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[ "Insurance Blog\n\nPlease read and comment on our blog about a wide variety of insurance topics. ", "Please feel free to ask us any questions.", "\n\n5 Workplace Safety Tips for Small Businesses and Startups\n\nMarch 4, 2016\n\nSafety may not be the sexiest part of running a business, but it’s an essential one. ", "No one wants to work in an unsafe environment. ", "And no company wants to be responsible for putting the life and well-being of its workers at risk.", "\n\nWhile you can’t prevent every accident, there are some steps you can take to minimize the chances of one happening. ", "Here are five workplace safety tips that can help keep your small business or startup safe.", "\n\n1. ", "Make safety rules accessible and visible.", "\n\nYour workplace should already have some safety measures in place. ", "But having them in the rule book isn’t enough—you need to make them accessible to employees as well. ", "Take the time to summarize your rules in a concise, clear list before posting them in several visible places as a reminder and precaution for all employees.", "\n\n2. ", "Get employees on board.", "\n\nThe job of keeping everyone safe becomes easier when your employees care as much as you do. ", "Rick Goggins, an ergonomist with the Washington State Department of Labor and Industries (DOSH), said that one of the best approaches is “to create a thorough ergonomics process that involves employees in finding hazards and development solutions to control them.” ", "Encouraging safety awareness helps employees stay mindful of their surroundings and be on the lookout for any potential dangers.", "\n\n3. ", "Cultivate team-oriented accountability and communication.", "\n\nRegardless of position or title, every employee should be a safety officer. ", "If something is potentially unsafe, anyone should feel empowered to say something before it’s too late. ", "There truly is no price on the value of safety for all employees.", "\n\n4. ", "Avoid shortcuts.", "\n\nWith orders to fill, customers to satisfy and other to-dos piling up on your desk, it’s easy to be tempted to compromise safety in the name of expediency. ", "But according to Arbill, a leader in industrial safety products, that kind of “get-it-done-quickly” attitude is the cause behind many accidents. ", "No matter what, encourage employees to follow proper procedures despite how long it takes.", "\n\n5. ", "Practice emergency preparedness.", "\n\nSafety training should be a part of your onboarding, team building and continuing education Doing so will help employees familiarize themselves with safety procedures and allow them to develop a set of solid strategies to respond effectively in the event of an emergency.", "\n\nSometimes an accident will happen despite your best efforts. ", "If one does, you’ll be glad to have workers’ compensation insurance. ", "Workers’ compensation insurance provides coverage for injury or disease sustained by your employees during the course and scope of their employment, regardless of negligence on your part. ", "If you have workers’ comp coverage through Erie Insurance, you may be able to access a staff of risk control consultants that can provide you with a variety of risk control and safety services for your business. ", "To learn more about workers’ comp coverage from ERIE and to get a free quote, contact an Erie Insurance agent in your community.", "\n\nTom Reddon is a Forklift Specialist and Blog Manager for National Forklift Exchange. ", "He also sits on the Material Handling Equipment Distributors Association Executive Dialogue team. ", "Connect with him via Twitter at @TomReddon.", "\n\nCasper Insurance is committed to providing you superior service. ", "We know that your insurance dollars can be spent in many ways. ", "We want to EARN your business by regularly reviewing your coverage, and helping you receive the best value for your insurance dollar." ]

{ "pile_set_name": "Pile-CC" }

