjury and resulted from burn wound or pulmonary sepsis. ", "We thus conclude that increases in EVLW after thermal and inhalational injury are primarily caused by systemic or pulmonary sepsis, and have a delayed onset. ", "Early increases in EVLW may be a result of the chemical toxicity of inhaled gases but are very uncommon, moderate in degree, and are seen only with the severest cases of inhalation injury." ]

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[ "Zimbabwe Communal Farmers Failing to Access Fertilizer\n\nCommunal farmers in the Buhera District of Manicaland province are back in their fields, but say the lack of fertilizer this farming season may mean a lackluster harvest.", "\n\nCommunal farmers in the Makumbe village of Buhera District say they are happy that the district is getting more rain this season than they got last year, but are worried about shortages of top dressing fertilizer for crops, such as maize.", "\n\nCommunal farmer Colletha Makumbe said her maize crop is yellowing as a result of leaching due to inadequate fertilizer and the heavy rains pounding the district since the new year.", "\n\nAnother grower, Simon Makuvise, said even when available in nearby shops, the top dressing fertilizer is too expensive for the average farmer.", "\n\nThe area's traditional leader, Chief Makumbe, wants to ask Prime Minister Morgan Tsvangirai, who helped many communal farmers with seed, to show his generosity again, this time by providing cheap ammonium nitrate fertilizer.", "\n\nThe prime minister, who hails from the district, provided maize seed to inhabitants of buhera and other parts of the country, while president robert mugabe did the same under the presidential inputs scheme." ]

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[ "/*****************************************************************\n * Licensed to the Apache Software Foundation (ASF) under one\n * or more contributor license agreements. ", " See the NOTICE file\n * distributed with this work for additional information\n * regarding copyright ownership. ", " The ASF licenses this file\n * to you under the Apache License, Version 2.0 (the\n * \"License\"); you may not use this file except in compliance\n * with the License. ", " You may obtain a copy of the License at\n *\n * https://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing,\n * software distributed under the License is distributed on an\n * \"AS IS\" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY\n * KIND, either express or implied. ", " See the License for the\n * specific language governing permissions and limitations\n * under the License.", "\n ****************************************************************/\n\npackage org.apache.cayenne.project.compatibility;\n\nimport java.util.", "Arrays;\nimport java.util.", "Collection;\n\nimport org.apache.cayenne.configuration.server.", "CayenneServerModuleProvider;\nimport org.apache.cayenne.configuration.server.", "ServerModule;\nimport org.apache.cayenne.di.", "Module;\nimport org.apache.cayenne.project.", "ProjectModule;\n\n/**\n * @since 4.1\n */\npublic class ProjectCompatibilityModuleProvider implements CayenneServerModuleProvider {\n\n @Override\n public Module module() {\n return new ProjectCompatibilityModule();\n }\n\n @Override\n public Class<? ", "extends Module> moduleType() {\n return ProjectCompatibilityModule.class;\n }\n\n @Override\n public Collection<Class<? ", "extends Module>> overrides() {\n // compatibility module overrides XML loaders defined in ServerModule and\n // upgrade services from ProjectModule\n return Arrays.asList(ServerModule.class, ProjectModule.class);\n }\n}\n" ]

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[ "Sandara Park passed on a handwritten letter to her fans, after news that 2NE1 would be disbanding broke out just one day earlier.", "\n\nDara, who was in the Philippines at the time, wrote a handwritten letter on a hotel note and passed it to her fans. ", "The heartwarming+breaking letter written to fans showed how much Dara really cares about BlackJacks. ", "It gave hope to her fans that no matter what, they could still be with Dara and continue as a family.", "\n\nREAD MORE: Why Did 2nE1 Disband? ", "Here’s The Reason That YG Entertainment\n\nThe letter uses some of 2NE1’s hit songs and most popular lyrics to share Dara’s feelings. ", "Below is the letter, completely unedited:\n\nIT HURTS… MTBD… PLEASE DON’T GO. ", "I’m so LONELY. ", "We gotta STAY TOGETHER. ", "BABY I MISS YOU.", "\n\nI DON’T CARE what other people say. ", "I wanna SCREAM to the whole world that I LOVE YOU.", "\n\nAnd I’m still FALLING IN LOVE with Blackjacks. ", "DON’T CRY. ", "CAN’T NOBODY hold us down.", "\n\nSo DON’T STOP THE MUSIC. ", "I will be MISSING YOU. ", "I hope you’re HAPPY.", "\n\nIt ain’t over till it’s over. ", "And it’s always GOTTA BE YOU.", "\n\nI’m sorry and thank you BLACKJACKS. ", "From the bottom of my heart. ", "Sincerely yours,\n\nDara of 2NE1\n\nA handwritten letter from Sandara Park. ", "She handed it to Parkers to share to all Blackjacks@SandaraBarCHINA @sgbjcrew @the2ne1hour pic.twitter.com/x2yDxYP8u4 — Parkers LOVE Sandara (@Parkers_Sandara) November 26, 2016\n\nDara went on to like the tweet, confirming that it was a real handwritten letter by her." ]

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[ "Hattori-tenjin Station\n\nis a railway station in Toyonaka, Osaka, Japan, on the Hankyu Takarazuka Line operated by the Hankyu Railway. ", "\n\nThe station name was changed from from December 21, 2013.", "\n\nLines\nHankyu Takarazuka Line\n\nAdjacent stations\n\nReferences\n\nSee also\nList of railway stations in Japan\n\nExternal links\nHattori-tenjin Station \n \n\nCategory:Railway stations in Osaka Prefecture\nCategory:Hankyu Railway Takarazuka Line\nCategory:Stations of Hankyu Railway\nCategory:Railway stations opened in 1910" ]

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[ "the loan store <a href=http://www.movingitalia.eu/index.php?option=com_k2&view=itemlist&task= user&id=3204>payday advance near me</a> pay day loans for bad credit <a href=\"http://lambi.com.mx/index.php?option=com_k2&view=itemlist&task=user& id=69476\"> how to apply for a loan</a>" ]

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[ "Irish prisoners given €500k in interest-free loans by prison service in last three years – with one woman using cash to buy DOG\n\nThe cash is repaid by deducting an amount from the lag’s pocket money each week.", "\n\nBy Darragh Mc Donagh\n\n14th November 2017, 2:42 pm\n\nUpdated: 14th November 2017, 2:42 pm\n\nINMATES have been given €500,000 in interest-free loans by the Irish Prison Service during the past three years, it can be revealed.", "\n\nThe loans were provided for a wide variety of purposes, including the purchase of discretionary items such as games consoles and stereos, as well as helping to cover the cost of Communions and Confirmations.", "\n\nThe next-biggest lender was Mountjoy Prison in Dublin, where prisoners borrowed a total of €88,003 over three years.", "\n\nThe Dochas Centre on the Mountjoy campus, where female offenders are detained, provided a total of €30,366 in loans to its inmates.", "\n\nA short list of examples in respect of loans that were approved last year was provided by the IPS. ", "These included a €300 “Christmas loan” for a prisoner in Mountjoy, €300 for an Xbox at Limerick Prison, €300 for a stereo at Midlands Prison, and €300 for a dog at the Dochas Centre.", "\n\nThe spokesperson said: \"When a loan is given to a prisoner, a direct debit is set up to automatically debit the prisoner’s account each Sunday night with the amount.", "\n\n\"The repayment amount is determined by the value of the loan, the regime the prisoner is on, and the expected release date of the prisoner.\"" ]

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[ "Monday, 7 April 2014\n\nThe Neverending Pile, Day 1: Glitter\n\nHello polish lovers!", "\n\nToday I have my first post in the new Challenge I am participating in, called The Neverending Pile Challenge (NPC), which means I need to get into posting more frequently(every Monday, Wednesday and Friday). ", "It also means my untried pile will finally shrink. ", "Today's prompt is Glitter.", "\n\nI am not a huge glitter fan, so most of what I have I either bought because I loved it, came as part of a set, or my mother bought them for me. ", "The one that I chose is one that I got as part of a set. ", "This is Color Club's Savoy Nights.", "\n\nSavoy Nights has a thick base that is lightly tinted blue but is totally translucent with tonnes and tonnes of micro and medium silver hex glitter. ", "Please excuse my messed up pinky, it smudged before I took my first photo. ", "It took 3 coats to be opaque...it might be better if I did a base first, because the first coat when the glitter was scattered actually looked pretty.", "\n\nI can see why this was an untried, it is not a win, it looks too messy and all the medium hex glitter seems to have curled. ", "This may be one that I give to my niece, now that I have tried it.", "\n\nThat is all for today, but I will be back on Wednesday with the next prompt, which is pastel." ]

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[ "Every other day there’s a hack. ", "Credit card information is stolen, leaving you stuck calling your bank for a new one, or waiting to see if yours is misused, but Privacy is a new tool that lets you create virtual, disposable numbers, then deactivate them instantly if one is stolen.", "\n\n\nYou know how you in Gmail you can create email addresses like “myname+service@gmail.com” and then, if you get spam to it, you know who sold your email address to a list somewhere? ", "Privacy is pretty much the same thing, except for your bank account. ", "You still have the fraud and liability protection that your bank or card issuing company offers, and your transactions happen like normal.", "\n\nInstant disposable Gmail addresses Gmail user Kevin Gunn creates web site specific addresses and sets up filters for them to catch… Read more\n\n\nPrivacy just gives you the ability to create virtual “accounts” that are authorized to charge a given amount to your account. ", "You can set that account to be single use or multi-use, and if the amount is used up, then the transaction doesn’t go through to your main account. ", "If one of your virtual accounts gets hit with an account you don’t recognize, you’ll be able to open the account from the Privacy Chrome or Firefox extension and shut it down immediately. ", "The Chrome extension lets you manage your account quickly, auto-fill shopping sites with your virtual account numbers, or quickly create or shut down numbers.", "\n\nPrivacy is completely free, and makes money by acting as a credit card processor (you can read more here), so that’s why they don’t have to charge you for the service. ", "From a security perspective, you can read all about how Privacy keeps your data safe here, as well as how the service secures its connection with your bank. ", "Hit the link below to learn more, see how it works, and sign up if you’re interested.", "\n\nPrivacy" ]

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[ "Tuesday, April 3, 2018\n\nGrab a look at the first of the dresses Presto remade from the dress I sent her! ", "For my 1:12 friends this is a Pullip doll. ", "She is smaller than Barbie. ", "Her body might be about the size of a Monster High doll.", "\n\nWelcome All!", "\n\nSearch This Blog\n\nFollow this blog with bloglovin\n\nTranslate\n\nAbout Me\n\nWelcome to my blog!I am so happy to see you here! ", "I am now doing what I have always loved...playing with dolls and making their accessories.", "Crafting has been fun for me since I was a child. ", "Although my daughters and I furnished our first dollhouse in the 90's, I didn't start making my own dollhouse accessories 1:12 scale until 2009.", "\nWon't you come join us?" ]

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[ "A study of different dietary survey methods among 30 civil servants.", "\nA sample of 30 volunteers from a population of 100 Ministry of Agriculture, Fisheries and Food (MAFF) civil servants took part in a series of dietary assessments. ", "Food frequency interview, 24-hour dietary recalls, 7-day weighed food record, duplicate diet analysis and 28-day household food purchase records were all used to estimate intakes of energy and a range of nutrients. ", "When results for energy, fat and iron, using the five different methods, were compared there appeared to be systematic differences between methods. ", "The highest results came from food purchase records for the women and from food frequency interviews for the men. ", "Lowest results came from the duplicate diet analysis for fat and energy but from the 24-hour recall for iron, for men and women alike. ", "The implications of these findings, together with possible explanations for them, are discussed." ]

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[ "Q:\n\nIs being able to talk evidence that you can breathe?", "\n\nIn discussions and articles about the death of Eric Garner I encountered several people denying that he was actually choked and couldn't breathe. ", "The essence of that argument most often was that \"if you can talk, you can breathe\", claiming that repeatedly saying \"I can't breathe\", as Eric Garner did according to the video evidence, is proof that he wasn't actually choked.", "\nA CBS News repeats this claim as well:\n\nGarner was overweight and in poor health. ", "Police and their supporters\n argue that if he could repeatedly say, \"I can't breathe,\" as he did\n several times, it means he could breathe.", "\n\nIs it actually a case that people simply cannot speak if they are choked? ", "Or is this wrong, and you can still asphyxiate while being able to talk?", "\nExisting health issues certainly can play a role here, I think answers for healthy as well as people with relevant health issues like asthma would be interesting here. ", "\n\nA:\n\nIs being able to talk evidence that you can breathe?", "\nAsthma guidelines (the victim was asthmatic) say you might talk a little even if you can't breathe enough:\n\nThe Asthma emergency page from \"Athsma Australia\" says that symptoms of a \"life-threatening\" emergency include:\n\nGasping for breath\nUnable to speak or 1-2 words per breath\nConfused or exhausted\nTurning blue\nCollapsing\nMay no longer have wheeze or cough\nNot responding to reliever medication\n\nIMO being able to say \"I can't breathe\" is compatible with \"1-2 words per breath\" symptom.", "\nWhen to seek emergency medical treatment on the Asthma attack page of the Mayo Clinic says,\n\nSeek medical attention right away if you have signs or symptoms of a\n serious asthma attack, which include:\n\nSevere breathlessness or wheezing, especially at night or in the early morning\nThe inability to speak more than short phrases due to shortness of breath\nHaving to strain your chest muscles to breathe\nLow peak flow readings when you use a peak flow meter\n\nAgain, IMO I would characterize \"I can't breathe\" as \"a short phrase\".", "\n\nWhat does 'choked and couldn't breathe' mean?", "\nComments below this answer suggests misunderstandings about the word \"choke\" (in the question and in the actual event).", "\n\nWikipedia says that there are two kinds of choke-hold (i.e. \"air choke\", and \"blood choke\")\nThis BBC article suggests that use of the word \"chokehold\" in a police/reporting context is ambiguous, and could mean either: Eric Garner death: What next for the chokehold?", "\nChoking is also a general/imprecise term for non-specific asphyxiation\n\nWhen I watched the video it seemed to me that:\n\nHe said he couldn't breathe, after being taken to the ground.", "\nWhile (as long as) the alleged choke-hold was being applied, which was for about 10 seconds, he said nothing intelligible/recorded.", "\n\nThat's consistent with the news report (note the word \"after\" in the following report):\n\nA 400-pound asthmatic Staten Island dad died Thursday after a cop put him in a chokehold and other officers appeared to slam his head against the sidewalk, video of the incident shows.", "\n“I can’t breathe! ", "I can’t breathe!” ", "Eric Garner, 43, repeatedly screamed after at least five NYPD officers took him down in front of a Tompkinsville beauty supply store when he balked at being handcuffed.", "\nWithin moments Garner, a married father of six children with two grandchildren, stopped struggling and appeared to be unconscious as police called paramedics to the scene. ", "\n\nI don't want my interpretation of the video to be part of this answer, but I say this in order to explain a limit/limitation of my answer.", "\nWhen I answer \"yes\" (i.e. that it's possible that he couldn't breathe enough, that he was \"choking\" even though he could say a few words) that is because, IMO:\n\nThe victim may still have \"been choking\" even while he was no longer \"being choked\", while he was complaining that he couldn't breathe. ", "\n\"Choking\" does not necessarily mean \"continuous/deliberate compression of the trachea\".", "\nThat isn't want the question is asking (the question doesn't presume that interpretation of choking)\n\nIf the question did imply/require that interpretation of choking, then this answer wouldn't be relevant.", "\nIMO the question is asking about \"choking\" as a synonym for \"asphyxiating\".", "\nThe victim was asthmatic.", "\n\n" ]

