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[ "Steelers fans need to clean up their language on Facebook.", "\n\nA new study by Proofpoint Nexgate researchers reveals that the Pittsburgh faithful use profanity more than any other fanbase in the NFL.", "\n\nFrom the study:\n\nArticle continues below ...\n\nOne can only wonder how much of the Steelers’ 6.1 percent is made up by Snoop Dogg.", "\n\nThe rest of the top five in \"profane content percentage\": Patriots, 1.13 percent; Lions, 1 percent; Bengals, 0.79 percent.", "\n\nOn the opposite end of the spectrum, Panthers fans keep things clean when it comes to Facebook.", "\n\nThe study also broke down the most active fan bases when it comes to Facebook posts by compiling the number of comments made over a two-week span:\n\n(Hat Tip: @DarrenRovell)" ]
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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 * http://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 */\npackage org.apache.struts2.util;\n\n/**\n * A bean that can be used to time execution of pages\n *\n * FIXME: remove?", "\n */\npublic class Timer {\n\n // Attributes ----------------------------------------------------\n long current = System.currentTimeMillis();\n long start = current;\n\n\n // Public --------------------------------------------------------\n public long getTime() {\n // Return how long time has passed since last check point\n long now = System.currentTimeMillis();\n long time = now - current;\n\n // Reset so that next time we get from this point\n current = now;\n\n return time;\n }\n\n public long getTotal() {\n // Reset start so that next time we get from this point\n return System.currentTimeMillis() - start;\n }\n}\n" ]
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[ "\n492 U.S. 1 (1989)\nMURRAY, DIRECTOR, VIRGINIA DEPARTMENT OF CORRECTIONS, ET AL.", "\nv.\nGIARRATANO ET AL.", "\nNo. ", "88-411.", "\nSupreme Court of United States.", "\nArgued March 22, 1989\nDecided June 23, 1989[*]\nCERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE FOURTH CIRCUIT\n*3 Robert Q. Harris, Assistant Attorney General of Virginia, argued the cause for petitioners. ", "With him on the briefs were Mary Sue Terry, Attorney General, H. Lane Kneedler, Chief Deputy Attorney General, Stephen D. Rosenthal, Deputy Attorney General, and Francis S. Ferguson, Assistant Attorney General.", "\nGerald T. Zerkin argued the cause for respondents. ", "With him on the brief were Jonathan D. Sasser and Martha A. Geer.[*]", "\nRobert D. Raven, Ronald J. Tabak, George H. Kendall, and Clifford D. Stromberg filed a brief for the American Bar Association as amicus curiae.", "\nCHIEF JUSTICE REHNQUIST announced the judgment of the Court and delivered an opinion, in which JUSTICE WHITE, JUSTICE O'CONNOR, and JUSTICE SCALIA join.", "\nVirginia death row inmates brought a civil rights suit against various officials of the Commonwealth of Virginia. ", "The prisoners claimed, based on several theories, that the Constitution required that they be provided with counsel at the Commonwealth's expense for the purpose of pursuing collateral proceedings related to their convictions and sentences. ", "The courts below ruled that appointment of counsel upon request was necessary for the prisoners to enjoy their *4 constitutional right to access to the courts in pursuit of state habeas corpus relief. ", "We think this holding is inconsistent with our decision two Terms ago in Pennsylvania v. Finley, 481 U. S. 551 (1987), and rests on a misreading of our decision in Bounds v. Smith, 430 U. S. 817 (1977).", "\nJoseph M. Giarratano is a Virginia prisoner under a sentence of death. ", "He initiated this action under 42 U. S. C. § 1983, by pro se complaint in Federal District Court, against various state officials including Edward W. Murray who is the Director of the Virginia Department of Corrections. ", "Some months later, the District Court certified a class comprising all current and future Virginia inmates awaiting execution who do not have and cannot afford counsel to pursue postconviction proceedings.[1] The inmates asserted a number of constitutional theories for an entitlement to appointed counsel and the case was tried to the court.", "\nAfter the evidence, post-trial briefs, and other memoranda, the District Court expressed \"serious doubts as to the viability of many of th[e] theories.\" ", "668 F. Supp. ", "511, 512 (ED Va. 1986). ", "It was, however, \"satisfied that the United States Supreme Court's decision in Bounds dictates that the plaintiffs here be granted some form of relief.\" ", "Ibid. ", "The District Court noted three special \"considerations\" relating to death row inmates that it believed required that these inmates receive greater assistance than Bounds had outlined. ", "It found that death row inmates had a limited amount of time to prepare their petitions, that their cases were unusually complex, and that the shadow of impending execution would interfere with their ability to do legal work. ", "These \"considerations\" *5 led the court to believe that the \"plaintiffs are incapable of effectively using lawbooks to raise their claims.\" ", "As a result, it found that Virginia's policy of either allowing death row inmates time in the prison law library or permitting them to have lawbooks sent to their cells did \"little to satisfy Virginia's obligation.", "\"[2] 668 F. Supp., ", "at 513. \"", "Virginia must fulfill its duty by providing these inmates trained legal assistance.\" ", "Ibid.", "\nThe District Court then evaluated the avenues by which inmates convicted of capital crimes could obtain the aid of counsel in Virginia. ", "It found inadequate the availability of \"unit attorneys\" appointed by Virginia to the various penal institutions to assist inmates in incarcertion-related litigation. ", "Id., at 514. ", "Further, it found that \"[e]ven if Virginia appointed additional institutional attorneys to service death row inmates, its duty under Bounds would not be fulfilled\" because, acting \"only as legal advisors,\" \"[t]he scope of assistance these attorneys provide is simply too limited.\" ", "Ibid. ", "Along the same lines, the District Court concluded that Virginia's provisions for appointment of counsel after a petition is filed did not cure the problem.[3] This was primarily because \"the *6 timing of the appointment is a fatal defect\" as the inmate \"would not receive the attorney's assistance in the critical stages of developing his claims.\" ", "Id., at 515.", "\nEven together, Virginia's efforts did not afford prisoners a meaningful right of access to the courts, in the opinion of the District Court, because they did not guarantee them \"the continuous assistance of counsel.\" ", "Ibid. ", "With what the District Court feared was the imminent depletion of the pool of volunteer attorneys willing to help Virginia death row inmates attack their convictions and sentences, the court felt that \"[t]he stakes are simply too high for this Court not to grant, at least in part, some relief.\" ", "It therefore ordered Virginia to develop a program for the appointment of counsel, upon request, to indigent death row inmates wishing to pursue habeas corpus in state court. ", "Id., at 517. ", "It decided, however, that the decision in Ross v. Moffitt, 417 U. S. 600 (1974), indicated that Virginia had no similar constitutional obligation to appoint counsel for the pursuit of habeas corpus in federal court. ", "668 F. Supp., ", "at 516-517.", "\nOn appeal to the United States Court of Appeals for the Fourth Circuit, a divided panel reversed the District Court's judgment that the Commonwealth was constitutionally required to provide personal attorneys to represent death row inmates in state collateral proceedings. ", "836 F. 2d 1421 (1988). ", "But that court, en banc, subsequently reheard the case and affirmed the District Court. ", "847 F. 2d 1118 (1988). ", "The en banc court viewed as findings of fact the special \"considerations\" relating to death row inmates which had led the District Court to conclude that Virginia was not in compliance with the constitutional rights of access. ", "It accepted these findings as not clearly erroneous and so affirmed the the District Court's remedial order. ", "The en banc court did not believe the case to be controlled by Pennsylvania v. *7 Finley, 481 U. S. 551 (1987), which held that the Constitution did not require States to provide counsel in postconviction proceedings. \"", "Finley was not a meaningful access case, nor did it address the rule enunciated in Bounds v. Smith.\" ", "847 F. 2d, at 1122. \"", "Most significantly,\" thought the Fourth Circuit, \"Finley did not involve the death penalty.\" ", "Ibid. ", "Four judges dissented. ", "We granted certiorari, 488 U. S. 923 (1988), and now reverse.", "\nIn Finley we ruled that neither the Due Process Clause of the Fourteenth Amendment nor the equal protection guarantee of \"meaningful access\" required the State to appoint counsel for indigent prisoners seeking state postconviction relief. ", "The Sixth and Fourteenth Amendments to the Constitution assure the right of an indigent defendant to counsel at the trial stage of a criminal proceeding, Gideon v. Wainwright, 372 U. S. 335 (1963), and an indigent defendant is similarly entitled as a matter of right to counsel for an initial appeal from the judgment and sentence of the trial court. ", "Douglas v. California, 372 U. S. 353 (1963); Griffin v. Illinois, 351 U. S. 12 (1956). ", "But we held in Ross v. Moffitt, supra, at 610, that the right to counsel at these earlier stages of a criminal procedure did not carry over to a discretionary appeal provided by North Carolina law from the intermediate appellate court to the Supreme Court of North Carolina. ", "We contrasted the trial stage of a criminal proceeding, where the State by presenting witnesses and arguing to a jury attempts to strip from the defendant the presumption of innocence and convict him of a crime, with the appellate stage of such a proceeding, where the defendant needs an attorney \"not as a shield to protect him against being `haled into court' by the State and stripped of his presumption of innocence, but rather as a sword to upset the prior determination of guilt.\" ", "417 U. S., at 610-611.", "\nWe held in Finley that the logic of Ross v. Moffitt required the conclusion that there was no federal constitutional right *8 to counsel for indigent prisoners seeking state postconviction relief:\n\"Postconviction relief is even further removed from the criminal trial than is discretionary direct review. ", "It is not part of the criminal proceeding itself, and it is in fact considered to be civil in nature. ", "See Fay v. Noia, 372 U. S. 391, 423-424 (1963). . . . ", "States have no obligation to provide this avenue of relief, cf. ", "United States v. MacCollom, 426 U. S. 317, 323 (1976) (plurality opinion), and when they do, the fundamental fairness mandated by the Due Process Clause does not require that the state supply a lawyer as well.\" ", "481 U. S., at 556-557.", "\nRespondents, like the courts below, believe that Finley does not dispose of respondents' constitutional claim to appointed counsel in habeas proceedings because Finley did not involve the death penalty.[4] They argue that, under the Eighth Amendment, \"evolving standards of decency\" do not permit a death sentence to be carried out while a prisoner is unrepresented. ", "Brief for Respondents 47. ", "In the same vein, they contend that due process requires appointed counsel in postconviction proceedings, because of the nature of the punishment and the need for accuracy. ", "Id., at 48-49.", "\nWe have recognized on more than one occasion that the Constitution places special constraints on the procedures used to convict an accused of a capital offense and sentence him to death. ", "See, e. g., Beck v. Alabama, 447 U. S. 625 (1980) (trial judge must give jury the option to convict of a lesser offense); Lockett v. Ohio, 438 U. S. 586, 604 (1978) (jury must be allowed to consider all of a capital defendant's mitigating character evidence); Eddings v. Oklahoma, 455 U. S. 104 (1982) (same). ", "The finality of the death penalty requires *9 \"a greater degree of reliability\" when it is imposed. ", "Lockett, supra, at 604.", "\nThese holdings, however, have dealt with the trial stage of capital offense adjudication, where the court and jury hear testimony, receive evidence, and decide the questions of guilt and punishment. ", "In Pulley v. Harris, 465 U. S. 37 (1984), we declined to hold that the Eighth Amendment required appellate courts to perform proportionality review of death sentences. ", "And in Satterwhite v. Texas, 486 U. S. 249, 256 (1988), we applied the traditional appellate standard of harmless-error review set out in Chapman v. California, 386 U. S. 18 (1967), when reviewing a claim of constitutional error in a capital case.", "\nWe have similarly refused to hold that the fact that a death sentence has been imposed requires a different standard of review on federal habeas corpus. ", "In Smith v. Murray, 477 U. S. 527, 538 (1986), a case involving federal habeas corpus, this Court unequivocally rejected \"the suggestion that the principles [governing procedural fault] of Wainwright v. Sykes[, 433 U. S. 72 (1977),] apply differently depending on the nature of the penalty a State imposes for the violation of its criminal laws\" and similarly discarded the idea that \"there is anything `fundamentally unfair' about enforcing procedural default rules . . . .\" ", "Id., at 538-539. ", "And, in Barefoot v. Estelle, 463 U. S. 880, 887 (1983), we observed that \"direct appeal is the primary avenue for review of a conviction or sentence, and death penalty cases are no exception.\"", "\nFinally, in Ford v. Wainwright, 477 U. S. 399 (1986), we held that the Eighth Amendment prohibited the State from executing a validly convicted and sentenced prisoner who was insane at the time of his scheduled execution. ", "Five Justices of this Court, however, rejected the proposition that \"the ascertainment of a prisoner's sanity as a predicate to lawful execution calls for no less stringent standards than those demanded in any other aspect of a capital proceeding.\" ", "Id., at 411-412. ", "Justice Powell recognized that the prisoner's *10 sanity at the time of execution was \"not comparable to the antecedent question of whether the petitioner should be executed at all.\" ", "Id., at 425. \"", "It follows that this Court's decisions imposing heightened procedural requirements on capital trials and sentencing proceedings do not apply in this context.\" ", "Ibid. (", "citations omitted); id., at 429 (O'CONNOR, J., joined by WHITE, J., dissenting in part and concurring in result in part) (due process requirements minimal); id., at 434 (REHNQUIST, J., joined by Burger, C. J., dissenting) (wholly executive procedures sufficient).", "\nWe think that these cases require the conclusion that the rule of Pennsylvania v. Finley should apply no differently in capital cases than in noncapital cases. ", "State collateral proceedings are not constitutionally required as an adjunct to the state criminal proceedings and serve a different and more limited purpose than either the trial or appeal.[5] The additional safeguards imposed by the Eighth Amendment at the trial stage of a capital case are, we think, sufficient to assure the reliability of the process by which the death penalty is imposed. ", "We therefore decline to read either the Eighth Amendment or the Due Process Clause to require yet another distinction between the rights of capital case defendants and those in noncapital cases.", "\n*11 The dissent opines that the rule that it would constitutionally mandate \"would result in a net benefit to Virginia.\" ", "Post, at 30. ", "But this \"mother knows best\" approach should play no part in traditional constitutional adjudication. ", "Even as a matter of policy, the correctness of the dissent's view is by no means self-evident. ", "If, as we said in Barefoot v. Estelle, supra, direct appeal is the primary avenue for review of capital cases as well as other sentences, Virginia may quite sensibly decide to concentrate the resources it devotes to providing attorneys for capital defendants at the trial and appellate stages of a capital proceeding. ", "Capable lawyering there would mean fewer colorable claims of ineffective assistance of counsel to be litigated on collateral attack.", "\nThe Court of Appeals, as an additional basis for its holding, relied on what it perceived as a tension between the rule in Finley and the implication of our decision in Bounds v. Smith, 430 U. S. 817 (1977); we find no such tension. ", "Whether the right of access at issue in Bounds is primarily one of due process or equal protection,[6] in either case it rests on a constitutional theory considered in Finley. ", "The Court held in Bounds that a prisoner's \"right of access\" to the courts required a State to furnish access to adequate law libraries in order that the prisoners might prepare petitions for judicial relief. ", "Bounds, supra, at 828. ", "But it would be a strange jurisprudence that permitted the extension of that holding to partially overrule a subsequently decided case such as Finley which held that prisoners seeking judicial relief from their sentence in state proceedings were not entitled to counsel.", "\nIt would be an even stranger jurisprudence to allow, as the dissent would, the \"right of access\" involved in Bounds v. Smith, supra, to partially overrule Pennsylvania v. Finley, *12 based on \"factual\" findings of a particular district court regarding matters such as the perceived difficulty of capital sentencing law and the general psychology of death row inmates. ", "Treating such matters as \"factual findings,\" presumably subject only to review under the \"clearly-erroneous\" standard, would permit a different constitutional rule to apply in a different State if the district judge hearing that claim reached different conclusions. ", "Our cases involving the right to counsel have never taken this tack; they have been categorical holdings as to what the Constitution requires with respect to a particular stage of a criminal proceeding in general. ", "See Powell v. Alabama, 287 U. S. 45 (1932); Griffin v. Illinois, 351 U. S. 12 (1956); Gideon v. Wainwright, 372 U. S. 335 (1963); Douglas v. California, 372 U. S. 353 (1963); Ross v. Moffitt, 417 U. S. 600 (1974); Pennsylvania v. Finley, 481 U. S. 551 (1987). ", "Indeed, as the dissent itself points out, post, at 17, and n. 2, it was the Court's dissatisfaction with the case-by-case approach of Betts v. Brady, 316 U. S. 455 (1942), that led to the adoption of the categorical rule requiring appointed counsel for indigent felony defendants in Gideon.", "\nThere is no inconsistency whatever between the holding of Bounds and the holding in Finley; the holding of neither case squarely decides the question presented in this case. ", "For the reasons previously stated in this opinion, we now hold that Finley applies to those inmates under sentence of death as well as to other inmates, and that holding necessarily imposes limits on Bounds.[7]\n*13 Petitioners and respondents disagree as to the practices currently in effect in Virginia state prisons with respect to death row prisoners. ", "Respondents contend that these prisoners are denied adequate and timely access to a law library during the final weeks before the date set for their execution. ", "If respondents are correct, the District Court on remand may remedy this situation without any need to enlarge the holding of Bounds.", "\nThe judgment of the Court of Appeals is Reversed.", "\nJUSTICE O'CONNOR concurring.", "\nI join in THE CHIEF JUSTICE's opinion. ", "As his opinion demonstrates, there is nothing in the Constitution or the precedents of this Court that requires that a State provide counsel in postconviction proceedings. ", "A postconviction proceeding is not part of the criminal process itself, but is instead a civil action designed to overturn a presumptively valid criminal judgment. ", "Nothing in the Constitution requires the States to provide such proceedings, see Pennsylvania v. Finley, 481 U. S. 551 (1987), nor does it seem to me that the Constitution requires the States to follow any particular federal model in those proceedings. ", "I also join in JUSTICE KENNEDY's opinion concurring in the judgment, since I do not view it as inconsistent with the principles expressed above. ", "As JUSTICE KENNEDY observes, our decision in Bounds v. Smith, 430 U. S. 817 (1977), allows the States considerable discretion in assuring that those imprisoned in their jails obtain meaningful access to the judicial process. ", "Beyond the requirements of Bounds, the matter is one of legislative choice based on difficult policy considerations and the allocation of scarce legal resources. ", "Our decision today rightly leaves these issues to resolution by Congress and the state legislatures.", "\n*14 JUSTICE KENNEDY, with whom JUSTICE O'CONNOR joins, concurring in the judgment.", "\nIt cannot be denied that collateral relief proceedings are a central part of the review process for prisoners sentenced to death. ", "As JUSTICE STEVENS observes, a substantial proportion of these prisoners succeed in having their death sentences vacated in habeas corpus proceedings. ", "Post, at 23-24, and n. 13. ", "The complexity of our jurisprudence in this area, moreover, makes it unlikely that capital defendants will be able to file successful petitions for collateral relief without the assistance of persons learned in the law.", "\nThe requirement of meaningful access can be satisfied in various ways, however. ", "This was made explicit in our decision in Bounds v. Smith, 430 U. S. 817 (1977). ", "The intricacies and range of options are of sufficient complexity that state legislatures and prison administrators must be given \"wide discretion\" to select appropriate solutions. ", "Id., at 833. ", "Indeed, judicial imposition of a categorical remedy such as that adopted by the court below might pretermit other responsible solutions being considered in Congress and state legislatures. ", "Assessments of the difficulties presented by collateral litigation in capital cases are now being conducted by committees of the American Bar Association and the Judicial Conference of the United States, and Congress has stated its intention to give the matter serious consideration. ", "See 134 Cong. ", "Rec. ", "33237 (1988) (providing for expedited consideration of proposals of the Judicial Conference committee).", "\nUnlike Congress, this Court lacks the capacity to undertake the searching and comprehensive review called for in this area, for we can decide only the case before us. ", "While Virginia has not adopted procedures for securing representation that are as far reaching and effective as those available in other States, no prisoner on death row in Virginia has been unable to obtain counsel to represent him in postconviction proceedings, and Virginia's prison system is staffed with institutional *15 lawyers to assist in preparing petitions for postconviction relief. ", "I am not prepared to say that this scheme violates the Constitution.", "\nOn the facts and record of this case, I concur in the judgment of the Court.", "\nJUSTICE STEVENS, with whom JUSTICE BRENNAN, JUSTICE MARSHALL, and JUSTICE BLACKMUN join, dissenting.", "\nTwo Terms ago this Court reaffirmed that the Fourteenth Amendment to the Federal Constitution obligates a State \" `to assure the indigent defendant an adequate opportunity to present his claims fairly in the context of the State's appellate process.' \" ", "Pennsylvania v. Finley, 481 U. S. 551, 556 (1987) (quoting Ross v. Moffitt, 417 U. S. 600, 616 (1974)). ", "The narrow question presented is whether that obligation includes appointment of counsel for indigent death row inmates who wish to pursue state postconviction relief. ", "Viewing the facts in light of our precedents, we should answer that question in the affirmative.", "\n\nI\nThe parties before us, like the Court of Appeals en banc and the District Court below, have accorded controlling importance to our decision in Bounds v. Smith, 430 U. S. 817 (1977).[1] In that case, inmates had alleged that North Carolina *16 violated the Fourteenth Amendment by failing to provide research facilities to help them prepare habeas corpus petitions and federal civil rights complaints. ", "Stressing \"meaningful\" access to the courts as a \"touchstone,\" id., at 823, we held:\n\"[T]he fundamental constitutional right of access to the courts requires prison authorities to assist inmates in the preparation and filing of meaningful legal papers by providing prisoners with adequate law libraries or adequate assistance from persons trained in the law.\" ", "Id., at 828.", "\nFar from creating a discrete constitutional right, Bounds constitutes one part of a jurisprudence that encompasses \"right-to-counsel\" as well as \"access-to-courts\" cases. ", "Although each case is shaped by its facts, all share a concern, based upon the Fourteenth Amendment, that accused and convicted persons be permitted to seek legal remedies without arbitrary governmental interference.", "\nAt the fountainhead of this body of law is Powell v. Alabama, 287 U. S. 45, 69 (1932), which recognized that \"[e]ven the intelligent and educated layman . . . ", "requires the guiding hand of counsel at every step in the proceedings against him.\" ", "The Court reversed the convictions and death sentences of seven black men, charged with the rape of two white women, because the state court failed to designate counsel until the morning of trial. ", "Reasoning that the \"notice and hearing\" guaranteed by the Due Process Clause \"would be, in many cases, of little avail if it did not comprehend the right to be heard by counsel,\" id., at 68-69, the Court held:\n\"[I]n a capital case, where the defendant is unable to employ counsel, and is incapable adequately of making his own defense because of ignorance, feeble mindedness, illiteracy, or the like, it is the duty of the court, whether *17 requested or not, to assign counsel for him as a necessary requisite of due process of law; and that duty is not discharged by an assignment at such a time or under such circumstances as to preclude the giving of effective aid in the preparation and trial of the case.\" ", "Id., at 71.", "\nParticular circumstances thus defined the degree to which the Fourteenth Amendment protected petitioners in Powell against arbitrary criminal prosecution or punishment. ", "Similarly, in Griffin v. Illinois, 351 U. S. 12, 18-19 (1956), the Court focused on \"[s]tatistics show[ing] that a substantial proportion of criminal convictions are reversed by state appellate courts\" in concluding that once a State allows appeals of convictions, it cannot administer its appellate process in a discriminatory fashion. ", "Finding no rational basis for requiring appellants to pay for trial transcripts, \"effectively den[ying] the poor an adequate appellate review accorded to all who have money enough to pay the costs in advance,\" the Court held that the Fourteenth Amendment required States to furnish transcripts to indigents. ", "Id., at 18. ", "Accord, Burns v. Ohio, 360 U. S. 252 (1959) ($20 fee to file appeal). ", "The principles articulated in Griffin soon were applied to invalidate similar restraints on state postconviction review. ", "Lane v. Brown, 372 U. S. 477 (1963) (transcript); Smith v. Bennett, 365 U. S. 708 (1961) (filing fee).", "\nOn the same day in 1963, the Court held that the Fourteenth Amendment guaranteed indigent defendants assistance of counsel both at trial, Gideon v. Wainwright, 372 U. S. 335, and on their first appeal as of right, Douglas v. California, 372 U. S. 353. ", "Applying the Sixth Amendment's express right of counsel to the States, the Court in Gideon departed from the special circumstances analysis in favor of a categorical approach.[2] But because of the absence *18 of a constitutional right to appeal, see McKane v. Durston, 153 U. S. 684 (1894), the Court decided Douglas by assessing the facts in light of the Fourteenth Amendment.[3] The Court's reasons for invalidating California's appellate procedure — by which the appellate court undertook an ex parte examination of \"the barren record\" to determine whether an appeal merited appointment of counsel, 372 U. S., at 356 — echoed its earlier statements in Griffin:\n\"When an indigent is forced to run this gantlet of a preliminary showing of merit, the right to appeal does not comport with fair procedure. . . . [", "T]he discrimination is not between `possibly good and obviously bad cases,' but between cases where the rich man can require the court to listen to argument of counsel before deciding on the merits, but a poor man cannot. . . . ", "The indigent, where the record is unclear or the errors are hidden, has only the right to a meaningless ritual, while the rich man has a meaningful appeal.\" ", "Douglas, 372 U. S., at 357-358.", "\nIn two subsequent opinions the Court rejected inmates' attempts to secure legal assistance. ", "In Ross v. Moffitt, 417 U. S. 600 (1974), the Court held there was no right to appointment of counsel for discretionary state appeals or certiorari petitions to this Court. ", "It later announced for the first *19 time that a State has no obligation to provide defendants with any collateral review of their convictions, and that if it does, \"the fundamental fairness mandated by the Due Process Clause does not require that the State supply a lawyer as well.\" ", "Pennsylvania v. Finley, 481 U. S., at 557. ", "Although one might distinguish these opinions as having a different legal basis than the present case,[4] it is preferable to consider them, like Powell, Griffin, Douglas, and Bounds, as applications of the Fourteenth Amendment's guarantees to particular situations. ", "Indeed the Court reaffirmed in Ross:\n\"The Fourteenth Amendment . . . ", "does require that the state appellate system be `free of unreasoned distinctions,' Rinaldi v. Yeager, 384 U. S. 305, 310 (1966), and that indigents have an adequate opportunity to present their claims fairly within the adversary system. ", "Griffin v. Illinois, supra; Draper v. Washington, 372 U. S. 487 (1963). ", "The State cannot adopt procedures which leave an indigent defendant `entirely cut off from any appeal at all,' by virtue of his indigency, Lane v. Brown, 372 U. S., at 481, or extend to such indigents merely a `meaningless ritual' while others in better economic circumstances have a `meaningful appeal.' ", "Douglas v. California, supra, at 358. ", "The question is not one of absolutes, but one of degrees.\" ", "417 U. S., at 612.", "\n\nII\nThese precedents demonstrate that the appropriate question in this case is not whether there is an absolute \"right to counsel\" in collateral proceedings, but whether due process requires that these respondents be appointed counsel in order to pursue legal remedies. ", "Three critical differences between Finley and this case demonstrate that even if it is *20 permissible to leave an ordinary prisoner to his own resources in collateral proceedings, it is fundamentally unfair to require an indigent death row inmate to initiate collateral review without counsel's guiding hand. ", "I shall address each of these differences in turn.", "\nFirst. ", "These respondents, like petitioners in Powell but unlike respondent in Finley, have been condemned to die. ", "Legislatures conferred greater access to counsel on capital defendants than on persons facing lesser punishment even in colonial times.[5] Our First Congress required assignment of up to two attorneys to a capital defendant at the same time it initiated capital punishment;[6] nearly a century passed before Congress provided for appointment of counsel in other contexts. ", "See Mallard v. United States District Court, 490 U. S. 296 (1989) (interpreting Act of July 20, 1892, ch. ", "209, § 1, 27 Stat. ", "252, now codified at 28 U. S. C. § 1915(d)). ", "Similarly, Congress at first limited the federal right of appeal to capital cases. ", "See Evitts v. Lucey, 469 U. S. 387, 409 (1985) (REHNQUIST, J., dissenting). ", "Just last year, it enacted a statute requiring provision of counsel for state and federal prisoners seeking federal postconviction relief — but only if they are under sentence of death.[7]\n*21 This Court also expanded capital defendants' ability to secure counsel and other legal assistance long before bestowing similar privileges on persons accused of less serious crimes.[8] Both before and after Furman v. Georgia, 408 U. S. 238 (1972), established that the Constitution requires channeling of the death-sentencing decision, various Members of this Court have recognized that \"the penalty of death is qualitatively different from a sentence of imprisonment, however long.\" ", "Woodson v. North Carolina, 428 U. S. 280, 305 (1976) (plurality opinion).[9]\n*22 The unique nature of the death penalty not only necessitates additional protections during pretrial, guilt, and sentencing phases,[10] but also enhances the importance of the appellate process. ", "Generally there is no constitutional right to *23 appeal a conviction. ", "See, e. g., McKane v. Durston, 153 U. S. 684 (1894). \"[", "M]eaningful appellate review\" in capital cases, however, \"serves as a check against the random or arbitrary imposition of the death penalty.\" ", "Gregg v. Georgia, 428 U. S. 153, 195, 206 (1976) (opinion of Stewart, Powell, and STEVENS, JJ.). ", "It is therefore an integral component of a State's \"constitutional responsibility to tailor and apply its law in a manner that avoids the arbitrary and capricious infliction of the death penalty.\" ", "Godfrey v. Georgia, 446 U. S. 420, 428 (1980).[11]\nIdeally, \"direct appeal is the primary avenue for review of a conviction or sentence, and death penalty cases are no exception. ", "When the process of direct review . . . ", "comes to an end, a presumption of finality and legality attaches to the conviction and sentence.\" ", "Barefoot v. Estelle, 463 U. S. 880, 887 (1983). ", "There is, however, significant evidence that in capital cases what is ordinarily considered direct review does not sufficiently safeguard against miscarriages of justice to warrant this presumption of finality.[12] Federal habeas *24 courts granted relief in only 0.25% to 7% of noncapital cases in recent years; in striking contrast, the success rate in capital cases ranged from 60% to 70%.[13] Such a high incidence of uncorrected error demonstrates that the meaningful appellate review necessary in a capital case extends beyond the direct appellate process.", "\nSecond. ", "In contrast to the collateral process discussed in Finley, Virginia law contemplates that some claims ordinarily heard on direct review will be relegated to postconviction proceedings. ", "Claims that trial or appellate counsel provided constitutionally ineffective assistance, for instance, usually cannot be raised until this stage. ", "See Frye v. Commonwealth, 231 Va. 370, 345 S. E. 2d 267 (1986). ", "Furthermore, some irregularities, such as prosecutorial misconduct, may not surface until after the direct review is complete. ", "E. g., Amadeo v. Zant, 486 U. S. 214 (1988) (prosecutor deliberately underrepresented black people and women in jury pools); Brady v. Maryland, 373 U. S. 83 (1963). ", "Occasionally, new evidence even may suggest that the defendant is innocent. ", "E. g., Ex parte Adams, No. ", "70,787 (Tex. ", "Cr. ", "App., ", "Mar. 1, 1989) (available on Lexis); McDowell v. Dixon, 858 *25 F. 2d 945 (CA4 1988), cert. ", "denied, 489 U. S. 1033 (1989). ", "Given the irreversibility of capital punishment, such information deserves searching, adversarial scrutiny even if it is discovered after the close of direct review.", "\nThe postconviction procedure in Virginia may present the first opportunity for an attorney detached from past proceedings to examine the defense and to raise claims that were barred on direct review by prior counsel's ineffective assistance. ", "A fresh look may reveal, for example, that a prior conviction used to enhance the defendant's sentence was invalid, e. g., Johnson v. Mississippi, 486 U. S. 578 (1988); or that the defendant's mental illness, lack of a prior record, or abusive childhood should have been introduced as evidence in mitigation at his sentencing hearing, e. g., Curry v. Zant, 258 Ga. 527, 371 S. E. 2d 647 (1988). ", "Defense counsel's failure to object to or assert such claims precludes direct appellate review of them.[14] The postconviction proceeding gives inmates another chance to rectify defaults.[15] In Virginia, *26 therefore, postconviction proceedings are key to meaningful appellate review of capital cases.", "\nState postconviction proceedings also are the cornerstone for all subsequent attempts to obtain collateral relief. ", "Once a Virginia court determines that a claim is procedurally barred, a federal court may not review it unless the defendant can make one of two difficult showings: that there was both cause for the default and resultant prejudice, or that failure to review will cause a fundamental miscarriage of justice. ", "Murray v. Carrier, 477 U. S. 478, 485, 495 (1986); Wainwright v. Sykes, 433 U. S. 72, 87 (1977). ", "If an asserted claim is tested in an evidentiary hearing, the state postconviction court's factual findings may control the scope of a federal court's review of a subsequent petition for a writ of habeas corpus pursuant to 28 U. S. C. § 2254.[16]\nNor may a defendant circumvent the state postconviction process by filing a federal habeas petition. ", "In Rose v. Lundy, 455 U. S. 509 (1982), this Court held that in order to comply with the exhaustion provision of 28 U. S. C. § 2254(c), federal courts should dismiss petitions containing claims that have not been \"fairly presented to the state courts,\" Picard v. Connor, 404 U. S. 270, 275 (1971), for both direct and postconviction review, Castille v. Peoples, 489 U. S. 346 (1989). ", "Given the stringency with which this Court adheres to procedural default rules,[17] it is of great importance to the prisoner *27 that all his substantial claims be presented fully and professionally in his first state collateral proceeding.[18]\nThird. ", "As the District Court's findings reflect, the plight of the death row inmate constrains his ability to wage collateral attacks far more than does the lot of the ordinary inmate considered in Finley.[19] The District Court found that the death row inmate has an extremely limited period to prepare and present his postconviction petition and any necessary applications for stays of execution. ", "668 F. Supp. ", "511, 513 (ED Va. 1986). ", "Unlike the ordinary inmate, who presumably has ample time to use and reuse the prison library and to seek guidance from other prisoners experienced in preparing pro se petitions, cf. ", "Johnson v. Avery, 393 U. S. 483 (1969), a grim deadline imposes a finite limit on the condemned person's capacity for useful research.[20]\nCapital litigation, the District Court observed, is extremely complex. ", "668 F. Supp., ", "at 513. ", "Without regard to the special characteristics of Virginia's statutory procedures,[21]*28 this Court's death penalty jurisprudence unquestionably is difficult even for a trained lawyer to master.[22] A judgment that it is not unfair to require an ordinary inmate to rely on his own resources to prepare a petition for postconviction relief, see Finley, 481 U. S., at 557, does not justify the same conclusion for the death row inmate who must acquire an understanding of this specialized area of the law and prepare an application for stay of execution as well as a petition for collateral relief.[23] This is especially true, the District Court concluded, because the \"evidence gives rise to a fair inference that an inmate preparing himself and his family for impending death is incapable of performing the mental functions necessary to adequately pursue his claims.", "\"[24] 668 F. Supp., ", "at 513.", "\n*29 These three critical factors demonstrate that there is a profound difference between capital postconviction litigation and ordinary postconviction litigation in Virginia. ", "The District Court's findings unequivocally support the conclusion that to obtain an adequate opportunity to present their postconviction claims fairly, death row inmates need greater assistance of counsel than Virginia affords them. ", "Cf. ", "id., at 514-515. ", "Meaningful access, and meaningful judicial review, would be effected in this case only if counsel were appointed, on request, in time to enable examination of the case record, factual investigation, and preparation of a petition containing all meritorious claims, which the same attorney then could litigate to its conclusion.", "\n\nIII\nAlthough in some circumstances governmental interests may justify infringements on Fourteenth Amendment rights, cf. ", "Mathews v. Eldridge, 424 U. S. 319, 334-335 (1976), Virginia has failed to assert any interest that outweighs respondents' right to legal assistance. ", "The State already appoints counsel to death row inmates who succeed in filing postconviction petitions asserting at least one nonfrivolous claim; therefore, the additional cost of providing its 32 death row inmates competent counsel to prepare such petitions should be minimal. ", "See 668 F. Supp., ", "at 512, 515. ", "Furthermore, multiple filings delay the conclusion of capital litigation and exacerbate the already serious burden these cases impose *30 on the State's judicial system and the legal department. ", "It seems obvious that professional preparation of the first postconviction petition, by reducing successive petitions, would result in a net benefit to Virginia.[25]\nOf the 37 States authorizing capital punishment, at least 18 automatically provide their indigent death row inmates counsel to help them initiate state collateral proceedings.[26] Thirteen of the 37 States have created governmentally funded resource *31 centers to assist counsel in litigating capital cases.[27] Virginia is among as few as five States that fall into neither group and have no system for appointing counsel for condemned prisoners before a postconviction petition is filed.[28] In Griffin, the Court proscribed Illinois' discriminatory barrier to appellate review in part because many other States already had rejected such a barrier. ", "351 U. S., at 19; cf. ", "Gideon, 372 U. S., at 345 (noting that 22 States supported right to trial counsel). ", "Similarly, the trend in most States to expand legal assistance for their death row inmates further *32 dilutes Virginia's weak justifications for refusing to do so, and \"lends convincing support to the conclusion\" of the courts below that these respondents have a fundamental right to the relief they seek. ", "See Powell, 287 U. S., at 78.", "\n\nIV\nThe basic question in this case is whether Virginia's procedure for collateral review of capital convictions and sentences assures its indigent death row inmates an adequate opportunity to present their claims fairly. ", "The District Court and Court of Appeals en banc found that it did not, and neither the State nor this Court's majority provides any reasoned basis for disagreeing with their conclusion. ", "Simple fairness requires that this judgment be affirmed.", "\nI respectfully dissent.", "\nNOTES\n[*] Briefs of amici curiae urging affirmance were filed for the American Civil Liberties Union et al. ", "by Elizabeth Alexander, Alvin J. Bronstein, Steven R. Shapiro, and John A. Powell; for the Maryland State Bar Association et al. ", "by John H. Blume; and for the National Legal Aid & Defender Association et al. ", "by Ephraim Margolin and Steven M. Pesner.", "\n[1] In precise terms, the class was defined as\n\n\"all persons, now and in the future, sentenced to death in Virginia, whose sentences have been or are subsequently affirmed by the Virginia Supreme Court and who either (1) cannot afford to retain and do not have attorneys to represent them in connection with their post-conviction proceedings, or (2) could not afford to retain and did not have attorneys to represent them in connection with a particular post-conviction proceeding.\" ", "App. ", "32.", "\n[2] Virginia houses its death row inmates at the Mecklenberg Correctional Center, the Virginia State Penitentiary, and the Powhatan Correctional Center. ", "Each of these three centers maintain law libraries. ", "Inmates at Mecklenberg are allowed two library periods per week; inmates at the other facilities may borrow materials from the prison library for use in their cells.", "\n[3] At the time the District Court decided the case, Virginia courts were authorized to appoint counsel to individual inmates as follows:\n\n\"Any person, who has been a resident of this State for a continuous period of six months, who on account of his poverty is unable to pay fees or costs may be allowed by a court to sue or defend a suit therein, without paying fees or costs; whereupon he shall have, from any counsel whom the court may assign him, and from all officers, all needful services and process, without any fees to them therefore, except what may be included in the costs recovered from the opposite party.\" ", "Va. Code § 14.1-183 (1950).", "\nThe Virginia Code was amended in 1987 to delete the 6-month residency requirement. ", "Va. Code § 14.1-183 (Supp. ", "1988). ", "It is unclear whether, in review of capital cases, counsel will be appointed under this statute or otherwise prior to filing and unless the petition presents a nonfrivolous claim. ", "See Darnell v. Peyton, 208 Va. 675, 160 S. E. 2d 749 (1968).", "\n[4] Respondents offer this theory — that the Constitution requires post-conviction cases involving the death penalty to be treated differently from other postconviction cases — as a basis for affirmance in addition to their reliance on Bounds v. Smith, 430 U. S. 817 (1977), discussed later.", "\n[5] The dissent offers surveys to show that Virginia is one of a handful of States without a \"system for appointing counsel for condemned prisoners before a postconviction petition is filed.\" ", "Post, at 31. ", "But even these surveys indicate that only 18 of the 37 States make such appointment automatic. ", "Post, at 30. ", "These 18 States overlap to a significant extent with the 13 States that have created \"resource centers to assist counsel in litigating capital cases,\" post, at 30-31, which in any event, is not the same thing as requiring automatic appointment of counsel before the filing of a petition. ", "Consequently, a substantial balance of States do not accord the right that the dissent would require Virginia to grant as a matter of constitutional law. ", "Virginia courts presently have the authority to appoint counsel to represent any inmate in state habeas proceedings, Va. Code § 14.1-183 (Supp. ", "1988), and the attorney general represents that such appointments have been made, upon request, before the filing of any petition. ", "Brief for Petitioners 6-7.", "\n[6] The prisoner's right of access has been described as a consequence of the right to due process of law, see Procunier v. Martinez, 416 U. S. 396, 419 (1974), and as an aspect of equal protection, see Pennsylvania v. Finley, 481 U. S. 551, 557 (1987).", "\n[7] Many States automatically provide counsel to death row inmates in state habeas corpus proceedings, as a matter of state law. ", "See, e. g., Ariz. Rule Crim. ", "Proc. ", "32.5(b); Conn. Gen. Stat. § ", "51-296(a) (1985); Okla. Stat., ", "Tit. ", "22, § 1089 (Supp. ", "1988); Ore. Rev. Stat. § ", "138.590(3) (1987). ", "Under the Anti-Drug Abuse Act of 1988, attorneys will be appointed in federal habeas corpus actions involving a challenge to a death sentence. ", "See § 7001(b), Pub. ", "L. 100-690, 102 Stat. ", "4393, 21 U. S. C. § 848(q)(4)(B) (1988 ed.). ", "Respondents suggest that appointment of counsel might even benefit Virginia by speeding, or at least clarifying, the Virginia postconviction process. ", "The situation of death row inmates may well be the basis for state policy to provide them extra legal assistance or more lenient standards of pro se pleading.", "\n[1] Compare Brief for Petitioners 23 (\"The notion that the access right is to be measured against the assistance that might be provided an inmate by a personal lawyer has no support in Bounds. ", "Indeed, the idea is entirely inconsistent with the limited nature of the right\") with Brief for Respondents 25 (\"The district court's findings, conclusion, and remedy all comprise a conventional application of Bounds in an extraordinary context\").", "\n\nAlthough the Court of Appeals en banc and the District Court placed singular reliance on Bounds, both indicated that they would have reached the same result on the other legal theories as well. ", "847 F. 2d 1118, 1122, n. 8 (CA4 1988) (\"Because of the peculiar nature of the death penalty, we find it difficult to envision any situation in which appointed counsel would not be required in state post-conviction proceedings when a prisoner under the sentence of death could not afford an attorney\"); 668 F. Supp. ", "511, 516, n. 4 (ED Va. 1986) (\"[C]hanging the theory under which relief is sought would not alter the analysis\").", "\n[2] See Gideon, 372 U. S., at 342-344. ", "Justice Harlan made explicit Gideon's abandonment of the special circumstances rule in the context of the right to counsel in serious criminal prosecutions. ", "Id., at 350-351 (concurring opinion). ", "But see id., at 348, n. 2 (Clark, J., concurring in result) (linking Gideon to Griffin v. Illinois, 351 U. S. 12 (1956), and Ferguson v. Georgia, 365 U. S. 570 (1961), also a Fourteenth Amendment case).", "\n[3] The Court consistently has adhered to Justice Sutherland's observation in Powell v. Alabama, 287 U. S. 45, 53, 71 (1932), that when assistance of counsel is required, that assistance must be \"effective\" rather than pro forma. ", "See Evitts v. Lucey, 469 U. S. 387 (1985); Strickland v. Washington, 466 U. S. 668 (1984); Wainwright v. Torna, 455 U. S. 586 (1982) (per curiam). ", "Cf. ", "Penson v. Ohio, 488 U. S. 75, 85 (1988) (\"The need for forceful advocacy does not come to an abrupt halt as the legal proceeding moves from the trial to appellate stage. ", "Both stages of the prosecution, although perhaps involving unique legal skills, require careful advocacy to ensure that rights are not forgone and that substantial legal and factual arguments are not inadvertently passed over\").", "\n[4] The en banc majority below, for instance, distinguished Pennsylvania v. Finley, 481 U. S. 551 (1987), in part on the ground that it \"was not a meaningful access case, nor did it address the rule enunciated in Bounds v. Smith.\" ", "847 F. 2d, at 1122.", "\n[5] The Colonies of Pennsylvania, South Carolina, and Virginia made counsel more available to capital defendants than to persons accused of other offenses. ", "See Powell, 287 U. S., at 61-63, 65.", "\n[6] Act of Apr. 30, 1790, ch. ", "9, §§ 1, 3, 8-10, 14, 1 Stat. ", "112-115 (authorizing death sentence for willful murder, treason, and other crimes); id., § 29, 1 Stat. ", "118, as amended, 18 U. S. C. § 3005 (requiring appointment of counsel for capital defendants).", "\n[7] The Anti-Drug Abuse Act of 1988, § 7001(b), Pub. ", "L. 100-690, 102 Stat. ", "4393-4394, codified at 21 U. S. C. §§ 848(q)(4)(B), (q)(8) (1988 ed.) ", "provides in pertinent part:\n\n\"(B) In any post conviction proceeding under section 2254 or 2255 of title 28, United States Code, seeking to vacate or set aside a death sentence, any defendant who is or becomes financially unable to obtain adequate representation or investigative, expert, or other reasonably necessary services shall be entitled to the appointment of one or more attorneys and the furnishing of such other services in accordance with paragrap[h] . . . (", "8). . . .", "\n.....\n\"(8) Unless replaced by similarly qualified counsel upon the attorney's own motion or upon motion of the defendant, each attorney so appointed shall represent the defendant throughout every subsequent stage of available judicial proceedings, including pretrial proceedings, trial, sentencing, motions for new trial, appeals, applications, for writ of certiorari to the Supreme Court of the United States, and all available post-conviction process, together with applications for stays of execution and other appropriate motions and procedures, and shall also represent the defendant in such competency proceedings and proceedings for executive or other clemency as may be available to the defendant.\"", "\n[8] Powell v. Alabama, 287 U. S. 45 (1932), for instance, established a right to appointment of counsel for capital defendants three decades before that right was extended to felony defendants facing imprisonment. ", "Gideon v. Wainwright, 372 U. S. 335 (1963), overruling Betts v. Brady, 316 U. S. 455 (1942). ", "See Hamilton v. Alabama, 368 U. S. 52 (1961) (reversing State's denial of postconviction relief for petitioner who was not represented by counsel at arraignment on capital charge). ", "In Bute v. Illinois, 333 U. S. 640, 674 (1948), the Court held that a state court was not required to query a defendant in a noncapital case regarding his desire for counsel. \"", "On the other hand,\" Justice Burton pointed out in the majority opinion, \"this Court repeatedly has held that failure to appoint counsel to assist a defendant or to give a fair opportunity to the defendant's counsel to assist him in his defense where charged with a capital crime is a violation of due process of law under the Fourteenth Amendment.\" ", "Id., at 676 (citing cases).", "\n[9] Among those making this point before Furman were Justice Frankfurter in Andres v. United States, 333 U. S. 740, 753 (1948) (concurring opinion) (\"The statute reflects the movement, active during the nineteenth century, against the death sentence. ", "The movement was impelled both by ethical and humanitarian arguments against capital punishment, as well as by the practical consideration that jurors were reluctant to bring in verdicts which inevitably called for its infliction\"), and again in Leland v. Oregon, 343 U. S. 790, 803 (1952) (dissenting opinion) (\"Even though a person be the immediate occasion of another's death, he is not a deodand to be forfeited like a thing in the medieval law\"), and Justice Reed in Andres, supra, at 752 (opinion of the Court) (\"In death cases doubts such as those presented here should be resolved in favor of the accused\").", "\n\nIn 1983, 11 years after Furman had been decided, JUSTICE O'CONNOR observed in a majority opinion that the \"Court, as well as the separate opinions of a majority of the individual Justices, has recognized that the qualitative difference of death from all other punishments requires a correspondingly greater degree of scrutiny of the capital sentencing determination.\" ", "California v. Ramos, 463 U. S. 992, 998-999; see id., at 999, n. 9 (citing cases). ", "See also, e. g., Ford v. Wainwright, 477 U. S. 399, 411 (1986) (MARSHALL, J., plurality opinion) (\"In capital proceedings generally, this Court has demanded that factfinding procedures aspire to a heightened standard of reliability. . . . ", "This especial concern is a natural consequence of the knowledge that execution is the most irremediable and unfathomable of penalties; that death is different\"); Ake v. Oklahoma, 470 U. S. 68, 87 (1985) (Burger, C. J., concurring in judgment) (\"In capital cases the finality of the sentence imposed warrants protections that may or may not be required in other cases\"); Gardner v. Florida, 430 U. S. 349, 357-358 (1977) (STEVENS, J., plurality opinion) (\"From the point of view of the defendant, it is different in both its severity and its finality. ", "From the point of view of society, the action of the sovereign in taking the life of one of its citizens also differs dramatically from any other legitimate state action. ", "It is of vital importance to the defendant and to the community that any decision to impose the death sentence be, and appear to be, based on reason rather than caprice or emotion\").", "\n[10] E. g., Satterwhite v. Texas, 486 U. S. 249 (1988); Booth v. Maryland, 482 U. S. 496 (1987); Caldwell v. Mississippi, 472 U. S. 320 (1985); Spaziano v. Florida, 468 U. S. 447, 456 (1984); Beck v. Alabama, 447 U. S. 625 (1980); Lockett v. Ohio, 438 U. S. 586 (1978) (plurality opinion). ", "Accord, ante, at 8-9.", "\n[11] Accord, Woodson v. North Carolina, 428 U. S. 280, 303 (1976) (plurality opinion); Proffitt v. Florida, 428 U. S. 242, 251, 253, 258-259 (1976) (opinion of Stewart, Powell, and STEVENS, JJ.); ", "Jurek v. Texas, 428 U. S. 262, 276 (1976) (opinion of Stewart, Powell, and STEVENS, JJ.); ", "Gregg v. Georgia, 428 U. S. 153, 188 (1976) (opinion of Stewart, Powell, and STEVENS, JJ.). ", "Cf. ", "Ramos, 463 U. S., at 999; Zant v. Stephens, 462 U. S. 862, 876 (1983); Griffin, 351 U. S., at 21 (Frankfurter, J., concurring in judgment) (\"Since capital offenses are sui generis, a State may take account of the irrevocability of death by allowing appeals in capital cases and not in others\").", "\n[12] Nor can we overlook our experience that capital litigation proceeds apace after affirmance of a conviction. ", "With the vigorous opposition of state legal departments, capital defendants seek not only review of state and federal judicial decisions, but also relief from state governors and parole boards. ", "See Powell, Capital Punishment, 102 Harv. ", "L. Rev. 1035, 1038-1041 (1989). ", "Thus the conviction and sentence in a capital case will not be \"final,\" or undisturbed, until the sentence either is executed or set aside. ", "Cf. ", "Barefoot v. Estelle, 463 U. S. 880, 888 (1983). ", "With the cases of over half the Nation's more than 2,100 inmates yet to move into collateral proceedings, Wilson & Spangenberg, State Post-Conviction Representation of Defendants Sentenced to Death, 72 Judicature 331, 332 (1989), the need for an orderly sequence of review is pellucid. ", "As THE CHIEF JUSTICE has remarked: \" `We judges have no right to insist that matters such as these proceed at a leisurely pace, or even at an ordinary pace, but I think we do have a claim to have explored the possibility of imposing some reasonable regulations in a situation which is disjointed and chaotic.' \" ", "Remarks before the National Conference of Chief Justices (Jan. 27, 1988), quoted in Powell, supra, at 1040.", "\n[13] Mello, Facing Death Alone: The Post-Conviction Attorney Crisis on Death Row, 37 Am. ", "U. L. Rev. 513, 520-521 (1988). ", "The former Chief Judge of the Eleventh Circuit, which has the greatest volume of capital litigation, recently estimated that in his Circuit capital defendants' success rate in collateral proceedings may be as high as one-third to one-half of all such cases. ", "Godbold, Pro Bono Representation of Death Sentenced Inmates, 42 Record of N. Y. C. B. A. 859, 873 (1987). ", "Cf. ", "Barefoot, 463 U. S., at 915 (MARSHALL, J., dissenting).", "\n[14] The Virginia Supreme Court requires contemporaneous objection before it will consider any asserted trial error on direct review. ", "Va. Sup. ", "Ct. ", "Rule 5:21. ", "Likewise, it does not review the entire case record, but only questions clearly assigned as errors on appeal. ", "See ibid.; ", "Va. Code § 17.110.1 (1988). ", "See also Quintana v. Commonwealth, 224 Va. 127, 295 S. E. 2d 643 (1982), cert. ", "denied, 460 U. S. 1029 (1983).", "\n\nThis Court abides by States' applications of rules precluding direct review of procedurally defaulted claims, see Caldwell, 472 U. S., at 327, sometimes in confidence that an obvious error will be corrected on collateral review. ", "E. g., Watkins v. Virginia, 475 U. S. 1099, 1100 (1986) (opinion of STEVENS, J., respecting the denial of petition for certiorari in 229 Va. 469, 331 S. E. 2d 422 (1985)).", "\n[15] The Virginia Supreme Court will consider previously defaulted claims on postconviction review if the petitioner shows that counsel was ineffective in failing to assert a claim or object to an error. ", "See Slayton v. Parrigan, 215 Va. 27, 205 S. E. 2d 680 (1974), cert. ", "denied, 419 U. S. 1108 (1975). ", "Failure to do so may forever bar review, for Virginia does not allow a claim that could have been raised in the first postconviction petition to be asserted in a successive petition. ", "Va. Code § 8.01-654(B)(2) (1984). ", "See 847 F. 2d, at 1120, n. 4; Whitley v. Bair, 802 F. 2d 1487 (CA4 1986), cert. ", "denied, 480 U. S. 951 (1987).", "\n[16] Indeed, if the petitioner is represented by counsel at the hearing, the court's factual findings attain a presumption of correctness that may bar further factual review by the federal court. ", "28 U. S. C. § 2254(d)(5). ", "See Sumner v. Mata, 449 U. S. 539 (1981).", "\n[17] See, e. g., Dugger v. Adams, 489 U. S. 401 (1989) (declining to review claim that jury was instructed inaccurately regarding its role in the capital sentencing process); Teague v. Lane, 489 U. S. 288 (1989) (holding procedurally barred claim, asserted by petitioner serving life term for murder, that jury was selected in a biased manner in violation of Swain v. Alabama, 380 U. S. 202 (1965)). ", "See also n. 14, supra.", "\n[18] The availability of appointed counsel on federal habeas, see n. 7, supra, thus presents the specter of a petitioner filing for federal habeas corpus and attaining counsel, only to have the petition dismissed as unexhausted and remanded to state court. ", "Such a haphazard procedure scarcely would serve any interest in finality. ", "It further would raise questions regarding the obligations not only of the appointed counsel to effect exhaustion at the state level, but also of the Federal Treasury to pay for those efforts. ", "Cf. ", "Ex parte Hull, 312 U. S. 546, 549 (1941) (\"[T]he state and its officers may not abridge or impair petitioner's right to apply to a federal court for a writ of habeas corpus\").", "\n[19] I am at a loss as to why the plurality today prefers to label the District Court findings of fact, based upon trial testimony and post-trial submissions, \" `considerations.' \" ", "See ante, at 4-5, 6.", "\n[20] An execution may be scheduled for any time 30 days after the date of sentencing. ", "Va. Code § 53.1-232 (1988); see 668 F. Supp., ", "at 513. ", "A 1988 study commissioned by the American Bar Association found that attorneys spent an average of 992 hours and $3,686 on each capital postconviction proceeding in Virginia. ", "Brief for American Bar Association as Amicus Curiae 34 (hereinafter ABA Brief).", "\n[21] The District Court commented:\n\n\"In Virginia, the capital trial is bifurcated, entailing separate proceedings to determine guilt and to set the appropriate punishment. ", "Aside from analyzing the voluminous transcript of the guilt determination phase which not infrequently lasts several days, a great deal of time must be devoted to analyzing the issues of mitigation and aggravation characteristic of the sentencing phase of a capital case.\" ", "668 F. Supp., ", "at 513.", "\n[22] In apparent recognition of this fact, Congress has required that when a court appoints counsel in capital postconviction proceedings, at least one attorney must have been a member of the bar for at least five years and have at least three years felony litigation experience. § ", "7001(b) of the Anti-Drug Abuse Act of 1988. ", "Pub. ", "L. 100-690, 102 Stat. ", "4394, codified at 21 U. S. C. §§ 828(q)(5), (q)(6) (1988 ed.).", "\n[23] Compounding matters is the typically low educational attainment of prisoners. ", "In 1982 more than half of Florida's general inmate population was found to be functionally illiterate, while in 1979 the State's death row inmates possessed a ninth-grade mean educational level. ", "ABA Brief 26-27. ", "Virginia's death row inmates apparently have similar educational backgrounds. ", "See Brief for American Civil Liberties Union et al. ", "as Amici Curiae 20-21, n. 7. ", "See also Brief for Maryland State Bar Association et al. ", "as Amici Curiae 16-17 (State Bar Brief) (citing similar statistics for other States' inmate populations).", "\n[24] For example, one lawyer testified:\n\n\"I have had lots of clients in those last 60 day time periods, and what they are forced to do is to prepare themselves mentally and spiritually and emotionally to deal with their family and their children, all of whom see them as about to die. ", "And that is a full time job.", "\n\"And very few of them, I think, even have the emotional resources to talk with you meaningfully at that point about their case. ", "Much less to take it over.\" ", "App. ", "66.", "\nCf. ", "Medley, 134 U. S. 160, 172 (1890) (\"[W]hen a prisoner sentenced by a court to death is confined in the penitentiary awaiting the execution of the sentence, one of the most horrible feelings to which he can be subjected during that time is the uncertainty during the whole of it, which may exist for the period of four weeks, as to the precise time when his execution shall take place\").", "\n[25] A representative of the Virginia attorney general's office testified regarding the office's policy not to oppose a death row inmate's motion for appointment of postconviction counsel as follows:\n\n\"Well, basically we want to see the inmate have an attorney at State Habeas for reasons of economy and efficiency.", "\n\"When you have a death case, we recognize that it is going to be prolonged litigation and we want to see all matters that the inmate or the petitioner wants to raise be raised at one proceeding, and we can deal more efficiently with an attorney. ", "And we prefer that from an economy stand-point we don't have to have more than one proceeding.\" ", "App. ", "272.", "\nCf. ", "Powell, 102 Harv. ", "L. Rev., at 1040 (attributing delay in carrying out capital punishment in part to lack of counsel on collateral review).", "\n[26] Ariz. Rule Crim. ", "Proc. ", "32.5(b); Cal. ", "Govt. ", "Code Ann. § ", "15421(c) (West 1980), Cal. ", "Penal Code Ann. § ", "1240 (West 1982); Conn. Super. ", "Ct. ", "Rules, Criminal Cases § 959, Conn. Gen. Stat. § ", "51-296(a) (1989); Fla. Stat. § ", "27.702 (1987); Idaho Code § 19-4904 (1987); Ind. Rule Proc. ", "for Post-Conviction Remedies 1, § 9; Md. Ann. ", "Code, Art. ", "27, § 645A(f) (Supp. ", "1988); Mo. Rules Crim. ", "Proc. ", "24.035(e), 29.15(e); N. J. Rules Governing Criminal Practice 3:22-6, 3:27-1, N. J. Stat. ", "Ann. § ", "2A:158A-5 (West Supp. ", "1989-1990); N. C. Gen. Stat. §§ ", "15A-1421 (1988), 7A-451(a)(2) (Supp. ", "1988), 7A-486.3 (1986); Okla. Stat., ", "Tit. ", "22, § 1089 (Supp. ", "1988); Ore. Rev. Stat. § ", "138.590(3) (1987); Pa. Rule Crim. ", "Proc. ", "1503; S. D. Codified Laws § 21-27-4 (1987); Tenn. Sup. ", "Ct. ", "Rule 13, § 1; Utah Rule Civ. ", "Proc. ", "65B(i)(5); Vt. ", "Stat. ", "Ann., ", "Tit. ", "13, §§ 5231-5233, 7131 (1974), as interpreted in In re Morse, 138 Vt. ", "327, 415 A. 2d 232 (1980); Wash. Super. ", "Ct. ", "Crim. ", "Rule 3.1(b)(2).", "\n\nIn addition to these 18 States, 3 — Montana, Nevada, and Wyoming — have no definitive case or statutory law on this point but are listed in a 1988 study commissioned by the American Bar Association as having a practice of mandatory appointment of counsel on request. ", "Wilson & Spangenberg, 72 Judicature, at 334 (Table 1).", "\n[27] They are Alabama, Arizona, California, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, and Texas. ", "State Bar Brief 34. ", "See Mello, 37 Am. ", "U. L. Rev., at 593-606 (discussing development of Florida's resource center); cf. ", "Godbold, 42 Record of N. Y. C. B. A., at 868-871 (state and federal efforts to provide legal assistance). ", "As a result of several studies it has commissioned concerning the significance of providing counsel in capital postconviction proceedings, the American Bar Association \"has recognized that the only feasible way to provide death row inmates with meaningful access to the courts is the implementation in each state which imposes capital punishment of a governmentally-funded system under which qualified, compensated attorneys represent death row inmates in state post-conviction proceedings.\" ", "ABA Brief 4-5.", "\n[28] Of 27 States that responded to a 1988 survey, only Virginia, Nebraska, Pennsylvania, and Nevada were reported to have no system \"to monitor and assure that counsel will be provided prior to the filing of a post-conviction petition.\" ", "Wilson & Spangenberg, supra, at 335. ", "Of those, only Virginia and Nevada have executed prisoners since this Court decided Furman v. Georgia, 408 U. S. 238 (1972). ", "NAACP Legal Defense and Education Fund, Inc., Death Row, U. S. A. 3 (March 1, 1989) (Death Row). ", "Pennsylvania, and perhaps Nevada, appoint counsel automatically upon request. ", "See n. 26, supra. ", "Of the 10 States that have death penalty statutes but were not part of the survey, only Arkansas, Colorado, and New Hampshire have neither rules for automatic appointment of counsel nor resource centers. ", "None of these States has conducted a post-Furman execution; New Hampshire, in fact, has no prisoner under sentence of death, and Colorado has none whose case has reached the state postconviction stage. ", "Death Row, supra, at 1; Wilson & Spangenberg, supra, at 334.", "\n" ]
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[ "Concept analysis of Diné Hózhó: a Diné wellness philosophy.", "\nAmerican Indian Alaska Native people of the United States face challenges in attaining physical, mental, spiritual, and environmental health. ", "This article presents a concept analysis of Diné Hózhó, a complex and misunderstood wellness concept the Diné (Navajo) strive to attain. ", "Findings from a literature review are presented to explore anthropological definitions and uses of the concept Hózhó. ", "The method of concept analysis of Walker and Avant is utilized, model cases are presented. ", "Recommendations for application in nursing practice are presented." ]
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[ "Berghoff 10-Inch Mixing Bowl with Cover,6.4-Quart\n\nBerghoff 10-Inch Mixing Bowl with Cover,6.4-Quart by Berghoff at The Littlest Bakehouse. ", "SKU: 1105178. ", "MPN: FBA_1105178. ", "Hurry! ", "Limited time offer. ", "Offer valid only while supplies last. ", "This mixing bowl won several design awards for the way it unifies form and\n\nProduct Description\n\nThis mixing bowl won several design awards for the way it unifies form and function.", "\n\nRelated Best Sellers\n\nYou can never have too many stainless steel mixing bowls when baking or kitchen prepping for your multiple dishes, and this Set of 24 Stainless Steel Bowls does the job! ", "These high-rimmed bowls are a size that is handy for many jobs, from cracking ...\n\nThis mixing bowl won several design awards for the way it unifies form and function.", "Black plastic lid can also be used as a base. ", "2009 winner of the Product Design Award. ", "An elegant addition to any kitchen. ", "Durable 18/10 Highly polished stainless ste...\n\nDr. Oetker's Creative Accessories. ", "Quality baking tools, for the first mix to the finishing touch. ", "Our mixing bowl is a generous 3.5 quarts and perfect for all your baking needs. ", "Since 1891, Dr. Oetker's line of products is a trusted brand all over ...\n\n100-Percent Made in Germany: Koziol has been creating fun award winning designs for the home since 1927 from their factory in Erbach Germany. ", "100-Percent Environmentally Aware: Less energy is needed to make Koziol products than items made of porcelai...\n\nMixing bowls don't have to be drab or dull. ", "Our 4-Piece Mixnbowl Set is anything but boring, offering vibrant color and a sophisticated black rim that screams \"put me on display.\" ", "With this mixing bow set of four bowls of varying sizes, you can do an..." ]
{ "pile_set_name": "Pile-CC" }
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[ "The Black Widow is the anonymous character that made her first appearance in 'A' is for A-l-i-v-e. After a fan, suggested the name The Black Widow, Marlene decided to keep it.", "\n\nSeason 4\n\n'A' is for A-l-i-v-e\n\nThe Black Widow attends Darren Wilden's funeral. ", "She is shown to be wearing the burned Alison Mask, and is apparently a member of the \"A Team\". ", "Earlier a mysterious person is seen fleeing the lodge after Spencer figures out that she and Toby are not alone. ", "It could have possibly been Black Widow since she had the burnt mask. ('", "A' is for A-l-i-v-e).", "\n\n\n\nTurn of the Shoe\n\nMona gets in her car, and right after, she is attacked by the someone in an Ali mask who was hiding on the back seat; this may or may not be The Black Widow. ", "If this is her, she may have gotten a new Ali mask because it isn't burnt on the side.", "\n\nPossible Identities\n\nEliminated Suspects (people already in attendance at Wilden's funeral)\n\nTrivia\n\nMarlene originally named her The Lady in Black .", "\n\n. ", "After a fan, suggested the name The Black Widow , Marlene decided to keep it.", "\n\n, Marlene decided to keep it. ", "She was given the\" fan-name\" Veiled Griever because she attended Wilden's funeral, and she is ' grieving' the loss of someone and she has a veil on.", "\n\nthe loss of someone and she has a veil on. ", "Based on the burnt mask, The Black Widow appears to have some connection to the fire.", "\n\nThe mask is A's mask so it may be Red Coat in disguise. ", "If this is true than the burnt mask signifies that Ali may not have been Red Coat and pulled them out of the fire; she is someone the Liars haven't figured out.", "\n\nThe Lady in Black Video\n\nGallery\n\nNavigational" ]
{ "pile_set_name": "OpenWebText2" }
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[ "I have a question about the program who do I ask?", "\n\nGet Points\n\nHow do I earn Points?", "\n\nTo see all points earning opportunities check out the Earn Points section.", "\n\nCan a friend and I pool our points together?", "\n\nNo, we do not allow for the pooling of points into one account.", "\n\nUse Points\n\nHow do I know if I won a Contest/Trade-In?", "\n\nIf you win, you will be notified via email if you are the winner of the Contest/Trade-In with instructions on how to claim your prize.", "\n\nHow do I know if I am an Instant Winner?", "\n\nYou will instantly receive a message on the screen confirming you are the Instant Winner. ", "You will then be notified via email that you are the Instant Winner with instructions on how to claim your prizes.", "\n\nI just won a Contest/Trade-In ...how do I get my prize?", "\n\nFor prizes we ship, we offer free shipping to addresses within the continental United States. ", "We will ship your prize to you 3-8 weeks from the closing of the Contest/Trade-In (as long as you have provided the correct shipping information), unless otherwise specified. ", "If you need to correct this information, edit your Profile by clicking your username in the upper right hand corner of the page.", "\n\nFor prizes you pick up, you will also receive a winner notification email with the pick-up details.", "\n\nHow do I enter a Contest?", "\n\nFirst choose a Contest you are interested in entering (be sure that you are logged in so that you have access to the points you have collected). ", "For Featured Contests, enter the number of entries you would like in the box - each Contest will indicate the points needed per entry. ", "Then click the Enter button. ", "Points will be deducted from your account once you submit your entry. ", "For Standard Contests, click the Enter button – each Contest will indicate the points needed for entry. ", "You may go back to the Standard Contest and enter again (pending the Contest will accept multiple entries).", "\n\nHow many Contest entries can I get?", "\n\nYou can use points for as many Contest entries as you want unless it’s limited. ", "In fact, the more entries you buy, the better your chances of winning!", "\n\nWelcome back to 1390 THE FAN\n\nIt appears that you already have an account created within our VIP network of sites on .", "\nTo keep your points and personal information safe, we need to verify that it's really you.", "\nTo activate your account, please confirm your password.", "\nWhen you have confirmed your password, you will be able to log in through Facebook on both sites.", "\n\n*Please note that your points, prizes and activities will not be shared between programs within our VIP network.", "\n\nWelcome back to 1390 THE FAN\n\nIt appears that you already have an account on this site associated with . ", "To connect your existing account just click on the account activation button below. ", "You will maintain your existing VIP profile. ", "After you do this, you will be able to always log in to http://1390thefan.com using your original account information." ]
{ "pile_set_name": "Pile-CC" }
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[ { "analysis_explanation": null, "end": 852, "entity_type": "LOCATION", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 839 }, { "analysis_explanation": null, "end": 894, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 885 }, { "analysis_explanation": null, "end": 2850, "entity_type": "URL", "recognition_metadata": { "recognizer_identifier": "UrlRecognizer_140094861343568", "recognizer_name": "UrlRecognizer" }, "score": 0.6, "start": 2829 } ]
[ "Q:\n\nThread.interrupt () doesn't work\n\nHy!", "\nMy Thread.interrupt doesn't work.", "\nCode (us is global):\n//Call\n\nus = new UpdateState(params, hup);\n us.start();\n\n//Interupt\n@Override\n public boolean onOptionsItemSelected(MenuItem item) {\n\n if (item.getItemId()== R.id.stopthread)\n {\n Log.e(\"Kill\", \"Kill\");\n us.interrupt();\n }\n return super.onOptionsItemSelected(item);\n }\n\nClass:\npackage android.skiptvad;\n\nimport java.util.", "List;\n\nimport org.apache.http.", "NameValuePair;\n\nimport android.os.", "Handler;\nimport android.os.", "Message;\nimport android.text.", "NoCopySpan.", "Concrete;\nimport android.util.", "Log;\nimport android.widget.", "TextView;\nimport android.widget.", "Toast;\nimport android.util.", "Log;\n\npublic class UpdateState extends Thread {\n\n public List<NameValuePair> params;\n public Handler handler;\n public Handler ins;\n\n public UpdateState(List<NameValuePair> params, final Handler handler) {\n this.handler = handler;\n this.params = params;\n this.ins = new Handler (){\n @Override\n public void handleMessage(Message msg) {\n\n if (msg.obj.toString()!= null)\n {\n JSONParse json = null;\n try \n { \n Message msg2 =new Message();\n Log.e(\"Channel_State_Update\",msg.obj.toString());\n json = new JSONParse(msg.obj.toString());\n String state = json.getChannelState();\n Log.e(\"Channel_State_Send\",state);\n msg2.obj = state;\n handler.sendMessage(msg2);\n\n } \n catch (final Exception e) \n {\n e.printStackTrace();\n }\n }\n }\n };\n }\n\n @Override\n public void run() {\n\n while (true)\n {\n if (!", "this.isInterrupted())\n {\n HttpConnection con = new HttpConnection(params, \"http://surfkid.redio.de/getChannelState\", this.ins);\n con.start();\n try {\n Log.e(\"Sleep\", \"Begin\");\n UpdateState.this.sleep(5000);\n Log.e(\"Sleep\", \"End\");\n } catch (InterruptedException e) {\n // TODO Auto-generated catch block\n Log.e(\"Sleep\", \"Error\");\n e.printStackTrace();\n }\n }\n\n //super.run();\n }\n }\n}\n\nPlease help\nLog:\n02-15 18:50:30.317: ERROR/Sleep(10696): End\n02-15 18:50:30.347: ERROR/Sleep(10696): Begin\n02-15 18:50:30.677: ERROR/Channel_State_Update(10696): {\"responseData\":{\"channelState\":\"0\"},\"responseDetails\":null,\"responseStatus\":200}\n02-15 18:50:30.677: ERROR/Channel_State_Send(10696): 0\n02-15 18:50:30.677: ERROR/UPDATE(10696): 0\n02-15 18:50:35.347: ERROR/Sleep(10696): End\n02-15 18:50:35.357: ERROR/Sleep(10696): Begin\n02-15 18:50:35.897: ERROR/Channel_State_Update(10696): {\"responseData\":{\"channelState\":\"0\"},\"responseDetails\":null,\"responseStatus\":200}\n02-15 18:50:35.897: ERROR/Channel_State_Send(10696): 0\n02-15 18:50:35.897: ERROR/UPDATE(10696): 0\n02-15 18:50:36.868: ERROR/Kill(10696): Kill\n02-15 18:50:36.878: ERROR/Sleep(10696): Error\n02-15 18:50:36.908: ERROR/Sleep(10696): Begin\n02-15 18:50:37.427: ERROR/Channel_State_Update(10696): {\"responseData\":{\"channelState\":\"0\"},\"responseDetails\":null,\"responseStatus\":200}\n02-15 18:50:37.427: ERROR/Channel_State_Send(10696): 0\n02-15 18:50:37.427: ERROR/UPDATE(10696): 0\n02-15 18:50:41.909: ERROR/Sleep(10696): End\n02-15 18:50:41.927: ERROR/Sleep(10696): Begin\n\nA:\n\nYou need to break a loop when thread is interrupted:\n@Override\npublic void run() {\n while (!", "this.isInterrupted()) { // Exit when thread's interrupt flag is set\n HttpConnection con = new HttpConnection(params, \"http://surfkid.redio.de/getChannelState\", this.ins);\n con.start();\n try {\n Log.e(\"Sleep\", \"Begin\");\n UpdateState.this.sleep(5000);\n Log.e(\"Sleep\", \"End\");\n } catch (InterruptedException e) {\n Log.e(\"Sleep\", \"Error\");\n e.printStackTrace();\n\n // Restore interrupt flag after catching InterruptedException\n // to make loop condition false\n Thread.currentThread().interrupt();\n }\n }\n}\n\n" ]