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[ "package com.example.senior;\n\nimport java.util.", "ArrayList;\n\nimport android.graphics.", "Color;\nimport android.os.", "Bundle;\nimport android.support.v7.app.", "AppCompatActivity;\nimport android.view.", "View;\nimport android.widget.", "AdapterView;\nimport android.widget.", "ArrayAdapter;\nimport android.widget.", "GridView;\nimport android.widget.", "Spinner;\nimport android.widget.", "AdapterView.", "OnItemSelectedListener;\n\nimport com.example.senior.adapter.", "PlanetGridAdapter;\nimport com.example.senior.bean.", "Planet;\nimport com.example.senior.util.", "Utils;\n\n/**\n * Created by ouyangshen on 2017/10/7.", "\n */\npublic class GridViewActivity extends AppCompatActivity {\n private final static String TAG = \"GridViewActivity\";\n private GridView gv_planet; // 声明一个网格视图对象\n\n @Override\n protected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n setContentView(R.layout.activity_grid_view);\n ArrayList<Planet> planetList = Planet.getDefaultList();\n // 构建一个行星队列的网格适配器\n PlanetGridAdapter adapter = new PlanetGridAdapter(this, planetList);\n // 从布局视图中获取名叫gv_planet的网格视图\n gv_planet = findViewById(R.id.gv_planet);\n // 给gv_planet设置行星网格适配器\n gv_planet.setAdapter(adapter);\n // 给gv_planet设置网格项的点击监听器\n gv_planet.setOnItemClickListener(adapter);\n // 给gv_planet设置网格项的长按监听器\n gv_planet.setOnItemLongClickListener(adapter);\n // 初始化分隔线下拉框\n initDividerSpinner();\n }\n\n // 初始化分隔线显示方式的下拉框\n private void initDividerSpinner() {\n ArrayAdapter<String> dividerAdapter = new ArrayAdapter<String>(this,\n R.layout.item_select, dividerArray);\n Spinner sp_grid = findViewById(R.id.sp_grid);\n sp_grid.setPrompt(\"请选择分隔线显示方式\");\n sp_grid.setAdapter(dividerAdapter);\n sp_grid.setOnItemSelectedListener(new DividerSelectedListener());\n sp_grid.setSelection(0);\n }\n\n private String[] dividerArray = {\n \"不显示分隔线\",\n \"只显示内部分隔线(NO_STRETCH)\",\n \"只显示内部分隔线(COLUMN_WIDTH)\",\n \"只显示内部分隔线(STRETCH_SPACING)\",\n \"只显示内部分隔线(SPACING_UNIFORM)\",\n \"显示全部分隔线(看我用padding大法)\"\n };\n class DividerSelectedListener implements OnItemSelectedListener {\n public void onItemSelected(AdapterView<?", "> arg0, View arg1, int arg2, long arg3) {\n int dividerPad = Utils.dip2px(GridViewActivity.this, 2); // 定义间隔宽度为2dp\n gv_planet.setBackgroundColor(Color.", "RED); // 设置gv_planet的背景颜色\n gv_planet.setHorizontalSpacing(dividerPad); // 设置gv_planet的水平方向空白\n gv_planet.setVerticalSpacing(dividerPad); // 设置gv_planet的垂直方向空白\n gv_planet.setStretchMode(GridView.", "STRETCH_COLUMN_WIDTH); // 设置gv_planet的拉伸模式\n gv_planet.setColumnWidth(Utils.dip2px(GridViewActivity.this, 120)); // 设置每列宽度为120dp\n gv_planet.setPadding(0, 0, 0, 0); // 设置gv_planet的四周空白\n if (arg2 == 0) { // 不显示分隔线\n gv_planet.setBackgroundColor(Color.", "WHITE);\n gv_planet.setHorizontalSpacing(0);\n gv_planet.setVerticalSpacing(0);\n } else if (arg2 == 1) { // 只显示内部分隔线(NO_STRETCH)\n gv_planet.setStretchMode(GridView.", "NO_STRETCH);\n } else if (arg2 == 2) { // 只显示内部分隔线(COLUMN_WIDTH)\n gv_planet.setStretchMode(GridView.", "STRETCH_COLUMN_WIDTH);\n } else if (arg2 == 3) { // 只显示内部分隔线(STRETCH_SPACING)\n gv_planet.setStretchMode(GridView.", "STRETCH_SPACING);\n } else if (arg2 == 4) { // 只显示内部分隔线(SPACING_UNIFORM)\n gv_planet.setStretchMode(GridView.", "STRETCH_SPACING_UNIFORM);\n } else if (arg2 == 5) { // 显示全部分隔线（使用padding）\n gv_planet.setPadding(dividerPad, dividerPad, dividerPad, dividerPad);\n }\n }\n\n public void onNothingSelected(AdapterView<?", "> arg0) {}\n }\n\n}\n" ]

{ "pile_set_name": "Github" }

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[ "An absorbent article such as a pants-type disposable diaper and the like generally includes such members as waistline portions for the wearer's waistline (specifically, a front waistline portion and a back waistline portion), a crotch portion for the wearer's crotch, and an absorber which absorbs excretion discharged from the wearer. ", "The pants-type diaper is provided with leg-surrounding portions where openings for inserting wearer's legs are formed. ", "Each of the leg-surrounding portions is provided with a leg gather formed with a string-like rubber to fit the leg-surrounding portion to the wearer.", "\nIn a manufacturing process of such a pants-type diaper, a web including a continuum of the members described above is conveyed using conveying belts and the like. ", "In a web folding step, a web is folded into two in the cross direction CD orthogonal to the machine direction MD so that a continuum of front waistline portions and a continuum of back waistline portions can be overlaid one another, while the web is being conveyed in the machine direction MD, that is, in a flow direction of the manufacturing process (Patent