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[ "Outline of clinical studies on recombinant human granulocyte colony stimulating factor (KRN 8601) in Japan.", "\nIn phase I studies of KRN 8601, single administration and six-day consecutive administration studies were conducted in healthy male adults using intravenous drip infusion and subcutaneous administration. ", "Safety and tolerance to KRN 8601 were confirmed and a dose-related increase of neutrophil counts by KRN 8601 was observed. ", "In an early phase II study, the safety and tolerance to KRN 8601 in cases of neutropenia following cancer chemotherapy were shown at doses of 25-800 micrograms/m2 and an improvement of neutropenia was seen at doses of more than 50 micrograms/m2. ", "In a phase II study, the optimal dose was investigated for subcutaneous administration and intravenous drip infusion in cases of neutropenia induced by chemotherapy for malignant lymphomas. ", "The optimal dose was 75 micrograms/body (about 50 micrograms/m2) for subcutaneous administration and 100-200 micrograms/m2 for intravenous drip infusion. ", "In a phase III study, a double-blind prospective randomized trial comparing KRN 8601 with an inactive placebo against malignant lymphomas was performed and the inhibitory, improvement and recovery-promoting effects of KRN 8601 (75 micrograms/body, sc) on neutropenia were demonstrated." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "An overview of how drugs are designed and developed.", "\nMedications have traditionally come from natural sources. ", "Recent advances in biology and chemistry have revolutionised the way in which drugs are designed and developed. ", "This article discusses drug discovery and the subsequent testing process." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Introduction {#Sec1}\n============\n\nMEDI0680, previously named AMP-514, is a humanized IgG4κ anti-programmed cell death-1 (PD-1) monoclonal antibody developed to block the immune suppressive PD-1 pathway. ", "The binding of tumoral programmed cell death ligand-1 and -2 (PD-L1 and PD-L2) to the PD-1 receptor on T cells suppresses their ability to launch an antigen-specific antitumor immune response \\[[@CR1]--[@CR3]\\]. ", "PD-1 expression increases on T cells when they are activated, and increased PD-1 expression on circulating T cells has been associated with poor clinical outcome \\[[@CR4]\\]. ", "Blockade of this ligand binding permits continued activation of T cells and has been associated with clinical efficacy in cancer patients \\[[@CR5], [@CR6]\\].", "\n\nIn recent years, antagonistic monoclonal antibodies (mAbs) targeting PD-1 and PD-L1 have demonstrated the ability to restore T-cell effector function and reduce tumor progression \\[[@CR4], [@CR5]\\]. ", "PD-1 targeted immunotherapies nivolumab, pembrolizumab, and cemiplimab have been approved in multiple solid tumor indications \\[[@CR7]--[@CR9]\\]. ", "Among these, melanoma and kidney cancer, specifically renal cell carcinoma (RCC), are considered two of the most immunogenic types of cancer. ", "The efficacy of PD-1-directed therapies in melanoma may be linked to the high mutational burden associated with this cancer type \\[[@CR10], [@CR11]\\]. ", "Although kidney cancer has a lower mutational burden than melanoma \\[[@CR11]\\], nivolumab has shown encouraging results in clinical trials and has been approved in the US for RCC \\[[@CR8]\\].", "\n\nDespite encouraging clinical activity, many patients do not respond to anti-PD-1 mAb therapy or relapse after an initial response, including some patients with evidence of pretreatment PD-L1 expression, immune-cell infiltration, or intermediate-to-high tumor mutational burden \\[[@CR12]\\]. ", "Combinations of anti-PD-1 agents with other immunotherapy agents may offer an opportunity to overcome some of these barriers to response to anti-PD-1 monotherapy. ", "Several combinations are being investigated in ongoing clinical trials, including nivolumab with BMS-986253 (an anti-interleukin-8 mAb; NCT03400332), ALT-803 (an interleukin-15 superagonist complex; NCT02523469), and interferon-gamma (IFNγ) (NCT02614456) \\[[@CR13]--[@CR15]\\] and pembrolizumab with p53MVA, an antitumor vaccine (NCT03113487, NCT02432963) \\[[@CR16]\\]. ", "Another possible combination is with an anti-PD-L1 mAb. ", "Currently, two clinical trials combining anti-PD-1 with anti-PD-L1 agents are ongoing, including one with MEDI0680 (NCT02936102 and NCT02118337) \\[[@CR17], [@CR18]\\]. ", "The biological rationale for this combination approach is simultaneous blockade of PD-1/PD-L1/PD-L2 and PD-1/PD-L1/CD80 interactions \\[[@CR19]--[@CR21]\\]. ", "The purpose of the current study is to characterize the initial safety and clinical efficacy of this anti-PD-1 mAb, and to confirm its intended pharmacodynamic activity.", "\n\nNivolumab and pembrolizumab have shown different safety and efficacy profiles in varying tumor types, despite sharing the same mechanism of action \\[[@CR22]--[@CR27]\\]. ", "Antagonistic antibodies targeting the same protein may have the same mechanism of action, but differences in immunogenicity, binding affinity, plasma half-life, and tissue penetration could affect clinical efficacy, safety, and pharmacokinetics \\[[@CR28]--[@CR30]\\]. ", "Anti-PD-1 mAbs vary due to the degree of antibody humanization and sequence differences in their complementarity-determining regions (CDRs), which determine the precise epitopes bound on the target \\[[@CR28]\\]. ", "MEDI0680 differs from nivolumab and pembrolizumab in its CDR sequence and affinity, which may impact its safety or clinical activity.", "\n\nHere we present the clinical results of the dose-escalation phase of the first-time-in-human (FTIH) phase I study of MEDI0680, including safety, tolerability, and efficacy in patients with solid tumors (NCT02013804). ", "We also describe the preclinical characterization of MEDI0680, as well as its pharmacokinetic and pharmacodynamic profiles in patients.", "\n\nMaterials and methods {#Sec2}\n=====================\n\nPatients and study design {#Sec3}\n-------------------------\n\nIn this open-label, multicenter, dose-escalation and expansion study in checkpoint inhibitor-naïve patients with advanced solid malignancies, MEDI0680 was administered intravenously every 2 weeks (Q2W) or every 3 weeks (Q3W) at doses of 0.1, 0.5, 2.5, 10 or 20 mg/kg as indicated in Table [1](#Tab1){ref-type=\"table\"}. ", "Two cohorts received 20 mg/kg every week (QW) for 2 or 4 weeks followed by 20 mg/kg Q2W. Patients were enrolled using a 3 + 3 study design. ", "One cycle of treatment was defined as 21 days for patients on the Q3W schedule and as 28 days for patients on the Q2W schedule. ", "Key eligibility criteria for the study are shown in Additional file [1](#MOESM1){ref-type=\"media\"}: Table S1. ", "Table 1Baseline patient characteristicsQ3W (mg/kg)Q2W (mg/kg)QW × 2 (mg/kg)QW × 4 (mg/kg)Total0.1 (n = 5)0.5 (*n* = 5)2.5 (n = 3)10 (*n* = 6)20 (*n* = 9)10 (*n* = 4)20 (*n* = 18)20 (*n* = 3)20 (*n* = 5)*N* = 58Median age, years (range)61 (23--69)62 (54--74)58 (51--69)65 (55--78)59 (46--81)68.5 (46--75)65.5 (48--86)65 (61--70)59 (50--64)62.5 (23--86)Male, n (%)5 (100)4 (80)2 (67)4 (67)8 (89)3 (75)13 (72)3 (100)5 (100)47 (81)Race, n (%) White5 (100)5 (100)3 (100)6 (100)9 (100)4 (100)16 (89)3 (100)5 (100)56 (97) Asian0000001 (6)001 (2) Other0000001 (6)001 (7)ECOG status, n (%)^a^ 03 (60)4 (80)2 (67)2 (40)4 (44)2 (50)8 (44)2 (67)2 (40)29 (51) 12 (40)1 (20)1 (33)3 (60)5 (56)2 (50)10 (56)1 (33)3 (60)28 (49)Median time from primary diagnosis to study entry, months (range)48 (4--80)10 (8--27)66 (34--140)26 (9--54)18 (5--46)47 (5--137)15 (0--109)72 (40--72)32 (8--57)19 (0--140)Smoking history, (%) Never smoked3 (60)1 (20)2 (67)3 (50)4 (44)2 (50)8 (44)03 (60)26 (45) Former/current smoker2 (40)4 (80)1 (33)3 (50)5 (56)2 (50)10 (56)3 (100)2 (40)32 (55)Tumor type, n (%) Renal cell1 (20)1 (20)02 (33)7 (78)3 (75)15 (83)3 (100)4 (80)36 (62) Melanoma with mutation^b^1 (20)0002 (22)1 (25)1 (6)005 (9) Non-squamous NSCLC2 (40)2 (40)01 (17)000005 (9) Melanoma-unknown0001 (17)002 (11)01 (20)4 (7) Other^c^01 (20)2 (67)0000003 (5) Squamous NSCLC1 (20)1 (20)00000002 (3) Bladder001 (33)0000001 (2) Ovarian0001 (17)000001 (2) Prostate0001 (17)000001 (2)Prior anti-cancer therapy, n (%)^a^ Biologic4 (80)0001 (11)1 (25)01 (33)1 (20)8 (14) Immunotherapy^de^1 (20)001 (17)000002 (4) Chemotherapy5 (100)4 (80)3 (100)3 (50)01 (25)7 (39)0023 (40) Surgery2 (40)3 (60)2 (67)4 (67)5 (56)2 (50)15 (83)2 (67)4 (80)39 (67) Radiation3 (60)1 (20)1 (33)03 (33)3 (75)9 (50)2 (67)2 (40)24 (41) Other3 (60)1 (20)2 (67)4 (67)5 (56)2 (50)9 (50)3 (100)3 (60)32 (55)*Abbreviations*: *ECOG* Eastern Cooperative Oncology Group, *Fc* fragment crystallizable, *NSCLC* non-small cell lung cancer, *PD-L2* programmed cell death ligand-2 ^a^Data unavailable for 1 patient ^b^All tumors harboring mutations had *BRAF* mutations except for 1 with *EGFR* mutation ^c^Includes adenoma of unknown primary, cellular uterine leiomyoma, and fallopian tube carcinoma ^d^Includes 1 patient enrolled before the May 2014 amendment who received prior AMP-224 PD-L2 Fc fusion protein and 1 patient who received prior pegylated interferon alfa-2b, recorded as an immunotherapy by the investigator ^e^Includes 1 patient who received the therapeutic anticancer vaccine, rocapuldencel-T, plus sunitinib\n\nThe study design is shown in Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S1a, including dose levels and administration frequency for each dose cohort. ", "Eligible patients had advanced solid malignancies that were refractory to standard therapy or for which no standard therapy existed. ", "They were enrolled if they had ≥1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), had not received previous anti-PD-1/PD-L1 antibodies (expanded in a protocol amendment in May 2014 to exclude any immunotherapy except therapeutic cancer vaccines), had sufficient organ function, and had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.", "\n\nBased on accumulating evidence of response to PD-1 inhibition in kidney cancer and melanoma \\[[@CR31]--[@CR35]\\], the study protocol was amended to enroll only patients with these tumor types in cohorts 5--9. ", "Therefore, the majority of patients had kidney cancer (62%) or melanoma (16%).", "\n\nPatients received MEDI0680 for 12 months or until progressive disease; those maintaining disease control were followed for an additional 12 months. ", "All patients were followed long-term for survival. ", "Retreatment was permitted in cases of progression during the 12-month follow-up period.", "\n\nEndpoints and assessments {#Sec4}\n-------------------------\n\n### Primary {#Sec5}\n\nThe primary endpoint was safety, assessed by evaluating dose-limiting toxicities (DLTs), adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiograms. ", "The National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 was used to classify and grade AEs and SAEs. ", "Laboratory abnormalities were monitored from the start of the study until 12 months after the last dose of study drug, or until the patient withdrew from follow-up.", "\n\nAdverse events of special interest (AESIs) included AEs of hepatic function abnormality meeting the definition of Hy's law, Grade ≥ 3 endocrinopathies, Grade ≥ 3 dermatologic AEs, Grade ≥ 3 pneumonitis, and other Grade ≥ 3 immune-related AEs.", "\n\n### Secondary endpoints {#Sec6}\n\nThe secondary endpoints of this study are shown in Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S1b and included assessment of the pharmacokinetics and immunogenicity of MEDI0680, as well as its efficacy.", "\n\n### MEDI0680 concentrations in patient serum {#Sec7}\n\nThe serum concentration of MEDI0680 was determined using a validated electrochemiluminescence (ECL) ligand binding assay format. ", "Standards, controls, and test samples were incubated with biotinylated anti-MEDI0680 bound to a streptavidin-coated plate. ", "Following incubation, ruthenylated anti-IgG4 was added to the plate to allow the formation of molecular complexes. ", "Unbound material was removed by washing the plate, adding MSD read buffer, and detecting bound complexes by ECL using a SECTOR 6000 MSD imager (MesoScale Discovery). ", "Data were analyzed by linear regression using Watson LIMS™ software (Thermo Fisher Scientific) and the concentrations of MEDI0680 in serum were interpolated from a standard curve. ", "The assay lower limit of quantitation was determined to be 0.5 μg/mL and the upper limit of quantitation was 100 μg/mL.\n\n### Anti-drug antibody responses {#Sec8}\n\nAnti-drug antibodies (ADAs) in serum samples were assessed using validated bridging format ECL assays. ", "For all assays, the samples were diluted 1:10 in assay diluent and then incubated with biotinylated and ruthenylated MEDI0680 to allow the formation of molecular complexes. ", "The negative control was a human serum pool, and positive control samples were prepared by spiking the negative control serum pool with ADA. ", "The complexed samples were loaded into wells of a blocked, streptavidin-coated MSD plate, washed, and the bound complexes detected by ECL using a SECTOR 6000 MSD imager (MesoScale Discovery). ", "The data were processed using Watson LIMS™ software (Thermo Fisher Scientific) and the presence of ADAs was determined based on an assay-specific cut-point. ", "Samples that screened as ADA-positive were further assessed using confirmatory and titer assays.", "\n\n### Efficacy {#Sec9}\n\nThe clinical efficacy and antitumor activity secondary endpoints included objective response (OR) and disease control (DC) based on RECIST v1.1 guidelines, modified to require confirmation of progressive disease by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. ", "The rationale for this modification was to discourage premature discontinuation of the investigational agent and provide a more complete evaluation of its antitumor activity than would be seen with conventional RECIST criteria. ", "Additional secondary endpoints assessed were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).", "\n\nExploratory endpoints {#Sec10}\n---------------------\n\nExploratory endpoints including PD-1 receptor occupancy and the pharmacodynamic profile of MEDI0680 were evaluated to assess the biological activity of the drug in both peripheral blood and tumor biopsy samples (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S1b and Table S2).", "\n\n### PD-1 receptor occupancy {#Sec11}\n\nOccupancy of the PD-1 receptor by MEDI0680 was determined using a whole blood drug saturation assay. ", "Briefly, potassium EDTA anti-coagulated whole blood samples from study patients were washed and then incubated with formalin buffer or with a saturating dose of MEDI0680 (30 μg/mL) at ambient temperature for 30 min. ", "Bound MEDI0680 was detected using a biotin-labeled anti-human IgG4 antibody followed by Phycoerythrin (PE)-conjugated streptavidin, after washes in between binding steps. ", "Fluorochrome labeled anti-human CD3 and CD45RO antibodies were used to determine PD-1 receptor occupancy on antigen-experienced (CD45RO+) CD3+ T cells. ", "Receptor occupancy was defined as the percentage of CD3+ CD45RO+ cells bound to MEDI0680 after incubation with formulation buffer divided by the percentage of MEDI0680 bound CD3+ CD45RO+ cells after MEDI0680 saturation.", "\n\n### T-cell activation and proliferation markers {#Sec12}\n\nPeripheral blood mononuclear cell (PBMC) samples were cryopreserved and subsequently evaluated in batches by flow cytometry (BD LSR Fortessa; BD Biosciences). ", "Monoclonal antibodies and viability dye used for flow cytometry panels included: Anti-CD3 BV605, clone SK7 (BD Biosciences); Anti-CD4 PerCP-eFlour710, clone SK3 (eBioscience); Anti-CD8 FITC, clone SK1 (Biolegend); Anti-CCR7 APC, clone G043H7 (Biolegend); Anti-CD45RA PE-Cy7, clone HIT100 (Biolegend); Anti-CD38 BV421, clone HIT2 (Biolegend); Anti-human leukocyte antigen (HLA)-DR PE antibody, clone L243 (Biolegend); Anti-Ki67 BV421, clone B56 (BD Biosciences); Mouse IgG1 BV421, clone X40 (BD Biosciences); Mouse IgG1 PE, clone MOPC21 (Biolegend); Zombie Near-IR Fixable dye (Biolegend). ", "Surface marker staining was followed by intracellular marker staining after fixation and permeabilization. ", "CD4+ and CD8+ T cells were identified after gating on live (Zombie fixable dye negative) CD3+ cells, and CD4 effector memory (T~EM~) cells were defined as CD3 and CD4 double positive cells that were CCR7-- and CD45RA--. ", "Levels of the activation markers CD38 and HLA-DR, as well as the intracellular proliferation marker Ki67, were determined on CD4+ and CD8+ T-cell subsets using FlowJo® Software (FlowJo LLC) by setting gates based on a mouse IgG1 isotype control panel.", "\n\n### Circulating cytokines {#Sec13}\n\nPlasma samples were assessed for levels of the cytokine IFNγ and the chemokines CXCL9 (monokine induced by IFNγ, MIG), CXCL10 (IFNγ-induced protein-10, IP-10), and CXCL11 (interferon-inducible T-cell alpha chemoattractant, I-TAC) using a custom human MULTI-SPOT cytokine 4-plex assay kit and an SI6000 MSD reader (MesoScale Discovery). ", "Sample signals were compared to calibration curves to determine the concentration of each analyte in plasma samples.", "\n\n### PD-L1 and CD8 immunohistochemistry {#Sec14}\n\nTumor biopsies were collected prior to treatment and during treatment (cycle 2 between day 1 and day 15); in addition, archival biopsies were assessed when available. ", "The PD-L1 status of tumor samples was determined from 22 evaluable pretreatment fresh (*n* = 21) or archival (*n* = 1) tumor biopsies formaldehyde fixed paraffin-embedded (FFPE) using the VENTANA PD-L1 (SP263) immunohistochemistry (IHC) assay \\[[@CR7]\\]. ", "Samples were classified as having PD-L1 membrane staining of any intensity in ≥ 25% of tumor cells or \\< 25% of tumor cells \\[[@CR36]\\]. ", "Immunohistochemical staining for CD8 was performed on 14 evaluable fresh paired pre- and on-treatment tumor biopsies (cycle 2 between day 1 and day 15) using rabbit anti-human CD8 monoclonal antibody clone SP239 (Spring Bioscience). ", "Images of immunostained slides were captured using an Aperio digital pathology slide scanner (Leica Biosystems) and examined at 20× magnification. ", "The numbers of CD8+ lymphocytes per entire tissue field containing tumor were counted manually, with a minimum of 3 and a maximum number of 10 fields of view (FOV) counted per case. ", "Areas of necrosis or tissue artifact were excluded. ", "A 20× Aperio image FOV represents 0.4 mm^2^; therefore, mean CD8+ tumor infiltrated lymphocyte (TILs) per mm^2^ were calculated by multiplying the mean number of CD8+ T cells/FOV by 2.5. ", "Non-evaluable specimens were defined as biopsies that did not contain at least 100 tumor cells or specimens that did not maintain adherence to slides during the IHC process.", "\n\n### Tumor gene expression {#Sec15}\n\nTotal RNA was isolated from 11 available and evaluable fresh frozen tumor biopsy samples collected pre- and on-treatment (cycle 2 between day 1 and day 15 in the Q2W or Q3W dosing schedule). ", "The level of RNA transcripts for 171 immune-related genes was measured by TaqMan real-time polymerase chain reaction (Thermo Fisher Scientific) using Fluidigm BioMark 96.96 Dynamic Array chips (Fluidigm Corp). ", "Delta-delta cycle thresholds (ΔΔCt) were calculated for each pre- and on-treatment sample pair and shown as Log2 fold change.", "\n\nStatistical analyses {#Sec16}\n--------------------\n\nMaximum tolerated dose (MTD) evaluation was based on the DLT-evaluable population, defined as patients who received the protocol-assigned treatment and completed the DLT evaluation period (≥ 21 days for the Q3W schedule and ≥ 28 days for the other dosing schedules) or experienced a DLT during this period. ", "Non-evaluable patients in the dose-escalation phase could be replaced. ", "Tolerability and clinical activity evaluations were based on the as-treated population (all patients receiving any dose of study drug).", "\n\nFor clinical activity, OR was defined as confirmed complete response (CR) or partial response (PR), and DC was defined as CR, PR, or stable disease (SD) for ≥ 24 weeks (DCR24). ", "The objective response rate (ORR) and disease control rate (DCR) were calculated as a percentage of the as-treated population.", "\n\nResults {#Sec17}\n=======\n\nPreclinical characterization of MEDI0680 {#Sec18}\n----------------------------------------\n\nMEDI0680 is a humanized mAb of the IgG4 isotype containing a serine-to-proline amino acid replacement in the immunoglobulin fragment crystallizable (Fc) hinge region to stabilize the immunoglobulin and prevent inter-strand fragment antigen-binding (Fab) arm exchange \\[[@CR37]\\]. ", "The mAb bound to PD-1 on activated human T cells with a mean apparent half-maximal (EC~50~) binding value (reflecting bivalent binding) of 822 ± 220 pM (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S2a). ", "The dissociation rate constant (K~D~) for binding of the antibody to recombinant human PD-1 (monovalent binding) was measured as 29 nM by surface plasmon resonance (Biacore). ", "This binding was highly specific for PD-1 as MEDI0680 bound poorly to closely related family members (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S2b and Table S3). ", "The antibody blocked the binding of recombinant human PD-L1 and PD-L2 to human PD-1 expressing Chinese hamster ovary (CHO) cells, with half-maximal inhibitory concentration (IC~50~) values of 2.6 nM and 3.6 nM for PD-L1 and PD-L2, respectively (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S3). ", "Consistent with its PD-1:PD-L1 ligand blocking activity, MEDI0680 enhanced in-vitro IFNγ production in allogeneic dendritic cell / T cell mixed lymphocyte reactions (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S4a) and killing of Epstein--Barr virus (EBV)-expressing esophageal squamous cell carcinoma tumor cells by EBV-reactive primary human T cells (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S4b). ", "The activity of MEDI0680 in these preclinical assays supported testing of the drug in this FTIH phase I clinical trial.", "\n\nPatient characteristics {#Sec19}\n-----------------------\n\nFrom December 2013 to August 2015, a total of 58 eligible patients with solid tumors were enrolled and treated. ", "Data were collected through November 7, 2017. ", "Patient baseline characteristics are summarized in Table [1](#Tab1){ref-type=\"table\"} and patient disposition is shown in Additional file [1](#MOESM1){ref-type=\"media\"}: Table S4.", "\n\nFive of the 9 patients with melanoma had tumors bearing known mutations (4 with *BRAF* mutations and 1 with *EGFR* mutation).", "\n\nSafety {#Sec20}\n------\n\nAn MTD was not reached, thus the highest protocol-defined dose was 20 mg/kg Q2W. Treatment-related AEs occurred in 48 patients (83%) across all cohorts (Table [2](#Tab2){ref-type=\"table\"}). ", "The most commonly reported (\\> 10%) treatment-related AEs of any grade in the study were fatigue (21%), nausea (16%), decreased appetite (16%), vomiting (14%), anemia (12%), pyrexia (12%), arthralgia (12%), pruritus (10%), and asthenia (10%) (Table [3](#Tab3){ref-type=\"table\"}). ", "Grade 1 or 2 treatment-related AEs occurred in 36/58 (62%) patients. ", "Grade 3 or 4 treatment-related AEs occurred in 12/58 (21%) patients; the most common were anemia (4 patients \\[7%\\]); fatigue and aspartate aminotransferase increase (each in 2 patients \\[3%\\]); and abdominal pain, alanine aminotransferase (ALT) increase, arthralgia, asthenia, autoimmune hepatitis, blood alkaline phosphatase increase, blood creatine phosphokinase increase, dehydration, diarrhea, hypercalcemia, hyperkalemia, hypertension, lipase increase, myasthenia gravis, myositis, and urinary tract infection (each in 1 patient \\[2%\\]). ", "Four patients (7%) discontinued due to treatment-related AEs: 1 due to grade 2 pyrexia; 1 due to grade 3 elevated ALT; 1 due to grade 1 creatinine increase, grade 1 potassium increase, grade 3 fatigue, and grade 2 myalgia; and 1 due to grade 2 asthenia. ", "No treatment-related deaths were observed. ", "Table 2Safety summary in the as-treated populationEvent, n (%)^a^Q3W (mg/kg)Q2W (mg/kg)QW × 2 (mg/kg)QW × 4 (mg/kg)TotalCohort 1\\\n0.1\\\n*n* = 5 (%)Cohort 2\\\n0.5\\\n*n* = 5 (%)Cohort 3\\\n2.5\\\n*n* = 3 (%)Cohort 4\\\n10\\\n*n* = 6 (%)Cohort 5\\\n20\\\n*n* = 9 (%)Cohort 6\\\n10\\\n*n* = 4 (%)Cohort 7\\\n20\\\n*n* = 18 (%)Cohort 8\\\n20\\\n*n* = 3 (%)Cohort 9\\\n20\\\n*n* = 5 (%)*N* = 58 (%)Any AE5 (100)5 (100)3 (100)6 (100)9 (100)4 (100)18 (100)3 (100)5 (100)58 (100)Any grade ≥ 3 AE2 (40)5 (100)1 (33)5 (83)6 (67)2 (50)11 (61)1 (33)1 (20)34 (59)Any death (grade 5 AE)1 (20)001 (17)002 (11)004 (7)Serious AE2 (40)4 (80)03 (50)5 (56)1 (25)10 (56)1 (33)2 (40)28 (48)AE leading to discontinuation1 (20)2 (40)01 (17)2 (22)02 (11)008 (14)Treatment-related AE5 (100)4 (80)3 (100)5 (83)5 (56)4 (100)15 (83)3 (100)4 (80)48 (83)Treatment-related grade ≥ 3 AE03 (60)002 (22)06 (33)01 (20)12 (21)Treatment-related death0000000000Treatment-related serious AE01 (20)01 (17)1 (11)1 (25)3 (17)01 (20)8 (14)Treatment-related AE leading to discontinuation02 (40)01 (17)1 (11)00004 (7)*Abbreviation*: *AE* adverse event^a^Patients were counted once for each category regardless of the number of events Table 3Any-grade treatment-related AEs occurring in ≥10% of total population and all grade ≥ 3 treatment-related AEsQ3W (mg/kg)Q2W (mg/kg)QW × 2 (mg/kg)QW × 4 (mg/kg)TotalCohort 1\\\n0.1 (*n* = 5)Cohort 2\\\n0.5 (*n* = 5)Cohort 3\\\n2.5 (*n* = 3)Cohort 4\\\n10 (*n* = 6)Cohort 5\\\n20 (*n* = 9)Cohort 6\\\n10 (*n* = 4)Cohort 7\\\n20 (*n* = 18)Cohort 8\\\n20 (*n* = 3)Cohort 9\\\n20 (*n* = 5)*N* = 58Any-grade treatment-related AE^a^5 (100)4 (80)3 (100)5 (83)5 (56)4 (100)15 (83)3 (100)4 (80)48 (83) Fatigue01 (20)01 (17)1 (11)1 (25)7 (39)1 (33)012 (21) Decreased appetite2 (40)1 (20)2 (67)1 (17)003 (17)009 (16) Nausea1 (20)2 (40)01 (17)1 (11)1 (25)2 (11)1 (33)09 (16) Vomiting2 (40)1 (20)0001 (25)3 (17)1 (33)08 (14) Anemia01 (20)001 (11)03 (17)02 (40)7 (12) Arthralgia00001 (11)03 (17)1 (33)2 (40)7 (12) Pyrexia1 (20)1 (20)01 (17)01 (25)2 (11)01 (20)7 (12) Asthenia01 (20)001 (11)04 (22)006 (10) Pruritus1 (20)01 (33)01 (11)03 (17)006 (10)Grade ≥ 3 treatment-related AEs^a^03 (60)002 (22)06 (33)01 (20)12 (20) Anemia01 (20)001 (11)01 (6)01 (20)4 (7) Fatigue01 (20)001 (11)00002 (3) Aspartate aminotransferase increased01 (20)00001 (6)002 (3) Asthenia00001 (11)00001 (2) Abdominal pain0000001 (6)001 (2) Diarrhea0000001 (6)001 (2) Autoimmune hepatitis01 (20)00000001 (2) Urinary tract infection0000001 (6)001 (2) Alanine aminotransferase increased01 (20)00000001 (2) Blood alkaline phosphatase increased01 (20)00000001 (2) Blood creatine phosphokinase increased0000001 (6)001 (2) Lipase increased00001 (11)00001 (2) Dehydration00001 (11)00001 (2) Hypercalcemia00001 (11)00001 (2) Hyperkalemia0000001 (6)001 (2) Arthralgia0000001 (6)001 (2) Myositis0000001 (6)001 (2) Myasthenia gravis0000001 (6)001 (2) Hypertension0000001 (6)001 (2)All grade ≥ 3 events were grade 3, with the exception of two grade 4 events (one event of increased blood creatine phosphokinase and one event of myositis)*Abbreviation*: *AE* adverse event^a^Patients were counted once for each category regardless of the number of events\n\n### AEs of special interest {#Sec21}\n\nGrade 3 treatment-related AESIs occurred in 4/58 patients (7%): ALT and AST increases and autoimmune hepatitis (*n* = 1, discontinued treatment as described above); lipase increase (*n* = 1, resolved); AST increase and myasthenia gravis (*n* = 1, both resolved); and diarrhea (*n* = 1, resolved; no report of colitis). ", "There were no Grade 4 or 5 treatment-related AESIs. ", "Pneumonitis was not observed.", "\n\nClinical activity {#Sec22}\n-----------------\n\nThe best objective responses at each dose level are shown in Table [4](#Tab4){ref-type=\"table\"}. ", "In total, 8/58 patients in the as-treated population (14%) had a confirmed OR: 3 had melanoma (2 with *BRAF* mutations) and 5 had kidney cancer, including 1 who had a CR. ", "The DCR24 was 17/58 (29%). ", "Tumor size change from baseline (spider plot) is shown in Fig.", " [1](#Fig1){ref-type=\"fig\"}a. ", "The timing and duration of response and onset of progressive disease or new lesions in the responding population (swimmer's plot) is shown in Fig. [", "1](#Fig1){ref-type=\"fig\"}b. ", "The DOR ranged from 9.1 to 110.7 weeks. ", "Three of the 8 responders discontinued study treatment without completing the protocol-defined 12 months of treatment; all had kidney cancer. ", "Of these, 1 with CR and 1 with PR discontinued treatment due to progressive disease, and 1 with PR discontinued due to new brain metastases. ", "Table 4Best overall response in the as-treated populationResponse, n (%)Q3W (mg/kg)Q2W (mg/kg)QW x 2 (mg/kg)QW x 4 (mg/kg)TotalCohort 1\\\n0.1\\\n*n* = 5 (%)Cohort 2\\\n0.5\\\n*n* = 5 (%)Cohort 3\\\n2.5\\\n*n* = 3 (%)Cohort 4\\\n10\\\n*n* = 6 (%)Cohort 5\\\n20\\\n*n* = 9 (%)Cohort 6\\\n10\\\n*n* = 4 (%)Cohort 7\\\n20\\\n*n* = 18 (%)Cohort 8\\\n20\\\n*n* = 3 (%)Cohort 9\\\n20\\\n*n* = 5 (%)*N* = 58 (%)Objective response0001 (17)3 (33)1 (25)3 (17)008 (14) CR00001 (11)^b^00001 (2) PR0001 (17)^c^2 (22)^d^1 (25)^e^3 (17)^b^007 (12) SD001 (33)2 (33)2 (22)1 (25)6 (33)2 (67)4 (80)18 (31) PD3 (60)3 (60)1 (33)1 (17)3 (33)2 (50)5 (28)1 (33)1 (20)20 (35)Non-evaluable^a^2 (40)2 (40)1 (33)2 (33)1 (11)04 (22)0012 (21)*Abbreviations*: *CR* complete response, *PD* progressive disease, *PR* partial response, *SD* stable disease^a^Includes patients who discontinued study before first disease assessment and patients for whom not all target lesions were evaluated^b^Kidney cancer^c^Melanoma^d^Kidney cancer (*n* = 1), melanoma with *BRAF* mutation (*n* = 1)^e^Melanoma with *BRAF* mutation Fig. ", "1Response to MEDI0680 therapy. **", "a** Tumor size change from baseline in the as-treated population. **", "b** The timing and duration of response and onset of progressive disease or new lesions in the responding population. ", "Blue bars indicate treatment initiation to censoring date or progression date. ", "One patient with kidney cancer and PR had an ongoing response but did not have a disease assessment at the time of the last dose\n\nAll 8 responders were in the 10 mg/kg or 20 mg/kg dose cohorts, where peripheral PD-1 receptor occupancy and blood drug concentrations reached a plateau (see pharmacokinetic and receptor occupancy results below). ", "In these pooled 10 and 20 mg/kg cohorts, the ORR was 8/45 (18%); all responses were observed in the Q2W and Q3W groups. ", "The DCR24 was 17/45 (37%) in this subset.", "\n\nTwo patients entered retreatment after the initial 12-month period (1 receiving 10 mg/kg Q3W and the other receiving 20 mg/kg Q2W), but discontinued due to progressive disease.", "\n\nMEDI0680 pharmacokinetic and pharmacodynamic profiles {#Sec23}\n-----------------------------------------------------\n\n### Pharmacokinetics, ADA responses, and PD-1 receptor occupancy {#Sec24}\n\nA dose-proportional increase in peak serum MEDI0680 concentration was observed (Fig.", " [2](#Fig2){ref-type=\"fig\"}a). ", "The mean terminal half-life was estimated to be 19 days, with a standard deviation of 5.6 days at 20 mg/kg Q2W dosing based on simulations in a MEDI0680 population pharmacokinetics model (*n* = 1000) \\[[@CR38]\\]. ", "Fifty-four patients were evaluated for the development of post-baseline ADAs and 8 (15%) tested positive post-dose. ", "Based on samples from 40 patients, a dose-dependent saturation of PD-1 was observed on CD3+ T cells, with median PD-1 receptor occupancy ≥70% after 1 cycle of MEDI0680 treatment at 10 or 20 mg/kg; the highest, most consistent occupancy was obtained with initial weekly dosing at 20 mg/kg (Fig. [", "2](#Fig2){ref-type=\"fig\"}b). ", "Fig. ", "2Pharmacokinetic and receptor occupancy analysis of MEDI0680. **", "a** Pharmacokinetic analysis of MEDI0680 in patient serum. ", "Data represent time points up to 150 days. ", "Abbreviation: *LLOQ* lower limit of quantitation. **", "b** PD-1 receptor occupancy by MEDI0680 on CD45 RO+ CD3 T cells among patients treated at various drug doses and schedules, as indicated. ", "Measurements were done at baseline, during the first cycle of MEDI0680 treatment, and on the first day after the completion of the first cycle\n\n### T-cell activation and proliferation, and cytokine levels in peripheral blood {#Sec25}\n\nAmong total CD4+ and CD8+ T cells from patients receiving \\< 10 mg/kg, 10 mg/kg or 20 mg/kg, at least a 2-fold median increase in the percentage of Ki67+ T cells and activated CD38^high^/HLA-DR^high^ CD4+ T~EM~ cells was observed on day 8 post-treatment during the first cycle (Fig.", " [3](#Fig3){ref-type=\"fig\"}a and Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S5). ", "Consistent with MEDI0680-dependent peripheral T-cell activation, plasma levels of IFNγ and CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) were increased on-treatment with a median 1.5-fold change among patients receiving 10 or 20 mg/kg MEDI0680, with the exception of CXCL11 in patients dosed within the 10 mg/kg cohorts, where no on-treatment median change was observed (Fig. [", "3](#Fig3){ref-type=\"fig\"}b). ", "There was no correlation between increased peripheral biomarkers and clinical response at any MEDI0680 dose level (Additional file [1](#MOESM1){ref-type=\"media\"}: Figure S6). ", "Fig. ", "3Peripheral and intratumoral measures of MEDI0680 activity. **", "a** Peripheral CD4+ and CD8+ T-cell activation and proliferation among treatment groups, as indicated. ", "Shown are the fold changes in the percentages of CD4+ and CD8+ Ki67+ and CD4+ T~EM~ CD38^high^/HLA-DR^high^ cells in whole blood post-treatment. ", "Abbreviation: *T*~*EM*~ effector memory T cells. **", "b** Change in plasma cytokines among treatment groups, as indicated. ", "Shown are the fold change in the plasma levels of IFNγ, CXCL-9, CXCL-10, and CXCL-11 at day 8 post-treatment with MEDI0680. **", "c** Examples of PD-L1+ and CD8+ IHC images (20× magnification) from matched pre- and on-treatment biopsies from an RCC patient. ", "The tumor at screening is characterized by abundant CD8+ TILs and PD-L1 on immune cells but not on tumor cells (\\* symbols on IHC images). ", "The on-treatment tumor has greater CD8+ T-cell infiltration and PD-L1 immunoreactivity on both immune and tumor cells (\\*). **", "d** Levels of CD8+ TILs in tumor biopsies pre- and on-treatment at various dose levels. ", "Abbreviation: *hpf* high power field. (**", "e**) Log~2~ fold change in on-treatment versus pretreatment *CD8A*, *IFNG*, *CXCL9*, and *GZMK* gene expression in RCC and melanoma tumor biopsies. ", "A 1.5-fold change is indicated by the dotted line\n\n### PD-L1 expression and T-cell density and activation in tumor biopsies {#Sec26}\n\nAmong 22 evaluable pretreatment tumor biopsies, 2/22 (9.1%) were scored PD-L1 ≥ 25% and 20/22 (91%) were PD-L1 \\< 25%. ", "None of the responders had evaluable tissue for PD-L1 staining. ", "The PD-L1 ≥ 25% biopsies were from a non-squamous non-small cell lung cancer (NSCLC) patient and a melanoma patient; the former was not evaluable for clinical response and the latter had progressive disease as the best OR. ", "Of the 20 patients with PD-L1 \\< 25%, 2 were not evaluable for clinical response, 10 had SD, and 8 had progressive disease. ", "CD8+ T-cell density and gene expression were evaluated from 14 paired pre- and on-treatment fresh tumor biopsies to determine MEDI0680 activity. ", "During treatment, 8/14 (57%) samples across all dose cohorts showed a 2-fold or greater increase in intratumoral CD8+ T-cell density as measured by IHC (Fig. [", "3](#Fig3){ref-type=\"fig\"}c and d). ", "This was consistent with an increase in *CD8A* gene expression and genes associated with T-cell effector function (Fig. [", "3](#Fig3){ref-type=\"fig\"}e). ", "On-treatment, 2-fold or greater increases in gene expression of *IFNG*, *CXCL9* (a T-cell chemoattractant), and *GZMK* (a marker of cytolytic T-cell activity) were also observed (Fig. [", "3](#Fig3){ref-type=\"fig\"}e). ", "Although association with clinical response could not be determined due to a small sample size of evaluable tumor biopsies, MEDI0680 treatment did elicit T-cell infiltration and/or expansion and showed pharmacodynamic evidence of immune-related antitumor activity.", "\n\nDiscussion {#Sec27}\n==========\n\nIn this FTIH phase I study, MEDI0680 had a tolerable safety profile and demonstrated clinical activity. ", "No treatment-related deaths were observed and the majority of treatment-related AEs were mild to moderate (62% grade 1/2 and 21% grade 3/4). ", "Four patients (7%) discontinued MEDI0680 due to treatment-related AEs. ", "An MTD was not reached.", "\n\nPD-1 receptor occupancy appeared to reach a peak in the 10 mg/kg Q2W and 20 mg/kg Q3W cohorts. ", "Additional patients were recruited at the 20 mg/kg Q2W dose level, including a cohort with weekly dosing for 2 weeks followed by Q2W dosing (20 mg/kg QWx2) and one with weekly dosing for 4 weeks followed by Q2W dosing (20 mg/kg QWx4) to increase confidence that receptor saturation had peaked. ", "No significant differences in receptor occupancy between these groups at cycle 2, day 1 were observed, although median values were numerically higher for the 20 mg/kg cohorts compared to the 10 mg/kg Q2W group. ", "Likewise, pharmacokinetic profiling showed similar trough serum drug levels between the 10 and 20 mg/kg doses, but with numerically higher values for the latter. ", "Considering peripheral PD-1 receptor occupancy and drug levels together with peripheral pharmacodynamic data showing comparable drug activity and similar tolerability profiles at the 10 mg/kg and 20 mg/kg dose levels, 20 mg/kg Q2W was declared the highest protocol-defined dose. ", "Because circulating drug must penetrate tumors against interstitial fluid pressure gradients and despite endocytic consumption within tumors \\[[@CR39]\\], the 20 mg/kg Q2W dose is expected to provide the optimal PD-1 receptor occupancy within tumor tissues themselves.", "\n\nThe safety profile observed in this study was consistent with that of other drugs targeting the PD-1 pathway in patients with solid tumors \\[[@CR40]--[@CR43]\\]. ", "For example, in a phase I study of 30 patients (with various advanced solid tumors) treated with pembrolizumab 1--10 mg/kg Q2W or 2--10 mg/kg Q3W, 70% of patients had treatment-related AEs (all grade 1 or 2) \\[[@CR27]\\]. ", "In another phase I study of advanced malignancies that included 107 patients with advanced melanoma, Topalian and colleagues showed an 84% incidence of treatment-related AEs with nivolumab 0.1--10 mg/kg Q2W; the events were grade 3/4 in 22% of patients \\[[@CR31]\\]. ", "In the current study, grade 3 treatment-related AESIs occurred in 7% of patients; no grade 4 or 5 AESIs were observed. ", "There were no reports of pneumonitis.", "\n\nIn the current study, confirmed objective clinical responses were seen in 8/58 (14%) patients. ", "All responses were in patients with melanoma or kidney cancer, including a single confirmed CR. ", "A response rate of 8/45 (18%) was seen in patients receiving 10--20 mg/kg. ", "Because the trial comprised 11 tumor types and 9 doses, it is not possible to directly compare the response rates seen with MEDI0680 to those of other PD-1 antibodies. ", "However, the 34 patients with kidney cancer and 8 patients with melanoma treated at the 10--20 mg/kg dose levels indicate the response may be similar to other PD-1 antibodies approved for those indications. ", "A 15% (5/34) response rate was seen in kidney cancer patients receiving 10--20 mg/kg doses. ", "Among patients with advanced/metastatic RCC, nivolumab showed response rates of 27% in a phase I study, 9--22% in a phase Ib study, and 20--22% in a phase II study \\[[@CR43]--[@CR45]\\]. ", "Pembrolizumab demonstrated an ORR of 34% in a phase II study as first-line treatment in advanced clear cell RCC \\[[@CR27]\\]; this may be numerically higher than response rates seen for nivolumab as well as MEDI0680 in the current study due to the enrollment of patients that had not received prior systemic therapy. ", "In melanoma patients receiving 10--20 mg/kg in this study, MEDI0680 demonstrated a 38% (3/8) response rate. ", "Pembrolizumab showed response rates of 26% and 38% in advanced melanoma in two phase I studies of 173 and 135 patients, respectively \\[[@CR24], [@CR32]\\]. ", "Response rates with nivolumab in advanced melanoma were 28% in the study of solid tumors described above, and 40% in a large phase III randomized trial \\[[@CR31], [@CR33]\\].", "\n\nAs secondary and exploratory endpoints, the pharmacokinetic and pharmacodynamic profiles of MEDI0680 were explored and examined for association with clinical response. ", "Doses of 10--20 mg/kg showed a maximum PD-1 receptor occupancy ≥70%, comparable to the peak occupancy reported for nivolumab \\[[@CR46]\\]. ", "PD-1 targeting by MEDI0680 showed consistent immunological modulation across dose levels, with a frequent increase of activated CD4+ T~EM~ cells (CD38^high^/HLA-DR^high^) and enhanced proliferation (Ki67 positivity) of CD4+ and CD8+ T cells. ", "This is consistent with the induction of peripheral T-cell activation and proliferation markers monitored in other anti-PD-1 clinical trials \\[[@CR46], [@CR47]\\]. ", "In plasma, MEDI0680 increased circulating IFNγ and IFNγ-induced cytokines (CXCL9, 10, and 11) as previously reported \\[[@CR48]\\]. ", "Similar to these findings, Das et al. ", "examined gene transcription changes in isolated peripheral blood T cells from melanoma patients treated with nivolumab and found changes indicative of natural killer (NK) cell expansion and cytolytic function that included upregulation of the *IFNG* transcript \\[[@CR49]\\]. ", "They also found increased serum levels of the IFNγ-inducible cytokine CXCL10; in their study, CXCL9 and CXCL11 were not examined. ", "However, they found neither increased plasma IFNγ cytokine levels nor upregulation of Ki67 transcript or protein in nivolumab-treated patients, as was found in the current study with MEDI0680. ", "This discrepancy could be the result of differences in the time of assessment and/or sensitivity of plasma cytokine assays used. ", "Peripheral biomarker modulation by MEDI0680 was observed in all patients regardless of clinical response, although some had only minimal changes. ", "A lack of correlation between peripheral immune response to PD-1 inhibitors and clinical response has been reported in melanoma patients treated with pembrolizumab \\[[@CR46]\\], although results in NSCLC patients treated with anti-PD-1 therapies suggest that an early versus late induction of immune activation in a specific subpopulation of CD8+ T cells (Ki67+ PD-1+) may enrich for response \\[[@CR47]\\].", "\n\nIn evaluable tumor biopsies, MEDI0680 showed intratumoral pharmacodynamic activity as evidenced by the induction of CD8+ T-cell infiltration and/or expansion and increases of *IFNG* and IFNγ-inducible gene expression consistent with the mechanisms of action of anti-PD-1 blocking agents. ", "Increased CD8+ T-cell infiltration/proliferation, PD-1, PD-L1, granzyme B, and phosphorylated STAT1 positive immune cells in melanoma tumors have been observed by IHC or gene expression after treatment with pembrolizumab or nivolumab in other trials \\[[@CR50], [@CR51]\\]. ", "In these studies, pretreatment or on-treatment levels of T cells within the tumor or at the tumor margin demonstrated predictive value for response to anti-PD-1 therapy \\[[@CR50], [@CR51]\\]. ", "Other trials with PD-1 inhibitors have also identified pretreatment and post-treatment immune cell correlates with response to therapy \\[[@CR52]--[@CR62]\\]. ", "For example, Daud et al. ", "showed that patients whose melanoma tumors contained ≥ 20% CD8+ T cells with a CTLA-4 high/PD-1 high phenotype demonstrated a significantly higher ORR to anti-PD-1 blockade compared to those whose tumors contained \\< 20% of these cells \\[[@CR56]\\]. ", "Inoue et al. ", "described higher pretreatment CD8+/Treg and CD8+/CD4+ expression ratios and higher lytic enzyme (*GZMA*) and major histocompatibility complex class I (*HLA-A*) expression correlating with anti-PD-1 mAb response in melanoma \\[[@CR57]\\]. ", "Likewise, others have demonstrated that pretreatment IFNγ-related immune gene signatures predicted response to anti-PD-1 therapy in head and neck squamous cell carcinoma, gastric cancer, and melanoma \\[[@CR48], [@CR49], [@CR51]\\]. ", "Collectively, these findings suggest that upregulation of CD8+ T cells and markers of effector T-cell function are common pharmacodynamic biomarkers of anti-PD-1 blockade, and pre- or post-treatment intratumoral levels in some settings are associated with clinical response.", "\n\nIn conclusion, this study demonstrated that MEDI0680 is a clinically active anti-PD-1 antibody with a tolerable safety profile. ", "Maximum receptor occupancy was achieved at doses where most patients showed evidence of peripheral and intratumoral immune-cell activation. ", "MEDI0680 is currently undergoing clinical testing in combination with the anti-PD-L1 mAb durvalumab versus nivolumab monotherapy in patients with kidney cancer (NCT02118337).", "\n\nAdditional file\n===============\n\n {#Sec28}\n\nAdditional file 1:**Figure S1.** ", "Study design and pharmacokinetic/pharmacodynamic assessment. (**", "a**) phase I study design. (**", "b**) Overview of pharmacokinetic and pharmacodynamic profile assessment. **", "Figure S2**. ", "MEDI0680 binding and specificity for PD-1. (**", "a**) MEDI0680 binding to activated primary human T cells. (**", "b**) Binding specificity of MEDI0680 to recombinant human proteins that share amino acid sequence homology with PD-1. **", "Figure S3.** ", "Inhibition of ligand binding to native PD-1 by MEDI0680. (**", "a**) Blockade by MEDI0680 of recombinant human PD-L1 or (**b**) recombinant human PD-L2 binding to CHO cells expressing human PD-1 protein. **", "Figure S4**. ", "In vitro T-cell activation and cytotoxicity mediated by MEDI0680. (**", "a**) IFNγ release into cell culture media of allogeneic dendritic cell--T cell mixed lymphocyte reactions. (**", "b**) Cellular cytotoxicity mediated by EBV-reactive CD8 T cells over time, as determined by non-invasive electrical impedance measurement in an xCelligence RTCA MP instrument as a surrogate for cell death. **", "Figure S5.** ", "Representative examples of flow cytometry of peripheral blood from patients treated with MEDI0680. (**", "a**) Ki67 staining in CD4+ and CD8+ T cells at cycle 1 day 1 pre-treatment (C1D1) and at cycle 1 day 8 post-treatment, as indicated. (**", "b**) HLA-DR and CD38 co-staining on CD4+ effector memory T cells (CD4+ TEM) at the same time points. **", "Figure S6.** ", "Lack of correlation between changes in peripheral pharmacodynamic markers and objective clinical response. (**", "a**) Fold change in the indicated cytokine and chemokine markers in all cohorts or (**b**) only in the 10 and 20mg/kg cohorts or (c) the fold change in T-cell proliferation and CD4+ TEM CD38high HLA-DRhigh (activated) T cells with respect to objective clinical responses are shown. **", "Table S1.** ", "Key eligibility criteria. **", "Table S2.** ", "Patient characteristics and samples evaluated for pharmacodynamic analysis. **", "Table S3.** ", "In silico identification of PD-1 paralogs using the protein Basic Local Alignment Search Tool BLASTp. **", "Table S4.** ", "Study disposition (as-treated population). (", "ZIP 5.02 mb)\n\nAb\n\n: Antibody\n\nADA\n\n: Anti-drug antibody\n\nAE\n\n: Adverse event\n\nALT\n\n: Alanine aminotransferase\n\nANOVA\n\n: Analysis of variance\n\nAUC\n\n: Area under the curve\n\nBOR\n\n: Best overall response\n\nCDR\n\n: Complementarity-determining region\n\nCHO\n\n: Chinese hamster ovary\n\nCR\n\n: Complete response\n\nDC\n\n: Disease control\n\nDCR\n\n: Disease control rate\n\nDCR24\n\n: Disease control rate ≥ 24 weeks\n\nDLT\n\n: Dose-limiting toxicity\n\nDOR\n\n: Duration of response\n\nE:T\n\n: Effector-to-target\n\nEBV\n\n: Epstein--Barr virus\n\nEC~50~\n\n: Drug concentration giving half-maximal response\n\nECACC\n\n: European Collection of Authenticated Cell Cultures\n\nECL\n\n: Electrochemiluminescence\n\nECOG\n\n: Eastern Cooperative Oncology Group\n\nEDTA\n\n: Ethylenediaminetetraacetic acid\n\nELISA\n\n: Enzyme-linked immunosorbent assay\n\nFab\n\n: Fragment antigen-binding\n\nFC\n\n: Fold change\n\nFc\n\n: Fragment crystallizable\n\nFFPE\n\n: Formaldehyde fixed paraffin-embedded\n\nFOV\n\n: Fields of view\n\nFTIH\n\n: First-time-in-human\n\nGM-CSF\n\n: Granulocyte-macrophage colony-stimulating factor\n\nHLA\n\n: Human leukocyte antigen\n\nIC~50~\n\n: Inhibitor concentration where the response (or binding) is reduced by half\n\nIFNγ\n\n: Interferon gamma\n\nIgG\n\n: Immunoglobulin G\n\nIHC\n\n: Immunohistochemistry\n\nIL-4\n\n: Interleukin-4\n\nIP-10\n\n: Interferon gamma-induced protein-10\n\nI-TAC\n\n: Interferon-inducible T-cell alpha chemoattractant\n\nK~D~\n\n: Dissociation rate constant\n\nmAbs\n\n: Monoclonal antibodies\n\nMdFI\n\n: Median fluorescence intensity\n\nMFI\n\n: Mean fluorescence intensity\n\nMTD\n\n: Maximum tolerated dose\n\nNK\n\n: Natural killer\n\nNSCLC\n\n: Non-small cell lung cancer\n\nOR\n\n: Objective response\n\nORR\n\n: Objective response rate\n\nOS\n\n: Overall survival\n\nPBMC\n\n: Peripheral blood mononuclear cell\n\nPCR\n\n: Polymerase chain reaction\n\nPD-1\n\n: Programmed cell death-1\n\nPD-L1\n\n: Programmed cell death ligand-1\n\nPD-L2\n\n: Programmed cell death ligand-2\n\nPE\n\n: Phycoerythrin\n\nPFS\n\n: Progression-free survival\n\nPR\n\n: Partial response\n\nQ2W\n\n: Every 2 weeks\n\nQ3W\n\n: Every 3 weeks\n\nQW\n\n: Every week\n\nRCC\n\n: Renal cell carcinoma\n\nRECIST\n\n: Response Evaluation Criteria in Solid Tumors\n\nSAE\n\n: Serious adverse event\n\nSD\n\n: Stable disease\n\nSPR\n\n: Surface plasmon resonance\n\nT~EM~\n\n: T effector memory cells\n\nTIL\n\n: Tumor infiltrating lymphocyte\n\nΔΔCt\n\n: Delta-delta cycle thresholds\n\n**Publisher's Note**\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "\n\nAung Naing and Jeffrey Infante contributed equally to this work.", "\n\nThe authors would like to thank the patients, their families, and the investigational site staff for their participation in the study; Michael Overstreet and Jessica Filderman of Amplimmune for their work on the peripheral flow cytometry data and Catherine Auge of AstraZeneca for her work on the binding specificity and cytokine data; and Tom O'Neill, Karla Maloveste, and Charmin King of Amplimmune and Serguei Soukharev, Philip Brohawn, Steven Eck, Song Ren, and Christine Kiefer of AstraZeneca for their contributions to the study and drug development program.", "\n\nAN, JI, SG, HB, SB, PL, AW, JE, BC: Acquisition of data; analysis and interpretation of data; review and revision of the manuscript. ", "CB, IA, SB, RM, CM, KP, XS, KS, FW, NE: Analysis and interpretation of data; writing, review and/or revision of the manuscript. ", "SM, SB, JK, MO: Conception and design; development of methodology; acquisition of data; analysis and interpretation of data; writing, review and/or revision of the manuscript. ", "All authors read and approved the final manuscript.", "\n\nThis study (NCT02013804) was funded by AstraZeneca and Amplimmune (Gaithersburg, MD, USA), the manufacturers of MEDI0680. ", "Medical editing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Susanne Gilbert, MA, of Cirrus Communications (New York, NY, USA) and was funded by AstraZeneca.", "\n\nThe clinical dataset analyzed during the current study is available at [clinicaltrials.gov](http://clinicaltrials.gov), <https://clinicaltrials.gov/ct2/show/results/NCT02013804>. ", "Other datasets used and/or analyzed during the current study are available and may be obtained in accordance with AstraZeneca's data sharing policy, which is described at <https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure>.", "\n\nThe study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with the International Conference on Harmonisation/Good Clinical Practice and applicable regulatory requirements. ", "The protocol was approved by Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs) at each center. ", "Patients provided written informed consent to participate.", "\n\nNot applicable.", "\n\nAung Naing: Research grants from NCI, EMD Serono, AstraZeneca, Healios Onc., ", "Nutrition, Atterocor, Amplimmune, Karyopharm Therapeutics, Incyte, Regeneron, Merck, BMS, Pfizer, Neon Therapeutics, Calithera BioSciences, and TopAlliance BioSciences; grants and advisory board membership with ARMO BioSciences, Novartis, and CytomX Therapeutics; grants from Immune Deficiency Foundation (spouse).", "\n\nJeffrey Infante: Consultant for Armo Biosciences and Biomed Valley; employee of Janssen Oncology.", "\n\nSanjay Goel: Funding to conduct clinical trial from AstraZeneca.", "\n\nHoward Burris: Consultant or advisor to Mersana, AstraZeneca, Bristol-Myers Squibb, FORMA Therapeutics, Janssen, Novartis, Roche/Genentech, and TG Therapeutics; research funding from Roche/Genentech, Bristol-Myers Squibb, Incyte, Tarveda Therapeutics, Mersana, AstraZeneca, Macrogenics, Novartis, Boehringer-Ingelheim, Eli Lilly, Seattle Genetics, AbbVie, Bayer, Celldex, Merck, Celgene, Agios, Jounce Therapeutics, Moderna Therapeutics, CytomX Therapeutics, GlaxoSmithKline, Verastem, Tesaro, Immunocore, Takeda, Millennium, BioMed Valley Discoveries, Pfizer, PTC Therapeutics, TG Therapuetics, Loxo, Vertex, eFFECTOR Therapetics, Janssen, Gilead Sciences, Valent Technologies, BioAtla, CicloMed, Harpoon Therapeutics, Jiangsu Hengrui Medicine, Revolution Medicines, Daiichi Sankyo, H3 Biomedicine, Neon Therapeutics, OncoMed, Regeneron, and Sanofi; expert testimony for Novartis.", "\n\nPatricia LoRusso: Advisory boards for Genentech, AstraZeneca, Ipsen, AbbVie, Genmab, Roche, CytomX, and SOTIO; Data Safety Monitoring Boards for Agios, Five Prime, Halozyme, and Tyme.", "\n\nAmy Weise: Speakers' bureau for Array Biopharma.", "\n\nJoseph Eder: No conflicts to disclose.", "\n\nBrendan Curti: Institution receives research funding from AstraZeneca.", "\n\nChelsea Black, Shannon Marshall, Ikbel Achour, Rena May, Chris Morehouse, Kristen Pollizzi, Xuyang Song, Keith Steele, Nairouz Elgeioushi, Farzana Walcott, Joyson Karakunnel, and Michael Oberst are current or former employees of AstraZeneca and own stocks/shares in AstraZeneca. ", "Susannah Barbee is a former employee of Amplimmune.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Why JCPenney's No-Coupon Experiment Is a Bust\n\nBrad Tuttle says people actually like sales and coupons.", "\n\nJCPenney's new plan -- stop offering huge markdowns on inflated, \"fake prices\" in order to offer \"fair and square\" pricing -- sounds good in theory. ", "Prices start at least 40% lower than they had been, with no need for customers to take advantage of sales or coupons to get the lowest price.", "\n\nBut, though CEO Ron Johnson insists that \"customers love the new JCP,\" first quarter results show that sales are way down. \"", "The consensus ... seems to be that the JCPenney ( JCP) makeover is shaping up as a major flop,\" writes Brad Tuttle in Time.", "\n\nWhy? ", "Shoppers like coupons and sales. ", "Johnson thinks this problem can be solved by \"educating\" shoppers about the new, fairer pricing strategy, but they don't want to be educated, Tuttle writes: They want \"that 'Wow! ", "What a deal!' ", "high\" that only markdowns bring, and that high can usually be found at an establishment right next door to your local JCPenney." ]