{ "pile_set_name": "StackExchange" }
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[ "1. ", "Introduction {#sec0005}\n===============\n\n*Helicobacter pylori* (*H. pylori*) is a spiral-shaped Gram-negative bacteria colonized in the gastrointestinal tract. *", "H. pylori* infection leads to peptic ulceration, gastritis, and gastric carcinoma \\[[@bib0005]\\]. ", "About 50 % of the world population is estimated to be infected by this bacterium \\[[@bib0010]\\]. ", "The colonization of *H. pylori* is caused by its infectious agents as shown in [Fig. ", "1](#fig0005){ref-type=\"fig\"} and [Table 1](#tbl0005){ref-type=\"table\"}.Fig. ", "1Virulence agents of *H. pylori*. ", "IL: Interleukin; TLR4: Toll-like receptor 4; NF-κB: Nuclear factor-kappaB; NIK: NF-κB-inducing kinase; VacA: Vacuolating cytotoxin A; CagA: Cytotoxin-associated gene antigen; PAK1: p21-activated kinase; IKKα/β: IκB kinase α/β; MAPK: Mitogen-activated protein kinase; MEK1/2: MAPK/ERK kinase 1/2; INF-γ: Interferon-γ; NOD1: Nucleotide-binding oligomerisation domain protein 1; ICAM-1: Intercellular adhesion molecule-1; iNOS: Inducible nitric oxide synthase, COX-2: Cyclooxygenase-2; MKK4: MAPK kinase 4; LPS: Lipopolysaccharide; TNF-α: Tumor necrosis factor-α.", "Fig. ", "1Table 1Virulence agents of *H. pylori*.Table 1Vrulence agent*H. pylori* FunctionVacuolating cytotoxin A (VacA)Induce Cyto C releaseCytotoxicityCag Pathogenicity Island (CagPAI)Induce inflammationCag genes (Cag E,G,I,H, L and M)Coding for 40-kb is a major virulence factor of *H. pylori*.UreaseCausing epithelium cells toxicityDisrupting cell tight junctionsBuffers stomach acidSheathing antigenDuodenal ulcer promoting A (DupA)Induce inflammationOuter inflammatory protein A (OipA)Induce inflammation for IL-8*H. pylori* neutrophil activation protein (HP-NAP)Activation of neutrophilBabAAdhesinFlagellaMovements through mucin\n\n2. ", "Pharmacological therapies {#sec0010}\n============================\n\nNumerous pharmacological studies have been reported for the eradication of *H. pylori*. ", "Proton-pump inhibitors, antibiotics, bismuth saltsand H2-blockers (intragastric pH control drug) are recommended standard therapies \\[[@bib0015]\\]. ", "A few issues may arise upon those eradication therapies, for example, the cost, the high global prevalence and the uprising resistance to available antibiotics. ", "Consequently, some patients undergoing many of these drug regimens experience therapeutic failure \\[[@bib0015]\\]. ", "Moreover, these therapies include getting too many medications which might cause side effects that, along with significant cost regarding the treatment, promote inadequate patient compliance. ", "It is extremely desirable to explore for alternative strategies with agents to prevent or manage *H. pylori*-associated gastric tumor.", "\n\nThe quest regarding new anti-*H. pylori* therapies has driven exploration in the field of therapeutic plants. ", "Many studies have been performed on a great number of plant varieties. ", "Natural products exhibit their own anti-*H. pylori* actions via different mechanisms. ", "While therapeutic agents have either antisecretory or healing effects, prophylactic compounds produce their effect via their antioxidant and anti-inflammatory mechanisms.", "\n\n3. ", "Mechanisms of medicinal plants as anti-*H. pylori* {#sec0015}\n=====================================================\n\nMany natural products have anti-*H. pylori* potentials. ", "The mechanisms of such potentials include urease inhibition, DNA damage, protein synthesis inhibition, and anti-inflammatory effects. ", "In addition to the anti-*H. pylori* effects due to some enzymes like dihydrofolate reductase and myeloperoxidase *N*-acetyltransferase.", "\n\n3.1. ", "Urease inhibition {#sec0020}\n----------------------\n\nThe potent effect of resveratrol as anti-*H. pylori* is mainly owing to ureaseinhibition \\[[@bib0020]\\]. ", "The anti- *H. pylori* actions of *Paeonia lactiflora* roots is due to the hydrophobicity of 1,2,3,4,6-penta-*O*-galloyl-β-[d]{.smallcaps}-glucopyranose which facilitates thebinding to membranes leading to the loss of membrane integrity as well as urease inhibition \\[[@bib0025]\\]. ", "Both the CHCl~3~ fraction and EtOH extract of *Calophyllum brasiliense* stem bark has been reported to decrease *H. pylori* and urease activity in Wistar rats as confirmed by histopathology \\[[@bib0030]\\]. ", "The mode of action of mixed cranberry and oregano water extract may be due to inhibition of proline dehydrogenase and urease activvity \\[[@bib0035]\\]. ", "Both*Calotropis procera* and *Acacia nilotica* extracts inhibit urease activity through competitive mechanisms \\[[@bib0040]\\].", "\n\n3.2. ", "Oxidative stress {#sec0025}\n---------------------\n\n2-Methoxy-1,4-naphthoquinoneexhibits strong anti *H. pylori* action. ", "2-methoxy-1,4-naphthoquinone is metabolized in *H. pylori* membrane by flavoenzymes and produces a high amount of free radicals that may damage cellular macromolecules and may lead to *H. pylori* death \\[[@bib0045]\\].", "\n\n3.3. ", "Anti-adhesion activity {#sec0030}\n---------------------------\n\nBorage, parsley, and turmeric water extracts are found to be able to decrease adhesion of *H. pylori* \\[[@bib0050]\\]. ", "The Liquoriceroot aqueous extract and polysaccharides exhibite strong anti-adhesive activity of human gastric mucosa aliquots with fluorescent-labeled *H. pylori* \\[[@bib0055]\\]. ", "The *Pelargonium sidoides* root extract display antiadhesive activity \\[[@bib0060]\\]. ", "The diterpene Plaunotol, isolated from the plau-noi leaves, is also found to inhibit adhesion of *H. pylori* as well as inhibition of IL-8 secretion \\[[@bib0065]\\].", "\n\n4. ", "Structure activity relationship {#sec0035}\n==================================\n\nPlantswith anti H. pylori activityconsist of various phytocompounds, such as alkaloids, flavonoids, saponins, terpenes, and polysaccharides, which responsible for antimicrobial activity ([Fig. ", "2](#fig0010){ref-type=\"fig\"}) are discussed within this review in [Table 2](#tbl0010){ref-type=\"table\"}.Fig. ", "2Mechanisms of action of phytocompounds against microorganisms.", "Fig. ", "2Table 2Restorative herbs having anti-*H. pylori* action.", "Table 2Plant NamesPart and extractActive ingredients responsible for the activityActivityRefs.*Aesculus hippocastanum*EtOH extractSaponin (Aescine)Antisecretory effect\\[[@bib0155]\\]*Acacia nilotica*flower aceton extractNot identifiedUrease inhibitor\\[[@bib0040]\\]*Achillea millefolium*MeOH extract of aerial partsNot identifiedAntioxidant\\[[@bib0225],[@bib0230]\\]*Ageratina pichinchensis*EtOH extract3,5-diprenyl-4-hydroxyacetophenoneMaintaenence NO, PG, SH release\\[[@bib0235]\\]*Ageratum conyzoides*MeOH extract of the entire plantNot identifiedNot detected\\[[@bib0240]\\]*Agrimonia pilosa Ledeb.*Aqueous extract of whole plantNot identifiedNot detected\\[[@bib0245]\\]*Alchornea triplinervia*MeOH and EtOAc extractsNot identifiedAntisecretory\\[[@bib0250],[@bib0255]\\]Increase PGE2Decrease gastric injuriesIncrease mucusPromote epithelial cell*Allium sativum*Oil and aqeous extractThiosulfinatesInterfere with cell wall\\[[@bib0260],[@bib0265],[@bib0270],[@bib0275],[@bib0280]\\]Diallyl disulfideCausing cell lysis and Triggering autolysis*Aloe vera*Polysachharide fractionLectinsIncrease mucus\\[[@bib0285]\\]Inhibit aminopyrin uptakeReduce TNF-α*Alpinia speciosa*EtOH extract of rootNot identifiedInhibit H.pylori\\[[@bib0290]\\]*Amphipterygium adstringens.*CH~2~Cl~2~ extract3a-hydroxymasticadienonic acid, b-sitosterolGastroprotective\\[[@bib0295]\\]3-*epi*-oleanolic acid*Angelica sinensis*EtOH extractPolysaccharide indomethacinInhibition of MPO activity\\[[@bib0300]\\]*Anisomeles indica*Stem and leaves EtOH extractNot identifiedInhibit IL-12 and TNF-α,\\[[@bib0290]\\]*Annona cherimola*Stem and leaves MeOH extractNot identifiedNot detected\\[[@bib0305]\\]*Anthemis altissima*Isolated compounds from arial partSesquiterpene lactonesNot detected\\[[@bib0310]\\]Tatridin-A, sivasinolide, 1-epi-tatridin B, altissin, desacetyl-β-cyclopyrethrosin,*Aralia elata*Root barkAraloside AGastric lesion inhibitor ulcer formation inhibitor\\[[@bib0165]\\]*Arrabidaea chica*HydroEtOHic extract of leavesFlavones and flavonolsInhibit H. pylori\\[[@bib0315]\\]*Artemisia ludoviciana*Leaves and stem aqueous extractArtemisinBactericidal kinetics\\[[@bib0305]\\]Morphological degeneration*Atractylodes ovata*EtOH extractSesquiterpenoid-Inhibition of MMP-2\\[[@bib0320]\\]Atractylenolide III-MMP-9 expression*Bixa orellana*EtOH extract of seedsNot identifiedNot detected\\[[@bib0325]\\]*Boesenbergia rotunda*EtOH extractFlavanoneAntioxidant\\[[@bib0330]\\]PinostrobinDecrease gastric motility*Bombax malabaricum*EtOH extract of rootNot identifiedNot detected\\[[@bib0290]\\]*Boronia pinnata*Whole shrub extractCinnamic acid derivative (boropinic acid)Anti-ulcer agent\\[[@bib0335]\\]*Brassica oleracea*Broccoli sproutsNot identifiedOn human volunteers\\[[@bib0340]\\]*Brazilian propolis*Propolis extract3-hydroxy-2,2dimethyl-8-prenylchromane-propenoic acidAnti-H.pylori invitro\\[[@bib0345]\\]*Bridelia micrantha*Acetone and EtOAc extracts of stem barkNot identifiedAnti-inflammatory\\[[@bib0350],[@bib0355]\\]*Byrsonima crassa*Leaves MeOH and CHCl~3~ extractsNot identifiedImmunostimulatory\\[[@bib0360]\\]*Byrsonima fagifolia*Leaves MeOH extractNot identifiedGastroprotective\\[[@bib0365]\\]AntidiarrhealAntibacterial Immunomodulatory*Byrsonima intermedia*Leaves MeOH extractNot identifiedAntioxidant\\[[@bib0370]\\]*Calophyllum b8rasiliense*Hexane, HydroEtOH extract and Ch~2~Cl~2~ fraction of stem barkMixture of chromanoneDecreased urease,\\[[@bib0030],[@bib0375]\\]Reduce H. pylori in pathological analysis*Calotropis procera*Acetone and MeOH extracts of leaves and flowersNot identifiedUrease inhibitor\\[[@bib0040]\\]*Camellia sinensis*MeOH and water extracts of young shootsCatechinUrease inhibitor\\[[@bib0135],[@bib0380],[@bib0385]\\]Anti-inflammatory*Carum carvi L.*Fruit MeOHNot identifiedNot detected\\[[@bib0390]\\]*Casearia sylvestris*Leaves EtOH extractTerpenoidsDecrease ulcerative size\\[[@bib0395]\\]Eradicate *H. pyloriChamomilla recutita*Oil extract of flowersCatechinUrease inhibitor\\[[@bib0325],[@bib0400],[@bib0405],[@bib0410]\\]70 % aqueousDecreasegastric mucosal injuryMeOH 96 % ethanol*Cinnamomum cassia*Bark aqueous EtOHNot identifiedSuppression of IL-8\\[[@bib0230]\\]*Cinnamomum verum*Essential oils of dry barkCinnamaldehydeUrease inhibitor\\[[@bib0415],[@bib0420],[@bib0425],[@bib0430]\\]*Cistus laurifolius*Flowers CHCl~3~ fractionIsorhamnetinInhibit ulcer\\[[@bib0435],[@bib0440]\\]Kaempferol 3,7-dimethyl ether, quercetin 3,7-dimethyl etherEradicate *H.pyloriCitrus aurantium*EtOH extractMonoterpeneindomethacin, ischemia reperfusion\\[[@bib0445]\\]b-Myrcene*Citrus lemon*Essential oilMonoterpeneMucus production\\[[@bib0450]\\]IndomethacinHSP-70 activationLimoneneVasoactive intestinal peptide and NO releaseMaintenance of PGE2 and glutathione levels*Cocculus hirsutus*EtOH extract of leavesAlkaloidsAnti *H. pylori*\\[[@bib0455]\\]*Cochlospermum tinctorium*Acidified EtOHPolysaccharideAntioxidant\\[[@bib0200]\\]Arabinogalactans IIImmunomodulatory*Combretum molle*Stem bark acetone extract was the bestFlavonoidsGastroprotective\\[[@bib0460]\\]*Coptis chinensis*Rhizome aqueous extractAlkaloidInhibit ulcer\\[[@bib0465]\\]Eradicate *H.pyloriCroton reflexifolius*EtOH extractDiterpenoidGastroprotective\\[[@bib0470]\\]Polyalthic acidBlock sulfhydryl groupsInhibit NO synthase*Croton sublyratus*Leaves extractTerpenoid (Plaunotol)Suppress IL-8 secretion\\[[@bib0475]\\]*Cuminum cyminum*EtOH extracts of seedsPhenolic compoundsAntioxidant\\[[@bib0480]\\]*Cuphea aequipetala*Leaves aqueous extractPhenolic compoundsReduce gastric lesions\\[[@bib0305]\\]Inhibit ulcer*Curcuma amada*Rhizome 70 % EtOHCurcuminInhibit proton potassium ATPase\\[[@bib0485]\\]*Cupressus sempervirens*Essential oilMonoterpenesNot detected\\[[@bib0490]\\]*Curcuma longa*Polyphenolic rich extract of the rootCurcuminChemo-preventative\\[[@bib0495]\\]*Cymbopogon citratus*Essential oilTerpenesInhibit COX\\[[@bib0490]\\]Inhibit NO synthase Activate K^+^ATP channel and α2 receptors.*Cyrtocarpa procera*Hexane extracts from stem barkNot identifiedGastroprotective\\[[@bib0295],[@bib0305],[@bib0500]\\]Anti-inflammatory*Davilla elliptica*Leaves MeOH extractNot identifiedAnti-inflammatory Gastroprotective\\[[@bib0505]\\]*Davilla nítida*Leaves MeOH extractNot identifiedAnti-inflammatory Gastroprotective\\[[@bib0505]\\]*Daucus carota*Essential oil of seedCarvacrol and nerolDecrease pH\\[[@bib0510]\\]*Derris trifoliate*Petroleum ether and stemCHCl~3~ extractsNot identifiedEradicate *H. Pylori*\\[[@bib0515]\\]Gastroprotective*Desmostachya bipinnata*WholeplantFlavonoids (4-methoxy quercetin-7-O-glucoside)Chemopreventive agent\\[[@bib0520],[@bib0525]\\]Diethyl ether extract*Dittrichia viscosa*Aerial parts essential oil (Oxygenated fractions)3-methoxy cuminyl isobutyrateAntibacterial action\\[[@bib0405],[@bib0530]\\]*Eucalyptus torelliana*Hexane extract of leavesSaponin and taninnsDecrease gastric acid\\[[@bib0535]\\]Increase pH gastric juice*Eugenia caryophillus*EtOH extracts of flowersEugenolIncrease activity at acidic pH\\[[@bib0420],[@bib0540]\\]*Eugenia caryophyllata*Flowers aqueous extractEssential oilAnti-inflammatory\\[[@bib0245]\\]*Eupatorium aschenbornianum*EtOH extractChromeneAntioxidant activity\\[[@bib0545]\\]Encecanescin*Evodia rutaecarpa*Alkaloids rich extract1-Methyl-2-\\[(Z)-7-tridecenyl\\]-4-(1 H)-quinoloneAnti-inflammatory\\[[@bib0550]\\]Very strong Anti-H.pylori*Feijoa sellowiana*Fruit Acetone ExtractFlavoneInhibit H^+^/K^+^ATPase activity and Increase PGE~2~\\[[@bib0555]\\]*Ferulago campestris*Root extractCoumarins (Aegelinol and Benzoyl aegelinol)Not detected\\[[@bib0560],[@bib0565],[@bib0570],[@bib0575]\\]*Foeniculum vulgare*MeOH extract of the seedsNot identifiedAntioxidant\\[[@bib0225],[@bib0230]\\]*Garcinia achachairu*Acidified ethanol of the seedsPolyisoprenylated benzophenoneGastroprotective\\[[@bib0580]\\]Guttiferone A*Geranium wilfordii*EtOH extracts and EtOAc fraction1,2,3,6-tetra-O-galloyl-β-[d]{.smallcaps}-glucose and corilaginNot detected\\[[@bib0585]\\]*Geum iranicum*Aqueous fraction of the rootsTanninsGastroprotective\\[[@bib0590]\\]Eugenol*Glycyrrhiza glabra*Water extract of the rootPolysaccharideAnti-adhesive activity\\[[@bib0055],[@bib0145]\\]Flavonoids (glabridin)Inhibit dihydrofolate reductaseInhibit DNA gyrase*Glycyrrhiza uralensis*MeOH extract of rootslicoricidin licoisoflavone BChemopreventive agents\\[[@bib0595],[@bib0600]\\]licoric*Guaiacum coulteri*Bark MeOH extractNot identifiedAntibacterial action\\[[@bib0305]\\]*Hancornia speciose*Hydroalcoholic extract of the barkNot identifiedAntibacterial action\\[[@bib0605]\\]*Hericium erinaceus*Hydroalcoholic extract of barkNot identifiedAntibacterial action\\[[@bib0610]\\]*Hydrastis canadensis*MeOH extract of rhizomeIsoquinoline alkaloidsInhibit bacterial efflux pumps, Inhibit of nucleic acid synthesis, Inhibite the enzyme dihydrofolate reductase\\[[@bib0615],[@bib0620],[@bib0625],[@bib0630]\\]BerberineHydrastine*Hyptis suaveolens*EtOH extractDiterpene, Indomethacin\\\nSuaveololNO, PGE2, SH compounds\\[[@bib0635]\\]*Impatiens balsamina*Pod acetone, EtoAc, terpenoid fraction2Methoxy1,4naphthoquinoneProduce ROS to damage *H pylori* cell membrane\\[[@bib0045]\\]Stigmasta7,22-diene3βol*Ixeris chinensis*Boiling water,EtOH and CHCl~3~ extract was the active oneNot identifiedAntibacterial\\[[@bib0640]\\]AntiadhesiveAnti-inflammatoryInhibit IL-8, NO, TNF-α*Jatropha isabelli*Acidified EtOHMonoterpeneGastroprotective\\[[@bib0645]\\]1,4-Epoxy-ρ-menthan- 2-olSesquiterpeneCyperenoic acidTriterpeneAcetyl aleuritolic acid9b,13a- DihydroxyisabellioneDiterpeneJatropholone AJatropholone B Jatrophone*Juglans regia*Fruit MeOH extractXanthanolideNot detected\\[[@bib0650]\\]*Larrea divaricata*Branches and leaves aqueous extractNordihydroguaiaretic acidAnti-inflammatory\\[[@bib0655]\\]GastroprotectiveAnti-gastric cancer*Lycopodium cernua*Whole plant hexane extractThe powerful compound was found in hexane fractionNot detected\\[[@bib0240]\\]*Magnoliae officinalis*Ether fraction of cortexMagnololAntigastritic, antioxidant, neutralize acid, inhibit the secretion of gastric acid\\[[@bib0660]\\]*Mallotus phillipinesis*70 % EtOH extract of fruitIsorottlerin, rottlerinNot detected\\[[@bib0485]\\]3′-prenylrubranine, 5,7-dihydroxy-8-methyl-6-prenylflavanone*Malva sylvestris*Inflorescence and leaves EtOH ExtractNot identifiedNot detected\\[[@bib0325]\\]*Mangifera indica*Pet-ether and EtOH extracts of leavesMangiferinGastroprotective Antisecretory, antioxidant\\[[@bib0665],[@bib0670]\\]*Mentha piperita*Leaves andstem aqueous extractEssential oilantisecretory,antioxidant, anti-inflammatory, and antiapoptotic actions\\[[@bib0305]\\]Menthol*Mentha sp.*EtOH extractMonoterpeneIncrease PGE2\\[[@bib0190],[@bib0195]\\]Indomethacin pyloric ligatureAntiapoptotic,AntioxidantMentholAnti-inflammatory*Morus alba*leaves EtOH extractSteroid, AlbosteroidAntisecretory\\[[@bib0675],[@bib0680]\\]Pyloric ligatureAntioxidant*Mitrella kentii*EtOH extractChalconeAntiapoptotic, antioxidant\\[[@bib0685]\\]Desmosdumotin CInhibit COX-2*Musa acuminata*Crude flavonoids extractFlavonoidsIncrease mucus\\[[@bib0690],[@bib0695]\\]Leucocyanidin*Myristica fragrans*MeOH extracts of seeds and aerial partsNot identifiedGastroprotective\\[[@bib0485],[@bib0700]\\]*Myroxylon peruiferum*Isolated compoundIsoflavoneInhibit NADH oxidation\\[[@bib0705]\\]Cabreuvin*Myrtus communis*Essential oilMonoterpenesInhibit urease\\[[@bib0430],[@bib0710]\\]*Olea europaea*Leaves MeOH extractNot identifiedIncrease gastric flora\\[[@bib0715]\\]Reduce H. pylori*Ocimum sanctum*Fixed oilNot identifiedInhibit lipoxygenase\\[[@bib0720]\\]AntisecretoryHistamine antagonistic*Origanum majorana L.*Aerial parts MeOH extractPhenolic compoundsEnhance protective host defence\\[[@bib0225]\\]*Oroxylum indicum*Crude Flavone glycosides7-*O*-methylchrysin, 5-hydroxy-749-dimethoxyflavone, oroxylin A, chrysin, and baicaleinGastroprotective\\[[@bib0725],\\\n\\[[@bib0730]\\]*Paeonia lactiflora*Root lipid fractionLysophosphatidic acid\\\nPaeonol\\\nbenzoic acid\\\nmethyl gallate,1,2,3,4,6-penta- *O*-galloyl-β -D-glucopyranoseIncrease PG E2\\\nDecrease membrane integrity\\\nInhibit urease\\\nInhibit UreB (an adhesin)\\[[@bib0025],[@bib0735]\\]*Panax ginseng*Polysaccharides fractionGalacturonic acidAnti-adhesive\\[[@bib0740],[@bib0745]\\]*Papaver somniferum*AlkaloidsPorphineNot detected\\[[@bib0750]\\]*Pausinystalia yohimbe*AlkaloidsYohimbineDecrease ulcer\\[[@bib0220]\\]*Peperomia pellucida*EtOH extractAllylbenzene\\\nDillapioleGastroprotective\\[[@bib0755]\\]*Persea americana*MeOH extracts of leafProcyanidinsInhibit urease\\[[@bib0305]\\]*Piper carpunya*Flavonoids rich extract of the leavesVitexin\\\nIsovitexin Rhamnopyranosylvitexin\\\nIsoembigeninReleasemyeloperoxidase\\\nInhibite H+,K + ATPase activity *N*-Acetylation\\[[@bib0770]\\]*Piper multiplinervium*Hydroxybenzoic acid prenylated derivative3-farnesyl-2-hydroxybenzoic acidTreat stomach aches\\[[@bib0775]\\]*Pistacia lentiscus*Mastic gumTriterpenic acidsInduce blebbing\\\nCellular fragmentation Morphological abnormalities in H. pylori cells\\[[@bib0780],[@bib0785],[@bib0790],[@bib0795]\\]*Plectranthus grandis*EtOH extractDiterpenes\\\n3b-Hydroxy-3- deoxibarbatusin BarbatusinK^+^ATP channel NO, TRPV1 channels\\[[@bib0800]\\]*Plumbago zeylanica*EtOAc of rhizomeNaphthoquinone\\\nPlumbaginBactericidal activity\\[[@bib0290],[@bib0805]\\]*Polygala cyparissias*EtOH extractXantoneAnti-ulcer\\\nGastroprotective\\[[@bib0810]\\]*Polygonum tinctorium*Leaf juiceTryptanthrin\\\nKaempferoldecrease numbers of colonies in gerbils stomachs\\[[@bib0815]\\]*Polygala cyparissias*EtOH extractSterol\\\na-SpinasterolReduce percentage of lesion area\\\nReduce ulcer index\\[[@bib0810]\\]*Potentilla fruticose*Aqueous extracts of aerial partNot identifiedAntibacterial action\\[[@bib0820]\\]*Prunus dulcis*Polyphenol-rich extracts of skinProtocatechuic acidPost gastric plus duodenal digestion\\[[@bib0825]\\]*Prumnopitys andina*Acidified EtOHDiterpene, acetic acid\\\nFerruginolPGE2 production\\\nInhibit lipoperoxidation\\[[@bib0185]\\]*Psoralea corylifolia*Seeds extractPsoracorylifolsAntibacterial\\[[@bib0830]\\]*Pteleopsis suberosa*MeOH extract of stem barkOleanane saponine Arjunglucoside IAnti*vacA/cagA* positive and metronidazole-resistant strains\\[[@bib0835]\\]*Punica granatum*EtOH, MeOH, BuOH and aqueous extracts from fruit peelPhenolic compoundsChang hydrophobicity of *H. pylori* cell surface\\[[@bib0650],[@bib0840],[@bib0845]\\]*Phyllanthus niruri*Aqueous extracts of leavesEllagic acid\\\nHydroxycinnamic acidDamage *H.pylori* cell membrane\\[[@bib0515],[@bib0760]\\]*Physalis alkekengi*EtOAc extract of the aerial partsQuercetin\\\nPhysalindicanols A kaempferol Blumenol AAntiinflammatory\\\nAntiulcer invivo\\\nAnalgesic\\[[@bib0765]\\]*Qualea parviflora*MeOH extract of barkTriterpenes\\\nSaponinsMaintaine GSH levels Increase SH compounds\\\nStimulate PGE2 synthesis\\[[@bib0850]\\]*Rabdosia trichocarpa*MeOH extract from entire plantsDiterpene\\\nTrichorabdal AStrong antibacterial action\\[[@bib0855]\\]*Rhei Rhizoma*RhizomeEmodinDamage DNA *H. Pylori*\\[[@bib0150]\\]*Rheum palmatum*RhizomeRheinInhibite *N-*acetyltransferase\\[[@bib0860]\\]*Rheum rhaponticum L.*Root EtOH ExtractNot identifiedAnti-inflammatory\\[[@bib0280]\\]*Rosmarinus officinalis*Leaves MeOH extractNot identifiedAntiulcer, vasodilator\\\nGastroprotective\\[[@bib0225]\\]*Rubus imperialis*EtOH extractTriterpene\\\n2b,3b-19a-Trihydroxy ursolic acidNot detected\\[[@bib0865]\\]*Rubus ulmifolius*Leaves extract FlavonoidsEllagic\\\nKampferolReduce gastric PH\\\nParticipate No and SH\\[[@bib0130]\\]*Ruta graveolens*Aqueous EtOH extract of leavesPolyphenolsAntioxidant\\\nAnti-inflammatory\\\nInhibit IL-8 secretion\\[[@bib0230]\\]*Salvia mirzayanii*MeOH extract of leavesNot identifiedNot detected\\[[@bib0870]\\]*Sanguinaria Canadensis*MeOH extracts of rhizomeSanguinarine, chelerythrine, two benzophenanthridine alkaloidsAnti ulcer\\[[@bib0615],[@bib0875]\\]*Santalum album*hydro-alcoholic extract of stem(Z)-R-santalol (7), (Z)-β-santalol, (Z)-lanceolStrong antiulcer\\[[@bib0880]\\]*Schinus molle*EtOH extractFlavonol, RutinAntioxidant\\[[@bib0885]\\]*Sclerocarya birrea*Essential oilTerpinen- 4-olDecrease membrane integrity\\[[@bib0550],[@bib0890]\\]*Senecio brasiliensis*InflorescencesIntegerrimine, retrorsine, senecionine, usaramine, and seneciphyllineIncrease mucus\\[[@bib0210],[@bib0215]\\]Pyrrolizidine alkaloidsIncrease PG*Simaba ferruginea*Rhizome fractionsAlkaloidAntiulcerogenic\\[[@bib0205]\\]Canthin-6-oneReduce myeloperoxidase malondialdehydeReduce plasma IL-8*Scleria striatinux*MeOH extract of rootsOkundoperoxideAntibacterial\\[[@bib0240]\\]*Solanum paniculatum L.*New isolated steroids saponinsdiosgenin 3-*O*-b-d-glucopyranosyl(10 → 69)-*O*-b-d-glucopyranoiside.", "Decrease gastric lesion\\[[@bib0895]\\]Decrease levels of MPO in the mucosa*Sphacele chamaedryoide*EtOH extract DiterpeneHorminone, CarnosolGastroprotective\\[[@bib0900]\\]TaxoquinoneInhibit gastric lesions*Stachys setifera*MeOH extracts of leavesNot identifiedNot detected\\[[@bib0905]\\]*Strychnos pseudoquina*Leaves MeOH extractAlkaloid enriched fractionIncrease cell proliferation in gastric mucosa\\[[@bib0910]\\]*Syzygium aromaticum*Flower budsFlavonoidsAntiulcerogenic\\[[@bib0915],[@bib0920]\\]TanninsAntisecretoryIncrease PGE*Tabebuia impetiginosa*Inner bark(hydroxymethyl)anthraquinStrong antibacterial\\[[@bib0925]\\]anthraquinone-2-carboxylicLapachol, plumbagin*Termitomyces eurhizus*MushroomPolysaccharides fractionStimulate mucosal regeneration and proliferation\\[[@bib0930]\\]Restoring gastric mucusIncrease PG E2Modulate COX-1 and COX-2Reduce TNF-α and IL-1b*Terminalia spinosa*Young branches crude extractNot identifiedNot detected\\[[@bib0935]\\]*Terminalia chebula*Aqueous extracts of fruitChebulinic acidImprove secretory of B runner gland\\[[@bib0940],[@bib0945],[@bib0950]\\]Ethyl gallate gallic acid*Thymus vulgaris*Essential oilsMonoterpenesGastroprotective\\[[@bib0955]\\]Anti-inflammatory*Tithonia diversifolia*EtOH extractSesquiterpeneGastroprotective\\[[@bib0960]\\]Indomethacin, Tagitinin C*Trachyspermum copticum*Mixture of petroleum / MeOH extract of fruit and leavesNot identifiedAntibacterial\\[[@bib0390],[@bib0965]\\]*Vaccinium macrocarpon*Cranberry juicePolyphenolsAnti-adhesive\\[[@bib0970],[@bib0975]\\]*Vitis venefera*Grape seedsResveratrolChemopreventative\\[[@bib0020]\\]FlavonoidsAntioxidant*Xanthium brasilicum*Aerial parts MeOH, diethyl ether and benzeneNot identifiedAntimicrobial\\[[@bib0390]\\]*Zataria multiflora*Essential oils of aerial partsThymol, carvacrolEnhance mucosa Cytoprotective\\[[@bib0415],[@bib0980]\\]*Zingiber officinalis*Root extract6-gingesulphonic acidInhibit thromboxane synthetase\\[[@bib0225],[@bib0985],[@bib0990],[@bib0995],[@bib1000],[@bib1005],[@bib1010]\\]6-shogaol, ArcurcumeneGingerols[^1]\n\n4.1. ", "Sterol {#sec0040}\n-----------\n\nThe presence of a free OH group in C-3 is necessary for the antiulcer action of triterpenoids and sterols consistently, the only structural difference between the active 3a-hydroxymasticadienonic acid ([Fig. ", "3](#fig0015){ref-type=\"fig\"}, 1) and the inactive masticadienonic acid ([Fig. ", "3](#fig0015){ref-type=\"fig\"}, 2) is the presence of an OH group and a C000000000000 000000000000 000000000000 111111111111 000000000000 111111111111 000000000000 000000000000 000000000000O group in the C-3 \\[[@bib0070],[@bib0075]\\].Fig. ", "3Chemical structure of 3a-hydroxymasticadienonic acid (1) and masticadienonic acid (2).Fig. ", "3\n\n4.2. ", "Flavonoids {#sec0045}\n---------------\n\nFlavonoids have been used in the treatment of countless diseases \\[[@bib0080], [@bib0085], [@bib0090], [@bib0095], [@bib0100], [@bib0105]\\]. ", "Flavonoids ([Fig. ", "4](#fig0020){ref-type=\"fig\"}) are found to display as antisecretory and cytoprotective agents by increasing PG levels, inhibiting *H. pylori*, decreasing histamine, and antioxidants \\[[@bib0110]\\]. ", "The structure activity relationship shows that the presence of OCH~3~ group in the C-5 or C-7 positions, the double bonds at C-2 and C-3 and the presence pof an intact C-ring appear to increase gastroprotection potential. ", "On the other hand, substitution with OH or OCH~3~ groups at C-3, C-6, or C-8 diminish the gastroprotective action.", "Fig. ", "4Chemical structure of anti-H.Pylori flavonoids 1) Quercetin 2) Kampferol 3) Catchin 4) tryptanthrin 5) Apigenin 6) Glabridin 7) Emodin.", "Fig. ", "4\n\nFlavonoids can kill microbs by 1) membrane disruption by apigenin, catechin, naringenin, quercetin, and rhamnetin and inhibition of nucleic acid synthesis 2) inhibit dihydrofolate reductase by epicatechin, 3) inhibithelicase by luteolin and myricetin, d) inhibitgyrase/topoisomerase by apigenin, kaempferol and quercetin, 4) inhibit bacterial virulence by quercetin and kaempferol 5) inhibit quorum sensing by epicatechin, naringenin, quercetin and kaempferol 6) inhibit fatty acid synthase and peptidoglycan synthesis by taxifolin, kaempferol, luteolin, myricetin and quercetin7) inhibit Ala--Ala dipeptide synthesis by gaiangin, kaempferol, and kaempferol-3-*O*-glucoside, 8) inhibitpeptidoglycan crosslinking by apigenin and quercetin. ", "9) inhibit refflux pumps by diadzein, genistein, epicatechin and quercetin10) inhibit NADH-cytochrome c reductase activity in the bacterial respiratory chain by chalcon11) inhibit ATP synthase by epicatchin, quercetin, quercetrin, and silymarin \\[[@bib0115]\\].", "\n\nAs shown in [Fig. ", "4](#fig0020){ref-type=\"fig\"}, quercetin decreases lipid peroxide and neutrophil leukocyte infiltration, in the *H. pylori* colonization \\[[@bib0120]\\]. ", "The blend of kaempferol and tryptanthrin reduce the viability of *H. pylori* invivo \\[[@bib0125],[@bib0130]\\]. ", "Upon giving green tea product that is consisted of catechin to *H. pylori*-infected Mongolian gerbils, both of gastritis and the prevalence of *H. pylori* were significantly suppressed \\[[@bib0135]\\]. ", "Besides, apigenin treatments effectively eradicated *H. pylori,* atrophic gastritis, and gastric cancer rates in *H. pylori*-infected Mongolian gerbils. ", "Apigenin is reported to have excellent ability to inhibit *H. pylori* as well as possessing potent anti-gastric cancer \\[[@bib0140]\\]. ", "As for Glabridin, it possesses a strong inhibitory effect on dihydrofolate reductase and DNA gyrase \\[[@bib0145]\\]. ", "While emodin; a major phytocompound of *Rhizoma Rhei* induces *H. pylori* DNA damage \\[[@bib0150]\\].", "\n\n4.3. ", "Steroid saponin {#sec0050}\n--------------------\n\nAescine ([Fig. ", "5](#fig0025){ref-type=\"fig\"}) reduces the severity of ulcers by decreasing gastric secretion \\[[@bib0155]\\], while Ginsenoside increases the amount of mucus \\[[@bib0160]\\].Fig. ", "5Chemical structure of Aescine (1) and Ginsenoside (2).Fig. ", "5\n\nAccording to Lee et al. ", "\\[[@bib0165]\\], the saponins display antisecretory action by inhibiting acid secretion, total acid output, and lowering the pH of gastric juice \\[[@bib0170]\\].", "\n\n4.4. ", "Terpenes {#sec0055}\n-------------\n\nNerolidol ([Fig. ", "6](#fig0030){ref-type=\"fig\"}) has an antiulcerogenic and cytoprotective effect by increasing mucus production via increasing the PG, improving the gastric blood flow, and increasing the secretion of gastric bicarbonate and mucus \\[[@bib0175]\\]. ", "In addition, terpenoids act as antioxidants, reduce the lipid peroxidation levels, and increase the activity of antioxidant enzymes in the gastric mucosa \\[[@bib0180],[@bib0185]\\]. ", "Menthol is a monoterpene that increases the maintenance of SH compounds and the amount of mucus and PG production. ", "It also possesses an antisecretory effect, in addition to antioxidant, anti-inflammatory, and antiapoptotic actions \\[[@bib0190],[@bib0195]\\]. ", "Oleanolic acid is a triterpene that improves healing in the ulcer model. ", "The low toxicity and the widespread occurrence in various plants support the potential development of new antiulcer drug based on triterpenes or their derivatives \\[[@bib0185]\\].Fig. ", "6Chemical structure of anti-H.pylori terpens 1) Nerolidol 2) Menthol 3) Oleanolic acid.", "Fig. ", "6\n\n4.5. ", "Polysaccharides {#sec0060}\n--------------------\n\nArabinogalactan ([Fig. ", "7](#fig0035){ref-type=\"fig\"}) has the ability to bind on the gastric mucosa acting as a protective layer, in addition to its antisecretory activity towards gastric juice. ", "The mucosal protective activity of Arabinogalactan is provided by an increased mucus synthesis and free radical scavenging activity. ", "The particular mechanisms of polysaccharides are described by their potential to bind on the surface of the gastrointestinal mucosa, thereby acting as a protective layer, in addition to their antisecretory action. ", "Their mucosal protective potentials are provided by an increased mucus synthesis and their antioxidant activity. ", "Pectic polysaccharides obtained by aqueous extraction represent examples of the main polysaccharides displaying gastric antiulcer action \\[[@bib0200]\\].Fig. ", "7chemical structure of Arabinogalactan.", "Fig. ", "7\n\n4.6. ", "Alkaloids {#sec0065}\n--------------\n\nCanthin-6-one ([Fig. ", "8](#fig0040){ref-type=\"fig\"}), isolated from *Simaba ferruginea* rhizome has been shown to be antiulcerogenic \\[[@bib0205]\\], while integerrimine isolated from *Senecio brasiliensis* was found to increase mucus and PG levels \\[[@bib0210],[@bib0215]\\]. ", "Melatonin, as a hormone, has the ability to scavenge free radical and ameliorating gastric blood flow \\[[@bib0215]\\]. ", "Yohimbine, isolated from *Pausinystalia yohimbe*, decreases ulcers \\[[@bib0220]\\].Fig. ", "8Chemical structure of Melatonin (1), Canthin-6-one (2), Integerrimine (3), Yohimbine (4).Fig. ", "8\n\n5. ", "Conclusion {#sec0070}\n=============\n\n*H. pylori* inhibition with antibiotic therapies has a limitation mainly owing to antibiotic resistance. ", "Medicinal herbs provide another opportunity to inhibit *H. pylori*. ", "Medicinal herbs might also provide successful approach to decrease stomach cancer. ", "However, potential cytotoxicity and side effects might present from those herbs. ", "Therefore, further cytotoxicity investigation will be required.", "\n\nDeclaration of Competing Interest\n=================================\n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.", "\n\n[^1]: Methanol: MeOH; Ethanol: EtOH; Butanol: BuOH; Dichloromethan: CH~2~Cl~2;~ Chloroform:CHCl~3~; Prostaglandin: PG; Tumor necrosis factor: TNF; Interlokin: IL; Cyclooxiginase: COX; Nitric oxide: NO; sulfhydryl : SH.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Q:\n\nIs there a way to detect when a standard iPhone View Controller push/pop animation has completed?", "\n\nFor custom animations in my app, I can use the setAnimationDidStopSelector: method to respond to the event that an animation has finished. ", " Is there a similar kind of mechanism for detecting that the animation has finished for a standard View Controller animation transition for pushes and pops? ", "\n(i.e. [self.navigationController pushViewController:vc animated:YES])\n\nA:\n\nI think you can try to overide the method:\n- (void)viewDidAppear:(BOOL)animated\n\nThis method will be called after your view appeared\nIn the interface comment for the code:\n- (void)viewWillAppear:(BOOL)animated; // Called when the view is about to made visible. ", "Default does nothing\n\n- (void)viewDidAppear:(BOOL)animated; // Called when the view has been fully transitioned onto the screen. ", "Default does nothing\n\nSo I think that if you override the viewDidAppear and put your logic here, the code will be executed exactly after the transition finished\nMore in viewWillAppear and viewDidAppear\n\n" ]
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[ "On Monday, the Investigatory Powers Tribunal, a special court that handles complaints related to British spy agencies, found that access to the datasets had not been subject to sufficient supervision through a 17-year period between 1998 and November 2015. ", "The tribunal said that due to “failings in the system of oversight” the surveillance regime had violated Article 8 of the European Convention on Human Rights, which protects the right to privacy.", "\n\nThe case was brought in June 2015 by the London-based human rights group Privacy International, which challenged the legality of the surveillance after the British government publicly admitted using an obscure provision of the 1984 Telecommunications Act to harvest the data.", "\n\n“Today’s judgment is a long overdue indictment of U.K. surveillance agencies riding roughshod over our democracy and secretly spying on a massive scale,” said Millie Graham Wood, legal officer at Privacy International. “", "It is unacceptable that it is only through litigation by a charity that we have learnt the extent of these powers and how they are used. ", "The public and Parliament deserve an explanation as to why everyone’s data was collected for over a decade without oversight in place and confirmation that unlawfully obtained personal data will be destroyed.”", "\n\nWhile the tribunal found that the mass collection of data lacked adequate oversight, it did not rule that the surveillance itself was illegal. ", "The judgment found in favor of the government on that front, stating that the use of the Telecommunications Act to harvest the bulk datasets was lawful.", "\n\nA spokesperson for the U.K. government said in a statement: “The powers available to the security and intelligence agencies play a vital role in protecting the U.K. and its citizens. ", "We are therefore pleased the tribunal has confirmed the current lawfulness of the existing bulk communications data and bulk personal dataset regimes.”", "\n\nAccording to documents that were released earlier this year, the bulk datasets can cover a wide variety of information, potentially revealing details such as people’s political opinions, religious beliefs, union affiliation, physical or mental health status, sexual preferences, biometric data, and spending habits. ", "They may also contain data revealing legally privileged information and journalists’ confidential sources. ", "And the spy agencies have acknowledged that “medical data may appear” in some of the data troves, too, though they claim they do not explicitly harvest people’s medical records.", "\n\nIt is often argued by government officials that mass collection of data is not on its face a violation of privacy, and that privacy is not breached until individual communications are looked at or analyzed by humans.", "\n\nNotably, the tribunal’s ruling on Monday disagreed with that notion, stating that the privacy protections contained in the European Convention on Human Rights are “engaged by the transfer and storage of communications data even if it is not accessed.” ", "This principle may turn out to be important in a separate case that remains ongoing in the European Court of Human Rights, which is expected to look more closely at the legality of the U.K.’s mass surveillance programs.", "\n\nTop photo: GCHQ headquarters in Cheltenham, England.", "\n\nWe depend on the support of readers like you to help keep our nonprofit newsroom strong and independent. ", "Join Us" ]
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[ "When a man died some 4,000 years ago in what is now western Greenland, he probably had no idea that his remains would provide the first genetic portrait of people of his era. ", "This man, known now as \"Inuk\" (a Greenlandic term for \"human\" or \"man\") left for posterity just four hairs and a few small fragments of bone frozen in permafrost, but that is now all researchers need to assemble a thorough human genome.", "\n\n\n\nAnd Inuk has just had his code cracked.", "\n\n\n\nThe researchers were able to sequence about 80 percent of the ancient genome, which is \"comparable to the quality of a modern human genome,\" Eske Willerslev, director of the Center for Ancient Genetics at the University of Copenhagen, said at a press conference held in the England February 9. ", "He and his team, led by Morten Rasmussen, an assistant professor at the University, were able to sequence about three billion base pairs (the human genome includes just over this amount), which is a finer resolution than that of previous genetic work on Neandertals and mammoths. ", "Their findings will be published February 11 in the journal Nature. (", "Scientific American is part of Nature Publishing Group.)", "\n\n\n\nAt this level of resolution, the researchers noted, individual features and traits began to emerge. \"", "The guy had most likely brown eyes, brown skin\" as well as a genetic predisposition for baldness, Willerslev said. ", "The presence of hair, then, might signal that he was rather young when he died and had yet to lose most of his hair, they noted. ", "The genome also tells us Inuk had the recessive gene for dry earwax (as opposed to the more common wet form) and \"a metabolism and body mass index commonly found in those who live in cold climates,\" David Lambert and Leon Huynenboth of the School of Biomolecular and Physical Sciences at Griffith University in Queensland, Australia, wrote in a commentary that accompanies the study.", "\n\n\n\nAside from painting a detailed picture of the individual the base pairs belonged to, the ancient code can tell scientists a lot about early human migration, much of which has so far been gleaned from archaeological sites and genetic studies of more contemporary people.", "\n\n\n\nThe researchers estimate that Inuk's forbearers arrived in the northern New World (which includes Alaska, Canada and Greenland) some 5,500 years ago, but neither they nor he are closely related to the populations of people that inhabit that part of the globe today, as many have proposed.", "\n\n\n\n\"People have been puzzled by the relation of these inhabitants,\" Willerslev said. ", "Two subsequent waves of cultures arrived in the Arctic area, and this new genetic study shows that Inuk's group, of the Saqqaq culture, was of the earliest and does not appear to have intermixed with later inhabitants. \"", "We can show that this individual was neither a direct relative of Inuits or Native Americans,\" Willerslev said. ", "In fact, Rasmussen noted, \"their closest living relatives are [a population] in Siberia now.\" ", "Such a definitive finding might clear up some of the mystery surrounding this culture's origins, which Lambert and Huynen described as \"hotly debated.\" ", "But it still does not reveal just how or why the Saqqaq came to Greenland in the first place—or what caused their eventual demise.", "\n\n\n\nInuk's remains were originally retrieved in the 1980s, the researchers noted, but then largely forgotten. ", "This period of obscurity actually helped to render them good candidates for sequencing, as it minimized the potential for contamination with contemporary human genetic material. \"", "The main difficulty with such work is that almost all excavated ancient tissues are contaminated with modern human DNA, not to mention substantial numbers of fungal and bacterial colonies,\" Lambert and Huynen wrote in their commentary. ", "To overcome this challenge, the researchers studying Inuk found that everyone who was known to have handled the samples was of European descent, so they could test for contamination by looking for traces of modern European DNA. ", "If it had been handled by someone with a similarly Asian background, the results might have been a little hazier, the researchers explained at the press conference. ", "Hair, as opposed to bone or other biological materials, is also typically less prone to fungal or bacterial growth, they said.", "\n\n\n\nAlthough Inuk's genome is the first ancient sample to be thoroughly sequenced, the researchers do not expect that it will be the last. ", "More rapid and accessible sequencing is feeding the field, Rasmussen noted. \"", "As prices go down, it will be easier to do these types of projects,\" he said. ", "Indeed, noted Lambert and Huynen in their commentary: \"We have an increasingly powerful forensic tool with which to 'reconstruct' extinct humans and the demographics of populations.\"", "\n\n\n\nSolid biological samples from millennia past might not be as common as stone tools or other archaeological evidence, but there are plenty of other candidates for sequencing, Willerslev noted. ", "The limiting factor will likely not be the number of specimens or even their potential contamination, Rasmussen said: \"What will limit us is fragment size.\" ", "In order to come up with enough genomic material to sequence and check as many as 20 times over, researchers need a large enough biological sample to study.", "\n\n\n\nSuch detailed insight can also provide new information about genetic mutations—from skin tone to genetic disease risk—across the millennia. ", "Establishing that sequencing the genome of ancient individuals is possible \"opens up the possibility to go back in time and see\" when genetic diseases became prevalent in different populations, Willerslev said. ", "And for more modern populations that met recent ends, such as many Native American groups and native Tasmanians, genetic sequencing can answer some previously unknowable information about those groups." ]
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[ "Q:\n\njavascript for jinja template\n\nI am trying to use a Jinja template to consume data to populate a webpage.", "\nThe code is:\n\"\n<div class=\"container\">\n <button type=\"button\" class=\"btn btn-md btn-info collapsed\" data-toggle=\"collapse\" data-target=\"#title\">Programme Title</button>\n <div id=\"title\" class=\"collapse\">\n <!-- ", "START of TABLE --> \n\n <table>\n <thead>\n <th> Programme Title </th>\n <th class=\"midc\"> Lead (s) </th>\n <th class=\"midc\"> Theme </th>\n <th class=\"midc\"> Cluster </th>\n </thead>\n <tbody>\n {% for p in progs %}\n <tr>\n <td><a href=\"programmes/{{ p.programme_ID }}\"><mark>{{ p.Programme }}</mark></a> </td>\n {% endfor %} \n <td>\n {% for pc in pclus %}\n <label for=\"content\"> Lead(s) </label>\n <select name=\"staffroles\">\n <option value=Null></option>\n {% if pc.cluster_ID == pclus % } \n <option value={{ p.cluster_ID }} selected> {{ p.Name }}</option>\n {% else %}\n <option value={{ pc.cluster_ID }}> {{ p.Name }}</option>\n {% endif %}\n </td>\n <td class=\"midc\"> {{ p.cluster_id }} </td>\n </tr> \n {% endfor %}\n </select>\n </tbody>\n\n </table>\n\n </div>\n <!-- ", "END OF TABLE -->\n</div> \n\nThe second block \"{% for pc in pclus %}\" is for a drop-down list.", "\nI had a block of code commented out. ", "I removed the commented out code.", "\nI got a new error message.", "\nError message:\njinja2.exceptions.", "TemplateSyntaxError: unexpected '}'\n\nA:\n\nIn your line {% if pc.cluster_ID == pclus % }, there is an extra space at the end right before the }, which makes jinja think that if pc.cluster_ID == pclus % is a complete python statement. ", "Remove the space and the error should be gone.", "\n\n" ]
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[ "1. ", "Field of the Invention\nThis invention relates to a material removing machine and more particularly to a high speed high pressure belt grinder.", "\n2. ", "Description of the Prior Art\nNumerous metal removal apparatus and methods are disclosed in the prior art. ", "Milling machines, vertical spindle grinders, double disc grinders, face broches, and planars have been utilized for removing material from flat planar surfaces. ", "The prior art also includes numerous belt grinding machines for material removal.", "\nU.S. Pat. ", "No. ", "3,668,814 issued to C. T. Freerks recognizes that with high pressure belt grinder, above a predetermined minimum pressure, metal is removed so swiftly that a large percentage of the heat generated is removed by the chips. ", "This results in a temperature rise of a work piece which is greatly reduced as compared with the temperature rise of the work piece when it is ground at pressures below the predetermined minimum pressure, so that damage to the part and to the abrasive belt is minimized.", "\nU.S. Pat. ", "No. ", "3,132,451 to J. A. Kline recognizes some of the problems such as clouding, dirt, or the like with respect to photoelectric detection. ", "Kline describes an air pressure sensitive system which may not be satisfactory at high belt speeds due to the boundry layer of air which causes false pressure differentials.", "\nSome other prior art patents such as U.S. Pat. ", "No. ", "2,813,383 issued to Pendergast tilt the idler pulley severly to achieve belt shift, and this may lead to premature belt failure.", "\nIt has been recognized that it is desirable to move the grinding belt relative to the work piece for uniform belt wear. ", "This has typically been achieved in the prior art by moving the belt back and forth along the contact and idler pulley. ", "The idler pulley can be shifted to cause this back and forth movement of the grinding belt relative to the contact pulley and idler pulley. ", "I recognized that this type of belt shifting causes premature belt failure since first all the tension is applied to one edge of the belt then the tension is transferred to the other belt edge. ", "This continues as long as the belt is moved back and forth. ", "In my belt grinder I maintain a relatively even tension over the whole belt as compared with other belt tracking systems.", "\nThe following U.S. Patents are exemplary of prior art belt grinders: (1) U.S. Pat. ", "No. ", "2,813,382; (2) U.S. Pat. ", "No. ", "3,132,451; (3) U.S. Pat. ", "No. ", "3,229,424; (4) U.S. Pat. ", "No. ", "3,325,947; (5) U.S. Pat. ", "No, 3,394,501; (6) U.S. Pat. ", "No. ", "3,510,988; (7) U.S. Pat. ", "No. ", "3,524,285; (8) U.S. Pat. ", "No. ", "3,739,535; and, (9) U.S. Pat. ", "No. ", "3,908,316." ]
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[ "Sports bring simplicity to every season. ", "Baseball in the summer is the perfect lazy sport for lazy days and a lazy guy… can’t miss. ", "NFL Sundays in the fall provide a weekly guarantee of mindless escape and camaraderie. ", "And of course hockey’s expanse through winter and spring makes a long hibernation enjoyable.", "\n\nIf possible, this simplicity has been enhanced by the addition of my first son who has the appropriate jersey for all three occasions. ", "A game on, Henry outfitted, and my mind checked out is about as good as it gets. ", "Throw in a cold one and I’m pretty sure I’ve got life figured out. ", "It’s simple living for a few hours.", "\n\nThere is one complication: the endless sponsorships of even the most insignificant parts of a game. ", "Now a double is not an insignificant play in baseball, but does it really need to be sponsored?", "\n\nIf you’re New York Life the answer is yes.", "\n\nLast season after every Red Sox double, Don Orsillo of NESN had to say, “Safe at Second. ", "Safe and Secure. ", "New York Life.” ", "The Red Sox hit 352 doubles in 2011. ", "Buddhist monks don’t repeat phrases that often.", "\n\nThe truth is sponsorships now abound in professional sports to the point of inescapability.", "\n\nEven hockey intermissions – a word that implies “respite” – offer nothing of the sort. ", "The intermission itself is sponsored, while the intermission show has another sponsor and the individual intermission show segments are individually sponsored.", "\n\nAs a result we get this promo with about 5 minutes left in the period, “Coming up in the Tim Horton’s second intermission the Labatt Blue intermission show featuring the Bauer expert hockey panel who will bring you the International Tire breakdown of all the second period goals plus scores and highlights from around the league on the Cialis Scoreboard.”", "\n\nAnd yet could you believe there are still missed opportunities? ", "As my father never said, “If you are going to sell out then sell out completely.”", "\n\nSo let’s have some fun with a top ten list of missed opportunities for sponsorships in hockey. ", "If the kiss cam can be sponsored by your local dentist then these can surely be considered.", "\n\n1) Goalie changes sponsored by Depends. “", "Depends, is it time for a change?”", "\n\n2) Goal reviews sponsored by WebMD. “", "WebMD, if you’re unsure just get it looked at.”", "\n\n3) Player or coach ejections brought to you by E-Z Pass. “", "Get home faster with E-Z Pass.”", "\n\n4) Playoff eliminations sponsored by The Golf Channel. “", "Check your local listings. ", "We look forward to seeing you soon.”", "\n\n5) Bad contracts sponsored by Match.com. “", "You look nothing like your profile.”", "\n\n6) Too many men on the ice penalties made possible by Geico. “", "Counting to five. ", "So easy even a caveman can do it.”", "\n\n7) Fights brought to you by YouTube. “", "YouTube, you better win because it’s going to be around forever.”", "\n\n8) Empty net goals sponsored by Activia. “", "It’s time to go.”", "\n\n9) Illegal stick penalties brought to you by Curves. “", "There’s no such thing as too much curve.”", "\n\n10) Offsides from the Border Patrol. “", "Hey, get back here.”" ]
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[ "Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus.", "\nExperimental studies on albino rats reported that leaf extract of Ocimum sanctum and Ocimum album (holy basil) had hypoglycemic effect. ", "To explore further evidence we studied the effects of treatment with holy basil leaves on fasting and postprandial blood glucose and serum cholesterol levels in humans through randomized, placebo-controlled, crossover single blind trial. ", "Results indicated a significant decrease in fasting and postprandial blood glucose levels during treatment with holy basil leaves compared to during treatment with placebo leaves. ", "Fasting blood glucose fell by 21.0 mg/dl, confidence interval of difference -31.4 - (-)11.2 (p < 0.001), and postprandial blood glucose fell by 15.8 mg/dl, confidence interval -27.0 - (-)5.6 (p < 0.02). ", "The lower values of glucose represented reductions of 17.6% and 7.3% in the levels of fasting and postprandial blood glucose, respectively. ", "Urine glucose levels showed similar trend. ", "Mean total cholesterol levels showed mild reduction during basil treatment period. ", "The findings from this study suggest that basil leaves may be prescribed as adjunct to dietary therapy and drug treatment in mild to moderate NIDDM." ]
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[ "Q:\n\nA computer represents information in groups of 64 bits. ", "How many different integers can be represented in BCD code?", "\n\nThis from my Interview-MCQ module:\n\nA computer represents information in groups of 64 bits. ", "How many\n different integers can be represented in BCD code?", "\n\nThe given answer is 1016, however no explanation is provided, I was just wondering if somebody could help me understand the answer.", "\n\nA:\n\nBCD is binary coded decimal. ", " In BCD, every 4 bits is used to represent a single digit from 0 to 9. ", " So if you have 64 bits, that gives you 64/4 = 16 decimal digits, which means you can have 10^16 different integers.", "\n\n" ]
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[ "Julian Assange of Wikileaks told Fox News’ Hannity that a teenager could have hacked into John Podesta’s email with the phishing technique found on his emails.", "\n\n“We published several … emails which show Podesta responding to a phishing email,” Assange said. “", "Podesta gave out that his password was the word ‘password’. ", "His own staff said this email that you’ve received, this is totally legitimate. ", "So, this is something … a 14-year-old kid could have hacked Podesta that way.”" ]
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[ "I have seen Dr Bates three times. ", "She listened to what I had to say and engaged me completely in the process of my care. ", "I found her extremely caring, emphatic, sincere and honest. ", "I felt she gave me a very balanced picture of the options available to me backed by research. ", "She was very knowledgeable, professional and kind. ", "Her appointments were lengthy and appeared to be about my needs rather than the time they took. ", "She listens to your difficulties with medication, pain control etc and acts accordingly\nShe listened and tried to put in place my wishes when I was an inpatient on the ward.", "\nDr Bates has responded quickly to my telephone calls when I have sought help. ", "I have an open ended appointment and feel she will respond totally to my needs as they arise.", "\nI feel I am very lucky to have such a good consultant. ", "She is excellent in every way.", "\n\nRight from the start Dr Bates was very welcoming. ", "She listens to what the problem is and then will try to work out the best pain relief regime that will hopefully work for you. ", "She works it out with you and doesn't force you take on something your not comfortable with. ", "I've had two appointment with Dr Bates and at each was very happy with the outcome. ", "I know if there is a problem I can ring and things will be sorted.", "\n\nDr Bates has a very caring and calming manor about her. ", "I found it very easy to talk to her and she is very knowledgable in her role. ", "She genuinely listened to what I had to say and took onboard what needed to be done and I felt good about the treatment I was going to have , making my life a little more stress free. ", "I very helpful and positive attitude and she seems to have a calming & positive nature in the way she speaks and this helps to reassure me." ]
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[ "The Miraculous Mandarin\n\nThe Miraculous Mandarin (; ) Op. ", "19, Sz. ", "73 (BB 82), is a one act pantomime ballet composed by Béla Bartók between 1918–1924, and based on the story by Melchior Lengyel. ", "Premiered November 27, 1926 in Cologne, Germany, it caused a scandal and was subsequently banned on moral grounds. ", "Although more successful at its Prague premiere, it was generally performed during the rest of Bartók's life in the form of a concert suite, which preserves about two-thirds of the original pantomime's music.", "\n\nSynopsis\nBeginning—Curtain rises\nFirst seduction game\nSecond seduction game\nThird seduction game—the Mandarin enters\nDance of the girl\nThe chase—the tramps leap out\nSuddenly the Mandarin's head appears\nThe Mandarin falls to the floor\n\nAfter an orchestral introduction depicting the chaos of the big city, the action begins in a room belonging to three tramps. ", "They search their pockets and drawers for money, but find none. ", "They then force a girl to stand by the window and attract passing men into the room. ", "The girl begins a lockspiel — a \"decoy game\", or saucy dance. ", "She first attracts a shabby old rake, who makes comical romantic gestures. ", "The girl asks, \"Got any money?\" ", "He replies, \"Who needs money? ", "All that matters is love.\" ", "He begins to pursue the girl, growing more and more insistent until the tramps seize him and throw him out.", "\n\nThe girl goes back to the window and performs a second lockspiel. ", "This time she attracts a shy young man, who also has no money. ", "He begins to dance with the girl. ", "The dance grows more passionate, then the tramps jump him and throw him out too.", "\n\nThe girl goes to the window again and begins her dance. ", "The tramps and girl see a bizarre figure in the street, soon heard coming up the stairs. ", "The tramps hide, and the figure, a Mandarin (wealthy Chinese man), stands immobile in the doorway. ", "The tramps urge the girl to lure him closer. ", "She begins another saucy dance, the Mandarin's passions slowly rising. ", "Suddenly, he leaps up and embraces the girl. ", "They struggle and she escapes; he begins to chase her. ", "The tramps leap on him, strip him of his valuables, and attempt to suffocate him under pillows and blankets. ", "However, he continues to stare at the girl. ", "They stab him three times with a rusty sword; he almost falls, but throws himself again at the girl. ", "The tramps grab him again and hang him from a lamp hook. ", "The lamp falls, plunging the room into darkness, and the Mandarin's body begins to glow with an eerie blue-green light. ", "The tramps and girl are terrified. ", "Suddenly, the girl knows what they must do. ", "She tells the tramps to release the Mandarin; they do. ", "He leaps at the girl again, and this time she does not resist and they embrace. ", "With the Mandarin's longing fulfilled, his wounds begin to bleed and he dies.", "\n\nMusic\nThe score begins with an orchestral depiction of the \"concrete jungle.\" ", "The violins have rapidly rising and falling, wave-like scales over the very unusual interval of an augmented octave. ", "One of the central motifs of the work is set forward in bar 3—a rhythm in minor seconds. ", "This motif will reappear at the violent actions of the tramps. ", "The sound of car horns is imitated by fanfares on the trumpets and trombones. ", "As the curtain rises, the violas play a wide-leaping theme that will be associated both with the tramps and the girl. ", "The 3 lockspiele are scored for the clarinet, each one longer and more florid than the last. ", "The old rake is represented by trombone glissandi spanning a minor third, another very important interval. ", "As the tramps throw him out, the minor second in returns. ", "The music for the shy young man is a slow dance in , also interrupted by the minor second as the tramps throw him out. ", "When the Mandarin is heard in the street, the trombone plays a simple pentatonic theme harmonized by 3 lines of parallel tritones in the other trombones and the tuba. ", "When the Mandarin enters the room, the trombones and tuba play downward glissandos, again spanning a minor third. ", "Three measures later, this interval is played fortississimo by the full brass.", "\n\nThe girl's dance for the Mandarin contains both a waltz and the viola theme associated with her and the tramps. ", "When the Mandarin seizes the girl, the minor second is heard again. ", "The chase is represented by a fugue, whose subject also has a pentatonic flavor. ", "The concert suite ends at this point. ", "In the complete ballet, the minor second returns again as the tramps rob the Mandarin. ", "The attempted suffocation and stabbing are illustrated with great force in the orchestra. ", "As the tramps hang the Mandarin from the lamp, the texture is blurred with glissandi on trombones, timpani, piano and cellos. ", "The glowing body of the Mandarin is represented by the entry of a chorus singing wordlessly, once again in the interval of a minor third. ", "The climax, after the girl embraces the Mandarin, is a theme given out fortissimo by the low brass against minor-second tremolos in the woodwinds. ", "As the Mandarin begins to bleed, the downward minor-third glissando heard at his entry is echoed in the trombone, contrabassoon and low strings. ", "The work then stutters arhythmically to a close.", "\n\nThe scoring is generally heavy, and Bartók employs many colorful techniques here, including chromatic scales, trills and tremolos in the woodwinds; glissandi in the horns, trombones and tuba; cluster chords and tremolos on the piano; scales and arpeggios on the piano, harp and celeste; and scales, double stops, trills, tremolos, and glissandi in the strings. ", "Other special effects include fluttertonguing in the flutes; muting the brasses and strings, a cymbal roll a deux (a cymbal crash followed by scraping the plates together); playing the bass drum with the wooden part of a timpani mallet; a roll on the gong; rolled timpani glissandi; string harmonics; col legno and sul ponticello playing in the strings; scordatura in the cellos; and, at one point, quarter-tones in the violins.", "\n\nIn 2000 a new edition edited by Peter Bartók, the composer's son, was published. ", " Based on the composer's written manuscripts, corrections, and the concurrently written score for piano with four hands, it restored a considerable amount of previously lost music.", "\n\nInstrumentation \n\nThe Miraculous Mandarin is scored for 3 flutes (2nd and 3rd doubling piccolo), 3 oboes (3rd doubling English horn), 3 clarinets, (2nd doubling E-flat clarinet and 3rd doubling bass clarinet ), 3 bassoons (2nd and 3rd doubling contrabassoon), 4 horns (2nd and 4th doubling Wagner tuba), 3 trumpets in C, 3 trombones, bass tuba, timpani, snare drum, tenor drum, bass drum, cymbals, triangle, tam-tam, xylophone, celesta, harp, piano, organ, choir, and strings.", "\n\nRecordings \n\nPerformances of the ballet suite outnumbered performances of the complete ballet until recent years. ", "Recordings of the suite include:\nAntal Doráti and the Chicago Symphony Orchestra in 1953 on Mercury (possibly the most famous)\nEugene Ormandy with the Philadelphia Orchestra\nSeiji Ozawa with the Boston Symphony Orchestra\nEsa-Pekka Salonen with the Los Angeles Philharmonic\nZubin Mehta with the Berlin Philharmonic\nJean Martinon with the Chicago Symphony Orchestra\nSusanna Mälkki with the Helsinki Philharmonic Orchestra \nNotable recordings of the complete ballet include:\nThe landmark 1983 performance of the complete ballet by Hungarian conductor Antal Doráti, a friend of the composer's, with the Detroit Symphony Orchestra brought the complete score to the attention of a wider public. ", "Performances of the complete ballet have grown in the years since.", "\nIván Fischer's performance with the Budapest Festival Orchestra (this received the 1998 Gramophone Award in the Orchestral category)\nPierre Boulez with the Chicago Symphony Orchestra and Chorus\nSeiji Ozawa with the Boston Symphony Orchestra\nMarin Alsop with the Bournemouth Symphony Orchestra\nClaudio Abbado with the London Symphony Orchestra\nSimon Rattle with the City of Birmingham Symphony Orchestra\nGerard Schwarz with the Seattle Symphony Orchestra\n\nNotes\n\nExternal links\n Video - About the work (CSO and Boulez).", "\n Video (01:07) – Béla Bartók – Miraculous Mandarin – Trailer.", "Ballet. ", "on Vimeo\n \n \n \n\nMiraculous Mandarin, The\nMiraculous Mandarin, The\nCategory:1926 ballet premieres\nCategory:Expressionist music\nCategory:Music for orchestra and organ\nCategory:Orchestral suites" ]
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[ "INTRODUCTION {#sec1_1}\n============\n\nDiarrhoeal disease continues to be a leading cause of morbidity and mortality worldwide. ", "Despite the advances occurring in water treatment and sanitary conditions, diarrhoea continues to remain a leading public-health problem worldwide. ", "Also, there is an increased recognition in the importance of *Shigella* species as an enteric pathogen due to its potential devastating consequences resulting from strains resistant to all available antimicrobial agents. ", "Shigellosis, in the past, was quite different from the current scenario. *", "Shigella dysenteriae,* once the most common species causing severe disease, has been replaced by *Shigella flexneri* in most of the countries ([@B1]).", "\n\nThe burden of shigellosis in a tertiary-care hospital of north India over a period of six years was found to be around 4% ([@B2]). ", "The clinical spectrum of shigellosis in children ranges from mild, self-limiting, non-inflammatory diarrhoea to severe, inflammatory, bloody diarrhoea with fever, abdominal cramps, and extra-intestinal complications. ", "Several mechanisms have been proposed to explain the varied clinical presentations, the most common being the ability to invade the intestinal cells. ", "The presence of several virulence genes, along with the host immune status, can modulate the presentation. ", "Therefore, in this study, an attempt was made to detect virulence genes in *Shigella* species by multiplex PCR.", "\n\nAntibiotic therapy is recommended in shigellosis to prevent complications and the spread of disease. ", "Over the last few decades, *Shigella* has demonstrated unique ability to acquire horizontally-transferred genetic material, thereby making previously-efficacious drugs, like sulphonamides, tetracycline, ampicillin, and cotrimoxazole largely ineffective. ", "The situation recently is further worsened by the emergence of multidrug-resistant strains worldwide. ", "Therefore, the present study was also carried out to correlate the antibiotic susceptibility pattern of *Shigella* isolates with the clinical features.", "\n\nMATERIALS AND METHODS {#sec1_2}\n=====================\n\nThe study was undertaken at the Department of Microbiology in JIPMER, Puducherry, India, from October 2010 to March 2012. ", "The Ethics Committee of the institute approved the study.", "\n\nA total of 33 children were included in the present study based on the inclusion criteria: children aged less than 12 years, either sex, those who came to hospital with symptoms of diarrhoea (passing stools at least 3 times in 24 hours) or dysentery (bloody stools or mucoid stools), and stool culture positive for *Shigella* species. ", "Informed and written consents were obtained from the parents or guardians.", "\n\nCollection and processing of stool specimens {#sec1_2_1}\n--------------------------------------------\n\nStool samples were plated on MacConkey and xylose lysine deoxycholate agar (Himedia, Mumbai, India). ", "Also, the sample was inoculated in Selenite F enrichment broth and subcultured after 18 hours on the abovementioned plates. ", "Identification of *Shigella* species was done using standard biochemical tests and confirmed using antisera (Denka-Seiken, Tokyo, Japan).", "\n\nAntibiotic susceptibility pattern of the strains isolated {#sec1_2_2}\n---------------------------------------------------------\n\nAntibiotic susceptibility testing was done using Kirby-Bauer disc diffusion method ([@B3]) for the antibiotics: ampicillin 10 µg, trimethoprim-sulphamethoxazole 1.25/23.75 µg, ciprofloxacin 5 µg, ceftriaxone 30 µg, tetracycline 30 µg, and chloramphenicol 30 µg (Himedia Laboratories, Mumbai). ", "The minimum inhibitory concentration (MIC) for ciprofloxacin and ceftriaxone were performed using Epsilometer test (E-test) strips according to the manufacturer\\'s instructions (AB Biomeriuex, India). ", "The inoculum for the susceptibility testing and the interpretation were done as per CLSI (Clinical Laboratory Standards Institute) guidelines ([@B3]). ", "ATCC *Escherichia coli* 25922 was used as the control for interpretation of zone diameters. ", "Combination disc method according to CLSI guidelines was used in order to detect ESBL production in ceftriaxone-resistant *Shigella* isolates.", "\n\nTotal DNA extraction {#sec1_2_3}\n--------------------\n\nThe rapid boiling method with minimal modifications was used for total DNA extraction from culture isolates ([@B4]). ", "Briefly, the procedure was this: 5-6 colonies of *Shigellae* were picked from overnight growth and suspended in 100 µL of sterile molecular-grade water and was boiled at 100 °C for 10 minutes, following which flash-cooling was done on ice for 5 minutes. ", "The suspension was then centrifuged at 10,000×g for 5 minutes, and the supernatant containing the DNA was stored at −20 °C till further use.", "\n\nPCR for detection of virulence genes from *Shigella* isolates {#sec1_2_4}\n-------------------------------------------------------------\n\nThe primers used in this study for detection of virulence genes are mentioned in [Table 1](#T1){ref-type=\"table\"} ([@B5],[@B6]). ", "The multiplex assay was standardized with 0.3 µM concentrations of Shig and ShET2 primers and 0.5 µM concentrations of ShET1B primers. ", "Briefly, 25 µL reaction volume consisted of 12.5 µL of master mix (Mix, Bangalore Genei/Merck), 4 µL of sterile nuclease-free water, 0.75 µL each of Shig and ShET2 primers, 1.25 µL of ShET1B primer and 3 µL of template DNA. ", "For other primers, simplex PCR was performed.", "\n\nThe DNA amplification was carried out in Corbett Thermocycler, using the cycling conditions described in a previous study ([@B5]). ", "The PCR was also done on five strains each of *Salmonella* species and *Aeromonas* species.", "\n\nPCR for ESBL detection {#sec1_2_5}\n----------------------\n\nThe primers encoding the ESBL genes: TEM, CTX, and SHV, which were used in this study, are mentioned in [Table 2](#T2){ref-type=\"table\"} ([@B7],[@B8]). ", "Multiplex PCR was done for the detection of CTX and SHV genes. ", "Simplex PCR was done to detect TEM gene.", "\n\n###### \n\nPrimers for detection of virulence genes ([@B5],[@B6])\n\n Gene targeted Primer Sequence Product-size (bp)\n --------------- -------- --------------------------- -------------------\n *set*1A ShET1A F:TCACGCTACCAT CAA AGA 309\n R:TATCCCCCTTTGGTGGTA \n *set*1B ShET1B F:GTGAACCTGCTGCCGATATC 147\n R:ATTTGTGGATAAAAATGACG \n *ial* Ial F:CTG GAT GGT ATG GTG AGG 320\n R:GGAGGCCAACAATTATTTCC \n *ipa*H Shig F:TGGAAAAACTCAGTGCCTCT 423\n R:CCAGTCCGTAAATTCATTCT \n *stx* Stx F:CAGTTAATGTGGTTGCGAAG 895\n R:CTGCTAATAGTTCTGCGCTC \n *sen* ShET2 F:ATGTGCCTGCTATTATTTAT 799\n R:CATAATAATAAGCGGTCGC \n\nMultiplex PCR for CTX and SHV {#sec1_2_6}\n-----------------------------\n\nThe multiplex PCR was done to identify *bla*SHV and *bla*CTX-M genes simultaneously. ", "The reaction mixture and the cycling conditions described in a previous study were followed in this study ([@B7]).", "\n\nPCR for TEM {#sec1_2_7}\n-----------\n\nThe PCR for TEM was performed using the conditions described earlier ([@B8]).", "\n\nThe resulting PCR products were documented on 1.5% agarose gel.", "\n\nSequence analysis {#sec1_2_8}\n-----------------\n\nAmplified products were sequenced to identify the virulence genes and β-lactamase resistance genes by the Macrogen Inc., Seoul, Korea. ", "The BLASTN program ([www.ncbi.nlm.nih.gov/BLAST](http://www.ncbi.nlm.nih.gov/BLAST)) was used for database searching.", "\n\nClinical profile of the study population {#sec1_2_9}\n----------------------------------------\n\nThe clinical features of the children showing their stool positive for *Shigella* species were collected from their parents, using a structured questionnaire. ", "The questionnaire included: age, sex of the child, number of times stool passed watery diarrhoea or associated with blood and mucus, dehydration, fever, abdominal pain, seizures, oliguria, pallor, and electrolyte abnormalities.", "\n\nStatistical analysis {#sec1_2_10}\n--------------------\n\nGraphPad Instat software was used for statistical analysis. ", "Fisher\\'s exact test was used for comparing the virulence gene expression, age and gender distribution, and antibiotic resistance pattern among strains causing mild and severe disease; a p value of \\<0.05 was considered significant.", "\n\nRESULTS {#sec1_3}\n=======\n\nA total of 1,424 stool specimens were collected, of which 580 were from children aged less than 12 years during the study period (October 2010 to March 2012). ", "A total of 33 strains of *Shigella* species were isolated from 580 children, thus showing a prevalence of 6% *Shigellae* among the paediatric population attending hospital. ", "The commonest species isolated was *S. flexneri* (79%), followed by *S. sonnei* (21%).", "\n\nAntibiotic susceptibility pattern of the strains isolated {#sec1_3_1}\n---------------------------------------------------------\n\nKirby-Bauer disc diffusion method demonstrated marked drug resistance in *Shigella* isolates to ampicillin (48%), tetracycline (88%), cotrimoxazole (84%), and chloramphenicol (12%). ", "The method also demonstrated ciprofloxacin resistance in 70% and ceftriaxone resistance in 9% of *Shigella* isolates. ", "MIC values by E-test method for ciprofloxacin and ceftriaxone are shown in [Table 3](#T3){ref-type=\"table\"} and 4. ", "Resistance to more than 3 drugs was noted in 70% of *Shigella* isolates.", "\n\nDetection and distribution of virulence genes in *Shigella* isolates {#sec1_3_2}\n--------------------------------------------------------------------\n\nMultiplex PCR detected *ipa*H gene in all 33 *Shigella* isolates while it detected *ial*, *set*1A, *set*1B, and *sen* in only 28, 16, 16, and 20 isolates respectively. ", "The method did not detect *stx* in any of the strains isolated. *", "Set*1A and *set*1B were found only in *S. flexneri.* ", "DNA extracted from *Salmonella* species, and *Aeromonas* species did not show amplification for any of the above genes ([Figure 1](#F1){ref-type=\"fig\"}).", "\n\n###### \n\nPrimers for detection of ESBL genes ([@B7],[@B8])\n\n Primer Sequence Product-size (bp)\n --------- ---------------------------------- -------------------\n SHV-F 5'ATT TGT CGC TTC TTT ACT CGC 3' 1,018 bp\n SHV-R 5'TTT ATG GCG TTA CCT TTG ACC 3' \n CTXMU-1 5'ATG TGC AGY ACC AGT AAR GT 3' 544 bp\n CTXMU-2 5'TGG GTR AAR TAR GTS ACC AGA 3' \n TEM F 5'ATA AAA TTC TTG AAG ACG AAA 3' 1,076 bp\n TEM R 5'GAC AGT TAC CAA TGC TTA ATC 3' \n\n###### \n\nMIC of ceftriaxone by E-test method\n\n Antibiotic No. (", "Sensitive) No. (", "Resistant) No. (", "Intermediate) MIC in µg/mL \n -------------------- ----------------- ----------------- -------------------- -------------- --- --- --- ---\n Ceftriaxone (n=33) 32 1 0 25 5 1 1 1\n\n###### \n\nMIC of ciprofloxacin by E-test method\n\n Antibiotic No. (", "Sensitive) No. (", "Resistant) No. (", "Intermediate) MIC in µg/mL \n -------------------- ----------------- ----------------- -------------------- -------------- --- --- --- --- --- --- --- ---\n Ceftriaxone (n=33) 3 23 7 3 2 1 4 9 5 6 1 2\n\nESBL detection {#sec1_3_3}\n--------------\n\nCombination disc method showed all three ceftriaxone-resistant *S. flexneri* strains to be positive for ESBL production ([Figure 2](#F2){ref-type=\"fig\"}). ", "Multiplex PCR for *bla*CTX and *bla*SHV genes showed 2 of these strains to be positive for *bla*CTX gene, with a band-size of 544 bp. ", "Simplex PCR for *bla*TEM beta-lactamase showed the third strain to be positive for TEM, with a band-size of 1,018 bp ([Figure 3](#F3){ref-type=\"fig\"}).", "\n\nSequencing of the amplified products {#sec1_3_4}\n------------------------------------\n\nThe sequencing results indicate that, out of the two strains harbouring the plasmid-encoded *bla*CTX genes, one matched the sequence of CTX-M-15 (with 99% identity; AC-FJ997866.1). ", "The other strain harboured *bla*CTX which matched that of CTX-M-14 (with 99% identity; AC JF779678.1). ", "The third ceftriaxone-resistant strain harboured a chromosomally-encoded *bla*TEM gene, whose sequence matched TEM-1 (with 99% identity; AC-HQ665010.1).", "\n\nClinical profile of the study population {#sec1_3_5}\n----------------------------------------\n\nIn the present study, shigellosis was found to be more prevalent in children (6 %) than in adult cases (1%). ", "A total of 27 out of 33 *Shigella* strains (81%) were isolated from children aged less than 5 years. ", "The average duration of the presenting illness was 7 days, with 2 days and 2 months being the least and maximum duration of presentation; 19 (58%) out of 33 children presented with dysentery with either blood or mucus in the stool while the rest 14 (42%) children presented with watery diarrhoea. ", "Abdominal pain, tenesmus, fever, dehydration, decreased urine output, vomiting, and pallor were the other features present in 6 (18%), 3 (9%), 17 (51%), 4 (15%), 2 (6%), 6 (18%), and 1 (3%) respectively. ", "Three children (9%) developed febrile seizures. ", "None of the children had any feature of meningitis and arthritis.", "\n\n![", "Combination disc method for ESBL detection](jhpn0032-0580_f01){#F1}\n\n![", "Multiplex PCR for ESBL genes](jhpn0032-0580_f02){#F2}\n\n![", "Multiplex PCR for virulence genes](jhpn0032-0580_f03){#F3}\n\nDISCUSSION {#sec1_4}\n==========\n\nThe frequency of different species of *Shigella* varies in different regions of the world. ", "In this study, *S. flexneri* was the most common species isolated. ", "Similar findings were noted in a study carried out earlier in our hospital ([@B9]). ", "Previous studies done in India, Egypt, Iran, and a multicentre study by Seilden *et al*. ", "done in China, Viet Nam, Bangladesh, Pakistan, Indonesia, and Thailand have also shown *S. flexneri* as the most common species, except in Thailand where *S. sonnei* was the most common species isolated ([@B1],[@B10]-[@B12]).", "\n\nWe noted a very high resistance to ciprofloxacin in this study, which is similar to a previous study done in this department ([@B9]) and also to the other studies carried out elsewhere ([@B2],[@B13],[@B14]). ", "Emergence of fluoroquinolone resistance has limited the number of antibiotics, like ceftriaxone, azithromycin, and pivmecillinam for use in shigellosis. ", "Unfortunately, resistance to the third-generation cephalosporins in *Shigella* species has been reported from several studies, and the same has been observed in this study ([@B15]-[@B17]).", "\n\nResistance to 3 or more antimicrobials were shown in previous studies done in North India and Viet Nam ([@B10],[@B18]). ", "In this study, multiple drug resistance was observed in more than two-thirds of *Shigella* isolates, regardless of the serotype.", "\n\nAll the 33 *Shigella* strains tested by multiplex PCR was positive for *ipa*H gene. ", "Similar findings have been shown in a study carried out in Malaysian *Shigella* species by Thong *et al*. ([", "@B5]). ", "Multiple copies of this gene being present on both plasmids and chromosomes may explain the gene being tested positive in all strains ([@B19]).", "\n\nMost isolates also showed the presence of *ial* gene. ", "A study by Thong *et al*. ", "showed 40% of strains possessing *ial* gene. ", "The *ial* gene being located only on *inv* plasmid, unlike *ipa*H which is present both on plasmid and chromosome, is prone to spontaneous deletions ([@B5],[@B19]). ", "This may probably explain less number of strains harbouring this gene when compared with *ipa*H gene.", "\n\nThe *Shigella* enterotoxin (ShET1) genes *set*1A and *set*1B encoded chromosomally were found in almost half of the *S. flexneri* strains. ", "Both of these genes were present in the same isolates; the finding supported the previous observations and showed that these genes exist as tandem in the *Shigella* genome ([@B5]). ", "A study by Farfan *et al*. ", "has shown that nearly 30% of the *Shigella* strains harboured *set* gene ([@B20]). ", "Previous studies have shown that these genes are most commonly present in *S. flexneri* 2a. ", "Although no further typing of *S. flexneri* was performed in our study, ShET 1 was found only in *S. flexneri* strains and not in *S. sonnei*, thus confirming the previous findings.", "\n\nIn this study, three ceftriaxone-resistant *S. flexneri* strains isolated showed the presence of CTX-M-15, CTX-M-14, and TEM-1. ", "There are several other reports of ESBL-producing *Shigella* from India ([@B15]-[@B17]). ", "In the recent years, various ESBL-producing *Shigellae* were also reported from Korea (CTX-M-14), Argentina (CTX-M-2), Viet Nam (CTX-M-15, and CTX-M-24), France, and Turkey ([@B21]-[@B24]).", "\n\nWorld over, the major burden of shigellosis is contributed by children aged less than five years. ", "In this study also, the majority of *Shigella* species were isolated from children aged less than 5 years. ", "The underdeveloped immune system and the fact that the faeco-oral transmission is more common in this age-group make this age-group more susceptible. ", "These findings were in contrast with a study by Ghosh *et al*. ", "from Kolkata, India, where shigellosis was more common in children aged above 5 years ([@B25]).", "\n\nThree children (2 with *S. flexneri* and 1 with *S. sonnei*) aged less than five years developed seizures during their hospital stay. ", "Hyperthermia was noted in all three children. ", "Hyponatraemia was seen in one child, and severe dehydration was seen in another. ", "Other risk factors, like hypoglycaemia, hyperkalaemia, and elevated serum creatinine concentrations, which were shown to be associated with seizures in previous studies, were not detected in our study ([@B26]-[@B28]). ", "This supports the findings of a study done by Khan *et al*. ", "that less than five years old children with fever and metabolic abnormalities were at increased risk of seizures in shigellosis ([@B26]). ", "This finding also suggests the fact that central nervous system manifestations are not always related to Shiga toxin, which is produced in appreciable amounts only by *S. dysenteriae*. ", "Therefore, early interventions to reduce fever and correction of metabolic abnormalities in children can help in preventing such complications. ", "Persistent diarrhoea was seen in a child with Grade III protein-energy malnutrition in this study. ", "No deaths were reported in this study.", "\n\nConclusions {#sec1_4_1}\n-----------\n\nDysentery was the most common presentation, followed by fever and abdominal pain. ", "Children aged less than five years having fever and metabolic abnormalities, like hyponatraemia, are at an increased risk of seizures in shigellosis. ", "Resistance to ciprofloxacin and ceftriaxone is an alarming situation warranting proper usage of antimicrobial agents and continuous monitoring of antimicrobial resistance.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Word has it there is great reward in heaven. ", "Here on earth, not so much:\n\nThe 401(k) generation is beginning to retire, and it isn’t a pretty sight. ", "The retirement savings plans that many baby boomers thought would see them through old age are falling short in many cases. ", "The median household headed by a person aged 60 to 62 with a 401(k) account has less than one-quarter of what is needed in that account to maintain its standard of living in retirement, according to data compiled by the Federal Reserve and analyzed by the Center for Retirement Research at Boston College for The Wall Street Journal. ", "Even counting Social Security and any pensions or other savings, most 401(k) participants appear to have insufficient savings. ", "Data from other sources also show big gaps between savings and what people need, and the financial crisis has made things worse. ", "This analysis uses estimates of 401(k) balances from the end of 2010 and of salaries from 2009. ", "It assumes people need 85% of their working income after they retire in order to maintain their standard of living, a common yardstick.", "\n\nIt’s important to keep in mind that this is the model for the future foisted upon us by our Galtian overlords (who fight any attempts to regulate the looting on Wall Street), and the austerity mobs are busy making sure that the pension you were promised is hatcheted and your social security is whittled away because we can’t afford it after lavishing all the social security proceeds on the rich in the form of the Bush and Obama tax cuts. ", "But don’t worry, you will also have your collective bargaining rights stripped away, removing the last upward pressure on wages, and with Medicare rate increases you’ll have the peace of mind to know that you are contributing more to your health care.", "\n\nHow does it feel being fisted by the Invisible Hand, America?" ]