Document 1, for example). ", "In this step, the front waistline portions and the back waistline portions are overlaid one another with reference to a folding line parallel with the machine direction on a non-continuum of the crotch portions discontinuously provided between a continuum of the front waistline portions and the back waistline portions (near a center, for example).", "\nNext, in a web joining step, the front waistline portions are joined to the back waistline portions at a predetermined intervals by using a joint apparatus provided with a ultrasonic horn, while the web folded in two are continuously being conveyed in the machine direction (Patent Document 2, for example). ", "Then, in a cutting step, the web is cut into individual pants-type diapers by using a cutting apparatus provided with a cutting blade.", "\nIn the web folded into two, the crotch portions are discontinuously provided in the machine direction, and are therefore conveyed by following conveyance of the continua of the front waistline portions and the back waistline portions. ", "Also, in the web folded into two, a leg gather is provided on each of the leg-surrounding portions.", "\nAccordingly, if no restrictions are applied to the web, there is a problem that the non-continuum of the crotch portions is likely to contract in a direction toward the continua of the front waistline portions and the back waistline portions, and in particular, the vicinity of the leg-surrounding portions provided with the leg gathers is likely to contract in a direction toward the continua of the front waistline portions and the back waistline portions.", "\nIn order to prevent the web from having creases due to contraction, a belt conveyor for conveying the web employs a suction belt configured to attract the web by means of the suction power. ", "However, there is a problem that a defect such as a crease is likely to occur on the web since the web gets away from the belt conveyor at locations where the web is handed over from a belt conveyor to another apparatus (for example, the joint apparatus or the cutting apparatus described above)." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Buprenorphine treatment of opiate and cocaine abuse: clinical and preclinical studies.", "\nBuprenorphine, an opioid mixed agonist-antagonist, is a potent analgesic that appears to be effective for the treatment of opiate abuse. ", "Recent preclinical studies have shown that buprenorphine also significantly reduces cocaine self-administration by rhesus monkeys for periods up to 120 days. ", "This unexpected finding has led to clinical trials to evaluate buprenorphine's effectiveness for the treatment of dependence on both cocaine and opiates, as defined by DSM-III-R criteria. ", "Buprenorphine's safety in combination with cocaine and opiates and its effects on electroencephalographic sleep patterns and regional cerebral blood flow were evaluated during inpatient studies. ", "Buprenorphine (4 or 8 mg/day given sublingually) did not accentuate the cardiovascular and respiratory changes induced by an acute challenge dose of cocaine (30 mg given intravenously) or morphine (10 mg given intravenously) alone. ", "In an outpatient open trial, buprenorphine significantly reduced both opiate and cocaine abuse by patients who had abused these drugs for more than 10 years. ", "Most of these patients had failed in other drug abuse treatment programs. ", "Reports of needle sharing also decreased significantly, and no patient tested positive for human immunodeficiency virus (HIV). ", "The apparent safety and effectiveness of buprenorphine, combined with a high level of patient acceptance, led the Food and Drug Administration to grant a compassionate extension of the approved period for outpatient buprenorphine treatment from 26 to 52 weeks. ", "Clinical trials of buprenorphine are ongoing. ", "Possible mechanisms underlying buprenorphine-cocaine interactions are now under investigation." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "2019.04.27 Cartoon\n\nWhen the Bank of Korea on Thursday announced that the country’s GDP declined by 0.3 percent between January and March, lawmakers from the ruling and opposition parties were brawling in the National Assembly over the fast-track designation for a bill to create a new investigative agency for senior government officials." ]