{ "pile_set_name": "Pile-CC" }

[ 0.019417475728155338, 0.006622516556291391, 0, 0.015873015873015872, 0.024390243902439025, 0, 0, 0.0111731843575419, 0, 0.007874015748031496 ]

[ "+ 1574*f**3/5 - 296106*f**2/5 - 57864366*f + 2815809480 = 0 for f.\n-615, 47, 396\nDetermine c, given that -2*c**2/9 + 21626*c/3 + 1038560/9 = 0.", "\n-16, 32455\nFactor g**2/8 + 3645*g/2 + 10672811/8.", "\n(g + 773)*(g + 13807)/8\nLet -2*b**2 + 58482888*b - 427531023602568 = 0. ", "What is b?", "\n14620722\nFactor h**3/2 + 1008*h**2 + 292325*h/2 + 429429.", "\n(h + 3)*(h + 154)*(h + 1859)/2\nSuppose -28*o**4 + 64592*o**3 - 1588172*o**2 - 228200*o = 0. ", "What is o?", "\n-1/7, 0, 25, 2282\nFind d, given that 80*d**2 + 9924*d - 297404 = 0.", "\n-149, 499/20\nFind h, given that -2*h**2/7 - 5176*h + 19918200/7 = 0.", "\n-18650, 534\nLet -4*b**2 + 3324*b + 824800 = 0. ", "Calculate b.\n-200, 1031\nFind i such that 1458*i**5 - 28664496*i**4 + 61570754*i**3 - 37311116*i**2 + 4560664*i - 157264 = 0.", "\n2/27, 1, 19658\nFactor 5*m**4 + 4610*m**3 + 45685*m**2 + 77560*m + 36480.", "\n5*(m + 1)**2*(m + 8)*(m + 912)\nFind w, given that -8962*w**2/3 + 161338*w/3 - 132 = 0.", "\n11/4481, 18\nSolve s**4 - 2558448*s**3 + 5116893*s**2 - 2558446*s = 0 for s.\n0, 1, 2558446\nFind z such that -3*z**4/2 + 33105*z**3/8 + 19202181*z**2/8 + 1199619*z/2 = 0.", "\n-492, -1/4, 0, 3251\nSolve -2*v**2/3 - 6218972*v/3 + 6218974/3 = 0.", "\n-3109487, 1\nSolve 2*o**2 - 34568*o - 2220544 = 0.", "\n-64, 17348\nSuppose 4*o**3 - 48816*o**2 - 2352384*o = 0. ", "What is o?", "\n-48, 0, 12252\nDetermine y, given that -3*y**2/5 - 438*y + 5165457/5 = 0.", "\n-1727, 997\nWhat is x in -965030*x**2/9 - 1930042*x/9 + 4 = 0?", "\n-2, 9/482515\nWhat is t in 5*t**3/4 + 98905065*t**2/4 + 489110346869955*t/4 - 2445554206977025/4 = 0?", "\n-9890509, 5\nSuppose 2*y**4/15 - 1414*y**3/3 - 155386*y**2 + 3809702*y/3 - 16710652/15 = 0. ", "Calculate y.\n-311, 1, 7, 3838\nDetermine q, given that 2*q**2/11 + 7324*q/11 + 2655264/11 = 0.", "\n-3254, -408\nFactor 2*h**2 - 40110*h - 642272.", "\n2*(h - 20071)*(h + 16)\nFind t, given that -2*t**4 - 898*t**3 + 12950*t**2 - 6638*t - 72228 = 0.", "\n-463, -2, 3, 13\nSuppose 200*o**5 - 519960*o**4 + 331569602*o**3 + 8328780720*o**2 + 1655806976*o + 82624512 = 0. ", "Calculate o.\n-24, -1/10, 1312\nFactor -5*v**2 - 3336210*v - 3336205.", "\n-5*(v + 1)*(v + 667241)\nFind v such that 2*v**4/15 - 748*v**3/15 - 32368*v**2/5 + 14106468*v/5 + 14138586/5 = 0.", "\n-231, -1, 303\nSuppose -5*b**2 + 5968890*b + 11937800 = 0. ", "Calculate b.\n-2, 1193780\nFactor -2*t**2/3 - 681880*t + 2045646.", "\n-2*(t - 3)*(t + 1022823)/3\nFactor 4*z**3 + 423008*z**2 + 2537904*z.", "\n4*z*(z + 6)*(z + 105746)\nFactor -i**2/2 + 106816327*i/2 - 53408163.", "\n-(i - 106816326)*(i - 1)/2\nSolve 4*p**3 + 17704*p**2 + 17739236*p - 4187125264 = 0 for p.\n-2311, 196\nDetermine k so that 5*k**5 - 2270*k**4 + 114960*k**3 + 7427150*k**2 + 14500315*k + 7190400 = 0.", "\n-35, -1, 107, 384\nDetermine s so that -s**2/2 + 95675357*s - 9153773937077449/2 = 0.", "\n95675357\nFactor -v**3 + 2674*v**2 + 2005079*v - 6039276.", "\n-(v - 3284)*(v - 3)*(v + 613)\nSolve -147375*b**3 + 39750*b**2 - 2740*b + 8 = 0.", "\n2/655, 2/15\nWhat is x in -x**3/7 - 18637*x**2/7 - 12347480*x + 3751130800/7 = 0?", "\n-9340, 43\nSuppose -5*o**3 - 7765*o**2 + 915205*o + 922965 = 0. ", "What is o?", "\n-1663, -1, 111\nSuppose -5*z**5 - 55645*z**4 - 146015330*z**3 + 49480548950*z**2 - 1035271892105*z + 5596006298135 = 0. ", "What is z?", "\n-5717, 11, 283\nFind o such that 3*o**5/4 + 12*o**4 - 1071*o**3/4 - 5559*o**2 - 21408*o - 16128 = 0.", "\n-16, -4, -1, 21\nDetermine z, given that 7*z**5 - 17921766*z**4 + 112650920*z**3 - 245783696*z**2 + 204819696*z - 40963936 = 0.", "\n2/7, 2, 2560246\nFactor -169*x**3/2 + 14063725*x**2/2 + 110361756*x + 432978066.", "\n-(x - 83233)*(13*x + 102)**2/2\nSolve 3*u**3/2 - 7026*u**2 - 883341*u/2 + 1388205 = 0 for u.\n-65, 3, 4746\nFactor -4*x**3 - 302244*x**2 - 906696*x.", "\n-4*x*(x + 3)*(x + 75558)\nFactor -q**2/5 + 13865572*q/5 - 48063521721796/5.", "\n-(q - 6932786)**2/5\nWhat is t in -2*t**5 - 212*t**4 + 38318*t**3 + 2508800*t**2 - 232109472*t - 1997017344 = 0?", "\n-133, -8, 84\nSolve 2*l**5 - 7326*l**4 + 138628*l**3 - 568184*l**2 - 1020720*l + 1457600 = 0 for l.\n-2, 1, 10, 3644\nFactor m**2/5 + 1544*m/5 - 2345241/5.", "\n(m - 943)*(m + 2487)/5\nLet 3*o**5 - 2397*o**4 - 2406*o**3 + 4800*o**2 = 0. ", "Calculate o.\n-2, 0, 1, 800\nFind r, given that -25*r**5/2 + 64049*r**4/6 - 14922721*r**3/6 + 173843773*r**2/2 - 249957148*r/3 - 3379138/3 = 0.", "\n-1/75, 1, 41, 406\nSolve -3*h**3 - 49710*h**2 + 2393139*h + 2442846 = 0.", "\n-16618, -1, 49\nFactor -f**2/5 + 127186*f + 635931/5.", "\n-(f - 635931)*(f + 1)/5\nDetermine p so that -2*p**5/15 - 8438*p**4/15 + 47598*p**3 - 139418*p**2/3 - 713968*p/15 + 235176/5 = 0.", "\n-4302, -1, 1, 82\nFactor 2*t**4 + 14474*t**3 + 34671546*t**2 + 26892386878*t - 1433119958900.", "\n2*(t - 50)*(t + 2429)**3\nFind u, given that -3*u**3 - 64974*u**2 - 6603939*u - 168201468 = 0.", "\n-21556, -51\nDetermine u, given that -u**2 + 361801*u/3 - 1567748/3 = 0.", "\n13/3, 120596\nFind v, given that -2*v**2/3 - 291322*v/3 + 582652/3 = 0.", "\n-145663, 2\nFind q such that -16108*q**2 - 563720*q + 2100 = 0.", "\n-35, 15/4027\nLet -u**2/4 - 18617390*u - 346607210412100 = 0. ", "Calculate u.\n-37234780\nSolve -5*j**5 - 20160*j**4 - 20401665*j**3 - 161864950*j**2 + 62532960*j + 1821664800 = 0.", "\n-2012, -6, -5, 3\nSolve -2*p**3/7 - 388656*p**2/7 + 22547094*p/7 - 326957252/7 = 0 for p.\n-194386, 29\nSuppose -3*v**2/4 + 711801*v/2 - 1423599/4 = 0. ", "Calculate v.\n1, 474533\nFactor -254*k**4/3 - 497*k**3/3 - 232*k**2/3 + 11*k/3.", "\n-k*(k + 1)**2*(254*k - 11)/3\nWhat is v in 4*v**4 + 4776*v**3 - 264816*v**2 - 562984*v + 823020 = 0?", "\n-1247, -3, 1, 55\nSuppose -72*b**5 - 300524*b**4 - 340834832*b**3 - 56852982524*b**2 - 2575288436160*b + 143247110400 = 0. ", "Calculate b.\n-1992, -95, 1/18\nSolve 26*i**2/15 + 6287276*i/15 = 0.", "\n-3143638/13, 0\nFind j, given that 2*j**5/7 + 136*j**4/7 - 4622*j**3/7 - 255436*j**2/7 + 259920*j/7 = 0.", "\n-76, -38, 0, 1, 45\nFind s such that 1681*s**3/4 + 2876*s**2 + 6461*s + 4780 = 0.", "\n-4780/1681, -2\nFactor 3*u**2 + 1106235*u - 19913202.", "\n3*(u - 18)*(u + 368763)\nSolve -2*d**5/7 - 4*d**4/7 + 142*d**3/7 + 144*d**2/7 = 0 for d.\n-9, -1, 0, 8\nSolve -12*k**4 + 21392*k**3 + 10676548*k**2 + 198469112*k + 64970880 = 0.", "\n-390, -19, -1/3, 2192\nFactor -b**3 + 108*b**2 - 1451*b + 5208.", "\n-(b - 93)*(b - 8)*(b - 7)\nFactor -3*b**2/4 + 147237*b/4 - 10065825.", "\n-3*(b - 48804)*(b - 275)/4\nDetermine d, given that -33*d**4/5 - 11856*d**3/5 + 32739*d**2/5 + 57594*d/5 + 13032/5 = 0.", "\n-362, -1, -3/11, 4\nFactor 5*r**2 + 7645380*r + 7645375.", "\n5*(r + 1)*(r + 1529075)\nFind r, given that 2*r**2 - 11828444*r + 17489010932642 = 0.", "\n2957111\nFind l, given that -28*l**5 - 292*l**4 + 980*l**3 + 5028*l**2 - 6552*l - 21600 = 0.", "\n-12, -3, -2, 3, 25/7\nWhat is d in -d**5/3 - 23*d**4 + 7652*d**3 - 246428*d**2/3 + 296160*d - 353856 = 0?", "\n-194, 3, 4, 114\nLet -2*u**2/5 - 70189784*u/5 - 615825722245832/5 = 0. ", "Calculate u.\n-17547446\nSolve 5*a**4 - 8010*a**3 + 328555*a**2 - 1490910*a + 1731600 = 0 for a.\n2, 3, 37, 1560\nSuppose 2*b**4/5 + 2824*b**3/5 + 1379258*b**2/5 + 269811516*b/5 + 18197337312/5 = 0. ", "What is b?", "\n-523, -198, -168\nFactor -2*c**2/5 + 1938516*c/5 - 36831082/5.", "\n-2*(c - 969239)*(c - 19)/5\nFactor -s**3/8 + 3307*s**2/4 + 99451*s/8 - 13258.", "\n-(s - 6629)*(s - 1)*(s + 16)/8\nFactor y**2/3 + 8140954*y + 49706349022587.", "\n(y + 12211431)**2/3\nDetermine c so that -3*c**4 - 789*c**3 + 963*c**2 + 1353849*c - 21208668 = 0.", "\n-257, -52, 23\nFind h, given that -2*h**2 - 2368*h + 703560 = 0.", "\n-1430, 246\nFactor 2*t**3/5 + 2972*t**2 + 27617304*t/5 + 55175184/5.", "\n2*(t + 2)*(t + 3714)**2/5\nSolve -3*i**3 + 1514718*i**2 + 12117996*i - 30294840 = 0 for i.\n-10, 2, 504914\nFactor -735*b**2/4 + 81*b/4.", "\n-3*b*(245*b - 27)/4\nDetermine t, given that 3*t**2 - 397075332*t + 13139068273575852 = 0.", "\n66179222\nFactor -s**2 - 4835799*s - 9671594.", "\n-(s + 2)*(s + 4835797)\nWhat is g in 20*g**4 - 139632*g**3 - 754556*g**2 - 279480*g = 0?", "\n-5, -2/5, 0, 6987\nFactor d**2/2 - 436819*d.", "\nd*(d - 873638)/2\nFactor -t**3 + 401468*t**2 + 115684992*t + 8330812416.", "\n-(t - 401756)*(t + 144)**2\nFind r such that 3*r**3/4 + 1463385*r**2/2 + 713831886075*r/4 = 0.", "\n-487795, 0\nDetermine t, given that 2*t**3 + 36654594*t**2 + 167944889335806*t - 167944925990402 = 0.", "\n-9163649, 1\nSolve 2*b**3 + 745886*b**2 + 69542867680*b - 69543613568 = 0 for b.\n-186472, 1\nSolve 4*m**4 + 6316912*m**3 - 151607424*m**2 + 1212863488*m - 3234308096 = 0 for m.\n-1579252, 8\nFind i such that 12*i**4 + 80188*i**3 + 132764024*i**2 - 4005077248*i + 7478456704 = 0.", "\n-3356, 2, 83/3\nLet 3*b**4 + 4343127*b**3 - 13029399*b**2 + 13029405*b - 4343136 = 0. ", "What is b?", "\n-144771" ]

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[ "Movie Madness or How to Lose Money Quickly in Film\n\nI must be imagining things. ", "Sandwiched around some huge movie blockbusters to be released in May, comes this independent film.", "\n\nMaggie Hyllenhall, Michael Fassbender and Domhnall Gleeson in Frank\n\nUnknown to me and probably a lot of other people, Lenny Abrahamson’s comedy about an eccentric band leader, Chris Sievey AKA Frank Sidebottom, will be released (unleashed) in May.\n\nIn case you’re like me and missed this excursion into musical entertainment, Frank Sidebottom was a fictional character assumed by Chris Seivey. ", "He would wear an over-sized papier-mache head as part of the act with a swimmers nose clip on under the mask to alter his voice. ", "None of his music caught a large market segment but several members of his entourage went on to become successful in their own way.", "\n\nSomehow this movie has managed to stay away from the spotlight and is now being promoted. ", "I can’t say this is a movie that attracts my ticket money. ", "We’ll see how it turns out, but to me it looks like a candidate for the Golden Turkey.", "\n\nAs strange as the object of the film may be, surely someone with the acting credentials of Michael Fassbender must look back and wonder, why did I make this film?! ", "Then again, no one in acting wants to be considered only for specific roles. ", "This film should break that mold, if there ever was one for Mr. Fassbender." ]

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[ "White Water Rafting Rishikesh\n\nIf you are adventure lover, white water rafting in Rishikesh won’t sound a word from different world to you! ", "Rishikesh situated near Haridwar a famous spot for white water rafting. ", "It is been popular internationally as the major centre of yoga where people come to rehabilitate their souls and discover themselves through the rich art of meditation. ", "But besides yoga, yoga capital has a lot to offer. ", "The river Ganges comes rushing from mountains, winding down to Shivpuri and Kaudiyala before reaching to Rishikesh. ", "River slows down all of a sudden here and as a result the water splits itself into whitewater. ", "This white water is totally perfect for chilling your spine through white water rafting.", "\nhttp://www.rainbowcamp.in/rafting-in-rishikesh.html" ]

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[ "|\n\n|\n\n|\n\nTrials Evolution announced for XBLA\n\nThe sequel to motorbike stunt/accident simulator Trials HD is due to be released on Xbox Live Arcade this year, packing local and online multiplayer.", "\n\nTrials HD developer RedLynx has announced a sequel to its splendid motorbike stunt and accident simulator, headed to Xbox Live Arcade this year under the name Trials Evolution.", "\n\nEvolution will introduce local and online multiplayer to the series, which sounds like a sure-fire recipe for terrible and beautiful disasters. \"", "True\" outdoor environments and \"a host of additional improvements\" are also promised.", "\n\n\"Trials Evolution is more than just a sequel to Trials HD,\" said Antti Ilvessuo, RedLynx creative director, in the announcement. \"", "We listened carefully to all the feedback we received from the previous game and added it to our own vision of what the ultimate Trials game could be, coming up with a gamer's wish list of must-play features.\"" ]

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[ "Effect of bromocriptine treatment on prolactin, noradrenaline and blood pressure in hypertensive haemodialysis patients.", "\nBromocriptine (2.5 mg/day orally) produced a significant fall in supine mean arterial pressure in nine hypertensive haemodialysis patients with high serum prolactin levels, without causing significant changes in heart rate. ", "On bromocriptine, there was a significant decrease in the mean value of both serum prolactin and plasma noradrenaline, without significant changes in the mean value of plasma renin activity. ", "A significant relationship was found between the changes in supine plasma noradrenaline and the changes in supine mean arterial pressure induced by bromocriptine. ", "The increase in mean arterial pressure in response to the tilt test was greater on bromocriptine than on placebo although the changes in plasma noradrenaline were reduced by bromocriptine. ", "Similar results were observed during the cold pressor test. ", "These findings suggest that the arterial pressure-lowering effect of bromocriptine is related to the reduction in sympathetic out-flow. ", "The parallel decrease in serum prolactin raises the question of the possible involvement of dopaminergic mechanisms in the development of hypertension in our patients. ", "Moreover, bromocriptine seems to enhance the vascular response to endogenous noradrenaline." ]

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[ "I didn't know what to expect from my secret santa this year and was amazed to find not 1 gift but 3 gifts in a package. ", "1 is a $30.00 card for NetFlix which is wonderful. ", "Then came a Google Chromecast which is amazing and finally an awesome book called \"Craft-a-Day.\" ", "These 3 gifts was more then what I had expected to receive and a big thank you to my santa. ", "My santa has a big heart and have a lovely Christmas, thank you :) Sincerely: Monica" ]

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[ "diff --git a/src/test/java/org/joda/time/format/TestISOPeriodFormat.java b/src/test/java/org/joda/time/format/TestISOPeriodFormat.java\nindex bef0d42..ff5e392 100644\n--- a/src/test/java/org/joda/time/format/TestISOPeriodFormat.java\n+++ b/src/test/java/org/joda/time/format/TestISOPeriodFormat.java\n@@ -99,7 +99,7 @@ public class TestISOPeriodFormat extends TestCase {\n \n //-----------------------------------------------------------------------\n public void testFormatStandard() {\n- Period p = new Period(1, 2, 3, 4, 5, 6, 7, 8);\n+ Period p = new Period(1, 2, 3, 4, 5, 6 ,7, 8);\n assertEquals(\"P1Y2M3W4DT5H6M7.008S\", ISOPeriodFormat.standard().print(p));\n p = new Period(1, 2, 3, 4, 5, 6 ,7, 0);\n assertEquals(\"P1Y2M3W4DT5H6M7S\", ISOPeriodFormat.standard().print(p));\n@@ -115,26 +115,6 @@ public class TestISOPeriodFormat extends TestCase {\n assertEquals(\"PT5H6M7.008S\", ISOPeriodFormat.standard().print(TIME_PERIOD));\n }\n \n- public void testFormatStandard_negative() {\n- Period p = new Period(-1, -2, -3, -4, -5, -6, -7, -8);\n- assertEquals(\"P-1Y-2M-3W-4DT-5H-6M-7.008S\", ISOPeriodFormat.standard().print(p));\n- \n- p = Period.years(-54);\n- assertEquals(\"P-54Y\", ISOPeriodFormat.standard().print(p));\n- \n- p = Period.seconds(4).withMillis(-8);\n- assertEquals(\"PT3.992S\", ISOPeriodFormat.standard().print(p));\n- \n- p = Period.seconds(-4).withMillis(8);\n- assertEquals(\"PT-3.992S\", ISOPeriodFormat.standard().print(p));\n- \n- p = Period.seconds(-23);\n- assertEquals(\"PT-23S\", ISOPeriodFormat.standard().print(p));\n- \n- p = Period.millis(-8);\n- assertEquals(\"PT-0.008S\", ISOPeriodFormat.standard().print(p));\n- }\n-\n //-----------------------------------------------------------------------\n public void testFormatAlternate() {\n Period p = new Period(1, 2, 3, 4, 5, 6 ,7, 8);\n" ]

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[ "Invasive hydatidiform mole: immunohistochemical labelling of inhibin/activin subunits, Ki67, p53 and glycodelin A in a rare case.", "\nInvasive trophoblastic mole is an extremely rare condition. ", "Its early recognition is essential since it can transform into an invasive type of tumour. ", "Immunohistochemistry was performed with monoclonal antibodies against inhibin-alpha, -betaA and -betaB, Ki67, p53 and glycodelin A in a rare case of accidentally diagnosed invasive trophoblastic mole. ", "There was labelling of the inhibin/activin subunits, Ki67 and p53, while glycodelin A showed minimal immunopositivity. ", "Therefore, since the pathological diagnosis of an invasive mole is difficult, the immunohistochemical detection of inhibin/activin subunits, Ki67, p53 and glycodelin A might be additional useful tumour markers." ]

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[ "From the beginning of the sausage industry, the sausage has always been made in a casing that would facilitate osmosis. ", "The first sausage was made from animal intestines and osmosis was used to get the smoke through the casing and onto the surface of the sausage without penetrating into the sausage. ", "The smoke, whether liquid smoke or natural, must not be mixed through the emulsion because it causes a bitter taste. ", "Eventually, the industry developed an artificial casing that had the qualities of osmosis, and that has been the standard for many years.", "\nWhen the casing is stuffed with sausage, it is then hung in a smokehouse so that natural smoke passes through the casing by osmosis and unites with the surface only of the sausage, the chemical reaction between the smoke and protein of the sausage forms an artificial skin on the outside surface of the sausage. ", "After processing, the original casing is discarded. ", "Again, it is very important that the smoke does not mix with the sausage other than just at the surface of the sausage, and under the artificial casing. ", "The artificial casing that is capable of osmosis is very expensive and yet it is used almost exclusively, other than natural casing, for making most kinds of sausage. ", "Some attempts have been made to introduce liquid smoke to a sausage strand, but they have not been greatly successful because the liquid became mixed into the sausage. ", "See U.S. Pat. ", "No. ", "5,238,442.", "\nWhen a long shirred casing is used, which is standard practice, the stuffing meat horn must be quite small in diameter in order to take the shirred casing. ", "This means that as the casing is stuffed on a small diameter horn, the velocity of the emulsion coming out of the horn is quite great and any liquid smoke on the inside of the casing would be mixed with the meat emulsion due to the turbulence of the emulsion. ", "This unavoidable turbulence, because of the diameter of the casing compared to the diameter of the small horn extruding the emulsion, is the principal reason why it has never been successful to put the smoke inside the surface of the casing as it is being injected with emulsion.", "\nA further problem of existing sausage machines is that the completed linked sausages are placed in loops of several sausage links on a conveyor having a plurality of moving hooks. ", "Enlongated sticks are then inserted through a number of loops, and the loaded stick is then transported to the smokehouse for cooking and for the introduction of smoke through the osmosis type casing material. ", "After cooking and smoking, the sausage strand is then cut into individual links and packaged. ", "This entire process takes time and is labor intensive.", "\nIt is therefore a principal object of this invention to provide a method and means of applying a liquid to the surface of an extruded strand of meat emulsion which will prevent the liquid from becoming intermixed with the strand of meat emulsion.", "\nA further object of this invention is to rotate a casing and a strand of meat emulsion in the same direction and at the same velocity so that when liquid is applied therebetween as the meat emulsion is discharged into the casing, turbulence in the meat emulsion will be avoided.", "\nA still further object of this invention is to provide a method and means of applying a liquid to the surface of an extruded strand of meat emulsion which can eliminate the use of an osmosis-type casing material.", "\nA still further object of this invention is to use a non-osmosis casing material with liquid smoke being delivered to the surface of the sausage in the sausage making process, to permit the sausage links to be directly delivered to a microwave cooker and thence to a cutting, cooling and package machine immediately downstream from the sausage making machine to avoid use of the conventional cooking and smokehouse procedure.", "\nThese and other objects will be apparent to those skilled in the art." ]

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[ "CBSs Axelrod Heats Up Energy Price By One-Third\n\nForecasting a bleak sweater-swaddled winter for middle class\nAmericans on the December 12 Evening News, CBS correspondent Jim\nAxelrod exaggerated the rise of natural gas heating costs by about\none third over the government-estimated average.", "\n\nAxelrod also omitted good news on the oil and gas\nindustrys faster-than-expected recovery in the Gulf of Mexico while\nportraying a New York woman with outstanding heating bills from 2004\nas just one of many middle class Americans who will suddenly find\nthemselves trapped by rising heating costs.", "\n\nAxelrod opened his piece in an Irvington, N.Y. womans\nkitchen: Nikki Wilson wishes that doing the math meant nothing more\ntroubling than helping her son with his homework, he said, adding,\nstill behind on last year's heating bill, she's looking at a 30\npercent hike in her natural gas prices this year, and has no idea\nhow to make the numbers work.", "\n\nAxelrod then aired a clip of Wilson complaining about\nhaving to choose between Christmas presents and paying her heating\nbill. ", "Rather than assign at least some personal responsibility for\nher plight to Wilson, who reportedly earned $42,000-per-year,\nAxelrod instead cast a dire warning for middle class income-earners.", "\nWith the price of home heating oil now, this is no longer a matter\nof just another blanket on the bed or lowering the thermostat a few\nmore degrees. ", "Its in our heads in a way its never been before, he\nclaimed.", "\n\nApparently to Axelrod the fear about the cost of home\nheating was worse than any time in American history, including the\nenergy crunch in the Carter administration or the dire straits of\nthe Great Depression.", "\n\nWhile Axelrod correctly blamed rising natural gas and\noil prices on Hurricanes Katrina and Rita damaging oil and gas\nfacilities in the Gulf Coast, the CBS reporter\nknown for\nhyping $6-a-gallon gas in Atlanta just after Katrina devastated\nNew Orleans, exaggerated the cost of natural gas, saying natural\ngas prices alone could spike by as much as 50 percent. ", "But in its\nlatest Short-Term\nEnergy Outlook released six days before Axelrods report, the\nEnergy Information Administration (EIA) estimated natural gas prices\nwill go up only an average of 37.8 percent. ", "Axelrod overstated the\ncost by about a third. ", "The EIA also found that overall average\nheating costs would rise 25.7 percent.", "\n\nThe same December 6 EIA forecast noted that the\ninterconnectivity of the natural gas gathering system has helped\nspeed the recovery of shut-in production as suppliers reroute gas\nflow around damaged pipelines to active processing plants.", "\n\nThe term shut-in\nrefers to natural gas that could be produced, but the production of\nwhich is curtailed either for lack of buyers, government mandate,\nor other reasons like pipeline disruptions following a major\nhurricane, the case with Katrina-related cost hikes.", "\n\nThe EIA also noted accelerated recovery from their\nNovember estimate, predicting, a 6.5 percent drop in shut-in natural\ngas by March 2006.", "\n\nAxelrods faulty economic reporting has been reported\nin Business & Media Institute publications such One\nEconomy, Two Spins, and the Media Research Centers October\n2004 study, The\nTen Worst Media Distortions of Campaign 2004, which documented\nAxelrod spinning a good economy into bad news.", "\n\nThe Business & Media Institute has also\ndocumented how CBS and other networks have covered energy\nprices with an alarmist tone while ignoring improving winter heating\nforecasts.", "\n\nFederal employees and military personnel can donate to the Media Research Center through the Combined Federal Campaign or CFC. ", "To donate to the MRC, use CFC #12489. ", "Visit the CFC website for more information about giving opportunities in your workplace." ]