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[ "With the increasing popularity of electronics such as desktop computers, laptop computers, and handheld devices such as smart phones and PDA's, communication networks, and in particular Ethernet networks, are becoming an increasingly popular means of exchanging data of various types and sizes for a variety of applications. ", "In this regard, Ethernet networks are increasingly being utilized to carry, for example, voice, data, and multimedia. ", "Broadband connectivity including internet, cable, phone and VOIP offered by service providers has led to increased traffic and more recently, migration to Ethernet networking. ", "Much of the demand for Ethernet connectivity is driven by a shift to electronic lifestyles involving desktop computers, laptop computers, and various handheld devices such as smart phones and PDA's. ", "Applications such as search engines, reservation systems and video on demand that may be offered at all hours of a day and seven days a week, have become increasingly popular. ", "These recent developments have led to increased demand on datacenters, aggregation, high performance computing (HPC) and core networking.", "\nAs the number of devices connected to data networks increases and higher data rates are required, there is a growing need for new transmission technologies which enable higher data rates. ", "Conventionally, however, increased data rates often results in significant increases in power consumption. ", "In this regard, as an increasing number of portable and/or handheld devices are enabled for Ethernet communications, battery life may be a concern when communicating over Ethernet networks. ", "Accordingly, ways of reducing power consumption when communicating over Ethernet networks may be needed.", "\nFurther limitations and disadvantages of conventional and traditional approaches will become apparent to one of skill in the art, through comparison of such systems with some aspects of the present invention as set forth in the remainder of the present application with reference to the drawings." ]
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[ "Fourcigny\n\nFourcigny is a commune in the Somme department in Hauts-de-France in northern France.", "\n\nGeography\nFourcigny is situated in the southeastern corner of the département, southwest of Amiens on the D98, a few hundred yards from the Oise department and a few miles from the border with the Seine-Maritime. ", "The hamlet of Beaurepaire adjoins.", "\n\nPopulation\n\nSee also\nCommunes of the Somme department\n\nReferences\nINSEE\n\nExternal links\n\n Fourcigny on the Quid website \n\nCategory:Communes of Somme (department)" ]
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[ "Q:\n\nWill lipid molecules 'flip-flop' over a membrane without the use of an enzyme?", "\n\nAll of the references to this I can find refer to enzymes like Flippase making it 'easier' or 'more likely' that the translocation will occur, rather than actually make it possible.", "\nThe following is from Alberts\n\nIn the ER, however, phospholipids equilibrate across the membrane within minutes, which is almost 100,000 times faster than can be accounted for by spontaneous “flip-flop.”", "\n\nDoes this mean that left unattended, any phospholipid membrane will 'flip-flop' spontaneously, just very slowly, and can this be observed?", "\n\nA:\n\nBilayer components will 'flip-flop' at measurable rates, but these are very different for different lipid classes. ", "Here are the results of an experiment using fluorescently-labelled analogues.", "\n\nBai, JN and Pagano, RE (1997) Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles. ", "Biochemistry 36:8840-8848 DOI: 10.1021/bi970145r \n\nThe authors followed the transbilayer (flip-flop) and interbilayer movement of fluorescently-labelled analogues of various membrane lipids: sphingomyelin (C-5-DMB-SM), ceramide (C-5-DMB-Cer), phosphatidylcholine (C-5-DMB-PC) and diacylglycerol (C-5-DMB-DAG) in a system of unilamellar vesicles consisting of 1-palmitoyl-2-oleoyl phosphatidylcholine. ", "\nThe results were analysed in terms of a model in which the labelled molecules could move between vesicles and between the two monolayers of the bilayer.", "\nhalf times:\n interbilayer transbilayer (flip-flop)\nC-5-DMB-SM >21 s 3.3 h \nC-5-DMB-Cer 350 s 22 min\nC-5-DMB-PC 400 s 7.5 h\nC-5-DMB-DAG 100 h 70 ms\n\nSo, for the phospholipid tested the half-time for flip-flop was 7.5 hours.", "\n\n" ]
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[ "Free forum : Welcome To the KoC Message boards! ", "Knights of Cydonia is a very succesful guild in Star Legends: The Blackstar Chronicles, suited for anyone who wants to be part of a helpful and friendly guild.", "\n\nIt is 50 years after the tales of Percy Jackson and Jason Grace, and Camp Half-Blood is still alive. ", "But with a whole new generation of demigods and a new prophecy, how will things turn out for the camp?" ]
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[ "Stimulation of sperm production by human luteinizing hormone in gonadotropin-suppressed normal men.", "\nThe relative roles of FSH and LH in the control of human spermatogenesis are not well established. ", "We previously reported that supraphysiological doses of hCG can stimulate sperm production in gonadotropin-suppressed normal men despite prepubertal FSH levels. ", "To determine whether more nearly physiological levels of human LH (hLH) also can stimulate spermatogenesis when FSH levels are suppressed, we administered hLH to normal men whose endogenous gonadotropin levels and sperm production were suppressed by exogenous testosterone enanthate (T). ", "After a 3-month control period, 11 normal men received 200 mg T, im, weekly to suppress LH and FSH. ", "T administration alone was continued for 3-4 months until 3 successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligospermia (sperm concentrations, less than 4 million/ml). ", "Then, while continuing T, 4 of the 11 men (experimental subjects) simultaneously received 1100 IU hLH, sc, daily for 4-6 months to replace LH activity, leaving FSH activity suppressed. ", "The effect on sperm production of the selective FSH deficiency produced by hLH plus T administration was determined. ", "The remaining 7 men (control subjects) continued to receive T alone at the same dosage, without gonadotropin replacement, for an additional 6 months. ", "In the four experimental subjects, sperm concentrations increased significantly from 0.7 +/- 0.7 million/ml (mean +/- SEM) during T treatment alone to 19 +/- 4 million/ml during hLH plus T administration (P less than 0.001). ", "However, none of the men achieved sperm concentrations consistently in their own pretreatment range. ", "Sperm motilities and morphologies were normal in all four subjects by the end of hLH plus T administration. ", "In contrast, sperm concentrations in the seven control subjects remained suppressed (less than 3 million/ml) throughout the entire period of prolonged T administration alone. ", "Serum LH bioactivity, determined monthly by in vitro mouse Leydig cell bioassay in all four experimental subjects, was markedly suppressed during T administration alone (120 +/- 10 ng/ml) compared to that during the control period (390 +/- 20 ng/ml; P less than 0.001). ", "With the addition of hLH to T, LH bioactivity returned to control levels (400 +/- 40 ng/ml; P = NS compared to control value). ", "Serum FSH levels determined monthly by RIA were reduced from 98 +/- 12 ng/ml during the control period to undetectable levels (less than 25 ng/ml) during the T alone and the hLH plus T periods (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)" ]
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[ "Q:\n\nWhy am I false?", "\n\nGetting this error around 9:30AM (CST):\n\nwhen visiting the Questions/newest tab.", "\n\nA:\n\nIt was a problem with some javascript code. ", "The devs have pushed out a fix.", "\n\n" ]
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[ "\"Previously, on no tomorrow...\" \"I loved her so much.\" \"", "You have to tell your brother.\" \"", "You're engaged to his ex-fiance.\" \"", "Wha...\" \"I'm going to.\" \"", "Will you make me the happiest man.\" \"", "In the world for the third time?\" \"", "I accept your proposition.\" \"", "What's the deal with your fox, man?\" \"", "Dude, she's great.\" \"", "I can't be with someone who refuses.\" \"", "To be his whole self.\" \"", "Am I your rebound?\" \"", "We're just living in the moment.\" \"", "Hey.\" \"", "Hey, yourself.\" \"", "I had the most amazing dream last night.\" \"", "That wasn't a dream.\" \"", "Yeah, no.\" \"", "That was also great.\" \"", "We were taking our kids to an amusement park.\" \"", "In a camaro.\" \"", "Kids?\" \"", "Wow.\" \"", "You looked super hot in mom jeans.\" \"", "So, what do you say,\" \"Should we make this,\" \"Like...\" \"Facepage official?\" \"", "That'd be tight.\" \"", "You know, I think that we've got.\" \"", "A pretty great future ahead of us.\" \"", "Hi.\" \"", "Hey.\" \"", "Can I come in?\" \"", "Um, of course.\" \"", "You didn't call me back last night.\" \"", "Last night?\" \"", "Yeah.\" \"", "I left you a message.\" \"", "I haven't checked yet.\" \"", "I got caught up in a little...\" \"Something.\" \"", "Well.\" \"", "If you had,\" \"You would know that, thanks to you,\" \"I checked off number three on my lyst.\" \"", "I'm really proud of you.\" \"", "Yeah.\" \"", "I mean, I punched him first,\" \"But then we made up, and,\" \"We exploded my mom over this hydroelectric dam.\" \"", "Now she's part of the power grid forever.\" \"", "Wow.\" \"", "That sou...\" \"That...\" \"That's I-incredible.\" \"", "I feel like I've just chucked off this this load off my life,\" \"And now we can get back on track.\" \"", "We can book that trip to iceland,\" \"See the northern lights, because why not?\" \"", "Also.\" \"", "I have a surprise for you.\" \"", "Evie,\" \"I would like you to meet...\" \"My mother.\" \"", "I kissed timothy.\" \"", "Finger?\" \"", "Yeah.\" \"", "On purpose?\" \"", "Yeah.\" \"", "Timothy l.\" \"Finger.\" \"", "Yes.\" \"'", "Cau...\" \"You and I have gotten into trouble in the past.\" \"", "Not being totally honest with each other, so...\" \"I felt like you should know.\" \"", "That...\" \"You've been kissing timothy I.\" \"Finger...\" \"On purpose.\" \"", "I have been spending time with him.\" \"", "It doesn't mean that he and I are back together,\" \"But you and I aren't either.\" \"", "You ask me to dig into some pretty emotional...\" \"Stuff,\" \"Which I did,\" \"And you moved on in the meantime?\" \"", "Look, I just need time to figure out...\" \"What, like, which one of us you want?\" \"", "Honesty scone?\" \"", "It's...\" \"It's not just about you guys.\" \"", "I have a lot going on in my life right now,\" \"And I need some time to sort it all out,\" \"And right now, I have to make eggs benedict.\" \"", "Because my grandparents are coming over for brunch.\" \"", "So I should...\" \"Well, I should.\" \"", "Get moving on that.\" \"", "Yeah.\" \"", "Benedict brunch...\" \"I forgot my mother.\" \"", "I'm gonna...\" \"Yeah.\" \"", "Yep.\" \"", "Lou, honey, how are those drinks coming along?\" \"", "I think that's strong enough, babe.\" \"", "I want to get buzzed, not blitzed.\" \"", "Hey, is he okay?\" \"", "He's been in a funk.\" \"", "Since he failed his driver's test.\" \"", "It's an injustice!\" \"", "This department of licensing dipwad,\" \"Bernard.\" \"", "He didn't like me from the jump.\" \"", "He said I didn't understand the rules of the road.\" \"", "16 years.\" \"", "Building engines on the indy circuit,\" \"And I don't know cars?\" \"", "He can suck a tailpipe.\" \"", "I'm sorry, grandpa.\" \"", "It's ageism.\" \"", "Nobody knows cars better than me.\" \"", "Well, you still rev my engine.\" \"", "You know what, why don't I make a couple of calls.\" \"", "And see if I can get you another test.\" \"", "Well, thanks, sweetheart.\" \"", "First time I've seen that smile in four days.\" \"", "It's the vodka.\" \"", "Jesse!\" \"", "Cuz!\" \"", "No.\" \"", "I-i think I nodded off, man.\" \"", "Is the macaroni ready?\" \"", "Mate, what are you doing here?\" \"", "Are you all right?\" \"", "Are you in trouble?\" \"", "Out of trouble, cuz.\" \"", "You remember the prison guard.\" \"", "That we bought off so he would spring me loose?\" \"", "Yeah.\" \"", "Well, he another guy out that turns out was way worse than me.\" \"", "So, I testified.\" \"", "In exchange for immunity.\" \"", "On my own little jailbreak.\" \"", "You're looking at a newly free cuz, my...\" \"My cuz, back to reclaim his future.\" \"", "Seriously, your timing could not have been better.\" \"", "No.\" \"", "What's going on?\" \"", "Is it your fox?\" \"", "Yeah, well, I wouldn't call her my fox.\" \"", "Is there a rooster in the fox house?\" \"", "I could be base jumping.\" \"", "Or mountaineering.\" \"", "Or sailing around the world.\" \"", "Or whatever you want to do.\" \"", "Scuba diving.\" \"", "Perfect.\" \"", "We could be doing that right now.\" \"", "Heck yeah.\" \"", "I shouldn't be pining over some chick.\" \"", "I mean, I have no interest in being part of a love triangle.\" \"", "That's not who I am, that's not what I want.\" \"", "And that's why I'm bowing out.\" \"", "Okay.\" \"", "But I wish you all the best,\" \"And I hope that you figure out what you want.\" \"", "But for now, if you'll excuse me, jesse's a free man again,\" \"So we're gonna go to the bottom of lake washington,\" \"And fish for golf balls.\" \"", "You know, this is gonna be great.\" \"", "I didn't want to be caught up in the love triangle, anyway.\" \"", "I mean, xavier lied to me, he was reckless, and sure,\" \"I'm glad he made up with his dad,\" \"But there's a lot of baggage there.\" \"", "So I am moving on.\" \"", "And I'm really excited.\" \"", "Not just about what might happen with timothy,\" \"But about life in general.\" \"", "Okay.\" \"", "I just asked if I can borrow your stapler, so...\" \"Can I?\" \"", "Yeah.\" \"", "It's ringing.\" \"", "You've reached bernard korwatch.\" \"", "At the department of licensing.\" \"", "Leave a message.\" \"", "Hi, bernard.\" \"", "This is evie covington again,\" \"Calling about a possible do-over.\" \"", "For my grandfather's driving test?\" \"", "I'm sure you can understand, bernard,\" \"He can't imagine a future without driving.\" \"", "You know, people need to have a say in their own futures.\" \"", "I know I do.\" \"", "I'm figuring that out right now.\" \"", "But that is a... another topic.\" \"", "Unrelated.\" \"", "Please call me back.\" \"", "Thank you.\" \"", "Wind her up and watch her go.\" \"", "Do you want us to ask if everything is okay, hank?\" \"", "Yeah.\" \"", "Evie?\" \"", "I-is everything okay, hank?\" \"", "Not at all.\" \"", "Went bunker shopping yesterday.\" \"", "There's only one in my price range.\" \"", "Well, it's a beautiful zero bed, quarter bath.\" \"", "What's a quarter bath?\" \"", "A murphy toilet?\" \"", "Well, that sounds cozy.\" \"", "There's only room for one more person.\" \"", "So I have to trim my survivor list.\" \"", "It's down to you, timothy and kareema.\" \"", "I'll make it easy for you.\" \"", "I'm out.\" \"", "I'd rather be obliterated.\" \"", "You're being extra, extra mean today.\" \"", "Sorry.\" \"", "I'm just nervous.\" \"", "This bitch is getting hitched.\" \"", "Okay, you're aware that is a pitch humans cannot hear?\" \"", "Pack of dogs going buck wild somewhere.\" \"", "I'm so excited!\" \"", "When?\" \"", "Where?\" \"", "Why didn't I get an invitation?\" \"", "No.\" \"", "How can I help?\" \"", "Wow, it's so much.\" \"", "Here.\" \"", "Hank also has a problem.\" \"", "Help him.\" \"", "You can't do squat,\" \"Because the only person who should be in that bunker with me.\" \"", "Is off the market.\" \"", "That guest list is looking a little lean.\" \"", "You have quibbles?\" \"", "Well, you cut my brother.\" \"", "Correct.\" \"", "And your own mom.\" \"", "We had to start somewhere.\" \"", "You sure nothing else is going on?\" \"", "It's quite time-intensive to plan.\" \"", "The most important day of my life for the third time.\" \"", "My schedule is not particularly accommodating.\" \"", "Didi,\" \"My darling...\" \"You look more stressed than a sunfish in a gator's mouth.\" \"", "I am.\" \"", "Why don't i...\" \"Handle all of the planning.\" \"", "From here on out?\" \"", "You're comfortable assuming that level of responsibility?\" \"", "Of course I am.\" \"", "All you need to do.\" \"", "Is pick a dress and let old three-pete.\" \"", "Take care of the rest.\" \"", "Mwah.\" \"", "Hey, little lady, you are didi's new assistant, is that right?\" \"", "Daphne.\" \"", "But you can call me daffy for short.\" \"", "How are you?\" \"", "Can I get you some coffee or water or soda water?\" \"", "I just need a little favor.\" \"", "Here's the deal.\" \"", "You and I, we are gonna put together.\" \"", "Her perfect wedding.\" \"", "I've been scouting apple orchards,\" \"And I would like you.\" \"", "To find us a good bluegrass band.\" \"", "Here is my credit card.\" \"", "And, daphne...\" \"Let's keep this on the just-between-us level.\" \"", "Okay.\" \"", "Hey, daffy!\" \"", "Hey, hank.\" \"", "How are you?\" \"", "Can I get you.\" \"", "Some coffee or water or soda water?\" \"", "Nah.\" \"", "And I wasn't eavesdropping or nothing.\" \"", "I didn't hear anything, and...\" \"Don't want to get involved with all your...\" \"Stuff.\" \"", "But on the “just-between-us level, ”.\" \"These days deirdre prefers continental jazz to bluegrass.\" \"", "She's not gonna want to get married in an orchard.\" \"", "She gets hay fever.\" \"", "Yeah.\" \"", "You want to write this down.\" \"", "Yes.\" \"", "Yes.\" \"", "Yes.\" \"", "Okay.\" \"", "Ready?\" \"", "Ye.\" \"", "Actually,\" \"No.\" \"", "I don't think I can do this.\" \"", "Without rohan.\" \"", "Really?\" \"", "Yeah.\" \"", "I ju...\" \"I never imagined myself getting married.\" \"", "Without my brother there.\" \"", "Okay, I never imagined myself getting married.\" \"", "But now that it's happening,\" \"It doesn't feel right to move forward.\" \"", "Without him.\" \"", "It's okay.\" \"", "I completely understand.\" \"", "Thank you.\" \"", "But we need to get married soon.\" \"", "If I'm going to stay in this country legally.\" \"", "I know.\" \"", "I know you like mediterranean.\" \"", "It's braised octopus,\" \"In a feta, tomato and olive sauce.\" \"", "Wow, it looks fantastic.\" \"", "You sound surprised.\" \"", "I am.\" \"", "I didn't know that you could cook.\" \"", "I took some classes.\" \"", "Fair warning, you should probably.\" \"", "Put on an extra pair of socks.\" \"", "Before you try this, because...\" \"It's gonna knock 'em right off.\" \"", "Bon apptit.\" \"", "No.\" \"", "What?\" \"", "What, is it okay?\" \"", "It happened.\" \"", "Socks...\" \"Knocked clear off.\" \"", "I told you!\" \"", "Hey,\" \"Let me ask you something.\" \"", "Yeah, shoot.\" \"", "If...\" \"If I wanted to go to iceland, like,\" \"Tomorrow,\" \"Would you want to come?\" \"", "Yeah, of course.\" \"", "Really?\" \"", "But you hate last minute plans.\" \"", "Yeah, I used to.\" \"", "But now I figure,\" \"As long as I have my laptop, I can work from anywhere.\" \"", "Chiyoko-san.\" \"", "Threw you around like a rag doll.\" \"", "Yeah, that's 'cause he's 450 pounds.\" \"", "Okay.\" \"", "Well, let's cross it off the lyst.\" \"", "What's next?\" \"", "Blowfish?\" \"", "Roll the dice?\" \"", "No, I'd like to,\" \"Cuz, but,\" \"I got other plans tonight.\" \"", "What?\" \"", "What are you doing?\" \"", "Well, I'm going out with amber.\" \"", "Do you remember her?\" \"", "Um...\" \"Amber... that's the same color as my energy\" \"Yeah, that's her!\" \"", "That's her!\" \"", "Come here, my beautiful love.\" \"", "Sweet muffin.\" \"", "I missed.\" \"", "This glorious mane.\" \"", "I want to run my fingers through it.\" \"", "All night long.\" \"", "Wow.\" \"", "Isn't she amazing?\" \"", "Yeah.\" \"", "She's got her own line of jewelry,\" \"Made out of dehydrated fruit.\" \"", "Lovely.\" \"", "We're gonna go, cuz, 'cause we have,\" \"A lot of catching up to do.\" \"", "See you later!\" \"", "I'll, I'll be there soon.\" \"", "I-I'm so sorry,\" \"I got to head down to the impropoganda offices.\" \"", "My story.\" \"", "On psychedelic fungi.\" \"", "Is getting bumped up to the cover.\" \"", "What?\" \"", "That is great.\" \"", "Yeah, but I'm gonna have to work fast.\" \"", "But we're still on for tomorrow, yeah?\" \"", "Yeah.\" \"", "Sorry again for taking off early.\" \"", "That's okay.\" \"", "Go do your thang.\" \"", "Kareema never got you off that?\" \"", "Nope.\" \"", "Good.\" \"", "Bye.\" \"", "Bye.\" \"", "Num, num, num.\" \"", "Okay, my stud.\" \"", "I have to get moving.\" \"", "I'm picking up a crate of dried papaya.\" \"", "For a new series of brooches.\" \"", "I'll come.\" \"", "I love crafting.\" \"", "No, no, no.\" \"", "You're getting a job today, remember?\" \"", "Okay.\" \"", "Okay.\" \"", "What?\" \"", "Nothing.\" \"", "No, nothing.\" \"", "I just... can't believe.\" \"", "You're getting a job because some girl tells you to.\" \"", "Heck, yeah, I am.\" \"", "I love her, cuz.\" \"", "Been trying to get back together for four years.\" \"", "Whipped.\" \"", "Hey, cuz.\" \"", "Careful, man.\" \"", "That kind of scoff in the pen will get you shivved.\" \"", "Here, here, potentially right here.\" \"", "Don't think you should change your life for a chick.\" \"", "That's all I'm saying.\" \"", "That's it.\" \"", "Well, whatever.\" \"", "You're just lonely.\" \"", "No.\" \"", "Not lonely at all...\" \"Nope.\" \"", "Yeah, get real, cuz.\" \"", "You know?\" \"", "You walked away from the woman you love.\" \"", "It's just sad.\" \"", "I just didn't want to be part.\" \"", "Of an awkward love triangle.\" \"", "Well, what are you gonna do instead?\" \"", "Are you just gonna travel the world?\" \"", "Y-yeah.\" \"", "Maybe, yeah.\" \"", "Great.\" \"", "Well, you already did that.\" \"", "Do you remember the pictures that you sent me.\" \"", "From your escapades?\" \"", "Yes.\" \"", "That was very mean, 'cause I was stuck in prison.\" \"", "You said you found them very uplifting.\" \"", "You came back for a reason.\" \"", "Something was missing.\" \"", "Who's it gonna be?\" \"", "Hey, you want to play charades again?\" \"", "No.\" \"", "It's a movie.\" \"", "No.\" \"", "You think evie survived?\" \"", "No.\" \"", "Okay.\" \"", "Heads evie, tails timothy.\" \"", "Psst!\" \"", "What is it, daffy?\" \"", "I said, psst.\" \"", "What?\" \"", "Did you say deirdre loves begonias or petunias?\" \"", "Petunias;\" \"She loves purple.\" \"", "Got it.\" \"", "Thanks, hank.\" \"", "No problem.\" \"", "Just don't ask me anything else.\" \"", "Unless it's a real, real, real, real emergency.\" \"", "I won't.\" \"", "Hank.\" \"", "I have a real, real, real, real emergency question...\" \"About place settings.\" \"", "I've got one word Sporks.\" \"", "Looks like you were his first choice to spend forever with.\" \"", "It would appear so.\" \"", "Now you'll die.\" \"", "In the nuclear holocaust along with the rest of us.\" \"", "Aw.\" \"", "It's a pretty sweet gesture.\" \"", "When you think about it.\" \"", "I will be leaving now.\" \"", "Ditto.\" \"", "Dol.\" \"", "Bernard speaking.\" \"", "Hi.\" \"", "Bernard.\" \"", "It's evie covington.\" \"", "Boy.\" \"", "Did you get my voice mails?\" \"", "Yes.\" \"", "All 16 of them.\" \"", "Fantastic.\" \"", "So...\" \"What do you say?\" \"", "Your grandfather's not getting a do-over.\" \"", "Please stop calling me.\" \"", "This isn't over, bernard.\" \"", "I can't decide.\" \"", "They're just so different.\" \"", "I mean, am I an ivory white.\" \"", "Pantsuit bride,\" \"Or am I a pearl white pantsuit bride?\" \"", "One is smart and sensible, the other is,\" \"You know, a real statement piece.\" \"", "Well, either way, didi, my darling,\" \"You are gonna look prettier.\" \"", "Than a lace doily on a chestnut nightstand.\" \"", "This choice demands more scrutiny.\" \"", "I have to say, I have not known you to be.\" \"", "An indecisive woman.\" \"", "Do I need to take the temperature of your feet?\" \"", "No, no.\" \"", "I just need a little more time to pick the proper outfit.\" \"", "For our happy occasion.\" \"", "You were right.\" \"", "I think I came back 'cause I was unfulfilled.\" \"", "The thing is, I didn't know it at the time,\" \"But evie was exactly what I was looking for.\" \"", "There you go.\" \"", "I knew that from the first time you talked.\" \"", "About her, when you were sawing those handcuffs off me.\" \"", "She got under your skin, cuz,\" \"Like a new, younger layer of skin.\" \"", "Right...\" \"Yeah.\" \"", "Well, anyway, the point is,\" \"We both lost sight of how special this is.\" \"", "I'm gonna fight for her.\" \"", "Yeah.\" \"", "Put a little “try” in that love triangle.\" \"", "This was such a good idea.\" \"", "Yeah.\" \"", "The site of our first date.\" \"", "Back to the scene of the crime.\" \"", "Crime is right.\" \"", "We had to use fake ids to get in.\" \"", "Yours was so bad, it didn't even look like you.\" \"", "He had a chinstrap.\" \"", "Yeah, well, what about yours?\" \"", "You remember blanche with the crazy eyes?\" \"", "Yeah.\" \"", "Because every time I tried to use it,\" \"I had to be like...\" \"I love how much we know about each other.\" \"", "Like our inside jokes, our long-term goals,\" \"Our real names, you know, the important stuff.\" \"", "Yeah, but you know what?\" \"", "Without the glasses.\" \"", "And with the cooking skills and the spontaneity,\" \"It's like you're a whole new person.\" \"", "Good evening ladies and gentlemen,\" \"This song if for a very special lady in the audience,\" \"Who I should never have let slip through my fingers.\" \"", "Into finger's fingers.\" \"", "Fig.\" \"", "What are you doing?\" \"", "I'm gonna piano duel for your love.\" \"", "No.\" \"", "Please, don't.\" \"", "You play the piano?\" \"", "Self-taught.\" \"", "You self-teach yourself this one?\" \"", "Yeah.\" \"", "In third grade.\" \"", "He's an amateur, evie.\" \"", "Yeah?\" \"", "How's this for amateur?\" \"", "Hamish!\" \"", "Finger!\" \"", "Evie's moved on.\" \"", "You should, too.\" \"", "Ten years, mate, and you couldn't close the deal.\" \"", "Break it up.\" \"", "Evie?\" \"", "Evie?\" \"", "Evie, would you please come on.\" \"", "Hey, evie, hang on.\" \"", "Just wait.\" \"", "I thought you bowed out.\" \"", "Yes, I-i did, but now I would like to bow back in.\" \"", "You can't do that.\" \"", "Hey, look,\" \"I don't want to walk away, all right, from what we have.\" \"", "And I would like to apologize.\" \"", "For finger's childish behavior.\" \"", "Okay, you know what, hamish?\" \"", "Okay,\" \"No, I'm nipping this in the bud.\" \"", "Either we all agree.\" \"", "To act like adults, or we go our separate ways.\" \"", "Fine.\" \"", "I'm an adult.\" \"", "Me, too.\" \"", "Also an adult.\" \"", "Then I will date you both, and we'll see how it goes.\" \"", "Great.\" \"", "Yeah.\" \"", "I'm not threatened by him.\" \"", "Yeah, and I'm-i'm not threatened by him.\" \"", "Not being threatened by me.\" \"", "Nice one.\" \"", "Great.\" \"", "Then I will see you tomorrow night.\" \"", "Boo-ya.\" \"", "And, timothy, I will see you.\" \"", "The day after...\" \"I need a date for deirdre's wedding.\" \"", "A wedding?\" \"", "Score.\" \"", "That sounds like a great plan.\" \"", "Yep.\" \"", "It's gonna be the most romantic date she's ever been on.\" \"", "She's gonna forget all about that finger puppet.\" \"", "Yep.\" \"", "Yes, sir, yes, sir.\" \"", "Okay, man...\" \"What do you think, would you hire me?\" \"", "I don't think the attire is the problem.\" \"", "Yeah.\" \"", "I think it's the whole ex-con thing.\" \"", "But the right suit might balance the scales a little.\" \"", "Well...\" \"This one's too tight, though.\" \"", "You can see the outline of my yankee doodle.\" \"", "Ooh.\" \"", "Back to the drawing board.\" \"", "That's a nice bolo tie.\" \"", "Thanks, partner.\" \"", "What is that, is that turquoise?\" \"", "Yeah, you betcha.\" \"", "Cool.\" \"", "I should get me one of those.\" \"", "Yeah.\" \"", "You can't pull that off.\" \"", "J...\" \"He's probably right.\" \"", "Hey, hope you don't mind my asking...\" \"Is that a irish accent?\" \"", "No, mate.\" \"", "I always wanted to go there.\" \"", "Ireland.\" \"", "Sit at the...\" \"Rapid-fire feet of michael flatley.\" \"", "And learn the ins and outs.\" \"", "Of irish step-dancing.\" \"", "Right.\" \"", "Why don't you do exactly that, then?\" \"", "I don't know.\" \"", "I always end up going to florida on vacation.\" \"", "Come home with a sunburn every time.\" \"", "Sounds like.\" \"", "The universe is trying to tell you something, doesn't it?\" \"", "I mean, you keep doing the same thing,\" \"You keep getting burned.\" \"", "Yeah.\" \"", "Y...\" \"There's a...\" \"There's a comfort in-in...\" \"Sticking with what you know.\" \"", "But life's short.\" \"", "Very short.\" \"", "But hey, you do what you want.\" \"", "Good luck to you.\" \"", "Vodka?\" \"", "Sure.\" \"", "Really?\" \"", "Yeah.\" \"", "It's been a strange couple of days.\" \"", "I'm kind of dating two guys at once.\" \"", "You've come so far.\" \"", "Yeah,\" \"It's pretty baller?\" \"", "It was, until you said the word baller.\" \"", "Speaking of love triangles, how's rohan?\" \"", "Not great.\" \"", "Told him I wanted him to be there for the wedding,\" \"And he unleashed.\" \"", "A truly spectacular string of curse words.\" \"", "And then hung up.\" \"", "I'm sorry.\" \"", "Is there anything I can do?\" \"", "Can you dress up.\" \"", "As a petulant 34-year-old indian man and forgive me?\" \"", "I could try, but it would probably come off as racist.\" \"", "It was just so much easier when we were kids.\" \"", "Just beat the crap out of each other with pillows.\" \"", "And then we could talk it out.\" \"", "Well, you're kind of acting like children now, so...\" \"Evie,\" \"I have something to give you.\" \"", "Is it a low five?\" \"", "No.\" \"", "It's the spare key to my bunker.\" \"", "In case of an apocalyptic event,\" \"We'll be spending forever together.\" \"", "Thanks, hank.\" \"", "Congratulations.\" \"", "I hope you like vienna sausage.\" \"", "Hey, hank.\" \"", "I got some bad news, tlc.\" \"", "I've chosen my forever bunker mate.\" \"", "I'm going with evie.\" \"", "I get it.\" \"", "I would do the same.\" \"", "If it falls on me to repopulate the earth,\" \"She's the smart choice.\" \"", "Okay.\" \"", "Well, th...\" \"Look, I-i can't really talk right now.\" \"", "I'm on a deadline, and I have to type with one hand,\" \"After hitting...\" \"After...\" \"Hitting the keys a little hard last night.\" \"", "It's taking forever.\" \"", "I-i got to go.\" \"", "Good luck, t-pot.\" \"", "Take it easy on those keys.\" \"", "Hi, bernard!\" \"", "It's evie covington.\" \"", "No.\" \"", "Did you get those chocolates I sent over?\" \"", "Yes.\" \"", "And the edible arrangement.\" \"", "Fantastic.\" \"", "So...\" \"What are my chances of a do-over?\" \"", "Fine.\" \"", "I love cupcakes.\" \"", "Hello?\" \"", "Choose your weapon.\" \"", "Are you serious?\" \"", "I want to talk.\" \"", "If a pillow fight is what it takes,\" \"Then a pillow fight is what it takes.\" \"", "Sure you want to do this?\" \"", "Say when, cowboy.\" \"", "Draw.\" \"", "What are we doing here?\" \"", "You want to go for a ride?\" \"", "A ride?\" \"", "A seaplane?\" \"", "Who's the pilot?\" \"", "You ever wonder what was number one on my apocalyst?\" \"", "Fig...\" \"Is it too late to turn around?\" \"", "Much too late.\" \"", "Holy hell!\" \"", "It's peaceful, isn't it?\" \"", "Are we going.\" \"", "Somewhere in particular?\" \"", "Absolutely not.\" \"", "The whole point of flying...\" \"Is to fly.\" \"", "Cool.\" \"", "Then I want to steer.\" \"", "Sorry?\" \"", "I want to fly the plane.\" \"", "Can't argue with that.\" \"", "Back...\" \"Is up, and forward...\" \"Is down.\" \"", "We don't want to go forward.\" \"", "Okay?\" \"", "Here you go.\" \"", "I'm flying.\" \"", "You're flying.\" \"", "I'm flying!\" \"", "You ready to talk?\" \"", "You are selfish.\" \"", "And destructive.\" \"", "I know I am.\" \"", "That's why I was never looking for this.\" \"", "You know me...\" \"I detest marriage and monogamy.\" \"", "But i...\" \"I've never felt this way.\" \"", "I didn't know it was possible.\" \"", "Then you should do it.\" \"", "You should get married.\" \"", "Really?\" \"", "Yeah.\" \"", "You have my blessing.\" \"", "Thank you.\" \"", "I just...\" \"Can't witness it.\" \"", "And I'm gonna need a little time and space.\" \"", "Hey, I love you, ro.\" \"", "Okay, now you're scaring me.\" \"", "I love you, too.\" \"", "It was a little rougher than expected,\" \"But overall, a pretty good landing.\" \"", "Thank you.\" \"", "You know what, I appreciate that,\" \"Considering it is the first time\" \"I've done it without an instructor.\" \"", "You've got to be kidding.\" \"", "No.\" \"", "Well, no harm done.\" \"", "Can I ask you a question?\" \"", "Okay.\" \"", "What if...\" \"The asteroid doesn't hit?\" \"", "I don't know.\" \"", "It will, so...\" \"No.\" \"", "But...\" \"Just for fun,\" \"What if it doesn't?\" \"", "What does your future look like?\" \"", "I don't know.\" \"", "It doesn't matter.\" \"", "It matters to me.\" \"", "I have hopes and dreams for my life.\" \"", "That go beyond the next six months,\" \"And i...\" \"I want to start planning for them.\" \"", "Why?\" \"", "What's the point?\" \"", "Planning for a future that you know is not gonna happen.\" \"", "Well, hypothetically.\" \"", "It's too painful.\" \"", "I have kept.\" \"", "An open mind about your theory this whole time,\" \"And you won't even entertain this as a hypothetical?\" \"", "And what if I can't?\" \"", "Then what?\" \"", "I mean, is that it?\" \"", "You're just gonna...\" \"Go off with finger?\" \"", "Honestly...\" \"I'm not sure whether I can see a future with timothy.\" \"", "Yeah, well...\" \"But...\" \"You can't even conceive.\" \"", "Of one for yourself.\" \"", "I don't know how to make that work.\" \"", "You flew a plane?\" \"", "Yeah.\" \"", "Sounds like a great date.\" \"", "Started great, then it got a little intense at the end.\" \"", "Are you trying to tell me you joined the mile-high club?\" \"", "No.\" \"", "We just...\" \"Didn't leave it on great terms.\" \"", "I have a hunch that what you really want is xavier,\" \"But with a future.\" \"", "Well, that's...\" \"Not on the table.\" \"", "Ladies, stop the chatter.\" \"", "I'm trying to get in the right head space here.\" \"", "You got this.\" \"", "Yeah.\" \"", "Oops...\" \"L-let me just...\" \"Here's to your new job, mate.\" \"", "Thank you so much for putting a good word in.\" \"", "With murray, cuz.\" \"", "Amber's pumped.\" \"", "We have officially.\" \"", "And consciously coupled.\" \"", "How are you and your fox?\" \"", "Not so good.\" \"", "She's having trouble accepting that I don't believe.\" \"", "In wasting time planning for the future.\" \"", "So...\" \"What?\" \"", "I just feel like you're being a wimp.\" \"", "I'm not being a wimp.\" \"", "I'm not being a wimp.\" \"", "Am I being a wimp?\" \"", "I'm-i'm being practical.\" \"", "Yeah.\" \"", "A practical wimp.\" \"", "Do you know who I was in the clink with, man?\" \"", "Guy named madoff.\" \"", "Serving a life sentence with no possibility.\" \"", "Of parole.\" \"", "Still woke up every morning.\" \"", "And he worked on his appeal.\" \"", "You know why?\" \"", "'Cause it gave him something to live for.\" \"", "You have to stop being such a coward, cuz,\" \"Let a little hope in.\" \"", "Dude, I can't believe you were in the slammer.\" \"", "With bernie madoff.\" \"", "No, ralph madoff.\" \"", "Moneyman for the mob.\" \"", "No relation.\" \"", "But the point stands.\" \"", "Evie was willing to go up in a seaplane with you,\" \"And you're not willing to entertain a future for her.\" \"", "Wimp.\" \"", "Hope.\" \"", "You get it.\" \"", "Hey.\" \"", "Hi.\" \"", "Do you remember that-that night in college.\" \"", "When I had that dream?\" \"", "About our future?\" \"", "Yeah.\" \"", "I still believe in it.\" \"", "I-I know in-in my bones.\" \"", "That...\" \"You and I end up together.\" \"", "But I also know that you're still in this exploration phase.\" \"", "And, honestly, I am, too.\" \"", "I-I'm really coming into my own professionally right now,\" \"And I love it.\" \"", "But, because of this injury,\" \"I missed my deadline yesterday, and i...\" \"It suddenly gave me some clarity.\" \"", "Our lives aren't in sync right now.\" \"", "We just can't seem to get our timing right, can we?\" \"", "Not yet.\" \"", "But in five months,\" \"When that asteroid doesn't hit.\" \"", "And you see everything with clear eyes...\" \"We should talk.\" \"", "Fig.\" \"", "It's perfect.\" \"", "Pete really outdid himself.\" \"", "So did hank.\" \"", "I'm sorry?\" \"", "For what?\" \"", "What did you just say?\" \"", "for what?\" \"", "Before that.\" \"", "Before what?\" \"", "About hank.\" \"", "Just that he put most of the wedding together.\" \"", "Here's your bouquet.\" \"", "I-i...\" \"There's my bride-to-be-once-again.\" \"", "Hello, pete.\" \"", "So, listen, didi, um,\" \"Before we re-re-tie the knot,\" \"Are we really going for it this time?\" \"", "We're here.\" \"", "All the trappings of a lovely wedding.\" \"", "Are in place.\" \"", "I don't care.\" \"", "So much about the trappings as I do your heart.\" \"", "And I don't fancy spending a lot of money.\" \"", "On legal fees for a third divorce.\" \"", "When I could spend it on my dream trip to ireland.\" \"", "Is your heart really in it?\" \"", "I know how much you love the lord of the dance.\" \"", "I don't want to deny you that.\" \"", "What is going on?\" \"", "I just talked to deirdre.\" \"", "The wedding is off.\" \"", "Halleluj...\" \"Although it's a shame that all this meticulous planning.\" \"", "Will go to waste.\" \"", "What?\" \"", "This is so weird.\" \"", "I love it.\" \"", "Okay.\" \"", "Dear colleagues,\" \"We were gathered here to celebrate marriage.\" \"", "Of two other people,\" \"But now we are doing this.\" \"", "Yeah, mikhail, can we skip ahead to the vows?\" \"", "Da.\" \"", "Great.\" \"", "Sofia,\" \"I've done a lot of crazy things...\" \"And people... in my life.\" \"", "But nothing like this.\" \"", "I don't know what the future holds.\" \"", "I just know you're in it, and that's all I need right now.\" \"", "Well, I couldn't have said it any better.\" \"", "You take her?\" \"", "Yes!\" \"", "You, too?\" \"", "Hell yes.\" \"", "By power vested in me.\" \"", "And by internet web site, you are married.\" \"", "Kiss brides!\" \"", "Yeah.\" \"", "Hey.\" \"", "Hi.\" \"", "So, it turns out.\" \"", "Having jesse around is a bit like having jiminy cricket.\" \"", "On your shoulder.\" \"", "Only,\" \"With a lot more hair.\" \"", "He still hasn't cut it?\" \"", "It's massive.\" \"", "It's enormous.\" \"", "I...\" \"Always imagined having a big family.\" \"", "Five kids.\" \"", "Maybe living on a farm,\" \"Somewhere with enough land we could grow our own food.\" \"", "Sounds dreamy.\" \"", "And I always wanted to make goat cheese.\" \"", "Goat cheese?\" \"", "Hey, this is my hypothetical, statistically unlikely scenario.\" \"", "And, in it, I want to make goat cheese.\" \"", "Well, thank you for sharing it with me.\" \"", "It means a lot.\" \"", "I realize that...\" \"All this time I've been asking you.\" \"", "To live in the moment,\" \"I haven't once asked you.\" \"", "What you hope your future would look like.\" \"", "I'll show you.\" \"", "But I need a favor first.\" \"", "Okay.\" \"", "Do you still have big carl's phone number?\" \"", "Who's snoopy?\" \"", "This is xavier.\" \"", "Lou, nan, I'm xavier.\" \"", "Hi.\" \"", "That's quite the getup.\" \"", "Well, xavier and I have a surprise for you guys.\" \"", "I know you love racing and feeling the wind in your hair.\" \"", "And those days aren't over.\" \"", "Days of thunder!\" \"", "Now you can speed race your heart out again,\" \"Within the safe confines of the track.\" \"", "Lou.\" \"", "That is what I want my future to look like.\" \"", "Those two.\" \"", "You turkeys ready to burn some rubber?\" \"", "Yeah!\" \"", "Let's do it.\" \"", "Yes!\" \"", "You won!\" \"", "You won!\" \"", "Yeah!\" \"", "They got the same moves.\" \"", "Yep.\" \"", "Spazzy.\" \"", "It's genetic.\" \"", "And I'll tell you a secret, kiddo.\" \"", "Gets better with every year.\" \"", "Hey.\" \"", "I thought I should return the wedding gift you gave me,\" \"Since I did not, in fact, enter matrimony.\" \"", "You can give it to kareema and sofia.\" \"", "It's two vials of homemade swine flu vaccine.\" \"", "While you're here,\" \"I want you to have my bunker key.\" \"", "I thought you crossed me off your bunker list.\" \"", "I crossed you back on.\" \"", "I...\" \"Would be honored to repopulate the planet with you.\" \"", "If needed and/or possible.\" \"", "What are you doing?\" \"", "Hey.\" \"", "I am trying to find another astrophysicist.\" \"", "To look at my research.\" \"", "No,\" \"It's not what you think.\" \"", "I'm not trying to find someone.\" \"", "To prove me right...\" \"I'm trying to find someone.\" \"", "To prove me wrong.\" \"", "What do you mean?\" \"", "Do you remember that-that first night on the rooftop?\" \"", "When I said the asteroid had liberated all of us?\" \"", "I don't feel that way anymore.\" \"", "I let you in.\" \"", "I let hope in.\" \"", "And if that thing is coming,\" \"Then I've got to find a way to stop it.\" \"", "Because I want to spend a lifetime with you.\"" ]
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[ "random thoughts (to be continue)\n\nDo you know what i hate about summer here? ", "That we think that the wheather is too beautiful to just stay in your studio and making your fucking boring model. ", "And sometimes we think that we have enough time to just do it in your weekend and go outside have some fun and then in your weekend, you'll realised that \"WHY DONT YOU MAKE IT YESTERDAY? ", "BLOODY HELL I HAVE TOO MANY THINGS TO DO!!!\"", "\n\nThat what happens to me this week. ", "Im spending my night till 2 am (most of) in my studio. ", "I cant do this anymore. ", "OMG. ", "And my record was till 6 am in the next morning. ", "And my work was never done till nowww. ", "I want to scream looooooooud, i want a holiday, i want a REAL holiday. ", "Too many things to think.", "\n\nHere are my random 'worry' thoughts lately:\n\ni fly in the same day with BAUGESCHICHTE PRUEFUNG, thats why i hate my ticket\n\nbecause of my ticket too, i cant attend DIA-party at Hochschule, can you imagine how i hate my ticket?", "\n\nmy study progress for exams: 10% and the exams are in fucking 2 weeks. ", "DAMN im too lazy this semester, i spent too too toooo much time for partying. ", "not good.", "\n\nWE GOT A NEW FLAT!!!! ", "yes its a loft!!!! ", "yuhuhuhuhuuhuhu... we're going to move to this new loft this summer.. next semester will be fun, I SWEAR IT WILL! (", "aber bitte weniger party na maedels!!!!)" ]
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[ "[Low back pain during gestation].", "\nThis research qualitatively analyzed the contents of national and international scientific publications, indexed in the period from 1999 to 2005, about low back pain in gestation. ", "Around 50 % of pregnant women complain about low back pain. ", "The physiologic modifications that occur happen in pregnancy alter the posture of pregnant women and the largest incidence of low back pain usually happens in the last three months. ", "Specific causes remain unknown. ", "However, treatment involves analgesics, antiphlogistics, exercises and physiotherapy. ", "Low back pain during gestation is a symptom that causes great discomfort and, depending on the level of pain, it generates motor disability and impairs daily activities, besides causing problems to take care of the baby after birth. ", "Some discomfort of low back pain can continue for a period of up to three years after childbirth. ", "We see a great need for further research in this subject area, in order to provide a better quality of life for pregnant women." ]
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[ "Martina Fietz gehört seit Mai 2010 zum Team von \"Focus Online\", wo sie von Berlin aus über das politische Geschehen berichtet. ", "Bereits in den 90er Jahren schrieb Fitz für die \"Welt\" aus Bonn. ", "Mit dem Regierungsumzug wechselte die studierte Historikerin 1999 nach Berlin. ", "Für die \"Bunte\" baute sie dort ein Hauptstadtbüro auf. ", "Nach zwei Jahren als Chefkorrespondentin der \"Welt am Sonntag\" gehörte Fietz 2004 zum Gründungsteam von \"Cicero\" und arbeitete für das Monatsmagazin bis zu ihrem Wechsel in den Online-Journalismus.", "\n\n\"Wir danken Martina Fietz für ihren großen Einsatz und die tolle Zusammenarbeit - ihre Expertise und ihr charmantes, humorvolles Wesen werden uns bei BurdaForward fehlen. ", "Zugleich freuen wir uns, dass Martina Fietz in einer für unsere Gesellschaft bewegten Zeit die wichtige Aufgabe übernimmt, die Politik der neuen Bundesregierung zu erklären, und wünschen ihr dafür alles Gute\", so ihr bisheriger Arbeitgeber.", "\n\nFietz wird ihr neues Amt im Sprecherteam mit Regierungssprecher Steffen Seibert und der stellvertretenden Regierungssprecherin Ulrike Demmer am 16. ", "April 2018 übernehmen.", "\n\nFietz folgt auf Georg Streiter, der im Jahr 2011 als stellvertretender Sprecher der Bundesregierung anfing. ", "Zuvor war er in Brüssel Sprecher von Silvana Koch-Mehrin. ", "In seiner Journalistenkarriere arbeitete Streiter für \"Bonner Rundschau\", \"Bild\", \"Express\", \"Hamburger Morgenpost\", \"stern\", \"Bild am Sonntag\" und \"Max\".", "\n\nRegierungssprecher von Angela Merkel ist seit August 2010 Steffen Seibert.", "\n\nExklusive Storys und aktuelle Personalien aus der Medien- und Kommunikationsbranche gibt es von Montag bis Freitag in unserem Newsletter \"kressexpress\". ", "Kostenlos abonnieren." ]
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[ "Kim:\n\nGlad you can attend. ", " Yes, please join us from 1PM-4PM. ", " \n\nColleen, can you add Kim Godfrey to the Experience Enron group?", "\n\nThanks.", "\n\nSarah-Joy\n---------------------- Forwarded by Sarah-Joy Hunter/NA/Enron on 12/01/2000 \n07:32 AM ---------------------------\nFrom: Kim Godfrey@ENRON COMMUNICATIONS on 11/30/2000 07:34 PM\nTo: Sarah-Joy Hunter/NA/Enron@ENRON\ncc: Colleen Koenig/NA/Enron@Enron, Jennifer Medcalf/NA/Enron@Enron \n\nSubject: Re: invitation to meeting with senior Compaq executives from 1-4PM 3 \nAllen Center 11C1, December 14th \n\nSarah,\n\nThanks to you and Jennifer for arranging. ", " I will be in attendance at 3:00 \npm and have asked either Jim Crowder or Everett Plante to also attend. ", " I do \nnot know their availability yet due to the Enron PRC meeting conflicts. ", " Is \nit possible for me to attend starting at 1:00 pm - I have not been through a \ncomplete Experience Enron meeting ?", "\n\nthanks again for your help.", "\n\nKim \n\n\n\n\n\tSarah-Joy Hunter@ENRON\n\t11/30/00 06:16 PM\n\t\t \n\t\t To: Kim Godfrey/Enron Communications@Enron Communications\n\t\t cc: Jennifer Medcalf/NA/Enron@Enron, Colleen Koenig/NA/Enron@Enron\n\t\t Subject: invitation to meeting with senior Compaq executives from 1-4PM 3 \nAllen Center 11C1, December 14th\n\nHi Kim,\n\nHope you had a great Thanksgiving. ", " Jennifer Stewart Medcalf had asked me to \ninvite you to a meeting with senior Compaq executives on\nDecember 14th. ", " Though the meeting will start at 1PM, Jennifer is \nspecifically requesting your presence from 3-4 PM when discussions will focus \non the Compaq/EBS relationship. ", " Other Compaq executives besides \"Keith\" will \nbe there.", "\n\n\nAn agenda and listing of attendees will be e-mailed to you the week of \nDecember 11th.", "\n\nThanks for confirming back with Jennifer Medcalf your availability, from 3-4 \nPM, December 14th. ", " She can be reached at ext.#6-8235.", "\n\nSarah-Joy Hunter" ]
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[ "We are humbly asking that you will sign this petition to let Chuck E Cheese know that it is a violation of the American Disabilities Act to deny my disabled daughter and her father access to an empty women's restroom.", "\n\nOUR STORY: My 9 year old, Marley Eschoe, was attending another child’s birthday party at a Chuck E. Cheese location in Georgia this May when her father, Mark Eschoe, who brought Marley to the party, was not allowed to take her into an empty women's restroom, when the men's restroom was occupied.", "\n\nMarley, who suffers from lupus, had been recently released from a 3 month stay in the hospital after suffering her 2nd stroke in 8 months. ", "She was using a wheelchair and needed assistance walking and going to the restroom. ", "This was one of Marley’s first time out for an event after her hospital stay and our family was so excited for a fun day as we were still adjusting to our “new normal.”", "\n\nMarley’s father, Mark Eschoe, was denied access to an empty female restroom and told he would have to take his then 8yr old daughter to the men's restroom regardless of it being overcrowded. ", "Knowing that Marley needed to use the bathroom urgently, my husband even requested that a female Chuck E. Cheese employee who was exiting the restroom stand by the door while he took his daughter into the empty female restroom. ", "That request was also denied by Chuck E. Cheese management. ", "Mark informed Chuck E. Cheese management about Marley's medical condition and asked for assistance. ", "The manager’s response was, “I don't care if she has special needs, I’m not going to treat her any differently from my other patron. ", "I’m done with you.” ", "Then, she abruptly walked away after threatening to call the police to have him removed.", "\n\nOur family was shocked. ", "We informed the national management of Chuck E. Cheese about our experience and the company said it would conduct an internal investigation. ", "After months of “investigating” (which did not include reaching out to us), Chuck E. Cheese informed us that they stood by the local manager who they feel did nothing wrong.", "\n\nBut what Chuck E. Cheese hasn’t said is that not only was the way their employee handled this situation offensive and hurtful to a vulnerable child and her family, it was also illegal. ", "The Americans with Disabilities Act (ADA) requires access to bathrooms for people with disabilities. ", "We’re concerned that Chuck E. Cheese did not comply with the ADA -- and that other families will be affected by this attitude as well.", "\n\nWe don’t want any other family to have to go through what we went through. ", "We’re asking Chuck E. Cheese to ensure that its locations across the country comply with the Americans with Disabilities Act and that staff are appropriately trained to handle these situations. ", "Chuck E. Cheese says its a place for “fun for all” -- we’re hoping your company will make this motto a reality." ]
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[ "p53 gene deletions in paraffin-preserved lymphoid tumors from irradiated mice.", "\nExperiments were performed to measure deletions in the p53 gene in paraffin-embedded tissues (tumors and control) derived from mice exposed to gamma-rays or neutrons up to 28 years ago. ", "Deletions in exons 1, 3, 4, 5, 6, 7 and 9 were monitored by PCR and Southern blotting techniques. ", "The results of these experiments demonstrated p53 deletions in only 1/6 spontaneous tumors but in 5/6 gamma-ray-induced and 5/6 neutron-induced tumors. ", "Exons deleted in tumors from gamma-ray exposed mice were similar to those deleted in tumors from neutron-exposed mice. ", "They document differences in spectra of p53 deletions in comparing spontaneous radiation-induced tumors." ]
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[ "Tinel's Sign: (Named after French neurosurgeon Jules Tinels, 1879-1952). ", "Tinel's sign is a tingling sensation in the distal part of an extremity in response to pressure or percussion over the site of a partially divided nerve. ", "It can signify regeneration of the nerve.", "\nEvaluation of the state of regeneration of peripheral nerves oftentimes involve attempts to elicit a Tinel's sign. ", "Unfortunately, clinicians try and elicit this sign using varying degrees of force when percussing the nerve. ", "However, any nerve will \"tingle\" if hit with enough force; hitting one's \"funny bone\" is an example. ", "Such tingling is a positive percussion result rather than a sign of a regenerating nerve. ", "Therefore, there can be a high incidence of false positive Tinel's signs due to high degrees of percussion force as well as a missed Tinel's sign because of too little force.", "\nDuring World War I, two different physicians observed, independently of each other, that when a damaged sensory nerve is regenerating the patient experiences a tingling sensation in the area of skin supplied by that nerve. ", "As the nerve regenerates, the sensation moves distally on the extremity, and the sign can be produced by tapping the course of the nerve on the wounded extremity. ", "Hoffman in Germany and Jules Tinel in France both reported this phenomena in 1915, and although Hoffman actually published first, it was Tinel who received credit. ", "In his later works, Tinel noted that the tingling sensation appeared 4-6 weeks after injury and he hypothesized that it was caused by regenerating axons.", "\nSince that time, the inferences that can be determined from a Tinel's sign has diverged markedly from its original conception. ", "A literature review discloses that there is really no consensus on what it actually indicates. ", "In 1966, Phalen.sup.1 tested 654 hands with carpal tunnel syndrome and found the Tinel's sign was present in 73% of them. ", "He concluded it was a good diagnostic sign of an entrapped nerve. ", "However, Stewart and Eisen.sup.2 in 1978 determined that Tinel's sign had little diagnostic value. ", "In a series of patients with carpal tunnel syndrome, 45% had a positive percussion test and, in a series of patients without carpal tunnel syndrome, 29% had a positive reading. ", "They concluded that Tinel's sign was of little diagnostic value. ", "Reports by Heller.sup.3 in 1986, Seror.sup.4 in 1987, and Katz.sup.5 in 1990 also concluded the Tinel sign had little diagnostic value. ", "FNT .sup.1 Phalen, G. S. The carpal tunnel syndrome. ", "Seventeen year's experience in diagnosis and treatment of six hundred fifty-four hands. ", "The Journal of Bone and Joint Surgery, 48-A (2): 211-228, 1966. ", "FNT .sup.2 Tinels sign and the carpal tunnel syndrome. ", "British Medical Journal, 1125-1126, Oct. 21, 1978. ", "FNT .sup.3 Heller, L., Ring, H., Costeff, H., and Solzi, P. Evaluation of Tinel's and Phalen's signs in the diagnosis of the carpal tunnel syndrome. ", "Eur. ", "Neuro, 25:40-42, 1986. ", "FNT .sup.4 Seror, P. Tinel's sign in the diagnosis of carpal tunnel syndrome. ", "The Journal of Hand Surgery, 12-B (3): 364-365, 1987. ", "FNT .sup.5 Katz, J. N., Larson, M. G., Sabra, A. Krarup, C., Stirrat, C. R., Sethi, R., Eaton, H. M., Fossel, A. H., & Liang, M. H. The carpal tunnel syndrome: Diagnostic utility of the history and physical examination findings. ", "Annals of Internal Medicine, 112:321-327, 1990.", "\nMore recently, applicant conducted tests to determine at what threshold force a positive percussion test is elicited for each of seven nerve locations in the forearm. ", "With knowledge of the amount of force necessary to produce a positive test in healthy subjects, examiners could use a lesser force to ensure that the response was a true Tinel's sign and not simply the nerve responding to an excessive amount of force.", "\nTesting was done using specially designed hammers capable of delivering a precise force of 1, 2, 3, 4, or 5 pounds. ", "Seven locations on each forearm were tested a multiple of times at each level using each weight force on each location. ", "If a subject felt tingling and paresthesia following an impact it was counted as a positive response. ", "This is termed the threshold force; e.g. the lowest force which elicited the tingling sensation for each location.", "\nThe seven specific locations tested were: (1) The radial nerve in the forearm under cover of the brachioradialis muscle near the lateral epicondyle of the humerus; (2) The median nerve where it passes between the two heads of the pronator teres in the antecubital fossa; (3) The median nerve where it lies deep to the flexor carpi radialis at the wrist; (4) The ulnar nerve where it passes behind the medial epicondyle at the elbow; (5) The ulnar nerve under cover of the flexor carpi ulnaris and under the flexor retinaculum at wrist; (6) The ulnar nerve at the carpus next to the pisiform bone, and (7) The median nerve at the base of thenar eminence. ", "These seven locations include all the nerves in the forearms which are accessible to surface touch.", "\nThreshold readings were as follows: Site number 1, the radial nerve in the forearm near the epicondyle of the humerus--3 pounds (5.8% false positive rate); Site number 2, the median nerve in the antecubital fossa--4 pounds (4.2% false positive rate); Site number 3, the median nerve at the wrist--3 pounds (10% false positive rate); Site number 4, the ulnar nerve at the elbow--2 pounds (10.8% false positive rate); Site number 5, the ulnar nerve at the wrist--3 pounds (5% false positive rate); Site number 6, the ulnar nerve at the carpus next to the pisiform bone at the base of the palm--2 pounds (5% false positive rate); and Site number 7, the median nerve at the base of the thenar eminence--3 pounds (5% false positive rate).", "\nThe results showed the ulnar nerve at the elbow had the lowest threshold for a positive response; that is, it took less force to elicit a positive percussion test in this location than the other locations. ", "It took only two pounds of force to elicit a tingling response in 10% of the subjects. ", "At the other end of the spectrum, the median nerve at the antecubital fossa had the highest threshold for a positive response, that is, it took more force to elicit a positive percussion test in this location than the other locations. ", "It took four pounds of force to elicit tingling sensation in only 4.2% of the subjects, and even at five pounds, only 6.7% had a positive response.", "\nIt was determined that each nerve has a specific threshold force which will elicit a positive percussion test. ", "Laplace's law states that Tension=Transmural Pressure.times.", "Radius of the Cylinder. ", "In other words, percussing with great force over the nerve will increase the pressure inside the nerve to the point where the nerve will depolarize and give a tingling sensation. ", "If the nerve is percussed at this force or above, the positive reaction may be falsely interpreted as a Tinel's sign.", "\nThe differing force necessary at each location can be explained by how close to the surface the nerve is. ", "Nerves which lie just under the skin require less force to elicit a response than those which lie under tendon and muscle. ", "In addition, nerves which are already under pressure from disease or injury will depolarize more rapidly than a nerve not under pressure. ", "Injured nerves, therefore, require less force to elicit a response.", "\nWith reference to the prior art, Alban, 4,505,278 discloses a plunger-type device to measure pain thresholds. ", "It is a gradual pressure device that would not work in applicant's methods. ", "The Torricelli patents, 2,685,286; 2,744,520 and 2,800,895, disclose spring charged reflex guns for striking reflex nerve areas. ", "There are no standards with which the force has been calculated. ", "The Torricelli design are apparently to act as a replacement for the ordinary reflex hammer found in most medical offices. ", "In each device, Torricelli obtains his strength by degree of compression. ", "Applicant, on the other hand, first determines the force necessary and then uses a force to accurately administer that force. ", "The spring is biased the same amount for each strike." ]
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[ " -5*v for g.\n4\nLet n(h) = 2*h**2 - 74*h - 48. ", "Let l(b) = b**2 - 25*b - 16. ", "Let q(k) = -8*l(k) + 3*n(k). ", "Let r be q(-10). ", "Solve -v - 4 = 4*s, 0*v = 5*s + r*v - 6 for s.\n-2\nSuppose 5*t + 3*u = 6*u + 112, 5*u = t - 18. ", "Solve 0 = -4*j + 2*f + f - t, 0 = -3*f + 3 for j.\n-5\nLet f be 0*((-5)/2 + 2). ", "Let a be (2 - f/(-4)) + 3. ", "Let q(v) = 24*v**3 + v. Let t be q(1). ", "Solve -4*g + 5*b = -a*g - t, -5*b - 25 = 4*g for g.\n0\nLet g(s) = -6*s - 4. ", "Let v be g(-3). ", "Suppose -2*n + v = 5*n. ", "Suppose 24 = w - 4*y, 0 = n*w - y + 3 - 16. ", "Solve j = -w*x + 20, 3*x = -2*j - 0*j + 20 for j.\n4\nLet z be (-3 - 68/(-20))*-5. ", "Let h = 4 + z. Suppose 2*q - 5 = 5. ", "Solve -q = l + g, g + 11 = -2*l - h*g for l.\n-4\nLet i(x) = -12*x - 56. ", "Let n be i(-6). ", "Solve -r = 4*p - n, -3*p = 2*r - 22 + 5 for r.\n4\nSuppose 0*q - 4*q + 280 = 0. ", "Let p = 70 - q. Solve 3*i + 15 = -0*n - 3*n, p = -2*n + 3*i for n.\n-3\nLet s be (-12)/3 - 2 - -8. ", "Solve -s*v - v - 3 = 5*k, 3*k + 5 = -5*v for k.\n0\nLet o(k) = -k**2 + 17*k + 25. ", "Let t be o(0). ", "Solve -5*m - t = 5*d, -3*d = m + 2 + 7 for d.\n-2\nSuppose -4*d = -b + 10, -b = -4*b + 4*d + 14. ", "Suppose -2*m + x = -33, b*x + 82 = -0*m + 5*m. ", "Solve -4*j + 13 = 1, 4*h - 4*j = -m for h.\n-1\nLet u be ((-26)/130)/((-2)/50). ", "Solve 0*v + 20 = 5*b + u*v, v + 8 = 5*b for b.\n2\nSuppose 4*d - 3*u = 51, 3*d - 50 = u - 8. ", "Suppose 0 = -5*q - 5*a + d + 15, 3 = q - 2*a. ", "Solve 0 = -q*t + 3*o + 2, 3*t - o - 2 = -0 for t.\n1\nLet a = 41 - 39. ", "Let r be 5/a*30/25. ", "Let h be 5 + 0 + 2/(-1). ", "Solve r*m + m - 4*f = -12, -h*f - 9 = 3*m for m.\n-3\nLet o = 25 - 21. ", "Solve -o*m = 4*j - 8, 2*m = -0*m + 10 for j.\n-3\nSuppose -3*n + 5*h + 55 = 0, 0 = 4*n + 4*h - 62 - 22. ", "Solve 0 = a + 3*a - 16, 0 = -4*z + 4*a - n for z.\n-1\nLet y = 11 - 3. ", "Let z(l) = l**3 - 7*l**2 - 7*l - 5. ", "Let k be z(y). ", "Suppose -k*t + 2*t + 5*r = -8, -7 = -3*t - 2*r. ", "Solve 2*h - 5*w = -7, t*h - 5*w = -w for h.\n4\nSuppose -31 + 13 = -6*n. ", "Suppose 4*j - 4*u - 63 = u, u + 39 = n*j. ", "Solve y = 2*t - 10, -2*y = -4*t + 2*t + j for y.\n-2\nLet g be -1*3*(-20)/15. ", "Let r be 38/57 - g/(-3). ", "Solve 2 = -4*x - r*i, -4*i + 5 = -3*x + 8*x for x.\n-3\nLet b be -3 - -6 - 2/2. ", "Let g(c) = 3*c**2 + 12*c - 18. ", "Let x be g(-8). ", "Suppose 7*z = 62 + x. Solve -3*a + 1 = 5*r + z, -b*r = -4*a - 8 for r.\n-2\nLet r be 3/(-7) - (-27)/63. ", "Solve r = -2*q - 3*w - 11, 2*w = -6 for q.\n-1\nLet p = 263 + -260. ", "Solve k + 2*f = -5, -5*f - 23 = 2*k - p*k for k.\n3\nSuppose t - 3*a + 7 = 2, 6*t - 30 = -2*a. ", "Solve -15 = x - t*z - 0*z, 5*z = 2*x + 21 for x.\n-3\nLet r be (-40)/12*51/(-34). ", "Let o be 4/6 + 39/9. ", "Solve -5*w = 0, -2*w + o = -r*x - w for x.\n-1\nLet x(k) = 5*k**2 - 2*k - 2. ", "Let t be x(-1). ", "Let m = -1 + t. Solve -4*b = -4*f + 4, 2*b + 13 = f + m*b for f.\n5\nLet p(b) = b**2 - 24*b + 3. ", "Let q be p(24). ", "Solve q*h - 2 - 19 = -3*i, 0 = -5*h + 2*i + 7 for h.\n3\nSuppose 4*s + 14 = 3*u + 48, 5*s = -4*u + 58. ", "Solve -2*m + s = -4*w, m + 5*w + 8 = -8 for m.\n-1\nLet n = -114 + 109. ", "Let c be 12*8/12 + n. Solve -r - 2*r - 12 = 0, -5*i = c*r - 8 for i.\n4\nLet m(y) = y**2 + 19*y - 46. ", "Let j be m(-22). ", "Solve 5*d + 2*b + j = 0, -5*d + 5*b + 5 = 2*b for d.\n-2\nLet g(n) = n**2 - 15*n - 181. ", "Let j be g(-8). ", "Solve 4*f = j*k - 0*f + 14, 2*f = 2*k + 8 for k.\n-2\nLet o be (0 - 76/(-12))/(1/3). ", "Let p = 15 + o. Solve -p = 5*a - 3*h, 4*a = -3*h + 4*h - 23 for a.\n-5\nSuppose 5*w - 4*w + 4*j = -10, 18 = -4*w - 5*j. ", "Let t = 0 - w. Solve t*v - 4*y + 20 = 4*v, -2*y + 14 = 2*v for v.\n4\nLet q(v) = 2*v**2 - 12*v - 12. ", "Let r be q(7). ", "Suppose 0 + 8 = g - 5*u, -3*u + 3 = r*g. ", "Solve -4*w = -g*w + 2*l - 3, l = w - 3 for w.\n3\nLet r(y) = y - 2. ", "Let s be r(4). ", "Suppose u + 4*b + 7 = 3, 1 = -4*u - b. Let d = -73 - -75. ", "Solve d*g - 3*v + 4 = u, -2*g + 2*v + s*v - 2 = 0 for g.\n-5\nLet r = -6 + -7. ", "Let y = -8 - r. Suppose -5*v + 5*m = -0*m + 5, -5*m = 2*v - y. Solve v*i = 3*i - 9, -4*d - 7 = -5*i for d.\n2\nLet q be 0 + -1 + 15*1. ", "Suppose -5*n + q = -11. ", "Let w be (0/(n + -2))/(-2). ", "Solve 5*b + 18 = 3*o - 4, w = 2*b + o for b.\n-2\nSuppose 0*h + 3*h - 168 = 0. ", "Suppose 3*l + h = 4*d + l, -69 = -5*d + 3*l. ", "Solve 3*o - d = -4*r, r + 2*o = 5*r + 10 for r.\n0\nLet l(v) = v**2 - 22*v + 18. ", "Let t be l(10). ", "Let w = -100 - t. Solve 2*k - d - 7 = 0, -4*d = -k + w*k - 8 for k.\n4\nLet d = -24 - -3. ", "Let t = d - -16. ", "Let z = -2 - t. Solve -z*j - 6 = 0, -4*v - v - 35 = 5*j for v.\n-5\nLet q be -12*2/(-12)*4. ", "Suppose -7*t = -5*t - q. Solve -t*r = -3*a - 32 + 8, -3*a + 2*r - 18 = 0 for a.\n-4\nSuppose u + 4*o - 16 = 3*u, 4*u - o = -4. ", "Let y be (1 + u - 21)*4/(-16). ", "Solve -4*s - 4*b + 0 = 8, s + y = 2*b for s.\n-3\nSuppose -18*r + 26 = -16*r. ", "Let u be 3 + (-4)/8*2. ", "Solve 6 = -4*w + 2*v, u*w + 0*w = 3*v - r for w.\n1\nLet a = -10 + 11. ", "Let k be 43 - (0 + 3) - a. Suppose -k = -4*m + m. Solve -l = -5*u + m, -2*l + u = -0*u - 1 for l.\n2\nLet z(d) = -3*d + 2*d**2 + 5*d + 1 + 2*d**2. ", "Let g be -4 - ((-6)/2 - 0). ", "Let o be z(g). ", "Solve -3 = -2*r + o*b, -2*r - 3*r + 13 = -2*b for r.\n3\nLet d = 25 - 9. ", "Let o be d/(-64) + 13/4. ", "Suppose 2*m + 3*q - 27 = -m, 3*q = -2*m + 15. ", "Solve -m + 5 = 2*f + 3*b, -o*f + 4*b - 19 = 0 for f.\n-5\nSuppose 5*f = w + 5, 9*w - 4*w = -4*f + 33. ", "Let r(b) = -b**2 + 12*b + 9. ", "Let a be r(12). ", "Solve -a = 3*x + v + f*v, -3*x = 2*v + 8 for x.\n-2\nSuppose 0 = 4*j + 3*f - 27, 0 = -5*j + 3*f. ", "Solve j*h + 3 = 3*c - 2*c, 4*c + 5 = -5*h for h.\n-1\nSuppose 0 = -n - 4*g - 6, 3*n - 5 + 3 = -2*g. ", "Let t = n + -10. ", "Let s(a) = -a**2 - 8*a + 5. ", "Let d be s(t). ", "Solve d*f = 5*r, 0 = -2*f - 2*r - 2*r - 12 for f.\n-2\nSuppose -7*s - 14 = -14*s. ", "Solve -s - 3 = 5*u, 0 = -2*g - 3*u - 7 for g.\n-2\nLet o(q) = q**3 - q**2 - q - 5. ", "Suppose 0 = -3*b + 4*w - 12, -b = 2*b + w - 3. ", "Let h be o(b). ", "Let k = -4 - h. Solve t = -2*g + k, -3*t + 2*g - g + 17 = 0 for t.\n5\nLet y(n) = n - 1. ", "Let j(z) = 8*z - 49. ", "Let a(t) = -j(t) + 5*y(t). ", "Let r be a(10). ", "Solve 5*w - 4*v = r, 4*v + 8 = 2*w - 0*w for w.\n2\nLet o be (2/(-4))/((-11)/44). ", "Let y = -6 + 10. ", "Let b = -3 + y. Solve -q - 3*w = -b + 7, -4 = -o*q + 2*w for q.\n0\nSuppose 0 = s - 5*s + 40. ", "Let u be 3 + 1 + -6 + 7. ", "Solve j + 4*j + 5*o - s = 0, 5*j - 10 = u*o for j.\n2\nLet j(l) = -l**2 - l. Let x be j(0). ", "Let u(z) = z**3 - 7*z**2 + 9*z + 9. ", "Let s be u(5). ", "Solve 1 = a - s*h, 5*a - 5 = 5*h - x for a.\n1\nSuppose l = 3*o + 2*o + 13, 5*o + 10 = 0. ", "Let i = 14 + -6. ", "Let g = 10 - i. Solve -2*j = -2*v - 18, 3*j = -g*v + l*v + 19 for v.\n-4\nSuppose -5 = 6*h - 29. ", "Suppose -h = -3*t + 11. ", "Solve t*q + 15 = y, -y - 2*q = 3*y + 6 for y.\n0\nSuppose o - 2*o = 5*r - 27, -2*o + 19 = 3*r. ", "Solve 8*j = 5*c + r*j + 9, 3*c + 5*j + 19 = 0 for c.\n-3\nLet d = -218 - -220. ", "Solve -3*y + 6 = -3*m - d*y, -4 = m - y for m.\n-1\nSuppose d - 5 = 0, 2*r - 6*r = -2*d + 2. ", "Solve 3 = 3*j - r*z, 3*j + 3*z - z + 9 = 0 for j.\n-1\nLet o(q) = -1 - 1 + 0 - q + 11. ", "Let s be o(9). ", "Suppose 3*x - x = s. Solve 0 = -l + 2*z - 7, 4*l - 4*z + 24 - 4 = x for l.\n-3\nSuppose 10*r - 30 = 11*r. ", "Let k be 8/10*r/(-12). ", "Suppose 4*t - 25 = -c + 2, 11 = -2*c + 5*t. ", "Solve k*v - v + c = -x, 0 = v + 5*x + 27 for v.\n-2\nSuppose -8*d + 25 = 9. ", "Solve 0*j + d*j - 2 = -f, 5*f - 2*j + 26 = 0 for f.\n-4\nLet d be 4176/(-108) - ((-5)/3 - -2). ", "Let p = -36 - d. Solve -2*q - 6 = -4*i - 0, 0 = i + p*q - 19 for i.\n4\nLet l(j) = j**2 + 8*j + 18. ", "Let p be l(-5). ", "Solve k - 1 + 4 = p*u, -12 = -4*k for u.\n2\nSuppose -8*h = -3*h. ", "Suppose -k + 0*k + 2 = h. Suppose -4*d + 31 = -5*f, -7*d + k*d + 8 = 4*f. ", "Solve 2*v - 30 = -m - d*m, 0 = 3*m - 2*v - 2 for m.\n4\nLet n(b) be the second derivative of -b**4/4 - 2*b**3 + 2*b**2 - 15*b. ", "Let j be n(-4). ", "Solve 4 = v + p + 3, v + j*p = 7 for v.\n-1\nSuppose 16*x - 13*x - 99 = 0. ", "Suppose -13 = 5*f - x. Solve 5*m = -y - 5, -7*y - 1 = -f*y + m for y.\n0\nLet c(v) = -v**3 - 8*v**2 - 7*v - 50. ", "Let x be c(-8). ", "Solve 0 = 4*p + 2*o - 16, -5*p - x = -3*o - o for p.\n2\nSuppose 5*s = -2*l + 21, 2*s + 2*s - 14 = -3*l. ", "Solve -2*p = -s*i - 18, 4 - 23 = -p + 5*i for p.\n-1\nSuppose -4*i + i = 0. ", "Suppose -v + 4 = 12. ", "Let c be (3 + -2)/((-4)/v). ", "Solve 2*l - 5*w = 15, i*w - c*w = 2 for l.\n5\nLet y be 1/4 - (-35)/20. ", "Let j be (-10)/(-4 - (-4 + y)). ", "Solve -m = 5*f - j, -2*f + 6 - 2 = 0 for m.\n-5\nSuppose 3*h - 38 = -5*o, -2*o - 22 = -5*h - 0*o. ", "Let u be 6 - (h/2 - 0). ", "Solve 4*f - 27 = f - u*l, 5*f - 2*l = 17 for f.\n5\nLet w(l) = 4*l + 1. ", "Let x be w(-5). ", "Let u = -19 - x. Suppose u = -0*v - v + 5. ", "Solve 0*f + 3 = 3*f - 3*s, v = f - 5*s for f.\n0\nSuppose " ]
{ "pile_set_name": "DM Mathematics" }
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[ "Research and Reflections on Zhang Taiyan\n\nNo metrics data to plot.", "\n\nThe attempt to load metrics for this article has failed.", "\n\nThe attempt to plot a graph for these metrics has failed.", "\n\nThe full text of this article is not currently available.", "\n\nBrill’s MyBook program is exclusively available on\nBrillOnline Books and Journals. ", "Students and scholars affiliated with an\ninstitution that has purchased a Brill E-Book on the BrillOnline platform\nautomatically have access to the MyBook option for the title(s) acquired by the\nLibrary. ", "Brill MyBook is a print-on-demand paperback copy which is sold at a\nfavorably uniform low price.", "\n\nHistorians generally describe Zhang Taiyan 章太炎 (Binglin 炳麟, 1869–1936) as an anti-Manchu revolutionary and treat his Buddhism as subordinate to this larger political project. ", "Far less commonly understood is Zhang’s role in preparing the groundwork for the establishment of Chinese philosophy as an academic discipline. ", "Against the backdrop of an intellectual climate in Japan and China during the decades either side of 1900, in which a premium had come to be placed on logic as a precondition for the development of philosophy, Zhang was one of the first Chinese intellectuals to follow the lead of Japanese scholars in maintaining that classical Chinese philosophers had developed indigenous forms of logic. ", "Significantly, he further argued that Chinese versions of Yogācāra texts on Buddhist logic and epistemology (yinming 因明; Skt. ", "hetu-vidyā) made it possible once again to gain a proper understanding of China’s earliest writings on logic. ", "In this paper I argue that Zhang sought to establish that early Chinese texts “bear witness” to insights into realities that transcend individual cultures but are most fully and systematically articulated in Yogācāra systems of learning; and that classical Chinese philosopher-sages had attained an awareness of the highest truths, evidence of which can be found in their writings. ", "In short, I will show that Zhang used Yogācāra to affirm the value of “Chinese philosophy” and, in doing so, helped shape its early definition." ]