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[ "The White House said other recipients were “recommended, at the invitation of the President, by members of the White House Press Corps,” the White House statement said.", "\n\nAD\n\nThe two biggest individual gifts were given to large, mainstream charities: the American Red Cross and the Salvation Army would get $300,000 each, the White House said.", "\n\nAD\n\nThe next-largest gifts went to charities associated with Christian ministries.", "\n\nThe White House said Trump would give $100,000 to Samaritan's Purse, an evangelical Christian aid agency run by Franklin Graham, the son of famed evangelist Billy Graham. ", "Franklin Graham has been a key political supporter of Trump's: Last month, while Trump was under fire for his comments about the violence in Charlottesville, Graham publicly defended Trump and said the blame lay instead with Satan, for “evil in men's hearts.” ", "Vice President Pence also met with Samaritan's Purse volunteers during his separate trip to hurricane-ravaged areas.", "\n\nTrump also said he would also give $100,000 to Reach Out America, a Houston-based charity connected to the United Pentecostal Church International.", "\n\nAD\n\nThe remaining gifts were all for $25,000 each. ", "The White House said they would go to:\n\nAD\n\n—Operation Blessing International, a faith-based disaster-relief charity based in Virginia Beach\n\n— The Houston Humane Society\n\n—Team Rubicon, a charity that sends teams of military veterans to help in disaster zones.", "\n\n—Portlight Inclusive Disaster Strategies, a nonprofit group that focuses on helping those with disabilities.", "\n\n—Direct Relief, a medical-aid group which has shipped doses of medicines and vaccines — all of which must be kept cold — to flood-ravaged areas in Texas.", "\n\nIt was not immediately clear, from the White House's statement whether the charities had received the donations or whether the checks would arrive in the coming days.", "\n\nAD\n\nBefore last summer, Trump had a long record of making pledges to give his personal money to charity but an uneven record of fulfilling them.", "\n\nIn years past, The Washington Post found, Trump had often promised to give the proceeds of various business ventures — a book, a TV show, and Trump University — to charity. ", "But, often, he paid off those pledges with money from the Donald J. Trump Foundation, a charity filled with other people's money. ", "Or, in some cases, Trump did not fulfill the pledges at all: none of the $5 million he earned from Trump University was actually given to charity.", "\n\nAD\n\nThen, last year, Trump made a bold promise to give $1 million of his own money to veterans' causes, along with $5 million he'd raised from other donors during a telethon-style fundraiser in late January, just before the Iowa caucuses. ", "Months later, Trump's then-campaign manager, Corey Lewandowski, told The Washington Post that Trump had given the money away — but that the details of his gift were secret.", "\n\nAD\n\nThat was false. ", "At the time Lewandowski said that, the money was still in Trump's pocket.", "\n\nTrump only gave away the $1 million later, under heavy media scrutiny. ", "When a reporter asked Trump whether Lewandowski's false statement had been part of an attempt to avoid actually making the donation, Trump called the reporter a “nasty guy.”", "\n\nSince that episode, however, Trump has made good on several new promises to give his own money away.", "\n\nAD\n\nLast summer, after devastating floods in Baton Rouge, Trump gave a $100,000 donation to Greenwell Springs Baptist Church, which was helping residents in the affected area. ", "That church's interim pastor at the time was Anthony Perkins, who is also president of the Family Research Council — a powerful and politically active Christian conservative group that condemns abortion, homosexuality and what it calls “transgenderism.” ", "Perkins has been a strong political supporter of Trump's." ]

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[ "Intel Post Fuels New Dem Fight In Congress\n\nA California lawmaker’s campaign to become chair of a key congressional committee over the objections of House Speaker-elect Nancy Pelosi is dividing Jewish lawmakers and failing to attract public support from Jewish groups.", "\n\nFor months, speculation has bubbled in Washington over Pelosi’s alleged desire to keep the reins of the House Intelligence Committee out of the hands of fellow California Rep. Jane Harman and instead elevate Rep. Alcee Hastings, a South Florida lawmaker who was previously removed from his federal judgeship because of influence peddling. ", "But the fight has taken center stage in recent days, since the Democratic congressional caucus rejected Pelosi’s candidate for majority leader, Pennsylvania Rep. John Murtha, another lawmaker whose reputation has been tainted by ethics allegations.", "\n\nHarman — a centrist panned by liberal critics as insufficiently tough on the Bush administration — appears to be winning the media battle. ", "Several prominent pundits, including Maureen Dowd of The New York Times, have accused Pelosi of allowing a petty personal feud to cloud her political and policy judgment.", "\n\nIn the corridors of Congress, however, Hastings has attracted the public backing of the Congressional Black Caucus and Florida’s House delegation, including two Jewish members. ", "Harman is Jewish, but that has no helped her with Jewish members.", "\n\n“I’m just a Hastings person,” said Rep. Robert Wexler, who recently joined fellow Florida Democrats in signing a letter in support of Hastings. ", "If the decision is “based on qualifications, Alcee wins, hands down… and with respect to impeachment and so forth, first of all, number one, Alcee was acquitted in a court of law, and we really should not be second-guessing an acquittal in a court of law.”", "\n\nDebbie Wasserman Schultz, another Jewish legislator, also signed the letter. ", "The South Florida districts of Wasserman Schultz and Hastings abut each other and are two of the most heavily Jewish in the nation. ", "Hastings, first elected to the House in 1992, is known as one of Israel’s strongest advocates in Congress, as is Harman.", "\n\nIn contrast to Hastings, Harman has failed to secure the public support of many erstwhile allies. ", "Rep. Steny Hoyer of Maryland, who was backed by Harman and opposed by Pelosi in his successful bid to become majority leader, subsequently told ABC’s “This Week With George Stephanopoulos” that he was deferring to the newly elected House speaker on the intelligence committee fight.", "\n\nBoth Harman and Hoyer belong to the moderate Blue Dog Coalition, which gained at least nine members in the last election and was seen as successfully flexing its muscles during the majority leader tussle. ", "But only 18 members, about half of the coalition’s current total, signed a November 15 letter to Pelosi urging her to make Harman the chair of the House Intelligence Committee.", "\n\nEven Harman’s public supporters are loath to openly challenge Pelosi over the appointment.", "\n\n“This is going to be the speaker’s decision,” said New York Rep. Steve Israel, a fellow Blue Dog who signed the group’s letter of support. “", "She has the right to make selections for chair — that’s her prerogative, so I’m going to defer to her prerogative, but I also have the right to co-sign letters putting forth recommendations, and that’s what I’ve done.”", "\n\nTwo other Jewish lawmakers — Rep. Eliot Engel of New York and Rep. Brad Sherman of California — praised Harman’s performance on the intelligence committee but also demurred to Pelosi over the leadership decision.", "\n\nRep. Sherman “abides by, and is in support of, House rules, which leave the decision of House Intel chair to the speaker. ", "It’s Pelosi’s decision,” the lawmaker’s spokesman, Michael Briggs, told the Forward. “", "That being said, he has voiced to Speaker Pelosi his personal opinion, which is that ‘Harman has done a spectacular job.’”", "\n\nHastings’s backers — most notably his colleagues in the Congressional Black Caucus — have backed him unequivocally. ", "Rep. Melvin Watt of North Carolina, the CBC’s chairman, recently said that the 40 plus members of the coalition would not consider a “compromise” candidate, who is rumored to be Silvestre Reyes, a Hispanic lawmaker from Texas.", "\n\n“There’s no reason for us to have that discussion or even consider that, when we are fully supportive of Alcee Hastings and believe that he should be appointed,” Watt told the Congressional Quarterly, a Washington newspaper, last week.", "\n\nWhile Hastings enjoys the support of his fellow Florida Democratic lawmakers, several of Harman’s fellow Jewish lawmakers from California have failed to back her publicly or even hinted that they may support Hastings.", "\n\nRep. Adam Schiff, who like Harman hails from southern California and belongs to the Blue Dog Coalition, declined to sign the centrist group’s letter backing her. ", "A representative for Schiff contacted by the Forward declined to comment.", "\n\nIn June, Rep. Henry Waxman — a Southern California kingmaker who has served in the House since 1974 and is one of its most liberal members — told the Forward that Hastings was “a fine man” who “would do an excellent job” as the committee’s ranking Democrat. ", "He suggested that it is Harman’s time to step down.", "\n\n“She’s trying to stay on, and I know she’s called a lot of people to generate news articles and a lot of pressure on Ms. Pelosi,” said Waxman, who represents a district adjacent to Harman’s on the heavily Jewish west side of Los Angeles. ", "He added, “The Democratic rules have been that the head of that panel is rotated off after a certain period of time… [and] the idea behind it was that we didn’t want members serving on the intelligence committee permanently; we wanted to give other members a chance to serve on it.”", "\n\nAllies of Pelosi have cited the unique term-limits governing the intelligence committee as a rationale for rotating Harman off the panel, even as the incoming House speaker and other Democratic leaders have pledged to implement the recommendations of the bipartisan 9-11 Commission. ", "The commission called for the repeal of term limits, arguing that it would improve congressional oversight of intelligence agencies.", "\n\nPelosi’s office, however, said she would not be wedded to maintaining senior members on the committee.", "\n\n“These recommendations were included by the commission, but left open to the Congress for consideration,” wrote Pelosi’s spokesperson Drew Hammill in an email to the Forward. ", "He added, “Speaker-Designate Pelosi has extensive experience with the Intelligence Committee having served there for 14 years…. [", "and] experience will be just one of many qualifications” she “will take into account when making her decision.”", "\n\nOutside the halls of Congress, African American organizations have openly backed Hastings, while Jewish groups have stayed predominantly neutral. ", "The Black Leadership Forum, an umbrella group that includes the National Association for the Advancement of Colored People, the National Urban League and other organizations, supported Hastings in a November 9 letter to Pelosi.", "\n\nIn late October, Time magazine posted an article on its Web site alleging that the FBI was investigating allegations that Harman and the American Israel Public Affairs Committee had entered into an illegal deal to promote her bid for the intelligence chairmanship. ", "Under the alleged deal — which both sides vigorously deny was ever made — Aipac would urge its donors to lobby Pelosi on Harman’s behalf; in return, Harman would press the government to go easy on two former Aipac staffers, Steve Rosen and Keith Weissman, who are being prosecuted under the Espionage Act for allegedly communicating classified information to Israeli diplomats and reporters.", "\n\nReportedly, Pelosi has been lobbied by some pro-Israel donors, but Aipac insists that it played no role and that it favors neither Harman nor Hastings. ", "Meanwhile, other Jewish groups have said publicly that they have high opinions of both Harman and Hastings.", "\n\n“Jane Harman has been a very strong and impressive voice on the intelligence committee,” said Jess Hordes, Washington director of the Anti-Defamation League. “", "We would certainly be pleased if Harman did get the position, but we probably would be pleased if others did, as well.”" ]

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[ "Santana 20\n\nThe Santana 20 is a one-design class of sailboat commonly used for racing. ", "The boat is popular on the western side of the United States with large fleets in Portland, Seattle, Eugene, Phoenix, Los Angeles, & San Diego. ", " There are also fleets in the Midwest including Denver, Kansas City, Tulsa, Oklahoma City and Atlanta. ", " In production since 1976 there are over 900 hulls manufactured to date. ", " In 1996 the manufacturer, WD Schock Corp, redesigned the deck of the boat creating an opened transom, and roomier, more ergonomic cockpit. ", " This change did not affect the performance characteristics of the boat and the old design boats and new design boats race one design. ", "Many boats have been exported to Mexico and at one time there was a Mexican class association.", "\n\nReferences\n\nCategory:One-make series" ]

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[ "\"Thrust!\" \"", "Thrust!\" \"", "Say, you son-of-a-gun, what are you doing?\" \"", "Say, you son-of-a-gun, what are you doing?\" \"", "Stand still!\" \"", "You think you can stab Yankees like that?\" \"", "Today I will chew you out until you fall!\" \"", "Yes, Sergeant.\" \"", "Thank you very much.\" \"", "Sergeant Tamura!\" \"", "I have told you these rough methods are not permitted here.\" \"", "But, sir, these lazy scum can't fight a war like this.\" \"", "We are on the foremost war front.\" \"", "You are right, but we have no enemy on this island.\" \"", "What we need here is not to know how to fight, but how to stand the long war.\" \"", "But, sir, we have forgotten that we are the lmperial Army soldiers.\" \"", "Soldiers?\" \"", "Tamura, and just what are the soldiers?\" \"", "The countless varieties of ordinary men blown together by the big wind called war.\" \"", "Do you call him a soldier?\" \"", "Tokumaru was a Buddhist priest.\" \"", "I still am, sir.\" \"", "The people say once you become a priest for three days you can never stop it.\" \"", "Is military service hard for you?\" \"", "No, it isn't, sir, if it is for our country.\" \"", "All right, keep it up.\" \"", "Yes, sir.\" \"", "You cannot be like this next time.\" \"", "Next time I'll chew your tails off until you fall.\" \"", "Dismissed!\" \"", "Detach bayonets.\" \"", "Attention!\" \"", "At ease.\" \" ", "Ando.\" \" ", "Sir.\" \"", "You are making good progress.\" \"", "If only we have this boat we can contact our main force and bring us supplies.\" \"", "I'm really glad that I can make use of my carpentry work.\" \"", "To be useful is a most important thing.\" \"", "I am fortunate to have a carpenter who can do such fine work with makeshift tools.\" \"", "Thank you very much, sir.\" \" ", "Say, Tamura!\" \" ", "Yes, sir!\" \"", "Sergeant, I notice two men here who are assigned to other duties.\" \"", "Hirano and Okuda.\" \"", "Yes, sir, but I thought the boat construction needs are urgent.\" \"", "You thought!\" \"", "Hirano is busy with potato fields and Okuda catches fish for us.\" \"", "Take them off the boat detail.\" \"", "Yes, sir.\" \"", "As you wish, sir.\" \"", "And one more thing.\" \"", "Don't overwork the men in this midday heat.\" \"", "Dismiss them until morning.\" \"", "Attention!\" \"", "Detail dismissed for the day!\" \"", "Say, we all have worked hard today.\" \"", "We can launch the boat tomorrow.\" \"", "Shall we celebrate now, though we don't have any sake?\" \"", "Corporal, I understand you are from Yamagata.\" \"", "Yes, Yamagata is noted for rice and the Hanagasa 'flower hat' dance song.\" \"", "Shall we start Bon dance?\" \"", "Try and stop me.\" \"", "Commander, you are a puzzle to me, if I may say so.\" \"", "On one hand you talk about the urgency of boat building while on the other hand you act as though time is nothing.\" \"", "That's true.\" \"", "This place is as timeless as the moon.\" \"", "Do you remember what day it is today?\" \"", "No, sir, I have forgotten.\" \"", "I only know I am being abandoned by the main force.\" \"", "I had volunteered for combat duty.\" \"", "So did I.\" \"I am prepared to risk my life for the country, sir.\" \"", "Commander, what's happening out there, sir?\" \"", "Sometimes I wonder if the war front isn't moving to distant places northward.\" \"", "What will become of Japan, sir?\" \"", "Aircraft!\" \"", "North, northeast, direction of Bougainville.\" \"", "Enemy aircraft approaching!\" \"", "Due south!\" \"", "There!\" \"", "Now one of our Zeros.\" \"", "Complete assembly!\" \"", "We must realize, sir, that time is against us.\" \"", "The plane must have contacted its base by radio.\" \"", "Yes.\" \"", "There will likely be an American rescue force.\" \"", "Then we should attack the landing area before they come.\" \"", "We shouldn't attack blindly.\" \"", "The enemy commander would know better than to stay where he landed.\" \"", "But, sir...\" \"That's enough!\" \"", "I will take command.\" \"", "Our first operation is to locate them and assess their strength.\" \"", "Tamura!\" \" ", "Sir!\" \" ", "You will reconnoiter northeast.\" \"", "Take Private Takumaru and Private Ishii with you.\" \"", "Yes, sir.\" \"", "Corporal Fujimoto, you will reconnoiter southeast.\" \" ", "Yes, sir.\" \" ", "Leave immediately!\" \"", "Yes, sir.\" \"", "Sergeant, it's unwise to disobey our commander.\" \"", "Commander!\" \"", "He is too tame for this job.\" \"", "They say he was the top of his class at officer's school.\" \"", "Shut up!\" \"", "Theory and practice is different.\" \"", "But we are ordered to report to him as soon as we rendezvous.\" \"", "Stop arguing!\" \"", "We can't depend on such a commander.\" \"", "Quiet.\" \"", "We are getting close.\" \"", "Follow me.\" \"", "Attach bayonets.\" \"", "Those Yankees, slippery as snakes.\" \"", "I may sound impertinent, sir, but I have more combat experience than you have.\" \"", "What's wrong with my trying to destroy the enemy?\" \"", "And I would do likewise again, sir, at any sacrifice.\" \"", "You fool!\" \"", "I had planned to attack them tonight, but your disobedience ruined the plan.\" \"", "Next time I will have your head chopped off.\" \"", "Yes, sir.\" \"", "Now listen.\" \"", "Our lookout has just reported that he had seen an enemy ship.\" \"", "We will go into the emergency operation immediately.\" \"", "Ando?\" \" ", "Yes, sir?\" \" ", "You know your orders.\" \" ", "I do, sir.\" \" ", "Carry on.\" \"", "Right face!\" \"", "Don't let them get off a signal to the ship.\" \"", "Shoot anyone who pops out of the jungle.\" \"", "Now let's go.\" \"", "Now let them come out.\" \"", "Let's go.\" \"", "The fish?\" \"", "Hey, this is good.\" \"", "That's all today.\" \"", "Fujimoto.\" \"", "You will re-enforce the spring immediately.\" \"", "Yes, sir.\" \"", "But return at once if you hear firing from this quarter.\" \"", "Yes, sir.\" \"", "I suspect a decoy maneuver to get at our camp.\" \"", "Commander, will the boat be all right?\" \"", "She is like a wife to me, sir.\" \"", "Don't worry.\" \"", "We will defend your wife's honor.\" \"", "Yes, sir.\" \"", "Corporal Fujimoto will take three men to re-enforce the spring, sir.\" \"", "Left face, forward on the double.\" \" ", "Don't waste ammunition.\" \" ", "I saw something moving there.\" \"", "You are impossible.\" \"", "No Yankee boat thieves can be here until the full tide covers the reef.\" \"", "But I am only telling you what I saw.\" \"", "You fool!\" \"", "Don't be a chicken!\" \"", "You are the worst soldier in the whole lmperial Army.\" \"", "I believe I share the distinction, Sergeant.\" \"", "I try to make allowances for a prayer reader.\" \"", "If anything happens to me, read me a prayer, will you?\" \"", "Oh, leave it up to me, Sergeant.\" \"", "Stop it!\" \"", "Not time yet.\" \" ", "Stay on your feet!\" \" ", "Why?\" \"", "Get up, you too!\" \"", "The boat is drifting!\" \"", "Commander!\" \"", "Commander!\" \" ", "Hold fire!\" \" ", "The fore cable has been cut.\" \"", "The cable's been cut off.\" \"", "Take the boat on the other side of the pier.\" \"", "Tamura!\" \"", "Cover them with fire.\" \"", "Go!\" \"", "There's enemy on the boat, too!\" \"", "Bastards!\" \"", "Hand grenade.\" \"", "Tamura, cover me.\" \"", "You took my boat.\" \"", "You took my boat.\" \"", "My boat!\" \"", "My boat.\" \"", "My boat!\" \"", "My boat.\" \"", "Port arms.\" \" ", "Tokumaru.\" \" ", "Yes, sir.\" \"", "You read the prayer for them.\" \"", "Yes, sir.\" \"", "I will bring my rosary.\" \"", "Lance Corporal!\" \"", "Lance Corporal!\" \"", "Please, somebody, come!\" \"", "Please, somebody, come!\" \"", "Commander!\" \"", "Lance Corporal is trying to commit suicide.\" \"", "Please come!\" \"", "Hurry!\" \"", "If I had been a step later we would have had another grave.\" \"", "You make light of your life!\" \"", "Hirano, why do you hurry to death?\" \"", "Because I cannot do anything when my comrades die fighting.\" \"", "Don't be silly.\" \"", "The fighting is not all of life.\" \"", "We have only a few of us left\" \"and we want to hear your songs.\" \"", "Now let's see your leg.\" \"", "And place the helmets from the graves in front of the barracks, pretend the owners are still alive.\" \" ", "Fujimoto.\" \" ", "Yes, sir.\" \"", "Place a layer of hand grenades on sand in this box.\" \"", "We don't want our enemy to know our real strength here.\" \"", "If any of you has any ideas for two plus two equal eight use your initiative.\" \"", "Yes, sir.\" \" ", "Ishii.\" \" ", "Yes, sir.\" \" ", "Is your malaria fever down yet?\" \" ", "I feel all right, sir.\" \"", "The physician is on the way, sir.\" \"", "And that captain is almost draining the well.\" \"", "Did you find out the enemy strength?\" \"", "I ordered you to count the canteens.\" \"", "Yes, sir, I counted, but...\" \"But what?\" \"", "Make it clear.\" \" ", "He fooled me.\" \" ", "Fooled you?\" \"", "He brought only one canteen.\" \"", "It's the world's biggest.\" \"", "A fuel tank from the plane.\" \"", "I can't do business with Yankee traders.\" \"", "Maybe he has a lot more soldiers than we estimated.\" \"", "So do we here.\" \"", "Look.\" \"", "It would look like lots of soldiers resting in the barracks.\" \"", "You couldn't have chosen better window-dressing than that sluggard.\" \"", "There he comes.\" \"", "I have brought the doctor, sir.\" \"", "Everybody out of the barracks!\" \"", "We have a visitor.\" \"", "No, no.\" \"", "Let them rest.\" \"", "As you were.\" \"", "Get your sleep.\" \"", "Tokumaru.\" \" ", "You take the doctor's case.\" \" ", "Yes, sir, I will.\" \"", "What fool left all this dangerous stuff around here?\" \"", "Put it out of the way.\" \"", "Tamura!\" \"", "Get him a glass of water.\" \"", "This is a medicine, this will relax you.\" \"", "Hirano.\" \"", "Your leg has to be operated on.\" \"", "Otherwise your life may be at risk.\" \"", "Did you take the malaria medicine that guy gave you?\" \"", "Could this be quinine?\" \"", "May be poison.\" \"", "Hey!\" \"", "Please cut off my leg.\" \"", "Sato.\" \"", "Bring Ando's tool.\" \"", "Save us, merciful Buddha.\" \"", "If I die without the operation I might as well die with it.\" \"", "If the ship will not take a girl\" \"I will cut my long hair\" \"And put myself in military uniform And follow you wherever you go.\" \"", "The coming of the monsoon!\" \"", "Tidal wave weather.\" \"", "Take all the supplies up the hill!\" \"", "Say.\" \"", "Oh, damn it, I missed one.\" \"", "You stay there.\" \"", "Don't move.\" \"", "Here we go.\" \"", "Damn, I missed again.\" \"", "This time I'll get it.\" \"", "Here I go.\" \"", "You can do nothing for me.\" \"", "Save us, merciful Buddha.\" \"", "Left face!\" \"", "Forward march!\" \"", "Keiko.\" \"", "Keiko.\"" ]

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[ "Q:\n\nHow to add a callback for setAttribute?", "\n\nIs it possible to add a callback on setAttribute on Prototype ? ", "\nFor this example, I would like to show an alert(\"done !\") ", "when setAttribute() is finished. ", "\nimg.setAttribute(\"src\", \"http://blabla.com/c.jpg\");\n\nA:\n\nYou could, but I wouldn't recommend it.", "\n(function() {\n\n var elementSetAttribute = Element.prototype.setAttribute;\n\n Element.prototype.setAttribute = function() {\n whateverFunctionYouWant.call(this);\n\n return elementSetAttribute.apply(this, arguments);\n }\n\n})();\n\njsFiddle.", "\nThis will call whateverFunctionYouWant() when you do something such as document.links[0].setAttribute('href', '/').", "\nYou seem to want this to call a callback when you change the src attribute of img elements and the new resource has loaded...\n(function() {\n\n var HTMLImageElementSetAttribute = HTMLImageElement.prototype.setAttribute;\n\n HTMLImageElement.prototype.setAttribute = function(attribute, value) {\n var image;\n\n if (attribute == 'src') {\n image = new Image;\n image.addEventListener('load', loaded, false);\n image.src = value;\n }\n\n return HTMLImageElementSetAttribute.apply(this, arguments);\n }\n\n})();\n\njsFiddle.", "\nYou could overload setAttribute() here with a third parameter, which would be the callback.", "\nIn my opinion and experience, I'd create a different function instead for doing this. ", "Modifying prototypes is one thing, but overloading native DOM methods to do extra things sounds like inviting trouble, especially once a developer unfamiliar with what you've done looks at the code.", "\nIt goes without saying that if you want the latter example to work < IE9, use the attachEvent() fallback for adding the event listener.", "\n\n" ]

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[ "// Copyright 2005, Google Inc.\n// All rights reserved.", "\n//\n// Redistribution and use in source and binary forms, with or without\n// modification, are permitted provided that the following conditions are\n// met:\n//\n// * Redistributions of source code must retain the above copyright\n// notice, this list of conditions and the following disclaimer.", "\n// * Redistributions in binary form must reproduce the above\n// copyright notice, this list of conditions and the following disclaimer\n// in the documentation and/or other materials provided with the\n// distribution.", "\n// * Neither the name of Google Inc. nor the names of its\n// contributors may be used to endorse or promote products derived from\n// this software without specific prior written permission.", "\n//\n// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS\n// \"AS IS\" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT\n// LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR\n// A PARTICULAR PURPOSE ARE DISCLAIMED. ", "IN NO EVENT SHALL THE COPYRIGHT\n// OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,\n// SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT\n// LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,\n// DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY\n// THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT\n// (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE\n// OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.", "\n//\n// The Google C++ Testing and Mocking Framework (Google Test)\n//\n// This header file declares functions and macros used internally by\n// Google Test. ", " They are subject to change without notice.", "\n\n// GOOGLETEST_CM0001 DO NOT DELETE\n\n#ifndef GTEST_INCLUDE_GTEST_INTERNAL_GTEST_INTERNAL_H_\n#define GTEST_INCLUDE_GTEST_INTERNAL_GTEST_INTERNAL_H_\n\n#include \"gtest/internal/gtest-port.h\"\n\n#if GTEST_OS_LINUX\n# include <stdlib.h>\n# include <sys/types.h>\n# include <sys/wait.h>\n# include <unistd.h>\n#endif // GTEST_OS_LINUX\n\n#if GTEST_HAS_EXCEPTIONS\n# include <stdexcept>\n#endif\n\n#include <ctype.h>\n#include <float.h>\n#include <string.h>\n#include <iomanip>\n#include <limits>\n#include <map>\n#include <set>\n#include <string>\n#include <vector>\n\n#include \"gtest/gtest-message.h\"\n#include \"gtest/internal/gtest-filepath.h\"\n#include \"gtest/internal/gtest-string.h\"\n#include \"gtest/internal/gtest-type-util.h\"\n\n// Due to C++ preprocessor weirdness, we need double indirection to\n// concatenate two tokens when one of them is __LINE__. ", " Writing\n//\n// foo ## __LINE__\n//\n// will result in the token foo__LINE__, instead of foo followed by\n// the current line number. ", " For more details, see\n// http://www.parashift.com/c++-faq-lite/misc-technical-issues.html#faq-39.6\n#define GTEST_CONCAT_TOKEN_(foo, bar) GTEST_CONCAT_TOKEN_IMPL_(foo, bar)\n#define GTEST_CONCAT_TOKEN_IMPL_(foo, bar) foo ## bar\n\n// Stringifies its argument.", "\n#define GTEST_STRINGIFY_(name) #name\n\nclass ProtocolMessage;\nnamespace proto2 { class Message; }\n\nnamespace testing {\n\n// Forward declarations.", "\n\nclass AssertionResult; // Result of an assertion.", "\nclass Message; // Represents a failure message.", "\nclass Test; // Represents a test.", "\nclass TestInfo; // Information about a test.", "\nclass TestPartResult; // Result of a test part.", "\nclass UnitTest; // A collection of test cases.", "\n\ntemplate <typename T>\n::std::string PrintToString(const T& value);\n\nnamespace internal {\n\nstruct TraceInfo; // Information about a trace point.", "\nclass TestInfoImpl; // Opaque implementation of TestInfo\nclass UnitTestImpl; // Opaque implementation of UnitTest\n\n// The text used in failure messages to indicate the start of the\n// stack trace.", "\nGTEST_API_ extern const char kStackTraceMarker[];\n\n// Two overloaded helpers for checking at compile time whether an\n// expression is a null pointer literal (i.e. NULL or any 0-valued\n// compile-time integral constant). ", " Their return values have\n// different sizes, so we can use sizeof() to test which version is\n// picked by the compiler. ", " These helpers have no implementations, as\n// we only need their signatures.", "\n//\n// Given IsNullLiteralHelper(x), the compiler will pick the first\n// version if x can be implicitly converted to Secret*, and pick the\n// second version otherwise. ", " Since Secret is a secret and incomplete\n// type, the only expression a user can write that has type Secret* is\n// a null pointer literal. ", " Therefore, we know that x is a null\n// pointer literal if and only if the first version is picked by the\n// compiler.", "\nchar IsNullLiteralHelper(Secret* p);\nchar (&IsNullLiteralHelper(...))[2]; // NOLINT\n\n// A compile-time bool constant that is true if and only if x is a\n// null pointer literal (i.e. NULL or any 0-valued compile-time\n// integral constant).", "\n#ifdef GTEST_ELLIPSIS_NEEDS_POD_\n// We lose support for NULL detection where the compiler doesn't like\n// passing non-POD classes through ellipsis (...).", "\n# define GTEST_IS_NULL_LITERAL_(x) false\n#else\n# define GTEST_IS_NULL_LITERAL_(x) \\\n (sizeof(::testing::internal::IsNullLiteralHelper(x)) == 1)\n#endif // GTEST_ELLIPSIS_NEEDS_POD_\n\n// Appends the user-supplied message to the Google-Test-generated message.", "\nGTEST_API_ std::string AppendUserMessage(\n const std::string& gtest_msg, const Message& user_msg);\n\n#if GTEST_HAS_EXCEPTIONS\n\nGTEST_DISABLE_MSC_WARNINGS_PUSH_(4275 \\\n/* an exported class was derived from a class that was not exported */)\n\n// This exception is thrown by (and only by) a failed Google Test\n// assertion when GTEST_FLAG(throw_on_failure) is true (if exceptions\n// are enabled). ", " We derive it from std::runtime_error, which is for\n// errors presumably detectable only at run time. ", " Since\n// std::runtime_error inherits from std::exception, many testing\n// frameworks know how to extract and print the message inside it.", "\nclass GTEST_API_ GoogleTestFailureException : public ::std::runtime_error {\n public:\n explicit GoogleTestFailureException(const TestPartResult& failure);\n};\n\nGTEST_DISABLE_MSC_WARNINGS_POP_() // 4275\n\n#endif // GTEST_HAS_EXCEPTIONS\n\nnamespace edit_distance {\n// Returns the optimal edits to go from 'left' to 'right'.", "\n// All edits cost the same, with replace having lower priority than\n// add/remove.", "\n// Simple implementation of the Wagner-Fischer algorithm.", "\n// See http://en.wikipedia.org/wiki/Wagner-Fischer_algorithm\nenum EditType { kMatch, kAdd, kRemove, kReplace };\nGTEST_API_ std::vector<EditType> CalculateOptimalEdits(\n const std::vector<size_t>& left, const std::vector<size_t>& right);\n\n// Same as above, but the input is represented as strings.", "\nGTEST_API_ std::vector<EditType> CalculateOptimalEdits(\n const std::vector<std::string>& left,\n const std::vector<std::string>& right);\n\n// Create a diff of the input strings in Unified diff format.", "\nGTEST_API_ std::string CreateUnifiedDiff(const std::vector<std::string>& left,\n const std::vector<std::string>& right,\n size_t context = 2);\n\n} // namespace edit_distance\n\n// Calculate the diff between 'left' and 'right' and return it in unified diff\n// format.", "\n// If not null, stores in 'total_line_count' the total number of lines found\n// in left + right.", "\nGTEST_API_ std::string DiffStrings(const std::string& left,\n const std::string& right,\n size_t* total_line_count);\n\n// Constructs and returns the message for an equality assertion\n// (e.g. ASSERT_EQ, EXPECT_STREQ, etc) failure.", "\n//\n// The first four parameters are the expressions used in the assertion\n// and their values, as strings. ", " For example, for ASSERT_EQ(foo, bar)\n// where foo is 5 and bar is 6, we have:\n//\n// expected_expression: \"foo\"\n// actual_expression: \"bar\"\n// expected_value: \"5\"\n// actual_value: \"6\"\n//\n// The ignoring_case parameter is true iff the assertion is a\n// *_STRCASEEQ*. ", " When it's true, the string \" (ignoring case)\" will\n// be inserted into the message.", "\nGTEST_API_ AssertionResult EqFailure(const char* expected_expression,\n const char* actual_expression,\n const std::string& expected_value,\n const std::string& actual_value,\n bool ignoring_case);\n\n// Constructs a failure message for Boolean assertions such as EXPECT_TRUE.", "\nGTEST_API_ std::string GetBoolAssertionFailureMessage(\n const AssertionResult& assertion_result,\n const char* expression_text,\n const char* actual_predicate_value,\n const char* expected_predicate_value);\n\n// This template class represents an IEEE floating-point number\n// (either single-precision or double-precision, depending on the\n// template parameters).", "\n//\n// The purpose of this class is to do more sophisticated number\n// comparison. ", " (Due to round-off error, etc, it's very unlikely that\n// two floating-points will be equal exactly. ", " Hence a naive\n// comparison by the == operation often doesn't work.)", "\n//\n// Format of IEEE floating-point:\n//\n// The most-significant bit being the leftmost, an IEEE\n// floating-point looks like\n//\n// sign_bit exponent_bits fraction_bits\n//\n// Here, sign_bit is a single bit that designates the sign of the\n// number.", "\n//\n// For float, there are 8 exponent bits and 23 fraction bits.", "\n//\n// For double, there are 11 exponent bits and 52 fraction bits.", "\n//\n// More details can be found at\n// http://en.wikipedia.org/wiki/IEEE_floating-point_standard.", "\n//\n// Template parameter:\n//\n// RawType: the raw floating-point type (either float or double)\ntemplate <typename RawType>\nclass FloatingPoint {\n public:\n // Defines the unsigned integer type that has the same size as the\n // floating point number.", "\n typedef typename TypeWithSize<sizeof(RawType)>::UInt Bits;\n\n // Constants.", "\n\n // # of bits in a number.", "\n static const size_t kBitCount = 8*sizeof(RawType);\n\n // # of fraction bits in a number.", "\n static const size_t kFractionBitCount =\n std::numeric_limits<RawType>::digits - 1;\n\n // # of exponent bits in a number.", "\n static const size_t kExponentBitCount = kBitCount - 1 - kFractionBitCount;\n\n // The mask for the sign bit.", "\n static const Bits kSignBitMask = static_cast<Bits>(1) << (kBitCount - 1);\n\n // The mask for the fraction bits.", "\n static const Bits kFractionBitMask =\n ~static_cast<Bits>(0) >> (kExponentBitCount + 1);\n\n // The mask for the exponent bits.", "\n static const Bits kExponentBitMask = ~(kSignBitMask | kFractionBitMask);\n\n // How many ULP's (Units in the Last Place) we want to tolerate when\n // comparing two numbers. ", " The larger the value, the more error we\n // allow. ", " A 0 value means that two numbers must be exactly the same\n // to be considered equal.", "\n //\n // The maximum error of a single floating-point operation is 0.5\n // units in the last place. ", " On Intel CPU's, all floating-point\n // calculations are done with 80-bit precision, while double has 64\n // bits. ", " Therefore, 4 should be enough for ordinary use.", "\n //\n // See the following article for more details on ULP:\n // http://randomascii.wordpress.com/2012/02/25/comparing-floating-point-numbers-2012-edition/\n static const size_t kMaxUlps = 4;\n\n // Constructs a FloatingPoint from a raw floating-point number.", "\n //\n // On an Intel CPU, passing a non-normalized NAN (Not a Number)\n // around may change its bits, although the new value is guaranteed\n // to be also a NAN. ", " Therefore, don't expect this constructor to\n // preserve the bits in x when x is a NAN.", "\n explicit FloatingPoint(const RawType& x) { u_.value_ = x; }\n\n // Static methods\n\n // Reinterprets a bit pattern as a floating-point number.", "\n //\n // This function is needed to test the AlmostEquals() method.", "\n static RawType ReinterpretBits(const Bits bits) {\n FloatingPoint fp(0);\n fp.u_.bits_ = bits;\n return fp.u_.value_;\n }\n\n // Returns the floating-point number that represent positive infinity.", "\n static RawType Infinity() {\n return ReinterpretBits(kExponentBitMask);\n }\n\n // Returns the maximum representable finite floating-point number.", "\n static RawType Max();\n\n // Non-static methods\n\n // Returns the bits that represents this number.", "\n const Bits &bits() const { return u_.bits_; }\n\n // Returns the exponent bits of this number.", "\n Bits exponent_bits() const { return kExponentBitMask & u_.bits_; }\n\n // Returns the fraction bits of this number.", "\n Bits fraction_bits() const { return kFractionBitMask & u_.bits_; }\n\n // Returns the sign bit of this number.", "\n Bits sign_bit() const { return kSignBitMask & u_.bits_; }\n\n // Returns true iff this is NAN (not a number).", "\n bool is_nan() const {\n // It's a NAN if the exponent bits are all ones and the fraction\n // bits are not entirely zeros.", "\n return (exponent_bits() == kExponentBitMask) && (fraction_bits() !", "= 0);\n }\n\n // Returns true iff this number is at most kMaxUlps ULP's away from\n // rhs. ", " In particular, this function:\n //\n // - returns false if either number is (or both are) NAN.", "\n // - treats really large numbers as almost equal to infinity.", "\n // - thinks +0.0 and -0.0 are 0 DLP's apart.", "\n bool AlmostEquals(const FloatingPoint& rhs) const {\n // The IEEE standard says that any comparison operation involving\n // a NAN must return false.", "\n if (is_nan() || rhs.is_nan()) return false;\n\n return DistanceBetweenSignAndMagnitudeNumbers(u_.bits_, rhs.u_.bits_)\n <= kMaxUlps;\n }\n\n private:\n // The data type used to store the actual floating-point number.", "\n union FloatingPointUnion {\n RawType value_; // The raw floating-point number.", "\n Bits bits_; // The bits that represent the number.", "\n };\n\n // Converts an integer from the sign-and-magnitude representation to\n // the biased representation. ", " More precisely, let N be 2 to the\n // power of (kBitCount - 1), an integer x is represented by the\n // unsigned number x + N.\n //\n // For instance,\n //\n // -N + 1 (the most negative number representable using\n // sign-and-magnitude) is represented by 1;\n // 0 is represented by N; and\n // N - 1 (the biggest number representable using\n // sign-and-magnitude) is represented by 2N - 1.", "\n //\n // Read http://en.wikipedia.org/wiki/Signed_number_representations\n // for more details on signed number representations.", "\n static Bits SignAndMagnitudeToBiased(const Bits &sam) {\n if (kSignBitMask & sam) {\n // sam represents a negative number.", "\n return ~sam + 1;\n } else {\n // sam represents a positive number.", "\n return kSignBitMask | sam;\n }\n }\n\n // Given two numbers in the sign-and-magnitude representation,\n // returns the distance between them as an unsigned number.", "\n static Bits DistanceBetweenSignAndMagnitudeNumbers(const Bits &sam1,\n const Bits &sam2) {\n const Bits biased1 = SignAndMagnitudeToBiased(sam1);\n const Bits biased2 = SignAndMagnitudeToBiased(sam2);\n return (biased1 >= biased2) ? (", "biased1 - biased2) : (biased2 - biased1);\n }\n\n FloatingPointUnion u_;\n};\n\n// We cannot use std::numeric_limits<T>::max() as it clashes with the max()\n// macro defined by <windows.h>.", "\ntemplate <>\ninline float FloatingPoint<float>::Max() { return FLT_MAX; }\ntemplate <>\ninline double FloatingPoint<double>::Max() { return DBL_MAX; }\n\n// Typedefs the instances of the FloatingPoint template class that we\n// care to use.", "\ntypedef FloatingPoint<float> Float;\ntypedef FloatingPoint<double> Double;\n\n// In order to catch the mistake of putting tests that use different\n// test fixture classes in the same test case, we need to assign\n// unique IDs to fixture classes and compare them. ", " The TypeId type is\n// used to hold such IDs. ", " The user should treat TypeId as an opaque\n// type: the only operation allowed on TypeId values is to compare\n// them for equality using the == operator.", "\ntypedef const void* TypeId;\n\ntemplate <typename T>\nclass TypeIdHelper {\n public:\n // dummy_ must not have a const type. ", " Otherwise an overly eager\n // compiler (e.g. MSVC 7.1 & 8.0) may try to merge\n // TypeIdHelper<T>::dummy_ for different Ts as an \"optimization\".", "\n static bool dummy_;\n};\n\ntemplate <typename T>\nbool TypeIdHelper<T>::dummy_ = false;\n\n// GetTypeId<T>() returns the ID of type T. Different values will be\n// returned for different types. ", " Calling the function twice with the\n// same type argument is guaranteed to return the same ID.", "\ntemplate <typename T>\nTypeId GetTypeId() {\n // The compiler is required to allocate a different\n // TypeIdHelper<T>::dummy_ variable for each T used to instantiate\n // the template. ", " Therefore, the address of dummy_ is guaranteed to\n // be unique.", "\n return &(TypeIdHelper<T>::dummy_);\n}\n\n// Returns the type ID of ::testing::Test. ", " Always call this instead\n// of GetTypeId< ::testing::Test>() to get the type ID of\n// ::testing::Test, as the latter may give the wrong result due to a\n// suspected linker bug when compiling Google Test as a Mac OS X\n// framework.", "\nGTEST_API_ TypeId GetTestTypeId();\n\n// Defines the abstract factory interface that creates instances\n// of a Test object.", "\nclass TestFactoryBase {\n public:\n virtual ~TestFactoryBase() {}\n\n // Creates a test instance to run. ", "The instance is both created and destroyed\n // within TestInfoImpl::Run()\n virtual Test* CreateTest() = 0;\n\n protected:\n TestFactoryBase() {}\n\n private:\n GTEST_DISALLOW_COPY_AND_ASSIGN_(TestFactoryBase);\n};\n\n// This class provides implementation of TeastFactoryBase interface.", "\n// It is used in TEST and TEST_F macros.", "\ntemplate <class TestClass>\nclass TestFactoryImpl : public TestFactoryBase {\n public:\n virtual Test* CreateTest() { return new TestClass; }\n};\n\n#if GTEST_OS_WINDOWS\n\n// Predicate-formatters for implementing the HRESULT checking macros\n// {ASSERT|EXPECT}_HRESULT_{SUCCEEDED|FAILED}\n// We pass a long instead of HRESULT to avoid causing an\n// include dependency for the HRESULT type.", "\nGTEST_API_ AssertionResult IsHRESULTSuccess(const char* expr,\n long hr); // NOLINT\nGTEST_API_ AssertionResult IsHRESULTFailure(const char* expr,\n long hr); // NOLINT\n\n#endif // GTEST_OS_WINDOWS\n\n// Types of SetUpTestCase() and TearDownTestCase() functions.", "\ntypedef void (*SetUpTestCaseFunc)();\ntypedef void (*TearDownTestCaseFunc)();\n\nstruct CodeLocation {\n CodeLocation(const std::string& a_file, int a_line)\n : file(a_file), line(a_line) {}\n\n std::string file;\n int line;\n};\n\n// Creates a new TestInfo object and registers it with Google Test;\n// returns the created object.", "\n//\n// Arguments:\n//\n// test_case_name: name of the test case\n// name: name of the test\n// type_param the name of the test's type parameter, or NULL if\n// this is not a typed or a type-parameterized test.", "\n// value_param text representation of the test's value parameter,\n// or NULL if this is not a type-parameterized test.", "\n// code_location: code location where the test is defined\n// fixture_class_id: ID of the test fixture class\n// set_up_tc: pointer to the function that sets up the test case\n// tear_down_tc: pointer to the function that tears down the test case\n// factory: pointer to the factory that creates a test object.", "\n// The newly created TestInfo instance will assume\n// ownership of the factory object.", "\nGTEST_API_ TestInfo* MakeAndRegisterTestInfo(\n const char* test_case_name,\n const char* name,\n const char* type_param,\n const char* value_param,\n CodeLocation code_location,\n TypeId fixture_class_id,\n SetUpTestCaseFunc set_up_tc,\n TearDownTestCaseFunc tear_down_tc,\n TestFactoryBase* factory);\n\n// If *pstr starts with the given prefix, modifies *pstr to be right\n// past the prefix and returns true; otherwise leaves *pstr unchanged\n// and returns false. ", " None of pstr, *pstr, and prefix can be NULL.", "\nGTEST_API_ bool SkipPrefix(const char* prefix, const char** pstr);\n\n#if GTEST_HAS_TYPED_TEST || GTEST_HAS_TYPED_TEST_P\n\nGTEST_DISABLE_MSC_WARNINGS_PUSH_(4251 \\\n/* class A needs to have dll-interface to be used by clients of class B */)\n\n// State of the definition of a type-parameterized test case.", "\nclass GTEST_API_ TypedTestCasePState {\n public:\n TypedTestCasePState() : registered_(false) {}\n\n // Adds the given test name to defined_test_names_ and return true\n // if the test case hasn't been registered; otherwise aborts the\n // program.", "\n bool AddTestName(const char* file, int line, const char* case_name,\n const char* test_name) {\n if (registered_) {\n fprintf(stderr, \"%s Test %s must be defined before \"\n \"REGISTER_TYPED_TEST_CASE_P(%s, ...).\\n\",\n FormatFileLocation(file, line).c_str(), test_name, case_name);\n fflush(stderr);\n posix::Abort();\n }\n registered_tests_.insert(\n ::std::make_pair(test_name, CodeLocation(file, line)));\n return true;\n }\n\n bool TestExists(const std::string& test_name) const {\n return registered_tests_.count(test_name) > 0;\n }\n\n const CodeLocation& GetCodeLocation(const std::string& test_name) const {\n RegisteredTestsMap::const_iterator it = registered_tests_.find(test_name);\n GTEST_CHECK_(it !", "= registered_tests_.end());\n return it->second;\n }\n\n // Verifies that registered_tests match the test names in\n // defined_test_names_; returns registered_tests if successful, or\n // aborts the program otherwise.", "\n const char* VerifyRegisteredTestNames(\n const char* file, int line, const char* registered_tests);\n\n private:\n typedef ::std::map<std::string, CodeLocation> RegisteredTestsMap;\n\n bool registered_;\n RegisteredTestsMap registered_tests_;\n};\n\nGTEST_DISABLE_MSC_WARNINGS_POP_() // 4251\n\n// Skips to the first non-space char after the first comma in 'str';\n// returns NULL if no comma is found in 'str'.", "\ninline const char* SkipComma(const char* str) {\n const char* comma = strchr(str, ',');\n if (comma == NULL) {\n return NULL;\n }\n while (IsSpace(*(++comma))) {}\n return comma;\n}\n\n// Returns the prefix of 'str' before the first comma in it; returns\n// the entire string if it contains no comma.", "\ninline std::string GetPrefixUntilComma(const char* str) {\n const char* comma = strchr(str, ',');\n return comma == NULL ? ", "str : std::string(str, comma);\n}\n\n// Splits a given string on a given delimiter, populating a given\n// vector with the fields.", "\nvoid SplitString(const ::std::string& str, char delimiter,\n ::std::vector< ::std::string>* dest);\n\n// The default argument to the template below for the case when the user does\n// not provide a name generator.", "\nstruct DefaultNameGenerator {\n template <typename T>\n static std::string GetName(int i) {\n return StreamableToString(i);\n }\n};\n\ntemplate <typename Provided = DefaultNameGenerator>\nstruct NameGeneratorSelector {\n typedef Provided type;\n};\n\ntemplate <typename NameGenerator>\nvoid GenerateNamesRecursively(Types0, std::vector<std::string>*, int) {}\n\ntemplate <typename NameGenerator, typename Types>\nvoid GenerateNamesRecursively(Types, std::vector<std::string>* result, int i) {\n result->push_back(NameGenerator::template GetName<typename Types::Head>(i));\n GenerateNamesRecursively<NameGenerator>(typename Types::Tail(), result,\n i + 1);\n}\n\ntemplate <typename NameGenerator, typename Types>\nstd::vector<std::string> GenerateNames() {\n std::vector<std::string> result;\n GenerateNamesRecursively<NameGenerator>(Types(), &result, 0);\n return result;\n}\n\n// TypeParameterizedTest<Fixture, TestSel, Types>::Register()\n// registers a list of type-parameterized tests with Google Test. ", " The\n// return value is insignificant - we just need to return something\n// such that we can call this function in a namespace scope.", "\n//\n// Implementation note: The GTEST_TEMPLATE_ macro declares a template\n// template parameter. ", " It's defined in gtest-type-util.h.", "\ntemplate <GTEST_TEMPLATE_ Fixture, class TestSel, typename Types>\nclass TypeParameterizedTest {\n public:\n // 'index' is the index of the test in the type list 'Types'\n // specified in INSTANTIATE_TYPED_TEST_CASE_P(Prefix, TestCase,\n // Types). ", " Valid values for 'index' are [0, N - 1] where N is the\n // length of Types.", "\n static bool Register(const char* prefix, const CodeLocation& code_location,\n const char* case_name, const char* test_names, int index,\n const std::vector<std::string>& type_names =\n GenerateNames<DefaultNameGenerator, Types>()) {\n typedef typename Types::Head Type;\n typedef Fixture<Type> FixtureClass;\n typedef typename GTEST_BIND_(TestSel, Type) TestClass;\n\n // First, registers the first type-parameterized test in the type\n // list.", "\n MakeAndRegisterTestInfo(\n (std::string(prefix) + (prefix[0] == '\\0' ? \"\" : \"/\") ", "+ case_name +\n \"/\" + type_names[index])\n .c_str(),\n StripTrailingSpaces(GetPrefixUntilComma(test_names)).c_str(),\n GetTypeName<Type>().c_str(),\n NULL, // No value parameter.", "\n code_location, GetTypeId<FixtureClass>(), TestClass::SetUpTestCase,\n TestClass::TearDownTestCase, new TestFactoryImpl<TestClass>);\n\n // Next, recurses (at compile time) with the tail of the type list.", "\n return TypeParameterizedTest<Fixture, TestSel,\n typename Types::Tail>::Register(prefix,\n code_location,\n case_name,\n test_names,\n index + 1,\n type_names);\n }\n};\n\n// The base case for the compile time recursion.", "\ntemplate <GTEST_TEMPLATE_ Fixture, class TestSel>\nclass TypeParameterizedTest<Fixture, TestSel, Types0> {\n public:\n static bool Register(const char* /*prefix*/, const CodeLocation&,\n const char* /*case_name*/, const char* /*test_names*/,\n int /*index*/,\n const std::vector<std::string>& =\n std::vector<std::string>() /*type_names*/) {\n return true;\n }\n};\n\n// TypeParameterizedTestCase<Fixture, Tests, Types>::Register()\n// registers *all combinations* of 'Tests' and 'Types' with Google\n// Test. ", " The return value is insignificant - we just need to return\n// something such that we can call this function in a namespace scope.", "\ntemplate <GTEST_TEMPLATE_ Fixture, typename Tests, typename Types>\nclass TypeParameterizedTestCase {\n public:\n static bool Register(const char* prefix, CodeLocation code_location,\n const TypedTestCasePState* state, const char* case_name,\n const char* test_names,\n const std::vector<std::string>& type_names =\n GenerateNames<DefaultNameGenerator, Types>()) {\n std::string test_name = StripTrailingSpaces(\n GetPrefixUntilComma(test_names));\n if (!", "state->TestExists(test_name)) {\n fprintf(stderr, \"Failed to get code location for test %s.%s at %s.\",\n case_name, test_name.c_str(),\n FormatFileLocation(code_location.file.c_str(),\n code_location.line).c_str());\n fflush(stderr);\n posix::Abort();\n }\n const CodeLocation& test_location = state->GetCodeLocation(test_name);\n\n typedef typename Tests::Head Head;\n\n // First, register the first test in 'Test' for each type in 'Types'.", "\n TypeParameterizedTest<Fixture, Head, Types>::Register(\n prefix, test_location, case_name, test_names, 0, type_names);\n\n // Next, recurses (at compile time) with the tail of the test list.", "\n return TypeParameterizedTestCase<Fixture, typename Tests::Tail,\n Types>::Register(prefix, code_location,\n state, case_name,\n SkipComma(test_names),\n type_names);\n }\n};\n\n// The base case for the compile time recursion.", "\ntemplate <GTEST_TEMPLATE_ Fixture, typename Types>\nclass TypeParameterizedTestCase<Fixture, Templates0, Types> {\n public:\n static bool Register(const char* /*prefix*/, const CodeLocation&,\n const TypedTestCasePState* /*state*/,\n const char* /*case_name*/, const char* /*test_names*/,\n const std::vector<std::string>& =\n std::vector<std::string>() /*type_names*/) {\n return true;\n }\n};\n\n#endif // GTEST_HAS_TYPED_TEST || GTEST_HAS_TYPED_TEST_P\n\n// Returns the current OS stack trace as an std::string.", "\n//\n// The maximum number of stack frames to be included is specified by\n// the gtest_stack_trace_depth flag. ", " The skip_count parameter\n// specifies the number of top frames to be skipped, which doesn't\n// count against the number of frames to be included.", "\n//\n// For example, if Foo() calls Bar(), which in turn calls\n// GetCurrentOsStackTraceExceptTop(..., 1), Foo() will be included in\n// the trace but Bar() and GetCurrentOsStackTraceExceptTop() won't.", "\nGTEST_API_ std::string GetCurrentOsStackTraceExceptTop(\n UnitTest* unit_test, int skip_count);\n\n// Helpers for suppressing warnings on unreachable code or constant\n// condition.", "\n\n// Always returns true.", "\nGTEST_API_ bool AlwaysTrue();\n\n// Always returns false.", "\ninline bool AlwaysFalse() { return !", "AlwaysTrue(); }\n\n// Helper for suppressing false warning from Clang on a const char*\n// variable declared in a conditional expression always being NULL in\n// the else branch.", "\nstruct GTEST_API_ ConstCharPtr {\n ConstCharPtr(const char* str) : value(str) {}\n operator bool() const { return true; }\n const char* value;\n};\n\n// A simple Linear Congruential Generator for generating random\n// numbers with a uniform distribution. ", " Unlike rand() and srand(), it\n// doesn't use global state (and therefore can't interfere with user\n// code). ", " Unlike rand_r(), it's portable. ", " An LCG isn't very random,\n// but it's good enough for our purposes.", "\nclass GTEST_API_ Random {\n public:\n static const UInt32 kMaxRange = 1u << 31;\n\n explicit Random(UInt32 seed) : state_(seed) {}\n\n void Reseed(UInt32 seed) { state_ = seed; }\n\n // Generates a random number from [0, range). ", " Crashes if 'range' is\n // 0 or greater than kMaxRange.", "\n UInt32 Generate(UInt32 range);\n\n private:\n UInt32 state_;\n GTEST_DISALLOW_COPY_AND_ASSIGN_(Random);\n};\n\n// Defining a variable of type CompileAssertTypesEqual<T1, T2> will cause a\n// compiler error iff T1 and T2 are different types.", "\ntemplate <typename T1, typename T2>\nstruct CompileAssertTypesEqual;\n\ntemplate <typename T>\nstruct CompileAssertTypesEqual<T, T> {\n};\n\n// Removes the reference from a type if it is a reference type,\n// otherwise leaves it unchanged. ", " This is the same as\n// tr1::remove_reference, which is not widely available yet.", "\ntemplate <typename T>\nstruct RemoveReference { typedef T type; }; // NOLINT\ntemplate <typename T>\nstruct RemoveReference<T&> { typedef T type; }; // NOLINT\n\n// A handy wrapper around RemoveReference that works when the argument\n// T depends on template parameters.", "\n#define GTEST_REMOVE_REFERENCE_(T) \\\n typename ::testing::internal::RemoveReference<T>::type\n\n// Removes const from a type if it is a const type, otherwise leaves\n// it unchanged. ", " This is the same as tr1::remove_const, which is not\n// widely available yet.", "\ntemplate <typename T>\nstruct RemoveConst { typedef T type; }; // NOLINT\ntemplate <typename T>\nstruct RemoveConst<const T> { typedef T type; }; // NOLINT\n\n// MSVC 8.0, Sun C++, and IBM XL C++ have a bug which causes the above\n// definition to fail to remove the const in 'const int[3]' and 'const\n// char[3][4]'. ", " The following specialization works around the bug.", "\ntemplate <typename T, size_t N>\nstruct RemoveConst<const T[N]> {\n typedef typename RemoveConst<T>::type type[N];\n};\n\n#if defined(_MSC_VER) && _MSC_VER < 1400\n// This is the only specialization that allows VC++ 7.1 to remove const in\n// 'const int[3] and 'const int[3][4]'. ", " However, it causes trouble with GCC\n// and thus needs to be conditionally compiled.", "\ntemplate <typename T, size_t N>\nstruct RemoveConst<T[N]> {\n typedef typename RemoveConst<T>::type type[N];\n};\n#endif\n\n// A handy wrapper around RemoveConst that works when the argument\n// T depends on template parameters.", "\n#define GTEST_REMOVE_CONST_(T) \\\n typename ::testing::internal::RemoveConst<T>::type\n\n// Turns const U&, U&, const U, and U all into U.\n#define GTEST_REMOVE_REFERENCE_AND_CONST_(T) \\\n GTEST_REMOVE_CONST_(GTEST_REMOVE_REFERENCE_(T))\n\n// ImplicitlyConvertible<From, To>::value is a compile-time bool\n// constant that's true iff type From can be implicitly converted to\n// type To.", "\ntemplate <typename From, typename To>\nclass ImplicitlyConvertible {\n private:\n // We need the following helper functions only for their types.", "\n // They have no implementations.", "\n\n // MakeFrom() is an expression whose type is From. ", " We cannot simply\n // use From(), as the type From may not have a public default\n // constructor.", "\n static typename AddReference<From>::type MakeFrom();\n\n // These two functions are overloaded. ", " Given an expression\n // Helper(x), the compiler will pick the first version if x can be\n // implicitly converted to type To; otherwise it will pick the\n // second version.", "\n //\n // The first version returns a value of size 1, and the second\n // version returns a value of size 2. ", " Therefore, by checking the\n // size of Helper(x), which can be done at compile time, we can tell\n // which version of Helper() is used, and hence whether x can be\n // implicitly converted to type To.", "\n static char Helper(To);\n static char (&Helper(...))[2]; // NOLINT\n\n // We have to put the 'public' section after the 'private' section,\n // or MSVC refuses to compile the code.", "\n public:\n#if defined(__BORLANDC__)\n // C++Builder cannot use member overload resolution during template\n // instantiation. ", " The simplest workaround is to use its C++0x type traits\n // functions (C++Builder 2009 and above only).", "\n static const bool value = __is_convertible(From, To);\n#else\n // MSVC warns about implicitly converting from double to int for\n // possible loss of data, so we need to temporarily disable the\n // warning.", "\n GTEST_DISABLE_MSC_WARNINGS_PUSH_(4244)\n static const bool value =\n sizeof(Helper(ImplicitlyConvertible::MakeFrom())) == 1;\n GTEST_DISABLE_MSC_WARNINGS_POP_()\n#endif // __BORLANDC__\n};\ntemplate <typename From, typename To>\nconst bool ImplicitlyConvertible<From, To>::value;\n\n// IsAProtocolMessage<T>::value is a compile-time bool constant that's\n// true iff T is type ProtocolMessage, proto2::Message, or a subclass\n// of those.", "\ntemplate <typename T>\nstruct IsAProtocolMessage\n : public bool_constant<\n ImplicitlyConvertible<const T*, const ::ProtocolMessage*>::value ||\n ImplicitlyConvertible<const T*, const ::proto2::Message*>::value> {\n};\n\n// When the compiler sees expression IsContainerTest<C>(0), if C is an\n// STL-style container class, the first overload of IsContainerTest\n// will be viable (since both C::iterator* and C::const_iterator* are\n// valid types and NULL can be implicitly converted to them). ", " It will\n// be picked over the second overload as 'int' is a perfect match for\n// the type of argument 0. ", " If C::iterator or C::const_iterator is not\n// a valid type, the first overload is not viable, and the second\n// overload will be picked. ", " Therefore, we can determine whether C is\n// a container class by checking the type of IsContainerTest<C>(0).", "\n// The value of the expression is insignificant.", "\n//\n// In C++11 mode we check the existence of a const_iterator and that an\n// iterator is properly implemented for the container.", "\n//\n// For pre-C++11 that we look for both C::iterator and C::const_iterator.", "\n// The reason is that C++ injects the name of a class as a member of the\n// class itself (e.g. you can refer to class iterator as either\n// 'iterator' or 'iterator::iterator'). ", " If we look for C::iterator\n// only, for example, we would mistakenly think that a class named\n// iterator is an STL container.", "\n//\n// Also note that the simpler approach of overloading\n// IsContainerTest(typename C::const_iterator*) and\n// IsContainerTest(...) doesn't work with Visual Age C++ and Sun C++.", "\ntypedef int IsContainer;\n#if GTEST_LANG_CXX11\ntemplate <class C,\n class Iterator = decltype(::std::declval<const C&>().begin()),\n class = decltype(::std::declval<const C&>().end()),\n class = decltype(++::std::declval<Iterator&>()),\n class = decltype(*::std::declval<Iterator>()),\n class = typename C::const_iterator>\nIsContainer IsContainerTest(int /* dummy */) {\n return 0;\n}\n#else\ntemplate <class C>\nIsContainer IsContainerTest(int /* dummy */,\n typename C::iterator* /* it */ = NULL,\n typename C::const_iterator* /* const_it */ = NULL) {\n return 0;\n}\n#endif // GTEST_LANG_CXX11\n\ntypedef char IsNotContainer;\ntemplate <class C>\nIsNotContainer IsContainerTest(long /* dummy */) { return '\\0'; }\n\n// Trait to detect whether a type T is a hash table.", "\n// The heuristic used is that the type contains an inner type `hasher` and does\n// not contain an inner type `reverse_iterator`.", "\n// If the container is iterable in reverse, then order might actually matter.", "\ntemplate <typename T>\nstruct IsHashTable {\n private:\n template <typename U>\n static char test(typename U::hasher*, typename U::reverse_iterator*);\n template <typename U>\n static int test(typename U::hasher*, ...);\n template <typename U>\n static char test(...);\n\n public:\n static const bool value = sizeof(test<T>(0, 0)) == sizeof(int);\n};\n\ntemplate <typename T>\nconst bool IsHashTable<T>::value;\n\ntemplate<typename T>\nstruct VoidT {\n typedef void value_type;\n};\n\ntemplate <typename T, typename = void>\nstruct HasValueType : false_type {};\ntemplate <typename T>\nstruct HasValueType<T, VoidT<typename T::value_type> > : true_type {\n};\n\ntemplate <typename C,\n bool = sizeof(IsContainerTest<C>(0)) == sizeof(IsContainer),\n bool = HasValueType<C>::value>\nstruct IsRecursiveContainerImpl;\n\ntemplate <typename C, bool HV>\nstruct IsRecursiveContainerImpl<C, false, HV> : public false_type {};\n\n// Since the IsRecursiveContainerImpl depends on the IsContainerTest we need to\n// obey the same inconsistencies as the IsContainerTest, namely check if\n// something is a container is relying on only const_iterator in C++11 and\n// is relying on both const_iterator and iterator otherwise\ntemplate <typename C>\nstruct IsRecursiveContainerImpl<C, true, false> : public false_type {};\n\ntemplate <typename C>\nstruct IsRecursiveContainerImpl<C, true, true> {\n #if GTEST_LANG_CXX11\n typedef typename IteratorTraits<typename C::const_iterator>::value_type\n value_type;\n#else\n typedef typename IteratorTraits<typename C::iterator>::value_type value_type;\n#endif\n typedef is_same<value_type, C> type;\n};\n\n// IsRecursiveContainer<Type> is a unary compile-time predicate that\n// evaluates whether C is a recursive container type. ", "A recursive container\n// type is a container type whose value_type is equal to the container type\n// itself. ", "An example for a recursive container type is\n// boost::filesystem::path, whose iterator has a value_type that is equal to\n// boost::filesystem::path.", "\ntemplate <typename C>\nstruct IsRecursiveContainer : public IsRecursiveContainerImpl<C>::type {};\n\n// EnableIf<condition>::type is void when 'Cond' is true, and\n// undefined when 'Cond' is false. ", " To use SFINAE to make a function\n// overload only apply when a particular expression is true, add\n// \"typename EnableIf<expression>::type* = 0\" as the last parameter.", "\ntemplate<bool> struct EnableIf;\ntemplate<> struct EnableIf<true> { typedef void type; }; // NOLINT\n\n// Utilities for native arrays.", "\n\n// ArrayEq() compares two k-dimensional native arrays using the\n// elements' operator==, where k can be any integer >= 0. ", " When k is\n// 0, ArrayEq() degenerates into comparing a single pair of values.", "\n\ntemplate <typename T, typename U>\nbool ArrayEq(const T* lhs, size_t size, const U* rhs);\n\n// This generic version is used when k is 0.", "\ntemplate <typename T, typename U>\ninline bool ArrayEq(const T& lhs, const U& rhs) { return lhs == rhs; }\n\n// This overload is used when k >= 1.", "\ntemplate <typename T, typename U, size_t N>\ninline bool ArrayEq(const T(&lhs)[N], const U(&rhs)[N]) {\n return internal::ArrayEq(lhs, N, rhs);\n}\n\n// This helper reduces code bloat. ", " If we instead put its logic inside\n// the previous ArrayEq() function, arrays with different sizes would\n// lead to different copies of the template code.", "\ntemplate <typename T, typename U>\nbool ArrayEq(const T* lhs, size_t size, const U* rhs) {\n for (size_t i = 0; i !", "= size; i++) {\n if (!", "internal::ArrayEq(lhs[i], rhs[i]))\n return false;\n }\n return true;\n}\n\n// Finds the first element in the iterator range [begin, end) that\n// equals elem. ", " Element may be a native array type itself.", "\ntemplate <typename Iter, typename Element>\nIter ArrayAwareFind(Iter begin, Iter end, const Element& elem) {\n for (Iter it = begin; it !", "= end; ++it) {\n if (internal::ArrayEq(*it, elem))\n return it;\n }\n return end;\n}\n\n// CopyArray() copies a k-dimensional native array using the elements'\n// operator=, where k can be any integer >= 0. ", " When k is 0,\n// CopyArray() degenerates into copying a single value.", "\n\ntemplate <typename T, typename U>\nvoid CopyArray(const T* from, size_t size, U* to);\n\n// This generic version is used when k is 0.", "\ntemplate <typename T, typename U>\ninline void CopyArray(const T& from, U* to) { *to = from; }\n\n// This overload is used when k >= 1.", "\ntemplate <typename T, typename U, size_t N>\ninline void CopyArray(const T(&from)[N], U(*to)[N]) {\n internal::CopyArray(from, N, *to);\n}\n\n// This helper reduces code bloat. ", " If we instead put its logic inside\n// the previous CopyArray() function, arrays with different sizes\n// would lead to different copies of the template code.", "\ntemplate <typename T, typename U>\nvoid CopyArray(const T* from, size_t size, U* to) {\n for (size_t i = 0; i !", "= size; i++) {\n internal::CopyArray(from[i], to + i);\n }\n}\n\n// The relation between an NativeArray object (see below) and the\n// native array it represents.", "\n// We use 2 different structs to allow non-copyable types to be used, as long\n// as RelationToSourceReference() is passed.", "\nstruct RelationToSourceReference {};\nstruct RelationToSourceCopy {};\n\n// Adapts a native array to a read-only STL-style container. ", " Instead\n// of the complete STL container concept, this adaptor only implements\n// members useful for Google Mock's container matchers. ", " New members\n// should be added as needed. ", " To simplify the implementation, we only\n// support Element being a raw type (i.e. having no top-level const or\n// reference modifier). ", " It's the client's responsibility to satisfy\n// this requirement. ", " Element can be an array type itself (hence\n// multi-dimensional arrays are supported).", "\ntemplate <typename Element>\nclass NativeArray {\n public:\n // STL-style container typedefs.", "\n typedef Element value_type;\n typedef Element* iterator;\n typedef const Element* const_iterator;\n\n // Constructs from a native array. ", "References the source.", "\n NativeArray(const Element* array, size_t count, RelationToSourceReference) {\n InitRef(array, count);\n }\n\n // Constructs from a native array. ", "Copies the source.", "\n NativeArray(const Element* array, size_t count, RelationToSourceCopy) {\n InitCopy(array, count);\n }\n\n // Copy constructor.", "\n NativeArray(const NativeArray& rhs) {\n (this->*rhs.clone_)(rhs.array_, rhs.size_);\n }\n\n ~NativeArray() {\n if (clone_ !", "= &NativeArray::InitRef)\n delete[] array_;\n }\n\n // STL-style container methods.", "\n size_t size() const { return size_; }\n const_iterator begin() const { return array_; }\n const_iterator end() const { return array_ + size_; }\n bool operator==(const NativeArray& rhs) const {\n return size() == rhs.size() &&\n ArrayEq(begin(), size(), rhs.begin());\n }\n\n private:\n enum {\n kCheckTypeIsNotConstOrAReference = StaticAssertTypeEqHelper<\n Element, GTEST_REMOVE_REFERENCE_AND_CONST_(Element)>::value\n };\n\n // Initializes this object with a copy of the input.", "\n void InitCopy(const Element* array, size_t a_size) {\n Element* const copy = new Element[a_size];\n CopyArray(array, a_size, copy);\n array_ = copy;\n size_ = a_size;\n clone_ = &NativeArray::InitCopy;\n }\n\n // Initializes this object with a reference of the input.", "\n void InitRef(const Element* array, size_t a_size) {\n array_ = array;\n size_ = a_size;\n clone_ = &NativeArray::InitRef;\n }\n\n const Element* array_;\n size_t size_;\n void (NativeArray::*clone_)(const Element*, size_t);\n\n GTEST_DISALLOW_ASSIGN_(NativeArray);\n};\n\n} // namespace internal\n} // namespace testing\n\n#define GTEST_MESSAGE_AT_(file, line, message, result_type) \\\n ::testing::internal::AssertHelper(result_type, file, line, message) \\\n = ::testing::Message()\n\n#define GTEST_MESSAGE_(message, result_type) \\\n GTEST_MESSAGE_AT_(__FILE__, __LINE__, message, result_type)\n\n#define GTEST_FATAL_FAILURE_(message) \\\n return GTEST_MESSAGE_(message, ::testing::TestPartResult::kFatalFailure)\n\n#define GTEST_NONFATAL_FAILURE_(message) \\\n GTEST_MESSAGE_(message, ::testing::TestPartResult::kNonFatalFailure)\n\n#define GTEST_SUCCESS_(message) \\\n GTEST_MESSAGE_(message, ::testing::TestPartResult::kSuccess)\n\n// Suppress MSVC warning 4702 (unreachable code) for the code following\n// statement if it returns or throws (or doesn't return or throw in some\n// situations).", "\n#define GTEST_SUPPRESS_UNREACHABLE_CODE_WARNING_BELOW_(statement) \\\n if (::testing::internal::AlwaysTrue()) { statement; }\n\n#define GTEST_TEST_THROW_(statement, expected_exception, fail) \\\n GTEST_AMBIGUOUS_ELSE_BLOCKER_ \\\n if (::testing::internal::ConstCharPtr gtest_msg = \"\") { \\\n bool gtest_caught_expected = false; \\\n try { \\\n GTEST_SUPPRESS_UNREACHABLE_CODE_WARNING_BELOW_(statement); \\\n } \\\n catch (expected_exception const&) { \\\n gtest_caught_expected = true; \\\n } \\\n catch (...) { \\\n gtest_msg.value = \\\n \"Expected: \" #statement \" throws an exception of type \" \\\n #expected_exception \".\\n Actual: it throws a different type.\"; \\", "\n goto GTEST_CONCAT_TOKEN_(gtest_label_testthrow_, __LINE__); \\\n } \\\n if (!", "gtest_caught_expected) { \\\n gtest_msg.value = \\\n \"Expected: \" #statement \" throws an exception of type \" \\\n #expected_exception \".\\n Actual: it throws nothing.\"; \\", "\n goto GTEST_CONCAT_TOKEN_(gtest_label_testthrow_, __LINE__); \\\n } \\\n } else \\\n GTEST_CONCAT_TOKEN_(gtest_label_testthrow_, __LINE__): \\\n fail(gtest_msg.value)\n\n#define GTEST_TEST_NO_THROW_(statement, fail) \\\n GTEST_AMBIGUOUS_ELSE_BLOCKER_ \\\n if (::testing::internal::AlwaysTrue()) { \\\n try { \\\n GTEST_SUPPRESS_UNREACHABLE_CODE_WARNING_BELOW_(statement); \\\n } \\\n catch (...) { \\\n goto GTEST_CONCAT_TOKEN_(gtest_label_testnothrow_, __LINE__); \\\n } \\\n } else \\\n GTEST_CONCAT_TOKEN_(gtest_label_testnothrow_, __LINE__): \\\n fail(\"Expected: \" #statement \" doesn't throw an exception.\\n\" \\\n \" Actual: it throws.\")", "\n\n#define GTEST_TEST_ANY_THROW_(statement, fail) \\\n GTEST_AMBIGUOUS_ELSE_BLOCKER_ \\\n if (::testing::internal::AlwaysTrue()) { \\\n bool gtest_caught_any = false; \\\n try { \\\n GTEST_SUPPRESS_UNREACHABLE_CODE_WARNING_BELOW_(statement); \\\n } \\\n catch (...) { \\\n gtest_caught_any = true; \\\n } \\\n if (!", "gtest_caught_any) { \\\n goto GTEST_CONCAT_TOKEN_(gtest_label_testanythrow_, __LINE__); \\\n } \\\n } else \\\n GTEST_CONCAT_TOKEN_(gtest_label_testanythrow_, __LINE__): \\\n fail(\"Expected: \" #statement \" throws an exception.\\n\" \\\n \" Actual: it doesn't.\")", "\n\n\n// Implements Boolean test assertions such as EXPECT_TRUE. ", "expression can be\n// either a boolean expression or an AssertionResult. ", "text is a textual\n// represenation of expression as it was passed into the EXPECT_TRUE.", "\n#define GTEST_TEST_BOOLEAN_(expression, text, actual, expected, fail) \\\n GTEST_AMBIGUOUS_ELSE_BLOCKER_ \\\n if (const ::testing::AssertionResult gtest_ar_ = \\\n ::testing::AssertionResult(expression)) \\\n ; \\\n else \\\n fail(::testing::internal::GetBoolAssertionFailureMessage(\\\n gtest_ar_, text, #actual, #expected).c_str())\n\n#define GTEST_TEST_NO_FATAL_FAILURE_(statement, fail) \\\n GTEST_AMBIGUOUS_ELSE_BLOCKER_ \\\n if (::testing::internal::AlwaysTrue()) { \\\n ::testing::internal::HasNewFatalFailureHelper gtest_fatal_failure_checker; \\\n GTEST_SUPPRESS_UNREACHABLE_CODE_WARNING_BELOW_(statement); \\\n if (gtest_fatal_failure_checker.has_new_fatal_failure()) { \\\n goto GTEST_CONCAT_TOKEN_(gtest_label_testnofatal_, __LINE__); \\\n } \\\n } else \\\n GTEST_CONCAT_TOKEN_(gtest_label_testnofatal_, __LINE__): \\\n fail(\"Expected: \" #statement \" doesn't generate new fatal \" \\\n \"failures in the current thread.\\n\" \\\n \" Actual: it does.\")", "\n\n// Expands to the name of the class that implements the given test.", "\n#define GTEST_TEST_CLASS_NAME_(test_case_name, test_name) \\\n test_case_name##_##test_name##_Test\n\n// Helper macro for defining tests.", "\n#define GTEST_TEST_(test_case_name, test_name, parent_class, parent_id)\\\nclass GTEST_TEST_CLASS_NAME_(test_case_name, test_name) : public parent_class {\\\n public:\\\n GTEST_TEST_CLASS_NAME_(test_case_name, test_name)() {}\\\n private:\\\n virtual void TestBody();\\\n static ::testing::TestInfo* const test_info_ GTEST_ATTRIBUTE_UNUSED_;\\\n GTEST_DISALLOW_COPY_AND_ASSIGN_(\\\n GTEST_TEST_CLASS_NAME_(test_case_name, test_name));\\\n};\\\n\\\n::testing::TestInfo* const GTEST_TEST_CLASS_NAME_(test_case_name, test_name)\\\n ::test_info_ =\\\n ::testing::internal::MakeAndRegisterTestInfo(\\\n #test_case_name, #test_name, NULL, NULL, \\\n ::testing::internal::CodeLocation(__FILE__, __LINE__), \\\n (parent_id), \\\n parent_class::SetUpTestCase, \\\n parent_class::TearDownTestCase, \\\n new ::testing::internal::TestFactoryImpl<\\\n GTEST_TEST_CLASS_NAME_(test_case_name, test_name)>);\\\nvoid GTEST_TEST_CLASS_NAME_(test_case_name, test_name)::TestBody()\n\n#endif // GTEST_INCLUDE_GTEST_INTERNAL_GTEST_INTERNAL_H_\n" ]