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[ "Almost Half Of All Working College Graduates Are Overqualified For Their Jobs\n\nWhile the rich have gotten richer from State bailouts and subsidies the 99% rest of the country have slid into wage slavery. ", "A slavery predicated on workers taking on suffocating debt just to be educated. ", "Education in most countries is partially or fully paid for by the government as it is seen as an investment in the future. ", "But America is a little different. ", "As Chairman Greenspan liked to point out heavily indebted workers don’t strike or make demands and the powers that be would rather destroy the middle class than dare have to pay out higher wages.", "\n\nBut there was always some vain hope and constantly repeated mantra from parents and the media that taking out epic amounts of debt to go to college was always worth it – not so much:\n\nNearly half of working Americans with college degrees are in jobs for which they’re overqualified…\n\nEarnings in 2011 averaged $59,415 for people with any earnings ages 25 and older whose highest degree was a bachelor’s degree, and $32,493 for people with a high school diploma but no college, the Census data show.", "\n\nVedder, whose study is based on 2010 Labor Department data, says the problem is the stock of college graduates in the workforce (41.7 million) in 2010 was larger than the number of jobs requiring a college degree (28.6 million).", "\n\nThat, he says, helps explain why 15% of taxi drivers in 2010 had bachelor’s degrees vs. 1% in 1970. ", "Among retail sales clerks, 25% had a bachelor’s degree in 2010. ", "Less than 5% did in 1970.", "\n\n“There are going to be an awful lot of disappointed people because a lot of them are going to end up as janitors,” Vedder says. ", "In 2010, 5% of janitors, 115,520 workers, had bachelor’s degrees, his data show.", "\n\nLiterally consigned to the dustbin of American society.", "\n\nTo recap America’s current economic system. ", "Those at the top are generally incompetent yet receive bailouts, guarantees, and in many cases outright welfare from the State. ", "The working (formerly middle) class is educated but poor, indebted, and increasingly underemployed. ", "While the poor are left to rot but are occasionally provided with some assistance so they do not starve or riot.", "\n\nHow much longer can this system go on? ", "How much longer should this system go on?" ]
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[ "Edward de Vere, Earl of Oxford was \"Shakespeare.\" ", "So... Who was Edward de Vere, Earl of Oxford? ", "Now we're talking.", "\n\nTuesday, April 24, 2007\n\nWill meets Queen! (", "Correction at 11)\n\nIf sunsets have seemed particularly red lately, this may be for good reason. ", "Clouds of housedust, blown from countless old anthologies the world over, have recently been lofted into the atmosphere over the announcement of the latest (ahem) Shakespeare \"discovery.\" ", "It was certainly true in this office, where, upon learning of a new Shakespeare poem, I (quite literally) turned to a cobwebby stack of dusty books that I've long been meaning to sell—so I could look this \"new\" poem up.", "\n\nThe verse is a choppy old thing. ", "It's an anonymous 18-line Elizabethan ditty that comes down to posterity as item 228 in an anthology of 400-year-old ditties and riddles and other miscellany, recorded by one Henry Stanford. ", "It's titled \"to ye Q. by ye players 1598.\" ", "It's hardly lustrous—though it does have some spear-shaking overtones. ", "Here: Read the old thing for yourself.", "\n\nPoint is that these 18 lines of anonymous verse, transcribed as part of their larger anthology in 1968, argued to (possibly) be by Shakespeare in 1972 and then published in book form in 1988, are just the latest dredgings that pass for bold new scholarship in the boneyard of conventional Shakespeare scholarship today.", "\n\nShakespeare, we are told, was \"a resident playwright at Richmond Palace\" at the time of this verse's royal recitation—which \"may well have been spoken by Shakespeare himself.\" ", "Plus Will was, says an editor of the new edition of the collected works that reprints the old thing, \"probably in the habit of dashing some lines down on the back of an envelope and then chucking them away.\"", "\n\nYuh-huh. ", "Did you know that there's just as much evidence that Shakespeare invented spaghetti? ", "That he whistled while he worked? ", "That he liked to wear red on Tuesdays?", "\n\nMost intriguing observation about the old thing, though, must go to James Shapiro, who in his recent book 1599: A Year in the Life of William Shakespeare writes:\n\n\"Shakespeare imagines Elizabeth as a timeless and rejuvenating force, likening her to a clock hand perpetually circling, resistant to the ravages of time, outliving generations. ", "There's a slight undertow to the conceit... the uncomfortable thought that Elizabeth will be around in a half century.\" [", "74-5]\n\nElizabeth was 65 years old at the time of this poem's known public reading. ", "Wishing that this senior citizen stick around for another couple generations is more than just a \"slight undertow.\" ", "It's downright bizarre.", "\n\nHowever, written to a much younger queen and then pulled out for old times' sake some two or three decades later is another story. ", "One of the tenets of both \"Shakespeare\" By Another Name and the larger Oxfordian movement is that proto-\"Shakespearean\" works first written for a courtly audience in the 1560s, '70s and '80s were later revised or just re-performed for Elizabeth in the waning years of her reign.", "\n\nIt's an open question. ", "Could this \"new\" poem, if indeed it is by the Bard, be like much of the rest of the Shakespeare canon: Bearing earmarks of a historical moment that was far too early to have been written by Will Shakspere of Stratford?" ]
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[ "Q:\n\nAuthentication Token Security\n\nWhat are the major flaws with authentication following the following logic.", "\nUser logs into a.example.com and clicks \"Login to b.example.com\". ", "This link generates a random string and saves it in the b.example.com database. ", "It then redirects to b.example.com/remotelogin.php?token=therandomstring which checks the database for that string and logs the user in. ", "\nThe only problem I could think of that it needs for security is a time limit for the token to be valid, which could be like 30 seconds or something.", "\n\nA:\n\nThis is hardly a user authentication scheme. ", "User authentication is about who the user is. ", "Also it is not very practical.", "\ne.g. If it expires in 30 seconds and the user makes a refresh in 40 seconds? ", "what then?", "\nWhat about malicious users sending links and having people logging in the web page? ", "Or what about malicious users flooding your database with loggins?", "\nDo you plan to have ssl or in those 30 seconds you are open to replay attacks? ", "The scheme you are proposing is not good at all and has many many more stuff that can go wrong.", "\nI guess what I am saying mostly is this (without trying be offensive):\nIf you do not hold any user relevant info why do you bother authenticating? ", "Against who doing what? ", "For example you cannot use this scheme in a social net app or a bank app or a forum like this. ", "If you do not do anything security sensitive then yes your scheme has no security flows but it has no flaws because it does not hold sensitive info. ", "\n\n" ]
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[ "Introduction\n============\n\nThe adolescent and young adult (AYA) generation means people in adolescent and young adulthood and is defined as a generation from 15 to 39 years old. ", "The study about cancer in this generation is defined as adolescent and young adult oncology (AYAO) by 2011 National Cancer Institute (NCI) Cancer Bulletin. ", "There are various definitions in the AYA generation. ", "The Surveillance, Epidemiology, and End Results (SEER), NCI and National Comprehensive Cancer Network (NCCN) define the ages from 15 to 29 years old and from 15 to 39 years old, respectively. ", "At SEER AYA Monograph 2006 \\[[@B1]\\] reported that cancer patients between the ages of 15 and 29 are only 2--3% of all cancer patients, but 2.7 times those of cancer patients under 15 years of age. ", "According to Clinical Practice Guidelines, Adolescent Young Adult Oncology and the SEER Cancer Statistics Review 2009--2013 in NIH (the NCI: SEER program), they reported that the most common cause of death to women in AYA generation excluding accidents and suicide and the most common in the order of cancer incidence (number per 100,000 people) is the thyroid cancer, breast cancer, cervical carcinoma, malignant melanoma, and colorectal cancer to women and gonadal cell tumor, malignant melanoma, non-Hodgkin\\'s lymphoma, colorectal cancer, thyroid cancer to men \\[[@B2][@B3]\\]. ", "In Japan, according to the 2015 cancer incidence rate (2011) based on areas and ages reported by Cancer Counseling Information Center of the National Cancer Center, the highest rates in order for female are thyroid cancer, leukemia, ovarian cancer at the ages of 20 to 24 years old, uterine cervical cancer (excluding carcinoma *in situ*), breast (not including carcinoma *in situ*), thyroid carcinoma at the age of 25 to 30 years old, uterine cervical cancer (not including carcinoma *in situ*) and thyroid carcinoma at the age of 30 to 34, and then breast (not including carcinoma *in situ*), uterine cervical cancer (not including carcinoma *in situ*) and thyroid carcinoma at the age of 35 to 39 years of age.", "\n\nFor male, leukemia, thyroid cancer, malignant lymphoma at the age of 20 to 24, colorectal cancer, leukemia, malignant lymphoma at the age of 25 to 30, colorectal cancer, malignant lymphoma, gastric cancer at the age of 30 to 34, and colorectal cancer, colon cancer, gastric cancer at the age of 35 to 39 years old \\[[@B4]\\]. ", "In fact, fertility preservation therapy to be prioritized by cancer type may be different in cancer/reproductive medicine (reproductive care for AYA generation cancer patients: Oncofertility). ", "This paper outlines the practical fertility preservation therapy using reproductive assisted technology for AYA generation cancer patients.", "\n\nGuideline on fertility preservation for cancer patients\n=======================================================\n\nIn 2006, guidelines on fertility preservation for young cancer patients were presented from the American Society of Clinical Oncology (ASCO), which was later revised in 2013 \\[[@B5][@B6]\\]. ", "ASCO, in collaboration with the American Society for Reproductive Medicine (ASRM), published the guideline on fertility preservation therapy for cancer patients for the first time in the world in 2006. ", "This ASCO 2006 presents guidelines on pregnancy rate, birth rate, and *in vitro* fertilization (IVF) success rate in papers meeting criteria among other report papers from 1985 to 2005, and it also states that the information about concerning the possibility of fertility decline by cancer treatment should be informed to cancer patients at all reproductive age. ", "In addition, cancer therapists should present problems on fertility to patients in the early stages of diagnosis and emphasize that cooperation with doctors specializing in reproductive medicine is important. ", "The change in the revised version in 2013 was that all providers (such as doctors, nurses, social workers, psychologists, etc.) ", "involved in fertility preservation treatment be referred to as healthcare providers and the needs to respond to patients by the entire healthcare provider is clearly indicated and they are responsible for providing information to cancer patients regarding the possibility of deteriorating fertility.", "\n\nOn the other hand, in Japan, the Japanese Society for Reproductive Medicine \"Guidelines on the Freezing and Preservation of Unfertilized Oocyte and Ovarian Tissue\" was published in 2013, and the Japan Society of Obstetrics and Gynecology issued \"Observation on Collection, Freezing and Preservation of Ovarian Tissue\" in April 2014 and was partially revised in 2016. ", "However, there are no comprehensive guidelines on fertility preservation for various cancers in Japan. ", "With a view to improving the quality of life of cancer survivors, cancer therapists need to reaffirm the importance of fertility preservation for AYA generation cancer patients. ", "Depending on the type and progress of cancer, cancer therapy is given as a top priority, and there are many circumstances in which we are forced to abandon future pregnancy and childbirth. ", "Therefore, the Japan Cancer Therapeutics Association started making guidelines focusing on cancer treatment from October 2015, carefully considering fertility preservation for AYA cancer patients and children (\\<15 years old) with cancer. ", "In July 2017, guidelines on fertility preservation for young cancer patients (children and AYA; CAYA) were published by the Japan Society of Clinical Oncology \\[[@B7]\\].", "\n\nOocyte cryopreservation and embryo cryopreservation\n===================================================\n\nOocyte cryopreservation is one of fertility preservation treatments for young cancer patients who do not have a partner, and ASRM has said that this method is not a research stage in 2013 \\[[@B8]\\]. ", "In oocyte freezing, patients will need to receive hormone preparations as they will store mature oocytes (second meiotic metaphase oocytes). ", "And since collection of oocytes depends on the menstrual cycle, it is common that it takes at least 2 weeks before harvesting. ", "The patient will receive an injection of follicle stimulating hormone (FSH) formulation soon after menstruation, but injections around 10 days are needed to raise follicles and mature oocytes. ", "When the follicle develops thereafter, the patient receives human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist (including nasal spray) preparation for oocyte acquisition, and oocyte collection is performed about 36 hours later. ", "Because it takes time to collect oocytes like this and the timing of oocyte collection depends on the menstrual cycle when a cancer patient visits obstetrics and gynecology department, it is also assumed that freezing cannot be done when no time to start treatment. ", "However, in recent years, the random start method \\[[@B9]\\], which is an attempt to enforce oocyte production irrespective of the patient\\'s menstrual cycle at the time of visit to obstetrics and gynecology, was devised and it became possible to have treatment for oocyte acquisition without waiting for the next cycle menstruation. ", "ASRM states that pregnancy rate in oocyte freezing depends on age. ", "Among them, quoting a large-scale study on the guidelines, it reports that the pregnancy rate per embryo transplant is 27.7% below 34 years old, 21.4% from 35 to 38 years old, 21.4% from 38 years old, and the pregnancy rate per embryo transplant is 48.6% below 34 years, 24.1% from 35 to 37 years old, 23.3% from 38 to 40 years old, and 22.2% from 41 to 43 years old \\[[@B8]\\]. ", "When multiple mature oocytes are collected, female hormone levels (estradiol values) increase due to ovulation stimulation by FSH, so that more attention must be paid to adverse effects, proliferation to cancer cells by estradiol values being caused for patients with hormone receptor positive breast cancer and endometrial cancer. ", "Therefore, when oocytes are harvested, hormone receptive positive breast cancer may select a treatment method to recover oocytes by ovarian stimulation with aromatase inhibitor combination for the purpose of suppressing increase in estradiol value \\[[@B9]\\]. ", "Reddy and colleagues \\[[@B10]\\] classified the number of acquired oocytes, the number of matured oocytes, the number of frozen embryos, the estradiol value, etc. ", "among the 2 groups in GnRH agonist and hCG ovulation determination medicine in fertility preservation treatment combined with an aromatase inhibitor. ", "The results are 14.1±6.6 and 12.4±8.6, respectively, the number of acquired eggs (individual) 10.5±5.1 and 7.7±5.3, the number of frozen embryos (pieces) 7.7±4.2 and 5.4±73.8, the estradiol value (pg/mL) 564.7±313.2 and 529.7±400.6, indicating that the increase in estradiol level is sufficiently suppressed. ", "Oktay and colleagues \\[[@B11]\\] obtained 25 live births as a result of carrying out 40 embryo transplantations to 33 patients in IVF with aromatase inhibitor combination, but it was reported that none of children were observed fetal malformation etc.", "\n\nOn the other hand, if a cancer patient has a partner, fertilization is frozen by embryo with the oocyte collected using the partner\\'s sperm. ", "There are two kinds of fertilization methods: Conventional IVF and intracytoplasmic sperm injection (ICSI). ", "Conventional IVF is a method of removing waste from semen after ejaculation on the collected mature oocytes, culturing the sperm together with oocytes in the culture solution, and confirming fertilization the next day. ", "On the other hand, ICSI is a method of placing one sperm into a matured oocyte under a microscope against cultured oocytes, culturing until the next day and confirming fertilization. ", "Although the summary of oocyte freezing and embryo (fertilized oocytes) freezing has been shown above, in principle the oocytes collection involves transvaginal operation, so there are cases where it cannot be performed in patients with AYA generation female cancer ([Fig. ", "1](#F1){ref-type=\"fig\"}). ", "The Japan Society of Obstetrics and Gynecology shows \"Views on unfertilized oocytes, embryos (fertilized oocytes) and ovarian tissues freezing and preservation by medical adaptation\" in June 2016, and in Japan when oocytes or fertilized oocytes for AYA generation cancer patient are frozen, it is required for physician to notify the Japan Society of Obstetrics and Gynecology \\[[@B12]\\]. ", "The following is excerpted from the sentence: \"By conducting surgical therapy, chemotherapy, radiation therapy, etc. ", "for women who are suffering from malignant tumor etc. (", "hereinafter called the original disease) for the purpose of treating the original disease,\" if ovarian function decreases before experiencing pregnancy/childbirth, and as a result it is predicted that fertility will be lost, unfertilized oocytes are collected based on the intention of the patient as a method of preserving fertility. ", "It is considered that this method is a medical practice as a part of countermeasures for adverse reactions occurring in the treatment of the original disease, so although there is no desire for childbirth at the time of receiving the treatment, it is necessary to acknowledge it as a medical practice if she wishes, but due to the influence of the implementation of this rule on the prognosis of the original disease, the possibility of pregnancy by the preserved oocyte in the future and its safety, since there are many things that are not clear yet, it is important that the patients make their own decisions by being provided sufficient information. ", "This rule is to carry out IVF/embryo transplantation and ICSI and it must be conducted in accordance with the \"Observations on IVF and embryo transplant\" and the \"Observations on microscopic insemination\" of the Japan Society of Obstetrics and Gynecology. ", "Furthermore, since this rule encompasses medical, ethical and social problems that are different from ordinary reproductive support medicine (assisted reproductive technology; ART), it needs to be done with the following points in mind. ", "The collection, freezing and preservation of ovarian tissue performed for the same purpose belongs to the same medical practice as in the case of unfertilized oocyte, and this view is basically applied, considering that it is included in this rule \\[[@B12]\\].", "\n\n![", "Female fertility preservation on young cancer patients in adolescent and young adult generation.\\\nFP, fertility preservation; IVM, *in vitro* maturation; IVFG, *in vitro* follicle growth; ASAP, as soon as possible.](ogs-61-443-g001){#F1}\n\nOvarian tissue freezing\n=======================\n\nFreezing ovarian tissue for AYA cancer patients was first reported by Oktay and Karlikaya in 2000 \\[[@B13]\\] and the firstborn baby acquisition was reported by Donnez et al. ", "\\[[@B14]\\] in 2004. ", "According to the report of von Wolff et al. ", "\\[[@B15]\\] in 2015, they reported that more than 1,000 cases of ovarian tissue freezing are performed in Europe, and this technology is becoming generalized, especially in Europe. ", "However, ASRM states that ovarian tissue freezing is not an established technique but an experimentally practiced technique \\[[@B16]\\]. ", "In ovarian tissue freezing, in principle, one ovary is removed by laparoscopic surgery and the ovary cortex is stored frozen outside the body. ", "Therefore, it is not a technique that depends on the patient\\'s menstrual cycle, but it can apply to all AYA generation cancer patients scheduled to undergo cancer treatment with sudden ovarian toxicity. ", "So far, there have been 86 live births after ovarian tissue freezing worldwide \\[[@B17]\\]. ", "The vast majority of the live births have been achieved after slow freezing of ovarian tissue, although there have been 3 live births after ovarian tissue vitrification in Japan. ", "Rapid freezing of ovarian tissue (vitrification) is relatively popular in Japan, where there have been over 1,000 cases of ovarian tissue cryopreservation by slow freezing and also over 250 cases of ovarian tissue vitrification for fertility preservation. ", "A total of 32 centers can perform ovarian tissue cryopreservation in Japan and are members of the JSFP. ", "Several articles concerning ovarian tissue vitrification have been published \\[[@B18][@B19][@B20]\\]. ", "In August 2017, Shi and colleagues \\[[@B21]\\] compared vitrification with slow freezing of human ovarian tissue, and they concluded that vitrification may be more effective than slow freezing, with fewer primordial follicular DNA strand breaks and better preservation of stromal cells. ", "At the ASRM meeting in 2017, we reported a comparison of follicle survival and DNA damage after vitrification versus slow freezing of human ovarian tissue. ", "The following parameters were compared: the primordial follicle density, γH2AX-positive primordial follicle percentage, AC3 positive primordial follicle percentage, non-apoptotic primordial follicle density, primary follicle density, γH2AX-positive primary follicle percentage, AC3-positive primary follicle percentage, and non-apoptotic primary follicle density. ", "AC3-positive primordial follicles were 17.5±2.3% at baseline, 20.1±2.7 after slow freezing, and 12.8±3.1% after vitrification, showing a statistically significant difference between slow freezing and vitrification (*P*=0.06, unpublished observations). ", "Based on the impact on primordial follicle survival and DNA damage after thawing of frozen tissue and culture, there may be no major differences between slow freezing and vitrification. ", "It seems that fewer apoptotic follicles survive after vitrification, but whether this has any impact on final non-apoptotic follicle density or survival in culture is unclear \\[[@B22]\\].", "\n\nWe have developed a closed device for ovarian tissue vitrification and we have performed comparison of open and closed methods for vitrification. ", "Our results showed that the closed method had similar or better efficacy compared to open vitrification of human ovarian tissue. ", "There was a higher primordial follicle survival rate after 96 hours of culture with closed vitrification, but the mechanism needs to be explored further. ", "It has been shown that the open method has similar efficacy with slow freezing of ovarian tissue. ", "Accordingly, the closed method should become the standard method of ovarian tissue cryopreservation \\[[@B23]\\]. ", "Except for histological examination, there are currently no suitable techniques for the detection and identification of primordial follicles in patients with primary ovarian insufficiency who have undetectable anti-mullerian hormone levels. ", "The ability to locate and quantify follicles in unfixed ovarian cortex strips would be useful in patients who are undergoing ovarian tissue transplantation. ", "Optical coherence tomography (OCT) is a well-established high-resolution imaging technique commonly used in biomedicine that does not require tissue fixation, and it has been suggested that OCT might be employed to measure the true ovarian reserve and localize follicles \\[[@B24]\\]. ", "However, ovarian cancer, leukemia, etc., ", "in which cancer cells are expected to be present in the ovarian tissue, are out of the indication. ", "That is, in the event that cancer cells are contained in frozen and thawed ovarian tissue pieces, there is a possibility that cancer cells may be transferred to themselves again by their own ovarian tissue after remission. ", "This is called minimal residual disease (MRD). ", "There have been several reports since MRD is reported by Dolmans et al. ", "\\[[@B25][@B26][@B27][@B28][@B29]\\]. ", "According to the report of Greve et al. ", "\\[[@B26]\\] in 2012, the ovaries of 4 patients with leukemia and lymphocytic leukemia who had positive cancer cells in ovarian tissue by quantitative reverse transcription polymerase chain reaction (RT-qPCR) were observed in immunodeficient mice for 20 weeks after transplantation. ", "As a result, it was reported that no tumor was formed. ", "There is a problem with the accuracy of RT-qPCR, and the investigation on detection of MRD in ovarian tissue is continuing in the research. ", "Therefore, since there is no established method for diagnosing MRD at this stage, there is a need to carefully study the adaptation of this technique to patients with a high possibility of the presence of cancer cells, especially in the ovary. ", "In addition, the birth rate for ovarian transplantation by ovarian tissue / freezing has been reported to be 25% \\[[@B29]\\], and in the report on the clinical application of this technology in accordance with Edinburgh criteria of Wallace. ", "Ovarian tissue freezing/transplantation safety and effectiveness have been shown \\[[@B30]\\].", "\n\nBy the way, when the ovarian tissue is frozen, ovarian medulla is removed in the culture medium, and only the ovary cortex where the primordial follicle is present is immersed in the cryoprotective agent to carry out the freezing of the ovarian tissue. ", "In this process, when there is a clearly developed follicle in the ovarian tissue, ovarian cortex is damaged by the formation of ice crystals in the follicular fluid \\[[@B31]\\]. ", "Therefore, in general, in order to prevent the formation of ice crystals, the follicles that grew in the ovarian tissue are aspirated by injection needle. ", "At the time of removal medulla and the culture solution upon aspiration with a stereoscopic microscope, premature oocytes in culture broth in a relatively frequent time can be confirmed comparatively and frequently. ", "Techniques for culturing immature oocytes in these cultures *in vitro* and cryopreserving them as mature oocytes are called combined procedure \\[[@B32]\\]. ", "That is, it is a method of combining ovarian tissue freezing and simultaneous oocyte freezing. ", "Because most of the oocytes in these cultures are in immature state, mature oocytes will be obtained by immature oocyte *in vitro* culture (*in vitro* maturation; IVM) or premature egg growth (*in vitro* follicle growth; IVFG). ", "Xiao and colleagues \\[[@B33]\\] reported that they acquired mature oocytes at a high rate in culture method using alginate beans in 150 μm immature follicles as IVFG, fertilized the mature oocytes, and reached the blastocyst.", "\n\nOvarian protection by GnRH analogue\n===================================\n\nGnRH analog is a fertility preservation therapy that minimally reduces the exposure of anticancer drugs by protecting the developmental process of primordial follicles \\[[@B34]\\]. ", "Unfortunately, most of the studies performed to date have had various methodological problems, such as a small patient population, short study period, high proportion of patients over 40 years old, or high rate of loss to follow up. ", "For example, the PROMISE-GIM6 study published in 2011 had a duration of only one year and most of the patients were over 40 years old \\[[@B35]\\]. ", "When this study was extended for several years to assess the occurrence of menopause, most of the patients could not be followed \\[[@B36]\\]. ", "In 2012, a randomized trial of the GnRH agonist triptorelin for preservation of ovarian function during neoadjuvant chemotherapy for breast cancer was published, but this was a small-scale study \\[[@B37]\\]. ", "Furthermore, The GBG 37 ZORO study published in 2012 \\[[@B38]\\] evaluated patients with or without a menstrual cycle for only 6 months. ", "In my opinion, the most reliable study published so far is the Prevention of Early Menopause Study (POEMS) trial. ", "The results of the POEMS trial reported by ASCO in 2014 resulted in a very disappointing result. ", "In ASCO, the ovarian failure rate was 22% and 8% in the standard treatment group and the GnRH analog administration group respectively 2 years after the trial registration and it was suggested the possibility of ovarian protection of GnRH analogue by anticancer drug. ", "However, the authors concluded in a report in the NEJM magazine in 2016 that \"We lost the reliability of the results of the POEMS exam because of some missing data\" \\[[@B39]\\]. ", "Meanwhile, Demeestere and colleagues \\[[@B40]\\] reported on the results of a randomized controlled trial with a median follow-up period of 5 years. ", "As a result, the incidence of premature ovarian failure did not change in the GnRH analog administration group compared with the non-administered group. ", "In 2016, Munhoz and colleagues \\[[@B41]\\] confirmed research results from January 1975 to March 2015 in the PubMed, SCOPUS and Cochrane databases, and further examined the meta-analysis results from ASCO\\'s 1995 to 2014, San Antonio Breast Cancer Symposium 2009 to 2014 that also confirmed the abstract indicate that there is a possibility of ovarian protection by GnRH analogue against early breast cancer. ", "However, Oktay and Turan \\[[@B42]\\] pointed out that there is a problem with the method of extracting meta-analysis as an Invited commentary for this paper. ", "Primordial follicles and eggs do not originally have receptors for GnRH, and DNA damage and apoptosis in eggs in the developing follicle are induced by alkylating agents and topoisomerase inhibitors, but not in primordial follicles, resulting in ovarian dysfunction. ", "It is said that GnRH analogs cannot protect the toxicity of anticancer drugs to primitive follicles, and further motivation for pregnancy of cancer patients assigned to the GnRH analog group is biasing, so that AYA generation cancer patient Ovarian protection by GnRH analog is not recommended as fertility preservation therapy \\[[@B40][@B42]\\]. ", "At this time ASCO does not recommend using GnRH analog in combination with anti-cancer drug. ", "It is expected that the discussion whether GnRH analog will be used when anticancer drug is used will continue in future.", "\n\nSperm freezing\n==============\n\nAccording to the AYA oncology guideline, version 2. ", "2014 reported by NCCN, sperm freezing (semen freezing) before anticancer treatment is the most reliable technology as a fertility preserving in AYA generation cancer-affected men and it states that this is well established as a treatment. ", "The NCCN guideline also recommends sperm cryopreservation before treatment ([Fig. ", "2](#F2){ref-type=\"fig\"}). ", "The reason is that sperm after anti-cancer treatment may induce genetic defect. ", "In addition, it is reported that the original disease may induce azoospermia in Hodgkin lymphoma and testicular cancer patients \\[[@B43]\\]. ", "Similar to the NCCN guidelines, Moss and colleagues also says that ejaculate semen is the most effective male fertility preservation therapy for AYA generation and should be collected before anticancer treatment. ", "If ejaculation is impossible and family members and patient can be accepted, artificial ejaculation such as Penile Vibratory Stimulator (machine to promote ejaculation) or Electroejaculation under general anesthesia (electric ejaculation) can also be performed. ", "If ejaculate semen cannot be obtained, it is said that surgically performing testicular sperm extraction (TESE) operation will collect sperm. ", "This is because radiation therapy and anti-cancer treatment are known to greatly affect spermatogenesis \\[[@B44]\\].", "\n\n![", "Male fertility preservation on young cancer patients in adolescent and young adult generation.\\\nFP, fertility preservation; IVM, *in vitro* maturation; IVFG, *in vitro* follicle growth; ASAP, as soon as possible.](ogs-61-443-g002){#F2}\n\nFreezing testicular tissue\n==========================\n\nBasal and clinical studies of testicular tissue freezing have been started in recent years. ", "With current technology, it is not possible to mature spermatogonial stem cells *in vitro* due to IVF in the future. ", "However, Gupta and colleagues \\[[@B45]\\] have conducted a testicular biopsy of 77 pre-adolescent boys and said that preserved tissue can contain preserved spermatogonial stem cells because they may contain spermatogonial stem cells. ", "It is not an option to preserve fertility. ", "In addition, Long and colleagues \\[[@B46]\\] also said that freezing testicular tissues is still at the research stage, however, it is indicated that there is adaptation to boys with pre-pubertal cancer. ", "Although it is possible to preserve spermatogonial stem cells by freezing testicular tissues, they say that they will re-transplant after treatment and it will be cryopreserved in anticipation of sperm differentiation resuming.", "\n\nFuture prospects\n================\n\nA report by Dr. Donnez et al. ", "\\[[@B14]\\] in 2004 of the young female Hodgkin\\'s disease patient for the first time to acquire a baby by ovarian tissue freezing and ovarian transplantation after cancer therapy has become a breakthrough in this area, and a new area called Oncofertility is established by Dr. Woodruff \\[[@B47]\\]. ", "Also in Japan, the practice of fertility preservation therapy for AYA generation cancer patients have conducted in 2012 by the JSFP (<http://www.j-sfp.org/index.html>), various societies and organizations have deepened interest in this area. ", "In June 2015, the \"Cancer Summit\" hosted by the Ministry of Health, Labor and Welfare formulated the \"Acceleration Plan for Cancer Countermeasures,\" so far there has been no clear description in the Basic Plan for Promotion of Cancer Countermeasures. ", "It is now that the aim of achieving sustainable cancer control in the future is indicated by the importance of \"cancer countermeasure according to life stage such as childhood, AYA generation, mature age, elderly age.\" ", "Since \"Implementation for reproductive dysfunction\" was included in cancer control according to the life stage this time, it is urgent for not only doctors but also all healthcare providers including nurses, psychologists, pharmacists, etc. ", "to construct a cancer and reproductive medical cooperative network aiming at practicing fertility preservation therapy for cancer patients in the AYA generation in Japan.", "\n\nI really appreciate my friend, Ms. Reiko Koda for helping English translation and editing my English.", "\n\n**Conflict of interest:** No potential conflict of interest relevant to this article was reported.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Over-the-counter topical skincare products: a review of the literature.", "\nTopical \"anti-aging\" products, with their seemingly limitless list of ingredients, make extensive claims to reduce wrinkles, fine lines, and sun damage, among others. ", "Sales in the United States alone for cosmeceutical products are expected to increase by 7.4% per year to $8.2 billion by 2012. ", "However, in this enormous industry, there has been a significant lack of rigorous controlled trials of efficacy. ", "It is difficult for both dermatologists and consumers to make informed decisions in a market that is yet to be clearly defined and regulated. ", "We elucidate the scientific basis for, as well as the literature behind, common active ingredients found in products intended to reverse photoaging, discuss some interesting new activities, and provide a review of several comprehensive studies on over-the-counter (OTC) products." ]
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[ "Condo dweller Maureen Dunn has a message for her Don Valley West MPP, Premier Kathleen Wynne: Put Leslie back on the Eglinton-Scarborough Crosstown LRT.", "\n\nThe stop is being eliminated as part of a change to the LRT construction plan. ", "Disappointed condo-dwellers at Leslie and Eglinton and, nearby Leaside are vowing to fight the decision by Metrolinx.", "\n\nTheirs is among the first major community complaints to surface as Metrolinx proceeds over the next eight years with construction of the $6.7 billion provincially funded LRT.", "\n\nThe provincial transportation agency has a team dedicated to community information and feedback. ", "But some city officials say the dispute is exactly what they feared when Toronto and the TTC signed a master agreement giving Metrolinx the final say on the project.", "\n\nIn Dunn’s 400-unit building, 300 residents have signed a petition, asking to have the Leslie stop reinstated. ", "So far, it’s made no difference.", "\n\nUnder the new construction plan Metrolinx wants to lengthen the LRT tunnel. ", "Stopping at Leslie would mean building another underground station — at a cost of $80 to $100 million — in a location expected to attract relatively few riders.", "\n\nThe change, which has to be approved by the province, is a disappointment to residents like Dunn. ", "Some bought their homes believing they would be steps from a transit stop.", "\n\n“I’d have been really happy to jump on that LRT that avoids the traffic,” said Dunn, who drives but would prefer to take transit when she goes downtown to the opera. ", "The bus trip takes too long because it gets snarled in traffic, she said.", "\n\nOriginally the Crosstown was supposed to run mostly underground from Black Creek Dr. in the west to about Laird Dr. in the east. ", "Leslie would have been a relatively inexpensive surface stop, costing about $3 million.", "\n\nBut in December, Metrolinx announced it was looking at a new route to avoid issues with traffic, contaminated soil and the construction of a residential development near Brentcliffe Rd.", "\n\nMetrolinx’s alternative — tunneling farther east to Don Mills Rd. — ", "meant eliminating the stops at Leslie and Ferrand Dr.\n\nLast month, to the relief of residents of Flemingdon and Thorncliffe Park, it announced it had restored the Ferrand surface stop.", "\n\nBut not Leslie.", "\n\n“It would be the lowest ridership and most expensive station on the line,” said Jamie Robinson of community relations and communications for the Toronto Transit Project at Metrolinx.", "\n\nApart from the condos and a car dealership, the Leslie intersection is dominated by parkland. “", "When you look at the city’s official plan, there really is no substantial increase in residential development or ridership,” said Robinson.", "\n\nGeoff Kettel, of the Leaside Property Owners’ Association, says the station could enhance park access. “(", "It) would actually serve the Don Valley Trail. ", "The city wants to increase access to its trails for walking, biking and commuting. ", "It would have been ideally situated to provide access to the Serena Gundy Park. ", "To say there’s nobody living there might discount some potential usage,” he said.", "\n\nThe issue is precisely what Councillor Gord Perks (Ward 14, Parkdale-High Park) said he feared when the city signed over control of the new line to Metrolinx, an unelected body.", "\n\n“The city can raise the issue, but at the end of the day they just provide advice. ", "The province is required to hear our objection. ", "They’re simply not required to implement it,” he said.", "\n\n“The purpose of transit isn’t just to generate ridership. ", "It’s to create a transit lifestyle in more neighbourhoods,” said Perks.", "\n\nResidents haven’t given up. “", "There may be some time for sober second thoughts. ", "Why couldn’t there be a viaduct across the valley so the LRT would pop out at the original place and go underground at Don Mills? ", "It would allow the opportunity for a Leslie station either now or at some time in the future,” said Kettel.", "\n\nMetrolinx doesn’t expect all the residents will change their mind, despite Metrolinx’s reinstatement of Ferrand and its extension of community consultations in the east end, said Robinson.", "\n\nLoading... Loading... Loading... Loading... Loading... Loading...\n\nThere is still time, he said, for people to speak with their city councillors and participate in the provincial environmental assessment process, he said, adding that Metrolinx doesn’t anticipate that any more stops will be eliminated.", "\n\n-\n\n-\n\nJOHN PARKER WONDERS: ‘WHAT IF’ EGLINTON WERE A SUBWAY?", "\n\nWhen it comes to debating whether Eglinton should have been a subway or an LRT, Councillor John Parker (Ward 26, Don Valley West) knows that train has left the station.", "\n\nIt doesn’t stop him, however, from reflecting on the implications of that decision a generation down the road.", "\n\nThere have been a couple of major developments since council approved the LRT plan last year: Metrolinx has decided to extend the tunneled portion of the Eglinton-Scarborough Crosstown farther east to Don Mills Rd., ", "and the downtown relief subway line has emerged at the top of the next round of city transit priorities.", "\n\nWouldn’t it make sense, wonders Parker, to connect the underground transit on Eglinton with the DRL, given that both are expected to terminate around Don Mills and Eglinton?", "\n\n“Why don’t we put some serious thought to having an actual subway line using subway technology from Black Creek Dr. along Eglinton underground all the way to Don Mills,” he said.", "\n\n“And then at Don Mills you would have a terminal where you would have surface rail operating on the surface, where God intended it to, and that would extend further east on Eglinton into Scarborough and north on Don Mills, and serve communities to the north,” he said.", "\n\nThe same could be done from the subway terminus in the west end.", "\n\nParker knows nobody is interested in revisiting the plan for Eglinton. “", "It’s an interesting academic debating point, but I don’t carry any delusions I’m going to change the course of history,” he said." ]
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[ "Relationship between spatial abilities, mental rotation and functional anatomy learning.", "\nThis study investigated the relationship between visuo-spatial representation, mental rotation (MR) and functional anatomy examination results. ", "A total of 184 students completed the Group Embedded Figures Test (GEFT), Mental Rotation Test (MRT) and Gordon Test of Visual Imagery Control. ", "The time spent on personal assignment was also considered. ", "Men were found to score better than women on both GEFT and MRT, but the gender effect was limited to the interaction with MRT ability in the anatomy learning process. ", "Significant correlations were found between visuo-spatial, MR abilities, and anatomy examination results. ", "Data resulting from the best students' analyzes underscore the effect of high MR ability which may be considered reliable predictor of success in learning anatomy. ", "The use of specific tests during learning sessions may facilitate the acquisition of anatomical knowledge." ]
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[ "Q:\n\nHow can i make app wait to get all data from module that get data from firestore before run in react-native?", "\n\nI have DATA from petData.js that get data from firestore\nimport firebase from '../fb';\nimport 'firebase/firestore';\nconst DATA = [];\nfirebase\n .firestore()\n .collection('pets')\n .get()\n .then(function(querySnapshot) {\n querySnapshot.forEach(function(doc) {\n DATA.push(doc.data());\n });\n });\n\nmodule.exports = DATA;\n\nAnd Popular.js to wait for data before running\nimport DATA from '../data/petData';\nclass Popular extends Component {\n render() {\n return (\n <View style={styles.container}>\n <FlatList\n data={DATA}\n renderItem={item => {\n return (\n <PetItem\n navigation={this.props.screenProps}\n source={item.item.source}\n name={item.item.name}\n info={item.item.info}\n price={item.item.price}\n />\n );\n }}></FlatList>\n </View>\n );\n }\n}\n\nIf i run before getting all data it become like this\n\nA:\n\nYeah, u should take a look to lifecycle methods in react, in your case the render method it's run the first one and every time u set a state, so u should get the data in didMount method that's run after ur component mounted \nSo expected behavior at first time \nData is null/undefined/empty so the flatlist will not appear\nSo u should put a get data function inside a componentDidMount()\n//Popular.js\nimport firebase from '../fb';\nimport 'firebase/firestore';\n\nclass Popular extends Component {\nconstructor(props) {\n super(props);\n this.state = {\n data: [], \n loading:true\n }\n}\nComponentDidMount(){\nfirebase\n .firestore()\n .collection('pets')\n .get()\n .then(function(querySnapshot) {\n querySnapshot.forEach(function(doc) {\n //DATA.push(doc.data());\n this.setState({data:doc.data(), loading:false})\n });\n });\n}\nrender() {\n //make a loading component that appears if the data is empty \n If(this.state.loading){\n return(\n <ActivityIndecator size=\"large\" />\n )else{\n return (\n <View style={styles.container}>\n <FlatList\n data={this.state.data}\n renderItem={item => {\n return (\n <PetItem\n navigation={this.props.screenProps}\n source={item.item.source}\n name={item.item.name}\n info={item.item.info}\n price={item.item.price}\n />\n );\n }}\n />\n </View>\n );\n }\n }\n}\n\n" ]
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[ "Police officers in the Coulee Region ‘Went Wild’ Friday, all for a good cause.", "\n\nThe Onalaska Police Department hosted its seventh annual “Cops Gone Wild” event at Buffalo Wild Wings. ", "Officers helped serve food and bus tables while also collecting donations for the Special Olympics of La Crosse. ", "They also held a wing-eating contest against officers from other local departments.", "\n\n“We’ve always had a special place in our heart for the Special Olympic athletes, we’ve helped coach, referee over the years, and just find that they’re such an enjoyable group of people to be around and we like to help them out any way we can,” said Peter Jakowski, Onalaska Police Department.", "\n\n“It makes me feel good inside because I can see all the officers and all the athletes helping them go to state and compete in that,” said athlete Scott Prairie.", "\n\nCops Gone Wild raises about $2,500 each year for Special Olympics." ]
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[ "<blockquote>\n <p>Bitcoin Silver runs on the speed of the Ethereum blockchain, an enormous global infrastructure that can move value around the world in a matter of minutes.</p>\n <footer><a href=\"https://www.bitcoinsilver.io\" target=\"_blank\">https://www.bitcoinsilver.io/</a></footer>\n</blockquote>\n" ]
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[ "EXXON CORPORATION, PETITIONER V. CENTRAL GULF LINES, INC., ", "ET AL.", "\nNo. ", "90-34\nIn The Supreme Court Of The United States\nOctober Term, 1990\nOn Writ Of Certiorari To The United States Court Of Appeals For The\nSecond Circuit\nBrief For The United States As Amicus Curiae Supporting Petitioner\nTABLE OF CONTENTS\nQuestion Presented\nInterest of the United States\nStatement\nSummary of argument\nArgument:\nI. Minturn v. Maynard should be overruled\nA. The historic antecedents of Minturn no\nlonger justify its result\nB. Overruling Minturn would be in keeping\nwith efforts to rationalize the scope of federal\nadmiralty jurisdiction\nII. ", "The present case falls within the admiralty\njurisdiction of the district court\nConclusion\nQUESTION PRESENTED\nWhether an agent who procures and pays for necessary maritime\nsupplies for a vessel in maritime commerce is entitled to assert a\nmaritime lien against the vessel.", "\nINTEREST OF THE UNITED STATES\nThe United States has a substantial interest in the scope of\nadmiralty jurisdiction, both in its capacity as an owner and operator\nof ships, and in its role as a major shipper. ", "Although maritime liens\ndo not lie against vessels owned by or operated for or by the United\nStates (46 U.S.C. App. ", "741; 46 U.S.C. App. ", "788), in personam actions\nmay be brought against the United States in all cases where admiralty\njurisdiction would lie if the vessel were privately owned or operated\n(46 U.S.C. App. ", "742). ", "Thus, the decision in this case may have a\nsignificant impact on the availability of in personam actions in\nadmiralty against the United States.", "\nMoreover, the United States has a general interest in the proper\nand uniform application of the laws governing admiralty jurisdiction.", "\nIn response to the Court's invitation at the petition stage of this\ncase, the Solicitor General filed a brief urging that the petition be\ngranted.", "\nSTATEMENT\n1. ", "This case involves a vessel, the M/V Green Harbour ex William\nHooper (the Hooper); the vessel's owner, respondent Central Gulf\nLines, Inc.; the vessel's charterer, Waterman Steamship Corporation\n(Waterman); and Waterman's fuel supplier, petitioner Exxon\nCorporation.", "\nPetitioner served for more than four decades as the exclusive\nworld-wide supplier of marine fuel for Waterman's vessels. ", "Under the\nterms of their agreement, Waterman notified petitioner when a Waterman\nvessel needed fuel. ", "Petitioner then either delivered the fuel to the\nvessel directly, or (where petitioner had no local delivery\nfacilities) arranged with a local supplier to provide the fuel. ", "When\na local supplier was used, petitioner paid the supplier and then\nbilled Waterman. ", "In these situations, the practical effect of the\nagreement was that the fuel supplier relied on petitioner's credit\nrather than Waterman's. ", "Pet. ", "App. ", "A23.", "\nThe local supplier used by petitioner at the port in Jeddah, Saudi\nArabia, was Arabian Marine Operating Co., Ltd. (Arabian Marine). ", "The\nagreement between Arabian Marine and petitioner stated that petitioner\nwould \"solicit and arrange\" for the sale of marine fuel to vessels\ncalling at the port of Jeddah; that Arabian Marine would supply this\nfuel and petitoner would pay for it; and that Arabian Marine would\npay petitioner a commission. ", "Petitioner never had title to the fuel;\nit passed directly from Arabian Marine to the receiving vessel. ", "Pet.", "\nApp. ", "A24-A25.", "\n2. ", "On October 26, 1983, Arabian Marine delivered 4,242.47 tons of\nmarine fuel to the Hooper, pursuant to the agreement between\npetitioner and Waterman and the agreement between petitioner and\nArabian Marine. ", "Petitioner paid Arabian Marine for the fuel, and in\nNovember 1983 billed Waterman for its $763,644 cost. ", "Pet. ", "App.", "\nA24-A25.", "\nThe bill to Waterman was not paid. ", "Instead, on December 1, 1983,\nWaterman sought reorganization under Chapter 11 of the bankruptcy\nlaws. ", "During reorganization proceedings, respondent agreed that,\nshould a court hold the Hooper liable in rem for the cost of the fuel,\nrespondent would assume personal liability for that cost. ", "Respondent\nprovided petitioner with a letter of credit as security for this\npromise. ", "Pet. ", "App. ", "A25.", "\nAfter a reorganization plan for Waterman was confirmed in June\n1986, petitioner was permitted to pursue its claim for the cost of\nsupplying marine fuel to the Hooper. ", "Pet. ", "App. ", "A25. ", "/1/ Accordingly,\npetitioner commenced this lawsuit in federal district court against\nboth respondent and the Hooper. ", "Petitioner asserted that its\nagreement with Waterman to procure fuel in Saudi Arabia fell within\nthe district court's admiralty jurisdiction. ", "Petitioner therefore\nclaimed to have a maritime lien on the Hooper pursuant to the Federal\nMaritime Lien Act, 46 U.S.C. 31342. ", "/2/\n3. ", "The district court concluded that there was no admiralty\njurisdiction over petitioner's claim, and that without such\njurisdiction there could be no maritime lien. ", "Pet. ", "App. ", "A27-A28. ", "The\ncourt noted that \"(w)hile admiralty jurisdiction provides 'fairly\ncomplete coverage of the primary operational and service contracts of\nthe shipping industry,' there still exist 'a few anomalous\nexceptions'\" (id. at A28, quoting G. Gilmore & C. Black, The Law of\nAdmiralty, Section 1-10 (2d ed. ", "1975)). ", "One of these \"anomalous\nexceptions,\" the court continued, is the rule that general agency\ncontracts -- agreements to arrange for the provision of supplies and\nservices to a vessel -- fall outside the scope of maritime\njurisdiction. ", "The court observed (Pet. ", "App. ", "A28) that in Peralta\nShipping Corp. v. Smith & Johnson (Shipping) Corp., 739 F.2d 798\n(1984), cert. ", "denied, 470 U.S. 1031 (1985), the Second Circuit adhered\nto this exception, holding itself bound by this Court's decision in\nMinturn v. Maynard, 58 U.S. (17 How.) ", "476 (1854). ", "Applying \"the\nprinciples enunciated in Peralta\" to the facts of this case (Pet. ", "App.", "\nA29), the district court concluded that the agreement whereby\npetitioner arranged for the provision of fuel to Waterman's vessels at\nJeddah constituted an agency contract (id. at A29-A30); that the\nservices supplied were strictly \"shoreside\" (id. at A30); and that\nthere was no legitimate basis for distinguishing the general agency,\nor husbanding, contract at issue in Peralta from the agreement here\n(id. at A31).", "\nIn a subsequent opinion (Pet. ", "App. ", "A3-A21), the court denied\npetitioner's motion for reconsideration. ", "The court reiterated that\n\"Exxon wore its agency hat when it procured (marine fuel) for the\nHooper in Jeddah,\" and that \"the locus of Exxon's relationship with\nWaterman was the United States, not the dock in Jeddah.\" ", "Id. at A6.", "\nAccordingly, the case fit within the exception for general agency\ncontracts forged by this Court in Minturn. ", "The court observed that\nalthough the Minturn rule was an \"anomalous exception to the broad\ncoverage of maritime jurisdiction (which) had 'suffered some erosion\nin other circuits'\" (id. at A11), the Second Circuit in Peralta had\nrefused to depart from Minturn, absent action by this Court. ", "Id. at\nA11-A12. ", "The district court declined \"to do what the Second Circuit\nrefused to do in Peralta.\" ", "Id. at A12.", "\nThe district court rejected petitioner's argument that in procuring\nfuel for Waterman it was acting as a special and not a general agent.", "\nPet. ", "App. ", "A13. ", "The court determined that the forty-year relationship\nbetween Waterman and petitioner, and petitioner's \"quite broad\"\nauthority under its agreement with Waterman, established petitioner as\nWaterman's general agent. ", "It observed that the Second Circuit had\nrefused to distinguish special agency agreements from general ones;\nand that in any event, special agents that provide preliminary\nservices fall outside admiralty jursidiction. ", "Id. at A13-A14. ", "/3/\nThe court specifically ruled that the \"services performed by\n(petitioner at Jeddah) were merely preliminary\" (id. at A17), and\nthat, accordingly, the contract at issue was not maritime, regardless\nof how the agency was characterized. ", "/4/\n4. ", "The court of appeals affirmed, \"substantially for the reasons\ngiven in (the district court's) two thorough opinions\" (Pet. ", "App. ", "A2).", "\nSUMMARY OF ARGUMENT\n1. ", "This Court's decision in Minturn v. Maynard should be overruled.", "\nThe Court's cryptic opinion in that case, which has been variously\ninterpreted by the lower courts ever since, may have rested on three\nnotions of admiralty jurisdiction: the tidewater exception to that\njurisdiction; the \"hypothecation\" requirement (that one claiming on a\ncontract must have a lien interest in the vessel before the contract\nwould be considered maritime); and the view that a demand for a\nbalance on accounts must be pursued in an action in assumpsit in a\ncommon law court. ", "Each of these notions has been squarely rejected by\nthis Court. ", "Thus, whatever the basis for the decision may have been\nin 1854, that basis no longer exists.", "\nMoreover, there is no agreement in the lower courts on the current\nmeaning or vitality of the Minturn holding. ", "The Second Circuit views\nthe holding as requiring the exclusion of all agency agreements from\nthe reach of admiralty jurisdiction. ", "Other circuits appear to view\nthe decision only as barring an action for \"an accounting as such\"\n(Hadjipateras v. Pacifica, S.A., 290 F.2d 697, 703 (5th Cir. ", "1961)),\nor as excluding only certain kinds of agency agreements. ", "Thus, a\ndetermination that Minturn is no longer binding precedent will not\nonly eliminate an anomaly in maritime law and help rationalize\nadmiralty jurisdiction, it will also eliminate widespread confusion as\nto the present impact of the Court's holding.", "\n2. ", "If this Court's decision in Minturn is overruled, the question\nwill remain as to what agency contracts fall within the reach of\nadmiralty jurisdiction. ", "Some contracts -- including agency contracts\n-- are sufficiently remote from maritime commerce that they do not\nfall within that reach, and the limits of the jurisdiction must be\ndefined in the context of particular cases. ", "But whatever those limits\nmay be, we do not believe they are exceeded here, since this agency\nagreement involves a suit by an agent for reimbursement for the cost\nof supplying a vessel with necessary marine fuel. ", "The Court should\ntherefore determine that, on the record in this case, admiralty\njurisdiction has been established.", "\nARGUMENT\nI. MINTURN v. MAYNARD SHOULD BE OVERRULED\nMinturn v. Maynard, supra, created an oddity of federal admiralty\njurisdiction; its historical antecedents have been eroded, and its\nserves no continuing purpose in current maritime law. ", "It is beyond\ndispute that an action seeking to recover the cost of supplying fuel\nto a vessel -- the purpose of this suit -- is within a federal court's\nadmiralty jurisdiction. ", "Yet, the rule of Minturn prevents the\nassertion of admiralty jurisdiction simply because the owner's agent,\nrather than a third party, seeks payment for the fuel. ", "/5/ This\nCourt, in the years since Minturn was decided, has refused to make\nadmiralty jurisdiction turn on such artificial distinctions.", "\nAccordingly, the rule that general agency contracts are outside\nadmiralty's reach should be abolished.", "\nA. The Historic Antecedents Of Minturn No Longer Justify Its Result\nEarly in the nineteenth century, Justice Story observed that the\nadmiralty jurisdiction of the United States includes \"all contracts\n(wheresoever they may be made or executed, or whatsoever may be the\nform of the stipulations) which relate to the navigation, business or\ncommerce of the sea.\" ", "De Lovio v. Boit, 7 F. Cas. ", "418, 444 (C.C.D.\nMass. 1815) (No. ", "3776). ", "Whether a contract is governed by maritime\nlaw thus depends on the subject matter of the agreement. ", "See North\nPacific S.S. Co. v. Hall Bros. Marine Ry. & ", "Shipbuilding Co., 249 U.S.\n119, 125 (1919); Kossick v. United Fruit Co., 365 U.S. 731, 736\n(1961). ", "Nonetheless, as this Court has noted, \"(t)he boundaries of\nadmiralty jurisdiction over contracts -- as opposed to torts or crimes\n-- being conceptual rather than spatial, have always been difficult to\ndraw.\" ", "Kossick v. United Fruit Co., 365 U.S. at 735. ", "See S. Friedell,\nBenedict on Admiralty Section 183, at 12-8 (7th ed. ", "1989). ", "It is not\nsurprising, therefore, that decisions marking this boundary are often\ndifficult to reconcile. ", "/6/ See Sisson v. Ruby, 110 S. Ct. ", "2892,\n2900, 2901 & n.4 (1990) (Scalia, J., joined by White, J, concurring in\nresult and noting \"(t)he impossibility of drawing a principled line\nwith respect to what, in addition to the fact that the contract\nrelates to a vessel * * * is needed in order to make the contract\nitself 'maritime.'\").", "\nThe source of one of the most idiosyncratic of admiralty's\njurisdictional rules is this Court's one-page decision in the 1854\ncase of Minturn v. Maynard, 58 U.S. (17 How.) ", "476. ", "Much criticized,\nMinturn has spawned an \"agency exception\" to the general rules\ngoverning maritime contracts. ", "Even when a contract's subject matter\nis indisputably maritime, Minturn has been interpreted as proscribing\nfederal admiralty jurisdiction if the contract is one of agency.", "\nThe libellant in Minturn, who was both a general agent and a\nbroker, sued in personam to recover from a vessel's owners money he\nhad spent in procuring ship's services and supplies. ", "Finding \"nothing\nin the nature of a maritime contract in the case,\" 58 U.S. (17 How.)", "\nat 477, this Court dismissed the suit in an extremely brief opinion.", "\nThe Court's entire explanation for this conclusion was as follows\n(ibid.):", "\nThe libel shows nothing but a demand for a balance of accounts\nbetween agent and principal, for which an action in assumpsit,\nin a common law court, is the proper remedy. ", "That the money\nadvanced and paid for respondents was, in whole or in part, to\npay bills due by a steamboat for repairs or supplies, will not\nmake the transaction maritime, or give the libellant a remedy in\nadmiralty. ", "Nor does the local law of California, which\nauthorized an attachment of vessels for supplies or repairs,\nextend to the balance of accounts between agent and principal,\nwho have never dealt on the credit, pledge, or security of the\nvessel.", "\nThe decision in Minturn may well have turned on restrictions\nbrought over from English admiralty practice -- principally the\ntidewater exception to maritime jurisdiction, which focuses on the\nlocation of the contract rather than its nature, and the hypothecation\nrequirement, i.e., that one suing on a maritime contract have a\nhypothecation (a lien interest) in the vessel. ", "To see the decision in\nproper perspective, therefore, requires a brief look at Minturn's\nhistorical antecedents.", "\n1. ", "a. In England, during the early Middle Ages, maritime matters\nwere dealt with by courts in English port towns. ", "By the\nmid-fourteenth century, however, English maritime supremacy and the\nneed for an efficient means to adjudicate maritime disputes led to the\ncreation of the High Court of Admiralty, a maritime tribunal with\nbroad powers. ", "/7/ Almost from its creation, this tribunal was\nunpopular with the local courts in the port towns, prompting\nParliament to enact two famous statutes narrowing admiralty's\njurisdiction. ", "In the first of these statutes, 13 Rich. ", "II, ch. ", "5\n(1390), Parliament declared that \"the admirals and their deputies\nshall not meddle from henceforth with anything done within the realm,\nbut only of a thing done upon the sea * * *.\" ", "In the second statute,\n15 Rich. ", "II, ch. ", "3 (1392), admiralty's jurisdiction was restricted\nwith more particularity: \"of all manner of contracts, pleas, and\nquarrels, and all other things rising within the bodies of the\ncounties, as well as by land as by water, and also of wreck of the\nsea, the Admiral's court shall have no manner of cognizance, power,\nnor jurisdiction.\"", "\nOver the years, the common law courts continued their efforts \"to\nprevent the admiralty court taking cognizance of contracts made in the\ncountry relating to maritime matters.\" ", "D. Robertson, Admiralty and\nFederalism 42 (1970), quoting Mears, The History of Admiralty\nJurisdiction, 2 Select Essays in Anglo-American Legal History 312, 335\n(1908). ", "For example (id. at 49-50):\nStarting about 1544, prohibitions began to be used against\nadmiralty with increasing frequency. ", "The great majority of\ncases involving the use of that writ were cases of maritime\ncontracts made on land. ", "The statutes of Richard II * * * were\ninterpreted literally, in order to oust the admiral of\njurisdiction over any case involving a contract made within the\nbody of a county (infra corpus comitatus). ", "Thus,\ncharter-parties, policies of insurance, and other clearly\nmaritime contracts were held not within the admiralty\njurisdiction.", "\nDuring the reigns of the Tudor kings, the Admiralty Court was\nrevived and enhanced, but it again came under attack from the\nchampions of the common law courts -- notably Sir Edward Coke. ", "As one\ncommentator noted, \"(i)mmediately upon assuming the chief justiceship\nof the Court of Common Pleas in 1606, Coke enthusiastically took up\nthe battle against admiralty * * *. ", "During his years on the bench,\nCoke's militancy against the admiralty led him to deny its\njurisdiction over any matters having connection with the land.\" ", "D.\nRobertson, supra, at 55, 56.", "\nOne manifestation of Coke's approach was the tidewater doctrine,\nwhich provided that admiralty courts had jurisdiction only over\nmatters taking place on the high seas and within the ebb and flow of\nthe tides. ", "Any action on land, or on inland nontidal waters, was\ntherefore deemed to be outside admiralty's jurisdiction. ", "See, E.\nCoke, The Fourth Part of the Institutes of the Laws of England\nConcerning the Jurisdiction of the Courts 137 (6th ed.) (", "London 1681);\nD. Robertson, supra, at 56-58; De Lovio v. Boit, 7 F. Cas. ", "at 421.", "\n/8/\nb. Article 3, Section 2 of the Constitution extends the judicial\npower of the United States \"to all Cases of admiralty and maritime\njurisdiction.\" ", "Several early decisions of this Court -- apparently\nassuming that this grant was limited by the English practice -- relied\non the tidewater doctrine in refusing to assert admiralty\njurisidiction over contracts whose subject matter was maritime but\nwhose locus was on land. ", "The Steamboat Thomas Jefferson, 23 U.S. (10\nWheat.) ", "428, 429 (1825); Pevroux v. Howard, 32 U.S. (7 Pet.) ", "324, 343\n(1833); The Steamboat Orleans v. Phoebus, 36 U.S. (11 Pet.) ", "175\n(1837); United States v. Coombs, 37 U.S. (12 Pet.) ", "72, 76 (1837).", "\nCf. ", "New Jersey Steam Navigation Co. v. Merchant's Bank, 47 U.S. (6\nHow.) ", "343, 392 (1848). ", "/9/ But see De Lovio v. Boit, 7 F. Cas. ", "at 444\n(Story, J.).", "\nIn the mid-nineteenth century, this Court rejected the view that\nthe constitutional grant of admiralty jurisdiction to the federal\ncourts adopted the limitations on the English admiralty courts (Waring\nv. Clark, 46 U.S. (5 How.) ", "440, 454-459 (1847)), and in 1851 the Court\nspecifically rejected the applicability of the tidewater doctrine,\nnoting \"the unreasonableness of giving a construction to the\nConsituation which would measure the jurisdiction of the admiralty by\nthe tide.\" ", "The Propeller Genesee Chief v. Fitzhugh, 53 U.S. (12 How.)", "\n443, 456 (1851). ", "See Hine v. Trevor, 71 U.S. (4 Wall.) ", "555, 566\n(1866) (\"The Genessee Chief * * * removed the imaginary line of\ntide-water which had been supposed to circumscribe the jurisdiction of\nthe admiralty courts\").", "\nMinturn was decided four years after The Genesee Chief and did not\nexpressly refer to the tidewater doctrine. ", "Nevertheless, the\nstatement that \"there is nothing in the nature of a maritime contract\nin the case,\" (58 U.S. at 477) may suggest that the decision has its\nroots in that doctrine; the contract was not \"in the nature of a\nmaritime contract\" because the reach of admiralty ended at the\ntideline, so that the contract at issue, which was executed on land,\nwas outside admiralty's jurisdiction. ", "/10/\n2. ", "Minturn also may reflect another 19th century exception to\nadmiralty jurisdiction -- the hypothecation requirement. ", "At the time\nMinturn was decided, it was deemed necessary for one claiming under a\ncontract to have a lien interest in a vessel before the contract would\nbe considered maritime. ", "/11/ And a ship's agent (the so-called\n\"ship's husband\") was not entitled to a lien. ", "See I. Parsons, A\nTreatise on Maritime Law 100 n.3 (1859); The Raleigh, 32 F. 633, 634\n(S.D.N.Y. 1887); The J.C. Williams, 15 F. 558, 559 (S.D.N.Y. 1883).", "\n/12/\nIn its short opinion, the Court in Minturn noted the absence of a\nlien: \"the local law of California, which authorizes an attachment of\nvessels for supplies or repairs, (does not) extend to the balance of\naccounts between agent and principal, who have never dealt on the\ncredit, pledge, or security of the vessel.\" ", "58 U.S. at 477. ", "As one\ncommentator has observed, \"(t)he Court's refusal to find that the\ncontract was maritime seems comprehensible only if Minturn is taken to\nrepresent the then-common line of cases that advocated the necessity\nof a lien interest against a vessel in all maritime contracts. ", "The\nCourt apparently reasoned that the agent could not assert a lien\nagainst a ship under any circumstances and therefore that the contract\ncould never be maritime.\" ", "See Note, General Agency Agreements and\nAdmiralty Jurisdiction, 17 Conn. L. Rev. 595, 604 (1985).", "\nLike the tidewater doctrine, the hypothecation requirement has long\nbeen abolished. ", "In Insurance Co. v. Dunham, 78 U.S. (11 Wall.) ", "1\n(1870), the Court held that a contract may be maritime, and give rise\nto a right to sue on the contract in personam, even when the contract\ndoes not create a lien. ", "As the Court explained (id. at 26), \"the true\ncriterion is the nature and subject-matter of the contract, as whether\nit was a maritime contract, having reference to maritime service or\nmaritime transactions.\" ", "Subsequent decisions have confirmed that\nadmiralty jurisdiction in the United States is not limited by any\nhypothecation requirement. ", "See, e.g., North Pacific S.S. Co. v. Hall\nBros. Marine Ry. & ", "Shipbuilding Co., 249 U.S. 119, 126 (1919);\nDetroit Trust Co. v. The Barlum, 293 U.S. 21, 47 (1934).", "\n3. ", "Finally, Minturn may have turned on the Court's observation (58\nU.S. at 477) that the case involved \"nothing but a demand for a\nbalance of accounts between agent and principal, for which an action\nin assumpsit, in a common law court, is the proper remedy.\" ", "This\nlimitation on admiralty jurisdiction has also been disavowed, albeit\nsomewhat more recently than those previously discussed. ", "In Archawski\nv. Hanioti, 350 U.S. 532, 536 (1956), the Court rejected the argument\nthat an action in assumpsit automatically puts the case beyond the\nreach of a court sitting in admiralty: \"It is sufficient this day to\nhold that admiralty has jurisdiction, even where the libel reads like\nindebitatus assumpsit at common law, provided that the unjust\nenrichment arose as a result of the breach of a maritime contract.\"", "\nIn short, Minturn rests on restrictions upon admiralty jurisdiction\nthat this Court has squarely rejected. ", "See e.g., 7A J. Moore & A.\nPalaez, Moore's Federal Practice Paragraph .250, at 3004-3005 (2d ed.", "\n1988). ", "Yet, the case remains as precedent and has been cited (at\nleast by the Second Circuit) as controlling authority for the broad\nproposition that general agency contracts are outside admiralty's\njurisdiction. ", "Pet. ", "App. ", "A11-A16, A31; accord Peralta Shipping Corp.\nv. Smith & Johnson (Shipping) Corp., 739 F.2d 798, 802-804 (1984),\ncert. ", "denied, 470 U.S. 1031 (1985); Admiralty Oriental Line v.\nAtlantic Gulf & Oriental S.S. Co., 88 F.2d 26, 27 (1937). ", "Cf.", "\nIngersoll Milling Mach. ", "Co. v. M/V Bodena, 829 F.2d 293, 301-302,\ncert. ", "denied, 484 U.S. 1042 (1987); Cory Bros. & Co. v. United\nStates, 51 F.2d 1010, 1012 (1931). ", "Minturn's agency rule is thus like\nthe divided damages rule this Court abrogated more than a decade ago:\n\"The reasons that originally led to the Court's adoption of the rule\nhave long since disappeared.\" ", "United States v. Reliable Transfer Co.,\n421 U.S. 397, 410 (1975).", "\nB. Overruling Minturn Would Be In Keeping With Efforts To\nRationalize The Scope Of Federal Admiralty Jurisdiction\nThe commentators are in broad agreement that \"(general agency)\nagreements are an integral part of, and in furtherance of, maritime\ncommerce and, consequently, should be cognizable within the admiralty\njurisdiction of the district court.\" ", "7A J. Moore & A. Palaez, Moore's\nFederal Practice Paragraph .250 at 3006 (2d ed. ", "1988); accord G.\nGilmore & C. Black, The Law of Admiralty 28 n.94b (2d ed. ", "1975); S.\nFriedell, Benedict on Admiralty Section 183, at 12-9 (7th ed. ", "1989).", "\nThis conclusion is consistent with the goal of uniformity underlying\nthe grant of admiralty jurisdiction to the federal courts, and with\nthe continuing trend toward rationalizing the scope of that\njurisdiction.", "\nA primary basis for the establishment of federal admiralty\njurisdiction was the need for a uniform national law. ", "Knickerbocker\nIce Co. v. Stewart, 253 U.S. 149, 160 (1920); 3 Elliot's Debates on\nthe Federal Constitution 352, 571 (2d ed. ", "1836); Sisson v. Ruby, 110\nS. Ct. ", "at 2898. ", "Yet, as Justice Blackmun, joined by Justice Marshall,\nnoted in dissenting from the denial of certiorari in Peralta (470 U.S.\nat 1031-1032), Minturn is an exception to admiralty jurisdiction \"that\nhas been applied inconsistently and that has created unnecessary\nconfusion in the federal courts.\" ", "Since \"uniformity and predictability\nin the maritime industry were the ends sought in the Constitution when\nfederal-court maritime jurisdiction was created in the first\ninstance,\" this inconsistency is particularly inappropriate in the\nadmiralty context (id. at 1034).", "\nThe inconsistencies in the interpretation of Minturn are pervasive.", "\nAs the district court noted, Pet. ", "App. ", "A11-A12, A29-A31, the Second\nCircuit remains committed to the view that, under Minturn, agency\nagreements are excluded from admiralty jurisdiction. ", "Although the\nSecond Circuit has stated that it would \"welcome\" Minturn's overruling\n(Peralta, 739 F.2d at 804), it has rejected a variety of distinctions\nthat limit the impact of Minturn in other circuits, noting that \"such\nhair-splitting distinctions would blur, if not obliterate, a rather\nclear admiralty demarcation\" (ibid.).", "\nThe Fifth Circuit has taken a diametrically different approach,\nrefusing to recognize any general rule excluding agency agreements\nfrom admiralty jurisdiction. ", "In Hadjipateras v. Pacifica, S.A., 290\nF.2d 697, 703 (1961), the Fifth Circuit held that an action for breach\nof an agency contract for the management and operation of a vessel is\nwithin the admiralty jurisdiction, since \"the contract is everything\nclassically known as a martime contract. ", "It concerns a ship. ", "It\nrelates not only to a ship; its very purpose is to effectuate the\nphysical, economic operation and employment of a vessel.\" ", "In so\nholding, the court observed that Minturn presumably forecloses\nadmiralty jurisdiction over an action for \"an accounting as such\" (290\nF.2d at 704 & n.15, noting \"doubts * * * cast\" on this restriction by\ncases such as Archawski v. Hanioti, supra).", "\nSimilarly, the Ninth Circuit, in Hinkins Steamship Agency v.\nFreighters, Inc., 498 F.2d 411, 412 (1974), questioned Minturn's\ncontinued vitality, and found the agency agreement at issue there to\nbe a maritime contract. ", "The Ninth Circuit emphasized that although\nthe husbanding agent had \"procured (maritime services) and did not\nperform them directly, * * * (the fact that) their performance was its\ndirect responsibility, that the services were clearly maritime and\nnecessary for the continuing voyage, and that (the agent) was directly\nengaged in supervision, makes (the service) maritime and the contract\nsued upon a maritime contract\" -- particularly since the agreement was\nlimited to a specific voyage and \"there was repeated attendance on\nboard the vessel\" by the agent. ", "Id. at 412.", "\nThe circuits, therefore, are clearly in disagreement about the\napplication of Minturn and the continued vitality of its holding.", "\nWhile some courts have strained to reconcile the disparate holdings,\nsee E.S. Binnings, Inc. v. M/V Saudi Riyadh, 815 F.2d 660, 664 (11th\nCir. ", "1987), the decisions appear in large measure to be\nirreconcilable. ", "For instance, the Second Circuit in Admiralty\nOriental Line v. Atlantic Gulf & Oriental S.S. Co., supra, ruled that\na \"managing operator\" agency contract was not within admiralty\njurisdiction, but the Ninth Circuit in Hinkins reached a contrary\nresult, precisely because the contract before it provided for direct\nmanagement services. ", "See Peralta, 739 F.2d at 804.", "\nIn addition, the circuits are at odds over whether the status of\n\"special agent\" removes the bar of the Minturn rule. ", "/13/ In Hinkins,\nthe agent had responsibility for only a specific voyage, and thus no\nlong-term relationship with the owner. ", "The Ninth Circuit found that\nadmiralty jurisdiction could be invoked, presumably since the duties\ninvolved were those most usually carried out by a special agent,\nrather than a general agent. ", "Similarly, in Ameejee Valleejee Sons v.\nM/V Victoria U., 661 F.2d 310, 312 (4th Cir. ", "1981), the court stated\nthat while a general agent cannot invoke admiralty jurisdiction, a\nspecial agent can. ", "The court found it difficult to formulate a test\nfor general agency, however, and observed that the Federal Maritime\nLien Act had \"somewhat impaired if not eliminated\" the rule that the\nenforcement of contracts by general agents falls outside admiralty's\njurisdiction. ", "See also Compagnia Maritima La Empresa, S.A. v.\nPickard, 320 F.2d 829 (5th Cir. ", "1963) (appearing to distinguish a\ngeneral agent from a special agent); The Eurana, 1 F.2d 684, 685 (3d\nCir. ", "1924) (suggesting that a lien would be available to a special\nagent, but not to a general agent). ", "On the other hand, the Second\nCircuit, in Peralta (739 F.2d at 803-804), refused to \"subdivid(e) the\ncategory of general agency contracts based on the degree of importance\nof the services rendered by the agent or on the extent of supervision\nof performance,\" and criticized the Hinkins distinction between\ngeneral and special agency agreements (739 F.2d at 803 n.4). ", "Accord\nContinental Cameras Co. v. FOA & Son Corp., 658 F. Supp. ", "287, 289\n(S.D.N.Y.), aff'd 831 F.2d 45 (2d Cir. ", "1987); Pet. ", "App. ", "A13-A16.", "\n/14/\nMinturn warrants reconsideration not only because of the confusion\nconcerning its scope, but also in light of the trend during the past\ncentury and a half to eliminate archaic restrictions on admiralty\njurisdiction. ", "Both Congress and this Court have participated in the\nprocess of rationalization. ", "Congress has enacted a series of\nliberalizing statutes beginning in 1884, /15/ and this Court has\nrepeatedly overturned earlier doctrines that are inconsistent with the\nprinciple that admiralty jurisdiction extends generally to\ntransactions \"related to ships and vessels, masters and mariners as\nagents of commerce\" Kossick v. United Fruit Co., 365 U.S. at 736.", "\n/16/ See United States v. Reliable Transfer Co., 421 U.S. at 409\n(noting that \"Congress has largely left to this Court the\nresponsibility for fashioning the controlling rules of admiralty\nlaw.