{ "pile_set_name": "Github" }

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[ "Scientists Print First Hybrid 3D Heart Model\n\nScientists have integrated computed tomography (CT) and 3D transesophageal echocardiography (3DTEE) imaging to create the first hybrid anatomical model of a patient’s heart.", "\n\nThe modeling technique, which requires special software to crunch and combine the data from the image sources, may soon allow cardiologists to better diagnose congenital heart conditions and help surgeons decide the best course of action when operating on a patient’s heart.", "\n\n“This is a huge leap for individualised medicine in cardiology and congenital heart disease. ", "The technology could be beneficial to cardiologists and surgeons,” said Dr. Joseph Vettukattil from Helen DeVos Children’s Hospital in Michigan.", "\n\nThe new method is unique because it combines multiple image sources for a more accurate model, making sure the important anatomical details are not left out.", "\n\n“Hybrid 3D printing integrates the best aspects of two or more imaging modalities,” Jordan Gosnell, cardiac sonographer and lead author of the study, explained.", "\n\nWhile still in the experimental stages for now, one day soon the scientists hope their anatomically accurate 3D printed hearts can help cardiologists save more lives.", "\n\nResources\n\nContact\n\n3D Printing Experts: Talk to 100,000 Readers a Month!", "\n\nIf you know your way around 3D printers or 3D modeling, whether you are a user, engineer, salesperson, vendor or blogger, we'd love to have you write an article for us. ", "We are getting about 3,000 readers a day and growing quickly. ", "Interested? ", "Click here.." ]

{ "pile_set_name": "Pile-CC" }

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[ " UNPUBLISHED\n\n UNITED STATES COURT OF APPEALS\n FOR THE FOURTH CIRCUIT\n\n\n No. ", "06-4363\n\n\n\nUNITED STATES OF AMERICA,\n\n Plaintiff - Appellee,\n\n versus\n\n\nHASSAN RICHARD MILLER, a/k/a Ernest Danielle\nSmith,\n\n Defendant - Appellant.", "\n\n\n\nAppeal from the United States District Court for the District of\nSouth Carolina, at Rock Hill. ", "Cameron McGowan Currie, District\nJudge. (", "0:97-cr-726-CMC-1)\n\n\nSubmitted: October 17, 2007 Decided: February 15, 2008\n\n\nBefore TRAXLER, KING, and DUNCAN, Circuit Judges.", "\n\n\nAffirmed in part, vacated in part, and remanded by unpublished per\ncuriam opinion.", "\n\n\nJack B. Swerling, LAW OFFICES OF JACK B. SWERLING, Columbia, South\nCarolina, for Appellant. ", " Reginald I. Lloyd, United States\nAttorney, Kevin F. McDonald, Assistant United States Attorney,\nColumbia, South Carolina, for Appellee.", "\n\n\nUnpublished opinions are not binding precedent in this circuit.", "\n\fPER CURIAM:\n\n Hassan Richard Miller pled guilty in 2003 to possession\n\nwith intent to distribute crack cocaine and was originally\n\nsentenced to 262 months imprisonment. ", " Miller appealed, claiming\n\nthat his sentence violated United States v. Booker, 543 U.S. 220\n\n(2005), and United States v. Hughes, 401 F.3d 540, 546 (4th Cir.", "\n\n2005). ", " This court agreed and vacated Miller’s sentence for\n\nresentencing consistent with those opinions.", "\n\n On remand, the district court conducted a resentencing\n\nhearing and determined that Miller’s total offense level remained\n\nat 36, which included a three-level enhancement for assaulting a\n\npolice officer under U.S. Sentencing Guidelines Manual (USSG)\n\n§ 3A1.2(b) (2002).1 With a criminal history category IV, Miller’s\n\nresulting guideline range remained at 262-327 months imprisonment.", "\n\nAfter Miller’s attorney argued for a sentence below his original\n\n262-month sentence, the district court stated:\n\n I agree it is a lengthy prison sentence. ", "I considered\n that. ", "I just don’t see any circumstances that warrant a\n different sentence than the sentence I imposed then. ", "I\n gave him ten years concurrent, which is pretty generous.", "\n And even though it is a long sentence, although he has a\n long sentence, it could have been a lot longer.", "\n So, pursuant to the Sentencing Reform Act of 1984,\n it is the judgment of the court that [Miller] is hereby\n committed to the custody of the Bureau of Prisons to be\n\n\n 1\n The “official victim” enhancement was amended, effective\nNovember 1, 2004, providing now for a six-level, versus a three-\nlevel, enhancement. ", "See USSG App. ", "C, Amend. ", "663; USSG § 3A1.2(c)\n(2004).", "\n\n\n - 2 -\n\f imprisoned for a term of 262 months; 120 months of which\n is to run concurrently with the undischarged term of\n imprisonment that you are now serving under the\n provisions of 5G1.3C.\n\nMiller noted a timely appeal.", "\n\n Miller first argues that the district court clearly erred\n\nin finding that he committed an aggravated assault on a law\n\nenforcement officer warranting an enhancement under USSG\n\n§ 3A1.2(b). ", "We review the district court’s factual finding on this\n\nissue for clear error. ", " United States v. Harrison, 272 F.3d 220,\n\n223 (4th Cir. ", "2001).", "\n\n At the time of Miller’s original sentencing, USSG\n\n§ 3A1.2(b) provided for a three-level enhancement if “during the\n\ncourse of the offense or immediate flight therefrom, the defendant\n\n. . . , ", "knowing or having reasonable cause to believe that a person\n\nwas a law enforcement or corrections officer, assaulted such\n\nofficer in a manner creating a substantial risk of serious bodily\n\ninjury.” ", " Application Note 4(A) further provided that this section\n\n“applies in circumstances tantamount to aggravated assault . . .", "\n\nagainst a law enforcement officer.” ", "The evidence established that,\n\nat the time of his arrest, Miller threw a juice bottle (which he\n\nhad just purchased from a convenience store) at one of the\n\narresting officers and hit him in the head. ", " Regardless of the\n\nextent of the officer’s actual injury, we find that the district\n\n\n\n\n - 3 -\n\fcourt did not clearly err in finding that the enhancement applied\n\nbecause there was a substantial risk of serious injury.2\n\n Next, Miller argues that the sentence imposed is\n\nunreasonable because, inter alia, the district court failed to\n\nconsider the requisite factors enumerated in 18 U.S.C.A. § 3553(a)\n\n(West 2000 & Supp. ", "2007). ", " We find insufficient evidence in the\n\nrecord to show Miller is in error.", "\n\n This court reviews a district court’s sentence for\n\nreasonableness. ", " Hughes, 401 F.3d at 546-47. ", " “Consistent with the\n\nremedial scheme set forth in Booker, a district court shall first\n\ncalculate (after making the appropriate findings of fact) the range\n\nprescribed by the guidelines.” ", " Id. at 546. ", " Next, the district\n\ncourt must consider this range in conjunction with other relevant\n\nfactors under the guidelines and § 3553(a) and impose a sentence.", "\n\nId. The sentence must be “within the statutorily prescribed range\n\nand . . . ", "reasonable.” ", " Id. at 546-47 (citations omitted). ", " “[A]\n\nsentence within the proper advisory Guidelines range is\n\npresumptively reasonable.” ", "United States v. Johnson, 445 F.3d 339,\n\n341 (4th Cir. ", "2006) (citations omitted); see also Rita v. United\n\nStates, 127 S. Ct. ", "2456, 2462-69 (2007) (upholding application of\n\nrebuttable presumption of reasonableness to within-guidelines\n\n\n 2\n Indeed, while the evidence of the injuries suffered by the\nofficer who Miller assaulted is somewhat sparse--no doubt at least\nin part because he had died prior to Miller’s sentencing--another\nofficer testified in a related proceeding that the victim officer\nwas left with a scar that remained visible long after the incident.", "\n\n - 4 -\n\fsentence). ", " “[A] defendant can only rebut the presumption by\n\ndemonstrating that the sentence is unreasonable when measured\n\nagainst the § 3553(a) factors.” ", " United States v. Montes-Pineda,\n\n445 F.3d 375, 379 (4th Cir. ", "2006) (internal quotation marks and\n\ncitation omitted), cert. ", "denied, 127 S. Ct. ", "3044 (2007).", "\n\n A post-Booker sentence may be unreasonable for procedural\n\nor substantive reasons. ", " “A sentence may be procedurally\n\nunreasonable, for example, if the district court provides an\n\ninadequate statement of reasons or fails to make a necessary\n\nfactual finding.” ", " United States v. Moreland, 437 F.3d 424, 434\n\n(4th Cir.) (", "citations omitted), cert. ", "denied, 126 S. Ct. ", "2054\n\n(2006). ", " While a district court must consider the various factors\n\nlisted in § 3553(a) and explain its sentence, it need not\n\n“robotically tick through § 3553(a)’s every subsection” or\n\n“explicitly discuss every § 3553(a) factor on the record.”", "\n\nJohnson, 445 F.3d at 345. ", " “This is particularly the case when the\n\ndistrict court imposes a sentence within the applicable Guidelines\n\nrange.” ", " Id. (citation omitted).", "\n\n However, “a district court’s explanation should provide\n\nsome indication (1) that the court considered the § 3553(a) factors\n\nwith respect to the particular defendant; and (2) that it has also\n\nconsidered the potentially meritorious arguments raised by both\n\nparties about sentencing.” ", " Montes-Pineda, 445 F.3d at 380\n\n(citations omitted). ", " “[I]n determining whether there has been an\n\n\n - 5 -\n\fadequate explanation, [the court does] not evaluate a court’s\n\nsentencing statements in a vacuum.” ", " Id. at 381. ", " Rather, “[t]he\n\ncontext surrounding a district court’s explanation may imbue it\n\nwith enough content for [the court] to evaluate both whether the\n\ncourt considered the § 3553(a) factors and whether it did so\n\nproperly.” ", " Id.\n\n On the record before us, we are unable to discern whether\n\nthe district court considered the § 3553(a) factors or whether it\n\ndid so properly. ", " Accordingly, we vacate Miller’s sentence and\n\nremand for resentencing in order to allow the district court to\n\narticulate its reasons in imposing sentence.3 We dispense with\n\noral argument because the facts and legal contentions are\n\nadequately presented in the materials before the court and argument\n\nwould not aid the decisional process.", "\n\n\n\n AFFIRMED IN PART,\n VACATED IN PART,\n AND REMANDED\n\n\n\n\n 3\n We note that the district court sentenced Miller prior to our\ndecisions in Johnson and Montes-Pineda, and thus did not have the\nbenefit of the guidance provided by those cases. ", "We further note\nthat the district court is free on remand to impose the same\nsentence or a different one; nothing in this opinion should be read\nto suggest that we have formed any view regarding the appropriate\noutcome of Miller’s resentencing.", "\n\n\n - 6 -\n\f" ]

{ "pile_set_name": "FreeLaw" }

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[ "The overall goal of this proposal is to define the molecular mechanisms by which osteoprotegerin (OPG) inhibits the progression of atherosclerosis. ", "Growing evidence indicates that serum levels of OPG correlate with the severity of cardiovascular disease, and that OPG levels are an independent predictor of cardiovascular risk in humans. ", "OPG, a secreted TNF-like decoy receptor for TRAIL and RANKL, plays a critical role in bone homeostasis and in chronic inflammatory diseases. ", "We have shown that in mice prone to develop atherosclerotic lesions (ApoE-/- mice), OPG deficiency worsen the lesion burden, thus, suggesting that OPG contributes to limit lesion expansion and is an atheroprotective factor. ", "Further, we have shown that OPG protects against lesion calcification in vivo, promotes smooth muscle cells (SMCs) survival, and induces MMP9 expression in SMCs and macrophages in vitro (Bennett et al. ", "ATVB, 2006 Sep;26(9):2117-24). ", "However, the molecular mechanisms underlying this new OPG effects are unknown. ", "New preliminary data indicate that SMCs deficient for OPG are more sensitive to cell death and calcify more in response to high phosphate than wild type SMCs. ", "We also find that the OPG ligand TRAIL increases OPG deficient SMC cell death and calcification while RANKL only exacerbates calcification but does not affect cell survival. ", "In addition, inflammatory cells deficient for OPG express higher levels of inflammatory factors (TNF1 IL-12, IL-23, and CD86). ", "Thus, it appears that endogenous OPG affects responses in SMCs and inflammatory cells. ", "The aims of this proposal are: 1) to determine the mechanisms of OPG-mediated SMCs survival in vitro and whether SMC- specific OPG inhibits lesion progression;2) to determine the mechanisms of OPG inhibition of SMCs mineralization in vitro and the role of SMC-specific OPG in lesion calcification;3) to determine the phenotype of inflammatory cells in the vessel wall;whether the reintroduction of OPG in bone marrow-derived cell rescues lesion development;the role of OPG in the regulation of SMC cell death and calcification by inflammatory cells. ", "PUBLIC HEALTH RELEVANCE: Cardiovascular disease, osteoporosis, and bone destructive inflammation often co-exist and they afflict especially the elderly and women. ", "Osteoprotegerin is a very important regulator of bone tissues and clinical trials are underway to establish the potential osteoprotegerin-related therapies for bone disease. ", "Our research is aimed at understanding whether the molecule osteoprotegerin may be also beneficial in cardiovascular disease. ", "We believe that osteoprotegerin links the bone and cardiovascular systems. ", "Thus our research may uncover new therapeutic approaches aimed to alleviate both bone and cardiovascular diseases." ]

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[ "Congresul PNL s-a încheiat ieri cu alegerea ca președinte a lui Ludovic Orban (linc), care a primit 3518 voturi comparativ cu numai 952 voturi primite de contracandidatul Cristian Bușoi.", "\n\nFratele noului președinte al PNL este Leonard Orban, consilier prezidențial pentru „afaceri europene” (linc). ", "Apreciez că prin noul său conducător, PNL va deveni și mai apropiat de președintele Klaus Iohanis.", "\n\nÎn 2006 Ludovic Orban a declarat la Realitatea TV că tatăl său a fost ofițer de securitate. ", "Hotnews (linc) informa pe acest subiect:\n\nOrban a recunoscut că tatăl său a fost angajat al Securității avînd gradul de căpitan în rezervă, dar spune că a încheiat orice colaborare cu Securitatea înainte de a se naște el.", "\n\nLa sfîrșitul lunii mai (deci cînd nu se știa cine va fi președintele PNL) am pus pe grupul facebook PNL o trimitere la articolul care arăta că tatăl lui Orban a fost ofițer de securitate. ", "Ca urmare am fost exclus din acel grup facebook.", "\n\nPe saitul CNSAS (linc) găsesc un ofițer de securitate Imre (Emeric) Orban, născut în 3 octombrie 1920 la Odorheiul Secuiesc și răposat în 2005 la Brașov, care a lucrat la Securitate între 1948 și 1956 și a fost trecut în rezervă cu gradul de căpitan.", "\n\nLudovic Orban e născut în 1963 la Brașov." ]

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[ "Q:\n\nHTTP based authentication/encryption protocol in a custom system\n\nWe have a custom built program that needs authenticated/encrypted communication between a client and a server[both in Python].", "\nWe are doing an overhaul from custom written Diffie-Hellman+AES to RSA+AES in a non-orthodox way. ", "So I would be very interested in comments about my idea.", "\nPrequisites: Klient has a 128bit RegistrationKey which needs to remain a secret during the authentication - this key is also the only shared secret between the server and client.", "\n\nClient contacts the server over an insecure channel and asks the servers RSA PubKey\nClient then queries the server:\n[pseudocode follows]\n\n RegistrationKey = \"1dbe665ac7a944beb67f106f779e890b\"\n clientname = \"foobar\"\n randomkey = random(bits=128)\n rsa_cp = RSA(key=pubkey, data=randomkey+clientname)\n aes_cp = AES(key=RegistrationKey, data=RegistrationKey+rsa_cp)\n send(aes_cp)\n\n3. ", "Server then responds:\n [pseudocode follows]\n\n # Server decrypts the data and sees if it has a valid RegistrationKey, if it does...\n clientuuid = random(bits=128)\n sharedkey = random(bits=128)\n rsa_cp = RSA(key=privkey, data=clientuuid+sharedkey)\n aes_cp = AES(key=randomkey[got from client], data= rsa_cp)\n send(aes_cp)\n\nNow both sides know the \"clientuuid\", \"sharedkey\" which the client can use later to authenticate itself. ", "The method above should be secure even when the attacker learns the regkey later since he would have to crack the RSA key AND man-in-the-middle attacks(on RSA) should stop the auth. ", "from completing correctly.", "\nThe only possible attack method I see would be the case where the attacker knows the regkey AND can alter the traffic during the authentication. ", "Am i correct?", "\n\nI really want to hear your ides on what to add/remove from this method and If you know a much better way to do this kind of exchange.", "\nPS! ", "We are currently using Diffie-Hellman(my own lib, so it probably has flaws) and we have tried TLSv1.2 with PreSharedKeys(didn't work for some reason) and we are CONSTRICTED to http protocols since we need to do this in django. ", "And because we are doing this in http we try to keep the request/answer count as low as possible(no sessions would be the best) - 1 would be the best :)\nIf you have any questions about the specifics, please ask.", "\nSo, you crypto/security geeks, please give me a helping hand :)\n\nA:\n\nDon't re-invent the wheal, use HTTPS. ", " \nThe server can issue certificates to the client and store them in the Database. ", " Clients can be distributed with the server's self-signed certificate for verification. ", " The server can verify clients by using Apache's HTTPS Environment Variables.", "\n\nA:\n\nNo. ", "Use SSL. ", "Reinventing cryptosystems is a bad idea.", "\nWhat you can easily do is set up a reverse proxy. ", "Run your Django app on a higher port (e.g., 8080) and set it to respond only to connections from the loopback address (127.0.0.1). ", "Run the reverse proxy on port 443 (standard HTTPS port) and proxy all requests to the Django app. ", "But setup the reverse proxy with the site's certificate and have it be an SSL endpoint. ", "The proxied requests going to the Django app would then just be \"regular old\" HTTP, not HTTPS.", "\nApache Mod_Proxy\nNginX as a Reverse Proxy\n\n" ]

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[ "Date\n\nTime\n\nNEW! ", "ArtCubs is our newest program for families with pre-toddlers. ", "ArtCubs invites parents, grandparents, and caregivers with children 13 to 23 months of age to sing and sway in the museum galleries during this 60 minute class. ", "Each program includes activities that strengthen rhythm and movement within our galleries, and age-appropriate activities in the comfort of our private studio. ", "Wobbling and waltzing are welcome!", "\n\nArtCubs classes are for children ages 13 to 23 months old only. ", "Single strollers, tandem strollers and front-carrying baby carriers are permitted.", "\n\nArtCubs class size is limited to 10 children. ", "One adult is required for every child. ", "Pre-registration is mandatory.", "\n\nIn the event this program is sold out, please email family programs to be placed on the wait list.", "\n\nPlease note: Online pre-registration required. ", "Fall 2013 (August-January) Program registration will be available in July: July 1 - Member registration begins; July 8 - Public registration begins. ", "Museum members can register early for this popular series!" ]

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[ "Rosa hybrida cultivar Roroone.", "\nThe present Invention relates to a new and distinct cultivar of Rose plant, botanically known as Rosa hybrida, commercially used as a hybrid tea cut Rose, and hereinafter referred to by the name xe2x80x98Roroonexe2x80x99.", "\nThe new Rose is a product of a planned breeding program conducted by the Inventor in Aalsmeer, The Netherlands. ", "The objective of the breeding program was to develop new cut Rose cultivars with large flowers with attractive color and good postproduction longevity.", "\nThe new Rose originated from a cross made by the Inventor in Aalsmeer, The Netherlands of the Rosa hybrida cultivar Tineke, disclosed in U.S. Plant Pat. ", "No. ", "8,055, as the female, or seed, parent and the Rosa hybrida cultivar Sandy Femma, not patented, as the male, or pollen, parent. ", "The new Rose was discovered and selected by the Inventor in 1998 as a flowering plant within the progeny of the stated cross in a controlled environment in Aalsmeer, The Netherlands. ", "The selection of this new Rose was based on its large flowers and attractive flower color.", "\nAsexual reproduction of the new cultivar by cuttings taken in a controlled environment in Aalsmeer, The Netherlands since 1998, has shown that the unique features of this new Rose are stable and reproduced true to type in successive generations of asexual propagation.", "\nPlants of the cultivar Roroone have not been observed under all possible environmental conditions. ", "The phenotype may vary somewhat with variations in environment such as temperature and light intensity without, however, any variance in genotype.", "\nThe following traits have been repeatedly observed and are determined to be the unique characteristics of xe2x80x98Roroonexe2x80x99. ", "These characteristics in combination distinguish xe2x80x98Roroonexe2x80x99 as a new and distinct cultivar:\n1. ", "Erect flowering stems with relatively few thorns.", "\n2. ", "Shiny dark green leaves.", "\n3. ", "Creamy white-colored flowers; outer petals overlain with green.", "\n4. ", "Fragrant flowers.", "\n5. ", "Good postproduction longevity.", "\nPlants of the new Rose differ primarily from plants of the male parent, the cultivar Sandy Femma, in the following characteristics:\n1. ", "Plants of the new Rose have larger flowers than plants of the cultivar Sandy Femma.", "\n2. ", "Flowers of plants of the new Rose and the cultivar Sandy Femma differ in flower color as plants of the cultivar Sandy Femma have light yellow brown-colored flowers.", "\nPlants of the new Rose are similar to plants of the female parent, the cultivar Tineke. ", "In side-by-side comparisons conducted in Aalsmeer, The Netherlands, plants of the new Rose differed from plants of the cultivar Tineke in the following characteristics:\n1. ", "Plants of the new Rose had shorter flowering stems than plants of the cultivar Tineke.", "\n2. ", "Flowering stems of plants of the new Rose had fewer thorns than flowering stems of plants of the cultivar Tineke.", "\n3. ", "Plants of the new Rose were more vigorous and produced flowering stems about two weeks earlier than plants of the cultivar Tineke.", "\n4. ", "Plants of the new Rose had smaller flowers than plants of the cultivar Tineke.", "\n5. ", "Flowers of plants of the new Rose were fragrant whereas flowers of plants of the cultivar Tineke were not fragrant.", "\n6. ", "Flowering stems of plants of the new Rose had better postproduction longevity than flowering stems of the cultivar Tineke." ]

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[ "The rapid and accurate identification of bioagents is a vital task for first-responders in order to facilitate timely and appropriate actions in the event of a biological attack. ", "Bacillus anthracis, a spore-forming bacterium and a dangerous pathogen for the disease anthrax, is an important example. ", "B. anthracis bacteria exist in two different forms: rod-shaped organisms and spores. ", "Rod-shaped organisms grow and divide in a nutrient rich environment. ", "When the food supply is depleted, the organisms turn into spores that can survive for decades. ", "Structurally, a spore consists of a central core cell surrounded by various protective layers. ", "Calcium dipicolinate (CaDPA) exists in these protective layers and accounts for ˜10% of the spore's dry weight (Bailey et al., ", "1965, J. Bacteriol. ", "89:984-987) therefore, it is a useful biomarker for bacillus spores (Goodacre et al., ", "2000, Anal. ", "Chem. ", "72:119-127).", "\nAmong the potential biological warfare agent candidates, B. anthracis spores are of particular concern. ", "First, they are highly resistant to environmental stress and are relatively easily produced into weapon-grade material outside the laboratory. ", "Second, anthrax is an infectious disease, requiring medical attention within 24-48 h of initial inhalation of more than 104 B. anthracis spores (Walt and Franz, 2000, Anal. ", "Chem. ", "72:738 A-746A). ", "However, the diagnosis of anthrax is not immediate because it takes 1-60 days for anthrax symptoms to appear in humans (Chin, 2000, Control of Communicable Diseases Manual; American Public Health Association: Washington, D.C., pp 20-25). ", "Therefore, the rapid detection of B. anthracis spores in the environment prior to infection is an extremely important goal for human safety.", "\nThus, a great need exists for a rapid and sensitive detection protocol suitable for use by first responders to detect dangerous microorganisms (e.g., anthrax) that may be used in a biological attack. ", "Furthermore, such materials and methods should be portable for use in the field at potential sites of exposure and capable of providing results on site in short order." ]

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[ "1984 Amílcar Cabral Cup\n\nThe 1984 Amílcar Cabral Cup was held in Freetown, Sierra Leone.", "\n\nGroup stage\n\nGroup A\n\nGroup B\n\nIt is unknown why Mali was placed second over Guinea-Bissau, as all possible tie-breakers (e.g. goals scored, head-to-head) are for Guinea-Bissau's favor.", "\n\nKnockout stage\n\nSemi-finals\n\nThird place match\n\nFinal\n\nReferences\nRSSSF archives\n\nCategory:Amílcar Cabral Cup" ]

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[ "Search\n\nIn 2014 new regulations were introduced by the FIA which restricted the total fuel usage and maximum fuel flow rate for Formula 1 and LMP1 world endurance cars. ", "This was to drive… The Gill Fuel Flow Meter was developed to provide real-time regulation of the 2014 fuel rules for Formula 1 and Le Mans Prototype WEC motorsport series. ", "http://gilltechnology.com/applications/2014/05/gill-fuel-flow-meter/" ]

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[ "Q:\n\nFirst-order logic and NBG\n\nI know that NBG set theory can be viewed as an interpretation of the first-order logic with equality. ", "However, I do not really understand how do I get this interpretation. ", "\nAs I see it: \nI call variables \"classes\" and add the class membership relation $\\in$. I call a class $x$ a \"set\" if $\\exists y \\ (x \\in y)$. \nBut what do I do with constants? ", "Also, there is an empty set and the universal class, and I do not know how to represent them in the form $\\emptyset = \\dots$ and $V = \\dots$\n\nA:\n\nIt's not that NBG is an interpretation of FOL, it's that NBG is a theory in FOL, in the same way that e.g. the theory of rings is a theory in FOL. ", "\nThe language of NBG has a single binary relation, \"$\\in$,\" and no constants or functions. ", "So there's no need to interpret those (any more than we would demand that a ring understand what \"$<$\" means, say). ", "As to $\\emptyset$ and $V$, those aren't constant symbols, but rather definable elements - e.g. NBG proves that there is a unique $x$ satisfying $\\forall y(y\\not\\in x)$, and a unique $z$ satisfying $\\forall w(\\exists u(w\\in u)\\implies w\\in z)$. We refer to these as \"$\\emptyset$\" and \"$V$,\" but this is done outside the formal language.", "\n\n" ]

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[ "The terminology wireless communication includes a wide range of products including handheld radios, PDAs, cell phones, and wireless networking. ", "There are other examples of wireless technology that can be found in devices like Maritime VHF, garage door openers, computer mice, satellite television, GPS, keyboards, and cordless telephones.", "\n\nWireless communication has the ability to be limited to small distances, like it’s done with bluetooth communications, or also to thousand mile distances like with short wave radio communication. ", "Very often wireless communication is applied where wires are not possible or costly.", "\n\nWireless communications can be found frequently within the telecommunication sector as a vehicle to transport data without the need to use wires. ", "This transfer of data over large distances to communicate with complex, electrical products can be found in devices like telegraphs, teletypes, telephones, the use of microwave and radio waves, fiber optics and their corresponding electronics, in addition to its use in various orbiting satellites and the Internet.", "\n\nWhile the focus of opportunity in the telecommunications industry continually changes from wired to wireless frameworks, the necessity to access a larger portion of the electromagnetic spectrum becomes increasingly valuable. ", "There are many competing opinions of the best way to free up spectrum under the present power and control of the government bureaucracy’s around the world.", "\n\n...The country market penetration rates for mobile and internet services is among the highest on the continent's, while regulatory measures and improved international bandwidth capacity has also meant that consumers benefit from relatively low prices. ... ", "Read More\n\n...are also referred to as landline or dedicated line services. ", "The Fixed Telephony Services Global Market Briefing provides strategists, marketers and senior management with the critical information they need to assess the fixed telephony services ... Read More\n\n...used for telecommunications. ", "Reasons to Purchase Outperform competitors using accurate up to date demand-side dynamics information. ", "Identify growth segments for investment. ", "Facilitate decision making on the basis of historic and forecast data and the drivers ... Read More\n\n...wireless internet. ", "The market is further segmented on the basis of application to residential and business. ", "The Wireless Internet Services Global Market Briefing provides strategists, marketers and senior management with the critical information they need ... Read More\n\n...and other communication equipment. ", "The General Communication Equipment Global Market Briefing provides strategists, marketers and senior management with the critical information they need to assess the general communication equipment sector. ", "Reasons to Purchase Get up ... Read More\n\n...The market is further classified by service type into voice, SMS, and MMS. ", "The Cellular/Mobile Telephone Services Global Market Briefing provides strategists, marketers and senior management with the critical information they need to assess the ... Read More\n\n...figures, address details and management information. ", "Annual figures officially published by the retailers themselves is included in turnover. ", "2 sources provide reliable data we use these to make estimates, when official figures are not available. ... ", "Read More\n\n...paging and wireless information services. ", "It reports on new products available to providers and monitors public service commission rulings as they apply to information services. ", "It also reports on the marketing strategies of the IPs. ", "Read More\n\n...Worldwide Videotex Update reports news and information on videotex, The Internet, online services, electronic mail, satellite communications and television related technologies, such as teleconferencing and teletext. ", "Read More\n\n...is because it increasingly involves the same technologies, locations and companies. ", "Why are people so enthusiastic when they experience ubiquitous phone charging? ", "How will the standards battles be resolved? ", "Why will the planned move to ... Read More\n\n...and development and business plans of RBOCs (Regional Bell Operating Companies), long distance carriers, and independent vendors. ", "Subjects of articles include cellular service, EDI (Electronic Data Interchange), gateways, fiber optics, and effects of government regulations. ", "Read More\n\n...on international telecommunications products, services, and contracts. ", "Emphasis is on U.S. telecommunications companies doing business in foreign markets and on products with a potential market overseas. ", "Coverage includes methods of system integration into foreign networks. ", "Read More\n\n...networks. ", "These systems are made of a combination of smaller systems such as converters, distributors, controllers, and backup systems that bear different technical specifications. ", "The primary application of telecom power systems is in wireless and ... Read More\n\n...project overview and location. ", "The profile also details project ownership and funding, gives a full project description, as well as information on contracts, tendering and key project contacts. ", "The \"CSC – Samuel Oschin Air and ... Read More\n\n...including a breakdown of the data by construction activity (new construction, repair and maintenance, refurbishment and demolition). ", "The databook provides historical and forecast valuations of the industry using the construction output and value-add methods. ", "Summary ... Read More\n\n...construction industry, including a breakdown of the data by construction activity (new construction, repair and maintenance, refurbishment and demolition). ", "The databook provides historical and forecast valuations of the industry using the construction output and value-add ... Read More\n\n...demand for more reliable and accurate weather forecast is a major factor driving the weather forecasting services market globally’’ The weather forecasting services market is projected to grow from USD 1.10 billion in 2016 to ... Read More\n\n...sold with SIM cards unlocked if requested by consumers. ", "In addition, a widening range of economy smartphones became available during the review period, with smartphones seeing 26% current value unit price decline overall. ", "Euromonitor International's ... Read More\n\n...potential market of only two million people. ", "With high mobile penetration, telcos have branched into offering both mobile and fixed-line services so as to offer bundled products This strategy saw the cableco Telemach acquire Tumobil ... Read More" ]

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[ "Bacterial drug resistance is a significant current health problem throughout the world. ", "Multiple drug resistance is being commonly seen in a number of human pathogens (see, e.g., Hiramatsu et al., ", "J. Antimicrob. ", "Chemother., ", "1998, 40, 311-313 and Montecalvo et al., ", "Antimicro. ", "Agents Chemother., ", "1994, 38, 1363-1367, and the incidence of drug-resistant hospital infections is growing at a rapid rate. ", "For example, in some U.S. hospitals, nosocomial pathogens, such as E. faecium and Acinetobacter species, have acquired multiple resistance determinants and are virtually untreatable with current antimicrobial agents. ", "Bacterial resistance has now reached epidemic proportions and has been attributed to a variety of abuses of antibiotic treatments, including overuse (Monroe et al., ", "Curr. ", "Opin. ", "Microbiol., ", "2000, 3, 496-501), inappropriate dosing at sub-therapeutic levels (Guillemot et al., ", "JAMA, 1998, 279, 365-370), and misuse as antimicrobial growth promoters in animal food (Lathers, J. Clin. ", "Pharmacol., ", "2002, 42, 587-600). ", "Moreover, the threat of bio-terrorism has provided a further impetus to develop novel classes of antibiotics, particularly ones against which it will be difficult to develop resistant bacterial strains.", "\nThe pharmaceutical scientific community is responding to this challenge by focusing on the development of new antibiotic drugs. ", "Much of this work, however, is directed to synthesizing analogs of known drugs, such as cephalosporins and quinolones, that, while potentially useful for a short time, will inevitably also encounter bacterial drug resistance and become ineffective. ", "Thus, therapeutically effective antimicrobial drugs that act by novel mechanisms would provide an economic as well as a human health benefit.", "\nA series of nonpeptidic mimics of the natural antimicrobial peptides have been developed that are polymers, oligomers and small molecules comprised of non-natural building blocks. ", "See, Tew et al., ", "Proc. ", "Natl. ", "Acad. ", "Sci. ", "U.S.A., 2002, 99, 5110-5116; Arnt et al., ", "J. Polym. ", "Sci., ", "Part A, 2004, 42, 3860-3864; and Liu et al., ", "Angew Chem. ", "Int. ", "Ed. ", "Engl., ", "2004, 43, 1158-1162. ", "Many of these compounds are significantly smaller and easier to prepare than the natural antimicrobial peptides and peptidic mimetics, with the shortest of these oligomers having molecular weights typical of small molecule drugs. ", "They have the same mechanism of action as magainin, are highly potent and have a broad spectrum of activity, killing gram-positive, gram-negative and antibiotic-resistant pathogens. ", "Relative to the antimicrobial peptides, the non-peptidic mimetics are significantly less toxic towards human crythrocytes, much less expensive to prepare, and more stable.", "\nSee, for example, U.S. Published Patent Appl. ", "Nos. ", "US 2006-0041023 A1, US 2004-0202639 A1, US 2005-0287108 A1, and US 2006-0024264 A1, and U.S. Pat. ", "No. ", "7,173,102.", "\nThere is a great need for improved compositions and methods of treatment based on the use of antimicrobials that are more effective than existing agents against key ophthalmic and otic pathogens, and less prone to the development of resistance by those pathogens. ", "In particular, there is a great need for effective compositions and methods for the treatment of otic infections, especially bacterial infections. ", "The use of oral antibacterials to treat otic infections in children has limited efficacy and creates a serious risk of pathogen resistance to the orally administered antibacterial agent.", "\nThus, a need remains for improved ophthalmic and otic antimicrobial compositions, in particular, for broad-spectrum antimicrobial agents useful for the treatment of ophthalmic and otic infections that are not prone to the development of resistance by ophthalmic and/or otic pathogens and that are effective in the treatment of ophthalmic and otic pathogens that have already developed resistance to existing antimicrobial agents." ]

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[ "2007 Tampa Bay Buccaneers season\n\nThe 2007 Tampa Bay Buccaneers season was the franchise's 32nd season in the National Football League the 10th playing their home games at Raymond James Stadium, and the 6th under head coach Jon Gruden. ", "On December 16, 2007, they clinched the NFC South division title, and returned to the playoffs after missing it in 2006. ", "However, they were defeated 24-14 in the Wildcard Round by the eventual Super Bowl champion New York Giants. ", "The Wildcard game was Jon Gruden’s final playoff appearance as head coach of the Buccaneers before being dismissed at the conclusion of the next season.", "\n\nAs of 2019, this has been the last season that the Tampa Bay Buccaneers have qualified for the playoffs and won their division, making it 12 straight years that the Tampa Bay Buccaneers have missed the playoffs. ", "On December 16, in a game against the Atlanta Falcons, Micheal Spurlock scored the first kickoff return touchdown in franchise history, snapping a streak of 32 seasons, 497 games (at 53 stadiums in 38 cities), 139 individuals, and 1,864 unsuccessful attempts. ", "The play earned Spurlock the NFC Special Teams Player of the Week award.", "\n\nCoaching staff\nHead coach Jon Gruden was in his sixth year with the Buccaneers. ", "He was joined by Offensive Coordinator Bill Muir and Defensive Coordinator Monte Kiffin.", "\n\nStaff\n\nOffseason\nThe 2007 offseason proved to be productive for the Buccaneers. ", "General manager Bruce Allen and head coach Jon Gruden had approximately US$24 million in salary cap space with which to maneuver during free agency. ", "They made a splash on the first day of free agency by signing two quarterbacks: unrestricted free agent Jeff Garcia (Eagles) and Jake Plummer (Broncos) in a trade for a conditional pick in the 2008 draft (believed to be a 4th round selection if Plummer played). ", "Controversy soon followed as Plummer announced his retirement on the same day, citing his health and his lack of a desire to compete for a job and learn a new system. ", "However, he did not complete his retirement paperwork with the league. ", "Many believed that Plummer was simply trying to retire so that he could later unretire and play for the Texans. ", "They are led by his former coach Gary Kubiak, under whom Plummer played his best three years of football. ", "The league reviewed the trade to make sure that Plummer had not retired before the trade (a retired player cannot be traded), but he had not and his rights officially belong to the Buccaneers. ", "Other free agent losses and signings are as follows:\n\nSignings\n\n New York Giants OT Luke Petitgout, signed after being waived by his former team due to medical reasons.", "\n Miami Dolphins UFA DE/DT Kevin Carter\n Indianapolis Colts UFA LB Cato June who was selected to the Pro Bowl two years ago\n New York Jets UFA FB B.J. Askew\n Denver Broncos UFA DE/LB Patrick Chukwurah who had 4.5 sacks last season off of the bench. ", "He is reunited with his former defensive coordinator, the current Buccaneers defensive line coach, Larry Coyer.", "\n San Francisco 49ers UFA CB Sammy Davis, a former first round pick by the San Diego Chargers.", "\n San Francisco 49ers UFA DT Lance Legree, who has recorded 138 tackles and seven sacks in 76 games, including 25 starts. ", " He was released on April 10.", "\n DT Kenny Smith, who was out of football last season, but spent four seasons with the New Orleans Saints and one year with the Oakland Raiders, totaling 69 tackles and 4½ sacks.", "\n New Orleans Saints UFA WR Levon Thomas who spent most of his time on the practice squad after being signed as an UFA by the Indianapolis Colts following the 2005 NFL Draft.", "\n\nLosses\n The key loss for the Buccaneers was standout DE and former second round pick, Dewayne White who left to sign with his former DL coach, the current head coach of the Detroit Lions, Rod Marinelli.", "\n Versatile Lineman Sean Mahan left to join the Pittsburgh Steelers to reunite with another former Tampa Bay coach, Mike Tomlin.", "\n The team released veteran linebacker Shelton Quarles after it was reported he failed a physical. ", " Quarles had long been a productive player for Tampa, having spent his entire ten-year NFL career with the team.", "\n Following the draft, the Buccaneers released cornerback Juran Bolden, safety Tra Boger, long snapper Adam Johnson and defensive tackle Kenny Smith.", "\n\nRe-signings\nAfter brief stays on the open market, the Buccaneers re-signed CBs Phillip Buchanon and Torrie Cox, the latter known as a special teams standout. ", "They also re-signed fan favorite Mike Alstott to a one-year contract, but ultimately lost him to injured reserve after a neck injury during the preseason.", "\n\nRoster\n\n2007 NFL Draft\nThe 2007 NFL Draft took place in Radio City Music Hall on April 28–29, 2007. ", "The Buccaneers were either to pick third or fourth in the draft, to be determined by a coin flip with the Cleveland Browns because the two teams had identical records and strength of schedule. ", "Buccaneers GM Bruce Allen called heads and the coin landed tails. ", "For the first round, the Buccaneers picked fourth. ", "The two teams alternated picking third and fourth in each round. ", "In addition to their given picks, Tampa Bay also holds the Colts' second round pick, the 64th pick overall (because of a midseason trade for Anthony McFarland), but also lost a sixth round pick in a trade for tight end Doug Jolley formerly of the New York Jets. ", "They also received two compensatory picks, awarded for losses during free agency. ", "During the draft, the Buccaneers swapped fourth-rounders with the Minnesota Vikings in exchange for their pick in the sixth round.", "\n\nPreseason\nThe Tampa Bay Buccaneers held Training Camp at Disney's Wide World of Sports Complex from July 26 through August 16. ", "They played four preseason games.", "\n\nNotes\nOn August 9, 2007, fullback Mike Alstott was placed on injured reserve due to a neck injury, ending his 2007 season.", "\nOn August 30, 2007, with three minutes left in preseason, during the final touchdown against the Texans, wide receiver Paris Warren suffered a severe injury to his leg, and he was placed on injured reserve.", "\nPrior to the beginning of the regular season, the Buccaneers made their final cuts. ", " Among others, notable players included DT Ellis Wyms, a starter last season, and CB Alan Zemaitis a 2005 Fourth Round Draft pick.", "\n\nSchedule\n\nStandings\n\nRegular season game summaries\n\nWeek 1: at Seattle Seahawks\n\nThe Buccaneers began their 2007 campaign on the road against their fellow 1976 expansion mate, the Seattle Seahawks. ", " In the first quarter, kicker Matt Bryant provided two field goals for Tampa Bay (a 38-yarder and a 32-yarder) to begin the game. ", " In the second quarter, the Seahawks took the lead with kicker Josh Brown's 28-yard field goal, while RB Shaun Alexander got a 1-yard TD run. ", "During a scoreless third quarter, injuries sidelined Tampa Bay running back Cadillac Williams (ribs) and quarterback Jeff Garcia (head). ", "Garcia, however, returned to the game. ", "Seattle wrapped up the win with Brown's 46-yard field goal, while QB Matt Hasselbeck completed a 34-yard TD pass to RB Maurice Morris.", "\n\nWith the loss, the Buccaneers began their season at 0–1, their third opening day defeat in the past four seasons.", "\n\nWeek 2: vs New Orleans Saints\n\nThe Buccaneers played their home opener against the 2006 NFC South champion New Orleans Saints. ", "After scoring only 6 points the week before, the Buccaneers dominated the Saints, on offense and defense, at one point taking a 28–0 lead. ", "Early in the first quarter, Barrett Ruud recovered a Deuce McAllister fumble, which set up a Tampa Bay scoring drive. ", "Carnell Williams, who was back in the lineup after injuring his ribs the week before, capped off the drive with a one-yard touchdown run. ", "Early in the second quarter, Joey Galloway scored on a 69-yard catch and run from quarterback Jeff Garcia. ", "Inside the two-minute warning, Garcia and Galloway scored again, this time with a 24-yard touchdown, to take a 21–0 halftime lead. ", "Halfway through the third quarter, Cato June intercepted a pass from Drew Brees. ", "Two plays later, Garcia and Galloway connected for yet another big play, a 41-yard completion to the New Orleans 9-yard line. ", "Williams capped off the drive with his second 1-yard touchdown. ", "New Orleans' first score came with a 1-yard touchdown run by Mike Karney, aided by a 58-yard catch by Phillip Buchanon moments earlier. ", "The Buccaneers improved to 1–1, into a tie for the NFC South lead. ", "New Orleans fell to 0–2.", "\n\nFollowing the game, with 16 tackles, and 2 forced fumbles, middle linebacker Barrett Ruud was named the NFC Defensive Player of the Week on Wednesday September 19.", "\n\nWeek 3: vs St. Louis Rams\n\nThe Buccaneers and St. Louis Rams renewed a rivalry that was popular from 1999–2004. ", "The early part of the game was a field position battle, with Rams running back Steven Jackson rushing effectively in the first half. ", "All of St. Louis' first half drives, however, came up empty on the scoreboard. ", "Tampa Bay's first quarter drivers were also scoreless, with kicker Matt Bryant missing a 54-yard field goal short after slipping in the damp grass. ", "Just before the two-minute warning, Rams kicker Jeff Wilkins missed a 42-yard field goal, setting up Tampa Bay's first score. ", "After driving to the 17-yard line, a heavy downpour drenched the stadium. ", "Matt Bryant connected on 27-yard field goal for the game's first points and concluded the first half. ", "Tampa Bay received the second half kickoff, and rolled into the endzone with a 7-yard touchdown run by Carnell Williams. ", "St. Louis drove to the Tampa Bay 10-yard line, aided by two uncharacteristic defensive penalties by Derrick Brooks (late hit) and Ronde Barber (taunting). ", "The threat was moot, however, as Phillip Buchanon intercepted Marc Bulger in the endzone. ", "In the fourth quarter, Carnell Williams, aggravated his sore ribs, and fumbled the ball while Oshiomogho Atogwe recovered for St. Louis. ", "The Rams finally got on the scoreboard with a 25-yard field goal, narrowing the lead to 10–3 with 12 minutes to play. ", "Back up running back Earnest Graham took over for Williams, and iced the game with two rushing touchdowns, the first of his career outside of the preseason.", "\n\nWeek 4: at Carolina Panthers\n\nThe Buccaneers and Panthers met for the first time this season, with first place in the NFC South on the line. ", "Carolina starting quarterback Jake Delhomme sat out the game with an elbow injury, and was replaced by David Carr. ", "The Buccaneer offense started the game with an exhausting, 11-play, 71-yard drive, capped off by a 3-yard scramble by Jeff Garcia for a touchdown. ", "With 3 minutes left in the first quarter, running back Carnell Williams blasted down the field for an 18-yard run, but his right leg buckled, seriously injuring his knee. ", "As he was being carted off the field, nearly the entire Buccaneers team, along with several Panthers players, huddled around Williams in support. ", "After the injury timeout, Earnest Graham salvaged the drive with a one-yard touchdown run. ", "Tampa Bay extended their halftime lead to 17–0 after a Matt Bryant field goal, meanwhile, Carolina's offense was sputtering, blasted by the Buccaneers defense, who sacked Carr three times, and intercepted him once. ", "Carr completed only 19 of 41 pass attempts, and Carolina was facing their first shutout in five seasons. ", "With 23 seconds left in regulation, Carolina finally got on the board with a touchdown pass to DeAngelo Williams. ", "An onside kick was unsuccessful, and the Buccaneers won their third straight game.", "\n\nThrough four games, the Buccaneers had not given up any points in the first quarter, and quarterback Jeff Garcia had not thrown an interception. ", "After the game, the Buccaneers announced that running back Carnell Williams (torn patellar ligament) and left tackle Luke Petitgout (torn ACL) would both face season-ending surgery. ", "On Wednesday, October 3, linebacker Barrett Ruud was named the NFC Defensive Player of Month for September with a league-leading 51 tackles, three forced fumbles, two fumble recoveries, and one interception.", "\n\nWeek 5: at Indianapolis Colts\n\nThe Buccaneers faced former head coach Tony Dungy for the second time. ", "The previous meeting between the two teams in 2003 saw the Colts erase a 21-point deficit in the final four minutes to win the game in overtime. ", "Both teams entered the game with players sidelined by injuries. ", "Marvin Harrison and Joseph Addai sat out for Indianapolis, while Carnell Williams and Luke Petitgout were placed on injured reserve for Tampa Bay.", "\n\nThe Colts controlled the tempo of most of the game, with a time of possession of over 38 minutes and 400 yards of offense. ", "The Buccaneers were held to only 177 total yards and only 17 yards rushing. ", "The first three Buccaneers possessions were three-and-outs. ", "Meanwhile, Indianapolis pulled out to a 13–0 lead. ", "In the second quarter, Tanard Jackson intercepted Peyton Manning and set up the Buccaneers' first scoring drive. ", "During the drive, running back Michael Pittman left the game with an injured ankle. ", "Two plays later Tampa Bay got on the board with a Jeff Garcia touchdown pass to Alex Smith, and narrowed the score to 13–7.", "\n\nIn the second half, Indianapolis continued to dominate both sides of the ball, and stretched their lead to 30–7. ", "Garcia and Smith connected for a second touchdown pass with just over 9 minutes left in the fourth quarter, and made the score 30–14. ", "Hoping to spark a comeback, Tampa Bay attempted a surprise onside kick, but it was called back by a penalty. ", "Indianapolis then took the re-kick, and put three more points on the board with an Adam Vinatieri field goal. ", "Bruce Gradkowski took over as quarterback for Tampa Bay, and subsequently threw an interception to seal the victory for the Colts.", "\n\nThe following day, on Monday, October 8, the Buccaneers announced that Michael Pittman would miss 6–8 weeks with a cracked fibula.", "\n\nWeek 6: vs Tennessee Titans\n\nThe Buccaneers hosted the Titans at Raymond James Stadium, their second inter-conference matchup in two weeks. ", "Buccaneers running back Earnest Graham was a part of the starting lineup for the first time in his career, replacing the injured Michael Pittman, who sat out the game.", "\n\nThe first half was a defensive struggle, with neither team scoring in the first quarter. ", "Early in the second quarter, Tennessee drove to the Buccaneers 32-yard line, but quarterback Vince Young fumbled the ball and the Buccaneers recovered. ", "Jeff Garcia connected on a 39-yard pass play to Michael Clayton, to help set up a 23-yard Matt Bryant field goal, the first points of the game. ", "Moments later, Phillip Buchanon intercepted Vince Young with 1:29 remaining in the half, to maintain a 3–0 halftime lead.", "\n \nTennessee took the second half kickoff, and executed a 12-play, 45-yard drive which resulted in a 48-yard field goal by Rob Bironas. ", "On their next possession, Vince Young ran out of bounds, and suffered a strained quad. ", "He would have to leave the game, and was replaced by Kerry Collins. ", "On Tampa Bay's next drive, Garcia connected with Joey Galloway for a 69-yard touchdown catch. ", "On the ensuing drive Ronde Barber intercepted a pass by Kerry Collins, but it ruled incomplete after review.", "\n\nWith less than four minutes remaining in regulation, Collins drove the Titans to the Buccaneers 23-yard line. ", "For the second time, Ronde Barber intercepted Collins, this time in the endzone, but it was again ruled incomplete after review. ", "The drive continued, and with 1:24 remaining, LenDale White tied the game 10–10 with a touchdown run. ", "With only one timeout, Garcia drove the Buccaneers 55 yards on seven plays. ", "With 11 seconds remaining, Matt Bryant kicked a game-winning 43-yard field goal.", "\n\nThis is the only time the Buccaneers have beaten the Titans since they moved from Houston, and one of only two Buccaneer victories against the Oilers/Titans franchise, the other occurring in 1983.", "\n\nWeek 7: at Detroit Lions\n\nWeek 8: vs Jacksonville Jaguars\n\nTampa bay faced in-state rival Jacksonville Jaguars for the fourth time in the regular season. ", "Injured Jacksonville starting quarterback David Garrard was replaced by Quinn Gray, while Jeff Garcia hoped to extend on a 217-consecutive passing streak without an interception.", "\n\nIn the first half, Jacksonville's running attack of Fred Taylor, LaBrandon Toefield and Maurice Jones-Drew rushed 15 times in their first 16 plays from scrimmage, and eventually set up a 10–3 lead. ", "In the second quarter, Garcia threw his first interception of the season, which was returned for a Jacksonville score. ", "Tampa Bay quickly responded, however, driving 81 yards in three plays, capped off with Garcia and Joey Galloway connecting for a 58-yard touchdown.", "\n\nA momentum shift appeared to occur near the end of the second quarter, as Tampa Bay forced Jacksonville into a 3-and-out. ", "Inside the two-minute warning, Garcia drove the Buccaneers to the 4-yard line. ", "Garcia scrambled on 3rd & 10, colliding with Reggie Nelson, losing his helmet, but fell one yard short of the first down. ", "Tampa Bay settled for a Matt Bryant field goal, and a 13–17 halftime deficit.", "\n\nTampa Bay's defense dominated the third quarter, forcing Jacksonville a turnover on downs, a fumble in the end zone (recovered by Gray on 1-yard line), and a blocked punt. ", "The good field position led to Michael Bennett's first touchdown as a Buccaneer.", "\n\nThe fourth quarter saw Jacksonville re-take the lead with an 8-yard touchdown pass. ", "Despite two late drives starting with decent field position, Tampa Bay's effort died when Garcia's pass was deflected and intercepted with 19 seconds remaining, his third pick of the game. ", "The loss dropped Tampa Bay to 4–4, second place in the NFC South.", "\n\nWeek 9: vs Arizona Cardinals\n\nThe Buccaneers beat the visiting Arizona Cardinals, snapping a two-game losing streak, and regained first place in the NFC South. ", "Tampa Bay dominated the game, maintaining a time of possession of over 43 minutes with running back Earnest Graham rushing for 124 yards and one touchdown. ", "Tampa Bay's defense held Arizona to only 23 yards rushing, and held them to 2 of 10 third down conversions.", "\n\nIn the first quarter, Arizona quickly drove down the field, connecting on a 47-yard pass from Kurt Warner to Larry Fitzgerald. ", "The drive stalled, however, and they settled for 43-yard Neil Rackers field goal. ", "Tampa bay answered on the ensuing drive. ", "On 3rd and 1, from the 42-yard line, Jeff Garcia fell, but avoided a sack, and scrambled for a first down. ", "Two plays later he scored a 37-yard touchdown pass to Joey Galloway.", "\n\nOn the first play of the second quarter, Tanard Jackson intercepted Warner's pass, and Arizona was penalized 15 yards for a facemask, setting up the Buccaneers on the Arizona 27-yard line. ", "Tampa Bay suffered two false start penalties, and settled for a field goal and took a 10–3 lead into halftime.", "\n\nTampa Bay took the second half kickoff and drove 64 yards in ten plays. ", "The drive was capped off by a 2-yard touchdown run by Earnest Graham. ", "Late in the third quarter, the Buccaneers started a 19-play, 86-yard drive, lasting nearly 9 minutes. ", "At the 8-yard line, Garcia threw to Alex Smith but the pass was incomplete in the endzone. ", "The drive came up empty when Matt Bryant missed a 26-yard field goal. ", "Arizona quickly drove down the field and scored a touchdown by Edgerrin James, narrowing the margin to 17–10.", "\n\nWith 2:43 remaining in the game, Tampa Bay punted to Arizona. ", "Maurice Stovall de-cleated receiver Steve Breaston at the Arizona 16-yard line, preventing a return. ", "On the very next play, Jermaine Phillips intercepted Warner's pass, sealing the victory for Tampa Bay.", "\n\nWeek 10: Bye week\nThe Buccaneers had their scheduled bye the weekend of November 11. ", "In week 10 action, Atlanta defeated Carolina, and St. Louis upset New Orleans, giving Tampa Bay sole possession of first place in the NFC South.", "\n\nWeek 11: at Atlanta Falcons\n\nTampa Bay faced their heated division rival for the first time this season, at the Georgia Dome. ", "Tampa Bay dominated, and enjoyed the return of Michael Pittman from injury. ", "Atlanta started quarterback Byron Leftwich. ", "Atlanta suffered four turnovers, and 11 penalties for 105 yards in the loss.", "\n\nIn the first quarter, both teams traded punts on their opening drive. ", "On Tampa Bay's second drive, Pittman caught an 11-yard pass but fumbled and it was recovered by Keith Brooking. ", "An instant replay challenge upheld the ruling on the field. ", "On the very next play, Byron Leftwich was hit as he released the ball, and it was intercepted by Barrett Ruud, who returned the ball to the 28-yard line. ", "Tampa Bay drove 72 yards in three plays, as Joey Galloway caught a 44-yard touchdown.", "\n\nIn the second quarter, Leftwich was sacked from behind and fumbled the ball. ", "Ronde Barber picked up the ball, and ran 41 yards for Tampa Bay's second touchdown. ", "On Atlanta's next drive, Warrick Dunn fumbled at the 45-yard line. ", "Atlanta challenged the ruling, and the call on the field was overturned and ruled an incomplete pass. ", "The following play, Roddy White fumbled, and Brian Kelly recovered for Tampa Bay. ", "He lateraled to Cato June, who then lost the ball. ", "Despite an instant replay challenge by Tampa Bay, the ruling on the field was upheld. ", "Atlanta, however, was unable to move down the field, and Tampa Bay took a 14–0 lead into halftime.", "\n\nIn the third quarter, Tampa Bay added a field goal, then Gaines Adams chopped Leftwich's arm as he threw and his floating pass was intercepted by Chris Hovan (later in the week NFL officials revised the play to a sack & fumble recovery). ", "Tampa Bay quickly scored another touchdown catch by Alex Smith. ", "In the fourth quarter, Earnest Graham took over the offense for Tampa Bay, rushing 102 yards total, and a touchdown score. ", "Atlanta avoided the shutout, replacing Leftwich with Joey Harrington, and scored a touchdown with 1:10 to go.", "\n\nWeek 12: vs. Washington Redskins\n\nTampa Bay hosted Washington for the third time in three seasons during the month of November. ", "Tampa Bay's defense dominated a good part of the game, forcing six turnovers, and despite quarterback Jeff Garcia sitting out most of the game, the Buccaneers held on for a 19–13 victory.", "\n\nOn the game's first play, Garcia tried to scramble, but injured his back upon being tackled by Cornelius Griffin. ", "He lasted only two more plays, and was replaced by Bruce Gradkowski until early in the fourth quarter. ", "Garcia's injury seemingly galvanized the Tampa Bay defense, who went on to cause 4 turnovers in the first half. ", "Phillip Buchanon forced a fumble off the Redskins' first pass which was recovered by Tanard Jackson who advanced it 8 yards to the Washington 19. ", "Three plays later, Earnest Graham scored a 1-yard touchdown run. ", "On the third play of Washington's next drive, Greg White hit Clinton Portis hard, forcing a fumble which Jackson recovered at the 19-yard line. ", "Tampa took a 10–0 lead after a Matt Bryant field goal.", "\n\nEarly in the second quarter, Greg White forced yet another fumble as he sacked Jason Campbell which Kevin Carter recovered. ", "The turnover led to another field goal. ", "Portis fumbled again on the following drive as he took a bone-jarring hit from Jermaine Phillips and Tampa Bay capitalized with a third field goal. ", "Before the half, Washington got on the board with a field goal, then Tampa Bay kicked a fourth field goal as the half expired to lead, 19–3.", "\n\nThe second half saw Washington attempt a comeback. ", "Despite injuring his hand, Campbell stayed in the game, and threw a 39-yard touchdown pass to Chris Cooley. ", "Meanwhile, Gradkowski stayed in at quarterback for Tampa Bay, and continued to perform poorly. ", "Tampa Bay managed only 9 yards of offense in the third quarter, and 0 yards passing. ", "The Redskins drove 66 yards in 13 plays and over nine minutes to the Tampa Bay 4-yard line. ", "Tampa Bay's defense held on 4th and 1 at the 4, however, as linebacker Derrick Brooks shed several blockers to down Portis for no gain.", "\n\nWashington narrowed the score to 19–13 in the fourth quarter. ", "With about 11 minutes to go, Jeff Garcia returned to the game, hoping to spark Tampa Bay's offense, and hold on for the win. ", "He was unable to do much against the Redskins' well-rested and fired up defense, however, and Tampa Bay ended up having to punt. ", "Josh Bidwell pinned the Redskins at their own 9-yard line, and Campbell drove them to the Tampa Bay 32-yard line. ", "Ronde Barber stopped the threat when he intercepted the ball at the 28-yard line. ", "With less than a minute to go, Campbell drove the Redskins to the Tampa Bay 16-yard line, but Brian Kelly intercepted the pass in the end zone with 17 seconds remaining, to clinch the victory for the Buccaneers.", "\n\nWeek 13: at New Orleans Saints\n\nTampa Bay took on the New Orleans Saints for the second time this season, this time at the Superdome. ", " Luke McCown started at quarterback for the Buccaneers in place of the injured Jeff Garcia. ", "McCown passed for 313 yards, and connected on his first 15 consecutive passes of the game.", "\n\nThe Buccaneers scored the first points of the game with Matt Bryant's 27-yard field goal. ", "New Orleans answered with WR Terrance Copper catching a 4-yard touchdown pass from Drew Brees. ", "Late in the first quarter, McCown connected with WR Joey Galloway for a 60-yard catch which set Tampa Bay up on 1-yard line.", "\n\nTampa Bay retook the lead early in the second quarter with TE Anthony Becht catching a 1-yard TD, and Matt Bryant making another field goal to increase the Tampa Bay lead to 13–7. ", "New Orleans scored a touchdown just before halftime, a 45-yard pass to WR Devery Henderson, to make it 13–14 at halftime.", "\n\nIn the second half, RB Earnest Graham scored a 25-yard touchdown run. ", " New Orleans had to punt on their ensuing possession, but disaster struck with 3 minutes remaining in the third quarter as miscommunication between McCown and Galloway led to a Saints interception which was returned for a touchdown.", "\n\nLeading 21–20 with 4 minutes remaining in the game, Saints punter Steve Weatherford made a successful coffin corner punt which pinned the Buccaneers at their own 2-yard line. ", "Two plays later, Delaware Will Smith sacked McCown for a safety. ", "After the safety kick, New Orleans looked to run the clock out and seal the victory. ", "However, in an unexpected and perhaps season-altering mistake, Reggie Bush fumbled a double reverse intended for WR Devery Henderson and Jovan Haye recovered for Tampa Bay at the New Orleans 37-yard line. ", "Three plays later, the Buccaneers found themselves in a predicament as they faced a fourth down and 1 at the New Orleans 28. ", "Instead of attempting a game-tying field goal, however, coach Jon Gruden went for it on fourth down, calling a run around right tackle which Graham converted for a first down. ", "Three plays later, McCown found TE Jerramy Stevens for a 4-yard touchdown to win the game.", "\n\nWith the win, Tampa Bay improved to 8–4 and maintained a perfect division record. ", "Tampa Bay only needed to win one game in the final four weeks to clinch the NFC South division crown.", "\n\nWeek 14: at Houston Texans\n\nTampa Bay faced the Texans for only the second time in the regular season, and for the first time during the regular season at Reliant Stadium. ", "With a win, or losses by New Orleans and Carolina, Tampa Bay would clinch the NFC South division title. ", "Tampa Bay's postseason berth, however, would have to wait at least another night, as the Texans capitalized on a sluggish Buccaneers squad.", "\n\nFor the second week in a row, Luke McCown started in place of injured Jeff Garcia. ", "Meanwhile, back-up quarterback Sage Rosenfels led the Texans. ", "Tampa Bay took the opening kickoff, and drove to the Houston 34-yard line. ", "Coach Jon Gruden elected to go for it on 4th down and 2, but running back Earnest Graham was tackled for no gain. ", "Houston took over on downs, and scored a quick and convincing touchdown pass. ", "On the ensuing kickoff, Tampa Bay's Micheal Spurlock returned the ball 45 yards to the Houston 47. ", "Even though the drive ended in a punt, the good field position helped pin the Texans deep on their next drive. ", "Greg White sacked Rosenfels and forced a fumble, which was recovered by Jovan Haye the Houston 25. ", "Five plays later, Earnest Graham scored his first rushing touchdown to tie the score 7–7.", "\n\nLater in the second quarter, Ike Hilliard caught a pass for a first down at the Houston 28, but Will Demps hit Hillard in an apparent helmet-to-helmet and forced a fumble, but did not draw a penalty. ", "Houston recovered, and soon scored a second touchdown to lead 14–7 at halftime.", "\n\nHouston received the second half kickoff, which André Davis returned 97 yards for a touchdown. ", "Just over two minutes later, Tampa Bay responded with a four-play, 69-yard drive, capped off by Graham's second rushing touchdown. ", "Tampa Bay, however, did not score again.", "\n\nHouston added another score early in the fourth quarter, and held on for a 28–14 victory. ", "Tampa Bay fell to 8–5, but still controlled their own destiny for the division championship and overall playoff picture. ", "A single victory in the final three weeks would clinch the NFC South championship. ", "In other week 14 action, Carolina lost to Jacksonville, eliminating them from the division race, and New Orleans defeated Atlanta, keeping themselves mathematically alive for the division title.", "\n\nWeek 15: vs. Atlanta Falcons\n\nThe Buccaneers stayed home this week for a rematch against their division rivals the Atlanta Falcons. ", "With the convincing victory, Tampa Bay clinched the NFC South division title, maintained a perfect 5–0 division record, and scored their first kickoff return touchdown in franchise history.", "\n\nTampa Bay's defense recorded the first points of the game, as Ronde Barber intercepted Chris Redman's pass on the third play of the game and returned it 29 yards for a touchdown. ", "Atlanta got on the board next with kicker Morten Andersen making a 33-yard field goal. ", "On the ensuing kickoff, Micheal Spurlock made team history by becoming the first Buccaneer player to return a kickoff for a touchdown. ", "It was the first kickoff return touchdown for Tampa Bay in 32 seasons, 498 games, and 1,865 attempts.", "\n\nAfter the Buccaneer defense forced a Falcons punt, Jeff Garcia commandeered a long, clock-eating 10-minute drive ending in a 33-yard field goal by Matt Bryant to make the score 17–3. ", "With just over five minutes remaining in the first half, Tampa bay recovered an Atlanta fumble, and Earnest Graham scored a 1-yard TD run. ", "Graham became the first player in club history to score a touchdown in six consecutive games. ", "With a 24–3 lead, Tampa Bay performed a pooch kickoff, and Atlanta muffed the return, while Kalvin Pearson recovered. ", "Tampa Bay drove to the 24-yard line, but DeAngelo Hall intercepted a pass intended for Joey Galloway at the Atlanta 11-yard line. ", "The Buccaneers would immediately regain possession as Greg White forced and recovered a fumble on the next play. ", "Matt Bryant then easily converted a 28-yard field goal to take a 27–3 lead into halftime.", "\n\nTampa Bay would receive the second half's opening kickoff, but was forced to punt after a 7-minute drive. ", "On Atlanta's third play, Jermaine Phillips intercepted a pass intended for Jerious Norwood which set Tampa Bay up at the Atlanta 23-yard line. ", "Matt Bryant then scored the half's first points with a 34-yard field goal to make the score 30–3. ", "In the fourth quarter, punter Josh Bidwell successfully pinned Atlanta at their own 6-yard line. ", "The resulting poor field position eventually led to Tampa Bay taking over near midfield. ", "Michael Bennett carried six times all the way to the Atlanta 1-yard line, from which Anthony Becht scored the game's final points off a 1-yard TD catch.", "\n\nStatistically, Tampa Bay's defense dominated Atlanta. ", "The Falcons managed only 133 yards of total offense, committed five turnovers, and were 0-for-9 on third down conversions. ", "The Falcons crossed midfield only once, and Tampa Bay's time of possession was 43 minutes. ", "On the following Wednesday, the kickoff return touchdown earned Spurlock the NFC Special Teams Player of the Week award.", "\n\nWeek 16: at San Francisco 49ers\n\nTampa Bay traveled west to San Francisco for the third time in five seasons. ", "Tampa Bay lost their eighth consecutive meeting at Monster Park, dating to 1980. ", "This game was originally scheduled for 8:15 p.m. on NBC's Sunday Night Football, but on December 10, in accordance with flex-scheduling, the game was moved to the afternoon. ", "Having already clinched a playoff berth, Tampa Bay rested most of their starters in the second half. ", "Despite a late rally, the Buccaneers fell two points short of victory.", "\n\nTampa Bay controlled most of the first half, capping off their first two drives of the first quarter with field goals by Matt Bryant. ", "On the first play of the second quarter, Shaun Hill connected with Darrell Jackson on a 21-yard touchdown.", "\n\nSan Francisco punted on their next drive, and Micheal Spurlock fielded the ball at the 19-yard line. ", "He was tackled and fumbled, while the 49ers recovered. ", "After an instant replay challenge, it was determined that Spurlock was down by contact, and Tampa Bay maintained possession. ", "The drive fizzled though, and ended with a punt. ", "Late in the fourth quarter, Barrett Ruud recovered a 49ers fumble, setting the Buccaneers up on the San Francisco 36-yard line. ", "Four plays later, Jerramy Stevens caught a touchdown pass from Jeff Garcia. ", "Tampa Bay took a 13–7 lead into halftime.", "\n\nOn the second-half kickoff, San Francisco recovered a surprise onside kick. ", "The drive came up empty, as they were forced to punt. ", "On Tampa Bay's next possession, however, Luke McCown (who had taken over for the benched Garcia) fumbled and the 49ers recovered at the 14-yard line. ", "In four plays, San Francisco scored a touchdown.", "\n\nEarly in the fourth quarter, Nate Clements intercepted a McCown pass, and led to another 49ers touchdown. ", "The 49ers led 21–13, but Tampa Bay still kept hopes alive for a rally. ", "With less than six minutes left in the game, the Buccaneers drove to the 49ers 25-yard line. ", "On 4th down and 6, McCown threw to Michael Clayton for an apparent one-handed touchdown catch, but the ball fell incomplete, and the drive turned over on downs. ", "Tampa Bay managed one final chance to tie the score. ", "Inside the two-minute warning, Tampa Bay drove to the 49ers 24-yard line. ", "McCown rolled out wide to his right, and connected with Stevens for a 24-yard touchdown. ", "McCown then attempted a game-tying two-point conversion. ", "Michael Clayton caught the pass, but one of his feet touched out-of-bounds in the back of the endzone, sealing the game for San Francisco.", "\n\nWeek 17: vs. Carolina Panthers\n\nTampa Bay concluded the regular season at home against the Panthers. ", "They dropped the season finale, and their second-straight game, but rested most of their starters (including Garcia, Graham, Galloway and Ruud). ", "Luke McCown started at quarterback.", "\n\nOn their opening drive, McCown drove the Buccaneers for the game's first score, a touchdown pass to Jerramy Stevens. ", "The drive included a 52-yard catch by Chad Lucas. ", "Carolina responded by driving to the Tampa Bay 4-yard line. ", "A field goal kick was good, but a holding penalty by Derrick Brooks gave the Panthers a first down. ", "They capitalized by scoring a touchdown.", "\n\nIn the second quarter, an interception by Phillip Buchanon led to a Tampa Bay field goal. ", "Late in the second quarter, Josh Bidwell punted to Carolina, but a fumble on the return was recovered by the Buccaneers. ", "Tampa Bay tacked on another field goal before halftime, and trailed, 14–13, at the half.", "\n\nMidway through the third quarter, Carolina punted and pinned the Buccaneers on their own 2-yard line. ", "McCown then led the Buccaneers on a 10-play, 98-yard touchdown drive, the longest such scoring drive in franchise history. ", "Carolina kept themselves in the game, however, quickly following up with a 46-yard reception to Drew Carter, and then a 1-yard touchdown run.", "\n\nTrailing 31–23 late in the fourth quarter, McCown drove the Buccaneers to the Carolina 36-yard line, but was intercepted by Richard Marshall. ", "The Buccaneers finished the regular season 9–7 (5–1 division, 6–2 home).", "\n\nPlayoffs\n\nNFC Wild Card playoff: New York Giants 24, Tampa Bay Buccaneers 14\n\nOffseason\nOn January 22, 2008, head coach Jon Gruden and general manager Bruce Allen were re-signed to a three-year contract extension.", "\nOn January 24, 2008, Mike Alstott scheduled a press conference, and is expected to retire.", "\n\nReferences \n\nTampa Bay Buccaneers season\nTampa Bay Buccaneers\nCategory:21st century in Tampa, Florida\nCategory:NFC South championship seasons\nCategory:Tampa Bay Buccaneers seasons" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "# Copyright 2018 The TensorFlow Authors. ", "All Rights Reserved.", "\n#\n# Licensed under the Apache License, Version 2.0 (the \"License\");\n# you may not use this file except in compliance with the License.", "\n# You may obtain a copy of the License at\n#\n# http://www.apache.org/licenses/LICENSE-2.0\n#\n# Unless required by applicable law or agreed to in writing, software\n# distributed under the License is distributed on an \"AS IS\" BASIS,\n# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n# See the License for the specific language governing permissions and\n# limitations under the License.", "\n# ==============================================================================\n\n\"\"\"Tests for tf_cnn_benchmarks.cnn_util.\"\"\"", "\n\nfrom __future__ import absolute_import\nfrom __future__ import division\nfrom __future__ import print_function\n\nimport threading\nimport time\n\nimport tensorflow as tf\n\nimport cnn_util\n\n\nclass CnnUtilBarrierTest(tf.test.", "TestCase):\n\n def testBarrier(self):\n num_tasks = 20\n num_waits = 4\n barrier = cnn_util.", "Barrier(num_tasks)\n threads = []\n sync_matrix = []\n for i in range(num_tasks):\n sync_times = [0] * num_waits\n thread = threading.", "Thread(\n target=self._run_task, args=(barrier, sync_times))\n thread.start()\n threads.append(thread)\n sync_matrix.append(sync_times)\n for thread in threads:\n thread.join()\n for wait_index in range(num_waits - 1):\n # Max of times at iteration i < min of times at iteration i + 1\n self.assertLessEqual(\n max([sync_matrix[i][wait_index] for i in range(num_tasks)]),\n min([sync_matrix[i][wait_index + 1] for i in range(num_tasks)]))\n\n def _run_task(self, barrier, sync_times):\n for wait_index in range(len(sync_times)):\n sync_times[wait_index] = time.time()\n barrier.wait()\n\n def testBarrierAbort(self):\n num_tasks = 2\n num_waits = 1\n sync_times = [0] * num_waits\n barrier = cnn_util.", "Barrier(num_tasks)\n thread = threading.", "Thread(\n target=self._run_task, args=(barrier, sync_times))\n thread.start()\n barrier.abort()\n # thread won't be blocked by done barrier.", "\n thread.join()\n\n\nclass ImageProducerTest(tf.test.", "TestCase):\n\n def _slow_tensorflow_op(self):\n \"\"\"Returns a TensorFlow op that takes approximately 0.1s to complete.\"\"\"", "\n def slow_func(v):\n time.sleep(0.1)\n return v\n return tf.py_func(slow_func, [tf.constant(0.)], ", "tf.float32).op\n\n def _test_image_producer(self, batch_group_size, put_slower_than_get):\n # We use the variable x to simulate a staging area of images. ", "x represents\n # the number of batches in the staging area.", "\n x = tf.", "Variable(0, dtype=tf.int32)\n if put_slower_than_get:\n put_dep = self._slow_tensorflow_op()\n get_dep = tf.no_op()\n else:\n put_dep = tf.no_op()\n get_dep = self._slow_tensorflow_op()\n with tf.control_dependencies([put_dep]):\n put_op = x.assign_add(batch_group_size, use_locking=True)\n with tf.control_dependencies([get_dep]):\n get_op = x.assign_sub(1, use_locking=True)\n with self.test_session() as sess:\n sess.run(tf.variables_initializer([x]))\n image_producer = cnn_util.", "ImageProducer(sess, put_op, batch_group_size,\n use_python32_barrier=False)\n image_producer.start()\n for _ in range(5 * batch_group_size):\n sess.run(get_op)\n # We assert x is nonnegative, to ensure image_producer never causes\n # an unstage op to block. ", "We assert x is at most 2 * batch_group_size,\n # to ensure it doesn't use too much memory by storing too many batches\n # in the staging area.", "\n self.assertGreaterEqual(sess.run(x), 0)\n self.assertLessEqual(sess.run(x), 2 * batch_group_size)\n image_producer.notify_image_consumption()\n self.assertGreaterEqual(sess.run(x), 0)\n self.assertLessEqual(sess.run(x), 2 * batch_group_size)\n\n image_producer.done()\n time.sleep(0.1)\n self.assertGreaterEqual(sess.run(x), 0)\n self.assertLessEqual(sess.run(x), 2 * batch_group_size)\n\n def test_image_producer(self):\n self._test_image_producer(1, False)\n self._test_image_producer(1, True)\n self._test_image_producer(2, False)\n self._test_image_producer(2, True)\n self._test_image_producer(3, False)\n self._test_image_producer(3, True)\n self._test_image_producer(8, False)\n self._test_image_producer(8, True)\n\n\nif __name__ == '__main__':\n tf.test.main()\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\ncheck element of one array in another array\n\nI have 3 arrays, I want to check if any element of subarray in mainArray is exist - then it should return true.", "\nI have tried this, but it is returning true only if mainArray containing all the item of sub array.", "\nMY js:\nvar sub1 = [\"0\", \"10\"];\nvar sub2 = [\"18\", \"3\", \"13\", \"4\"];\nvar mainArr = [\"0\", \"1\", \"5\", \"8\", \"9\", \"10\"];\nif (containsChk(sub1, mainArr)) {\n alert('yes');\n} else {\n alert('no');\n}\n\nfunction containsChk(sub, main) {\n for (var i = 0, len = sub.length; i < len; i++) {\n if ($.inArray(sub[i], main) == -1) return false;\n }\n return true;\n}\n\nJsfiddle\n\nA:\n\nYou should just use array.indexOf() (http://www.w3schools.com/jsref/jsref_indexof_array.asp).", "\nfor (var i = 0; i < sub1.length; i++)\n if (mainArray.indexOf(sub1[i]) !", "= -1)\n return true;\nreturn false;\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Efficacy of soft splints in reducing severe knee-flexion contractures.", "\nThis study evaluated the effectiveness of soft splints made from polyurethane foam in reducing severe knee-flexion contractures of patients with cerebral palsy. ", "The splints were applied nightly over a period of 10 months. ", "Knee-flexion contractures were reduced by an average of 24 degrees in all patients. ", "Younger patients generally presented with less severe initial contractures and had the greatest percentage of improvement. ", "When used on a single limb when bilateral contractures were present, sympathetic reduction of the contracture occurred to varying degrees in the unsplinted limb. ", "It is recommended that the splints be replaced regularly to maximize their effectiveness. ", "The benefit-to-cost ratio is extremely high and their low cost makes soft splints feasible for use in developing countries and by low-income families." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nReturn an Object from BackgroundWorker\n\nI am dithering an image in a BackgroundWorker thread and need to update the UI after the image is done processing. ", " The image I need to update exists in the same class as the DitherWorker. ", " How do I pass the BitmapSource so that the noted error does not occur?", "\npublic void DitherWorker()\n{\n double scalebox = Double.", "Parse(myWindow.scaleBox.", "Text);\n int slider = (int)myWindow.convolutionBiasSlider.", "Value;\n BitmapSource final = null;\n ditherobj output = new ditherobj(scalebox, originalImage, slider);//.Get_Halftone();\n\n worker = new BackgroundWorker();\n worker.", "WorkerSupportsCancellation = true;\n\n worker.", "DoWork += delegate(object s, System.", "ComponentModel.", "DoWorkEventArgs args)\n {\n ditherobj dob = (ditherobj)args.", "Argument;\n Binarize bn = new Binarize(dob.scalebox, dob.localbms, dob.slider);\n BitmapSource bms = (BitmapSource)bn.", "Get_Halftone();\n final = bms;\n args.", "Result = new ditherobj(0,null,0,bms);\n };\n\n worker.", "RunWorkerCompleted += delegate(object s, RunWorkerCompletedEventArgs args)\n {\n ditherobj dob = (ditherobj)args.", "Result;\n image1.Source = dob.localbms; //ERROR. ", "The calling thread cannot access this object because another thread owns it\n\n myWindow.", "Dispatcher.", "Invoke(DispatcherPriority.", "Normal, new ThreadStart(() =>\n {\n myWindow.activityBar.", "IsBusy = false;\n }));\n };\n\n worker.", "RunWorkerAsync((ditherobj)output);\n}\n\npublic class ditherobj\n {\n public double scalebox;\n public BitmapSource localbms;\n public BitmapImage localbmi;\n public int slider;\n\n public ditherobj(double scalebox, BitmapImage localbmi, int slider, BitmapSource bms = null)\n {\n this.scalebox = scalebox;\n this.slider = slider;\n if (bms == null)\n {\n BitmapImage test = localbmi.", "Clone();\n localbms = (BitmapSource)test;\n }\n else\n localbms = bms;\n }\n }\n\nProblem solved. ", " The BitmapSource must be frozen in the background thread before being passed. ", " Here is the final comented code:\nBackgroundWorker worker;\n public void DitherWorker()\n {\n double scalebox = Double.", "Parse(myWindow.scaleBox.", "Text); //get values from UI for the job\n int slider = (int)myWindow.convolutionBiasSlider.", "Value;\n DitherSettings output = new DitherSettings(scalebox, originalImage, slider); //create holder object to be passed to BackgroundWorker\n worker = new BackgroundWorker();\n\n worker.", "DoWork += delegate(object s, System.", "ComponentModel.", "DoWorkEventArgs args)\n {\n\n DitherSettings ds = (DitherSettings)args.", "Argument; //cast argument as our holder object\n Binarize bn = new Binarize(ds.scalebox, ds.localbms, ds.slider); //create object to do our work\n BitmapSource bms = (BitmapSource)bn.", "Get_Halftone(); //do work\n bms.", "Freeze(); //freeze resulting BitmapSource so it can be utilized elsewhere\n args.", "Result = new DitherSettings(0,null,0,bms); //create new object with resulting BitmapSource\n\n };\n\n worker.", "RunWorkerCompleted += delegate(object s, RunWorkerCompletedEventArgs args)\n {\n DitherSettings ds = (DitherSettings)args.", "Result; //get object with our BitmapSource\n\n if (image1.Dispatcher.", "CheckAccess())\n this.image1.Source = ds.localbms; //update class image\n\n myWindow.", "Dispatcher.", "Invoke(DispatcherPriority.", "Normal, new ThreadStart(() =>\n {\n myWindow.activityBar.", "IsBusy = false; //Update UI control\n }));\n };\n\n worker.", "RunWorkerAsync((DitherSettings)output);\n\n }\n\n public class DitherSettings\n {\n public double scalebox;\n public BitmapSource localbms;\n public BitmapImage localbmi;\n public int slider;\n\n public DitherSettings(double scalebox, BitmapImage localbmi, int slider, BitmapSource bms = null)\n {\n this.scalebox = scalebox;\n this.slider = slider;\n if (bms == null)\n localbms = (BitmapSource)localbmi;\n else\n localbms = bms;\n }\n }\n\nA:\n\nCall the Freeze() function on the BitmapSource when you are still on the background thread.", "\nThis makes the object immutable, and can therefore be used on the main thread.", "\nLearn here more about freezable wpf objects. ", "The page discusses a lot of other aspects of Freezables, but it also explicitly states: \"A frozen Freezable can also be shared across threads, ...\". ", "This ability built in WPF to build GUI elements (such as bitmaps) on background threads is the #1 underadvertized WPF feature if you ask me.", "\n\n" ]