\").", "\nMinturn is just such a relic of archaic doctrine. ", "Whether or not a\ncontract is to be considered maritime, and thus within the admiralty\njurisdiction of the federal courts, should not turn simply on whether\nor not the contract is one of agency. ", "Indeed, the conclusion that\ngeneral agency contracts are not within admiralty jurisdiction appears\ninconsistent with the broad terms of the Federal Maritime Lien Act,\nwhich provides (46 U.S.C. 31342):\n(a) person providing necessaries to a vessel * * * (1) has a\nmaritime lien on the vessel; (2) may bring a civil action in\nrem to enforce the lien; and (3) is not required to allege or\nprove in the action that credit was given to the vessel.", "\nThe district court rejected the applicability of the Federal Maritime\nLien Act on the ground that it did not extend the bounds of admiralty\njurisdiction (Pet. ", "App. ", "A26-A28). ", "It seems equally appropriate to\nconclude, however, that the Act reflects the current view of the scope\nof admiralty, and that Minturn is simply an outmoded reflection of an\nearlier, more limited view of that jurisdiction.", "\nNor do we believe that any settled expectations require adherence\nto Minturn. ", "In the first place, even assuming universal agreement on\nthe meaning of that decision, it is hard to see precisely what\njustified reliance interests will be undermined if Minturn is\noverruled. ", "Second, and more important, there is no such universal\nagreement, and thus continuance of the Minturn precedent can only lead\nto uncertainty in some instances, and forum shopping in others.", "\nII. ", "THE PRESENT CASE FALLS WITHIN THE ADMIRALTY JURISDICTION OF THE\nDISTRICT COURT\nIf, as we suggest, the Court determines that Minturn should be\noverruled and that agency agreements are not per se excluded from the\nscope of admiralty jurisdiction, the question will remain whether\nparticular agency agreements fall within that jurisdiction. ", "As the\ndistrict court noted (Pet. ", "App. ", "A16-A17), some contracts are\nsufficiently remote from maritime commerce, and so much a part of\nregular domestic commerce, that they are regarded as \"preliminary\" and\nbeyond the reach of admiralty jurisdiction. ", "A contract to sell timber\nto a shipbuilder, for example, is well-removed from the affairs of\nmaritime commerce. ", "Cf. ", "The Thames, 10 F. 848 (S.D.N.Y. 1881) (broker\nwho procured a charter party has no lien on a vessel); note 3, supra.", "\nIn the present case, the district court regarded the Minturn rule\nas a subset of the rule excluding preliminary contracts from the scope\nof admiralty. ", "Pet. ", "App. ", "A16-A17. ", "It therefore might be appropriate,\nonce that ground of decision has been rejected, to remand the case for\ndetermination of the question whether this particular agency contract\nis \"preliminary\" in nature.", "\nBut in our view, no such remand is required on the facts presented.", "\nThe marine fuel supplied to the ship was clearly \"necessary\" to the\nship's operation. ", "/17/ Moreover, petitioner did not simply arrange\nfor the sale of fuel by Arabian Marine to Waterman; rather,\npetitioner paid Arabian Marine for the fuel and seeks reimbursement\nfor that payment here. ", "/18/ Thus, whatever the limits of admiralty\njurisdiction with respect to agency agreements, those limits are not\napproached in this case.", "\nCONCLUSION\nThe decision of the court of appeals should be reversed.", "\nRespectfully submitted.", "\nKENNETH W. STARR\nSolicitor General\nSTUART M. GERSON\nAssistant Attorney General\nDAVID L. SHAPIRO\nDeputy Solicitor General\nHARRIET S. SHAPIRO\nAssistant to the Solicitor General\nROBERT S. GREENSPAN\nRICHARD A. OLDERMAN\nAttorneys\nFEBRUARY 1991\n/1/ Petitioner received certain cash and stock dividends under the\nreorganization plan; any judgment recovered in this action would be\nreduced to reflect these receipts. ", "Pet. ", "App. ", "A25.", "\n/2/ Formerly 46 U.S.C. 971 (1982). ", "See Pet. ", "App. ", "A26.", "\n/3/ Commencing at least as early as 1881, in The Thames, 10 F. 848\n(S.D.N.Y. 1881), courts in the Second Circuit embraced the rule that\ncontracts of a \"preliminary\" nature are outside federal admiralty\njurisdiction. ", "Ultimately, the holding of this Court in Minturn and\nthe rule declared in The Thames became entwined. ", "In Cory Bros. & Co.\nv. United States, 51 F.2d 1010, 1012 (1931), the Second Circuit\nexplained Minturn as involving a preliminary service contract.", "\nThe district court in this case, observing that \"the agency\nexception to maritime jurisdiction is less of an anomaly when viewed\nas a subset of the preliminary contract doctrine,\" rejected\npetitioner's invitation to \"disentangle the preliminary contract rule\nfrom the general agency rule.\" ", "Pet. ", "App. ", "A16-A17. ", "See id. at A29\n(quoting The Thames).", "\n/4/ The district court also rejected petitioner's claim that it was\nentitled to an admiralty lien by virtue of subrogation (Pet. ", "App.", "\nA18-A21). ", "Petitioner does not seek further review of this claim.", "\n/5/ For example, in this case, petitioner's claim for recovery\nunder its contract with Waterman for fuel supplied from its own\nfacilities in New York fell within admiralty jurisdiction (Pet. ", "App.", "\nA33), although deliveries under the same contract through the local\nsupplier in Jeddah did not.", "\n/6/ It has been held, for example, that a contract to repair a\nvessel is maritime, New Bedford Dry Dock Co. v. Purdy, 258 U.S. 96\n(1922), yet a contract to build a vessel is not, Thames Towboat Co. v.\nThe Schooner Francis McDonald, 254 F.2d 242 (1920), People's Ferry Co.\nv. Beers, 61 U.S. (20 How.) ", "393 (1857); that a policy of insurance on\na vessel is maritime, Wilburn Boat Co. v. Fireman's Fund Insurance\nCo., 348 U.S. 310 (1955), Insurance Co. v. Dunham, 78 U.S. (11 Wall.)", "\n1 (1870), although a contract to obtain such insurance is not, F.S.\nRoyster Guano Co. v. W.E. Hedger Co., 48 F.2d 86 (2d Cir.), ", "cert.", "\ndenied, 283 U.S. 858 (1931); Marquardt v. French, 53 F. 603 (S.D.N.Y.\n1893); and that a charter party is a maritime contract, Fisser v.\nInternational Bank, 175 F. Supp. ", "305 (S.D.N.Y. 1958), but a broker's\ncontract to secure such a charter party is not, Cory Bros. & Co. v.\nUnited States, 51 F.2d 1010 (2d Cir. ", "1931); Brown v. West Hartlepool\nSteam Navigation Co., 112 F. 1018 (5th Cir. ", "1902). ", "Moreover, while a\nlease of cargo containers for use on a ship is maritime, CTI-Container\nLeasing v. Oceanic Operations, 682 F.2d 377 (2d Cir. ", "1982), as is a\ncontract to purchase equipment for a ship, e.g., Radiomarie Corp. v.\nGulf Northern Co. 394 F. Supp. ", "381 (E.D. Mo. 1975), a contract to\npurchase a vessel is not, Economou v. Bates, 222 F. Supp. ", "988\n(S.D.N.Y. 1963).", "\n/7/ According to one writer, the court's jurisdiction included\n\"torts and offenses on the high seas, on British seas, and in ports\nwithin the ebb and flow of the tide, matters of prize, * * *, and\ncauses arising on the seashore and in ports.\" ", "D. Robertson, Admiralty\nand Federalism 40 (1970), quoting Mears, The History of Admiralty\nJurisdiction, 2 Select Essays in Anglo-American Legal History, 312,\n328-329 (1908).", "\n/8/ As the Court explained in Grant v. Poillon, 61 U.S. (20 How.)", "\n162, 168 (1857), under the tidewater doctrine \"contracts upon land,\nthough to be executed on the sea, and contracts at sea, if to be\nexecuted on the land, are not cognizable by the English admiralty.\"", "\n/9/ The acceptance of the tidewater doctrine may have been in part\ndue to a desire not to interfere with state court jurisdiction.", "\nChancellor Kent observed (1 J. Kent, Commentaries 372 (12th ed. ", "1873))\nIf the admiralty and maritime jurisdiction of the district\ncourts embrace all maritime contracts, then suits upon policies\nof insurance, charter-parties, martime hypothecations, contracts\nfor building, repairing, supplying, and navigating ships, and\ncontracts between part owners of ships, must be tried in the\nadmiralty by a single judge, to the exclusion of the trial by\njury; and the state courts would be divested, at one stroke, of\na vast field of commercial jurisdiction.", "\n/10/ As Professor Moore has noted, \"some remnant of the restrictive\nEnglish mentality regarding the admiralty appears to have been present\nin the minds of the court that decided the early cases.\" ", "7A J. Moore &\nA. Palaez, Moore's Federal Practice Paragraph .250, at 3004-3005 n.10\n(2d ed. ", "1988). ", "Indeed, \"(o)nly by applying a location test (i.e., the\ntidewater doctrine) could it be convincingly stated that agreements to\nprocure charters, to arrange contracts or maritime affreightment, and\nto arrange for or oversee the numerous other necessary activities\noften delegated to brokers and agents are not directly related to\nmaritime commerce.\" ", "Id. at 3004-3005.", "\n/11/ See Gardner v. The New Jersey, 9 F. Cas. ", "1192, 1195 (D. Pa.\n1806) (No. ", "5233); Note, General Agency Agreements and Admiralty\nJurisdiction, 17 Conn. L. Rev. 595, 597-598 (1985).", "\n/12/ At the time Minturn was decided, the ship's husband was\nusually a part owner. ", "See Gould v. Stanton, 16 Conn. 12, 23 (1843);\nI. Parsons, A Treatise on Maritime Law 97 (1859); G. Abbott, Treatise\nof the Law Relative to Merchant Ships and Seamen 136 (5th American ed.", "\n1846). ", "The rationale for denying the lien was that a part owner\nacting as ship's husband dealt on the credit of his fellow owners, not\nthe credit of the vessel. ", "It was thus generally accepted that\n\"admiralty has no jurisdiction at all in matters of account between\npart-owners.\" ", "The Steamboat Orleans v. Phoebus, 36 U.S. at 182; cf.", "\nDavis v. Child, 7 F. Cas. ", "112, 116-117 (D. Me. ", "1840) (No. ", "3628).", "\nWhen the Court in Minturn was faced with an action for an\naccounting brought by a general agent against a vessel's owners, it\nmay have appeared that the controversy was one between co-owners\nseeking an accounting. ", "In fact, however, Minturn was not a co-owner\nof the vessel. ", "See Note, supra, at n.31 citing Minturn Supreme Court\nRecord at 3. ", "Thus, the Minturn Court may have based its conclusion on\nan assumption not supported by the facts.", "\n/13/ \"A special agency properly exists, when there is a delegation\nof authority to do a single act; a general agency properly exists\nwhere there is a delegation to do all acts acts connected with a\nparticular trade, business, or employment.\" ", "J. Story, Commentaries On\nThe Law Of Agency Section 17 (9th ed. ", "1982).", "\n/14/ The Second Circuit has cited Hinkins with approval, however,\nin concluding that \"(t)he preparation and processing of export\ndeclarations, delivery orders, dock receipts, bills of lading and\nadvance notification of shipment are not services endered preliminary\nto a voyage(,) rather they are essential to it,\" and that,\naccordingly, a freight forwarder who carries out these functions may\nsue in admiralty. ", "Ingersoll Milling Mach. ", "Co. v. M/V Bodena, 829 F.2d\n293, 302-303, cert. ", "denied, 484 U.S. 1042 (1987).", "\n/15/ In Detroit Trust Co. v. The Barlum, 293 U.S. at 43-44, this\nCourt recognized that Congress has the power to define the precise\nscope of the constitutional grant of admiralty jurisdiction to the\nfederal courts, even if that definition expands the limits of that\njurisdiction, so long as the grant remains within the purposes and\ngeneral understanding of the concept. ", "Congress has acted on that\nauthority. ", "See e.g., Act of June 26, 1884, ch. ", "121, Section 18, 23\nStat. ", "57-58, a interpreted by the Court in Richardson v. Harmon, 222\nU.S. 96, 101-102 (1911) (extending admiralty jurisdiction to include\ndamages by a vessel to a land structure); the Federal Maritime Lien\nAct of 1910, ch. ", "373, 36 Stat. ", "604, and the Act of June 5, 1920, ch.", "\n250, 41 Stat. ", "1005 (permitting a person providing necessaries for a\nvessel on the order of the owner to assert a maritime lien on the\nvessel, and to bring a civil action in rem to enforce the lien,\nwithout proving that credit was given to the vessel); the Death on\nthe High Seas Act of 1920, ch. ", "111, 41 Stat. ", "537 (giving admiralty\njurisdiction over suits for damages for death caused by a wrongful act\non the high seas); the Merchant Marine Act of 1920, ch. ", "250, 41 Stat.", "\n1007 (incorporating into the maritime law rules drawn from the Federal\nEmployers Liability Act); the Longshoremen's and Harbor Workers'\nCompensation Act of 1927, ch. ", "509, 44 Stat. ", "1424; the Admiralty\nJurisdiction Extenstion Act of 1948, ch. ", "526, 62 Stat. ", "496 (extending\nadmiralty jurisdiction to damages to person or property on land caused\nby vessel on navigable water); Act of Nov. 23, 1988, Pub. ", "L. No.", "\n100-711, 102 Stat. ", "4735 (revising ship mortgage and lien laws to\nsimplify administration of those laws, \"to make (them) less cumbersome\nfor the maritime community, and to make (them) more understandable for\neveryone involved.\" ", "H.R. Rep. No. ", "918, 100th Cong. ", "2d Sess. ", "1 (1988)).", "\n/16/ E.g., The Propeller Genesee Chief, 53 U.S. (12 How.) ", "443\n(1851) (rejecting tidewater doctrine); Insurance Co. v. Dunham, 78\nU.S. (11 Wall.) ", "1 (1870) (constitutional grant of admiralty\njurisdiction not limited by restrictive English precedents);\nArchawski v. Hanioti, 350 U.S. at 536 (admiralty jurisdiction extends\nto quasi-contract claim for unjust enrichment, \"even where the libel\nreads like indebitatus assumpsit at common law\"). ", "Cf. ", "Executive Jet\nAviation, Inc. v. City of Cleveland, 409 U.S. 249, 268 (1972) (no\nadmiralty jurisdiction where tort had no \"significant relationship to\ntraditional maritime activity\").", "\n/17/ Cf. ", "the Federal Martime Lien Act, 46 U.S.C. 31342, p.24,\nsupra, which provides for a maritime lien for a person supplying\n\"necessaries\" to a vessel. ", "The term \"necessaries\" includes \"supplies\nwhich are necessary to keep the ship going.\" ", "Dampskibsselskabet v.\nSignal Oil & Gas Co., 310 U.S. 268, 280 (1940) (fuel oil); Tramp Oil\n& Marine Ltd. v. M/V Mermaid I, 630 F. Supp. ", "630, 632 (D.P.R.), aff'd,\n805 F.2d 42, 44 (1st Cir. ", "1986) (same).", "\n/18/ Even before the enactment of the Federal Maritime Lien Act, an\naction to recover money owed for the supply of fuel to a vessel in a\nforeign port would have been deemed within admiralty's jurisdiction.", "\nSee, e.g., Supreme Court Rule 12, 80 U.S. (13 Wall.) ", "xiv (1872); The\nJ.E. Rumbell, 148 U.S. 1, 12 (1893); J. Moore & A. Palaez, Moore's\nFederal Practice Paragraph .230 (4-5), at 2853, (citing Martran S.S.\nCo. v. Aegean Tankers Ltd., 170 F. Supp. ", "477, 479 (S.D.N.Y. 1950)).", "\nCf. ", "S. Friedell, Benedict on Admiralty Section 36 (7th ed. ", "1989) (\"In\nthe older codes of Continental Europe, the concept of (the\nmaterialman's lien) existed although it was not definitely defined.", "\nUnder this law, the lien was given unqualifiedly to the furnisher of\nnecessaries, and it made no difference who he was, or where or how the\nnecessaries were obtained.\")." ]
{ "pile_set_name": "Pile-CC" }
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[ "Q:\n\nprohibitory sign on application icon (broken folder) on Snow Leopard\n\nI have prepared a disk image with my application,which i want to install in Applications folder. ", "When i copy the application from the disk image to the applications folder, i see that first it gets generic application icon (sometimes my application icon with a prohibitory sign (or broken folder) ). ", "It becomes executable application after a couple of seconds (some 10 seconds)\nI wonder if somebody has experienced something similar?", "\nEDIT: On my customer computer with Snow Leopard the application stayed with a prohibitory sign (broken folder) . ", "How do i fix it? ", "It worked on Leopard\n\nA:\n\nAs I suspected it was a permissions problem. ", "When build an installer with a Packager all items have to have a root as owner and wheel as group for permissions.", "\n\n" ]
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[ "India’s ATMs Are Running Out of Cash. ", "Again.", "\n\nNEW DELHI — For the second time in 18 months, India has a shortage of cash. ", "And like last time, economists say, it’s primarily the government’s fault.", "\n\nEmpty ATMs and bank restrictions on withdrawals have been reported in eight states this week, and some bank managers said the cash crunch has been building for months.", "\n\nThe government says the cash problem was caused by an unusual spurt in demand and will be eased within days. ", "But if it persists, the shortage poses a political threat to Prime Minister Narendra Modi, whose administration has been hit in recent weeks from a series of stumbles. ", "Most recently, he was criticized for his long silence over the horrific gang rape and murder of an 8-year-old Muslim girl that police say was committed by a group of Hindu men to terrorize the Muslim population.", "\n\nOn Monday, Sampath Kumar Lohati drove his scooter around Warangal, a city in the south Indian state of Telangana, for more than four hours trying to withdraw money.", "\n\n“I tried at least 50 to 60 ATMs,” he said in a telephone interview. “", "But I could not find any cash.” ", "Mr. Lohati, an insurance agent, finally got money on Tuesday after an ATM near his home was refilled.", "\n\nIndia’s last cash crisis was caused in November 2016, when Mr. Modi decided to suddenly void most of India’s paper currency. ", "The current shortage is also rooted in government policy decisions, as well as growing public mistrust of banks after several costly scandals.", "\n\nMost Indians work at informal jobs that operate almost entirely in cash, from roadside food stands to day laborers. ", "People in such jobs had already seen some work dry up because of the shock 2016 demonetization, as well as the imposition of a cumbersome national tax on goods and services in 2017 that has sought to formalize transactions that had previously been off the books.", "\n\nDepending on how long it lasts, the current cash crunch will further dent the incomes of those workers, who are a critical part of the voter base of Mr. Modi’s governing Bharatiya Janata Party.", "\n\n“If this kind of shortage is there and the unorganized sector gets hit again, which it will, if the cash shortage persists, then there has got to be fallout from that,” said Arun Kumar, a professor at the Institute of Social Sciences in New Delhi who studies public finance and the illicit economy. “", "That will be very damaging to the ruling party.”", "\n\nOpposition leaders are already trying to gain political mileage from the situation. ", "Mamata Banerjee, the chief minister of the state of West Bengal and a frequent critic of Mr. Modi’s policies, said on Twitter Tuesday, “Seeing reports of ATMs running out of cash in several States. ", "Big notes missing. ", "Reminder of #DeMonetisation days. ", "Is there a Financial Emergency going on in the country? #", "CashCrunch #CashlessATMs.”", "\n\nEconomists say that the cash shortage has no single cause, but rather is the result of a combination of factors.", "\n\nFollowing the 2016 currency cancellation, the government did not print enough new bank notes to keep up with India’s growing economy, betting that cash-loving Indians would embrace digital transactions. (", "They did not.)", "\n\nMeanwhile, hoarders and black market operators started stockpiling 2,000-rupee notes, worth about $30 each. ", "Rather than expanding the supply to compensate, the government decided to stop printing the high-value bills, forcing banks to fill ATMs with lower denomination notes, which run out more quickly.", "\n\nPublic faith in the safety of India’s banks has also faltered over the past year, prompting people to keep more cash at home.", "\n\nThe Modi government, warning of a growing problem with bad bank loans, last fall pledged $32 billion in taxpayer funds to bail out weak lenders. ", "It also proposed legislation that could force depositors with more than $1,500 in an account to take a loss if their bank failed.", "\n\nJitters rose further in February after Punjab National Bank, a major state-owned lender, and government investigators accused the jeweler Nirav Modi of stealing $1.8 billion in a scheme that went undetected for years because of poor controls at the bank.", "\n\n“Many people got scared,” said Radha Rani, a senior manager at Indian Bank, another state-owned bank, in Warangal. “", "They are keeping money in their houses or investing in real estate. ", "They have fear of losing money if deposited in the bank. ", "So many people directly told us that.”", "\n\nG. Ravinder, 55, an architect and consultant in Warangal, said that he has issued paychecks to the laborers working on his projects, but they have been unable to cash them.", "\n\nHis bank, the State Bank of India, the country’s largest bank, will not allow him to withdraw enough cash from the branch either. “", "I went to the bank to withdraw 40,000 rupees, but they said, ‘Sorry, we can give you only 20,000 rupees,’” he said. “", "So how do I do my work?”", "\n\nThe harvest and marriage seasons are looming, increasing demand for cash. ", "If the shortage is not quickly eased, more customers will demand their money, potentially causing a much bigger problem: a bank run.", "\n\n“We have deposited our own money in the bank with the assumption that whenever we need money, we can get it from the bank. ", "When banks are not giving money, then people are scared that bank deposits are not safe,” Mr. Ravinder said. “", "That is why people are withdrawing their money from the banks.”" ]
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[ "How accurate are food labels?", "\n\nIf you think your favorite snack is void of trans fat, saturated fat, or or even sugar - think again. ", "The FDA has a little known loop hole regarding food labels that could be giving you a bit more of these ingredients than you realize. \"", "You can see we have evaporated cane juice, organic molasses,\" explains dietitian Alyse Levine.", "\n\nChecking out a box cereal, Alyse Levine reveals all the aliases she found for sugar.", "\n\n\"Anything with 'ose,' glucose, sucrose fructose, if you see 'ose' at the end of the word, it's a sugar,\" said Levine.", "\n\nIt is something we get too much of she says. ", "But surprisingly, even if it's organic the body metabolizes all these sweeteners the same.", "\n\nExperts suggest we get just ten percent of our daily intake from added sugars, yet Americans get far more.", "\n\nNaturally occurring sugar from dairy and fresh fruit is the exception since they provide much needed nutrients.", "\n\nBut perhaps the larger problem is stealth trans and saturated fats. ", "Often hidden due to a little known label loop hole.", "\n\nIt could be sugar, trans fat, saturated fat the regulation is the same.", "\n\nIf there is less than one gram of any ingredient, the manufacturer is allowed to list it as .5 or a half a gram, which means free. ", "Sugar free, saturated fat free, trans fat free is still legal.", "\n\n\"So lets say something was .9, and they are writing .5 on the label -- if you think by having 2 or 3 servings you're only having a gram to a gram and a half, you're actually consuming close to 3 grams,\" explains Levine.", "\n\nKeep in mind there is no established upper limit for trans fat. ", "Having none at all is best.", "\n\nTrans fat is featured in the ingredient list as partially hydrogenated oil. ", "Saturated fat generally appears as palm or coconut oil.", "\n\nAnd the higher it's up on the ingredient list, the more the product contains. ", "As always scrutinize those food facts." ]
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[ "Header Right\n\nSearch\n\nMain navigation\n\nPersonal Branding\n\nPicture this: your laptop has broken down and you desperately need it fixed. ", "A friend recommends a computer technician and he promises to get it repaired within three hours. ", "The techie turns up to collect said laptop looking disheveled, unshaven and wearing a dirty t-shirt. ", "Are you having second thoughts? ", "Of course you are.", "\n\nThe technician’s appearance has not been consistent with what you had heard about him from your friend (that he is very reliable and extremely good at fixing computers) or with the prior telephone call you had with him (during which he sounded serious and professional). ", "If you had any other option you would probably go back on your decision to hand over your laptop to this scruffy looking individual, but instead you go with it, and you are hugely relieved (and not a little surprised) when your laptop arrives back three hours later as good as new and working faster than it ever had before.", "\n\nThe technician’s ‘brand’ had preceded him, by his ‘brand’ I mean his reputation, what people think or say about him. ", "It made you make that first call, and it almost lost him a client when he showed up at your door. ", "Everyone has a ‘brand’ whether they are aware of it or not. ", "People formulate perceptions about you and your business according to what they see and hear about you. ", "In the recent financial environment, more and more people are realizing how taking control of your reputation and brand can help you stand out from the crowd and succeed in your professional and personal life. ", "This ‘Reputation Management’ is often referred to as Personal Branding and can be summarized as the process of taking control of your brand and making sure it is saying what you want it to say.", "\n\nTo achieve successful personal branding you need to establish your own “Unique Promise of Value”. ", "The world’s foremost personal branding expert, William Arruda, puts it very clearly; “What makes you unique, makes you successful”. ", "You need to establish what your strengths are and focus on promoting them. ", "Thus your “Unique Promise of Value” is what makes you stand out from your competitors.", "\n\nWilliam Arruda is also the founder of Reach Personal Branding, the US company which has trained Joanne Shawcross, Mallorca -based Personal Branding expert and the only qualified Reach Personal Branding Specialist in Spain. “", "Consistency is key for a successful brand”, said Joanne at a recent keynote speech she gave in Palma. “", "You need to consistently project the same image of yourself and your business in order to create a brand that is strong and lasting.” ", "That includes your physical appearance, your web presence, your logo, everything that people hear about you and what you put out there for them to see. ", "Think of Volvo cars, for example. ", "When you think Volvo you probably think ‘safety’, most people do. ", "And that is not a coincidence. ", "Volvo has worked very hard on their brand and has successfully managed to make it so that people consistently relate their cars with safety and reliability.", "\n\nJoanne can take you or your company through a complete personal branding process, from assessing what your brand is currently saying about you, to identifying what you want it to say and putting strategies and systems in place to make it so. ", "A vital and extremely interesting part of this process is the 360˚Reach Assessment. ", "This entirely confidential process involves getting your friends and colleagues to reply to a series of questions describing what they think about you and what you do. ", "It is a reputation-based analysis of you as a company or individual. ", "It sheds light on the perception people have of you, often with surprising results. ", "Joanne can then help you assess the results of the test, and see whether you are projecting the image you want to be projecting. ", "This involves every aspect of your personality, professional life and image and so gives you an honest and complete analysis of your personal brand as people see it. ", "In short it gives you critical, anonymous feedback about what people think about you; invaluable insight you are not likely to get any other way.", "\n\nFor some it may provide a harsh awakening, for others pleasant surprises and a great confidence boost. “", "The 360˚Reach Assessment can really validate a person’s brand, as well as highlight areas that need extra work”, said Joanne. “", "And the great thing is that it can be carried out with individuals or with whole teams, so companies can see how best to improve the way their staff represents their brand. ", "It also sheds light on each member of staff’s individual assets and can help managers understand them better and ultimately boost productivity.”", "\n\nI interviewed Joanne over a coffee at one of the Cappuccino cafes in Palma, the Mallorca grown luxury cafeterias that have recently opened branches in Saudi Arabia and Dubai. ", "Now there’s an example of a strong brand. ", "Think of Cappuccino and you think luxury, quality, style and exclusivity. ", "You know that whichever branch of Cappuccino you go to you are going to experience the same unique promise of value. ", "It´s the kind of place you can take a potential client to and know that they will be suitably impressed, provided you don´t turn up looking like a disheveled computer technician!", "\n\nFollow us on facebook\n\nFollow us on facebook\n\nFooter\n\nabcmallorca\n\nabcMallorca is the leading luxury lifestyle magazine, website and networking community for the Spanish Balearic island of Mallorca, published in English, Spanish and German. ", "Interesting articles, guides, expert review & fabulous photo-shoots and videos provide a wealth of valuable insider information designed to help make living, doing business or spending time on this beautiful island a memorable experience.", "\n\nWe use our own cookies and third-party cookies to provide our services and to analyse activity on the web site in order to improve its content. ", "If you continue to browse without modifying the settings of your browser, we will consider that you accept their use. ", "Further information in our cookies Policy.x" ]
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[ "A case of sulphasalazine-induced DRESS syndrome with delayed acute interstitial nephritis.", "\nDrug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. ", "Renal failure has been rarely described. ", "We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. ", "After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. ", "A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. ", "Kidney function normalized after a further 2 weeks of corticosteroid treatment. ", "This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome." ]
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[ "María Pineda Gochi\n\nMaría del Rocío Pineda Gochi (born 8 September 1955) is a Mexican politician affiliated with the PRI. ", "She currently serves as Senator of the LXII Legislature of the Mexican Congress representing Michoacán.", "\n\nReferences\n\nCategory:1955 births\nCategory:Living people\nCategory:Politicians from Michoacán\nCategory:Women members of the Senate of the Republic (Mexico)\nCategory:Members of the Senate of the Republic (Mexico)\nCategory:Institutional Revolutionary Party politicians\nCategory:People from Zacapu\nCategory:21st-century Mexican politicians\nCategory:21st-century Mexican women politicians" ]
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[ "Related Articles\n\nNarendra Modi’s hunkar had barely died down in Patna when Bihar Chief Minister Nitish Kumar pounced on his rally speech. ", "According to Nitish, Modi got his Chandraguptas wrong, shifted Taxila from Pakistan to Bihar and sent Alexander the Great to the banks of the Ganges instead of having him turn back at the Sutlej. ", "Intriguing set of counterfactuals, this. ", "But for the less fanciful, this election season will be fertile ground for a game of true or false.", "\n\nPolitical speeches in recent months have betrayed a tenuous relationship with facts. ", "Modi, for instance, lavished praise on China, claiming it spent 20% of its GDP on education, though other sources claimed it spent only 3.93%. ", "His take on mathematics seems rather like his approach to history—interpretive. ", "Indeed, leaders across the political spectrum seem happy to gently elide the details as they reach out to voters. ", "At a rally in Madhya Pradesh, Congress vice president Rahul Gandhi claimed that, according to a Unicef study, more people went hungry in the state than in all of Africa. ", "In reality, it was a Unicef analysis of Indian government data, sub-Saharan Africa and malnutrition rather than hunger—but who’s listening? ", "Meanwhile, waxing eloquent on the MNREGA in Kerala, Shashi Tharoor claimed half the women employed under the scheme were over 50, a somewhat generous estimate.", "\n\nThe new age politician has a penchant for data, rattling off facts and figures with remarkable efficiency. ", "It lends a certain heft to political rhetoric, and is meant to persuade voters that their leaders have done their homework. ", "Except, in recent months, the line between the two seems to have blurred. ", "And facts, when wielded as rhetoric, have a peculiar habit of doubling back on the speaker." ]
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[ "Pluronic block copolymers as modulators of drug efflux transporter activity in the blood-brain barrier.", "\nDrug efflux transporters can influence the absorption, tissue distribution and elimination of many therapeutic agents. ", "Modulation of drug efflux transporter activity is being explored as a means for improving the pharmacokinetic and pharmacodynamic properties of various drugs. ", "In this regard, several polymer formulations have been shown to inhibit drug efflux transporters such as P-glycoprotein (P-gp). ", "The current review will focus on Pluronic block copolymers in particular, the mechanisms involved in the effects of Pluronic on drug efflux transporters, and the optimal polymer compositions required for inhibition of drug efflux transporters. ", "Special emphasis will be placed on the potential applications of Pluronic in enhancing the blood-brain barrier (BBB) penetration of drugs." ]
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[ "LaRose by Louise Erdich\n\nLate summer in North Dakota, 1999: Landreaux Iron stalks a deer along the edge of the property bordering his own. ", "He shoots with easy confidence but only when he staggers closer does he realise he has killed his neighbour's son.", "\n\nDusty Ravich, the deceased boy, was best friends with Landreaux's five-year-old son, LaRose. ", "The two families have been close for years and their children played together despite going to different schools. ", "Landreaux is horrified at what he's done; fighting off his longstanding alcoholism, he ensconces himself in a sweat lodge and prays for guidance. ", "And there he discovers an old way of delivering justice for the wrong he's done. ", "The next day he and his wife Emmaline deliver LaRose to the bereaved Ravich parents. ", "Standing on the threshold of the Ravich home, they say, 'Our son will be your son now'.", "\n\nLaRose is quickly absorbed into his new family. ", "Gradually he's allowed visits with his birth family, whose grief for the son and brother they gave away mirrors that of the Raviches. ", "The years pass and LaRose becomes the linchpin that links both families. ", "As the Irons and the Raviches grow ever more entwined, their pain begins to subside. ", "But when a man who nurses a grudge against Landreaux fixates on the idea that there was a cover-up the day Landreaux killed Dusty - and decides to expose this secret - he threatens the fragile peace between the two families..." ]
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[ "\n182 S.W.3d 244 (2005)\nJohn Kent FLAIZ, Respondent,\nv.\nDIRECTOR OF REVENUE FOR the STATE OF MISSOURI, Appellant.", "\nNo. ", "WD 64637.", "\nMissouri Court of Appeals, Western District.", "\nDecember 20, 2005.", "\nMotion for Rehearing and/or Transfer Denied January 31, 2006.", "\n*245 Jeffrey S. Eastman, Gladstone, MO, for respondent.", "\nJeremiah W. (Jay) Nixon, Atty. ", "Gen., Don Willoh, Assistant Attorney General, Jefferson City, MO, for appellant.", "\nBefore: HOWARD, P.J., EDWIN H. SMITH, C.J., and NEWTON, J.\nMotion for Rehearing and/or Transfer to Supreme Court Denied January 31, 2006.", "\nEDWIN H. SMITH, Chief Judge.", "\nThe Director of Revenue (Director) appeals from the judgment of the Circuit Court of Platte County setting aside the Director's revocation of the driver's license of respondent, John Flaiz, pursuant to § 577.041,[1] for his refusal to submit to a Breathalyzer test, authorized by § 577.020.", "\n*246 In her sole point on appeal, the Director claims that the trial court erred in reinstating the respondent's driver's license because she made a prima facie case for revocation, in accordance with § 577.041, which was not rebutted by the respondent.", "\nWe affirm.", "\n\nFacts\nAt approximately 12:30 a.m. on March 22, 2004, Trooper John W. Dick, Jr., of the Missouri State Highway Patrol, was just finishing up a traffic stop near the 64th Street exit of Interstate 29 in Kansas City, Missouri, when he noticed a black Acura approaching from the south, with one headlight out. ", "Trooper Dick pursued the Acura and eventually stopped it. ", "At the time, it was being driven by the respondent. ", "Trooper Dick's vehicle was equipped with a video camera, which recorded the stop and arrest.", "\nAfter stopping the respondent's vehicle, Trooper Dick exited his vehicle and approached the driver's side window of the Acura. ", "He explained to the respondent that he had stopped him because of an inoperable headlight. ", "After engaging the respondent in conversation, Trooper Dick noticed that his speech was slurred and that his eyes were bloodshot and watery. ", "He also smelled an odor of alcohol emanating from the respondent's vehicle. ", "Trooper Dick asked the respondent for his driver's license and proof of insurance. ", "The respondent handed him his license and registration. ", "The respondent continued to look for his proof of insurance, but was unable to locate it.", "\nTrooper Dick requested that the respondent have a seat in his patrol vehicle. ", "The respondent complied and sat in the front passenger seat, but did not close the door. ", "Trooper Dick and the respondent continued to converse while sitting in the patrol vehicle. ", "Trooper Dick asked the respondent why he was on the road at this time of night. ", "The respondent explained that he had just driven from St. Louis. ", "Trooper Dick asked him whether he had stopped anywhere along the way, and the respondent said, \"No.\" ", "A few minutes later, the respondent mentioned that he had stopped to eat. ", "When Trooper Dick confronted him with this apparent inconsistency in his story, the respondent stated that \"he may have just driven through.\" ", "Trooper Dick asked him whether he had anything to drink that night, and he said, \"No.\" ", "He then asked him if he would submit to a Breathalyzer test. ", "The respondent refused \"because it wasn't fair to him.\" ", "Trooper Dick then requested him to submit to field sobriety tests, which the respondent refused. ", "At that juncture, Trooper Dick informed him that he would be arrested if he continued to refuse to submit to field sobriety tests. ", "The respondent continued to refuse, and he was arrested for driving while intoxicated, DWI.", "\nHaving arrested the respondent for DWI, Trooper Dick transported him to the Platte County Jail where he read him the implied consent advisory and again asked him to submit to a Breathalyzer test, which the respondent refused. ", "The respondent was then given Revenue Form 4323, advising him that his driving privileges were being revoked for a one-year period for a Breathalyzer refusal.", "\nPursuant to § 577.041.3, the Director revoked the respondent's driver's license for his refusal to submit to the Breathalyzer test requested by Trooper Dick. ", "Pursuant to § 577.041.4, the respondent appealed his revocation to the Circuit Court of Platte County. ", "The appeal was heard by the Honorable Daniel Czamanske on August 19, 2004. ", "At the hearing, the only witness to testify on behalf of the Director was Trooper Dick. ", "Trooper Dick's report was introduced into evidence. ", "The respondent *247 did not testify nor call any witnesses on his behalf. ", "The only evidence he offered was the Patrol's videotape of the incident, which was admitted without objection and played in open court. ", "At the close of the evidence, the trial court took the matter under advisement. ", "On August 23, 2004, the trial court, not finding all of the issues specified in § 577.041 to be in the affirmative, specifically, the issue of probable cause to believe that the respondent was DWI, entered judgment for the respondent, ordering the Director to reinstate his driver's license.", "\nThis appeal follows.", "\n\nStandard of Review\nWe must affirm the judgment of the trial court setting aside the revocation of the respondent's driver's license by the Director, in accordance with § 577.041, unless we find that there is no substantial evidence to support it, it is against the weight of the evidence, or it erroneously declares or applies the law. ", "Hinnah v. Dir. ", "of Revenue, 77 S.W.3d 616, 620 (Mo. banc 2002). ", "We will set aside a judgment on the basis that it is against the weight of the evidence only when there is a firm belief that the judgment is wrong. ", "Wilson v. Dir. ", "of Revenue, 35 S.W.3d 923, 926 (Mo.App.2001).", "\nWhen the Director's \"evidence is uncontroverted or admitted so that the real issue is a legal one as to the legal effect of the evidence, then there is no need to defer to the trial court's judgment.\" ", "Hinnah, 77 S.W.3d at 620. ", "We cannot disregard the Director's uncontroverted evidence and presume that the trial judge found a lack of credibility in order to affirm the judgment. ", "Hockman v. Dir. ", "of Revenue, 103 S.W.3d 382, 386 (Mo.App. ", "2003).", "\nBut, where evidence is presented which, if believed, would support a finding in favor of one party, but contrary or inconsistent evidence is also presented, then it is up to the judge to resolve the factual issues, including determining the credibility of witnesses. ", "So long as its determination is supported by substantial evidence, we will affirm, regardless whether we would have reached the same result.", "\nHampton v. Dir. ", "of Revenue, 22 S.W.3d 217, 220 (Mo.App.2000).", "\nIn assessing if there is substantial evidence, we must defer to the trial court on factual issues and cannot substitute our judgment for that of the trial judge. ", "Such deference is not limited to the issue of credibility of witnesses, but also to the conclusions of the trial court. ", "Appellate courts view the evidence in the light most favorable to the trial court's judgment, and we deem all facts to have been found in accordance with the result reached by the trial court. ", "A trial court is accorded wide discretion even if there is evidence that would support a different result. ", "In a driver's license revocation case, a trial court has the prerogative when weighing witness credibility, to accept or reject all, part, or none of the testimony of any witness.", "\nLong v. Dir. ", "of Revenue, 65 S.W.3d 545, 548 (Mo.App.2001) (internal citations omitted).", "\n\nI.\nIn her sole point on appeal, the Director claims that the trial court erred in reinstating the respondent's driver's license because she made a prima facie case for revocation, in accordance with § 577.041, which was not rebutted by the respondent. ", "Specifically, she claims that the trial court's reinstatement of the respondent's driver's license was not supported by substantial evidence and was against the weight of the evidence in that the respondent *248 did not present any evidence controverting the evidence, on which her prima facie case for revocation was based.", "\nSection 577.041.3 mandates that the Director revoke, for one year, the driver's license of a person under arrest for DWI for refusing, when requested by the arresting officer, to submit to a chemical test, authorized by § 577.020. ", "Pursuant to § 577.041.4, \"[i]f a person's license has been revoked because of the person's refusal to submit to a chemical test, [as authorized by § 577.020], such person may petition for a hearing before a circuit or associate circuit court in the county in which the arrest or stop occurred.\"", "\nIn order to make a prima facie case for upholding a § 577.041 revocation for a refusal in a DWI case, the Director is required to show that: (1) the driver was arrested; (2) the arresting officer had reasonable grounds to believe the driver was DWI; and (3) the driver refused to submit to an authorized chemical test as requested. § ", "577.041.4; Hinnah, 77 S.W.3d at 620. ", "If the court determines any of the three elements of the Director's case for revocation not to be in the affirmative, it shall order the Director to reinstate the driver's license. § ", "577.041.5; Hinnah, 77 S.W.3d at 620. \"", "The director, thus, has the burden of proof at the hearing.\" ", "Hinnah, 77 S.W.3d at 620.", "\nWhile the respondent did not contest at the § 577.041 hearing that he was arrested and refused to submit to the Breathalyzer test, as requested by the arresting officer, Trooper Dick, he did contest the fact that Trooper Dick had reasonable grounds to believe he was DWI. ", "On appeal, the respondent does not contest the fact that the Director made a prima facie case for revocation. ", "However, he contends that the evidence was sufficient for the trial court to find that the Director's prima facie case was rebutted; specifically, that the evidence was sufficient for the trial court to find that Trooper Dick did not have reasonable grounds to believe the appellant was DWI. ", "The Director claims that such a finding was not supported by substantial evidence and was against the weight of the evidence in that the respondent failed to controvert the evidence on which the Director's prima facie case was based.", "\n\"Reasonable grounds to arrest a driver for DWI to support a revocation for refusal is virtually synonymous with probable cause to arrest a driver.\" ", "Roberts v. Wilson, 97 S.W.3d 487, 492 (Mo.App.2002); see also Hinnah, 77 S.W.3d at 620. \"", "Probable cause to arrest exists when the arresting officer's knowledge of the particular facts and circumstances is sufficient to warrant a prudent person's belief that a suspect has committed an offense.\" ", "Hinnah, 77 S.W.3d at 621. ", "In determining whether there were reasonable grounds to arrest a driver for DWI, the trial court must evaluate the situation from the viewpoint of a cautious, trained, and prudent police officer at the time of the arrest. ", "Roberts, 97 S.W.3d at 492. ", "There is no precise test for determining whether reasonable grounds existed; rather, it is based on the particular facts and circumstances of the individual case. ", "Hinnah, 77 S.W.3d at 621. \"[", "W]hat is at issue in a refusal case is whether the officer had reasonable grounds to believe [d]river was intoxicated, not whether [he] was actually intoxicated.\" ", "McCarthy v. Dir. ", "of Revenue, 120 S.W.3d 760, 763 (Mo.App.2003).", "\nHere, at the § 577.041.4 hearing, the Director, in making a case for revocation of the respondent's license for a refusal, relied solely on the testimony of Trooper Dick. ", "In that regard, he testified, concerning the issue of probable cause to arrest the respondent for DWI, that there was a strong odor of alcohol emanating from *249 both the respondent's vehicle and his person. ", "The odor of alcohol is one of the classic indicia of intoxication. ", "Saladino v. Dir. ", "of Revenue, 88 S.W.3d 64, 71 (Mo. App.2002). ", "Trooper Dick also testified that the respondent's eyes were \"watery\" and \"bloodshot,\" and his speech was slurred, which are sufficient indicators of intoxication and provide reasonable grounds for the officer to believe that the driver was DWI. ", "Norris v. Dir. ", "of Revenue, 156 S.W.3d 786, 788 (Mo.App.2005). ", "He testified that when he asked the respondent for his driver's license and proof of insurance, he gave him his driver's license and registration. ", "It is well settled that the failure to follow instructions can be a factor in establishing a reasonable belief that a driver is intoxicated. ", "Roberts, 97 S.W.3d at 493. ", "Trooper Dick testified, further, that the respondent made inconsistent statements regarding whether he had stopped on his way back from St. Louis. ", "In addition, Trooper Dick observed that when the respondent entered the trooper's vehicle, he did not close the door. ", "Trooper Dick testified that in his experience, when a person does this, it usually means he is under the influence of alcohol. ", "Finally, the respondent refused to submit to any field sobriety tests, which can also be used as evidence for a reasonable belief of intoxication. ", "Edmisten v. Dir. ", "of Revenue, 92 S.W.3d 270, 274 (Mo.App.2002). ", "Thus, the testimony of Trooper Dick was sufficient to make a prima facie case for revocation for a refusal with respect to the issue of whether Trooper Dick had reasonable grounds to believe that the respondent was DWI.", "\nThe respondent did not testify or call any witnesses at the hearing. ", "Rather, the only evidence he offered was the Highway Patrol's videotape of his stop and arrest, shot from Trooper Dick's patrol vehicle. ", "The videotape was offered and admitted without objection, and was played in open court. ", "The videotape shows first the respondent pulling his vehicle to the side of the road, after being stopped by Trooper Dick for having an \"inoperable headlight.\" ", "It shows next Trooper Dick leaving his vehicle and approaching the driver's side window of the respondent's vehicle. ", "Trooper Dick can be heard asking the respondent several questions; however, for the most part, the respondent's answers to those questions are inaudible. ", "The tape shows the respondent exiting his vehicle and walking back to Trooper Dick's vehicle, after being asked to do so. ", "The respondent's face is shown on the tape for a brief moment. ", "Although Trooper Dick and the respondent are not visible on the tape while seated in the trooper's vehicle, due to the position of the camera, the conversation between the two is clearly audible. ", "Trooper Dick questioned the respondent about his job and his itinerary that night. ", "The tape also includes the auditory portion of the respondent's refusal to submit to a Breathalyzer test, as requested by Trooper Dick, and being placed under arrest for DWI. ", "The respondent contends that the videotape clearly demonstrates that he was not intoxicated, and, therefore, constituted substantial evidence that controverted the Director's evidence of probable cause for Trooper Dick to arrest the respondent for DWI and was sufficient for the trial court to find that he did not have such probable cause in support of its judgment ordering his operator's license reinstated.", "\nAs we note in our standard of review, supra, if the Director's evidence is uncontroverted, such that the \"real issue is a legal one as to the legal effect of the evidence,\" then we do not defer to the trial court's judgment. ", "Hinnah, 77 S.W.3d at 620. ", "We cannot disregard the Director's uncontroverted evidence and presume that the trial judge found a lack of credibility in *250 order to affirm the judgment. ", "Hockman, 103 S.W.3d at 386. ", "From this, the Director contends that the videotape was not sufficient to controvert her evidence supporting a reasonable belief by Trooper Dick that the respondent was DWI, such that the trial court was bound to accept it and affirm the revocation of the respondent's license.", "\nIn contending as she does, the Director is arguing, necessarily, that to constitute evidence sufficient to controvert her evidence of Trooper Dick's reasonable belief that the respondent was DWI, sufficient, in turn, to allow the trial court's reinstatement of the respondent's driver's license, the videotape had to expressly controvert the Director's evidence of the underlying facts or \"indicia\" establishing such a belief, rather than merely controverting the issue of whether Trooper Dick had a reasonable belief that the respondent was DWI. ", "In other words, she is arguing that the videotape was irrelevant to the trial court's determination of whether Trooper Dick had a reasonable belief that the respondent was DWI in that it did not controvert the fact that the respondent refused to submit to requested field sobriety tests; his eyes were bloodshot and watery; his speech was slurred; there was an odor of an alcoholic beverage emanating from his vehicle and person, etc. ", "We disagree.", "\nThe Director does not cite any authority for her argument that to controvert her evidence, supporting a probable cause finding for Trooper Dick to arrest the respondent for DWI, so as to require us to defer to the judgment of the trial court, the respondent had to introduce evidence controverting the facts on which she relied to show probable cause to arrest for DWI, and we can find none. ", "In fact, the case law holds otherwise. ", "In Hinnah, the Missouri Supreme Court was confronted with the same issue that confronts us here: whether the evidence was sufficient for the trial court to find, in reinstating the driver's license, in accordance with § 577.041, that the arresting officer did not have probable cause to arrest the driver for DWI. ", "77 S.W.3d at 621.", "\nIn Hinnah, the Court acknowledged that the Director had introduced evidence, which if believed by the trial court, was sufficient to support a finding of reasonable grounds to believe the driver was DWI. ", "Id. In that regard, the Court pointed to the arresting officer's testimony that he found the driver \"alone inside a truck with its engine running, parked alongside the interstate, that he had a strong odor of alcohol on his breath, had watery, glassy, bloodshot eyes, had difficulty maintaining his balance, and that he admitted to driving the vehicle, striking a concrete barrier and flattening the tire.\" ", "Id. The Court, however, found that there was evidence in the record that controverted the Director's evidence of probable cause and supported the trial court's finding that the arresting officer lacked probable cause to arrest the driver for DWI, stating:\nThe trial court had evidence to support a finding of probable cause, but was free as well to draw the conclusion that there was no probable cause. ", "Either conclusion was sustainable under the record, depending upon the trial court's assessment of the credibility of the officer's testimony that Hinnah said he was driving or upon the court's assessment of the evidence of probable cause as to intoxication.", "\nId. at 622. ", "In finding that the record supported the conclusion reached by the trial court, the Court pointed to the admissions of the arresting officer on cross-examination that he did not see the driver in the driver's seat; that he could not determine from the odor of alcohol the \"number, recency, quantity or quality of *251 that alcohol and that he could not determine whether [the driver] was intoxicated from it\"; that the [driver's] bloodshot eyes could not lead him to the conclusion that [he] was intoxicated; and, that the driver's balancing himself with the truck door may have been caused by his having just woke up, and the inclement weather and questionable footing. ", "Id. at 621. ", "The Court also pointed to the testimony of the driver's two witnesses, who testified that he was not driving. ", "Id.\nWhile there was evidence that controverted the Director's evidence that the driver was driving the vehicle, there was no evidence to controvert the fact that there was an odor of alcohol on the driver's breath; that the driver had bloodshot, watery eyes; or that he had to balance himself using the truck door. ", "Rather, the Court, in finding that there was sufficient evidence for the trial court to conclude that the arresting officer did not have probable cause to arrest the respondent for DWI, relied on competing inferences from the same evidence relied upon by the Director to show probable cause to arrest for DWI. ", "This approach was soundly condemned by then Chief Justice Limbaugh in his dissent, arguing that: \"The points made on cross-examination are in the nature of mere inconsistencies that do not effectively rebut what the majority agrees is prima facie proof of reasonable grounds to believe that Hinnah was intoxicated.\" ", "Id. at 623. ", "With respect to these \"points,\" he went on to say:\n[T]he points made were 1) that the officer could not determine the `number, recency, quantity or quality' of the alcohol he smelled on Hinnah's breath, 2) that he could not determine solely from the odor of alcohol whether Hinnah was intoxicated, 3) that he could not determine solely from Hinnah's bloodshot eyes whether Hinnah was intoxicated, 4) that Hinnah did not have slurred speech, and 5) that Hinnah's instability in exiting the pick-up might have been due to the fact that he had just awakened and needed time to balance himself. ", "None of these points controverts the evidence that Hinnah had alcohol on his breath and that his eyes were watery, glassy and bloodshot. ", "Although the officer conceded that neither the smell of alcohol nor the appearance of Hinnah's eyes was alone sufficient to determine that Hinnah was intoxicated, those factors, when combined with the other circumstances surrounding the arrest — that there had been an accident and that Hinnah had fallen asleep with the engine running — were more than enough to establish reasonable grounds that Hinnah was intoxicated.", "\nId. (emphasis added).", "\nIt is crystal clear to us that Hinnah stands for the proposition that, in order to controvert the Director's case for revocation for a refusal, pursuant to § 577.041, requiring us to defer to the trial court with respect to its conclusions and its resolution of factual issues, including credibility determinations, the driver need only present evidence that is inconsistent with a reasonable belief of the arresting officer that the driver was DWI. ", "There does not have to be evidence controverting each and every indicia of intoxication on which the Director has introduced evidence in support of a finding of probable cause. ", "That being the case, the issue then for us becomes whether the videotape of the respondent's stop and arrest constituted evidence that was inconsistent with a reasonable belief of Trooper Dick that the respondent was DWI.", "\nAs noted supra, the issue in a refusal case is not whether the driver was actually intoxicated, but whether he had reasonable grounds to believe that he was. ", "McCarthy, *252 120 S.W.3d at 763. ", "Thus, to the extent that the videotape showed that the respondent was not actually impaired or intoxicated, it is largely irrelevant as to the issue we must decide. ", "Hinnah, 77 S.W.3d at 621; Cain v. Dir. ", "of Revenue, 130 S.W.3d 1, 7 (Mo.App.2004). ", "However, it is relevant in deciding whether the record, here, was sufficient to support the trial court's finding that Trooper Dick did not have reasonable grounds to believe that the respondent was DWI, which would support reinstatement of his license. ", "Cain, 130 S.W.3d at 7.", "\nThe videotape shows that the respondent was able to walk quickly and steadily to the Trooper's vehicle. ", "The tape shows that the respondent was able to answer questions from Trooper Dick and carry on a coherent conversation with him. ", "Specifically, the tape shows the respondent coherently answering questions about his whereabouts earlier in the evening, his job selling medical products, and the amount of time he spends on the road because of his job. ", "In addition, through the admission of Trooper Dick, the trial court was informed that the respondent was driving carefully and under the speed limit. ", "All these facts could lead the trial court to believe that Trooper Dick did not have reasonable grounds for believing that the respondent was DWI. ", "Thus, it appears that there was evidence in the record sufficient to controvert the issue of whether Trooper Dick had reasonable grounds to believe that he was DWI.", "\nSince the Director's evidence of probable cause to arrest for DWI was controverted and there was no request for findings of fact and conclusions of law, in accordance with Rule 73.01(c);[2] and none were made, we must consider all the relevant factual issues to have been found by the trial court in accordance with the result reached. ", "Rule 73.01(c); Hinnah, 77 S.W.3d at 621. \"", "Accordingly, we view the evidence and all reasonable inferences drawn therefrom in the light most favorable to the prevailing party[, the respondent,] and must give due regard to the trial court's credibility determinations.\" ", "Williams v. Williams, 99 S.W.3d 552, 556 (Mo.App.2003) (citations omitted).", "\nViewing the evidence in a light most favorable to the respondent and considering the facts to have been found by the trial court in accordance with its judgment, we conclude that the trial court could have reasonably determined, from the videotape, that the respondent was not slurring his words. ", "Likewise, we can conclude that the trial court did not interpret the failure of the respondent to give the trooper proof of insurance, as requested, rather than his registration, as being indicative of DWI in that the tape has him apologizing for not having his insurance card with him. ", "In other words, it was not a matter of failing to follow instructions, but simply a matter of not having the requested document. ", "Further, we can infer that the trial court found that the respondent's bloodshot, watery eyes were not caused from intoxication, but being tired, having driven all night. ", "As to the apparent inconsistent statements of the respondent concerning whether he stopped during his trip to eat, the trial court may have interpreted that as simply a slip of the tongue. ", "These findings, coupled with what the trial court learned from the videotape, were sufficient for it to find that the trooper did not have reasonable grounds to believe the respondent was DWI.", "\n*253 Based on the foregoing analysis, it is clear that the trial court had evidence to support a finding that the trooper had reasonable grounds to believe that the respondent was DWI or a contrary finding, which was sufficient to rebut the Director's prima facie case for revocation of the respondent's driver's license for a Breathalyzer refusal. ", "Because the trial court was free to find either way based on the record, depending on the trial court's assessment of the credibility of Trooper Dick's testimony, we cannot find that the trial court's judgment was not supported by substantial evidence or was against the weight of the evidence.", "\n\nConclusion\nThe judgment of the trial court, setting aside the Director's revocation of the respondent's driver's license and ordering its reinstatement, is affirmed.", "\nHOWARD, P.J., and NEWTON, J., concur.", "\nNOTES\n[1] All statutory references are to RSMo, 2000, unless otherwise indicated.", "\n[2] All rule references are to the Missouri Rules of Civil Procedure, 2005, unless otherwise indicated.", "\n" ]
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[ "Introduction {#s1}\n============\n\nRett Syndrome (RTT) is neurodevelopmental disorder primarily caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (*MECP2*) [@pone.0031896-Amir1]. ", "RTT has broad phenotypic effects that include cognitive, motor, language, and social deficits, as well as autonomic dysregulation [@pone.0031896-Hagberg1], [@pone.0031896-Chahrour1]. ", "Concordant with this wide spectrum of neurological symptoms, MeCP2 appears to regulate activity-dependent synaptic maturation and maintenance [@pone.0031896-Asaka1]--[@pone.0031896-Chapleau1]. ", "The typical RTT brain has been characterized as developmentally arrested at approximately one year of age, although this effect is highly variable [@pone.0031896-Armstrong1]. ", "Global brain volume is reduced but gross morphology is preserved, with frontal regions tending to exhibit more severe effects, which correlate with measures of clinical severity [@pone.0031896-Carter1], [@pone.0031896-Subramaniam1]. ", "Early human studies indicated that reductions in brain volume were not caused by neurodegeneration but were instead a consequence of increased neuronal density arising from reduced soma size and dendritic arborization [@pone.0031896-Belichenko1]--[@pone.0031896-Armstrong3].", "\n\nMapping the impact of MeCP2 mutations on the nervous system has been complicated by a high degree of phenotypic variability in both human patients and animal models. ", "At the cellular level, the emerging perspective is that RTT neuronal phenotypes potentially depend on several interacting factors, including X-chromosome inactivation (XCI) ratio, specific mutation type, brain region, and cellular subtype. ", "Human phenotype-genotype correlation studies have shown that both skewed XCI ratios and mutation type correlate with variations in clinical severity [@pone.0031896-Amir2]--[@pone.0031896-Neul1]. ", "A similar spectrum of variability has been observed in several murine RTT models carrying different *Mecp2* mutations [@pone.0031896-Chen1]--[@pone.0031896-Jentarra1]. ", "Neuroanatomical studies in these different mouse lines have revealed both overlapping and divergent effects on brain region volumes, neuronal density, dendritic and axonal morphology, dendritic spine density, and spine morphology [@pone.0031896-Chapleau1], [@pone.0031896-Fukuda1]--[@pone.0031896-Tropea1]. ", "Both cell-autonomous and non-cell-autonomous effects have been reported and different mutations selectively affect specific morphological features while leaving others intact [@pone.0031896-Kishi2], [@pone.0031896-Belichenko5]. ", "Collectively, these studies point to a crucial role for cellular context in modulating the effects of different mutations. ", "The use of precisely defined cellular subtypes is therefore necessary for resolving the manner in which MeCP2 mutation effects may be generalized across different cell subpopulations in the CNS.", "\n\nMotor cortex is of particular interest because of the frontal volume reductions and prominent motor dysfunctions observed in RTT, which include apraxia, ataxia, repetitive stereotyped hand movements, impaired balance, and loss of ambulation [@pone.0031896-Hagberg1], [@pone.0031896-Percy1]. ", "Early Golgi impregnation studies of neuron morphology identified dendritic branching losses in Layer 5 (L5) pyramidal cells of the motor cortex [@pone.0031896-Armstrong2], [@pone.0031896-Armstrong3]. ", "L5 pyramidal neurons are not a unitary class, however, and can be grouped into subtypes based on phylogeny, gene expression profiles, morphology, electrophysiology, and axonal projection targets [@pone.0031896-Akemann1]--[@pone.0031896-Hattox1]. ", "Since MeCP2 mutations could potentially affect any of these features, the selection of a cell population for phenotypic analysis must take these properties into account.", "\n\nTransgenic labeling provides a convenient method for identifying some of these populations, as in the widely used YFP-H line (B6.Cg-Tg(Thy1-YFPH)2Jrs/J ([@pone.0031896-Feng1] also [@pone.0031896-Sugino1], [@pone.0031896-Zhang1]--[@pone.0031896-Li1]). ", "YFP-H mice express yellow fluorescent protein under the *Thy-1* promoter in a restricted set of L5 cortical neurons. ", "In the motor-frontal cortex of YFP-H mice, YFP-expressing (YFP^+^) pyramidal neurons have electrophysiological properties and patterns of synaptic connectivity that are distinct from both neighbouring non-YFP^+^ cells and from YFP^+^ cells in other cortical regions [@pone.0031896-Sugino1], [@pone.0031896-Yu1], [@pone.0031896-Miller1]. ", "We crossed YFP-H mice with the \"Jaenisch\" (MeCP2J) mouse line, *Mecp2^tm1.1Jae^*/Mmcd, which has an in-frame N-terminal deletion of *Mecp2* exon 3 [@pone.0031896-Chen1]. ", "A similar cross-breeding strategy was used for a different mutation, the protein-null *Mecp2^tm1.1Bird^* or \"Bird\" line (MeCP2B), in which Thy-1-GFP-labeled L5 neurons revealed significant spine losses throughout the dendritic arbor [@pone.0031896-Belichenko5]. ", "The rationale for the current study was motivated in part by the erroneous initial classification of both MeCP2B and MeCP2J mice as harboring protein-null mutations [@pone.0031896-Chen1], [@pone.0031896-Guy1]. ", "In addition to our own immunohistochemical findings (unpublished data), multiple lines of evidence have emerged demonstrating that the MeCP2J line expresses a partly functional truncated MeCP2. ", "These include the presence of stable MeCP2 mRNA transcripts, divergent gene expression profiles, and a milder phenotype in terms of brain weight, brain region volumes, and dendritic spine morphology [@pone.0031896-Belichenko3], [@pone.0031896-Belichenko4], [@pone.0031896-Jordan1]--[@pone.0031896-Braunschweig1]. ", "In the context of these reports and previous analyses focused on L2/3 neurons in MeCP2J mice [@pone.0031896-Kishi1], [@pone.0031896-Kishi2], [@pone.0031896-Belichenko4], we examined dendrite architecture and spine density in YFP^+^ L5 cells in the motor cortex of wildtype (WT) and MeCP2J mutant animals.", "\n\nResults {#s2}\n=======\n\nYFP^+^ mutant neurons have selective reductions in dendrite length, branching, and spine density {#s2a}\n------------------------------------------------------------------------------------------------\n\nThe large size of L5 pyramidal neurons and the density of YFP labeling in YFP-H mice precluded the imaging of entire cells, so 3D confocal fluorescence image stacks were obtained independently for dendrites in both the apical and basal compartments. ", "Basal dendrite image stacks were centered on L5 YFP^+^ somata, while apical stacks were bounded by the pial surface, allowing visualization of the most distal branches of the apical tuft ([Fig. ", "1A](#pone-0031896-g001){ref-type=\"fig\"}). ", "Manual 3D reconstructions were made of the complete dendritic arbor in each compartment for all neurons passing exclusion criteria ([Fig. ", "1B](#pone-0031896-g001){ref-type=\"fig\"}; *see* [*Methods*](#s4){ref-type=\"sec\"}).", "\n\n![", "3D Sholl analysis of apical and basal arbors in YFP^+^ L5 motor cortical neurons.\\\nA) Confocal microscopic image stacks from 200 µm tissue sections showing YFP^+^ dendrites in apical (upper) and basal (lower) compartments (WT male mouse). ", "Scale bar = 50 µm. ", "B) Representative 3D traces from a WT neuron. ", "10 µm Sholl radii were used in the basal compartment and 20 µm radii in the apical compartment. ", "The pial surface is shown as a dotted line with the apical Sholl origin defined as a point 300 µm from the pial surface. ", "Depth in the z-axis is color-coded.](pone.0031896.g001){#pone-0031896-g001}\n\nThe largest differences we observed in YFP^+^ mutant cell morphology were in the basal arbor ([Fig. ", "2C~1--3~](#pone-0031896-g002){ref-type=\"fig\"}). ", "First, although very long individual dendrites were often observed in mutant neurons, the average maximum dendritic length was reduced by 9.1% (128.1 µm±3.463 in mutant vs. 140.9 µm±3.782 in WT, *t* ~8~ = 2.490, *P* = 0.0375). ", "3D Sholl analysis revealed no difference in the number of primary dendrites in mutant neurons, but fewer bifurcations in a zone 40--70 µm from the soma ([Fig. ", "2C~1~](#pone-0031896-g002){ref-type=\"fig\"}; one-way ANOVA, F~14,112~ = 3.908, *P*\\<0.001; *t* ~8~\\>2.999, *P*\\<0.05). ", "Two-way repeated measures ANOVA also revealed a significant interaction between branch order and genotype ([Fig. ", "2C~2~](#pone-0031896-g002){ref-type=\"fig\"}; F~6,28~ = 6.849, *P* = 0.0001). ", "Mutant neurons showed a corresponding increase in the proportion of dendrite length within the first branch order (+5.93%; *t* ~6~ = 5.053, *P*\\<0.01), and significantly less in the third branch order (−3.5%; *t* ~6~ = 2.987, *P*\\<0.05). ", "Plotting the cumulative increase in total basal dendritic length vs. distance from the soma ([Fig. ", "2C~3~](#pone-0031896-g002){ref-type=\"fig\"}) showed that the loss of higher-order branching close to the soma reduced the total dendritic length for MeCP2 mutant neurons by 18.6% (WT: 1192.0 µm±61.54; Mut 969.8 µm±65.54; *t* ~8~ = 2.472, *P* = 0.0386). ", "The largest divergence in cumulative dendritic length occured between approximately 40--130 µm from the soma. ", "WT YFP^+^ neurons therefore maintain a larger number of dendritic branches in proximal portions of the basal arbor, as shown in reconstructions of representative \"average\" neurons from the Sholl analysis for each genotype ([Fig. ", "2A--B](#pone-0031896-g002){ref-type=\"fig\"}).", "\n\n![", "Dendritic branching and length is reduced in YFP^+^ MeCP2J mutant neurons.\\\nA, B) Reconstructions of representative WT and mutant YFP^+^ L5 pyramidal neurons based on the Sholl analysis branch patterns in C~1~ and D~1~. Scale bar (A) = 50 µm. ", "C~1~) Basal compartment Sholl analysis showing the number of dendrite crossings as a function of distance from the soma. ", "Mutant YFP^+^ neurons have significantly fewer dendritic branches 40--70 µm from the cell body. ", "D~1~) Apical compartment Sholl analysis of the summed dendritic length per Sholl radius. ", "Mutant YFP^+^ neurons have less total dendritic length per Sholl radius in L1--2. ", "Dendrite lengths in radii greater than 300 µm correspond to long, laterally extending dendrites that are near and parallel to the pial surface. ", "C~2~, D~2~) Percent dendritic length as a function of branch order in basal and apical compartments. ", "The inset in (D~2~) shows branch order hierarchy. ", "In basal dendrites only, mutant YFP^+^ neurons exhibit significantly reduced dendritic complexity with proportionally more dendritic length in lower branch orders. ", "C~3~) A cumulative total length plot for basal dendrites shows that the main divergence in total dendritic length occurs less than ∼120 µm from the soma. ", "The average maximum dendritic length is also reduced in mutant YFP^+^ neurons. ", "D~3~) A cumulative total dendritic length plot of apical tuft branches shows no minimal divergence except close to the pial surface, where mutant YFP^+^ cells extend fewer lateral branches.](pone.0031896.g002){#pone-0031896-g002}\n\nIn the apical compartment the Sholl analysis was modified to accommodate the fact that secondary apical dendrites can extend over long distances roughly parallel to the pial surface without crossing a Sholl radius. ", "We therefore measured the summed dendritic lengths per 20 µm radius. ", "The Sholl origin was arbitrarily defined as a point on the apical dendrite 300 µm from the pial surface ([Fig. ", "1B](#pone-0031896-g001){ref-type=\"fig\"}). ", "In motor cortex this point is situated in cortical layer 3 in both mutant and WT mice, and corresponds to a distance of ∼100--200 µm from L5A somata in the WT and slightly less in the mutant. ", "Differences in the apical compartment were more subtle than those seen in basal dendrites ([Fig. ", "2D~1--3~](#pone-0031896-g002){ref-type=\"fig\"}). ", "Mutant neurons had up to 26.6% less summed dendritic length in Sholl radii 60 µm from the pial surface, corresponding to losses in the neuropil-dense cortical Layer 1 ([Fig. ", "2D~1~](#pone-0031896-g002){ref-type=\"fig\"}; one-way ANOVA, F~16,128~ = 2.143, *P* = 0.01; Bonferroni post-hoc tests *t* ~8~\\>3.174, *P*\\<0.05). ", "This did not significantly change the total dendritic length in tuft branches (WT: 526.1 µm±28.86; Mut: 472.9 µm±22.07; *t* ~8~ = 2.472, *P* = 0.1809), and we found no difference in the average maximum length of individual apical dendrites. ", "Similarly, no difference was observed when total length analysis was restricted to apical tuft branches within less than 100 µm of the pia (not shown). ", "Although there was an interaction between branch order and genotype (F~6,28~ = 2.547, *P* = 0.0428), with mutant neurons tending to have a larger proportion of total dendritic length in primary and secondary branches, post-hoc tests found no significant differences at any specific branch order ([Fig. ", "2D~2~](#pone-0031896-g002){ref-type=\"fig\"}). ", "The cumulative average dendritic lengths only diverged close to the pial surface to a final difference of 10.3% less total apical length in mutant cells, although this effect was not statistically significant ([Fig. ", "2D~3~](#pone-0031896-g002){ref-type=\"fig\"}). ", "Overall, these findings suggest that, in contrast to the basal compartment, the MeCP2J mutation reduces higher-order branching in YFP^+^ L5 apical tuft dendrites in a relatively non-specific manner, with some reductions of lateral dendritic branching in L1. ", "Representative apical tuft dendrites (reconstructed from the Sholl analysis) are shown in [Fig. ", "2A and 2B](#pone-0031896-g002){ref-type=\"fig\"}.", "\n\nAny net losses in total dendritic length will reduce the total synaptic input for a given neuron, but this may be either mitigated or exacerbated by changes in dendritic spine density. ", "To address this question we quantified the number of spines in the dendritic regions that showed the largest differences in the Sholl analyses, i.e. proximal basal dendrites and the apical tuft ([Fig. ", "3A, 3D](#pone-0031896-g003){ref-type=\"fig\"}). ", "Basal spine counts started after the first bifurcation (typically 20--50 µm from the soma) and apical tuft segments were not more than 60 µm from the pial surface. ", "We also counted spines along the primary apical dendrite, 100--200 µm from the soma, and secondary oblique dendrites immediately projecting from the primary apical dendrite over this same region ([Fig. ", "3B, 3C](#pone-0031896-g003){ref-type=\"fig\"}). ", "Mutant neurons exhibited altered spine density, but only in some dendritic compartments ([Fig. ", "3E](#pone-0031896-g003){ref-type=\"fig\"}). ", "Spine density in the apical tuft was reduced by 47.4% (WT: 0.854 µm^−1^±0.0774; Mut: 0.449 µm^−1^±0.0261; *t* ~23~ = 4.469, *P* = 0.0002); in secondary apical dendrites, density was reduced by 54.5% (WT: 1.751 µm^−1^±0.123; Mut: 0.797 µm^−1^±0.0657; *t* ~28~ = 6.860, *P*\\<0.0001). ", "In mutant primary apical and basal dendrites, however spine density remained unchanged (Primary apical, WT: 1.933 µm^−1^±0.167, Mut: 1.648 µm^−1^±0.0903; *t* ~28~ = 1.623, *P* = 0.1159); (Basal, WT: 0.720 µm^−1^±0.0539, Mut: 0.756 µm^−1^±0.0733; *t* ~23~ = 0.3716, *P* = 0.3716). ", "These compartment-specific effects suggest that mutant neurons experience a significant net loss of synaptic input in the apical tuft, due to the compounded effects of both lower spine density and reduced dendritic branching.", "\n\n![", "Spine density is variably affected in different dendritic compartments in YFP^+^ MeCP2J mutant L5 pyramidal neurons.\\\nA--D) Spines were quantified in 20--30 µm segments in four dendritic compartments for WT and mutant YFP^+^ neurons. ", "Scale bar (A) = 5 µm (all images). ", "A) Apical tuft dendrites were sampled \\<60 µm from the pial surface. ", "B) Primary apical dendrites were imaged between 100--200 µm from the soma. ", "C) Secondary apical dendrites originating in the same region as (B) were sampled beginning at the branch point from the primary apical dendrite. ", "D) Basal dendrite spine counts were initiated following the first dendritic bifurcation. ", "E) Spine density is reduced by 47.4% in the apical tuft and by 54.5% in secondary apical dendrites.](pone.0031896.g003){#pone-0031896-g003}\n\nThy-1-YFP expression is reduced in MeCP2J mutant mice {#s2b}\n-----------------------------------------------------\n\nIn addition to the morphological differences in MeCP2J mutant YFP^+^ neurons, we also observed an unexpected reduction in the number of YFP^+^ cells in mutant animals relative to WT littermates. ", "To further characterize these differences we performed a qualitative survey of cortical YFP expression patterns ([Fig. ", "4](#pone-0031896-g004){ref-type=\"fig\"}). ", "YFP expression varied in two significant ways (summarized in [Fig. ", "4E](#pone-0031896-g004){ref-type=\"fig\"}). ", "First, despite some inter-litter variability, the density of labeling in both genotypes followed a similar pattern of variation across cortical regions. ", "In some cases these differences had sharp boundaries correspondent with functional divisions of the cortex [@pone.0031896-Paxinos1]. ", "The highest densities of YFP expression tended to occur in more rostral and medial regions (e.g. motor, cingulate, and retrosplenial cortex) while the lowest densities tended to occur in caudal and lateral regions (e.g. visual, ectorhinal, entorhinal, and piriform cortex). ", "Second, YFP density appeared to be lower in MeCP2 mutants relative to WT littermates in most cortical regions. ", "Some regions were more dramatically affected than others, such as visual cortex, which was usually marked by an almost complete absence of YFP^+^ cells ([Fig. ", "4A, 4C](#pone-0031896-g004){ref-type=\"fig\"}). ", "We quantified the percentage of YFP^+^ cells in three areas (frontal association, motor, and retrosplenial cortex) as a fraction of all fluorescent Nissl-stained L5 neurons ([Fig. ", "4B](#pone-0031896-g004){ref-type=\"fig\"}). ", "In all three regions, mutant mice had fewer YFP^+^ neurons (one-way ANOVA, F~5,17~ = 63.36, *P*\\<0.0001). ", "The fraction of YFP^+^ neurons was decreased by 65.6% in frontal cortex, 65.3% in motor cortex, and 71.8% in retrosplenial cortex (*t~5~*\\>6.751, *P\\<*0.001 in all pairs) ([Fig. ", "4F](#pone-0031896-g004){ref-type=\"fig\"}). ", "The reductions occurred in spite of higher neuronal density in these same regions ([Fig. ", "4D](#pone-0031896-g004){ref-type=\"fig\"}; one-way ANOVA, F~5,12~ = 3.689, *P\\<*0.0001), with density increases of 46% in frontal cortex, 32% in motor cortex and 24% in retrosplenial cortex.", "\n\n![", "MeCP2J mutant mice have reduced numbers of YFP-expressing cortical neurons.\\\nA, C) Fewer YFP^+^ cells are observed across the entire cortex in mutant males (200 µm coronal sections, ∼ Bregma −2.2 mm in WT). ", "Some cortical regions are more dramatically affected than others, such as visual cortex (red arrow) and auditory cortex (blue arrow). ", "Sharp boundaries correspond to functional regions (Au, auditory; S, somatosensory; V, visual; RS, retrosplenial). ", "Scale bar = 0.5 mm. ", "Overall cortical YFP expression patterns are shown as a qualitative heat map in E), where white indicates few to no neurons and dark orange indicates the most dense cortical labeling. ", "The number of YFP^+^ cells is generally higher in rostral and medial region in both genotypes. ", "B) Fluorescent Nissl staining (red) of L5 motor cortex. ", "A limited subset of pyramidal neurons express YFP. ", "Scale bar = 100 µm. ", "D) Neuronal density is increased in frontal (Fr), motor (M) and retrosplenial (RS) cortex in mutant mice. ", "F) The percentage of YFP^+^ pyramidal neurons is reduced in three cortical regions (F, frontal; M, motor; RS, retrosplenial).](pone.0031896.g004){#pone-0031896-g004}\n\nThe reduced number of observed YFP^+^ cells could result from 1) more extensive transgene silencing in the mutant animals, with YFP^+^ neurons having similar expression levels in both genotypes or 2) overall downregulation of YFP expression levels in MeCP2 mutant animals, so that some neurons expressed YFP below detection limits.", "\n\nNeuronal transgene expression under the *thy1.2* cassette begins during postnatal days P6--P10 [@pone.0031896-Caroni1], so we examined the developmental expression patterns of YFP in littermates from both genotypes at early postnatal stages to late maturity (1--18 wks) to compare these two alternatives. ", "Representative examples are shown in [Fig. ", "5](#pone-0031896-g005){ref-type=\"fig\"}. ", "In both genotypes, we found large, bright individual neurons as early as P9. ", "By P12--P14 the number of YFP^+^ cells increased sharply in WT, but remained low in MeCP2 mutants. ", "YFP^+^ cells continued to increase in number in both genotypes until reaching stable mature levels at approximately one month of age. ", "MeCP2 mutant mice maintained lower numbers of YFP^+^ cells at all later developmental stages. ", "Similar confocal fluorescence imaging conditions (exposure, gain, laser intensity) were used in all cases, but increasing any or all of these parameters did not reveal any additional cells in either genotype. ", "Furthermore, while the somata of YFP^+^ L5 pyramidal cells were 24.1% smaller in mutant male mice (WT: 181.1 µm^2^±11.1, Mut: 137.4 µm^2^±9.0; *t* ~9~ = 3.097, *P* = 0.0128), there was no correlation between soma size and fluorescence intensity level in either genotype (r^2^\\<0.06471, d.f.\\>41, both genotypes; data not shown). ", "These results suggest that the reduced number of YFP^+^ neurons in mutant mice results from transgene silencing rather than as a consequence of a higher proportion of cells expressing YFP below detection limits.", "\n\n![", "Developmental progression of cortical YFP expression.\\\nLeft column: 200 µm coronal sections from YFP-H MeCP2J littermate pairs (∼ Bregma 0.14 mm in WT). ", "The anterior commissure was used as a reference anatomical marker. ", "Right column: maximum intensity projections of confocal fluorescence imaging z-stacks from cingulate cortex. ", "The red box in P9 mutant (rotated 90° clockwise) corresponds to the region imaged in each brain. ", "Single bright YFP^+^ L5 pyramidal neurons are observed in both genotypes as early as P9. ", "By P12 YFP expression has been strongly upregulated in the WT, after which the number of YFP^+^ cells continues to increase more slowly until stabilizing to mature levels sometime between P21 and P40. ", "The number of YFP^+^ cells in mutant males also continues to increase, but at a slower rate, and final levels remain below those seen in the WT. ", "All confocal fluorescence images shown were obtained from the brain section shown except P9 WT, which was obtained from a tissue section 400 µm anterior due to sparse YFP labeling at this age. ", "Left column scale bar = 0.5 mm. ", "Right column scale bar = 100 µm.](pone.0031896.g005){#pone-0031896-g005}\n\nDiscussion {#s3}\n==========\n\nMorphological Analysis {#s3a}\n----------------------\n\nWe analyzed the impact of the MeCP2J mutation on YFP^+^ L5 pyramidal cells and found two principal effects: 1) reduced branching and length in proximal basal and apical tuft dendrites, and 2) selective reductions in spine density limited to the apical tuft and secondary apical dendrites. ", "These results contribute to a growing body of evidence showing that the effects of different MeCP2 mutations are highly sensitive to cellular context and cannot be readily generalized.", "\n\nThe morphological differences observed in MeCP2 mutant neurons vary both across mutation types in the same cell population and within mutation types across different cell populations. ", "In MeCP2J mice, our secondary apical dendrite spine density values are in close agreement with those previously reported for Golgi-stained L5 motor cortical neurons [@pone.0031896-Tropea1]. ", "By contrast, in a comparable study that used a highly similar transgenic cell population (Thy-1-GFP-labeled L5 neurons in the motor cortex), but harboring the protein-null MeCP2B mutation, spine density was significantly reduced in all dendritic compartments analyzed, including primary apical, secondary apical, and basal dendrites [@pone.0031896-Belichenko5]. ", "In L2/3 pyramidal neurons, MeCP2J mutant cells were reported to exhibit no changes in spine density, but had relatively large reductions in both apical and basal dendritic branching [@pone.0031896-Kishi1], [@pone.0031896-Kishi2], [@pone.0031896-Belichenko4]. ", "At the other phenotypic extreme, in the B6.129S-*Mecp2^tm1Hzo^*/J (MeCP2^308/Y^) mouse line, which has a C-terminal truncating deletion in MeCP2, neither dendritic branching nor spine density are affected, in both L2/3 as well as L5 cells [@pone.0031896-Moretti1].", "\n\nThe varied and contradictory nature of these results may be a direct consequence of the intrinsically disordered structure of MeCP2, which confers autonomous functionality to several biochemical domains that may act alone or in concert [@pone.0031896-Adams1]. ", "The pairing of a highly flexible tertiary structure with independently operating functional domains presents an attractive explanation for the multifunctional nature of MeCP2 as well as the diversity of mutant phenotypes. ", "In conjunction with physiological and transcriptional profiling, direct morphological comparison between cellular subpopulations, both within and across mutant mouse lines, may present a valuable tool for dissociating how each MeCP2 domain contributes to the generation or maintenance of cellular character in the CNS.", "\n\nInteraction of Mecp2 Mutation with the Thy-1-YFP Transgene {#s3b}\n----------------------------------------------------------\n\nWe analyzed the effects of a specific *Mecp2* mutation on a fluorescently labeled population of cortical neurons. ", "Similar strategies using *Thy-1-YFP/-GFP* mice have been been employed elsewhere in studies of *Mecp2* and other transgenes (e.g. [@pone.0031896-Belichenko5], [@pone.0031896-Beirowski1]--[@pone.0031896-Matter1]). ", "The principal utility of this approach arises from the use of cell type-specific promoters to restrict analysis to defined cellular subtypes. ", "Given the increasingly evident taxonomic diversity of neuronal subpopulations based on clustered patterns of hodology, morphology, gene expression, and electrophysiological properties [@pone.0031896-Migliore1]--[@pone.0031896-Molyneaux2], this type of approach is most salient when evaluating gene mutations with highly context-dependent effects.", "\n\nThe diverse and often contradictory effects of MeCP2 mutation are not surprising given its complex regulatory network and multifunctional capacity. ", "Expression levels of the two MeCP2 isoforms are non-homogeneous and vary with brain region and cortical layer [@pone.0031896-Shahbazian1], [@pone.0031896-Kriaucionis1]--[@pone.0031896-Samaco1]. ", "MeCP2 is also subject to multiple transcriptional, post-transcriptional, and post-translational regulatory influences [@pone.0031896-Reichwald1]--[@pone.0031896-Tao1]. ", "Furthermore, the full functional repertoire of MeCP2 remains incompletely understood, but at present includes chromatin remodelling, gene silencing, transcriptional modulation, RNA splicing, and regulation of microRNAs [@pone.0031896-Nan1]--[@pone.0031896-Young1]. ", "Transcriptional regulation alone differentially affects thousands of genes and varies by neuroanatomical region [@pone.0031896-Chahrour2]--[@pone.0031896-Gibson1]. ", "Selectively labeled subpopulations like those in the YFP-H line present an attractive means to address questions about the context-dependent effects of different MeCP2 mutations.", "\n\nHowever, this advantage is complicated by the potential for interactions between the mutant protein and the reporter transgene. ", "We found that in MeCP2J mutant male mice, the number of YFP-expressing cells was decreased by 65--70% in several brain regions, while the intensity of YFP fluorescence in individual cells was preserved. ", "More extensive *Thy-1-YFP* silencing in mutant mice would appear at odds with the role of MeCP2 as a transcriptional repressor [@pone.0031896-Nan1], [@pone.0031896-Nan2], but MeCP2 does influence the expression of other transcriptional regulators [@pone.0031896-Peddada1]. ", "Furthermore, the *Thy-1* promoter expression cassette is highly sensitive to chromosomal context, and identical constructs can produce highly variable expression patterns across transgenic lines [@pone.0031896-Feng1], [@pone.0031896-Caroni1]. ", "To date, the *Thy-1* gene has not emerged as significantly altered in any gene profiling studies, but effects on *Thy-1* promoter-driven transgenes are not entirely surprising given the involvement of MeCP2 in chromatin remodelling. ", "The sharply delineated, region-dependent decreases in YFP^+^ cell numbers that we observed in some cortical areas suggests that these changes are not a random consequence of altered chromatin architecture, but may instead reflect distinct changes in regulatory pathways for different cell populations.", "\n\nOur study does not rule out the possibility that the reduced number of YFP^+^ cells in MeCP2J mutants correlates with a selective alteration in the proportions of certain subclasses of Layer 5 pyramidal neurons. ", "Although variegation between founders in transgenic mouse lines has been considered a stochastic effect arising from random chromosome insertion site and transgene copy number [@pone.0031896-Walters1], [@pone.0031896-Graubert1], several reports suggest that the pattern of YFP^+^ pyramidal cells in the YFP-H line is not random, but constitutes a limited set of distinct functional subclasses defined in part by their principal axonal targets [@pone.0031896-Sugino1], [@pone.0031896-Yu1], [@pone.0031896-Miller1]. ", "Intriguingly, axonal targeting is disordered in MeCP2 mutant mice [@pone.0031896-Belichenko4], [@pone.0031896-Degano1] and the developmental timing of axonal pruning partially overlaps with that of MeCP2 expression in cortex [@pone.0031896-Shahbazian1], [@pone.0031896-Mullaney1], [@pone.0031896-OLeary1]--[@pone.0031896-Cohen1]. ", "Establishing how the MeCP2J mutation affects factors driving *Thy-1-YFP* expression could reveal new roles for distinct functional domains of MeCP2 in establishing or maintaining subtle differences between closely related neuronal subpopulations.", "\n\nMethods {#s4}\n=======\n\nEthics Statement {#s4a}\n----------------\n\nAll procedures performed on animals were in compliance with the Canadian Council on Animal Care guidelines and were approved by the University of Victoria Animal Care Committee (Approval number 2008-021).", "\n\nAnimal Breeding {#s4b}\n---------------\n\n*Mecp2* mutant mice (*Mecp2^tm1.1Jae^/*Mmcd) (MMRRC, UC Davis) [@pone.0031896-Chen1] were maintained on a 129S2/SvPasCrl background (Charles River) and YFP-H transgenic mice (B6.Cg-Tg(Thy1-YFPH)2Jrs/J, Jackson Laboratory) [@pone.0031896-Feng1] were independently maintained on a C57BL/6J background. *", "Mecp2* heterozygous female mice were crossed with YFP-H male mice homozygous for the YFP transgene to generate experimental F1 animals. *", "Mecp2* and *YFP* were genotyped by PCR of genomic DNA extracted from earclips. *", "Mecp2* genotype was determined using primer sequences \\[5′- CAC CAC AGA AGT ACT ATG ATC\\] and \\[ATG CTG ACA AGC TTT CTT CTA-3′\\] which detect wildtype and mutant *Mecp2* alleles as 3 kb and 250 bp bands respectively. ", "Presence of the YFP transgene was determined using primers \\[5′- TCT GAG TGG CAA AGG ACC TTA GG\\] and \\[CGC TGA ACT TGT GGC CGT TTA CG-3′\\], detecting a 300 bp band.", "\n\nHistological Preparation {#s4c}\n------------------------\n\nAnimals were anaesthetized using urethane (2 g/kg i.p.) (", "Sigma) and transcardially perfused with 10 ml 0.1 M phosphate-buffered saline (PBS, pH 7.4) and 40 ml room-temperature 4% formaldehyde in 0.1 M phosphate buffer (PFA, pH 7.4). ", "Brain tissue was dissected out and fixed in 4% PFA at 4°C overnight, washed three times in PBS, and sunk in 30% sucrose-PBS. ", "Agar-embedded 200 µm coronal sections were cut on a Pelco Vibratome 1000 and coverslipped with Shandon Immunomount (Thermo Scientific).", "\n\nImaging {#s4d}\n-------\n\n1024×1024 pixel 3D confocal fluorescence image stacks were obtained using a Nikon Eclipse TE2000-U confocal microscope and Nikon EZ-C1 3.60 software or an Olympus Fluoview FV1000 with Fluoview software (v. 1.7c) and 488, 515 or 543 nm lasers. ", "Multi-channel imaging was done sequentially. ", "All images were averaged twice with scan speeds of 1.68--3.94 µs/pixel unless otherwise indicated. ", "Image stacks were converted to 16-bit .tif files using ImageJ software for further analysis.", "\n\nImages for neuron density and percentage of YFP^+^ cells were obtained using a Nikon Plan APO NA 0.95 20× air objective, 10×1 µm z-step and 30 µm pinhole. ", "For reconstructions of apical and basal compartments of YFP-H neurons, images were obtained using a Nikon 40×/1.3 NA S Fluor oil immersion objective, 400 nm z-step, and 30 µm pinhole. ", "Laser power and gain were manually adjusted during imaging to maintain maximal subsaturation pixel intensities at the apical dendrite. ", "For dendritic spine counts of the apical and basal dendrites of YFP^+^ neurons, images were obtained using an Olympus UPlanFL N 100×/1.3 NA oil immersion objective, 5× zoom, 200 nm z-step, and 190 µm pinhole.", "\n\nFor qualitative analysis of YFP expression patterns, 1600×1200 pixel widefield images of cerebral hemispheres were obtained using a 4×/0.13 NA objective with a 0.5× projection lens on an Olympus IX70 inverted epifluorescence microscope. ", "Images were captured with a Retiga 2000R digital CCD camera (QImaging). ", "For the developmental staging of YFP expression, 2560×1920 pixel images were obtained using a Nikon 4×/0.13 NA Plan Fluor objective with a Nikon DS-U1 camera and ACT-2U software. ", "Images were adjusted for brightness and contrast and tiled using Adobe Photoshop CS4.", "\n\nHistology & Morphological Analysis {#s4e}\n----------------------------------\n\nL5 neuron density was measured by staining 200 µm coronal tissue sections with the neuron-specific fluorescent Nissl stain Neurotrace 530/615 (Invitrogen, 1∶300 dilution).", "\n\nThe upper boundary of L5 was determined with reference to the YFP^+^ cell somata. ", "Only superficial (\\<40 µm depth) tissue was imaged due to limited dye penetration. ", "Counts from five tissue sections per animal were averaged for each brain region analyzed. ", "Confocal image stacks were flattened into maximum intensity projections (MIPs) prior to cell counts using the ImageJ Cell Counter plugin (Kurt De Vos, University of Sheffield). ", "Cells occluded by the image boundary or lacking a nucleus clearly delineated by the Nissl stain were not counted, to eliminate partially imaged cells from above and below the planes included in the MIP. ", "For YFP cell counts, YFP^+^ cells whose Nissl stains did not fit these criteria were similarly excluded.", "\n\nQualitative analysis of YFP expression patterns in the cortex used five WT/mutant littermate pairs (11--13 wks). ", "Entire brains were cut in 200 µm coronal sections (excluding the olfactory bulbs and cerebellum) and serially mounted. ", "Due to the marked volume reduction in the mutant mouse brains relative to WT, rostrocaudal position was established with reference to distinctive anatomical features visible in the coronal plane instead of Bregma, with reference to coronal plates in the Paxinos Mouse Brain Atlas [@pone.0031896-Paxinos1]. ", "These included: fusion of the medial orbital cortex to the anterior olfactory bulb; disappearance of the rhinal fissure; fusion of the genu of the corpus callosum; emergence of the anterior commissure and third ventricle; appearance of the dentate gyrus; and appearance and separation of the medial mammillary nucleus. ", "After establishing the range of tissue sections over which a cortical region occurred each region was assigned a score from 0 to 4 as a qualitative estimate of the number of large YFP^+^ pyramidal cells. ", "A score of 0 reflected very few or no cells and 4 indicated very dense labeling. ", "A median value of the score for each cortical region was taken from all mice within each genotype and plotted using a heat map, where white represents few to no cells and dark orange represents the highest observed density of YFP-expressing neurons.", "\n\nSoma traces and dendritic analyses were performed on five F1 WT/mutant littermate pairs (8--13 wks). ", "Neuron reconstructions and soma traces were performed by a single observer blind to genotype. ", "All 3D confocal image stacks of motor cortex were obtained from coronal tissue sections rostrally bounded by the first appearance of the corpus callosum and caudally by appearance of the anterior commissure, corresponding to a rostrocaudal depth of ∼2 mm.", "\n\nSoma traces were performed using ImageJ. YFP^+^ somata were outlined in the focal plane where each cell had its maximum in-focus area. ", "Partially occluded cell bodies at the image boundaries were not used. ", "Prior to outlining each cell, the image was zoomed 12×. Post-hoc analysis of the mean signal∶background ratio defining the cell boundary was determined by examining 20 neurons randomly selected from previous traces in two YHM littermates. ", "The average YFP fluorescence intensity at the cell boundary was 7.8× background intensity and not less than 3×.\n\nApical and basal dendrite tracings were performed on confocal image stacks using Igor Pro 6.05 software (Wavemetrics) with the Migor 4 custom analysis plugin developed by Jamie Boyd (UBC). ", "3D traces of apical or basal compartments were generated in Migor using a Cintiq 21 UX interactive pen display (Wacom). ", "Apical and basal compartments were separately imaged to allow adequate resolution of fine dendritic branches in YFP^+^ neurons. ", "For basal compartments, image stacks were oriented such that somata of YFP^+^ Layer 5 pyramidal neurons were centered along the y- axis, to permit capture of the maximum length of dendritic branching possible, as well as a minimum of 100 µm of the apical dendrite. ", "Somata were selected from a sub-volume of the z-stack defined by a zone of exclusion comprising ∼100 µm from the outer edges of the x and y axes and the central 100 µm within the z-axis. ", "At 40× magnification the field of view in the x-y axes was 318 µm^2^. Due to variable shrinkage in the z-axis during the mounting process the excluded z-axis guard zones were of variable length but typically ∼25 µm. ", "Traces of the first 100 µm of the primary apical dendrite (and any secondary branches) were included as part of the basal compartment. ", "For apical compartment traces, the pial surface of the brain was aligned parallel and contiguous with the upper boundary of the x-axis in the image plane, permitting capture of apical dendrite into deep Layer 3. ", "A standard reference point for comparing dendritic structures was established by initiating all traces 300 µm from the pial surface. ", "Traces were not included if obvious truncations of lateral branches occurred.", "\n\nStatistical analysis of the 3D Sholl data from individual neuron reconstructions used a repeated measures ANOVA with genotype and distance from origin as predictor variables and number of dendrite crossings per Sholl radius (basal) or summed dendrite length per Sholl radius (apical) as the response variables. ", "Differences at specific radii were analysed using Bonferroni post-hoc *t*-tests. ", "In the basal compartment, 3D Sholl cross analysis was performed by counting the number of dendrites intersecting concentric spherical radii at 10 µm intervals. ", "In the apical compartment, Sholl lengths were measured by summing all of the segments of dendrite length occurring within each 20 µm Sholl radius. ", "Maximum dendritic length was defined as the largest Sholl radius crossed by at least one dendritic segment. ", "Total cumulative dendrite length measurements were the summed length of all dendrites in each of the basal and apical compartments. ", "Percent dendritic length was calculated as a function of branch order in each compartment. ", "Branch order was defined by the number of branch nodes occurring following a given primary node, such that dendrites with fewer branches would have proportionally more branch length in lower branch orders.", "\n\nDendritic spine counts were performed using confocal fluorescence image stacks up to 10 µm deep in the z-axis. ", "Image stacks were smoothed using a 2.0 pixel median filter prior to analysis. ", "Spine counts were obtained from 20--30 µm dendritic segments of randomly selected neurons using the ImageJ Cell Counter plugin. ", "Spines projecting directly above and below the dendrite in the z-axis were not counted. ", "In regions of high spine density (e.g. WT primary apical) potentially overlapping spines were identified by vertically scrolling through confocal z-stacks. ", "Due to the difficulty of unequivocally distinguishing filopodia from long thin spines, spine counts included all types of dendritic protrusions. ", "Tissue sections were obtained from three WT/mutant littermate pairs (11--13 wks). ", "15--20 cells were analyzed per animal, with total spine counts of 1641 (WT) and 1440 (mutant). ", "Spine density was calculated by dividing the total spine count by the length of dendrite analyzed. ", "Representative images in [Fig. ", "3](#pone-0031896-g003){ref-type=\"fig\"} were rotated, cropped and adjusted for brightness and contrast.", "\n\nStatistical Analysis {#s4f}\n--------------------\n\nStatistics were performed using the Migor 4 plugin (Jamie Boyd, UBC) for Igor Pro (Wavemetrics), Prism 5 v.5.0b (Graphpad Software) and R v.2.9.2 (WU). ", "Unless otherwise stated, all parameters were analyzed using the two-tailed unpaired student\\'s t-test and results considered significant at P\\<0.05, with measurements reported as mean ± SEM. ", "Bonferroni\\'s Multiple Comparison Test was used for pairwise comparisons for all ANOVAs. ", "Dataset distributions were tested for normality using D\\'Agostino & Pearson omnibus normality test. ", "Figures were prepared using Prism 5, ImageJ, and Photoshop CS3 v.10.0 (Adobe; San Jose, CA).", "\n\n**Competing Interests:**The authors have declared that no competing interests exist.", "\n\n**Funding:**This work was supported by the Rett Syndrome Research Foundation (now the IRSF, below) (to Dr. Levin and Dr. Delaney; grant title \"MeCP2 Replacement Therapy for Rett Syndrome: A mouse mode\"l). ", "The International Rett Syndrome Foundation (<http://www.rettsyndrome.org/>) (to Dr. Delaney; grant title \"Cell autonomous versus environmental effects on neuronal morphology in brains of a Rett syndrome mouse model), and by graduate scholarships (to Dr. Stuss) from Canadian Institutes of Health Research (<http://www.cihr-irsc.gc.ca/e/193.html>) and the Michael Smith Foundation for Health Research (<http://www.msfhr.org/>). ", "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.", "\n\n[^1]: Conceived and designed the experiments: DPS JDB DBL KRD. ", "Performed the experiments: DPS. ", "Analyzed the data: DPS KRD. ", "Contributed reagents/materials/analysis tools: JDB DBL KRD. ", "Wrote the paper: DPS.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Q:\n\n2 animations working strange together...?", "\n\nAs described in the title im trying to make two animations sync... \nI will link both individual animations in 2 fiddles so you can see each of them and i will also link a fiddle to my weird result..\n1st fiddle https://jsfiddle.net/oxc12av7/\n2nd fiddle https://jsfiddle.net/5knf0xtr/\nThis is my code to connect them: (chrome only)\n#pot{\n bottom:15%;\n position:absolute;\n -webkit-animation:linear infinite alternate;\n -webkit-animation-name: run, swap;\n -webkit-animation-duration: 8s;\n animation:linear infinite alternate;\n animation-name: run, swap;\n animation-duration: 8s;\n}\n\n@-webkit-keyframes run {\n 0% { left: 0;}\n 50%{ left : 82%;}\n 100%{ left: 0;}\n}\n\n@-webkit-keyframes swap {\n 0% {\n -webkit-transform: scaleX 1;\n -webkit-animation-timing-function: steps(1, end);\n }\n 50% {\n -webkit-transform: scaleX(-1);\n -webkit-animation-timing-function: steps(1, end);\n 100%{-webkit-transform: scaleX 1;\n -webkit-animation-timing-function: steps(1, end);\n }\n} \n\nSo you can see that it works the first time to mirror it but the next time it doesn't... https://jsfiddle.net/j3c1rqb0/\nany ideas why?", "\nThe potatos face should be looking like this..\n-> -> -> -> -> -> -> -> ->\n<- <- <- <- <- <- <- <- <-\nThanks!", "\n\nA:\n\nYou just need to remove alternate from -webkit-animation:linear infinite alternate;\n#pot{\nbottom:15%;\nposition:absolute;\n-webkit-animation:linear infinite;\n-webkit-animation-name: run, swap;\n-webkit-animation-duration: 8s;\n}\n\nand you missed } somewhere in the keyframe.", "\nlook here: https://jsfiddle.net/wsp2z5py/\nAnd here is alternative keyframe\n\n" ]
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[ "INTRODUCTION {#s1}\n============\n\nVascular endothelial cell growth factor (VEGF) is a multifaceted cytokine \\[[@R1]\\]. ", "It promotes embryonic and postnatal neovascularization \\[[@R2]--[@R5]\\], maintains heterogeneity of endothelial cell and organ \\[[@R6]\\], repairs ischemic tissues and injured organs \\[[@R7], [@R8]\\]. ", "Highly elevated levels of VEGF in pathological tissues, as compared with those in normal tissues, are a major threat in a number of diseases including cancer, rheumatoid arthritis, atherosclerosis, diabetic retinopathy, and sepsis \\[[@R9]--[@R13]\\]. ", "Normally seen at low levels \\[[@R14]--[@R16]\\], VEGF gene is among the first set of genes that respond to tissue hypoxia, triggered by hypoxia-inducible factor-1 \\[[@R17], [@R18]\\]. ", "How VEGF gene expression is down-regulated, which has important implications in clinical settings, remains unclear, however.", "\n\nTumor necrosis factor superfamily 15 (TNFSF15; also known as VEGI or TL1A), a cytokine largely produced by endothelial cells, is a specific inhibitor of endothelial cell proliferation and angiogenesis \\[[@R19]--[@R21]\\]. ", "TNFSF15 can induce proliferating endothelial cells to undergo apoptosis \\[[@R22]\\] and thus inhibit angiogenesis \\[[@R23]\\]. ", "It can also inhibit the differentiation of endothelial progenitor cell into endothelial cell \\[[@R24]\\] by facilitating the production of a soluble form of VEGF receptor-1 (VEGFR1), which competes with the full length, signal-transmitting form of VEGFR1 for VEGF, thus blocking VEGF activity \\[[@R25]\\]. ", "The expression of the TNFSF15 gene in endothelial cells is often found at high levels in mature vasculature in normal tissues, it diminishes in angiogenic vasculatures such as in cancers \\[[@R26]--[@R28]\\] and wound tissues \\[[@R29]\\]. ", "A number of cytokines, noticeably VEGF, can effectively suppress TNFSF15 production \\[[@R26]\\]. ", "These experimental data indicate that VEGF and TNFSF15 may act as a pair of counter-balancing factors in the maintenance of vascular integrity and regulation of neovascularization.", "\n\nWe report here that TNFSF15 is able to stimulate in endothelial cell the production of a microRNA, miR-29b, whose targets include VEGF mRNA. ", "We also show that TNFSF15 activates the JNK signaling pathway to promote the activation of transcription factor GATA3, which drives the expression of miR-29b, thus the inhibition of VEGF production.", "\n\nRESULTS {#s2}\n=======\n\nTNFSF15 inhibits VEGF expression in mouse endothelial cells {#s2_1}\n-----------------------------------------------------------\n\nWe treated the mouse endothelial cell line bEnd.3 with recombinant human TNFSF15, and found that the treatment resulted in a substantial decrease of VEGF production within 24 hrs at both protein and mRNA levels in a TNFSF15 dose-dependent manner (Figures [1A, 1B](#F1){ref-type=\"fig\"}). ", "VEGF mRNA levels declined within 12 hrs of the treatment, and became about 2-times lower than that in vehicle-treated cells within 24 hrs (Figure [1C](#F1){ref-type=\"fig\"}) while VEGF protein levels decreased by 3-fold (Figure [1D](#F1){ref-type=\"fig\"}). ", "Additionally, we transfected these cells with the mouse TNFSF15 gene, and found that the engineered overexpression of TNFSF15 was accompanied by a markedly lowered VEGF expression (Figure [1E](#F1){ref-type=\"fig\"}). ", "Moreover, we found that the presence of a TNFSF15 neutralizing antibody, 4-3H \\[[@R25]\\], in the culture media prevented TNFSF15 inhibition of VEGF production at mRNA and protein levels (Figure [1F, 1G](#F1){ref-type=\"fig\"}); the amount of secreted VEGF in the cell culture media also declined under the experimental conditions (Figure [1H](#F1){ref-type=\"fig\"}). ", "These findings indicate that TNFSF15 is able to specifically and effectively inhibit VEGF expression in endothelial cells.", "\n\n![", "TNFSF15 down-regulates VEGF expression in bEnd.3 cells\\\n**A.** Changes in VEGF protein levels in bEnd.3 cells treated with recombinant TNFSF15 treatment at concentrations indicated. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. **", "B.** Changes in VEGF mRNA levels in bEnd.3 cells following TNFSF15 treatment at indicated concentrations. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. **", "C.** VEGF mRNA levels in vehicle- (white) or TNFSF15-treated (black) bEnd.3 determined at indicated time intervals by RT-PCR. ", "Data are mean±SD. ", "\\*\\**p* \\< 0.01; \\*\\*\\**p* \\< 0.001; Student\\'s *t*-test. **", "D.** VEGF protein levels in vehicle- (white) or TNFSF15-treated (black) bEnd.3 at indicated time intervals. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; Student\\'s *t*-test. **", "E.** Western blot analysis of VEGF protein levels in bEnd.3 cells transiently transfected with either the TNFSF15 gene or an empty vector. ", "Values are normalized to β-actin. ", "Data are mean±SD. ", "\\**p* \\< 0.05; Student\\'s *t*-test. **", "F.** Changes in VEGF mRNA levels in TNFSF15-treated bEnd.3 in the presence or absence of TNFSF15 neutralizing antibody 4-3H at indicated concentrations. **", "G.** Changes in VEGF protein levels in vehicle- or TNFSF15-treated bEnd.3 in the presence or absence of 4-3H (0.2 mg/mL). ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "H.** Concentrations of secreted VEGF in culture media determined by ELISA following TNFSF15 treatment in the presence or absence of 4-3H. Data are mean±SD. ", "\\**p* \\< 0.05; Student\\'s *t*-test. ", "Each experiment was performed three times.](oncotarget-07-69436-g001){#F1}\n\nTNFSF15 up-regulates VEGF-targeting miR-29b in bEnd.3 cells {#s2_2}\n-----------------------------------------------------------\n\nMicroRNA-29b is known to be involved in the down-regulation of VEGF \\[[@R30], [@R31]\\], We found that miR-29b level in bEnd.3 cells increased by 2-times within 24 hrs of TNFSF15 treatment (Figure [2A](#F2){ref-type=\"fig\"}), and the increase of miR-29b was dose-dependent (Figure [2B](#F2){ref-type=\"fig\"}). ", "Presence of 4-3H in the culture media prevented TNFSF15 from stimulating miR-29b levels (Figure [2C](#F2){ref-type=\"fig\"}). ", "Overexpressing mouse TNFSF15 in bEnd.3 cells also led to an up-regulation of miR-29b (Figure [2D](#F2){ref-type=\"fig\"}). ", "Carrying out computational miRNA target analysis, we identified sequences in the 3\\'-untranslated region of the VEGF gene (VEGF3′UTR) that are complementary to the sequences of miR-29b, suggesting that VEGF be a molecular target for miR-29b. ", "The miR-29 family consists of three members, miR-29a, -29b and -29c, with the same seed sequence (Figure [2E](#F2){ref-type=\"fig\"}) \\[[@R30]\\]. ", "In addition to that of miR-29b, intracellular levels of miR-29a in bEnd.3 also increased in response to TNFSF15 treatment, although to a less extent compared with miR-29b (Figure [2F](#F2){ref-type=\"fig\"}). ", "To determine whether miR-29b directly targeted to VEGF 3′UTR, we constructed luciferase reporter with WT and point mutations VEGF 3′UTR (WT3′UTR and Mut3′UTR) for miR-29b. ", "We found that co-transfection of miR-29b and WT3′UTR in human embryonic kidney cell line 293T cells resulted in repressed luciferase activity; co-transfection of an unrelated miRNA had little effect (miR-Ctr). ", "Co-transfection of miR-29b and Mut3′UTR, abolished the repression of luciferase activity (Figure [2G](#F2){ref-type=\"fig\"}). ", "To further demonstrate the impact of miR-29b on VEGF, we transfected miR-29b and anti-miR-29b mimics into bEnd.3 cells. ", "Western blotting showed a significant decrease in VEGF protein level after treatment with the miR-29b mimic, while inhibition of miR-29b by anti-miR-29b increase VEGF protein levels (Figure [2H](#F2){ref-type=\"fig\"}). ", "We then generated stable miR-29b overexpression cells with lentivirus encoding miR-29b or a scrambled miRNA control and miR-29b knockdown cells using miR-Zip29b lentivirus (Figure [2I](#F2){ref-type=\"fig\"}). ", "We also examined VEGF expression level in these three cell lines and find that VEGF was down-regulated in bEnd.3-miR-29b cell line and up-regulated in bEnd.3-Zip-miR-29b cell line as compared with bEnd.3-control (Figure [2J](#F2){ref-type=\"fig\"}). ", "These data indicate that miR-29b directly interact with VEGF 3′UTR, repressing VEGF expression. ", "We therefore reasoned that TNFSF15 regulates VEGF through miR-29b.", "\n\n![", "TNFSF15 up-regulates VEGF-targeting miR-29b in bEnd.3 cells\\\n**A.** MiR-29b levels in vehicle- (white) or TNFSF15-treated (black) bEnd.3 at indicated time intervals determined by RT-PCR. ", "Data are mean±SD. ", "\\**p* \\< 0.05; Student\\'s *t*-test. **", "B.** Changes in miR-29b levels following TNFSF15 treatment at indicated concentrations. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA; Student\\'s *t*-test. **", "C.** Changes in miR-29b levels in TNFSF15-treated bEnd.3 in the presence of 4-3H at indicated concentrations. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA; **D.** Changes in miR-29b levels in TNFSF15- or vector-transfected bEnd.3 cells. ", "Data are mean±SD. ", "\\*\\*\\**p* \\< 0.001; Student\\'s *t*-test. **", "E.** Sequences of miR-29a, miR-29b, and miR-29c; Seed sequence and the complementary binding sites are in green. ", "The mutations generated within the 3\\' UTR in red. **", "F.** Relative expression of miR-29a, miR-29b and miR-29c in vehicle- or TNFSF15-treated bEnd.3 measured by qPCR. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; Student\\'s *t*-test. **", "G.** Regulation of VEGF by miR-29b was confirmed by luciferase reporter and mutagenesis assays. ", "WT indicates wild-type. ", "Mut indicates mutant-type. ", "Data are mean±SD. ", "\\*\\*\\**p* \\< 0.001; Student\\'s *t*-test. **", "H.** Changes of VEGF protein in bEnd.3 transfected with miR-29b and anti-miR-29b mimics. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; Student\\'s *t*-test.**I.** Relative levels of miR-29b in bEnd.3 infected with lentivirus encoding miR-ctr, miR-29b or miR-Zip29b, determined by RT-PCR. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\*\\**p* \\< 0.001; one-way ANOVA. **", "J.** Changes of VEGF protein levels in bEnd.3 cells infected with lentivirus encoding miR-ctr, miR-29b or miR-Zip29b. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. ", "Each experiment was performed three times.](oncotarget-07-69436-g002){#F2}\n\nTNFSF15 enhances GATA3 expression to promote miR-29b production {#s2_3}\n---------------------------------------------------------------\n\nSince it is known that transcription factor GATA3 promotes miR-29b expression in other types of cells \\[[@R30]\\], we treated bEnd.3 cells with TNFSF15 and found that GATA3 was up-regulated at both protein and mRNA levels by TNFSF15 (Figures [3A-3C](#F3){ref-type=\"fig\"}), and this was accompanied by a down-regulation of VEGF (Figure [3C](#F3){ref-type=\"fig\"}). ", "To determine whether GATA3 was required for miR-29b expression, we treated bEnd.3 with GATA3 siRNA (160 pmol/mL) prior to TNFSF15 treatment, and found that GATA3 gene silencing prevented the TNFSF15-stimulation of up-regulation of miR-29b (Figure [3D](#F3){ref-type=\"fig\"}). ", "GATA3 siRNA treatment also prevented TNFSF15-induced down-modulation of VEGF (Figure [3E, 3F](#F3){ref-type=\"fig\"}). ", "These findings indicate that GATA3 activation by TNFSF15 is necessary in miR-29b up-regulation.", "\n\n![", "TNFSF15 up-regulates GATA3 expression, which promotes miR-29b production to silencing VEGF\\\n**A.** GATA3 mRNA levels in bEnd.3 cells treated with TNFSF15 at indicated concentrations. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "B.** GATA3 mRNA levels in vehicle- (white) or TNFSF15-treated (black) bEnd.3 at indicated time intervals. ", "Data are mean±SD. ", "\\**p* \\< 0.05; Student\\'s *t*-test. **", "C.** Changes of GATA3 and VEGF protein levels in bEnd.3 cells following TNFSF15 treatment at indicated concentrations. ", "Values are normalized to β-actin **D.** Changes of miR-29b levels in response to TNFSF15 treatment in the presence or absence of GATA3 siRNA (160 pmol/mL), determined by RT-PCR. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. **", "E.** Changes of VEGF protein levels following TNFSF15 treatment (0.3 Unit, 24 hrs) in the presence or absence of GATA3 siRNA (160 pmol /mL). **", "F.** Densitometry analysis of GATA3 and VEGF protein band intensities shown in panel E. Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. ", "Each experiment was performed three times.](oncotarget-07-69436-g003){#F3}\n\nDR3 mediates TNFSF15-stimulated activation of GATA3, up-regulation of miR-29b and down-regulation of VEGF {#s2_4}\n---------------------------------------------------------------------------------------------------------\n\nTo determine whether the up-regulation of GATA3 and miR-29b was mediated by DR3, the cell surface receptor for TNFSF15, we treated bEnd.3 cells with DR3 siRNA. ", "Western blotting analysis revealed that TNFSF15 was no longer able to stimulate an increase of the GATA3 protein in the cells, or to inhibit VEGF production once the DR3 gene is silenced (Figure [4A](#F4){ref-type=\"fig\"}). ", "DR3 gene-silencing also resulted in a blockage of TNFSF15-induced up-regulation of GATA3 at mRNA level by using RT-PCR (Figure [4B](#F4){ref-type=\"fig\"}). ", "Concomitantly, DR3 siRNA treatment resulted in an inhibition of TNFSF15-stimulated miR-29b up-regulation (Figure [4C](#F4){ref-type=\"fig\"}), as well as the inability of TNFSF15 to inhibit VEGF gene expression at mRNA level (Figure [4D](#F4){ref-type=\"fig\"}). ", "These findings indicate that DR3 is responsible for mediating TNFSF15 activities that lead to the activation of GATA3, the up-regulation of miR-29b and, consequently, the down-modulation of VEGF gene expression in bEnd.3 cells.", "\n\n![", "DR3 mediates TNFSF15- stimulate activation of GATA3, up-regulation of miR-29b and down-regulation of VEGF\\\n**A.** Changes of GATA3 and VEGF protein levels following TNFSF15 treatment (0.3 Unit, 24 hrs) in the presence or absence of DR3 siRNA (40 pmol/mL), determined by Western blotting analysis. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "B.** Changes of GATA3 mRNA levels in response to TNFSF15 treatment in the presence or absence of DR3 siRNA (40 pmol/mL). ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "C.** Changes of miR-29b levels in response to TNFSF15 treatment in the presence or absence of DR3 siRNA (40 pmol/mL). ", "Data are mean±SD. ", "\\**p*\\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "D.** Changes of VEGF mRNA levels in response to TNFSF15 treatment in the presence or absence of DR3 siRNA (40 pmol/mL). ", "Data are mean±SD. ", "\\*\\**p* \\< 0.01; one-way ANOVA; Each experiment was performed three times.](oncotarget-07-69436-g004){#F4}\n\nJNK signaling is involved in TNFSF15-stimulated GATA3 and miR-29b up-regulation {#s2_5}\n-------------------------------------------------------------------------------\n\nIt is known that TNFSF15 activates JNK pathway in a DR3-dependent manner \\[[@R32]--[@R34]\\]. ", "To find out the role of JNK signaling in TNFSF15-facilitated VEGF down-modulation, we treated bEnd.3 cells with TNFSF15 (0.3 Unit) and evaluated the phosphorylation of JNK. ", "Western blotting analysis of the treated cells indicated that TNFSF15 treatment led to a substantial increase in phosphorylated JNK (p-JNK) within 10 min (Figure [5A](#F5){ref-type=\"fig\"}). ", "This effect remained profound when measured at 24 hrs post treatment, and coincided with delined VEGF gene expression (Figure [5B](#F5){ref-type=\"fig\"}). ", "Additionally, silencing the DR3 gene with siRNA (40 pmol/mL) efficiently abolished TNFSF15 activation of JNK (Figure [5C](#F5){ref-type=\"fig\"}). ", "We then treated bEnd.3 cells with a JNK inhibitor, SP600125 (50 μM, 2 hrs), prior to TNFSF15 treatment, and found that SP600125 effectively inhibited phosphorylation of c-Jun, the transcriptor that transmits JNK signal \\[[@R35], [@R36]\\]; SP600125 treatment also completely abolished TNFSF15-induced GATA3 upregulation, and prevented TNFSF15 from inhibiting VEGF production (Figure [5D](#F5){ref-type=\"fig\"}). ", "Additionally, SP600125 treatment effectively prevented TNFS15-induced miR-29b up-regulation (Figure [5E](#F5){ref-type=\"fig\"}). ", "These findings support the view that TNFSF15 activates JNK signaling pathway to promote the expression of GATA3, which drives the expression of miR-29b.", "\n\n![", "Involvement of JNK signaling pathway in TNFSF15-facilitated GATA3 and miR-29b up-regulation and VEGF down-regulation\\\n**A.** Western blotting analysis of phosphorylated JNK proteins following TNFSF15 treatment within 60 min. ", "Data are mean±SD. ", "\\**p*\\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "B.** Western blotting analysis of phosphorylated JNK proteins following TNFSF15 treatment after 24 hours. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; Student\\'s *t*-test. **", "C.** Changes of DR3 and phosphorylated JNK protein levels following TNFSF15 treatment (0.3 Unit, 24 hrs) in the presence or absence of DR3 siRNA (40 pmol/mL). ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "D.** Effect of SP600125 (50 μM) on TNFSF15-induced VEGF degradation, GATA3 up-regulation, JNK phosphorylation and c-jun phosphorylation. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA. **", "E.** Changes of miR-29b levels following TNFSF15 treatment (24 hrs) in the presence or absence of SP600125 (50 μM). ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. ", "Each experiment was performed three times.](oncotarget-07-69436-g005){#F5}\n\nAs an alternate approach to examine the significance of JNK for TNFSF15-stimulated GATA3 and miR-29b up-regulation, we silenced the JNK gene by using a siRNA molecule that recognizes a common sequence in both JNK1 and JNK2 from both mice and humans \\[[@R37]\\]. ", "We found that treatment of bEnd.3 cells with the JNK siRNA prevented TNFSF15-induced GATA3 upregulation and resulted in lowered VEGF production ([Figure S1A](#SD1){ref-type=\"supplementary-material\"}). ", "We also found that JNK siRNA effectively prevented TNFS15-induced miR-29b up-regulation ([Figure S1B](#SD1){ref-type=\"supplementary-material\"}). ", "These data, which are in good agreement with those obtained with JNK inhibitor SP600125, demonstrated an critical role for JNK in the modulation of TNFSF15-stimulalted expression of GATA3 and miR-29b.", "\n\nMiR-29b inhibits angiogenesis *in vitro* and *in vivo* {#s2_6}\n------------------------------------------------------\n\nTo investigate the effect of miR-29b modulation on angiogenesis, we transfected bEnd.3 cells with miR-29b mimics, and found that the miR-29b mimics markedly inhibited bEnd.3 cells to form capillary-like tubules on Matrigel coating (Figure [6A, 6B](#F6){ref-type=\"fig\"}). ", "On the other hand, when we overexpressed anti-miR-29b in bEnd.3 cells in order to inhibit miR-29b, we found that the cells were more capable of tubule formation (Figure [6C, 6D](#F6){ref-type=\"fig\"}). ", "In addition, to determine the impact of miR-29b on the ability of bEnd.3 cell to migrate, we infected the cells with Lentivirus-linked miR-29b vector. ", "The results indicated that miR-29b overexpression led to a marked reduction of bEnd.3 cells to migrate through microporous filters (Figure [6E](#F6){ref-type=\"fig\"}). ", "Furthermore, inhibition of miR-29b by Zip-miR-29b led to more than a doubling of the ability of bEnd.3 cells to migrate (Figure [6F](#F6){ref-type=\"fig\"}).", "\n\n![", "miR-29b inhibits angiogenesis *in vitro* and *in vivo*\\\n**A.** Images of capillary-like tubules formed by bEnd.3 cells transfected with miR-Ctrl or miR-29b mimics on Matrigel in 24 hrs after seeding; scale bar, 100 μm. **", "B.** Average lengths and areas of the capillary-like tubules formed by miR-Ctrl or miR-29b mimics transfected cells. ", "Data are mean±SD of three independent experiments; \\**p* \\< 0.05; Student\\'s *t*-test. **", "C.** Images of capillary-like tubules formed by bEnd.3 cells transfected with anti-Ctrl or anti-miR-29b mimics in 24 hrs after seeding; scale bar, 100 μm. **", "D.** Average lengths and areas of the capillary-like tubules formed by anti-Ctrl or anti-miR-29b mimics-transfected cells. ", "Data are mean±SD of three independent experiments; \\**p* \\< 0.05; Student\\'s *t*-test. **", "E.** Images of migrated bEnd.3 cells in transwell assays for miR-control, miR-29b or Zip-miR-29b-transfected cells (arrows); scale bar, 25 μm. **", "F.** Quantitative analysis of the numbers of migrated cells transfected with miR-control, miR-29b or Zip-miR-29b. ", "Data are mean±SD of three independent experiments; \\**p* \\< 0.05;\\*\\**p* \\< 0.01; one-way ANOVA. **", "G.** Comparison of blood vessel formation in Matrigel plugs on C57BL/6J mice (*n* = 6 per group) of bEnd.3-control (a, d), bEnd.3-miR-29b (b, e), or bEnd.3-Zip-miR-29b (c, f); scale bar for images of Matrigel plugs (a, b, and c): 2 mm; scale bar for H&E-stained cross-sections: 5 μm (d, e and f). **", "H.** Quantitative analysis of blood vessel densities in H&E-stained sections of miR-control or miR-29b or Zip-miR-29b plugs. ", "Data are mean±SD. ", "\\*\\**p* \\< 0.01; one-way ANOVA.**I.** Fluorescent confocal microscopic images of frozen sections of Matrigel plugs from miR-control or miR-29b or Zip-miR-29b groups; red, CD31; green, GFP; blue, DAPI; yellow, CD31-GFP double positive; scale bar, 25 μm. **", "J.** Quantitative analysis of microvessel densities of the gel plugs (*n* = 6 per group) determined by counting the number of CD31-positive vascular structures containing lumens in the fluorescent confocal microscopic images; 3 images from 3 sections for each gel plug were analyzed. ", "Data are mean±SD. ", "\\**p* \\< 0.05; one-way ANOVA. **", "K.** Western blotting analysis of VEGF protein levels in the gel plugs. **", "L.** Densitometric analysis of VEGF protein band intensities shown in panel K; measurements from three independent Western analyses were used. ", "Data are mean±SD. ", "\\**p* \\< 0.05; \\*\\**p* \\< 0.01; one-way ANOVA.](oncotarget-07-69436-g006){#F6}\n\nTo investigate miR-29b modulation of angiogenesis *in vivo*, we injected a Matrigel solution containing bEnd.3-miR-29b cells, bEnd.3-Zip-miR-29b cells, or bEnd.3-control cells subcutaneously on C57BL/6J mice. ", "When retrieved on day 14 post-implantation, we found that the gel plugs contained bEnd.3-Zip-miR-29b cells became highly vascularized compared with those containing bEnd.3-control cells, whereas those contained bEnd.3-miR-29b cell had much fewer blood vessels compared with bEnd.3-control cells (Figure [6G](#F6){ref-type=\"fig\"}). ", "Analysis of blood vessel densities of the three groups by counting the number of red blood cell-containing blood vessels confirmed the ability of miR-29b to inhibit angiogenesis in this model (Figure [6H](#F6){ref-type=\"fig\"}). ", "As the cells in this experiment were labeled with green fluorescent protein (GFP), we sectioned the freshly frozen gel plugs, carried out immunostaining for endothelial cell marker CD31, and subjected the sections to confocal microscopic analysis. ", "The new blood vessels were CD31-positive (red) and GPF-positive (green) and therefore appeared yellow (Figure [6I](#F6){ref-type=\"fig\"}). ", "Quantitative analysis of the microscopic images indicated that, compared with empty vector transfected bEnd.3 cells, miR29b overexpressing cells were much less capable of forming blood vessel, whereas removal of miR-29b by Zip-miR-29b facilitated blood vessel growth (Figure [6J](#F6){ref-type=\"fig\"}). ", "Moreover, Western blotting analysis of the plugs indicated that VEGF protein levels of the bEnd.3-miR-29b group decreased by 2-fold, compared with the bEnd.3-control group. ", "In contrast, VEGF levels of bEnd.3-Zip-miR-29b group increased by 2.5-fold by the same comparison (Figure [6K, 6L](#F6){ref-type=\"fig\"}). ", "These findings indicate that miR-29b down-regulation of VEGF expression leads to inhibition of angiogenesis in this animal model.", "\n\nDISCUSSION {#s3}\n==========\n\nWe show in this study that TNFSF15, a cytokine produced largely by endothelial cells and a potent inhibitor of endothelial cell proliferation, is able to down-regulate VEGF gene expression. ", "This is achieved by TNFSF15-stimulated expression of miR-29b, which marks VEGF mRNA for destruction. ", "Additionally, we demonstrate that DR3, the cell-surface receptor for TNFSF15, mediates the stimulation of miR-29b expression by activating the JNK signaling pathway, which leads to the activation of transcription factor GATA3 that promotes miR-29b expression. ", "The overall outcome of this sequence of signals is an inhibition of VEGF-driven neovascularization.", "\n\nThese findings are interesting because they reveal a new signaling pathway by which the activity of VEGF, possibly the most prominent factor that drives blood vessel growth under a variety of pathological conditions, including inflammation and cancer, can be directly modulated. ", "We showed previously that VEGF effectively down-regulate TNFSF15 expression in ovarian cancer, indicating that TNFSF15 as a negative regulator of blood vessel growth is targeted by VEGF for down-modulation in order to initiate angiogenesis \\[[@R26]\\]. ", "Taken together, our findings suggest that TNFSF15 and VEGF be a pair of counter-balancing factors that play a pivotal role in the modulation of neovascularization in physiological or pathological settings.", "\n\nDR3, the cell surface receptor for TNFSF15, has been shown to mediate TNFSF15 activities in T cells, dendritic cells and lymphatic endothelial cells \\[[@R38]--[@R40]\\]. ", "The experimental data from this study indicate that DR3 is also involved in mediating TNFSF15 activity in miR-29b up-regulation and VEGF down-regulation through the activation of JNK signaling pathway, offering a mechanism underlying the promotion of miR-29b by TNFSF15. ", "That JNK inhibitor SP600125 treatment of the cells results in a blockage of TNFSF15-induced GATA3 up-regulation indicates that TNFSF15-activated JNK signaling pathway can be directly linked to the promote the expression of transcription factor GATA3. ", "In agreement with a previous report that GATA3 is able to induce the production of miR-29b by enhancing the activity of the miR-29b promoter \\[[@R30]\\], we demonstrate in this study that silencing the GATA3 gene results in an abrogation of TNSF15-induced miR-29b up-modulation and subsequent VEGF down-modulation.", "\n\nIn summary, the results of this study bring forward insights into a mechanism through which the down-modulation of VEGF gene expression can be achieved *via* TNFSF15-DR3-mediated activation of the JNK-GATA3 signaling pathway that leads to miR-29b upregulation. ", "These findings are of significance in aiding the development of new approaches to interfere with VEGF-driven neovascularization in disease conditions such as in cancers.", "\n\nMATERIALS AND METHODS {#s4}\n=====================\n\nCell culture {#s4_1}\n------------\n\nMouse endothelial cell line bEnd.3 were maintained in DMEM supplemented with 10% FBS and 1% penicillin/streptomycin (complete media) and incubated at 37°C and 5% CO~2~.\n\nMice {#s4_2}\n----\n\nSix-to 8-week-old female C57BL/6J mice were purchased from Academy of Military Medical Science (Beijing, China). ", "Studies using experimental animals were performed according to protocols approved by Nankai University Ethics Committee on Pre-Clinical Studies.", "\n\nMicroRNA transfection {#s4_3}\n---------------------\n\nScramble miRNA mimics (miR-Ctr, \\#24), miR-29b mimics (miR-29b, \\#miR10000127), scramble anti-miRNA mimics (anti-Ctr, \\#22) and anti-miR-29b mimics (anti-miR-29b, \\#miR20000127) were purchased from Ribobio (Guangzhou, China). ", "Before transfection, bEnd.3 cells were seeded in 12-well plates (80000 cells per well) and cultured in Dulbecco\\'s modified Eagle\\'s medium (DMEM) containing 10% FBS for 12 hrs. ", "For transient overexpression of miR-29b, cells was transfected with 50 nM miR-29b or miR-Ctr using Lipofectamine 2000 (\\#11668-019, Invitrogen, Carlsbad, CA, USA). ", "For transient down-regulaton of miR-29b, cells were transfected with 100 nM anti-miR-29b or anti-Ctr, according to the manufacturer\\'s instructions. ", "Samples were collected after 24 hrs for quantification of miRNA or protein expression.", "\n\nConstruction of bEnd.3-control cell line, bEnd.3-miR-29b cell line and bEnd.3-Zip-miR-29b cell line {#s4_4}\n---------------------------------------------------------------------------------------------------\n\nThe GFP-expressing lentivectors encoding miR-29b or Zip-miR-29b, miR-control and polybrene were purchased from GenePharma (Shanghai, China). ", "The lentivector stably knockdown miR-29b (Zip-miR-29b) expression contained the following shRNA sequence: 5\\'- GATCCGTAGCACCATGAAATCAGTGTTTCAA GAGAACACTGATTTCAAATGGTGCTACTTTTTTG- 3\\'. ", "Prior to transfection, bEnd.3 cell were seeded in six-well plates (2×10^5^ cells per well) and incubated overnight, then transduced with lentiviral supernatants containing lentiviral vectors coding for the miR-29b, Zip-miR-29b, or miR-control, respectively, and 5μg/mL polybrene at room temperature for 24 hrs. ", "Culture media were then removed and replaced with fresh DMEM containing 10% FBS and incubated for 72 hrs in the presence of puromycin (10μg/mL) for selection. ", "The transduction efficiency was monitored by qPCR for the miR-29b expression.", "\n\nLuciferase assays {#s4_5}\n-----------------\n\nFor 3\\'-untranslated region (3\\'-UTR) assays, human embryonic kidney cell line 293T cells were co-transfected with miR-Ctrl or miR-29b mimics (50 nM final concentration), firefly luciferase reporter constructs containing WT or mutated 3\\'-UTR of VEGF using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA, USA), and a renilla luciferase reporter vector to normalize the transfection efficiency. ", "For the Dual-Luciferase^®^ Reporter Assay System, renilla and firefly luciferase activities were measured 24 hrs post transfection using the Dual-Luciferase Reporter System E1910 and a GloMax luminometer E6501 (Promega, Madison, USA). ", "The luciferase activities represent the firefly/renilla luciferase ratios, and transfection efficiency was normalized to the control luciferase.", "\n\nQuantitative real-time polymerase chain reaction {#s4_6}\n------------------------------------------------\n\nMicroRNA isolation kit and Trizol were purchased from Qiagen (Valencia, CA, USA). ", "MiR-29b RT Primer (\\#ssD1301049265), miR-29b Forward Primer (\\#ssD1301049267), miR-Reverse Primer (\\#ssD089261711), U6-RT Primer (\\#ssD0904071008), U6-Forward Primer (\\#ssD0904071006) and U6-Reverse Primer (\\#ssD0904071007) were purchased from Ribobio (Guangzhou, China). ", "Cells were collected and homogenized in Trizol, total RNA including miRNAs extracted, and reverse transcription were performed according to the manufacturer\\'s protocol. ", "For PCR amplification of the cDNA fragment encoding targeted genes, the sense and antisense primer sequences for VEGF, GATA3, and β-actin were, respectively, 5′-GGCGATTTAG CAGCAGATAT AAGAA-3′ and 5′-GGAGATCCTT CGAGGAGCAC TT-3, 5′-CCATTACCAC CTATCCGCCC-3′ and 5′-CACACTCCCT GCCTTCTGTG, 5′-CAGAAGGAGA TTACTGCTCT-3′ and 5′-TACTCCTGCT TGCTGATCCA CATC-3.", "\n\nELISA {#s4_7}\n-----\n\nMouse VEGF ELISA Kit was purchased from R&D Systems (Minneapolis, MA, USA). ", "The assays were carried out according the manufacturer\\'s instructions. ", "The absorbance was measured at 450nm with an iMark^TM^ Microplate Reader (Bio-Rad Laboratories, Hercules, CA, USA).", "\n\nWestern blotting {#s4_8}\n----------------\n\nCells were homogenized and subjected to SDS/PAGE. ", "The proteins were transferred to a polyvinylidene difluoride membrane (Roche Molecular Biochemicals, Quebec, Canada), blocked with 5% nonfat milk powder in TBS-T buffer (20 mM Tris-HCl, pH 7.4, 137 mM NaCl, and 0.1% Tween) for 1 hour at RT, incubated overnight at 4°C with primary antibody against the target proteins and then incubated with appropriate HRP-conjugated secondary antibodies. ", "The films were developed with the ECL System (Millipore, Billerica, MA, USA). ", "VEGF (\\#sc-152, 1:1000), GATA-3(\\#sc-9009, 1:1000) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). ", "DR3 (1:3000) was purchased from Sigma (St Louis, MO, USA). ", "JNK(\\#9258S, 1:1000), phospho-JNK(\\#4668S, 1:1000), c-Jun(\\#9165S, 1:1000), phospho-c-Jun (\\#3270S, 1:1000) were obtained from Cell Signaling Technology (Danvers, MA).", "\n\nRNA interference {#s4_9}\n----------------\n\nThe siRNA for DR3 and GATA3 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). ", "Scrambled siRNA control was purchased from GenePharma (Shanghai, China). ", "The sense and antisense sequences of the scrambled siRNA were as follows: 5′-UUCUCCGAAC GUGUCACGUT T-3′ and 5′-ACGUGACACG UUCGGAGAAT T-3. ", "Cells were transfected with siRNAs using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA, USA). ", "Messenger RNA and protein levels of the target gene products were determined 24 hrs post transfection or as indicated in the text.", "\n\n*In vitro* angiogenesis assay {#s4_10}\n-----------------------------\n\nForty-eight-well plates were coated with 40 μL of Matrigel (R&D Systems) and let to solidify for 30 min at 37°C. ", "The bEnd.3 cells stably transfected miR-control or miR-29b mimics, anti-control or anti-miR-29b mimics were seeded (3×10^4^ cells/well) on top of the solidified Matrigel and incubated at 37°C for 24 hrs. ", "The cells were stained with 3 μM calcein-AM (Invitrogen) for 30 min at 37°C and 5% CO~2~. Formation of the capillary tubule structures was observed and digitally photographed under an inverted light microscope at 5× magnification (Axiovert 200M; Zeiss, Oberkochen, Germany). ", "Tubule lengths and areas were quantified by using Image-Pro Plus 6.0 software (Media Cybernetics, Rockville, MD, USA).", "\n\n*In vivo* angiogenesis assay {#s4_11}\n----------------------------\n\nThe bEnd.3 cells transduced with lentivirus encoding miR-ctr, miR-29b or Zip-miR-29b, respectively, were resuspended on ice in phenol red-free Matrigel solution and implanted into female C57BL/6J mice by s.c. ", "injection (200 μL) in the abdominal region. ", "Matrigel plugs were retrieved 14 days post implantation, photographed with a Leica M165FC stereoscopic microscope (Leica, Wetzlar, Germany). ", "The plugs were each divided into three portions for hematoxylin and eosin (H&E) staining, fluorescent immunostaining, and Western blotting. ", "For H&E staining, the plugs was fixed with 4% paraformaldehyde, paraffin embedded, and sectioned (5 μm). ", "The sections were subjected to H&E staining. ", "Red blood cell-containing luminal structures on the sections were counted under a microscope (Nikon 50i; Nikon, Tokyo, Japan). ", "Three fields (magnification, 100×) per section were examined. ", "For immunostaining, the plugs were fresh-frozen in OCT embedding medium, then sectioned (10 μm), The sections were equilibrated, hydrated with phosphate buffered saline (PBS) for 5 min at RT, and fixed in 4% paraformaldehyde for 15 min at RT, rinsed with PBS, blocked with 5% BSA for 1 hr at RT, and then incubated at 4°C overnight with anti-CD31 antibody (\\#553370, BD Biosciences, San Jose, CA, USA), then with Alexa Fluor 555-conjugated secondary antibody (\\#A-21434, Thermo Scientific, Rockford, IL, USA) for 1 hr at RT, mounted with DAPI Mounting Medium (Vector Laboratories, Burlingame, CA), and analyzed by using a Leica TCS SP5 confocal microscope (Leica, Wetzlar, Germany).", "\n\nCell migration assays {#s4_12}\n---------------------\n\nEight μm-pore Transwells were used (Corning Inc, Corning, NY, USA). ", "Cells (5000/well) were seeded in the inserts pre-equilibrated with DMEM containing 10% FBS. ", "The inserts were then placed in the culture wells and incubated for 24 hrs, rinsed, fixed in 4% paraformaldehyde for 10 min, and then subjected to crystal violet (Beyotime, Haimen, Jiangsu, China) staining. ", "Digital images (10× magnification) of the underside of the inserts were taken with a microscope (ECLIPSE TS100, Nikon, Tokyo, Japan). ", "The numbers of cells on six randomly selected fields per well per insert were counted.", "\n\nStatistical analysis {#s4_13}\n--------------------\n\nThe data were subjected to variance analysis (ANOVA), followed by 2-tailed, unpaired Student\\'s *t*-tests. ", "Differences between two groups with p-values less than 0.05 were considered to be statistically significant.", "\n\nSUPPLEMENTARY MATERIAL {#s5}\n======================\n\nThis study was supported in part by grants from the Natural Science Foundation of China (NSFC 81272356 to LYL, 81672747 to QZZ), Tianjin Municipality Science and Technology Commission (10ZCK-FSH00100 to LYL), Fundamental Research Funds for the Central Universities of China (No. ", "65141026 to QZZ), Tianjin Municipality Science and Technology Commission (15JCYBJC50100 to QZZ), and the Ministry of Education Science and Technology Development Center (No 20130031120040 to QZZ).", "\n\n**CONFLICTS OF INTEREST**\n\nThe authors disclosed no potential conflicts of interest.", "\n\n**Author\\'s Contribution**\n\nKZ, HXC performed the experiments. ", "KZ, HXC and QZZ produced the figures. ", "KZ, QZZ, and LYL designed the study, analyzed the data, and wrote the manuscript. ", "JH participated in discussion during the preparation of the manuscript. ", "All authors had final approval of the submitted and published versions.", "\n" ]
{ "pile_set_name": "PubMed Central" }
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[ "Q:\n\nCan I mix arm-eabi with arm-elf?", "\n\nI have a product which bootloader and application are compiled using a compiler (gnuarm GCC 4.1.1) that generates \"arm-elf\".", "\nThe bootloader and application are segregated in different FLASH memory areas in the linker script.", "\nThe application has a feature that enables it to call the bootloader (as a simple c-function with 2 parameters).", "\nI need to be able to upgrade existing products around the world, and I can safely do this using always the same compiler.", "\nNow I'd like to be able to compile this product application using a new GCC version that outputs arm-eabi.", "\nEverything will be fine for new products, where both application and bootloader are compiled using the same toolchain, but what happens with existing products?", "\nIf I flash a new application, compiled with GCC 4.6.x and arm-none-eabi, will my application still be able to call the bootloader function from the old arm-elf bootloader?", "\n\nFurthermore, not directly related to the above question, can I mix object files compiled with arm-elf into a binary compiled with arm-eabi?", "\n\nEDIT:\nI think is good to make clear I am building for a bare metal ARM7, if it makes any difference...\n\nA:\n\nNo. ", "An ABI is the magic that makes binaries compatible. ", "The Application Binary Interface determines various conventions on how to communicate with other libraries/applications. ", "For example, an ABI will define calling convention, which makes implicit assumptions about things like which registers are used for passing arguments to C functions, and how to deal with excess arguments.", "\nI don't know the exact differences between EABI and ABI, but you can find some of them by reading up on EABI. ", "Debian's page mentions the syscall convention is different, along with some alignment changes.", "\nGiven the above, of course, you cannot mix arm-elf and arm-eabi objects.", "\nThe above answer is given on the assumption that you talk to the bootloader code in your main application. ", "Given that the interface may be very simple (just a function call with two parameters), it's possible that it might work. ", "It'd be an interesting experiment to try. ", "However, it is not ** guaranteed** to work.", "\nPlease keep in mind you do not have to use EABI. ", "You can generate an arm-elf toolchain with gcc 4.6 just as well as with older versions. ", "Since you're using a binary toolchain on windows, you may have more of a challenge. ", "I'd suggest investigating crosstool-ng, which works quite well on Linux, and may work okay on cygwin to build the appropriate toolchain.", "\n\nA:\n\nThere is always the option of making the call to bootloader in inline assembly, in which case you can adhere to any calling standard you need :).", "\nHowever, besides the portability issue it introduces, this approach will also make two assumptions about your bootloader and application:\n\nyou are able to detect in your app that a particular device has a bootloader built with your non-EABI toolchain, as you can only call the older type bootloader using the assembly code.", "\nthe two parameters you mentioned are used as primitive data by your bootloader. ", "Should the bootloader use them, for example, as pointers to structs then you could be facing issues with incorrect alignment, padding and so forth.", "\n\n" ]
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[ "1. ", "Field of the Invention\nThis invention relates generally to Rotary garden tiller tines and more particularly to a pulverizer/edger tine assembly used for establishing and maintaining perimeter edges along flower beds, driveways, sidewalks, and fence lines etc.", "\n2. ", "General Background\nRotary garden tillers are generally configured with various types of tines for breaking, mulching, and otherwise tilling the soil in rows or beds. ", "Such tillers are chiefly concerned with the cultivation of the soil within a given area with little or no concern with the location of the plot to be worked or the maintenance of the plot relative to adjacent or surrounding lands or obstacles, such as walks, driveways, fences, etc. ", "Furthermore, many plots are surrounded by grass which will invade the tilled area when given a chance. ", "It is therefore essential that a well defined perimeter be established and maintained around the tilled area. ", "This is often done with landscape timbers, edge moldings and the like and maintained with a lawn edger, weed eater, etc. ", "Such edging often presents as many problems as it solves and makes maintaining such barriers difficult at best.", "\nIt is therefore more advantageous to eliminate such barriers and provide a natural perimeter, no-grow zone around the tilled soil that can be easily maintained with the rotary tiller." ]
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[ "(ns spec-tools.impl\n (:refer-clojure :exclude [resolve])\n #?(:", "cljs (:require-macros [spec-tools.impl :refer [resolve]]))\n (:require\n #?(:", "cljs [cljs.analyzer.api])\n [clojure.spec.alpha :as s]\n [spec-tools.form :as form]\n [clojure.walk :as walk])\n (:import\n #?", "@(:clj\n [(clojure.lang Var)])))\n\n#?(:", "clj\n (defn in-cljs? [", "env]\n (:ns env)))\n\n;; ClojureScript 1.9.655 and later have a resolve macro - maybe this can be\n;; eventually converted to use it.", "\n#?(:", "clj\n (defmacro resolve\n [env sym]\n `(if (in-cljs? ", "~env)\n ((clojure.core/resolve 'cljs.analyzer.api/resolve) ~env ~sym)\n (clojure.core/resolve ~env ~sym))))\n\n(defn- cljs-sym [x]\n (if (map? ", "x)\n (:name x)\n x))\n\n(defn- clj-sym [x]\n (if (var? ", "x)\n (let [^Var v x]\n (symbol (str (.name (.ns v)))\n (str (.sym v))))\n x))\n\n(defn ->sym [x]\n #?(:", "clj (clj-sym x)\n :cljs (cljs-sym x)))\n\n(defn- unfn [cljs? ", "expr]\n (if (clojure.core/and (seq? ", "expr)\n (symbol? (", "first expr))\n (= \"fn*\" (name (first expr))))\n (let [[[s] & form] (rest expr)]\n (conj (walk/postwalk-replace {s '%} form) '[%] (if cljs? '", "cljs.core/fn 'clojure.core/fn)))\n expr))\n\n#?(:", "clj\n (defn cljs-resolve [env symbol]\n (clojure.core/or (->> symbol (resolve env) cljs-sym) symbol)))\n\n(defn polish [x]\n (cond\n (seq? ", "x) (flatten (keep polish x))\n (symbol? ", "x) nil\n :else x))\n\n(defn polish-un [x]\n (some-> x polish name keyword))\n\n(defn un-key [x]\n (some-> x name keyword))\n\n(defn with-key->spec [{:keys [req req-un opt opt-un] :as data}]\n (let [key->spec (->> (concat opt req) (map (juxt identity identity)) (into {}))\n un-key->spec (->> (concat opt-un req-un) (map (juxt un-key identity)) (into {}))]\n (assoc data :key->spec (merge key->spec un-key->spec))))\n\n(defn with-real-keys [{:keys [req-un opt-un] :as data}]\n (cond-> data\n req-un (update :req-un (partial mapv un-key))\n opt-un (update :opt-un (partial mapv un-key))))\n\n(defn parse-keys [form]\n (let [m (some->> form (rest) (apply hash-map))]\n (cond-> m\n (:req m) (update :req #(->> % flatten (keep polish) (into [])))\n (:req-un m) (update :req-un #(->> % flatten (keep polish) (into [])))\n (:opt-un m) (update :opt-un #(->> % (keep polish) (into [])))\n true (-> with-key->spec with-real-keys))))\n\n(defn extract-keys [form]\n (let [{:keys [req opt req-un opt-un]} (some->> form (rest) (apply hash-map))]\n (flatten (map polish (concat req opt req-un opt-un)))))\n\n#?(:", "clj\n (defn resolve-form [env pred]\n (let [cljs? (", "in-cljs? ", "env)\n res (if cljs? (", "partial cljs-resolve env) clojure.core/resolve)]\n (->> pred\n (walk/postwalk\n (fn [x]\n (if (symbol? ", "x)\n (let [y (res x)\n -var-get (fn [v] (if cljs? ", "@v (var-get v)))\n sym-or-x (fn [v] (or (->sym v) x))]\n (cond\n (var? ", "y) (if (s/get-spec (-var-get y))\n (-var-get y)\n (sym-or-x y))\n (some? ", "y) (sym-or-x y)\n :else x))\n x)))\n (unfn cljs?)))))", "\n\n(defn extract-pred-and-info [x]\n (if (map? ", "x)\n [(:spec x) (dissoc x :spec)]\n [x {}]))\n\n(defn strip-fn-if-needed [form]\n (let [head (first form)]\n ;; Deal with the form (clojure.core/fn [%] (foo ... %))\n ;; We should just use core.match...\n (if (and (= (count form) 3) (= head #?(:", "clj 'clojure.core/fn :cljs 'cljs.core/fn)))\n (nth form 2)\n form)))\n\n(defn normalize-symbol [kw]\n (case (and (symbol? ", "kw) (namespace kw))\n \"spec-tools.spec\" (symbol \"clojure.core\" (name kw))\n \"cljs.core\" (symbol \"clojure.core\" (name kw))\n \"cljs.spec.alpha\" (symbol \"clojure.spec.alpha\" (name kw))\n kw))\n\n(defn extract-form [spec]\n (if (seq? ", "spec) spec (s/form spec)))\n\n(defn qualified-name [key]\n (if (keyword? ", "key)\n (if-let [nn (namespace key)]\n (str nn \"/\" (name key))\n (name key))\n key))\n\n(defn nilable-spec? [", "spec]\n (let [form (and spec (s/form spec))]\n (boolean\n (if (seq? ", "form)\n (some-> form\n seq\n first\n #{'clojure.spec.alpha/nilable\n 'cljs.spec.alpha/nilable})))))\n\n(defn unwrap\n \"Unwrap [x] to x. Asserts that coll has exactly one element.\"", "\n [coll]\n {:pre [(= 1 (count coll))]}\n (first coll))\n\n(defn deep-merge [& values]\n (cond\n (every? ", "map? ", "values)\n (apply merge-with deep-merge values)\n\n (every? ", "coll? ", "values)\n (reduce into values)\n\n :else\n (last values)))\n\n(defn unlift-keys [data ns-name]\n (reduce\n (fn [acc [k v]]\n (if (= ns-name (namespace k))\n (assoc acc (keyword (name k)) v)\n acc))\n {} data))\n\n;;\n;; FIXME: using ^:skip-wiki functions from clojure.spec. ", "might break.", "\n;;\n\n(defn register-spec! [", "k s]\n (s/def-impl k (s/form s) s))\n\n;;\n;; functional clojure.spec\n;;\n\n(defn coll-of-spec [pred type]\n (let [form (form/resolve-form pred)\n cpred (if (set? ", "type) set? ", "vector?)]", "\n (clojure.spec.alpha/every-impl\n form\n pred\n {:into type\n ::s/conform-all true\n ::s/describe `(s/coll-of ~form :into ~type),\n ::s/cpred cpred,\n ::s/kind-form (quote nil)}\n nil)))\n\n(defn map-of-spec [kpred vpred]\n (let [forms (map form/resolve-form [kpred vpred])\n tuple (s/tuple-impl forms [kpred vpred])]\n (clojure.spec.alpha/every-impl\n `(s/tuple ~@forms)\n tuple\n {:into {}\n :conform-keys true\n ::s/kfn (fn [_ v] (nth v 0))\n ::s/conform-all true\n ::s/describe `(s/map-of ~@forms :conform-keys true),\n ::s/cpred map?,", "\n ::s/kind-form (quote nil)}\n nil)))\n\n(defn keys-spec [{:keys [req opt req-un opt-un]}]\n (let [req-specs (flatten (map polish (concat req req-un)))\n opt-specs (flatten (map polish (concat opt opt-un)))\n req-keys (flatten (concat (map polish req) (map polish-un req-un)))\n opt-keys (flatten (concat (map polish opt) (map polish-un opt-un)))\n pred-exprs (concat\n [#(map? %)]", "\n (map (fn [x] #(contains? % ", "x)) req-keys))\n pred-forms (concat\n [`(fn [~'%] (map? ", "~'%))]\n (map (fn [k] `(fn [~'%] (contains? ", "~'% ~k))) req-keys))\n keys-pred (fn [x]\n (reduce\n (fn [_ p]\n (clojure.core/or (p x) (reduced false)))\n true\n pred-exprs))]\n\n (s/map-spec-impl\n {:req-un req-un\n :opt-un opt-un\n :pred-exprs pred-exprs\n :keys-pred keys-pred\n :opt-keys opt-keys\n :req-specs req-specs\n :req req\n :req-keys req-keys\n :opt-specs opt-specs\n :pred-forms pred-forms\n :opt opt})))\n\n(defn nilable-spec [pred]\n (let [form (form/resolve-form pred)]\n (s/nilable-impl form pred nil)))\n\n(defn or-spec [v]\n (let [ks (mapv first v)\n preds (mapv second v)\n forms (mapv form/resolve-form preds)]\n (s/or-spec-impl ks forms preds nil)))\n" ]
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[ "Deregulation of Stat5 expression and activation causes mammary tumors in transgenic mice.", "\nMembers of the signal transducers and activators of transcription (Stat) family regulate essential cellular growth and survival functions in normal cells and have also been implicated in tumorigenesis. ", "We have studied the potential role of Stat5 in mammary tumorigenesis by targeting Stat5 variants to the mammary gland of transgenic mice using regulatory sequences of the beta-lactoglobulin gene. ", "Mammary-directed expression of the wild-type Stat5, constitutively activated Stat5 and carboxyl-terminally truncated dominant negative Stat5 forms resulted in mammary tumors with incidence rates of up to 22% and latency periods of 8-12 months. ", "Undifferentiated carcinomas most frequently occurred in mice expressing the carboxyl-terminally truncated Stat5. ", "The more differentiated papillary and micropapillary adenocarcinomas were primarily found in mice overexpressing the native and constitutively active transgenes. ", "Higher levels of translation initiation factor 4E (eIF4E) and cyclin D1 expression but lower levels of activated Stat3 were found in tumors of mice expressing the constitutively active Stat5 when compared to mice expressing the wild-type or truncated forms. ", "A higher expression of the estrogen receptor (ERalpha) was observed in carcinomas compared to other phenotypes. ", "The ability of both forms of Stat5, the transactivating form and the dominant negative form, to participate in oncogenesis indicates that there is more than one mechanism by which Stat5 contributes to this process. ", "The transactivation function of Stat5 is involved in the determination of tumors with a more differentiated phenotype." ]