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[ "Watch Talking Bad Free Online\n\nTalking Bad is a weekly, half-hour live after-show and companion piece for AMC's Emmy Award-winning series, Breaking Bad. ", "Hosted by Chris Hardwick, Talking Bad will analyze and examine every detail of Breaking Bad’s final eight episodes.", "\nTalking Bad feat... Show More\n\nTalking Bad is a weekly, half-hour live after-show and companion piece for AMC's Emmy Award-winning series, Breaking Bad. ", "Hosted by Chris Hardwick, Talking Bad will analyze and examine every detail of Breaking Bad’s final eight episodes.", "\nTalking Bad features Hardwick spending time with fans, actors, producers and television enthusiasts, recapping the most recent Breaking Bad episode, and taking questions and comments from viewers. ", "Fans may continue to engage with the after-show following the on-air conclusion, online, at amc.com for more videos, weekly polls and photo galleries of the guests featured on the series.", "\nShow Less" ]

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[ "Pages\n\nSaturday, February 19, 2011\n\nhaving fun, wish they were here\n\nYou don't know what an achievement this is, updating my blog from my parents house. ", "Guys...they don't have wireless internet here! ", "It's, like, dial-up modem, with the beeps and boops! ", "Not quite, but still kinda bad. ", "They use AOL to get their e-mail! ", "Like in the 1990s! ", "All this I could have worked around, except that my laptop is a MacBook Air, which does not even have an Ethernet jack, as I guess that would have been like putting pockets on a cocktail dress. ", "Also, because it is the year 2011. ", "There used to be people in surrounding apartments from whom we used to steal internet, but they either moved away or realized that they needed to password protect their networks, so...yeah. ", "Luckily, I am borrowing some weak-ish coverage from some nice guy named WLAN, so I'm going to do this quick while I'm still getting a signal.", "\n\n(Yes, I know WLAN is not a guy. ", "GOD, guys, it was a JOKE. ", "Nerds.)", "\n\nSo we got into New York yesterday afternoon. ", "On the way in from Laguardia, we stopped by my grandmother's house in Flushing (Flushing: Official Home of the Chinese Grandmother!) ", "and then I had to hustle to my parents' house for a quick shower and change of clothes to say hi to some people at my publisher.", "\n\nLook, I know that to some degree it must be a job, just like any other job, but can I just tell you that it looks incredibly fun to work in book publishing? ", "Because there are books everywhere! ", "Like, books falling out of the sky! ", "And you can just pick up and read any of them! ", "Also, they had a lot of high-end office supplies; obviously this is the world of the gigantic professional printer in the kingdom of the extra-large padded mailing envelope, and I don't know why I love that so much but I DO. ", "So anyway, I stopped by, we chatted a bit, and then I walked through Midtown to the West Side to meet up with everyone else for dinner.", "\n\nI won't say too much about the meal because I basically live-Tweeted the thing last night, and probably some of you are going to kill me over that, because some people get very persnickety about their feeds. ", "Sincere apologies for those who don't like me clogging up their tweet stream, but my reasons for live-tweeting were two-fold. ", "First is that one of my partners at work (hi Kim!) ", "told me to take pictures of the meal, SO I DID. ", "Secondly, I had some scheme that I was going to Twitter Guilt executive chef Eric Ripert to come out into the dining room to say hi to us. (", "Unfortunately, he did not, because he is important. ", "Also, it's possible he wasn't there last night, because from his Twitter feed, it sounded like he went skiing. ", "Either way.)", "\n\nToday dawned sunny but cold, so we scrapped our plans for riding bikes in the park and just went straight off to the Natural History Museum, where we looked at some dead stuff. ", "Cal was suitably impressed. ", "I always like to seek out the older, unrenovated wings because they look exactly the same as they did when I was a kid and therefore exercise upon me some kind of memory vortex, but mostly we just looked at the whale and the dinosaurs and they were pretty neat.", "\n\nCal was still pretty creeped out by the whale and the squid, by the way. ", "He didn't want to go near it at first, though he warmed to it eventually. ", "I tried to get a picture of that exhibit, but it really was still pretty dark and the picture didn't turn out. ", "So instead, just picture some kind of deep-sea horror tableau that will haunt your dreams. ", "There you go.", "\n\nIf I were making this trip with Joe, without the kids, undoubtedly we'd be spending all our time downtown, eating every two hours, window-shopping and people-watching until we passed out from sheer exhaustion. ", "Well, except for maybe one day, which we'd spend all the way up up uptown in Washington Heights, where we could revisit old haunts and eat at Malecon, home of the garlic dipping sauce and on-call 2:00am regret. ", "Being here with a kid sort of pulls the center of gravity towards Central Park, which is fine, but maybe we'll find some time over the next day or two to go below 14th Street. (", "I know, I know, there's tons of kids stuff down there too, but it's different when you live here versus when you're only in town for two or three days. ", "We have to cluster our activities a little more is all.)", "\n\nWe're having fun, but we really miss Mack and Joe. ", "That's the problem with everyone in our lives being so spread out--wherever you are, you always end up missing someone. ", "When we get home, I'm going to grab Mack and just squeeze the snot out of him." ]

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[ "Zygmunt Kiszkurno\n\nZygmunt Kiszkurno (6 January 192124 August 2012) was a Polish sport shooter who competed in the men's trap event at the 1956 Summer Olympics in Melbourne, where he finished 15th in a field of 32 competitors. ", "He was born in Brudzew, Turek County and completed high school in 1939 in Warsaw. ", "He trained in Łódź to be a dentist and received a medical degree from the University of Warsaw in 1969. ", "During this time he also served in the Polish Land Forces, eventually achieving the rank of Pułkownik.", "\n\nKiszkurno continued shooting competitively following his Olympic appearance and was the Polish national champion in trap shooting in 1957 and 1969. ", "Additionally, he won a silver medal at the 1964 European Shooting Championships. ", "His father Józef competed in the same event in the previous year's Olympic Games and placed 9th.", "\n\nReferences\n\nCategory:1921 births\nCategory:2012 deaths\nCategory:Polish male sport shooters\nCategory:Shooters at the 1956 Summer Olympics\nCategory:Olympic shooters of Poland\nCategory:People from Turek County\nCategory:Sportspeople from Greater Poland Voivodeship" ]

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[ "Spread the love\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nWhen you run a Charles Bukowski fan site you end up finding out all kinds of things about the old guy you never knew.", "\n\nLike, for instance, that Bukowski used to go hang out in the recently reopened Japanese Garden at The Huntington Library, in San Marino.", "\n\nThe Huntington, fans may recall, recently exhibited Bukowski manuscripts, and various ephemera (such as his typewriter and the radio on which he listened to classical music while he worked), in an exhibition called Charles Bukowski: Poet on the Edge.", "\n\nThis comes from an article in the Glendale News-Press:\n\nThe tranquil garden was a favorite stop for tough-guy poet Charles Bukowski after a day at Santa Anita. ", "The ability to soothe that savage beast is proof positive of the site’s calming and restorative powers.", "\n\nHere we see the well worn portrayal of Bukowski as tough old bastard, raging through life, which, while it holds some truth, is only a fraction of the true story of his personality.", "\n\nBukowski could be quite soft spoken and tranquil, as witnessed in numerous interviews. ", "Still, if you asked most people to close their eyes and picture Charles Bukowski, they wouldn’t place him in the setting of a Japanese Garden.", "\n\nCharles Bukowski & Buddhism\n\nThis revelation is made less surprising, however, by recalling that he took a real interest in Buddhism later in life. ", "His funeral was even presided over by Buddhist Monks.", "\n\nThe influence was strong enough to show up in his work, as well, such as in his poem “As Buddha Smiles”:\n\nas Buddha smiles the ladies in blue and green and red,\n\nthe ladies in all their colors,\n\ncircle about. ", "there is nothing quite like\n\nthe arrogance of a\n\nbeginning writer\n\nunless it is the conceit\n\nof\n\na successful\n\none. ", "anger\n\nis but a mask\n\nthat covers\n\nnothing. ", "looking at her\n\nsitting at the bar she’s the best thing\n\nin sight: silent, blazing,\n\nnowhere. ", "the same sun\n\nmixed and grinding\n\ndancing toward what’s left of your\n\nmind. ", "I keep pondering the\n\nimponderable.", "\n\nAdam and Eve without belly buttons?", "\n\nand if so, why? ", "at times\n\nsmall children\n\nwake up screaming\n\nas something\n\nleaps toward them\n\nthat they have never\n\nseen\n\nbefore. ", "if we can laugh, fine.", "\n\nif we’ve got to cry, we’ve\n\ngot to cry. ", "summer followed summer\n\nflea fucked flea\n\nas my parents\n\nprepared themselves for an\n\nearly grave. ", "the 3 a.m.\n\nradio sings\n\nas a\n\nsquadron\n\nof diminutive\n\nflying bugs now\n\nrush in to\n\nkeep me\n\ncompany. ", "as the swans circle\n\nthe truly damned are the\n\ntruly talented\n\nas the swans circle\n\nthe truly talented are the\n\ntruly damned\n\nas the swans circle. ", "it’s easier\n\nto write a symphony\n\nthan it is to love\n\nand respect\n\nyour neighbor. ", "head down\n\nsitting by the\n\nfireplace\n\nstaring at my\n\nshoes\n\nas the wife tells me\n\nhow well I’m\n\ndoing. ", "anybody can be a genius\n\nat 25. ", "at 50, it takes\n\nsome\n\ndoing. ", "I think of Li Po\n\nso\n\nmany centuries ago\n\ndrinking his wine\n\nwriting his poems\n\nthen\n\nsetting them\n\non fire\n\nand sailing them\n\ndown the river\n\nas the emperor\n\nwept. ", "I light another cigarette\n\nand wait patiently for lady\n\nluck to\n\narrive. ", "we’ve just got to get rid of\n\nall those poor souls\n\nwho eat pizza and go to\n\nbaseball games. ", "I shot the cat\n\nstole a webster’s dictionary\n\nand ate a green apple. ", "the same sun\n\nmixed and grinding\n\ndancing toward what’s left of your\n\nmind. ", "O my God\n\nall that blue sky\n\nsenseless I take my prickly heart and\n\nthrow it away\n\nas far into the dark as possible and\n\nlaugh. ", "I am\n\nlike a bug\n\na dog\n\na flower. ", "the knife cuts into the\n\nsun.", "\n\nthe plate\n\nbreaks.", "\n\nthe cat yawns. ", "the once young\n\nhero has grown\n\nold\n\nas Buddha\n\nsmiles.", "\n\nWhether Bukowski felt any spiritual desire to spend time in The Huntington Library’s Japanese Garden, or if he simply liked the calm and quiet after experiencing the loud, swirling mass of humanity of the track, is anyone’s guess.", "\n\nBut if nothing else, true devotees now have another stop to make on their Bukowski pilgrimages. ", "Now that it is once again open to the public after a year long renovation project, fans can go check it out and picture the old man strolling along the pebble path, celebrating a victorious day, or soothing the wounds of failure.", "\n\n\n\n\n\n\n\n\n\n\n\n\n\nComments\n\ncomments" ]

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