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[ "Automating the testing of Windows 8 apps\n\nIn the blog post for testing Windows Store apps, we’ve primarily covered what to test your apps for. ", "While you can manually execute the verification areas we’ve discussed in the previous post, it is more efficient to automate some of these verification areas. ", "Automating the verification of your app has many benefits. ", "Automated testing saves time and money that you’d otherwise spend doing manual testing. ", "Once created, automated tests can be run over and over again at minimal cost and are much faster than manual tests. ", "This helps ensure that the quality of your app stays high and the cost stays low with every new release of the app. ", "Automated testing also improves the accuracy of the verification because even the most conscientious tester might make mistakes during tedious manual testing.", "\n\nIn this post, we provide some tips and techniques on automating the testing of Windows 8 apps. ", "Keep in mind that automated testing is a powerful technique and it requires some initial investment to reap the full rewards. ", "The advice and examples in this post are meant to get you started, but you’ll need to build and maintain your own infrastructure on top of them. ", "If you are looking for some lighter weight testing techniques, check out the recent blog on testing apps with Visual Studio.", "\n\nLet’s cover each of these steps in detail and the automation tools/technologies to use for each of them.", "\n\nNote about testing on Windows RT\n\nBefore we dive into the automation topics, we wanted to make a quick note about testing on Windows RT. ", "You can’t build or port x86/64 processes to run on Windows RT. ", "Thus, all the tools and technologies discussed in the rest of this post do not apply for testing on Windows RT. ", "We recommend that you use Visual Studio to test on Windows RT.", "\n\nAutomating the installation of your app\n\nTo test your app, you first need to install it on your test machine. ", "Using Visual Studio to share an app package locally is the recommended approach for creating your app package and installing it on the test machine. ", "In this option Visual Studio creates a folder that contains all the relevant files along with a PowerShell script that installs the appropriate certificate and license, the dependency packages, and the app package itself. ", "You have to package your app manually, but the installation is PowerShell based and can be automated. ", "Here is how the installation goes.", "\n\nStep 1:\n\nEnable PowerShell script execution. ", "For security reasons, the default PowerShell execution policy restricts the execution of PowerShell scripts, so you need to override this policy. ", "This step is manual because it requires user interaction. ", "Luckily, you need to do this one time per machine. ", "Execute this command from an elevated PowerShell window to enable PowerShell script execution.", "\n\nPS C:\\> Set-ExecutionPolicy AllSigned\n\nFigure 1: Enable PowerShell script execution\n\nStep 2:\n\nCopy the app package folder created by Visual Studio to the test machine and execute the Add-AppDevPackage PowerShell script from a PowerShell window. ", "Use this command:\n\nPS C:\\JSGrid1_1.0.0.0_AnyCPU_Debug_Test> .\\Add-AppDevPackage.ps1\n\nFigure 2: Run the Add-AppDevPackage script\n\nStep 3:\n\nAcquire a developer license. ", "This step is manual because it requires user interaction. ", "But you need to do this one time per machine for the validity period of the license. ", "If your test machine already has the developer license, you can skip this step.", "\n\nAccept the UAC prompt, and follow the instructions for acquiring a developer license. ", "The below screenshots illustrate what you will see.", "\n\nThis first screen shot requires that you agree to the licensing terms for installing a developer license. ", "Click I Agree if you do to proceed.", "\n\nFigure 3: Accept the developer license acquisition prompt\n\nIn the Microsoft account dialog box, type your Microsoft account. ", "If you don’t have a Microsoft account, click Sign up to create one.", "\n\nFigure 4: Sign in with Microsoft account credentials\n\nYou receive a confirmation that your developer license has been created and the date that it expires.", "\n\nFigure 5: Developer License acquired successfully\n\nThe next screen shot indicates that you got your developer license and your package successfully installed.", "\n\nIn this code snippet, the call to CoAllowSetForegroundWindow is crucial. ", "Without this call, the app will be launched but will not be brought to the foreground. ", "From experience, this has tripped up a number of people trying to write a launch tool.", "\n\nFinally, a quick note about AppUserModelId. ", "In this approach, the input required to launch your app is the AppUserModelId of your app. ", "The AppUserModelId functions as a unique identifier of your app. ", "To retrieve it, we recommend that you use PowerShell. ", "Here’s a PowerShell script that illustrates how you can retrieve the AppUserModelId for all installed apps on your machine.", "\n\nYou can also use IAppxManifestReader to enumerate the apps in the package and obtain the AppUserModelId using the IAppxManifestApplication::GetAppUserModelId method. ", "But if your primary focus is a single app that you are testing, using the registry is far simpler than writing a tool that reads your app’s manifest.", "\n\nAutomating the core functionality of your app\n\nYour app has now been installed on the test machine and your automation can launch it. ", "The next step involves automating the testing of the core functionality of your app. ", "You can achieve this by a combination of unit testing and automating the app via its user interface using UI automation.", "\n\nUnit testing and UI automation are complementary techniques that when used together can result in a broadly tested, higher quality app. ", "Unit testing allows you to automate the core business logic within your app. ", "UI automated testing allows you to verify your app’s functionality by simulating the usage of its user interface. ", "A combination of these approaches enables you to get broader test coverage of your app.", "\n\nLet’s go over some tools and techniques for each of these approaches.", "\n\nUnit testing\n\nUnit testing is a powerful technique for verifying the core functionality of your app. ", "Visual Studio 2012 supports building unit tests for apps written using C# or C++. ", "For more info on creating and running unit tests from Visual Studio 2012 see Creating and running unit tests. ", "If you are already familiar with other unit testing frameworks, you can also continue to use those to unit test your Windows Store app.", "\n\nUI automation\n\nUnit testing can be useful for testing the inner workings of your app, but it doesn’t exercise the user interface of your app. ", "We recommend UI automation (UIA) for verifying an app’s functionality through its user interface.", "\n\nIn the Windows 8 security model, apps don’t have the privileges required to be a UI automation client. ", "But you can write a desktop app that acts as an automation client with your app as the target. ", "To do this, your desktop automation client app needs to be built with UIAccess permissions as outlined inUI Automation Security Overview.", "\n\nThe Windows SDK includes some tools that serve as good examples of UI automation clients: Inspect.exe and AccEvent.exe. ", "Inspect allows you to inspect the UI automation tree of both kinds of apps. ", "AccEvent listens for UIA events. ", "On a machine that has the Windows SDK installed, these tools are usually under %ProgramFiles(x86)%\\Windows Kits\\8.0\\bin\\<architecture>. ", "Here are both these tools in action.", "\n\nFigure 7: Inspect tool running against the Bing News app\n\nFigure 8: AccEvent tool running against the Bing Sports app\n\nSimilar to the approach used by these tools, you can use UIA to write a desktop client app that automates your app. ", "The Building UI Automation client applications in C++ and C# blog post is a great starting point for learning about how to build a UIA client. ", "This blog post speaks about traditional UI automation, but the same techniques will work for any app.", "\n\nAs mentioned earlier, Unit testing and UI automation are complementary techniques that allow you to automate both the core business logic within your app and its functionality when exercised from the user interface. ", "Use both these techniques to debug your app.", "\n\nAutomating lifecycle state of your app\n\nAs outlined in the managing app lifecycle blog post, an app can transition between various runtime states. ", "From a testing perspective, it is important to verify your app in all these states. ", "Automating the transition into these states is possible using a tool (PLMDebug) that ships with the Debugging Tools for Windows, a ready-to-use command-line tool that you can use to automate the transition of your app between lifecycle states.", "\n\nIf PLMDebug is not sufficient for your needs, you can use the IPackageDebugSettings interface to implement your own tool that can change the lifecycle state of your app. ", "This API is available as part of the Windows SDK, which is installed by default with Visual Studio. ", "The code illustrates how to use the IPackageDebugSettings API to change the lifecycle state of your app to verify that your app works as expected during these state transitions.", "\n\nFinally, a quick note about PackageFullName. ", "All approaches we looked at for managing lifecycle state require the PackageFullName as the input argument by which to identify the app. ", "To retrieve the PackageFullName we recommend that you use the Get-AppxPackage PowerShell cmdlet as the next example demonstrates (output trimmed for readability).", "\n\nConclusion\n\nIn this blog post, we’ve covered a number of tips, tools and techniques for automating the testing of your apps. ", "Automated testing can be a cost effective way to increase the level of verification of your app and ensure that the quality never drops. ", "That said, it is important to remember that manual testing also plays a key role in verification. ", "It provides the human element to the verification of your app. ", "As such, a combination of automated and manual testing will give you a well-rounded approach to testing your app.", "\n\n-- Ashwin Needamangala, Principal Test Lead, Windows\n\nSpecial thanks to Mete Goktepe, J. Kalyana Sundaram, Ben Betz, Will Wei, Chris Edmonds, Craig Campbell and Jake Sabulsky for their help and contributions to this post." ]
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[ "Synopses & Reviews\n\nPublisher Comments\n\nIt was all part of man's greatest adventure--landing men on the Moon and sending a rover to Mars, finally seeing the edge of the universe and the birth of stars, and launching planetary explorers across the solar system to Neptune and beyond.", "\n\nThe ancient dream of breaking gravity's hold and taking to space became a reality only because of the intense cold-war rivalry between the superpowers, with towering geniuses like Wernher von Braun and Sergei Korolyov shelving dreams of space travel and instead developing rockets for ballistic missiles and space spectaculars. ", "Now that Russian archives are open and thousands of formerly top-secret U.S. documents are declassified, an often startling new picture of the space age emerges:\n\nthe frantic effort by the Soviet Union to beat the United States to the Moon was doomed from the beginning by gross inefficiency and by infighting so treacherous that Winston Churchill likened it to \"dogs fighting under a carpet\";\n\nthere was more than science behind the United States' suggestion that satellites be launched during the International Geophysical Year, and in one crucial respect, Sputnik was a godsend to Washington;\n\nthe hundred-odd German V-2s that provided the vital start to the U.S. missile and space programs legally belonged to the Soviet Union and were spirited to the United States in a derring-do operation worthy of a spy thriller;\n\ndespite NASA's claim that it was a civilian agency, it had an intimate relationship with the military at the outset and still does--a distinction the Soviet Union never pretended to make;\n\nconstant efforts to portray astronauts and cosmonauts as \"Boy Scouts\" were often contradicted by reality;\n\nthe Apollo missions to the Moon may have been an unexcelled political triumph and feat of exploration, but they also created a headache for the space agency that lingers to this day.", "\n\nThis New Ocean is based on 175 interviews with Russian and American scientists and engineers; on archival documents, including formerly top-secret National Intelligence Estimates and spy satellite pictures; and on nearly three decades of reporting. ", "The impressive result is this fascinating story--the first comprehensive account--of the space age. ", "Here are the strategists and war planners; engineers and scientists; politicians and industrialists; astronauts and cosmonauts; science fiction writers and journalists; and plain, ordinary, unabashed dreamers who wanted to transcend gravity's shackles for the ultimate ride. ", "The story is written from the perspective of a witness who was present at the beginning and who has seen the conclusion of the first space age and the start of the second.", "\n\nFrom the Hardcover edition.", "\n\nAbout the Author\n\nWilliam E. Burrows has reported on aviation and space for The New York Times, The Washington Post, The Wall Street Journal, and the Richmond Times-Dispatch. ", "He has had articles in The New York Times Magazine, Foreign Affairs, The Sciences, and other publications and is a contributing editor for Air & Space/Smithsonian. ", "He is also the author of seven previous books, including Deep Black, the award-winning classic work on spying from space.", "\n\nMr. Burrows is a professor of journalism at New York University and the founder and director of its graduate" ]
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[ "(intense music)\n- So TRT means testosterone\nreplacement therapy.", "\nAnd we get this question a lot\nbecause in my first podcast,\nand sort of the soft launch of X3,\nI was on Dave Asprey's podcast\nand I talked about how I've\nhad prescription for TRT\nfor 12 years before developing the X3,\nand then was that a help\nor something like that.", "\nWell in the 12 years that I was just using\nregular weights, and not having X3.", "\nMy first year with X3, I\nput on 30 pounds of muscle.", "\nBefore that, the previous 12 years,\nI think I put on five pounds of muscle.", "\nSo did TRT help?", "\nNo, and I'm gonna\nparaphrase what WebMD says.", "\nBut it gives you a natural\nlevel of testosterone.", "\nWebMD goes further in\ndefining the difference\nbetween steroids and TRT,\nis not only higher doses of testosterone,\nbut it's stacked with\nother illegal chemicals,\nwhen somebody does quote steroid cycle\nthat can cause a lot of harm,\nand I certainly don't recommend.", "\nAnd so, of course they're illegal anyways,\nso there's really nothing to worry about.", "\nBut, I also want to point out,\nthere's a body builder who died.", "\nHe was 21 years old, it's really sad.", "\nBut he was one of the top\ncompetitors in the world.", "\nHis name was Dallas McCarver.", "\nAnd so like a natural level\nof testosterone can come\nfrom 150 milligrams of\ninjectable testosterone per week.", "\nNow, I don't know what\nthis guy put in himself,\nbut forget about all the other\ndrugs, just the testosterone.", "\nWhen he died, and of course\nnobody knows when his last shot was,\nso it could have actually\nbeen higher than this.", "\nBut the guy had 57 times\nthe amount of testosterone in his body,\nthat the average person does.", "\nSo that's a huge difference.", "\nSo that's the difference\nbetween a steroid user\nthat we know of, and a\nreplacement type dosage, 57 fold.", "\nNow does everybody take\nwhat that guy took?", "\nI don't know, probably not.", "\nThat seems extreme.", "\nBut again, I don't know.", "\nI don't know a lot of\ncompetitive body builders.", "\nMostly competitive body builders\nthat we've worked with as a company,\nlike the steroid days are in their past,\nand what they did was way less than what\nsome of the pros do now.", "\nAnd the pros we do work with\nthat are continuing to compete,\nthey use far less than that,\nso it's kind of strange\nto see this happen.", "\nBut ultimately, TRT is replacement.", "\nSo it is the same as being natural.", "\nAnd if you got tested, it\nmight show some markers\nthat are put in with\npharmaceutical grade testosterone,\nso that you can see the markers.", "\nBecause some sports don't\nallow TRT, for whatever reason.", "\nProbably because somebody could say,\nthey were on TRT, and they\nwould like do a little bit more,\nor they will try and use that\nas a justification to\ndo some other things,\nand think that the TRT is gonna sort of\ncreate a smoke screen there.", "\nBut that's just my theory.", "\nNow, some people use this as an excuse\nfor why they're not in shape,\nand they're just jealous people online.", "\nSo I urge all those people\nwho think WebMD is wrong,\nthat they should email WebMD,\nand explain that they're\nsmarter than WebMD,\nand that WebMD should\nchange the definition\nto whatever their definition is.", "\nAnd when you do that, please email us.", "\n'Cause we can't wait.", "\n" ]
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[ "Also popular with travelers from the USA\n\nSpecial features\n\nSpa\n\nLa Sante has 12 treatment rooms including rooms for couples. ", "Services include Swedish massages, facials, body wraps, and body scrubs. ", "A variety of treatment therapies are provided, including aromatherapy and reflexology. ", "The spa is equipped with a mud bath, a sauna, a spa tub, and a steam room.", "\n\nThe spa is open daily. ", "Guests under 16 years old are not allowed in the spa.", "\n\nPolicies\n\nSome facilities may have restricted access. ", "Guests can contact the property for details using the contact information on the booking confirmation.", "\n\nGuests under 16 years old are not allowed in the spa.", "\n\nParking height restrictions apply.", "\n\nPlease note that cultural norms and guest policies may differ by country and by property. ", "The policies listed are provided by the property.", "\n\nTransfers via airport shuttle are required and must be arranged at least 72 hours before travel by contacting the property at the number on the booking confirmation.", "\n\nReservations are required for massage services and spa treatments and can be made by contacting the property before arrival at the number on the booking confirmation.", "\n\nMandatory fees\n\nYou’ll be asked to pay the following charges at check in or check out:\n\nA tax is imposed by the city and collected at the property. ", "Exemptions or reductions might apply. ", "For more details, please contact the property using the information on the reservation confirmation received after booking.", "\n\nA tax of MYR 10 per accommodation, per night is imposed by the country of Malaysia and collected at the property. ", "Permanent residents and Malaysian nationals are exempt from the tax. ", "For more details, please contact the property using the information on the reservation confirmation received after booking.", "\n\nOptional extras\n\nRollaway beds are available for MYR 150.0 per night\n\nWe have included all charges provided to us by this property. ", "However, charges can vary, for example, based on length of stay or the unit you book.", "\n\nOverall was excellent but only the food at the cafe in front of the pool needs to improve. ", "The food at the French restaurant n the breakfast at the tea lounge was good.", "\nWill consider to go back if overall are kept the same n will recommend to friends." ]
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[ "Seanna Adcox\n\nAssociated Press\n\nCOLUMBIA – A proposed change in South Carolina’s biology standards for teaching evolution is designed to encourage discussion in the classroom.", "\n\nA six-member panel voted unanimously Tuesday to recommend the compromise to the full state Board of Education and Education Oversight Committee. ", "Approval from both is needed for any change to education standards.", "\n\nThe compromise essentially defines science and says evolution is a scientific theory. ", "It could end months of disagreement between the boards, which meet again next month, in South Carolina’s latest flap over religion and science.", "\n\n“Scientific conclusions are tested by experiment and observation, and evolution, as with any aspect of science, is continually open to and subject to experimental and observational testing,” reads the proposed addition to the evolution standard.", "\n\nOther parts of the standard, which lay out what high school biology students should learn about evolution, weren’t in dispute.", "\n\nOversight committee director Melanie Barton, who helped write the compromise, said it means teachers would need to stay up to date on scientific discoveries and how they relate to evolution, to help students have a deeper understanding of it.", "\n\nSen. Mike Fair, a member of the oversight board, had pushed for language calling for students to question Charles Darwin’s theory of natural selection — to “construct scientific arguments that seem to support and scientific arguments that seem to discredit” it. ", "But the state Board of Education rejected that proposed addition last month.", "\n\nThe compromise, if approved next month, could have little practical effect in the classroom.", "\n\nFair said the language is in line with a nationwide effort to teach students more critical thinking skills.", "\n\n“It doesn’t change anything,” he said before the vote. “", "It enables teachers to get their students more involved in critical thinking on these matters.”", "\n\nRob Dillon, founder of South Carolinians for Science Education, said he doesn’t have a problem with the wording, but rather the placement of the two paragraphs. ", "They would be more appropriate as an overall header for high school standards in biology, chemistry and physics, he said.", "\n\n“I object to evolution being singled out,” said Dillon, a biology professor at the College of Charleston. “", "It attracts controversy to evolution. … ", "It’s no more controversial than photosynthesis.”", "\n\nThe back-and-forth between the two boards over evolution is a repeat of the debate in 2005, the last time science standards were up for periodic review.", "\n\nFair led the charge then for students to “critically analyze” evolution.", "\n\nThe compromise eventually approved in 2006 called for students to “summarize ways that scientists use data from a variety of sources to investigate and critically analyze aspects of evolutionary theory.”", "\n\nExpert panels began the latest review of science standards in January 2012. ", "The high school biology standard for evolution was the only standard not adopted by both boards by mid-February." ]
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[ "Q:\n\nWhat does it mean to be compact in the $w^{*}$-topology?", "\n\nWhat does it mean to be compact in the $w^{*}$-topology?", "\nHow is it related to polytopes unit balls?", "\n\nA:\n\nA set $\\rm K$ is compact in the $\\ast$-weak topology if and only if given any covering of $\\rm K$ by $\\ast$-weak open sets $(\\rm U_i)_{i \\in \\rm I}$, there exists a finite subset $\\rm J \\subset \\rm I$ such that the $(\\rm U_j)_{j \\in \\rm J}$ is a covering of $\\rm K$.\n\n" ]
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[ "Military of the Kingdom of Poland\n\nMilitary of the Kingdom of Poland can refer to:\n Military of the Kingdom of Poland during the Piast and Jagiellon dynasties (10th–16th centuries)\n Military of the Polish-Lithuanian Commonwealth\n Military of the Congress Kingdom of Poland" ]
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[ "2012 CSIO Gijón\n\nThe 2012 CSIO Gijón was the 2012 edition of the Spanish official show jumping horse show, at Las Mestas Sports Complex in Gijón. ", "It was held as CSIO 5*.", "\n\nThis edition of the CSIO Gijón was held between August 29 and September 3.", "\n\nNations Cup\nThe 2012 FEI Nations Cup of Spain was the fifth competition of the 2012 FEI Nations Cup Promotional League and was held on Saturday, September 1, 2012.", "\n\nThe competition was a show jumping competition with two rounds. ", "The height of the fences were up to 1.60 meters. ", "The best six teams of the eleven which participated were allowed to start in the second round. ", "As participant in the Promotional League, Denmark was also allowed to participate in the second round.", "\n\nThe competition was endowed with €64,000.", "\n\nGrey penalties points do not count for the team result.", "\n\nGijón Grand Prix\nThe Gijón Grand Prix, the Show jumping Grand Prix of the 2012 CSIO Gijón, was the major show jumping competition at this event. ", "It was held on Monday 2 August 2013. ", "The competition was a show jumping competition over two rounds, the height of the fences were up to 1.60 meters.", "\n\nIt was endowed with 125,000 €.", "\n\n(Top 10 of 45 Competitors)\n\nReferences\n\nExternal links\nOfficial website\nAll results of CSIO Gijón 2012\n\nCategory:CSIO Gijón\nCategory:2012 in show jumping\nCategory:2012 FEI Nations Cup" ]
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[ "Q:\n\nTransclude ignoring template text\n\nCan anyone tell me why in the example below the text \"Say Hello\" is not being included in the transclusion? ", "So you can see the button and the \"Goodbye\" link but not the text from the template.", "\nMany thanks\n<greeting ng-transclude>\n <a href=\"\">Goodbye</a>\n </greeting>\n\n <script>\n angular.module('myApp', []).directive('greeting', function() {\n return {\n restrict: 'E',\n replace: true,\n transclude : true,\n template: \"<button class='btn'>Say Hello</button>\"\n };\n });\n </script>\n\nFiddle here:)\n\nA:\n\ntemplate: \"<button class='btn'>Say Hello</button>\"\n\nShould be:\ntemplate: \"<button class='btn' ng-transclude>Say Hello</button>\"\n\nIt's mean's use inner of ng-transclude prop's code instead of the original.", "\n\n" ]
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[ "“Hellboy in Hell” has ended, “Abe Sapien” has ended, and “B.P.R.D. Hell on Earth” ends next month. ", "You could be forgiven for thinking the Hellboy Universe is shutting up shop, but that’s simply not the case. ", "There are a great many more irons in the fire, and this week Dark Horse is announcing a few of them. ", "Today’s announcement is an upcoming trade collection…\n\nCOMING IN 2017\n\nAbe Sapien – Volume 9: Lost Lives and Other Stories\n\nCover by Sebastián Fiumara\n\nCollecting:\n\n• “The Land of the Dead” (from “Abe Sapien” #8)\n\nWritten by Scott Allie and Mike Mignola\n\nArt by Michael Avon Oeming\n\nColors by Dave Stewart\n\nLettering by Clem Robins\n\n• “Witchcraft & Demonology” (from “Abe Sapien” #30)\n\nWritten by Scott Allie and Mike Mignola\n\nArt by Santiago Caruso\n\nLettering by Clem Robins\n\n• “The Ogopogo” (from “Abe Sapien” #23)\n\nWritten by Scott Allie and Mike Mignola\n\nArt and lettering by Kevin Nowlan\n\n• “Subconscious” (from “Dark Horse Presents – Volume 3” #11)\n\nWritten by John Arcudi\n\nArt by Mark Nelson\n\nLettering by Clem Robins\n\n• “Lost Lives” (from “Abe Sapien” #15)\n\nWritten by Scott Allie and Mike Mignola\n\nArt by Juan Ferreyra\n\nColor assistance by Eduardo Ferreyra\n\nLettering by Clem Robins\n\n• “Icthyo Sapien” (from “Abe Sapien” #27)\n\nWritten by Scott Allie and Mike Mignola\n\nArt by Alise Gluškova\n\nLettering by Clem Robins\n\nFor a full recap of this week’s surge of announcements, check ’em out here." ]
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[ "KHOJ (AM)\n\nKHOJ is a radio station broadcasting out of St. Charles, Missouri with a Catholic format. ", "It broadcasts on AM frequency 1460 kHz and is part of the Covenant Network.", "\n\nKHOJ's studios are located on Hampton Avenue in St. Louis, while its transmitter is located north of St. Charles.", "\n\nHistory\nKIRL went on the air in 1968, the successor to KADY, which had previously operated on the frequency from 1958 to 1965 (and built the transmitter site used by KHOJ today). ", "It was owned by Contemporary Media, Inc. In 1979, Contemporary Media sold KIRL to the Bronco Broadcasting Company. ", "Bronco relaunched KIRL as a gospel music station for the African American community. ", "Zella Jackson Price and other pioneering announcers were on its air staff.", "\n\nIn 2005, Bronco sold KIRL to the Covenant Network for $730,000. ", "The sale marked the end of KIRL's gospel programming as of April 30 and scattered many of the religious programs it carried. ", "Covenant immediately relaunched the station as KHOJ with its programming.", "\n\nReferences\n\nExternal links\n\n The Covenant Network\n WRYT / KHOJ Programming Schedule\n \n \n \n \n FCC History Cards for KHOJ\n\nHOJ (AM)\nCategory:Catholic radio stations" ]
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[ " FILED\n United States Court of Appeals\n Tenth Circuit\n\n December 9, 2013\n PUBLISH Elisabeth A. Shumaker\n Clerk of Court\n UNITED STATES COURT OF APPEALS\n\n TENTH CIRCUIT\n\n\n\nIn re: ELOISA MARIA TAYLOR,\n\n Debtor.", "\n__________________________\n\nMATTHEW E. TAYLOR,\n Nos. ", "12-2163 & 12-2164\n Cross - Appellant/\n Appellee.", "\n\nv.\nELOISA MARIA TAYLOR,\n\n Cross - Appellee/\n Appellant.", "\n\n\n\n\n APPEAL FROM THE UNITED STATES BANKRUPTCY COURT\n FOR THE DISTRICT OF NEW MEXICO AND\n THE BANKRUPTCY APPELLATE PANEL OF THE TENTH CIRCUIT\n (Bankr. ", "C. No. ", "1:10-bk-15832-j7; BAP No. ", "11-103; Adv. ", "No. ", "11-BK-01020-J)\n\n\nKarl F. Kalm, of Kalm Law Firm, P.C., Albuquerque, New Mexico, for Eloisa\nMaria Taylor, Appellant.", "\n\nBonnie B. Gandarilla, (George M. Moore with her on the briefs), of Moore,\nBerkson, & Gandarilla, P.C., Albuquerque, New Mexico, for Matthew E. Taylor,\nAppellee.", "\n\fBefore BRISCOE, Chief Judge, SEYMOUR and LUCERO, Circuit Judges.", "\n\n\nBRISCOE, Chief Judge.", "\n\n\n\n Eloisa Taylor appeals from a decision of the Bankruptcy Appellate Panel of\n\nthe Tenth Circuit (“BAP”) affirming a decision of the United States Bankruptcy\n\nCourt for the District of New Mexico. ", "The bankruptcy court granted summary\n\njudgment in favor of Eloisa’s former spouse, Matthew Taylor. ", "The bankruptcy\n\ncourt determined that a $50,660.59 debt Eloisa owed to Matthew for overpayment\n\nof spousal support was nondischargeable because Eloisa incurred the debt “in\n\nconnection with a separation agreement” under 11 U.S.C. § 523(a)(15).", "\n\nMatthew’s assertion that the debt was nondischargeable under 11 U.S.C. §\n\n523(a)(5) as a “domestic support obligation” was previously dismissed by the\n\nbankruptcy court for failure to state a claim. ", "Matthew has filed a cross appeal\n\nfrom that ruling and from the BAP’s ruling that neither it, nor the bankruptcy\n\ncourt, had authority under the parties’ divorce settlement agreement to award\n\nMatthew attorney fees that he incurred during the bankruptcy proceeding.", "\n\nExercising jurisdiction under 28 U.S.C. § 158(d), we affirm the bankruptcy\n\ncourt’s ruling that the debt is nondischargeable under § 523(a)(15). ", "As regards\n\nMatthew’s cross appeal, we affirm both the bankruptcy court’s ruling that the\n\ndebt was not excepted from discharge under § 523(a)(5), and the BAP’s denial of\n\n 2\n\fMatthew’s request for attorney fees.", "\n\n I\n\n In 1988, Eloisa and Matthew Taylor were married in Albuquerque, New\n\nMexico. ", "In 2005, they divorced and entered into a Marital Settlement Agreement\n\n(“MSA”). ", "A circuit court in Fairfax County, Virginia entered a final decree of\n\ndivorce on September 22, 2005, which incorporated the MSA. ", "As part of the final\n\ndecree, the Virginia circuit court ordered Matthew to pay $2,500 per month to\n\nEloisa as spousal support, said payments to begin on August 1, 2005, and to\n\ncontinue until “the death of either party, or the remarriage of [Eloisa], or after”\n\nten years of payments, “whichever event first . . . ", "occurred.” ", "Aplt. ", "App. ", "at 43.", "\n\nThe final decree also stated that the spousal support obligation was governed by\n\nVa. Code § 20-109, and that the Virginia circuit court retained jurisdiction to\n\nenter orders to implement the Taylors’ agreement.", "\n\n On April 21, 2009, Matthew moved to terminate spousal support in the\n\nVirginia circuit court, arguing that Eloisa had been living with a man for the past\n\ntwo years and that the two were in a marriage-like relationship. ", "Matthew claimed\n\nthat Eloisa’s cohabitation should result in the termination of his spousal support\n\nobligation under the divorce decree pursuant to Va. Code § 20-109. ", "1 On October\n\n 1\n The pertinent part of that statute states:\n\n Upon order of the court based upon clear and convincing evidence\n that the spouse receiving support has been habitually cohabiting with\n (continued...)\n\n 3\n\f4, 2010, after conducting a trial on the matter, the Virginia circuit court agreed\n\nwith Matthew and retroactively terminated his spousal support obligation.", "\n\nSpecifically, the Virginia circuit court ordered Eloisa to repay $40,660.59 in\n\noverpaid spousal support payments, plus $10,000.00 for Matthew’s attorney fees\n\nincurred in prosecuting the motion for termination. ", "Accordingly, the Virginia\n\ncircuit court entered a judgment against Eloisa for $50,660.59.", "\n\n On November 22, 2010, Eloisa filed for bankruptcy under Chapter 7 of the\n\nBankruptcy Code in the United States Bankruptcy Court for the District of New\n\nMexico. ", "On January 26, 2011, Matthew filed a complaint objecting to the\n\ndischargeability of the $50,660.59 judgment, and initiated an adversary\n\nproceeding. ", "Fed. ", "Bankr. ", "R. 7001(6). ", "In his complaint, Matthew alleged that the\n\noverpayment debt was not dischargeable and he cited as support three different\n\nBankruptcy Code provisions. ", "First, he argued that the overpayment debt\n\nconstituted a debt to a former spouse incurred by the debtor “in connection with a\n\nseparation agreement” under 11 U.S.C. § 523(a)(15). ", "Second, Matthew argued\n\nthat the overpayment debt constituted a “domestic support obligation” under 11\n\nU.S.C. § 523(a)(5). ", "Finally, he argued that Eloisa knew that she was not entitled\n\n\n 1\n (...continued)\n another person in a relationship analogous to a marriage for one year\n or more commencing on or after July 1, 1997, the court shall\n terminate spousal support and maintenance . . . .", "\n\nVa. Code § 20-109(A).", "\n\n 4\n\fto spousal support under Va. Code § 20-109, and that her acceptance of such\n\nsupport constituted fraud under 11 U.S.C. § 523(a)(2)(A). ", "2 Eloisa moved to\n\ndismiss Matthew’s complaint. ", "The bankruptcy court granted in part Eloisa’s\n\nmotion by rejecting Matthew’s reliance on § 523(a)(5) and § 523(a)(2)(A).", "\n\nHowever, the bankruptcy court denied Eloisa’s motion to dismiss as regards\n\nMatthew’s claim that § 523(a)(15) applied to the overpayment debt and was\n\ntherefore nondischargeable.", "\n\n Thereafter, both Matthew and Eloisa filed motions for summary judgment\n\nregarding the applicability of § 523(a)(15) to the dischargeability issue.", "\n\nMatthew’s motion also sought an award of attorney fees incurred during the\n\nadversary proceeding pursuant to the parties’ MSA. ", "After deciding that the\n\noverpayment debt fell within the plain language of § 523(a)(15), the bankruptcy\n\ncourt noted that the legislative history likewise supported a conclusion that the\n\noverpayment debt was nondischargeable. ", "Accordingly, the bankruptcy court\n\ngranted Matthew’s motion for summary judgment and denied Eloisa’s motion for\n\nsummary judgment. ", "The bankruptcy court did not address Matthew’s claim that\n\nhe was entitled to attorney fees incurred while pursuing the bankruptcy adversary\n\ncomplaint.", "\n\n Both parties appealed to the BAP. ", "The BAP affirmed the bankruptcy\n\n 2\n 11 U.S.C. § 523(a)(2)(A) states that debts obtained by “false pretenses, a\nfalse representation, or actual fraud, other than a statement respecting the debtor’s\nor an insider’s financial condition” are nondischargeable.", "\n\n 5\n\fcourt’s ruling that the overpayment debt was not a “domestic support obligation”\n\nunder § 523(a)(5), as well as the bankruptcy court’s ruling that the overpayment\n\ndebt did qualify for an exception from discharge under § 523(a)(15). ", "Finally, the\n\nBAP ruled that neither it nor the bankruptcy court had authority to award attorney\n\nfees under the MSA’s fee-shifting agreement. ", "Eloisa appeals the bankruptcy\n\ncourt’s summary judgment ruling that the overpayment debt is nondischargeable\n\nunder § 523(a)(15); Matthew cross-appeals the bankruptcy court’s dismissal of his\n\n§ 523(a)(5) claim and the BAP’s ruling on attorney fees.", "\n\n II\n\n “Although this appeal is from a decision by the BAP, we review only the\n\nBankruptcy Court’s decision.” ", "Miller v. Deutsche Bank Nat’l Trust Co. (In re\n\nMiller), 666 F.3d 1255, 1260 (10th Cir. ", "2012) (quotation omitted). “", "We review\n\nmatters of law de novo, and we review factual findings made by the bankruptcy\n\ncourt for clear error.” ", "Id. (quotation omitted). ", "In so doing, we “treat[] the BAP\n\nas a subordinate appellate tribunal whose rulings may be persuasive.” ", "Cohen v.\n\nBorgman (In re Borgman), 698 F.3d 1255, 1259 (10th Cir. ", "2012).", "\n\n Ordinarily, “[w]hether an obligation to a former spouse is actually in the\n\nnature of support is a factual question subject to a clearly erroneous standard of\n\nreview.” ", "Sampson v. Sampson (In re Sampson), 997 F.2d 717, 721 (10th Cir.", "\n\n1993). ", "Because the parties argue that the bankruptcy court erred in its\n\ninterpretation of the Bankruptcy Code, however, we review those legal rulings de\n\n 6\n\fnovo. ", "See Search Mkt. ", "Direct, Inc. v. Jubber (In re Paige), 685 F.3d 1160, 1178\n\n(10th Cir. ", "2012) (“When a lower court’s factual findings are premised on\n\nimproper legal standards or on proper ones improperly applied, they are not\n\nentitled to the protection of the clearly erroneous standard, but are subject to de\n\nnovo review.” (", "alteration and quotation omitted)).", "\n\n III\n\n One of the principal purposes of the Bankruptcy Code is to grant insolvent\n\ndebtors a “fresh start.” ", "Grogan v. Garner, 498 U.S. 279, 286-87 (1991).", "\n\nHowever, by providing limited exceptions to discharge, the Bankruptcy Code\n\nrecognizes that certain interests outweigh the “fresh start” for the debtor. ", "Id.\n\nTwo provisions of the Bankruptcy Code except from discharge debts arising out\n\nof obligations to the family: § 523(a)(5) excepts from discharge any “domestic\n\nsupport obligation,” as defined in the Bankruptcy Code; and § 523(a)(15) excepts\n\nfrom discharge obligations arising in connection with a divorce proceeding or\n\nsettlement agreement. ", "11 U.S.C. § 523(a)(5), (15). “", "These provisions reflect the\n\ncongressional preference for the rights of spouses to alimony, maintenance or\n\nsupport over the rights of debtors to a ‘fresh start’ free of debts.” ", "See Gianakas v.\n\nGianakas (In re Gianakas), 917 F.2d 759, 761 (3d Cir. ", "1990); see also Miller v.\n\nGentry (In re Miller), 55 F.3d 1487, 1489 (10th Cir. ", "1995) (“The policy\n\nunderlying § 523(a)(5), however, favors enforcement of familial support\n\nobligations over a ‘fresh start’ for the debtor.”). ", "Because § 523(a)(15) will apply\n\n 7\n\fto a debt only if that debt does not qualify as a “domestic support obligation”\n\nunder § 523(a)(5), we first address whether the overpayment debt at issue\n\nqualifies as a “domestic support obligation.” ", "3\n\n A. Section 523(a)(5)\n\n i) § 523(a)(5) Background\n\n Before Congress amended the Bankruptcy Code in 2005, § 523(a)(5) stated\n\nthat a bankruptcy court may deny a debtor discharge for a debt owed\n\n to a spouse, former spouse, or child of the debtor, for alimony\n to, maintenance for, or support of such spouse or child, in connection\n with a separation agreement, divorce decree or other order of a court\n of record, determination made in accordance with State or territorial\n law by a governmental unit, or property settlement agreement, but\n not the extent that—\n (A) such debt is assigned to another entity,\n voluntarily, by operation of law, or otherwise (other than\n debts assigned pursuant to section 408(a)(3) of the\n Social Security Act, or any such debt which has been\n assigned to the Federal Government or to a State or any\n political subdivision of such State); or\n (B) such debt includes a liability designated as\n alimony, maintenance, or support, unless such liability is\n\n 3\n Notably, some courts have determined that a debt that would be excepted\nfrom discharge under § 523(a)(15) essentially moots the necessity of determining\nwhether the debt is a “domestic support obligation” under § 523(a)(5). ", "See, e.g.,\nBerse v. Langman (In re Langman), 465 B.R. 395, 405 (Bankr. ", "D. N.J. 2012) (“As\na practical consequence, it is now no longer necessary for bankruptcy courts to\ndetermine the exact extent to which a state court matrimonial judgment\nconstitutes a ‘domestic support obligation’ if the plaintiff can demonstrate that the\njudgment would be nondischargeable in any event under § 523(a)(15).”). ", "While\nwe agree with the practical consequences of this conclusion (i.e., the debt will be\nnondischargeable either way), we nevertheless address whether the overpayment\ndebt qualifies as a “domestic support obligation” because § 523(a)(15)’s plain\nlanguage requires that the debt not be a “domestic support obligation.”", "\n\n 8\n\f actually in the nature of alimony, maintenance, or\n support.", "\n\n11 U.S.C. § 523(a)(5) (2000) (emphasis added).", "\n\n Effective October 17, 2005, the Bankruptcy Abuse Prevention and\n\nConsumer Protection Act (“BAPCPA”) amended § 523(a)(5) to delete the\n\nsubsection’s previous verbiage and to simply state that a bankruptcy court may\n\ndeny a debtor discharge “for a domestic support obligation.” ", "Bankruptcy Abuse\n\nPrevention and Consumer Protection Act of 2005, Pub. ", "L. No. ", "109-8, 119 Stat.", "\n\n23. ", "The BAPCPA defined “domestic support obligation” as a debt\n\n (A) owed to or recoverable by--\n (i) a spouse, former spouse, or child of the\n debtor or such child’s parent, legal\n guardian, or responsible relative; or\n (ii) a governmental unit;\n (B) in the nature of alimony, maintenance, or support\n (including assistance provided by a governmental unit)\n of such spouse, former spouse, or child of the debtor or\n such child’s parent, without regard to whether such debt\n is expressly so designated;\n (C) established or subject to establishment before, on, or\n after the date of the order for relief in a case under this\n title, by reason of applicable provisions of--\n (i) a separation agreement, divorce decree,\n or property settlement agreement;\n (ii) an order of a court of record; or\n (iii) a determination made in accordance\n with applicable nonbankruptcy law by a\n governmental unit; and\n (D) not assigned to a nongovernmental entity, unless\n that obligation is assigned voluntarily by the spouse,\n former spouse, child of the debtor, or such child’s\n parent, legal guardian, or responsible relative for the\n purpose of collecting the debt.", "\n\n 9\n\f11 U.S.C. § 101(14A) (emphases added). ", "This new definition “give[s] section\n\n523(a)(5) a broader scope than the former terms” in the following ways: the\n\ndefinition now explicitly includes support obligations that accrue post-petition;\n\nthe order, agreement, or determination creating the obligation can now be either\n\npre- or post-petition; and, as pertinent here, the definition now expressly includes\n\n“assistance provided by a governmental unit.” ", "See William Houston Brown,\n\nBankruptcy and Domestic Relations Manual, § 6.1 (2012). ", "This definition affects\n\nprovisions throughout the Bankruptcy Code, including discharge of debt, the\n\nautomatic stay, priorities, and exemptions. ", "See, e.g., 11 U.S.C. § 507(a)(1)\n\n(giving domestic support obligations first priority up from seventh priority under\n\nthe pre-BAPCPA Bankruptcy Code).", "\n\n When determining whether an obligation is in the nature of alimony,\n\nmaintenance, or support, this court conducts a “dual inquiry” looking first to the\n\nintent of the parties at the time they entered into their agreement, and then to the\n\nsubstance of the obligation. ", "See Sampson, 997 F.2d at 723; Sylvester v.\n\nSylvester, 865 F.2d 1164, 1165 (10th Cir. ", "1989). ", "4 The nature of the obligation is\n\n 4\n While these cases were decided before the 2005 BAPCPA amendments,\ncourts continue to apply pre-BAPCPA case law to determine whether an\nobligation is in the nature of support. ", "See DeHart v. Miller (In re Miller), 424\nB.R. 171, 175 n.6 (Bankr. ", "M.D. Penn. ", "2010). ", "Here, the bankruptcy court\nconcluded that\n\n [a]lthough the Bankruptcy Abuse Prevention and Consumer\n Protection Act of 2005 (“BAPCPA”) changed the language in 11\n (continued...)\n\n 10\n\fnot restricted to the parties’ label in the settlement agreement and is a question of\n\nfederal law. ", "Sylvester, 865 F.2d at 1166; see Young v. Young (In re Young), 35\n\nF.3d 499, 500 (10th Cir. ", "1994) (finding that shared intent “is not limited to the\n\nwords of the settlement agreement, even if unambiguous” and stating that “the\n\nbankruptcy court is required to look behind the words and labels of the agreement\n\nin resolving this issue.”). ", "That said, state law may inform the nature of the\n\ninterest. ", "As “[t]he party seeking to hold the debt nondischargeable,” Matthew\n\nbore the burden of establishing by a preponderance of the evidence that the\n\nparties intended the debt to be in the nature of support and that the obligation was\n\n\n 4\n (...continued)\n U.S.C. § 523(a)(5) to apply to “domestic support obligations” as\n defined in 11 U.S.C. § 101(14A), this change “did not change the\n standard for whether an obligation is in the nature of support.”", "\n Consequently, it is appropriate to continue to apply the same test for\n determining whether a debt is in the nature of support that was\n applicable under 11 U.S.C. § 523(a)(5) prior to the enactment of\n BAPCPA.", "\n\nAplt. ", "App. ", "at 84-85 (citation omitted). ", "Neither party takes issue with the\nbankruptcy court’s application of pre-BAPCPA case law. ", "We agree that the pre-\nBAPCPA case law continues to have relevance post-BAPCPA because both\nversions of the statute require a determination that the debt be in the nature of\nsupport. ", "See Wis. Dep’t of Workforce Dev. ", "v. Ratliff, 390 B.R. 607, 612 (E.D.\nWis. 2008) (“‘[D]omestic support obligation’ is a term derived from the definition\nof a nondischargeable debt for alimony, maintenance, and support contained in\nthe former Section 523(a)(5); therefore, case law construing the former Section\n523(a)(5) is relevant and persuasive.” (", "quotation omitted)). ", "Pre-BAPCPA\n§ 523(a)(5) explicitly required the debt to be “actually in the nature of alimony,\nmaintenance, or support.” ", "Post-BAPCPA § 101(14A) requires the debt to be “in\nthe nature of alimony, maintenance, or support,” without consideration of the\nparties’ label.", "\n\n 11\n\fin substance support. ", "Sampson, 997 F.2d at 723.", "\n\n ii) Bankruptcy Court’s and BAP’s rulings\n\n The bankruptcy court determined that Matthew’s complaint failed to allege\n\nany facts that supported a conclusion that the debt was actually in the nature of\n\nsupport as to him, and the BAP agreed. ", "The bankruptcy court concluded that\n\n§ 523(a)(5) required that it analyze whether the obligation was “in substance[] in\n\nthe nature of support for the creditor-spouse entitled to reimbursement, taking\n\ninto account the relative financial circumstances of the parties at the time of the\n\ndivorce.” ", "Aplt. ", "App. ", "at 86, 88 (finding that Matthew could not “solely rely on the\n\noriginal character of the debt owed by him to his former spouse to state a claim\n\nthat a debt owed to him by his former spouse for overpayment of spousal support\n\nis non-dischargeable”).", "\n\n The BAP agreed that the debt was not in the nature of support. ", "The BAP,\n\nhowever, concluded that the debt arose at the time the state court entered the\n\noverpayment judgment. ", "5 Aplt. ", "App. ", "at 114 (rejecting Matthew’s assertion that he\n\nalleged sufficient facts because such facts only supported a conclusion that Eloisa\n\nno longer needed support, not that the debt was in the nature of support for\n\n 5\n This difference between the bankruptcy court’s and BAP’s analysis of the\nactual nature of the debt does not affect the outcome here. ", "Because Matthew\nfailed to allege any facts to establish that the debt arose from support owed to\nhim, when the court should evaluate the nature of the debt is immaterial (i.e., at\nthe time of the divorce, as the bankruptcy court concluded; or at the time the debt\nin question arose, when the state court retroactively terminated spousal support\nand entered judgment against Eloisa, as the BAP ruled).", "\n\n 12\n\fMatthew). ", "Accordingly, the BAP affirmed the bankruptcy court’s dismissal of\n\nMatthew’s § 523(a)(5) claim.", "\n\n iii) Matthew’s argument on cross appeal\n\n The crux of Matthew’s argument in his cross appeal of the bankruptcy\n\ncourt’s dismissal of his § 523(a)(5) claim is that the BAPCPA’s inclusion of\n\n“governmental units” in the definition of “domestic support obligation” in\n\n§ 101(14A) precludes an analysis of “the nature of the debt at the time it arose.”", "\n\nAplee. ", "Br. ", "at 5. ", "Specifically, he argues that this newly defined term precludes a\n\nbankruptcy court from evaluating the nature of the debt “with respect to the party\n\nclaiming that the debt is non-dischargeable.” ", "Id. at 6. ", "Otherwise, Matthew\n\nargues, the bankruptcy court would be ignoring the inclusion of governmental\n\nunits in the definition of “domestic support obligation.” ", "He urges that because a\n\ndebt owed to a governmental unit will never be in the nature of support,\n\n§ 101(14A)’s inclusion of governmental units signals that the original nature of\n\nthe debt remains constant for purposes of the Bankruptcy Code regardless of\n\nwhether the creditor is a spouse or governmental unit. ", "Section 523(a)(5) provides\n\nlittle guidance on this issue because that exception applies to all “domestic\n\nsupport obligation[s].” ", "Accordingly, we look first to the plain language of\n\n§ 101(14A), which defines “domestic support obligation.”", "\n\n iv) Plain language of § 101(14A)\n\n “Our primary task in construing statutes is to determine congressional\n\n 13\n\fintent, using traditional tools of statutory interpretation.” ", "See N.M. Cattle\n\nGrowers Ass’n v. U.S. Fish & Wildlife Serv., ", "248 F.3d 1277, 1281 (10th Cir.", "\n\n2001). ", "Supreme Court “precedents make clear that the starting point for [the]\n\nanalysis is the statutory text. ", "And where, as here, the words of the statute are\n\nunambiguous, the judicial inquiry is complete.” ", "Desert Palace, Inc. v. Costa, 539\n\nU.S. 90, 98 (2003) (citation and quotation omitted); see also Park ‘N Fly, Inc. v.\n\nDollar Park & Fly, Inc., 469 U.S. 189, 194 (1985) (“Statutory construction must\n\nbegin with the language employed by Congress and the assumption that the\n\nordinary meaning of that language accurately expresses the legislative purpose.”).", "\n\n Section 101(14A)(A) defines a debt as a “domestic support obligation”\n\nwhen four requirements are satisfied. ", "First, the debt must be owed to either “a\n\nspouse, former spouse, or child of the debtor,” 6 which is listed under subpart (i),\n\nor “a governmental unit,” which is listed under subpart (ii). ", "Id. § 101(14A)(A)(i),\n\n(ii). ", "Second, § 101(14A)(B) next requires that the “nature” of the debt be\n\n“alimony, maintenance, or support (including assistance provided by a\n\ngovernmental unit) of such spouse, former spouse, or child of the debtor . . .", "\n\nwithout regard to whether such debt is expressly so designated.” ", "Id.\n\n§ 101(14A)(B). ", "Third, the debt must arise from a separation agreement, divorce\n\ndecree, or property settlement agreement. ", "Id. § 101(14A)(C). ", "Finally, the debt\n\n\n 6\n For simplicity’s sake, the parties listed in § 101(14A)(A)(i) will be\nreferred to as “spouse.”", "\n\n 14\n\fmust not have been assigned to a nongovernmental entity, unless for collection\n\npurposes. ", "Id. § 101(14A)(D). ", "The only requirement at issue in this appeal is\n\nwhether the debt meets the second requirement that it be in the nature of support.", "\n\n Under the plain language of the statute, the debt must be “in the nature of\n\nalimony, maintenance, or support (including assistance provided by a\n\ngovernmental unit) of such spouse.” ", "Because “such” is not defined in the\n\nBankruptcy Code, we turn to the ordinary meaning of the term. ", "See Hamilton v.\n\nLanning, 130 S. Ct. ", "2464, 2471 (2010). “", "Such” means “previously characterized\n\nor specified: aforementioned.” ", "Webster’s Third New International Dictionary\n\n2283 (1993). ", "When read in context, “such spouse” in § 101(14A)(B) refers to “a\n\nspouse” in § 101(14A)(A)(i). ", "Accordingly, when read together, the modifier\n\n“such” limits the determination of the nature of the debt with respect to the\n\ncreditor-spouse referenced in § 101(14A)(A)(i). ", "See Ransom v. FIA Card Servs.,", "\n\nN.A., 131 S. Ct. ", "716, 724 (2011) (interpreting the Bankruptcy Code and noting\n\nthat “[w]e must give effect to every word of a statute wherever possible”\n\n(quotation omitted)). ", "Therefore, pursuant to the plain language defining\n\n“domestic support obligation,” the debt must be in the nature of support to the\n\ncreditor-spouse – or in this case, the debt must be in the nature of support for\n\nMatthew.", "\n\n Matthew argues that the plain language of the statute requires some\n\nanalysis, but not that the statutory language is ambiguous. ", "Aplee. ", "Br. ", "at 15\n\n 15\n\f(stating that his analysis is the “only approach that makes sense of Congress’[s]\n\naddition of ‘a governmental unit’ to the class of entities who may be owed debts\n\nin the nature of support”). ", "We agree with Matthew’s contention that the nature of\n\nthe debt owed to a governmental unit will not be “in the nature of support” to that\n\ngovernmental unit—in such circumstances the statutory language supports a\n\nconclusion that the debt retains its original supportive nature. ", "But the same\n\nconclusion does not arise regarding debts owed to spouses pursuant to the plain\n\nlanguage of § 523(a)(5). ", "7 Accordingly, Matthew’s proffered interpretation of §\n\n101(14A) goes against the plain language of the Bankruptcy Code. ", "See In re\n\nMiller, 55 F.3d at 1489 (“[W]ith regard to the Bankruptcy Code, . . . ", "where the\n\nstatutory language is clear, [the courts’] sole function . . . ", "is to enforce it\n\naccording to its terms.”). ", "Because Matthew alleged no facts to support his\n\ncontention that the nature of the overpayment debt was actually for his support,\n\nthe bankruptcy court did not err by dismissing his § 523(a)(5) claim. ", "Because the\n\noverpayment debt here does not qualify as “domestic support obligation,” we\n\nmust now determine whether that debt is nevertheless excepted from discharge\n\nunder § 523(a)(15).", "\n\n\n 7\n Furthermore, we note that the Ratliff court gave effect to §§ 101(14A)(A)\nand (B) when it held that an obligation to repay the state for food stamp\noverpayments was a “domestic support obligation.” ", "390 B.R. at 617. ", "Under the\ncourt’s reading, the debt was owed to a governmental unit (satisfying subpart\n(A)), and the debt was in the nature of support of a “child of the debtor”\n(satisfying subpart (B)). ", "Id. at 616-17.", "\n\n 16\n\f B. Section 523(a)(15)\n\n In 1994, Congress amended the bankruptcy law by adding § 523(a)(15),\n\nwhich permitted a bankruptcy court to deny a debtor discharge for debts\n\n not of the kind described in paragraph (5) that [are] incurred by the\n debtor in the course of a divorce or separation or in connection with\n a separation agreement, divorce decree or other order of a court of\n record, a determination made in accordance with State or territorial\n law by a governmental unit unless—\n (A) the debtor does not have the ability to pay such debt\n from income or property of the debtor not reasonably\n necessary to be expended for the maintenance or support\n of the debtor or a dependent of the debtor and, if the\n debtor is engaged in a business, for the payment of\n expenditures necessary for the continuation,\n preservation, and operation of such business; or\n (B) discharging such debt would result in a benefit to\n the debtor that outweighs the detrimental consequences\n to a spouse, former spouse, or child of the debtor[.]", "\n\nBankruptcy Reform Act of 1994, Pub. ", "L. No. ", "103-394, § 304(e).", "\n\n In 2005, Congress again amended this section by removing the two\n\n“defenses” to § 523(a)(15) dischargeability (subparts (A) and (B)), so that a\n\nbankruptcy court may deny a debtor a discharge for\n\n [debts] to a spouse, former spouse, or child of the debtor and not of\n the kind described in paragraph (5) that [are] incurred by the debtor\n in the course of a divorce or separation or in connection with a\n separation agreement, divorce decree or other order of a court of\n record, or a determination made in accordance with State or\n territorial law by a governmental unit.", "\n\n11 U.S.C. § 523(a)(15).", "\n\n For reasons previously discussed, the overpayment debt here does not\n\n\n 17\n\fqualify as a “domestic support obligation” under § 523(a)(5). ", "Additionally, the\n\nparties do not dispute that the overpayment debt is a debt owed to a former\n\nspouse, Matthew. ", "Accordingly, the only disputed portion of § 523(a)(15)’s\n\napplication to the overpayment judgment is whether that debt was “incurred by\n\nthe debtor in the course of a divorce . . . ", "or in connection with a separation\n\nagreement, divorce decree or other order of a court of record.” ", "Id. Eloisa does\n\nnot dispute that the overpayment debt satisfies the plain language of the statute\n\nthat the debt was incurred in the course of or in connection with a divorce; rather,\n\nshe makes a broad argument that such a “literal application” of this provision is\n\ncontrary to the intentions of the Bankruptcy Code drafters.", "\n\n i) Plain Statutory Language\n\n “[I]f an act is unambiguous, that ends the matter and resort should not be\n\nhad to the statutory history.” ", "Wyodak Res. ", "Dev. ", "Corp. v. United States, 637 F.3d\n\n1127, 1135 (10th Cir. ", "2011). ", "Pursuant to § 523(a)(15)’s plain and unambiguous\n\nlanguage, the overpayment debt qualifies as a nondischargeable debt: the debt\n\narose as a result of a judgment against a spouse, Eloisa, in favor of her former\n\nspouse, Matthew, by the Virginia circuit court “in connection with a separation\n\nagreement [or] divorce decree.” ", "11 U.S.C. § 523(a)(15). ", "The state court entered\n\nthe overpayment judgment after retaining jurisdiction to modify the amount of\n\nMatthew’s spousal support obligation to Eloisa. ", "Accordingly, under the plain\n\nlanguage of the statute, the overpayment judgment is a nondischargeable debt.", "\n\n 18\n\fBecause “[t]he language before us expresses Congress’[s] intent . . . ", "with\n\nsufficient precision[,] . . . ", "reference to legislative history and to pre-Code practice\n\nis hardly necessary.” ", "United States v. Ron Pair Enters., ", "Inc., 489 U.S. 235, 241\n\n(1989).", "\n\n Eloisa recognizes that the overpayment debt falls within the plain language\n\nof the statute, so she instead asserts that application of the unambiguous language\n\nhere would be contrary to Congress’s purpose in enacting § 523(a)(15). ", "Eloisa\n\nargues that § 523(a)(15) was enacted to protect the dependent spouse and that the\n\n“‘plain language’ [of the statute] should be applied in [that] context.” ", "Aplt. ", "Br. ", "at\n\n5. ", "She contends that if the debt is not dischargeable, she will be “left in the\n\nlurch” because her wages will be garnished for decades in order to satisfy the\n\noverpayment judgment. ", "Id. This outcome, she argues, is “manifestly at odds with\n\nCongress’[s] intent in enacting §523(a)(15), with the Bankruptcy Code as a\n\nwhole, and with Congress’[s] intent in elevating certain marital debts above the\n\ndebtor’s fresh start.” ", "Id.\n\n ii) Absurdity Doctrine\n\n In her brief, Eloisa cites two Supreme Court cases as support for her\n\nargument that the plain language of the statute should “yield to the legislative\n\nintent of the Bankruptcy Code drafters.” ", "Id. at 8 (citing Ron Pair Enters., ", "Inc.,\n\n489 U.S. at 242-43; Griffin v. Oceanic Contractors, Inc., 458 U.S. 564, 571\n\n\n\n\n 19\n\f(1982)). ", "Both cited cases deal with the absurdity doctrine. ", "8 The absurdity\n\ndoctrine applies to unambiguous statutes “as a means to avoid applying the\n\nunequivocal language of a statute. ", "But the doctrine has been strictly limited.”", "\n\nRobbins v. Chronister, 435 F.3d 1238, 1241 (10th Cir. ", "2006) (en banc). ", "The\n\nabsurdity doctrine applies “in only the most extreme of circumstances,” when an\n\ninterpretation of a statute “leads to results so gross as to shock the general moral\n\nor common sense,” which is a “formidable hurdle” to the application of this\n\ndoctrine. ", "United States v. Husted, 545 F.3d 1240, 1245 (10th Cir. ", "2008);\n\nRobbins, 435 F.3d at 1241 (quotation omitted). ", "It is not enough to show that\n\nCongress intended a different result from the one produced by the plain language\n\nof the statute. ", "Robbins, 435 F.3d at 1241.", "\n\n The problem with Eloisa’s argument on this point is that application of\n\n§ 523(a)(15)’s exception to the overpayment debt here does not produce a result\n\nat odds with the intentions of its drafters. ", "Even if this court were to rely on the\n\nlegislative history of § 523(a)(15) as originally enacted, as Eloisa argues, there is\n\nno indication that congressional concern extended to the protection of a debtor-\n\n\n 8\n The drafters’ intentions rather than the plain language controls when\n“‘literal application of a statute will produce a result demonstrably at odds with\nthe intentions of its drafters.’” ", "Ron Pair Enters., ", "Inc., 489 U.S. at 242 (quoting\nGriffin, 458 U.S. at 571) (noting that only in the “‘rare case’” will this doctrine\napply). ", "In Griffin, the Supreme Court stated that it had “reserved some scope for\nadopting a restricted rather than a literal or usual meaning of its words where\nacceptance of that meaning . . . ", "would thwart the obvious purpose of the statute.”", "\n458 U.S. at 571 (quotations omitted).", "\n\n 20\n\fdependent spouse who may be responsible for repayment of wrongfully paid\n\nspousal support. ", "As Eloisa points out, when Congress originally enacted\n\n§ 523(a)(15), it was concerned with the dependent spouse who, as part of the\n\ndivorce agreement, negotiated a lower support payment in exchange for the\n\nnondependent spouse shouldering more of the marital debt. ", "See, e.g., H.R. Rep.\n\nNo. ", "103-835, reprinted in 1994 U.S.S.C.A.N. 3340, at 3342, 3363-64 (noting that\n\namendments “ensure[d] that the bankruptcy process cannot be utilized to avoid\n\nalimony and child support obligations” and that amendment intended to provide\n\ngreater protection for marital and child support obligations because “a debtor\n\nshould not use the protection of a bankruptcy filing in order to avoid legitimate\n\nmarital and child support obligations”); see also 103 Cong. ", "Rec. ", "H10,752-01,\n\n§ 304 (1994) (recognizing that § 523(a)(15) would prevent “hold harmless”\n\nagreements that function as support from being discharged in bankruptcy, with the\n\nresult that the “nondebtor spouse may be saddled with substantial debt and little\n\nor no alimony or support”).", "\n\n Despite Eloisa’s assertion to the contrary, Congress’s concern for the\n\ndependent spouse as the creditor when “hold harmless” agreements are in play\n\ndoes not equate to concern for the dependent spouse as the debtor when\n\nrepayment is sought of wrongfully paid spousal support. ", "Eloisa argues that\n\nCongress’s protective purpose extends to the dependent spouse regardless of the\n\nnature of the debt, or to whom the debt is owed. ", "But she cites no support for her\n\n 21\n\fcontention that applying § 523(a)(15) here is contrary to the intent of the\n\nBAPCPA drafters.", "\n\n In fact, the BAPCPA’s deletion of the two defenses (former\n\n§ 523(a)(15)(A) and (B)) and its failure to exclude from those exceptions debts\n\nowed to the nondependent spouse, counsel against a conclusion that Congress\n\nplaced importance only on marital debts owed to a dependent spouse. ", "See, e.g.,\n\nH.R. Rep. No. ", "109-31(1), at 61 (2005) (“Section 215(3) amends section\n\n523(a)(15) to provide that obligations to a spouse, former spouse, or a child of the\n\ndebtor . . . ", "incurred in connection with a divorce or separation or related action\n\nare nondischargeable irrespective of the debtor’s inability to pay such debts.”).", "\n\n Even if Congress only intended to protect marital debts owed to a\n\ndependent spouse, “the reality [is] that the reach of a statute often exceeds the\n\nprecise evil to be eliminated.” ", "Brogan v. United States, 522 U.S. 398, 403\n\n(1998). ", "And “[w]hatever Congress’s motivation, we can apply the [absurdity]\n\ndoctrine only when it would have been unthinkable for Congress to have intended\n\nthe result commanded by the words of the statute.” ", "United States v. Brown, 529\n\nF.3d 1260, 1266 (10th Cir. ", "2008) (quotation omitted). “[", "W]e cannot reject an\n\napplication of the plain meaning of the words in a statute on the ground that we\n\nare confident that Congress would have wanted a different result.” ", "Robbins, 435\n\nF.3d at 1241. ", "It is not unthinkable that Congress would place importance on all\n\nmarital obligations, regardless of whether the debt was owed to or by the\n\n 22\n\fdependent spouse – even above the need for the debtor’s fresh start. ", "Accordingly,\n\nEloisa’s citations to Ron Pair Enterprises, Inc. and Griffin as support for\n\ndisregarding the plain language of the statute are not persuasive. ", "9\n\n C. Attorney Fees\n\n Matthew also appeals the BAP’s ruling that neither it, nor the bankruptcy\n\ncourt, had authority under the Taylors’ MSA to award Matthew attorney fees\n\nincurred pursuing the adversary proceeding. ", "Upon review of the attorney fee\n\nprovisions set forth in the MSA, the BAP’s ruling on this issue is clearly correct.", "\n\n IV\n\n Accordingly, we AFFIRM the bankruptcy court’s ruling that the debt\n\narising from the overpayment of spousal support is nondischargeable under 11\n\nU.S.C. § 523(a)(15). ", "We also AFFIRM the bankruptcy court’s dismissal of\n\nMatthew’s claim that this same debt is also nondischargeable as a “domestic\n\nsupport obligation” under 11 U.S.C. § 523(a)(5). ", "Further, we AFFIRM the BAP’s\n\nruling that Matthew is not entitled to attorney fees because neither the BAP nor\n\nthe bankruptcy court had authority to award attorney fees under the MSA’s fee-\n\nshifting agreement.", "\n\n\n 9\n Eloisa makes a one-sentence argument that the bankruptcy court should\nhave used its “broad authority” to find that the overpayment debt was\ndischargeable. ", "Aplt. ", "Br. ", "at 8. ", "We conclude that Eloisa’s perfunctory brief on this\npoint is not sufficient. ", "See, e.g., Adler v. Wal-Mart Stores, Inc., 144 F.3d 664,\n679 (10th Cir. ", "1998) (“Arguments inadequately briefed in the opening brief are\nwaived.”).", "\n\n 23\n\f" ]
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[ "Importance of acclimation to environmentally relevant zinc concentrations on the sensitivity of Daphnia magna toward zinc.", "\nDaphnia magna was acclimated for six generations to an acclimation range of 0.02 to 74 microg/L of Zn2+. ", "This range was determined by combining physicochemical water characteristics of European surface waters with total Zn concentrations in these waters in such a way that they resulted in minimal and maximal free (i.e., assumed bioavailable) Zn ion activities. ", "No significant differences were found in acute Zn tolerance between the different acclimation concentrations: Average 48-h median effective concentration (EC50) values ranged from 608+/-94 to 713+/-249 microg/L of Zn2+. ", "Also, no significant shifts in chronic tolerance were observed: Average 21-d EC50 (based on net reproductive rate) ranged from 91+/-20 to 124+/-22 microg/L of Zn2+. ", "However, at test concentrations less than the 21-d EC50, acclimation significantly increased the reproductive capacity of the offspring produced. ", "This indicates that metal acclimation is not necessarily accompanied by an increase in tolerance but also may manifest in other responses (e.g., reproduction rate). ", "Organisms acclimated to a range from 6 to 22 microg/L of Zn2+ produced significantly more offspring than organisms acclimated to lower and higher Zn concentrations in test concentrations up to 50 microg/L of Zn2+. ", "This range corresponds to a previously established optimal concentration range for D. magna. ", "Bioconcentration factors indicated that Zn was actively regulated in the acclimation range tested." ]
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[ "Q:\n\nGtk-ERROR **: GTK+ 2.x symbols detected\n\nI'm compiling my c application with gcc with the following flags:\ngcc evis.c `pkg-config --cflags --libs gtk+-2.0 --libs clutter-gtk-1.0 --libs gthread-2.0` -Wall -o evis\n\nNow my code compiles with a few warnings but still finishes. ", "When I try to run my program I get:\n(evis:1820): Gtk-ERROR **: GTK+ 2.x symbols detected. ", "Using GTK+ 2.x and GTK+ 3 in the same process is not supported\n\nHow do I troubleshoot this error? ", "How do I know where to look? ", "Is there some kind of tool I could use online that would scan for GTK3 symbols in my code? ", "I'm compiling with GTK+2 so I don't understand how this is happening.", "\n\nA:\n\nYou are linking the same program to Gtk+2.0 and Gtk+3.0. ", "And that will not work.", "\nIt is easy to check: just run the pkg-config command standalone. ", "BTW, you do not need to repeat --libs so many times, and since we are looking for linking errors, I'm ommiting the --cflags for clarity:\n$ pkg-config --libs gtk+-2.0 clutter-gtk-1.0 gthread-2.0\n\nNow, it writes a lot of library names, but if you look carefully you'll find these ones:\n... -lgtk-x11-2.0 ... -lgtk-3 ...\n\nBut where do they come from? ", "Well, the Gtk+-2 part is easy: you are asking for it in the command line! ", "The Gtk+-3 part has only one candidate:\n$ pkg-config --libs clutter-gtk-1.0\n... -lgtk-3 ...\n\nBingo! ", "So Clutter-gtk is a Gtk+-3 library. ", "And so should be your program is you want to use Clutter-gtk.", "\nThe solutions to your problem are:\n\nPort your program to Gtk+-3 and change your compiler command accordingly.", "\nUse a different version of Clutter-gtk that uses Gtk+-2. ", "I think you can choose the dependency if you compile Clutter-gtk yourself.", "\nDo not use Clutter-gtk.", "\n\n" ]
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[ "Closed-End Pouches\n\nQuestion:\n\nI have had a colostomy for 5 years and have been using a 2-piece pouch with a drainable pouch/clip. ", "Recently, a friend told me that I should try closed-end pouches. ", "What are the advantages of a closed end pouch?", "\n\nAnswer:\n\nClosed end pouches are an option for people with colostomies. ", "This type of pouch is clip-less, with all peripheral edges completely sealed. ", "It is intended to be removed and disposed when the pouch is 1/3rd to ½ full of stool, and replaced with a fresh pouch. ", "Some closed end pouches have a charcoal filter, which allows any gas/flatus to escape the pouch while being deodorized; other pouches are available without filters. ", "Most companies have a range of sizes in closed end pouches, with small ones that have a limited capacity of perhaps only a couple ounces (60 millilitres) of stool, to larger pouches that may comfortably hold up to 1 ½ cups (375 millilitres). ", "Closed end pouches are also available as a 1-piece system, with a light barrier. ", "The advantages and disadvantages of these pouches will be discussed below.", "\n\nThe most significant advantage of a closed end pouch is its contribution to simplifying ostomy care. ", "Rather than needing to sit on a toilet and to milk thick/formed stool from your drainable pouch, a closed end can be easily detached from your flange, discarded in a plastic bag/waste container and a new pouch quickly reapplied. ", "It can minimize the amount of time and effort required for routine ostomy care. ", "Closed end pouches can also help to ease management in social environments and with physical activities. ", "Concerns about emptying a drainable pouch in a public washroom can be eliminated by removing full closed end pouches, sealing it in a Ziploc™ bag and discarding in a waste container.", "\n\nWhile there are several sizes of closed end pouches available, not each ostomy supply company will have a full range of sizes in each of their product lines. ", "You may need to consider switching to an alternate product line if variety is important to you. ", "Finding one that will suit your needs is dependent upon the volume of your stool and the frequency/predictability of your bowel movements. ", "If your pattern of movement is predictable, you can try wearing a larger closed end pouch to accommodate your stool, then switch to a smaller stoma cap with gas filter for the remainder of the day. ", "If you tend to have smaller, more frequent movements, you may want to use a medium sized pouch, and change it once or twice daily.", "\n\nYour choice of closed end pouch may also be determined by the quality of the gas release filter, if this is a feature that you would like to have. ", "Not all filters function the same: if your stool is a bit looser or if you have periods of liquid stool, you may find that the filter is ineffective. ", "It can become clogged with stool, causing break-through odor and seepage of tiny amounts of stool through the filter itself, subsequently staining your clothes. ", "Filters are also rendered ineffective by outside moisture, such as that from bathing or showering. ", "Most companies provide adhesive filter protectors that can be attached/removed in these circumstances. ", "The filters also tend to work better if there is some external compression on the pouch; this helps to force the gas through the filter. ", "For large volumes of gas, or if you opt to try a non-filtered pouch, “burping” the pouch to release the gas may be easier (releasing the top edge of the pouch from the flange, to quickly release gas).", "\n\nPerhaps the most significant difference of a closed end pouch is the cost: typically individuals who use closed end pouches will use 1 to 2 pouches each day (rather than 1-2 drainable pouches in a week). ", "Your decision to use closed ends may be dependent upon your financial situation. ", "Extended medical programs will usually reimburse 80-100% of ostomy supplies used after payment of a nominal deductible fee. ", "Some provinces may have government support programs that allow for specific groups of individuals to obtain funding for supplies (income assistance or welfare programs, seniors programs). ", "Federal programs, such as the Department of Veteran Affairs or the Department of Indian and Northern Affairs, may also cover the cost of closed end pouches with a physician subscription. ", "Financial support for ostomy supplies differs widely across the provinces. ", "I suggest contacting a local Enterostomal Therapy Nurse to help you find appropriate funding sources.", "\n\nSome of the costs can be ameliorated with creativity. ", "There are thin plastic liners available that work in conjunction with closed end pouches. ", "These are cheaper than the closed end pouches, and may make a closed end more financially feasible. ", "These liners go inside the closed end pouch. ", "Once the liner is filled with stool, the pouch and liner are removed; the filled liner is removed/discarded and a new liner placed inside the same closed end pouch. ", "Use of liners, however, prevents the filter option from functioning, and the liner may also prevent a secure seal between the pouch and the flange. ", "You may want to continue to use drainable pouches, and reserve the use of closed ends for specific scenarios, such as outings to restaurants or for travel.", "\n\nWhile usually closed end pouches are reserved for those individuals with colostomies and formed stool, people with ileostomies may also choose to use closed ends. ", "Poor hand strength and dexterity may make traditional clipped pouches difficult to use, while a closed end system may facilitate self-care and independence. ", "As with colostomies, there may also be events when or places where discarding a pouch may be easier than trying to empty.", "\n\nLastly, there are also one-piece closed end pouches. ", "These have a very thin barrier with less tack than traditional 2-piece systems. ", "These are intended to not be worn more than 1-2 days (depending upon stool volume and frequency), and the whole appliance is removed and discarded. ", "No paste is used with this type of pouching, and is best reserved for those with formed stool. ", "This system has a low profile and most closely mimics usual bathroom habits: filled pouch is removed/discarded, stoma and skin quickly cleansed and a new pouch applied.", "\n\nUse of closed end pouches is an option for care. ", "An Enterostomal Therapy Nurse can help you to determine appropriate products and samples. ", "See our article on pouch liners for more information.", "\n\nSearch\n\nShare This Post\n\nWe’re committed to improving the lives of people with GI and liver conditions, supporting research, advocating for appropriate patient access to health care, and promoting gastrointestinal and liver health." ]
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[ "/*\n * AAC encoder psychoacoustic model\n * Copyright (C) 2008 Konstantin Shishkov\n *\n * This file is part of FFmpeg.", "\n *\n * FFmpeg is free software; you can redistribute it and/or\n * modify it under the terms of the GNU Lesser General Public\n * License as published by the Free Software Foundation; either\n * version 2.1 of the License, or (at your option) any later version.", "\n *\n * FFmpeg is distributed in the hope that it will be useful,\n * but WITHOUT ANY WARRANTY; without even the implied warranty of\n * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU\n * Lesser General Public License for more details.", "\n *\n * You should have received a copy of the GNU Lesser General Public\n * License along with FFmpeg; if not, write to the Free Software\n * Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA\n */\n\n/**\n * @file\n * AAC encoder psychoacoustic model\n */\n\n#include \"libavutil/attributes.h\"\n#include \"libavutil/libm.h\"\n\n#include \"avcodec.h\"\n#include \"aactab.h\"\n#include \"psymodel.h\"\n\n/***********************************\n * TODOs:\n * try other bitrate controlling mechanism (maybe use ratecontrol.c?)", "\n * control quality for quality-based output\n **********************************/\n\n/**\n * constants for 3GPP AAC psychoacoustic model\n * @{\n */\n#define PSY_3GPP_THR_SPREAD_HI 1.5f // spreading factor for low-to-hi threshold spreading (15 dB/Bark)\n#define PSY_3GPP_THR_SPREAD_LOW 3.0f // spreading factor for hi-to-low threshold spreading (30 dB/Bark)\n/* spreading factor for low-to-hi energy spreading, long block, > 22kbps/channel (20dB/Bark) */\n#define PSY_3GPP_EN_SPREAD_HI_L1 2.0f\n/* spreading factor for low-to-hi energy spreading, long block, <= 22kbps/channel (15dB/Bark) */\n#define PSY_3GPP_EN_SPREAD_HI_L2 1.5f\n/* spreading factor for low-to-hi energy spreading, short block (15 dB/Bark) */\n#define PSY_3GPP_EN_SPREAD_HI_S 1.5f\n/* spreading factor for hi-to-low energy spreading, long block (30dB/Bark) */\n#define PSY_3GPP_EN_SPREAD_LOW_L 3.0f\n/* spreading factor for hi-to-low energy spreading, short block (20dB/Bark) */\n#define PSY_3GPP_EN_SPREAD_LOW_S 2.0f\n\n#define PSY_3GPP_RPEMIN 0.01f\n#define PSY_3GPP_RPELEV 2.0f\n\n#define PSY_3GPP_C1 3.0f /* log2(8) */\n#define PSY_3GPP_C2 1.3219281f /* log2(2.5) */\n#define PSY_3GPP_C3 0.55935729f /* 1 - C2 / C1 */\n\n#define PSY_SNR_1DB 7.9432821e-1f /* -1dB */\n#define PSY_SNR_25DB 3.1622776e-3f /* -25dB */\n\n#define PSY_3GPP_SAVE_SLOPE_L -0.46666667f\n#define PSY_3GPP_SAVE_SLOPE_S -0.36363637f\n#define PSY_3GPP_SAVE_ADD_L -0.84285712f\n#define PSY_3GPP_SAVE_ADD_S -0.75f\n#define PSY_3GPP_SPEND_SLOPE_L 0.66666669f\n#define PSY_3GPP_SPEND_SLOPE_S 0.81818181f\n#define PSY_3GPP_SPEND_ADD_L -0.35f\n#define PSY_3GPP_SPEND_ADD_S -0.26111111f\n#define PSY_3GPP_CLIP_LO_L 0.2f\n#define PSY_3GPP_CLIP_LO_S 0.2f\n#define PSY_3GPP_CLIP_HI_L 0.95f\n#define PSY_3GPP_CLIP_HI_S 0.75f\n\n#define PSY_3GPP_AH_THR_LONG 0.5f\n#define PSY_3GPP_AH_THR_SHORT 0.63f\n\nenum {\n PSY_3GPP_AH_NONE,\n PSY_3GPP_AH_INACTIVE,\n PSY_3GPP_AH_ACTIVE\n};\n\n#define PSY_3GPP_BITS_TO_PE(bits) ((bits) * 1.18f)\n\n/* LAME psy model constants */\n#define PSY_LAME_FIR_LEN 21 ///< LAME psy model FIR order\n#define AAC_BLOCK_SIZE_LONG 1024 ///< long block size\n#define AAC_BLOCK_SIZE_SHORT 128 ///< short block size\n#define AAC_NUM_BLOCKS_SHORT 8 ///< number of blocks in a short sequence\n#define PSY_LAME_NUM_SUBBLOCKS 3 ///< Number of sub-blocks in each short block\n\n/**\n * @}\n */\n\n/**\n * information for single band used by 3GPP TS26.403-inspired psychoacoustic model\n */\ntypedef struct AacPsyBand{\n float energy; ///< band energy\n float thr; ///< energy threshold\n float thr_quiet; ///< threshold in quiet\n float nz_lines; ///< number of non-zero spectral lines\n float active_lines; ///< number of active spectral lines\n float pe; ///< perceptual entropy\n float pe_const; ///< constant part of the PE calculation\n float norm_fac; ///< normalization factor for linearization\n int avoid_holes; ///< hole avoidance flag\n}AacPsyBand;\n\n/**\n * single/pair channel context for psychoacoustic model\n */\ntypedef struct AacPsyChannel{\n AacPsyBand band[128]; ///< bands information\n AacPsyBand prev_band[128]; ///< bands information from the previous frame\n\n float win_energy; ///< sliding average of channel energy\n float iir_state[2]; ///< hi-pass IIR filter state\n uint8_t next_grouping; ///< stored grouping scheme for the next frame (in case of 8 short window sequence)\n enum WindowSequence next_window_seq; ///< window sequence to be used in the next frame\n /* LAME psy model specific members */\n float attack_threshold; ///< attack threshold for this channel\n float prev_energy_subshort[AAC_NUM_BLOCKS_SHORT * PSY_LAME_NUM_SUBBLOCKS];\n int prev_attack; ///< attack value for the last short block in the previous sequence\n}AacPsyChannel;\n\n/**\n * psychoacoustic model frame type-dependent coefficients\n */\ntypedef struct AacPsyCoeffs{\n float ath; ///< absolute threshold of hearing per bands\n float barks; ///< Bark value for each spectral band in long frame\n float spread_low[2]; ///< spreading factor for low-to-high threshold spreading in long frame\n float spread_hi [2]; ///< spreading factor for high-to-low threshold spreading in long frame\n float min_snr; ///< minimal SNR\n}AacPsyCoeffs;\n\n/**\n * 3GPP TS26.403-inspired psychoacoustic model specific data\n */\ntypedef struct AacPsyContext{\n int chan_bitrate; ///< bitrate per channel\n int frame_bits; ///< average bits per frame\n int fill_level; ///< bit reservoir fill level\n struct {\n float min; ///< minimum allowed PE for bit factor calculation\n float max; ///< maximum allowed PE for bit factor calculation\n float previous; ///< allowed PE of the previous frame\n float correction; ///< PE correction factor\n } pe;\n AacPsyCoeffs psy_coef[2][64];\n AacPsyChannel *ch;\n}AacPsyContext;\n\n/**\n * LAME psy model preset struct\n */\ntypedef struct {\n int quality; ///< Quality to map the rest of the vaules to.", "\n /* This is overloaded to be both kbps per channel in ABR mode, and\n * requested quality in constant quality mode.", "\n */\n float st_lrm; ///< short threshold for L, R, and M channels\n} PsyLamePreset;\n\n/**\n * LAME psy model preset table for ABR\n */\nstatic const PsyLamePreset psy_abr_map[] = {\n/* TODO: Tuning. ", "These were taken from LAME. */", "\n/* kbps/ch st_lrm */\n { 8, 6.60},\n { 16, 6.60},\n { 24, 6.60},\n { 32, 6.60},\n { 40, 6.60},\n { 48, 6.60},\n { 56, 6.60},\n { 64, 6.40},\n { 80, 6.00},\n { 96, 5.60},\n {112, 5.20},\n {128, 5.20},\n {160, 5.20}\n};\n\n/**\n* LAME psy model preset table for constant quality\n*/\nstatic const PsyLamePreset psy_vbr_map[] = {\n/* vbr_q st_lrm */\n { 0, 4.20},\n { 1, 4.20},\n { 2, 4.20},\n { 3, 4.20},\n { 4, 4.20},\n { 5, 4.20},\n { 6, 4.20},\n { 7, 4.20},\n { 8, 4.20},\n { 9, 4.20},\n {10, 4.20}\n};\n\n/**\n * LAME psy model FIR coefficient table\n */\nstatic const float psy_fir_coeffs[] = {\n -8.65163e-18 * 2, -0.00851586 * 2, -6.74764e-18 * 2, 0.0209036 * 2,\n -3.36639e-17 * 2, -0.0438162 * 2, -1.54175e-17 * 2, 0.0931738 * 2,\n -5.52212e-17 * 2, -0.313819 * 2\n};\n\n#if ARCH_MIPS\n# include \"mips/aacpsy_mips.h\"\n#endif /* ARCH_MIPS */\n\n/**\n * Calculate the ABR attack threshold from the above LAME psymodel table.", "\n */\nstatic float lame_calc_attack_threshold(int bitrate)\n{\n /* Assume max bitrate to start with */\n int lower_range = 12, upper_range = 12;\n int lower_range_kbps = psy_abr_map[12].quality;\n int upper_range_kbps = psy_abr_map[12].quality;\n int i;\n\n /* Determine which bitrates the value specified falls between.", "\n * If the loop ends without breaking our above assumption of 320kbps was correct.", "\n */\n for (i = 1; i < 13; i++) {\n if (FFMAX(bitrate, psy_abr_map[i].quality) !", "= bitrate) {\n upper_range = i;\n upper_range_kbps = psy_abr_map[i ].quality;\n lower_range = i - 1;\n lower_range_kbps = psy_abr_map[i - 1].quality;\n break; /* Upper range found */\n }\n }\n\n /* Determine which range the value specified is closer to */\n if ((upper_range_kbps - bitrate) > (bitrate - lower_range_kbps))\n return psy_abr_map[lower_range].st_lrm;\n return psy_abr_map[upper_range].st_lrm;\n}\n\n/**\n * LAME psy model specific initialization\n */\nstatic av_cold void lame_window_init(AacPsyContext *ctx, AVCodecContext *avctx)\n{\n int i, j;\n\n for (i = 0; i < avctx->channels; i++) {\n AacPsyChannel *pch = &ctx->ch[i];\n\n if (avctx->flags & CODEC_FLAG_QSCALE)\n pch->attack_threshold = psy_vbr_map[avctx->global_quality / FF_QP2LAMBDA].st_lrm;\n else\n pch->attack_threshold = lame_calc_attack_threshold(avctx->bit_rate / avctx->channels / 1000);\n\n for (j = 0; j < AAC_NUM_BLOCKS_SHORT * PSY_LAME_NUM_SUBBLOCKS; j++)\n pch->prev_energy_subshort[j] = 10.0f;\n }\n}\n\n/**\n * Calculate Bark value for given line.", "\n */\nstatic av_cold float calc_bark(float f)\n{\n return 13.3f * atanf(0.00076f * f) + 3.5f * atanf((f / 7500.0f) * (f / 7500.0f));\n}\n\n#define ATH_ADD 4\n/**\n * Calculate ATH value for given frequency.", "\n * Borrowed from Lame.", "\n */\nstatic av_cold float ath(float f, float add)\n{\n f /= 1000.0f;\n return 3.64 * pow(f, -0.8)\n - 6.8 * exp(-0.6 * (f - 3.4) * (f - 3.4))\n + 6.0 * exp(-0.15 * (f - 8.7) * (f - 8.7))\n + (0.6 + 0.04 * add) * 0.001 * f * f * f * f;\n}\n\nstatic av_cold int psy_3gpp_init(FFPsyContext *ctx) {\n AacPsyContext *pctx;\n float bark;\n int i, j, g, start;\n float prev, minscale, minath, minsnr, pe_min;\n const int chan_bitrate = ctx->avctx->bit_rate / ctx->avctx->channels;\n const int bandwidth = ctx->avctx->cutoff ? ", "ctx->avctx->cutoff : AAC_CUTOFF(ctx->avctx);\n const float num_bark = calc_bark((float)bandwidth);\n\n ctx->model_priv_data = av_mallocz(sizeof(AacPsyContext));\n pctx = (AacPsyContext*) ctx->model_priv_data;\n\n pctx->chan_bitrate = chan_bitrate;\n pctx->frame_bits = chan_bitrate * AAC_BLOCK_SIZE_LONG / ctx->avctx->sample_rate;\n pctx->pe.min = 8.0f * AAC_BLOCK_SIZE_LONG * bandwidth / (ctx->avctx->sample_rate * 2.0f);\n pctx->pe.max = 12.0f * AAC_BLOCK_SIZE_LONG * bandwidth / (ctx->avctx->sample_rate * 2.0f);\n ctx->bitres.size = 6144 - pctx->frame_bits;\n ctx->bitres.size -= ctx->bitres.size % 8;\n pctx->fill_level = ctx->bitres.size;\n minath = ath(3410, ATH_ADD);\n for (j = 0; j < 2; j++) {\n AacPsyCoeffs *coeffs = pctx->psy_coef[j];\n const uint8_t *band_sizes = ctx->bands[j];\n float line_to_frequency = ctx->avctx->sample_rate / (j ? ", "256.f : 2048.0f);\n float avg_chan_bits = chan_bitrate * (j ? ", "128.0f : 1024.0f) / ctx->avctx->sample_rate;\n /* reference encoder uses 2.4% here instead of 60% like the spec says */\n float bark_pe = 0.024f * PSY_3GPP_BITS_TO_PE(avg_chan_bits) / num_bark;\n float en_spread_low = j ? ", "PSY_3GPP_EN_SPREAD_LOW_S : PSY_3GPP_EN_SPREAD_LOW_L;\n /* High energy spreading for long blocks <= 22kbps/channel and short blocks are the same. */", "\n float en_spread_hi = (j || (chan_bitrate <= 22.0f)) ? ", "PSY_3GPP_EN_SPREAD_HI_S : PSY_3GPP_EN_SPREAD_HI_L1;\n\n i = 0;\n prev = 0.0;\n for (g = 0; g < ctx->num_bands[j]; g++) {\n i += band_sizes[g];\n bark = calc_bark((i-1) * line_to_frequency);\n coeffs[g].barks = (bark + prev) / 2.0;\n prev = bark;\n }\n for (g = 0; g < ctx->num_bands[j] - 1; g++) {\n AacPsyCoeffs *coeff = &coeffs[g];\n float bark_width = coeffs[g+1].barks - coeffs->barks;\n coeff->spread_low[0] = pow(10.0, -bark_width * PSY_3GPP_THR_SPREAD_LOW);\n coeff->spread_hi [0] = pow(10.0, -bark_width * PSY_3GPP_THR_SPREAD_HI);\n coeff->spread_low[1] = pow(10.0, -bark_width * en_spread_low);\n coeff->spread_hi [1] = pow(10.0, -bark_width * en_spread_hi);\n pe_min = bark_pe * bark_width;\n minsnr = exp2(pe_min / band_sizes[g]) - 1.5f;\n coeff->min_snr = av_clipf(1.0f / minsnr, PSY_SNR_25DB, PSY_SNR_1DB);\n }\n start = 0;\n for (g = 0; g < ctx->num_bands[j]; g++) {\n minscale = ath(start * line_to_frequency, ATH_ADD);\n for (i = 1; i < band_sizes[g]; i++)\n minscale = FFMIN(minscale, ath((start + i) * line_to_frequency, ATH_ADD));\n coeffs[g].ath = minscale - minath;\n start += band_sizes[g];\n }\n }\n\n pctx->ch = av_mallocz_array(ctx->avctx->channels, sizeof(AacPsyChannel));\n\n lame_window_init(pctx, ctx->avctx);\n\n return 0;\n}\n\n/**\n * IIR filter used in block switching decision\n */\nstatic float iir_filter(int in, float state[2])\n{\n float ret;\n\n ret = 0.7548f * (in - state[0]) + 0.5095f * state[1];\n state[0] = in;\n state[1] = ret;\n return ret;\n}\n\n/**\n * window grouping information stored as bits (0 - new group, 1 - group continues)\n */\nstatic const uint8_t window_grouping[9] = {\n 0xB6, 0x6C, 0xD8, 0xB2, 0x66, 0xC6, 0x96, 0x36, 0x36\n};\n\n/**\n * Tell encoder which window types to use.", "\n * @see 3GPP TS26.403 5.4.1 \"Blockswitching\"\n */\nstatic av_unused FFPsyWindowInfo psy_3gpp_window(FFPsyContext *ctx,\n const int16_t *audio,\n const int16_t *la,\n int channel, int prev_type)\n{\n int i, j;\n int br = ctx->avctx->bit_rate / ctx->avctx->channels;\n int attack_ratio = br <= 16000 ? ", "18 : 10;\n AacPsyContext *pctx = (AacPsyContext*) ctx->model_priv_data;\n AacPsyChannel *pch = &pctx->ch[channel];\n uint8_t grouping = 0;\n int next_type = pch->next_window_seq;\n FFPsyWindowInfo wi = { { 0 } };\n\n if (la) {\n float s[8], v;\n int switch_to_eight = 0;\n float sum = 0.0, sum2 = 0.0;\n int attack_n = 0;\n int stay_short = 0;\n for (i = 0; i < 8; i++) {\n for (j = 0; j < 128; j++) {\n v = iir_filter(la[i*128+j], pch->iir_state);\n sum += v*v;\n }\n s[i] = sum;\n sum2 += sum;\n }\n for (i = 0; i < 8; i++) {\n if (s[i] > pch->win_energy * attack_ratio) {\n attack_n = i + 1;\n switch_to_eight = 1;\n break;\n }\n }\n pch->win_energy = pch->win_energy*7/8 + sum2/64;\n\n wi.window_type[1] = prev_type;\n switch (prev_type) {\n case ONLY_LONG_SEQUENCE:\n wi.window_type[0] = switch_to_eight ? ", "LONG_START_SEQUENCE : ONLY_LONG_SEQUENCE;\n next_type = switch_to_eight ? ", "EIGHT_SHORT_SEQUENCE : ONLY_LONG_SEQUENCE;\n break;\n case LONG_START_SEQUENCE:\n wi.window_type[0] = EIGHT_SHORT_SEQUENCE;\n grouping = pch->next_grouping;\n next_type = switch_to_eight ? ", "EIGHT_SHORT_SEQUENCE : LONG_STOP_SEQUENCE;\n break;\n case LONG_STOP_SEQUENCE:\n wi.window_type[0] = switch_to_eight ? ", "LONG_START_SEQUENCE : ONLY_LONG_SEQUENCE;\n next_type = switch_to_eight ? ", "EIGHT_SHORT_SEQUENCE : ONLY_LONG_SEQUENCE;\n break;\n case EIGHT_SHORT_SEQUENCE:\n stay_short = next_type == EIGHT_SHORT_SEQUENCE || switch_to_eight;\n wi.window_type[0] = stay_short ? ", "EIGHT_SHORT_SEQUENCE : LONG_STOP_SEQUENCE;\n grouping = next_type == EIGHT_SHORT_SEQUENCE ? ", "pch->next_grouping : 0;\n next_type = switch_to_eight ? ", "EIGHT_SHORT_SEQUENCE : LONG_STOP_SEQUENCE;\n break;\n }\n\n pch->next_grouping = window_grouping[attack_n];\n pch->next_window_seq = next_type;\n } else {\n for (i = 0; i < 3; i++)\n wi.window_type[i] = prev_type;\n grouping = (prev_type == EIGHT_SHORT_SEQUENCE) ? ", "window_grouping[0] : 0;\n }\n\n wi.window_shape = 1;\n if (wi.window_type[0] !", "= EIGHT_SHORT_SEQUENCE) {\n wi.num_windows = 1;\n wi.grouping[0] = 1;\n } else {\n int lastgrp = 0;\n wi.num_windows = 8;\n for (i = 0; i < 8; i++) {\n if (!((", "grouping >> i) & 1))\n lastgrp = i;\n wi.grouping[lastgrp]++;\n }\n }\n\n return wi;\n}\n\n/* 5.6.1.2 \"Calculation of Bit Demand\" */\nstatic int calc_bit_demand(AacPsyContext *ctx, float pe, int bits, int size,\n int short_window)\n{\n const float bitsave_slope = short_window ? ", "PSY_3GPP_SAVE_SLOPE_S : PSY_3GPP_SAVE_SLOPE_L;\n const float bitsave_add = short_window ? ", "PSY_3GPP_SAVE_ADD_S : PSY_3GPP_SAVE_ADD_L;\n const float bitspend_slope = short_window ? ", "PSY_3GPP_SPEND_SLOPE_S : PSY_3GPP_SPEND_SLOPE_L;\n const float bitspend_add = short_window ? ", "PSY_3GPP_SPEND_ADD_S : PSY_3GPP_SPEND_ADD_L;\n const float clip_low = short_window ? ", "PSY_3GPP_CLIP_LO_S : PSY_3GPP_CLIP_LO_L;\n const float clip_high = short_window ? ", "PSY_3GPP_CLIP_HI_S : PSY_3GPP_CLIP_HI_L;\n float clipped_pe, bit_save, bit_spend, bit_factor, fill_level;\n\n ctx->fill_level += ctx->frame_bits - bits;\n ctx->fill_level = av_clip(ctx->fill_level, 0, size);\n fill_level = av_clipf((float)ctx->fill_level / size, clip_low, clip_high);\n clipped_pe = av_clipf(pe, ctx->pe.min, ctx->pe.max);\n bit_save = (fill_level + bitsave_add) * bitsave_slope;\n assert(bit_save <= 0.3f && bit_save >= -0.05000001f);\n bit_spend = (fill_level + bitspend_add) * bitspend_slope;\n assert(bit_spend <= 0.5f && bit_spend >= -0.1f);\n /* The bit factor graph in the spec is obviously incorrect.", "\n * bit_spend + ((bit_spend - bit_spend))...\n * The reference encoder subtracts everything from 1, but also seems incorrect.", "\n * 1 - bit_save + ((bit_spend + bit_save))...\n * Hopefully below is correct.", "\n */\n bit_factor = 1.0f - bit_save + ((bit_spend - bit_save) / (ctx->pe.max - ctx->pe.min)) * (clipped_pe - ctx->pe.min);\n /* NOTE: The reference encoder attempts to center pe max/min around the current pe. */", "\n ctx->pe.max = FFMAX(pe, ctx->pe.max);\n ctx->pe.min = FFMIN(pe, ctx->pe.min);\n\n return FFMIN(ctx->frame_bits * bit_factor, ctx->frame_bits + size - bits);\n}\n\nstatic float calc_pe_3gpp(AacPsyBand *band)\n{\n float pe, a;\n\n band->pe = 0.0f;\n band->pe_const = 0.0f;\n band->active_lines = 0.0f;\n if (band->energy > band->thr) {\n a = log2f(band->energy);\n pe = a - log2f(band->thr);\n band->active_lines = band->nz_lines;\n if (pe < PSY_3GPP_C1) {\n pe = pe * PSY_3GPP_C3 + PSY_3GPP_C2;\n a = a * PSY_3GPP_C3 + PSY_3GPP_C2;\n band->active_lines *= PSY_3GPP_C3;\n }\n band->pe = pe * band->nz_lines;\n band->pe_const = a * band->nz_lines;\n }\n\n return band->pe;\n}\n\nstatic float calc_reduction_3gpp(float a, float desired_pe, float pe,\n float active_lines)\n{\n float thr_avg, reduction;\n\n if(active_lines == 0.0)\n return 0;\n\n thr_avg = exp2f((a - pe) / (4.0f * active_lines));\n reduction = exp2f((a - desired_pe) / (4.0f * active_lines)) - thr_avg;\n\n return FFMAX(reduction, 0.0f);\n}\n\nstatic float calc_reduced_thr_3gpp(AacPsyBand *band, float min_snr,\n float reduction)\n{\n float thr = band->thr;\n\n if (band->energy > thr) {\n thr = sqrtf(thr);\n thr = sqrtf(thr) + reduction;\n thr *= thr;\n thr *= thr;\n\n /* This deviates from the 3GPP spec to match the reference encoder.", "\n * It performs min(thr_reduced, max(thr, energy/min_snr)) only for bands\n * that have hole avoidance on (active or inactive). ", "It always reduces the\n * threshold of bands with hole avoidance off.", "\n */\n if (thr > band->energy * min_snr && band->avoid_holes !", "= PSY_3GPP_AH_NONE) {\n thr = FFMAX(band->thr, band->energy * min_snr);\n band->avoid_holes = PSY_3GPP_AH_ACTIVE;\n }\n }\n\n return thr;\n}\n\n#ifndef calc_thr_3gpp\nstatic void calc_thr_3gpp(const FFPsyWindowInfo *wi, const int num_bands, AacPsyChannel *pch,\n const uint8_t *band_sizes, const float *coefs)\n{\n int i, w, g;\n int start = 0;\n for (w = 0; w < wi->num_windows*16; w += 16) {\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n\n float form_factor = 0.0f;\n float Temp;\n band->energy = 0.0f;\n for (i = 0; i < band_sizes[g]; i++) {\n band->energy += coefs[start+i] * coefs[start+i];\n form_factor += sqrtf(fabs(coefs[start+i]));\n }\n Temp = band->energy > 0 ? ", "sqrtf((float)band_sizes[g] / band->energy) : 0;\n band->thr = band->energy * 0.001258925f;\n band->nz_lines = form_factor * sqrtf(Temp);\n\n start += band_sizes[g];\n }\n }\n}\n#endif /* calc_thr_3gpp */\n\n#ifndef psy_hp_filter\nstatic void psy_hp_filter(const float *firbuf, float *hpfsmpl, const float *psy_fir_coeffs)\n{\n int i, j;\n for (i = 0; i < AAC_BLOCK_SIZE_LONG; i++) {\n float sum1, sum2;\n sum1 = firbuf[i + (PSY_LAME_FIR_LEN - 1) / 2];\n sum2 = 0.0;\n for (j = 0; j < ((PSY_LAME_FIR_LEN - 1) / 2) - 1; j += 2) {\n sum1 += psy_fir_coeffs[j] * (firbuf[i + j] + firbuf[i + PSY_LAME_FIR_LEN - j]);\n sum2 += psy_fir_coeffs[j + 1] * (firbuf[i + j + 1] + firbuf[i + PSY_LAME_FIR_LEN - j - 1]);\n }\n /* NOTE: The LAME psymodel expects it's input in the range -32768 to 32768.", "\n * Tuning this for normalized floats would be difficult. */", "\n hpfsmpl[i] = (sum1 + sum2) * 32768.0f;\n }\n}\n#endif /* psy_hp_filter */\n\n/**\n * Calculate band thresholds as suggested in 3GPP TS26.403\n */\nstatic void psy_3gpp_analyze_channel(FFPsyContext *ctx, int channel,\n const float *coefs, const FFPsyWindowInfo *wi)\n{\n AacPsyContext *pctx = (AacPsyContext*) ctx->model_priv_data;\n AacPsyChannel *pch = &pctx->ch[channel];\n int i, w, g;\n float desired_bits, desired_pe, delta_pe, reduction= NAN, spread_en[128] = {0};\n float a = 0.0f, active_lines = 0.0f, norm_fac = 0.0f;\n float pe = pctx->chan_bitrate > 32000 ? ", "0.0f : FFMAX(50.0f, 100.0f - pctx->chan_bitrate * 100.0f / 32000.0f);\n const int num_bands = ctx->num_bands[wi->num_windows == 8];\n const uint8_t *band_sizes = ctx->bands[wi->num_windows == 8];\n AacPsyCoeffs *coeffs = pctx->psy_coef[wi->num_windows == 8];\n const float avoid_hole_thr = wi->num_windows == 8 ? ", "PSY_3GPP_AH_THR_SHORT : PSY_3GPP_AH_THR_LONG;\n\n //calculate energies, initial thresholds and related values - 5.4.2 \"Threshold Calculation\"\n calc_thr_3gpp(wi, num_bands, pch, band_sizes, coefs);\n\n //modify thresholds and energies - spread, threshold in quiet, pre-echo control\n for (w = 0; w < wi->num_windows*16; w += 16) {\n AacPsyBand *bands = &pch->band[w];\n\n /* 5.4.2.3 \"Spreading\" & 5.4.3 \"Spread Energy Calculation\" */\n spread_en[0] = bands[0].energy;\n for (g = 1; g < num_bands; g++) {\n bands[g].thr = FFMAX(bands[g].thr, bands[g-1].thr * coeffs[g].spread_hi[0]);\n spread_en[w+g] = FFMAX(bands[g].energy, spread_en[w+g-1] * coeffs[g].spread_hi[1]);\n }\n for (g = num_bands - 2; g >= 0; g--) {\n bands[g].thr = FFMAX(bands[g].thr, bands[g+1].thr * coeffs[g].spread_low[0]);\n spread_en[w+g] = FFMAX(spread_en[w+g], spread_en[w+g+1] * coeffs[g].spread_low[1]);\n }\n //5.4.2.4 \"Threshold in quiet\"\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &bands[g];\n\n band->thr_quiet = band->thr = FFMAX(band->thr, coeffs[g].ath);\n //5.4.2.5 \"Pre-echo control\"\n if (!(", "wi->window_type[0] == LONG_STOP_SEQUENCE || (wi->window_type[1] == LONG_START_SEQUENCE && !", "w)))\n band->thr = FFMAX(PSY_3GPP_RPEMIN*band->thr, FFMIN(band->thr,\n PSY_3GPP_RPELEV*pch->prev_band[w+g].thr_quiet));\n\n /* 5.6.1.3.1 \"Preparatory steps of the perceptual entropy calculation\" */\n pe += calc_pe_3gpp(band);\n a += band->pe_const;\n active_lines += band->active_lines;\n\n /* 5.6.1.3.3 \"Selection of the bands for avoidance of holes\" */\n if (spread_en[w+g] * avoid_hole_thr > band->energy || coeffs[g].min_snr > 1.0f)\n band->avoid_holes = PSY_3GPP_AH_NONE;\n else\n band->avoid_holes = PSY_3GPP_AH_INACTIVE;\n }\n }\n\n /* 5.6.1.3.2 \"Calculation of the desired perceptual entropy\" */\n ctx->ch[channel].entropy = pe;\n desired_bits = calc_bit_demand(pctx, pe, ctx->bitres.bits, ctx->bitres.size, wi->num_windows == 8);\n desired_pe = PSY_3GPP_BITS_TO_PE(desired_bits);\n /* NOTE: PE correction is kept simple. ", "During initial testing it had very\n * little effect on the final bitrate. ", "Probably a good idea to come\n * back and do more testing later.", "\n */\n if (ctx->bitres.bits > 0)\n desired_pe *= av_clipf(pctx->pe.previous / PSY_3GPP_BITS_TO_PE(ctx->bitres.bits),\n 0.85f, 1.15f);\n pctx->pe.previous = PSY_3GPP_BITS_TO_PE(desired_bits);\n\n if (desired_pe < pe) {\n /* 5.6.1.3.4 \"First Estimation of the reduction value\" */\n for (w = 0; w < wi->num_windows*16; w += 16) {\n reduction = calc_reduction_3gpp(a, desired_pe, pe, active_lines);\n pe = 0.0f;\n a = 0.0f;\n active_lines = 0.0f;\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n\n band->thr = calc_reduced_thr_3gpp(band, coeffs[g].min_snr, reduction);\n /* recalculate PE */\n pe += calc_pe_3gpp(band);\n a += band->pe_const;\n active_lines += band->active_lines;\n }\n }\n\n /* 5.6.1.3.5 \"Second Estimation of the reduction value\" */\n for (i = 0; i < 2; i++) {\n float pe_no_ah = 0.0f, desired_pe_no_ah;\n active_lines = a = 0.0f;\n for (w = 0; w < wi->num_windows*16; w += 16) {\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n\n if (band->avoid_holes !", "= PSY_3GPP_AH_ACTIVE) {\n pe_no_ah += band->pe;\n a += band->pe_const;\n active_lines += band->active_lines;\n }\n }\n }\n desired_pe_no_ah = FFMAX(desired_pe - (pe - pe_no_ah), 0.0f);\n if (active_lines > 0.0f)\n reduction += calc_reduction_3gpp(a, desired_pe_no_ah, pe_no_ah, active_lines);\n\n pe = 0.0f;\n for (w = 0; w < wi->num_windows*16; w += 16) {\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n\n if (active_lines > 0.0f)\n band->thr = calc_reduced_thr_3gpp(band, coeffs[g].min_snr, reduction);\n pe += calc_pe_3gpp(band);\n band->norm_fac = band->active_lines / band->thr;\n norm_fac += band->norm_fac;\n }\n }\n delta_pe = desired_pe - pe;\n if (fabs(delta_pe) > 0.05f * desired_pe)\n break;\n }\n\n if (pe < 1.15f * desired_pe) {\n /* 6.6.1.3.6 \"Final threshold modification by linearization\" */\n norm_fac = 1.0f / norm_fac;\n for (w = 0; w < wi->num_windows*16; w += 16) {\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n\n if (band->active_lines > 0.5f) {\n float delta_sfb_pe = band->norm_fac * norm_fac * delta_pe;\n float thr = band->thr;\n\n thr *= exp2f(delta_sfb_pe / band->active_lines);\n if (thr > coeffs[g].min_snr * band->energy && band->avoid_holes == PSY_3GPP_AH_INACTIVE)\n thr = FFMAX(band->thr, coeffs[g].min_snr * band->energy);\n band->thr = thr;\n }\n }\n }\n } else {\n /* 5.6.1.3.7 \"Further perceptual entropy reduction\" */\n g = num_bands;\n while (pe > desired_pe && g--) {\n for (w = 0; w < wi->num_windows*16; w+= 16) {\n AacPsyBand *band = &pch->band[w+g];\n if (band->avoid_holes !", "= PSY_3GPP_AH_NONE && coeffs[g].min_snr < PSY_SNR_1DB) {\n coeffs[g].min_snr = PSY_SNR_1DB;\n band->thr = band->energy * PSY_SNR_1DB;\n pe += band->active_lines * 1.5f - band->pe;\n }\n }\n }\n /* TODO: allow more holes (unused without mid/side) */\n }\n }\n\n for (w = 0; w < wi->num_windows*16; w += 16) {\n for (g = 0; g < num_bands; g++) {\n AacPsyBand *band = &pch->band[w+g];\n FFPsyBand *psy_band = &ctx->ch[channel].psy_bands[w+g];\n\n psy_band->threshold = band->thr;\n psy_band->energy = band->energy;\n }\n }\n\n memcpy(pch->prev_band, pch->band, sizeof(pch->band));\n}\n\nstatic void psy_3gpp_analyze(FFPsyContext *ctx, int channel,\n const float **coeffs, const FFPsyWindowInfo *wi)\n{\n int ch;\n FFPsyChannelGroup *group = ff_psy_find_group(ctx, channel);\n\n for (ch = 0; ch < group->num_ch; ch++)\n psy_3gpp_analyze_channel(ctx, channel + ch, coeffs[ch], &wi[ch]);\n}\n\nstatic av_cold void psy_3gpp_end(FFPsyContext *apc)\n{\n AacPsyContext *pctx = (AacPsyContext*) apc->model_priv_data;\n av_freep(&pctx->ch);\n av_freep(&apc->model_priv_data);\n}\n\nstatic void lame_apply_block_type(AacPsyChannel *ctx, FFPsyWindowInfo *wi, int uselongblock)\n{\n int blocktype = ONLY_LONG_SEQUENCE;\n if (uselongblock) {\n if (ctx->next_window_seq == EIGHT_SHORT_SEQUENCE)\n blocktype = LONG_STOP_SEQUENCE;\n } else {\n blocktype = EIGHT_SHORT_SEQUENCE;\n if (ctx->next_window_seq == ONLY_LONG_SEQUENCE)\n ctx->next_window_seq = LONG_START_SEQUENCE;\n if (ctx->next_window_seq == LONG_STOP_SEQUENCE)\n ctx->next_window_seq = EIGHT_SHORT_SEQUENCE;\n }\n\n wi->window_type[0] = ctx->next_window_seq;\n ctx->next_window_seq = blocktype;\n}\n\nstatic FFPsyWindowInfo psy_lame_window(FFPsyContext *ctx, const float *audio,\n const float *la, int channel, int prev_type)\n{\n AacPsyContext *pctx = (AacPsyContext*) ctx->model_priv_data;\n AacPsyChannel *pch = &pctx->ch[channel];\n int grouping = 0;\n int uselongblock = 1;\n int attacks[AAC_NUM_BLOCKS_SHORT + 1] = { 0 };\n int i;\n FFPsyWindowInfo wi = { { 0 } };\n\n if (la) {\n float hpfsmpl[AAC_BLOCK_SIZE_LONG];\n float const *pf = hpfsmpl;\n float attack_intensity[(AAC_NUM_BLOCKS_SHORT + 1) * PSY_LAME_NUM_SUBBLOCKS];\n float energy_subshort[(AAC_NUM_BLOCKS_SHORT + 1) * PSY_LAME_NUM_SUBBLOCKS];\n float energy_short[AAC_NUM_BLOCKS_SHORT + 1] = { 0 };\n const float *firbuf = la + (AAC_BLOCK_SIZE_SHORT/4 - PSY_LAME_FIR_LEN);\n int att_sum = 0;\n\n /* LAME comment: apply high pass filter of fs/4 */\n psy_hp_filter(firbuf, hpfsmpl, psy_fir_coeffs);\n\n /* Calculate the energies of each sub-shortblock */\n for (i = 0; i < PSY_LAME_NUM_SUBBLOCKS; i++) {\n energy_subshort[i] = pch->prev_energy_subshort[i + ((AAC_NUM_BLOCKS_SHORT - 1) * PSY_LAME_NUM_SUBBLOCKS)];\n assert(pch->prev_energy_subshort[i + ((AAC_NUM_BLOCKS_SHORT - 2) * PSY_LAME_NUM_SUBBLOCKS + 1)] > 0);\n attack_intensity[i] = energy_subshort[i] / pch->prev_energy_subshort[i + ((AAC_NUM_BLOCKS_SHORT - 2) * PSY_LAME_NUM_SUBBLOCKS + 1)];\n energy_short[0] += energy_subshort[i];\n }\n\n for (i = 0; i < AAC_NUM_BLOCKS_SHORT * PSY_LAME_NUM_SUBBLOCKS; i++) {\n float const *const pfe = pf + AAC_BLOCK_SIZE_LONG / (AAC_NUM_BLOCKS_SHORT * PSY_LAME_NUM_SUBBLOCKS);\n float p = 1.0f;\n for (; pf < pfe; pf++)\n p = FFMAX(p, fabsf(*pf));\n pch->prev_energy_subshort[i] = energy_subshort[i + PSY_LAME_NUM_SUBBLOCKS] = p;\n energy_short[1 + i / PSY_LAME_NUM_SUBBLOCKS] += p;\n /* NOTE: The indexes below are [i + 3 - 2] in the LAME source.", "\n * Obviously the 3 and 2 have some significance, or this would be just [i + 1]\n * (which is what we use here). ", "What the 3 stands for is ambiguous, as it is both\n * number of short blocks, and the number of sub-short blocks.", "\n * It seems that LAME is comparing each sub-block to sub-block + 1 in the\n * previous block.", "\n */\n if (p > energy_subshort[i + 1])\n p = p / energy_subshort[i + 1];\n else if (energy_subshort[i + 1] > p * 10.0f)\n p = energy_subshort[i + 1] / (p * 10.0f);\n else\n p = 0.0;\n attack_intensity[i + PSY_LAME_NUM_SUBBLOCKS] = p;\n }\n\n /* compare energy between sub-short blocks */\n for (i = 0; i < (AAC_NUM_BLOCKS_SHORT + 1) * PSY_LAME_NUM_SUBBLOCKS; i++)\n if (!", "attacks[i / PSY_LAME_NUM_SUBBLOCKS])\n if (attack_intensity[i] > pch->attack_threshold)\n attacks[i / PSY_LAME_NUM_SUBBLOCKS] = (i % PSY_LAME_NUM_SUBBLOCKS) + 1;\n\n /* should have energy change between short blocks, in order to avoid periodic signals */\n /* Good samples to show the effect are Trumpet test songs */\n /* GB: tuned (1) to avoid too many short blocks for test sample TRUMPET */\n /* RH: tuned (2) to let enough short blocks through for test sample FSOL and SNAPS */\n for (i = 1; i < AAC_NUM_BLOCKS_SHORT + 1; i++) {\n float const u = energy_short[i - 1];\n float const v = energy_short[i];\n float const m = FFMAX(u, v);\n if (m < 40000) { /* (2) */\n if (u < 1.7f * v && v < 1.7f * u) { /* (1) */\n if (i == 1 && attacks[0] < attacks[i])\n attacks[0] = 0;\n attacks[i] = 0;\n }\n }\n att_sum += attacks[i];\n }\n\n if (attacks[0] <= pch->prev_attack)\n attacks[0] = 0;\n\n att_sum += attacks[0];\n /* 3 below indicates the previous attack happened in the last sub-block of the previous sequence */\n if (pch->prev_attack == 3 || att_sum) {\n uselongblock = 0;\n\n for (i = 1; i < AAC_NUM_BLOCKS_SHORT + 1; i++)\n if (attacks[i] && attacks[i-1])\n attacks[i] = 0;\n }\n } else {\n /* We have no lookahead info, so just use same type as the previous sequence. */", "\n uselongblock = !(", "prev_type == EIGHT_SHORT_SEQUENCE);\n }\n\n lame_apply_block_type(pch, &wi, uselongblock);\n\n wi.window_type[1] = prev_type;\n if (wi.window_type[0] !", "= EIGHT_SHORT_SEQUENCE) {\n wi.num_windows = 1;\n wi.grouping[0] = 1;\n if (wi.window_type[0] == LONG_START_SEQUENCE)\n wi.window_shape = 0;\n else\n wi.window_shape = 1;\n } else {\n int lastgrp = 0;\n\n wi.num_windows = 8;\n wi.window_shape = 0;\n for (i = 0; i < 8; i++) {\n if (!((", "pch->next_grouping >> i) & 1))\n lastgrp = i;\n wi.grouping[lastgrp]++;\n }\n }\n\n /* Determine grouping, based on the location of the first attack, and save for\n * the next frame.", "\n * FIXME: Move this to analysis.", "\n * TODO: Tune groupings depending on attack location\n * TODO: Handle more than one attack in a group\n */\n for (i = 0; i < 9; i++) {\n if (attacks[i]) {\n grouping = i;\n break;\n }\n }\n pch->next_grouping = window_grouping[grouping];\n\n pch->prev_attack = attacks[8];\n\n return wi;\n}\n\nconst FFPsyModel ff_aac_psy_model =\n{\n .name = \"3GPP TS 26.403-inspired model\",\n .init = psy_3gpp_init,\n .window = psy_lame_window,\n .analyze = psy_3gpp_analyze,\n .end = psy_3gpp_end,\n};\n" ]
{ "pile_set_name": "Github" }
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[ "SNP rules not to endorse sitting MP as general election candidate\n\nImage caption\nMichelle Thomson has been sitting as an independent MP since withdrawing from the SNP whip\n\nThe SNP’s national executive has ruled not to endorse one of its sitting MPs as a candidate in the general election.", "\n\nMichelle Thomson, who was elected as an SNP MP but is now an independent member, was summoned to a meeting of the party’s ruling body to be told she would not be selected.", "\n\nShe withdrew from the SNP whip last year amid an ongoing police investigation into property deals.", "\n\nMs Thomson said she was “very disappointed with the decision”.", "\n\nAnd she confirmed that “after careful consideration” she had decided not to put herself forward for election.", "\n\n‘No charges’\n\nThe Edinburgh West MP said: “Since September 2015 there have been reports concerning a solicitor I used some seven years ago.", "\n\n“I have always made it clear that I have done nothing wrong and it is a matter of public record that it was the solicitor who was under investigation and not myself, that no charges have ever been brought and that I assisted PS on a purely voluntary basis.", "\n\n“I must note that, even in political parties, the concept of natural justice must apply, as must the need for defined processes that are applied fairly, rigorously and transparently.", "\n\n“I would advise the SNP to employ the services of an external body to help them develop a process as soon as possible.”", "\n\nImage caption\nSNP leader Nicola Sturgeon visited her MPs the day after the snap election was announced\n\nShe added: “I have been privileged to be the MP for Edinburgh West. ", "After careful consideration I have decided not to stand again at this time and I would encourage all the political parties to avoid personal smears and instead focus on what people really want to hear about.", "\n\n“I thank all those who have supported me, those who elected me, my family and my colleagues in Westminster who so vociferously and consistently spoke out on my behalf but to no avail.”", "\n\nA decision is also due to be made about the fate of Natalie McGarry who was elected as an SNP MP, but now sits as an independent member.", "\n\nIf she is not returned, the SNP will need to find five candidates, including three for the seats the party did not win in 2015.", "\n\nImage caption\nNatalie McGarry is yet to learn whether she will be endoresed\n\nA number of party activists have already announced their intention to bid for the SNP ticket in the Glasgow East and Edinburgh West seats formerly occupied by the two women.", "\n\nOn Friday, the UK Labour party issued a call for prospective for parliamentary candidates over Twitter, inviting party members to apply with a deadline of noon on Sunday.", "\n\nThe Scottish party’s executive group is meeting over the weekend to agree their selection procedure, with leader Kezia Dugdale saying they were ready and had already been preparing for an election.", "\n\nImage caption\nDavid Mundell set out his stall against a second independence referendum, while Ian Murray said it with “JC4PM” cupcakes\n\nThe party’s sole MP north of the border, Ian Murray, launched his campaign to defend Edinburgh South on Friday. ", "Scottish Secretary David Mundell then followed suit in Dumfriesshire, Clydesdale and Tweeddale.", "\n\nRepresentatives of other parties have started to declare their candidacies for various seats.", "\n\nTory MSP Douglas Ross, who was elected to Holyrood in 2016, has announced he will challenge SNP depute leader Angus Robertson in Moray.", "\n\nAnd former Lib Dem MP Jo Swinson said she would seek a rematch with John Nicolson in East Dunbartonshire, two years after the SNP member ousted her from the seat.", "\n\nThe Lib Dems are operating all-female shortlists in a number of target seats, some of which – Edinburgh West included – may be decided over the weekend." ]
{ "pile_set_name": "Pile-CC" }
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[ "'use strict';\n\nvar range; // Create a range object for efficently rendering strings to elements.", "\nvar NS_XHTML = 'http://www.w3.org/1999/xhtml';\n\nvar doc = typeof document === 'undefined' ? ", "undefined : document;\nvar HAS_TEMPLATE_SUPPORT = !!", "doc && 'content' in doc.createElement('template');\nvar HAS_RANGE_SUPPORT = !!", "doc && doc.createRange && 'createContextualFragment' in doc.createRange();\n\nfunction createFragmentFromTemplate(str) {\n var template = doc.createElement('template');\n template.innerHTML = str;\n return template.content.childNodes[0];\n}\n\nfunction createFragmentFromRange(str) {\n if (!", "range) {\n range = doc.createRange();\n range.selectNode(doc.body);\n }\n\n var fragment = range.createContextualFragment(str);\n return fragment.childNodes[0];\n}\n\nfunction createFragmentFromWrap(str) {\n var fragment = doc.createElement('body');\n fragment.innerHTML = str;\n return fragment.childNodes[0];\n}\n\n/**\n * This is about the same\n * var html = new DOMParser().parseFromString(str, 'text/html');\n * return html.body.firstChild;\n *\n * @method toElement\n * @param {String} str\n */\nfunction toElement(str) {\n str = str.trim();\n if (HAS_TEMPLATE_SUPPORT) {\n // avoid restrictions on content for things like `<tr><th>Hi</th></tr>` which\n // createContextualFragment doesn't support\n // <template> support not available in IE\n return createFragmentFromTemplate(str);\n } else if (HAS_RANGE_SUPPORT) {\n return createFragmentFromRange(str);\n }\n\n return createFragmentFromWrap(str);\n}\n\n/**\n * Returns true if two node's names are the same.", "\n *\n * NOTE: We don't bother checking `namespaceURI` because you will never find two HTML elements with the same\n * nodeName and different namespace URIs.", "\n *\n * @param {Element} a\n * @param {Element} b The target element\n * @return {boolean}\n */\nfunction compareNodeNames(fromEl, toEl) {\n var fromNodeName = fromEl.nodeName;\n var toNodeName = toEl.nodeName;\n var fromCodeStart, toCodeStart;\n\n if (fromNodeName === toNodeName) {\n return true;\n }\n\n fromCodeStart = fromNodeName.charCodeAt(0);\n toCodeStart = toNodeName.charCodeAt(0);\n\n // If the target element is a virtual DOM node or SVG node then we may\n // need to normalize the tag name before comparing. ", "Normal HTML elements that are\n // in the \"http://www.w3.org/1999/xhtml\"\n // are converted to upper case\n if (fromCodeStart <= 90 && toCodeStart >= 97) { // from is upper and to is lower\n return fromNodeName === toNodeName.toUpperCase();\n } else if (toCodeStart <= 90 && fromCodeStart >= 97) { // to is upper and from is lower\n return toNodeName === fromNodeName.toUpperCase();\n } else {\n return false;\n }\n}\n\n/**\n * Create an element, optionally with a known namespace URI.", "\n *\n * @param {string} name the element name, e.g. 'div' or 'svg'\n * @param {string} [namespaceURI] the element's namespace URI, i.e. the value of\n * its `xmlns` attribute or its inferred namespace.", "\n *\n * @return {Element}\n */\nfunction createElementNS(name, namespaceURI) {\n return !", "namespaceURI || namespaceURI === NS_XHTML ?", "\n doc.createElement(name) :\n doc.createElementNS(namespaceURI, name);\n}\n\n/**\n * Copies the children of one DOM element to another DOM element\n */\nfunction moveChildren(fromEl, toEl) {\n var curChild = fromEl.firstChild;\n while (curChild) {\n var nextChild = curChild.nextSibling;\n toEl.appendChild(curChild);\n curChild = nextChild;\n }\n return toEl;\n}\n\nfunction syncBooleanAttrProp(fromEl, toEl, name) {\n if (fromEl[name] !", "== toEl[name]) {\n fromEl[name] = toEl[name];\n if (fromEl[name]) {\n fromEl.setAttribute(name, '');\n } else {\n fromEl.removeAttribute(name);\n }\n }\n}\n\nvar specialElHandlers = {\n OPTION: function(fromEl, toEl) {\n var parentNode = fromEl.parentNode;\n if (parentNode) {\n var parentName = parentNode.nodeName.toUpperCase();\n if (parentName === 'OPTGROUP') {\n parentNode = parentNode.parentNode;\n parentName = parentNode && parentNode.nodeName.toUpperCase();\n }\n if (parentName === 'SELECT' && !", "parentNode.hasAttribute('multiple')) {\n if (fromEl.hasAttribute('selected') && !", "toEl.selected) {\n // Workaround for MS Edge bug where the 'selected' attribute can only be\n // removed if set to a non-empty value:\n // https://developer.microsoft.com/en-us/microsoft-edge/platform/issues/12087679/\n fromEl.setAttribute('selected', 'selected');\n fromEl.removeAttribute('selected');\n }\n // We have to reset select element's selectedIndex to -1, otherwise setting\n // fromEl.selected using the syncBooleanAttrProp below has no effect.", "\n // The correct selectedIndex will be set in the SELECT special handler below.", "\n parentNode.selectedIndex = -1;\n }\n }\n syncBooleanAttrProp(fromEl, toEl, 'selected');\n },\n /**\n * The \"value\" attribute is special for the <input> element since it sets\n * the initial value. ", "Changing the \"value\" attribute without changing the\n * \"value\" property will have no effect since it is only used to the set the\n * initial value. ", " Similar for the \"checked\" attribute, and \"disabled\".", "\n */\n INPUT: function(fromEl, toEl) {\n syncBooleanAttrProp(fromEl, toEl, 'checked');\n syncBooleanAttrProp(fromEl, toEl, 'disabled');\n\n if (fromEl.value !", "== toEl.value) {\n fromEl.value = toEl.value;\n }\n\n if (!", "toEl.hasAttribute('value')) {\n fromEl.removeAttribute('value');\n }\n },\n\n TEXTAREA: function(fromEl, toEl) {\n var newValue = toEl.value;\n if (fromEl.value !", "== newValue) {\n fromEl.value = newValue;\n }\n\n var firstChild = fromEl.firstChild;\n if (firstChild) {\n // Needed for IE. ", "Apparently IE sets the placeholder as the\n // node value and vise versa. ", "This ignores an empty update.", "\n var oldValue = firstChild.nodeValue;\n\n if (oldValue == newValue || (!", "newValue && oldValue == fromEl.placeholder)) {\n return;\n }\n\n firstChild.nodeValue = newValue;\n }\n },\n SELECT: function(fromEl, toEl) {\n if (!", "toEl.hasAttribute('multiple')) {\n var selectedIndex = -1;\n var i = 0;\n // We have to loop through children of fromEl, not toEl since nodes can be moved\n // from toEl to fromEl directly when morphing.", "\n // At the time this special handler is invoked, all children have already been morphed\n // and appended to / removed from fromEl, so using fromEl here is safe and correct.", "\n var curChild = fromEl.firstChild;\n var optgroup;\n var nodeName;\n while(curChild) {\n nodeName = curChild.nodeName && curChild.nodeName.toUpperCase();\n if (nodeName === 'OPTGROUP') {\n optgroup = curChild;\n curChild = optgroup.firstChild;\n } else {\n if (nodeName === 'OPTION') {\n if (curChild.hasAttribute('selected')) {\n selectedIndex = i;\n break;\n }\n i++;\n }\n curChild = curChild.nextSibling;\n if (!", "curChild && optgroup) {\n curChild = optgroup.nextSibling;\n optgroup = null;\n }\n }\n }\n\n fromEl.selectedIndex = selectedIndex;\n }\n }\n};\n\nvar ELEMENT_NODE = 1;\nvar DOCUMENT_FRAGMENT_NODE = 11;\nvar TEXT_NODE = 3;\nvar COMMENT_NODE = 8;\n\nfunction noop() {}\n\nfunction defaultGetNodeKey(node) {\n if (node) {\n return (node.getAttribute && node.getAttribute('id')) || node.id;\n }\n}\n\nfunction morphdomFactory(morphAttrs) {\n\n return function morphdom(fromNode, toNode, options) {\n if (!", "options) {\n options = {};\n }\n\n if (typeof toNode === 'string') {\n if (fromNode.nodeName === '#document' || fromNode.nodeName === 'HTML' || fromNode.nodeName === 'BODY') {\n var toNodeHtml = toNode;\n toNode = doc.createElement('html');\n toNode.innerHTML = toNodeHtml;\n } else {\n toNode = toElement(toNode);\n }\n }\n\n var getNodeKey = options.getNodeKey || defaultGetNodeKey;\n var onBeforeNodeAdded = options.onBeforeNodeAdded || noop;\n var onNodeAdded = options.onNodeAdded || noop;\n var onBeforeElUpdated = options.onBeforeElUpdated || noop;\n var onElUpdated = options.onElUpdated || noop;\n var onBeforeNodeDiscarded = options.onBeforeNodeDiscarded || noop;\n var onNodeDiscarded = options.onNodeDiscarded || noop;\n var onBeforeElChildrenUpdated = options.onBeforeElChildrenUpdated || noop;\n var childrenOnly = options.childrenOnly === true;\n\n // This object is used as a lookup to quickly find all keyed elements in the original DOM tree.", "\n var fromNodesLookup = Object.create(null);\n var keyedRemovalList = [];\n\n function addKeyedRemoval(key) {\n keyedRemovalList.push(key);\n }\n\n function walkDiscardedChildNodes(node, skipKeyedNodes) {\n if (node.nodeType === ELEMENT_NODE) {\n var curChild = node.firstChild;\n while (curChild) {\n\n var key = undefined;\n\n if (skipKeyedNodes && (key = getNodeKey(curChild))) {\n // If we are skipping keyed nodes then we add the key\n // to a list so that it can be handled at the very end.", "\n addKeyedRemoval(key);\n } else {\n // Only report the node as discarded if it is not keyed. ", "We do this because\n // at the end we loop through all keyed elements that were unmatched\n // and then discard them in one final pass.", "\n onNodeDiscarded(curChild);\n if (curChild.firstChild) {\n walkDiscardedChildNodes(curChild, skipKeyedNodes);\n }\n }\n\n curChild = curChild.nextSibling;\n }\n }\n }\n\n /**\n * Removes a DOM node out of the original DOM\n *\n * @param {Node} node The node to remove\n * @param {Node} parentNode The nodes parent\n * @param {Boolean} skipKeyedNodes If true then elements with keys will be skipped and not discarded.", "\n * @return {undefined}\n */\n function removeNode(node, parentNode, skipKeyedNodes) {\n if (onBeforeNodeDiscarded(node) === false) {\n return;\n }\n\n if (parentNode) {\n parentNode.removeChild(node);\n }\n\n onNodeDiscarded(node);\n walkDiscardedChildNodes(node, skipKeyedNodes);\n }\n\n // // TreeWalker implementation is no faster, but keeping this around in case this changes in the future\n // function indexTree(root) {\n // var treeWalker = document.createTreeWalker(\n // root,\n // NodeFilter.", "SHOW_ELEMENT);\n //\n // var el;\n // while((el = treeWalker.nextNode())) {\n // var key = getNodeKey(el);\n // if (key) {\n // fromNodesLookup[key] = el;\n // }\n // }\n // }\n\n // // NodeIterator implementation is no faster, but keeping this around in case this changes in the future\n //\n // function indexTree(node) {\n // var nodeIterator = document.createNodeIterator(node, NodeFilter.", "SHOW_ELEMENT);\n // var el;\n // while((el = nodeIterator.nextNode())) {\n // var key = getNodeKey(el);\n // if (key) {\n // fromNodesLookup[key] = el;\n // }\n // }\n // }\n\n function indexTree(node) {\n if (node.nodeType === ELEMENT_NODE || node.nodeType === DOCUMENT_FRAGMENT_NODE) {\n var curChild = node.firstChild;\n while (curChild) {\n var key = getNodeKey(curChild);\n if (key) {\n fromNodesLookup[key] = curChild;\n }\n\n // Walk recursively\n indexTree(curChild);\n\n curChild = curChild.nextSibling;\n }\n }\n }\n\n indexTree(fromNode);\n\n function handleNodeAdded(el) {\n onNodeAdded(el);\n\n var curChild = el.firstChild;\n while (curChild) {\n var nextSibling = curChild.nextSibling;\n\n var key = getNodeKey(curChild);\n if (key) {\n var unmatchedFromEl = fromNodesLookup[key];\n // if we find a duplicate #id node in cache, replace `el` with cache value\n // and morph it to the child node.", "\n if (unmatchedFromEl && compareNodeNames(curChild, unmatchedFromEl)) {\n curChild.parentNode.replaceChild(unmatchedFromEl, curChild);\n morphEl(unmatchedFromEl, curChild);\n } else {\n handleNodeAdded(curChild);\n }\n } else {\n // recursively call for curChild and it's children to see if we find something in\n // fromNodesLookup\n handleNodeAdded(curChild);\n }\n\n curChild = nextSibling;\n }\n }\n\n function cleanupFromEl(fromEl, curFromNodeChild, curFromNodeKey) {\n // We have processed all of the \"to nodes\". ", "If curFromNodeChild is\n // non-null then we still have some from nodes left over that need\n // to be removed\n while (curFromNodeChild) {\n var fromNextSibling = curFromNodeChild.nextSibling;\n if ((curFromNodeKey = getNodeKey(curFromNodeChild))) {\n // Since the node is keyed it might be matched up later so we defer\n // the actual removal to later\n addKeyedRemoval(curFromNodeKey);\n } else {\n // NOTE: we skip nested keyed nodes from being removed since there is\n // still a chance they will be matched up later\n removeNode(curFromNodeChild, fromEl, true /* skip keyed nodes */);\n }\n curFromNodeChild = fromNextSibling;\n }\n }\n\n function morphEl(fromEl, toEl, childrenOnly) {\n var toElKey = getNodeKey(toEl);\n\n if (toElKey) {\n // If an element with an ID is being morphed then it will be in the final\n // DOM so clear it out of the saved elements collection\n delete fromNodesLookup[toElKey];\n }\n\n if (!", "childrenOnly) {\n // optional\n if (onBeforeElUpdated(fromEl, toEl) === false) {\n return;\n }\n\n // update attributes on original DOM element first\n morphAttrs(fromEl, toEl);\n // optional\n onElUpdated(fromEl);\n\n if (onBeforeElChildrenUpdated(fromEl, toEl) === false) {\n return;\n }\n }\n\n if (fromEl.nodeName !", "== 'TEXTAREA') {\n morphChildren(fromEl, toEl);\n } else {\n specialElHandlers.", "TEXTAREA(fromEl, toEl);\n }\n }\n\n function morphChildren(fromEl, toEl) {\n var curToNodeChild = toEl.firstChild;\n var curFromNodeChild = fromEl.firstChild;\n var curToNodeKey;\n var curFromNodeKey;\n\n var fromNextSibling;\n var toNextSibling;\n var matchingFromEl;\n\n // walk the children\n outer: while (curToNodeChild) {\n toNextSibling = curToNodeChild.nextSibling;\n curToNodeKey = getNodeKey(curToNodeChild);\n\n // walk the fromNode children all the way through\n while (curFromNodeChild) {\n fromNextSibling = curFromNodeChild.nextSibling;\n\n if (curToNodeChild.isSameNode && curToNodeChild.isSameNode(curFromNodeChild)) {\n curToNodeChild = toNextSibling;\n curFromNodeChild = fromNextSibling;\n continue outer;\n }\n\n curFromNodeKey = getNodeKey(curFromNodeChild);\n\n var curFromNodeType = curFromNodeChild.nodeType;\n\n // this means if the curFromNodeChild doesnt have a match with the curToNodeChild\n var isCompatible = undefined;\n\n if (curFromNodeType === curToNodeChild.nodeType) {\n if (curFromNodeType === ELEMENT_NODE) {\n // Both nodes being compared are Element nodes\n\n if (curToNodeKey) {\n // The target node has a key so we want to match it up with the correct element\n // in the original DOM tree\n if (curToNodeKey !", "== curFromNodeKey) {\n // The current element in the original DOM tree does not have a matching key so\n // let's check our lookup to see if there is a matching element in the original\n // DOM tree\n if ((matchingFromEl = fromNodesLookup[curToNodeKey])) {\n if (fromNextSibling === matchingFromEl) {\n // Special case for single element removals. ", "To avoid removing the original\n // DOM node out of the tree (since that can break CSS transitions, etc.),", "\n // we will instead discard the current node and wait until the next\n // iteration to properly match up the keyed target element with its matching\n // element in the original tree\n isCompatible = false;\n } else {\n // We found a matching keyed element somewhere in the original DOM tree.", "\n // Let's move the original DOM node into the current position and morph\n // it.", "\n\n // NOTE: We use insertBefore instead of replaceChild because we want to go through\n // the `removeNode()` function for the node that is being discarded so that\n // all lifecycle hooks are correctly invoked\n fromEl.insertBefore(matchingFromEl, curFromNodeChild);\n\n // fromNextSibling = curFromNodeChild.nextSibling;\n\n if (curFromNodeKey) {\n // Since the node is keyed it might be matched up later so we defer\n // the actual removal to later\n addKeyedRemoval(curFromNodeKey);\n } else {\n // NOTE: we skip nested keyed nodes from being removed since there is\n // still a chance they will be matched up later\n removeNode(curFromNodeChild, fromEl, true /* skip keyed nodes */);\n }\n\n curFromNodeChild = matchingFromEl;\n }\n } else {\n // The nodes are not compatible since the \"to\" node has a key and there\n // is no matching keyed node in the source tree\n isCompatible = false;\n }\n }\n } else if (curFromNodeKey) {\n // The original has a key\n isCompatible = false;\n }\n\n isCompatible = isCompatible !", "== false && compareNodeNames(curFromNodeChild, curToNodeChild);\n if (isCompatible) {\n // We found compatible DOM elements so transform\n // the current \"from\" node to match the current\n // target DOM node.", "\n // MORPH\n morphEl(curFromNodeChild, curToNodeChild);\n }\n\n } else if (curFromNodeType === TEXT_NODE || curFromNodeType == COMMENT_NODE) {\n // Both nodes being compared are Text or Comment nodes\n isCompatible = true;\n // Simply update nodeValue on the original node to\n // change the text value\n if (curFromNodeChild.nodeValue !", "== curToNodeChild.nodeValue) {\n curFromNodeChild.nodeValue = curToNodeChild.nodeValue;\n }\n\n }\n }\n\n if (isCompatible) {\n // Advance both the \"to\" child and the \"from\" child since we found a match\n // Nothing else to do as we already recursively called morphChildren above\n curToNodeChild = toNextSibling;\n curFromNodeChild = fromNextSibling;\n continue outer;\n }\n\n // No compatible match so remove the old node from the DOM and continue trying to find a\n // match in the original DOM. ", "However, we only do this if the from node is not keyed\n // since it is possible that a keyed node might match up with a node somewhere else in the\n // target tree and we don't want to discard it just yet since it still might find a\n // home in the final DOM tree. ", "After everything is done we will remove any keyed nodes\n // that didn't find a home\n if (curFromNodeKey) {\n // Since the node is keyed it might be matched up later so we defer\n // the actual removal to later\n addKeyedRemoval(curFromNodeKey);\n } else {\n // NOTE: we skip nested keyed nodes from being removed since there is\n // still a chance they will be matched up later\n removeNode(curFromNodeChild, fromEl, true /* skip keyed nodes */);\n }\n\n curFromNodeChild = fromNextSibling;\n } // END: while(curFromNodeChild) {}\n\n // If we got this far then we did not find a candidate match for\n // our \"to node\" and we exhausted all of the children \"from\"\n // nodes. ", "Therefore, we will just append the current \"to\" node\n // to the end\n if (curToNodeKey && (matchingFromEl = fromNodesLookup[curToNodeKey]) && compareNodeNames(matchingFromEl, curToNodeChild)) {\n fromEl.appendChild(matchingFromEl);\n // MORPH\n morphEl(matchingFromEl, curToNodeChild);\n } else {\n var onBeforeNodeAddedResult = onBeforeNodeAdded(curToNodeChild);\n if (onBeforeNodeAddedResult !", "== false) {\n if (onBeforeNodeAddedResult) {\n curToNodeChild = onBeforeNodeAddedResult;\n }\n\n if (curToNodeChild.actualize) {\n curToNodeChild = curToNodeChild.actualize(fromEl.ownerDocument || doc);\n }\n fromEl.appendChild(curToNodeChild);\n handleNodeAdded(curToNodeChild);\n }\n }\n\n curToNodeChild = toNextSibling;\n curFromNodeChild = fromNextSibling;\n }\n\n cleanupFromEl(fromEl, curFromNodeChild, curFromNodeKey);\n\n var specialElHandler = specialElHandlers[fromEl.nodeName];\n if (specialElHandler) {\n specialElHandler(fromEl, toEl);\n }\n } // END: morphChildren(...)\n\n var morphedNode = fromNode;\n var morphedNodeType = morphedNode.nodeType;\n var toNodeType = toNode.nodeType;\n\n if (!", "childrenOnly) {\n // Handle the case where we are given two DOM nodes that are not\n // compatible (e.g. <div> --> <span> or <div> --> TEXT)\n if (morphedNodeType === ELEMENT_NODE) {\n if (toNodeType === ELEMENT_NODE) {\n if (!", "compareNodeNames(fromNode, toNode)) {\n onNodeDiscarded(fromNode);\n morphedNode = moveChildren(fromNode, createElementNS(toNode.nodeName, toNode.namespaceURI));\n }\n } else {\n // Going from an element node to a text node\n morphedNode = toNode;\n }\n } else if (morphedNodeType === TEXT_NODE || morphedNodeType === COMMENT_NODE) { // Text or comment node\n if (toNodeType === morphedNodeType) {\n if (morphedNode.nodeValue !", "== toNode.nodeValue) {\n morphedNode.nodeValue = toNode.nodeValue;\n }\n\n return morphedNode;\n } else {\n // Text node to something else\n morphedNode = toNode;\n }\n }\n }\n\n if (morphedNode === toNode) {\n // The \"to node\" was not compatible with the \"from node\" so we had to\n // toss out the \"from node\" and use the \"to node\"\n onNodeDiscarded(fromNode);\n } else {\n if (toNode.isSameNode && toNode.isSameNode(morphedNode)) {\n return;\n }\n\n morphEl(morphedNode, toNode, childrenOnly);\n\n // We now need to loop over any keyed nodes that might need to be\n // removed. ", "We only do the removal if we know that the keyed node\n // never found a match. ", "When a keyed node is matched up we remove\n // it out of fromNodesLookup and we use fromNodesLookup to determine\n // if a keyed node has been matched up or not\n if (keyedRemovalList) {\n for (var i=0, len=keyedRemovalList.length; i<len; i++) {\n var elToRemove = fromNodesLookup[keyedRemovalList[i]];\n if (elToRemove) {\n removeNode(elToRemove, elToRemove.parentNode, false);\n }\n }\n }\n }\n\n if (!", "childrenOnly && morphedNode !", "== fromNode && fromNode.parentNode) {\n if (morphedNode.actualize) {\n morphedNode = morphedNode.actualize(fromNode.ownerDocument || doc);\n }\n // If we had to swap out the from node with a new node because the old\n // node was not compatible with the target node then we need to\n // replace the old DOM node in the original DOM tree. ", "This is only\n // possible if the original DOM node was part of a DOM tree which\n // we know is the case if it has a parent node.", "\n fromNode.parentNode.replaceChild(morphedNode, fromNode);\n }\n\n return morphedNode;\n };\n}\n\nmodule.exports = morphdomFactory;\n" ]
{ "pile_set_name": "Github" }
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[ "Q:\n\nDo there exist families of groups $G_{s}$ such that $\\forall s\\in[0,1], |G_{s}|=\\mathfrak{c}$\n\nDo there exist families of isomorphism classes of groups $G_{s}$ such that $\\forall s\\in[0,1], |G_{s}|=\\mathfrak{c}$, where $\\mathfrak{c}$ is the cardinality of the continuum, and for any $a,b\\in[0,1], a\\neq b$, $G_{a}$≇$G_{b}$?", "\n\nA:\n\nI think you are asking if there are families $\\{G_t:t\\in[0,1]\\}$ of Lie groups of positive dimension whose elements are non-isomorphic in pairs.", "\nThere are examples of curves of non-isomorphic Lie groups in the class of nilpotent groups. ", "In fact, as soon as the dimension is greater or equal to $7$, there are continuously-many non-isomorphic filiform Lie algebras, so the same thing happens for groups (filiform Lie algebras are \"maximally non-abelian\" nilpotent Lie algebras) This is discussed in detail, for example, in the book by Goze on Nilpotent Lie algebras. ", "\nAs the dimension grows, we find families of unbounded dimension.", "\nIn general, the nilpotent part of the world is filled with many, many examples.", "\n\n" ]
{ "pile_set_name": "StackExchange" }
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[ "/*\n * Copyright (C) Google 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 */\n\n#include \"game_consts.hpp\"\n#include \"obstacle_generator.hpp\"\n\nvoid ObstacleGenerator::Generate(Obstacle *result) {\n static const int PROB_TABLE[] = {\n // EASY MED INT HARD\n 100, 0, 0, 0, // difficulty 0\n 75, 25, 0, 0, // difficulty 1\n 50, 50, 0, 0, // difficulty 2\n 25, 75, 0, 0, // difficulty 3\n 0, 100, 0, 0, // difficulty 4\n 0, 75, 25, 0, // difficulty 5\n 0, 50, 50, 0, // difficulty 6\n 0, 25, 75, 0, // difficulty 7\n 0, 0, 100, 0, // difficulty 8\n 0, 0, 75, 25, // difficulty 9\n 0, 0, 50, 50, // difficulty 10\n 0, 0, 25, 75, // difficulty 11\n 0, 0, 0, 100 // difficulty 12+\n };\n result->Reset();\n result->style = 1 + Random(7);\n\n int d = Clamp(mDifficulty, 0, 12);\n int easyProb = PROB_TABLE[d * 4];\n int medProb = PROB_TABLE[d * 4 + 1];\n int intermediateProb = PROB_TABLE[d * 4 + 2];\n int roll = Random(100);\n if (roll <= easyProb) {\n GenEasy(result);\n } else if (roll <= easyProb + medProb) {\n GenMedium(result);\n } else if (roll <= easyProb + medProb + intermediateProb) {\n GenIntermediate(result);\n } else {\n GenHard(result);\n }\n result->PutRandomBonus();\n}\n\nvoid ObstacleGenerator::FillRow(Obstacle *result, int row) {\n for (int i = 0; i < OBS_GRID_SIZE; ++i) {\n result->grid[i][row] = true;\n }\n}\n\nvoid ObstacleGenerator::FillCol(Obstacle *result, int col) {\n for (int i = 0; i < OBS_GRID_SIZE; ++i) {\n result->grid[col][i] = true;\n }\n}\n\nvoid ObstacleGenerator::GenEasy(Obstacle *result) {\n int n = Random(4);\n int i, j;\n Obstacle *o = result; // shorthand\n switch (n) {\n case 0:\n i = Random(1, OBS_GRID_SIZE - 1); // i is the row of the bonus\n FillRow(result, i + (Random(2) ? ", "1 : -1)); // horizontal bar next to i\n break;\n case 1:\n i = Random(1, OBS_GRID_SIZE - 1); // i is the column of the bonus\n FillCol(result, i + (Random(2) ? ", "1 : -1)); // vertical bar next to i\n break;\n case 2:\n FillRow(result, 0);\n FillRow(result, OBS_GRID_SIZE - 1);\n FillCol(result, 0);\n FillCol(result, OBS_GRID_SIZE - 1);\n break;\n default:\n i = Random(0, OBS_GRID_SIZE - 2); // i is the row of the bonus\n j = Random(0, OBS_GRID_SIZE - 2); // i is the row of the bonus\n o->grid[i][j] = o->grid[i+1][j] = o->grid[i][j+1] = o->grid[i+1][j+1] = true;\n break;\n }\n}\n\nvoid ObstacleGenerator::GenMedium(Obstacle *result) {\n int n = Random(3);\n int i;\n switch (n) {\n case 0:\n i = Random(1, OBS_GRID_SIZE - 1); // i is the row of the bonus\n FillRow(result, i + 1);\n FillRow(result, i - 1);\n break;\n case 1:\n i = Random(1, OBS_GRID_SIZE - 1); // i is the column of the bonus\n FillCol(result, i - 1);\n FillCol(result, i + 1);\n break;\n default:\n i = Random(1, OBS_GRID_SIZE - 1); // i is the column of the bonus\n FillRow(result, i);\n FillCol(result, i);\n break;\n\n }\n}\n\nvoid ObstacleGenerator::GenIntermediate(Obstacle *result) {\n int n = Random(3);\n int i;\n switch (n) {\n case 0:\n i = Random(0, OBS_GRID_SIZE - 2);\n FillRow(result, i);\n FillRow(result, i + 1);\n FillRow(result, i + 2);\n break;\n case 1:\n i = Random(0, OBS_GRID_SIZE - 2); // i is the column of the bonus\n FillCol(result, i);\n FillCol(result, i + 1);\n FillCol(result, i + 2);\n break;\n default:\n i = Random(1, OBS_GRID_SIZE - 2); // i is the column of the bonus\n FillCol(result, i - 1);\n FillCol(result, i + 1);\n FillCol(result, i + 2);\n break;\n }\n}\n\nvoid ObstacleGenerator::GenHard(Obstacle *result) {\n int n = Random(4);\n int i;\n int j;\n switch (n) {\n case 0:\n i = Random(0, OBS_GRID_SIZE - 3);\n FillRow(result, i);\n FillRow(result, i + 1);\n FillRow(result, i + 2);\n FillRow(result, i + 3);\n result->grid[Random(0, OBS_GRID_SIZE)][Random(0, OBS_GRID_SIZE)] = false;\n break;\n case 1:\n i = Random(0, OBS_GRID_SIZE - 3);\n FillCol(result, i);\n FillCol(result, i + 1);\n FillCol(result, i + 2);\n FillCol(result, i + 3);\n result->grid[Random(0, OBS_GRID_SIZE)][Random(0, OBS_GRID_SIZE)] = false;\n break;\n case 2:\n i = Random(0, OBS_GRID_SIZE);\n for (j = 0; j < OBS_GRID_SIZE; j++) {\n if (i !", "= j) {\n FillCol(result, i);\n }\n }\n result->grid[Random(0, OBS_GRID_SIZE)][Random(0, OBS_GRID_SIZE)] = false;\n break;\n default:\n i = Random(0, OBS_GRID_SIZE);\n for (j = 0; j < OBS_GRID_SIZE; j++) {\n if (i !", "= j) {\n FillRow(result, i);\n }\n }\n result->grid[Random(0, OBS_GRID_SIZE)][Random(0, OBS_GRID_SIZE)] = false;\n break;\n }\n}\n\n" ]
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[ "Q:\n\nDifferences between Steam and Age of Steam?", "\n\nWhat are the key differences between the Steam and Age of Steam games? ", "\n\nA:\n\nAssuming you're referring to the \"standard\" version of Steam, the two major differences from Age of Steam are:\n\nSplit income and VP tracks. ", "When delivering goods, you must choose where your points go, either to an income track (that goes from -10 to +10) or to your victory point track. ", "Early in the game, you'd usually concentrate on income to grow your business, then at some point switch to VPs.", "\nThere is no board with randomized upcoming goods for each city and therefore no \"production\" action. ", "Instead, 12 sets of 3 goods are available for use with the new \"city growth\" action or when you place down a new city tile while \"urbanizing\". ", "A startup city can only get one new set of goods with city growth, and urbanized cities cannot get another set after being placed.", "\n\nSmaller rule changes include tile costs, tile distribution, no income reduction, loco is not allowed if you're on 6 already, final scoring for tracks is 1 VP per link, and when shipping you can't give more points to any other player.", "\nThis great review contains a more detailed list of differences.", "\n\n" ]
{ "pile_set_name": "StackExchange" }
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[ "Daymark\n\nA daymark or a day marker is the daytime identifier (attached signboard) of an aid to navigation (ATON) or daybeacon.", "\n\nGenerally, the daymark conveys to the mariner during daylight hours the same significance as does the aid's light or reflector at night.", "\n\nDaymark chart symbols\n\nSee also \n\n Buoy\n Day beacon\n Landmark\n Sea mark\n Lighthouse\n Lightvessel\n Trinity House Obelisk\n\nReferences \n\nCategory:Aids to navigation" ]
{ "pile_set_name": "Wikipedia (en)" }
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[ "Vortex Cores of Inertial Particles.", "\nThe cores of massless, swirling particle motion are an indicator for vortex-like behavior in vector fields and to this end, a number of coreline extractors have been proposed in the literature. ", "Though, many practical applications go beyond the study of the vector field. ", "Instead, engineers seek to understand the behavior of inertial particles moving therein, for instance in sediment transport, helicopter brownout and pulverized coal combustion. ", "In this paper, we present two strategies for the extraction of the corelines that inertial particles swirl around, which depend on particle density, particle diameter, fluid viscosity and gravity. ", "The first is to deduce the local swirling behavior from the autonomous inertial motion ODE, which eventually reduces to a parallel vectors operation. ", "For the second strategy, we use a particle density estimation to locate inertial attractors. ", "With this, we are able to extract the cores of swirling inertial particle motion for both steady and unsteady 3D vector fields. ", "We demonstrate our techniques in a number of benchmark data sets, and elaborate on the relation to traditional massless corelines." ]
{ "pile_set_name": "PubMed Abstracts" }
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0.000868
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[ "/*-\n * <<\n * sag\n * ==\n * Copyright (C) 2019 sia\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\n\npackage com.creditease.gateway.helper;\n\nimport java.text.", "ParseException;\nimport java.text.", "SimpleDateFormat;\nimport java.util.", "Calendar;\nimport java.util.", "Date;\n/***\n * \n * @author admin\n *\n */\npublic class TimeHelper {\n\n public static String getCurTimeStr() {\n\n return getCurTimeStr(\"yyyy-MM-dd HH:mm\");\n }\n\n public static String getCurTimeStr(String format) {\n\n return getDateTimeStr(new Date(), format);\n }\n\n public static String getDateTimeStr(Date date, String format) {\n\n SimpleDateFormat formatter = new SimpleDateFormat(format);\n String dateString = formatter.format(date);\n return dateString;\n }\n \n public static Date getDateTime(String timeStr, String format){\n \t\n \tDate date = null;\n \tSimpleDateFormat sdf = new SimpleDateFormat(format);\n \ttry {\n\t\t\tdate = sdf.parse(timeStr);\n\t\t} catch (ParseException e) {\n\t\t\t\n\t\t\te.printStackTrace();\n\t\t}\n \treturn date;\n }\n \n public static Calendar str2Calendar(String timeStr, String format){\n \t\n\t\treturn str2Calendar(getDateTime(timeStr, format)) ;\n }\n\n public static Calendar str2Calendar(Date date){\n \t\n \tCalendar calendar = null;\n \tif(null == date){\n \t\treturn calendar;\n \t}\n \t\n \tcalendar = Calendar.getInstance();\n \tcalendar.setTime(date);\n\t\treturn calendar;\n } \n \n public static String calendar2Str(Calendar calendar, String format){\n \t\n \treturn getDateTimeStr(calendar.getTime(), format);\n \t\n }\n \n}\n" ]
{ "pile_set_name": "Github" }
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[ "#\n# kernel/controllers/cpuset/cpuset_hierarchy_test testcase Makefile.", "\n#\n# Copyright (C) 2009, Cisco Systems Inc.\n#\n# This program is free software; you can redistribute it and/or modify\n# it under the terms of the GNU General Public License as published by\n# the Free Software Foundation; either version 2 of the License, or\n# (at your option) any later version.", "\n#\n# This program is distributed in the hope that it will be useful,\n# but WITHOUT ANY WARRANTY; without even the implied warranty of\n# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n# GNU General Public License for more details.", "\n#\n# You should have received a copy of the GNU General Public License along\n# with this program; if not, write to the Free Software Foundation, Inc.,\n# 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301 USA.", "\n#\n# Ngie Cooper, July 2009\n#\n\ntop_srcdir ?", "= ../../../../..\n\ninclude $(top_srcdir)/include/mk/testcases.mk\ninclude $(abs_srcdir)/../Makefile.inc\n\nMAKE_TARGETS\t\t:=\n\ninclude $(top_srcdir)/include/mk/generic_leaf_target.mk\n" ]
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[ "1. ", "Field of the Invention\nThe present invention relates to a medical report creating apparatus operating in a medical information system to create, for example, a report on results of interpretation of medical images that a medical specialist is requested to interpret, and in particular, to a technique for allowing the easy linkage of a string in observations in a report to an image, a past medical report, or another file which corresponds to the contents of the string.", "\n2. ", "Description of the Related Art\nActs of medical treatment have hitherto been classified into a large number of technical fields. ", "Medical specialists have been commonly requested to interpret medical images obtained using an image diagnosis apparatus such as X ray diagnostic apparatus, X ray CT apparatus, and MRI apparatus. ", "When requested to interpret such an image, a medical specialist causes the image to be displayed, makes a report on it (a report on interpretation of the medical image; referred to as a medical report below), and delivers the report to the requester.", "\nAn apparatus that electronically creates such a medical report has already been put to practical use. ", "With this apparatus, for example, medical images delivered by the requester through network distribution are stored in a server. ", "When the image interpreter gives an instruction on creation of a medical report, the apparatus displays a sheet used to create a report, on a screen, and accepts inputs to required items shown in the sheet. ", "Then, the apparatus sequentially displays the images to be interpreted in accordance with the image interpreter's input instructions. ", "If the image interpreter has added his or her opinion to observations on the images, the apparatus enters the opinion in an observation column in the sheet. ", "If the image interpreter has input the results of a diagnosis on the basis of the image observations and in view of the requester's purpose of the check, the apparatus writes the contents of the results to a diagnosis column. ", "On this occasion, for images pointed out in the observations, the apparatus can create and paste reduced/enlarged images or cut images to an image pasted column or the like as required. ", "The apparatus then delivers sheet data in the medical report created using the above procedure, to the requester through, for example, a network.", "\nFor reports created using conventional medical report creating apparatuses such as the one described above, some people have pointed out difficulties in understanding the relationship between the contents of the entries in the observations and the pasted images. ", "For example, if a plurality of similar images is pointed out in the sentences of the observations, the images pointed-out may be mistaken. ", "Further, if pasted images are displayed on the report screen, the observation information may not be correctly understood depending on the resolution of a monitor or the size of the screen. ", "Furthermore, if the image interpreter desires to reference not only images to be interpreted but also a past medical report, historical information, and the like, the image interpreter must perform a cumbersome operation of reading, editing, and pasting information files to the report.", "\nJpn. ", "Pat. ", "Appln. ", "KOKAI Publication No. ", "1998-079770 provides a technique for utilizing link information required to reference a particular group of files as external information in order to share diagnostic information in an electronic health record system. ", "However, the technique described in this publication only enables any medical institutions to extract a particular group of files on the basis of link information by presenting a patient card in which the link information is stored. ", "Accordingly, the technique cannot simply be utilized for the creation of a medical report." ]
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[ "With the popularization of smartphones, location based services (LBS) are increasingly concerned, and a requirement of a user on global positioning system (GPS) experience is increasingly high. ", "A GPS positioning speed is a key factor affecting user experience.", "\nAn assisted GPS (AGPS, network assisted GPS) positioning technology integrates advantages of GPS positioning and cellular base station positioning. ", "When a mobile terminal performs GPS positioning by using the AGPS positioning technology, the mobile terminal can acquire, from a cellular network, auxiliary information required during the GPS positioning, for example, information about a satellite frequency band available in a current region, a position, an elevation angle, and the like, so that a full-band and large-scale search is avoided, thereby greatly increasing a first-time satellite searching speed. ", "Therefore, the AGPS positioning technology, by virtue of a data transmission function of the cellular network, can increase a positioning speed and improve positioning precision.", "\nHowever, the AGPS positioning technology is implemented only by performing multiple times of data transmission through a network, and has a relatively high requirement on network signal quality, and when the network signal quality is poor, an AGPS positioning speed is significantly affected." ]
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[ "Q:\n\nWrite IPTable rules\n\nHow to write IPTable rules such that the administrator on 128.238.66.2 has ssh access to the firewall and no one else is allowed access?", "\nIs it like: iptables –A INPUT –s 128.238.66.2 –j ACCEPT?", "\n\nA:\n\nTry like this (please be aware that if the IP is wrong, you're locked out):\niptables -A INPUT -p tcp --dport ssh -j REJECT\niptables -A INPUT -p tcp -s 128.238.66.2 --dport ssh -m state --state NEW,ESTABLISHED -j ACCEPT\niptables -A OUTPUT -p tcp --sport ssh -m state --state ESTABLISHED -j ACCEPT\n\n" ]
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[ "The system and method described herein relates generally to generator repair. ", "More specifically, the system and method relates to repairing a wind turbine generator in-situ.", "\nAt least some known wind turbines include machines for converting variable speed mechanical input from blades of the wind turbine into electric power that is compliant with an electrical grid. ", "For example, some known wind turbines include a doubly fed induction generator (DFIG) for converting the variable speed mechanical input.", "\nSome known DFIG generator rotors have a floating neutral point. ", "This is frequently provided by a Wye ring. ", "The Wye ring is typically made from a copper bar and is located at the non-drive end (NDE) of the generator. ", "Due to operational stresses which fatigue the brazed connection between the Wye ring and its rotor connection points (or terminal lugs), cracks can develop which lead to discontinuity. ", "When the first crack occurs, the generator continues to function satisfactorily since the current can still reach all three rotor connection points. ", "However, if a second crack occurs in the Wye ring, at least one part (e.g., one phase) of the rotor windings are now disconnected from the floating neutral. ", "This results in severe arcing across one of the cracks, and leads to failure of the insulation around the Wye ring. ", "Eventually, cross-over arcing occurs between the Wye ring and the phase lead. ", "The wind turbine monitoring system detects this cross-over arcing condition and recognizes it as a phase fault, and accordingly shuts the wind turbine down.", "\nIn the past, the only way to repair a cracked Wye ring was to replace the entire generator. ", "To accomplish this repair, a crane capable of lifting heavy loads (e.g., 10 metric tons) to great heights (e.g., 80 meters-100 meters) is required. ", "Cranes of this type are expensive and the generator replacement operation is costly and time consuming. ", "In addition, the wind turbine must be out of service until the new generator is installed." ]
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[ "Induced Pluripotent Stem Cell-Derived Hematopoietic Embryoid Bodies Secrete Sphingosine-1-Phosphate and Revert Endothelial Injury.", "\nThe possibility of sphingosine-1-phosphate production by induced pluripotent stem cells is examined to assess their potential in treatment of sepsis. ", "The hematopoietic embryoid bodies were derived from the culture of 6-day-old differentiated induced pluripotent stem cells. ", "These embryoid bodies secreted sphingosine-1-phosphate, an important bioactive lipid that regulates integrity of the pulmonary endothelial barrier, prevents elevation of its permeability, and impedes the formation of stress fibers in human endotheliocytes derived from umbilical vein. ", "The data attest to potentiality of induced pluripotent stem cells in treatment of sepsis." ]
{ "pile_set_name": "PubMed Abstracts" }
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[ "Scottish Renewables\n\nScottish Renewables is the representative body of the Scottish renewable energy industry. ", "Since 1996, it has aimed to present a united voice to decision makers who make energy policy. ", " Scottish Renewables represents over 300 members and member organisations are wide ranging across all technologies and supply chains. ", "Scottish Renewables has developed 14 focus areas to fully represent the renewable energy industry. ", "These include: offshore wind power, onshore wind power, bioenergy, heat, hydro, marine energy, and microgeneration.", "\n\nJohanna Yates, offshore policy manager for Scottish Renewables, has said Scotland is the natural home to offshore renewable energy, with abundant natural resources and long heritage of maritime industry – principally oil and gas and fisheries. ", "Scotland’s potential is well known and in recent months there has been investment from significant international players, such as Doosan, Mitsubishi and Gamesa, all vying to establish their wind turbines in Scottish waters. ", "Future employment for offshore wind projects is promising, with up to 28,000 direct jobs being created by 2020, leading to an economic input of £7 billion.", "\n\nSee also\nForum for Renewable Energy Development in Scotland\nRenewable energy in Scotland\nWind power in Scotland\n\nReferences\n\nExternal links\n \n\nCategory:Renewable energy in Scotland\nCategory:1996 establishments in Scotland\nCategory:Industry trade groups based in Scotland\nCategory:Industry in Scotland\nCategory:Organizations established in 1996\nCategory:Organisations based in Glasgow\nCategory:Renewable energy organizations" ]
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