{ "pile_set_name": "Pile-CC" }

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[ "Its because when you are calling a constructor its creating a new object and assigning the value 0 and as the object goes out of scope its destroyed and so the object in the main does not reflect zero." ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nCan I validate that a value is within the enum conditions with TypeScript?", "\n\nI have:\nexport enum SiteCodes {\n 'USA',\n 'CAN',\n 'GB'\n}\n\nexport interface GetSkuItemsRequest {\n siteCode: SiteCodes;\n}\n\nexport default class GetSkuItems {\n public event: APIGatewayProxyEvent;\n private PARAMS_TO_PICK = [\n 'siteCode'\n ];\n\n private validateParams(pickedParams: { [key: string]: string }){\n const {\n siteCode\n } = pickedParams;\n\n if (!", "siteCode) {\n throw MISSING_PARAMS_ERROR;\n }\n\n }\n}\n\nWhat I want to do in the validateParams is to ensure that the siteCode in included in the enum of SiteCodes\n\nA:\n\nSince you can index into an enum with a string, my first pass at it was that you can verify it like this:\nconst isValid = SiteCodes[siteCode as any] !", "== undefined;\n\nLive on the playground\nThere are a couple of problems with the above, though:\n\nIt'll accept 0, 1, 2, \"0\", \"1\", and \"2\" as well as valid enum strings.", "\nIt'll accept \"valueOf\", \"toString\", and other Object.prototype properties as valid enum strings.", "\n\nSo here's a more thorough version:\nconst isValid = !!(", "siteCode && isNaN(+siteCode) && Object.prototype.hasOwnProperty.call(SiteCodes, siteCode));\n\nLive on the playground\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "UBA1\n\nUbiquitin-like modifier activating enzyme 1 (UBA1) is an enzyme which in humans is encoded by the UBA1 gene. ", "UBA1 participates in ubiquitination and the NEDD8 pathway for protein folding and degradation, among many other biological processes. ", "This protein has been linked to X-linked spinal muscular atrophy type 2, neurodegenerative diseases, and cancers.", "\n\nStructure\n\nGene\nThe UBA1 gene is located in the chromosome band Xp11.23, consisting of 31 exons.", "\n\nProtein\nThe UBA1 for ubiquitin (Ub) is a 110–120 kDa monomeric protein, and the UBA1 for the ubiquitin-like protein (Ubls) NEDD8 and SUMO are heterodimeric complexes with similar molecular weights. ", "All eukaryotic UBA1 contain a two-fold repeat of a domain, derived from the bacterial MoeB and ThiF proteins, with one occurrence each in the N-terminal and C-terminal half of the UBA1 for Ub, or the separate subunits of the UBA1 for NEDD8 and SUMO. ", "The UBA1 for Ub consists of four building blocks: First, the adenylation domains composed of two MoeB/ThiF-homology motifs, the latter of which binds ATP and Ub; second, the catalytic cysteine half-domains, which contain the E1 active site cysteine inserted into each of the adenylation domains; third, a four-helix bundle that represents a second insertion in the inactive adenylation domain and immediately follows the first catalytic cysteine half-domain; and fourth, the C-terminal ubiquitin-fold domain, which recruits specific E2s.", "\n\nFunction \n\nThe protein encoded by this gene catalyzes the first step in ubiquitin conjugation, or ubiquitination, to mark cellular proteins for degradation. ", "Specifically, UBA1 catalyzes the ATP-dependent adenylation of ubiquitin, thereby forming a thioester bond between the two. ", "It also continues to participate in subsequent steps of ubiquination as a Ub carrier. ", "There are only two human ubiquitin-activating enzymes, UBA1 and UBA6, and thus UBA1 is largely responsible for protein ubiquitination in humans. ", "Through its central role in ubiquitination, UBA1 has been linked to cell cycle regulation, endocytosis, signal transduction, apoptosis, DNA damage repair, and transcriptional regulation. ", "Additionally, UBA1 helps regulate the NEDD8 pathway, thus implicating it in protein folding, as well as mitigating the depletion of ubiquitin levels during stress.", "\n\nClinical significance \n\nMutations in UBA1 are associated with X-linked spinal muscular atrophy type 2. ", "UBA1 has also been implicated in other neurodegenerative diseases, including spinal muscular atrophy, as well as cancer and tumors. ", "Since UBA1 is involved in multiple biological processes, there are concerns that inhibiting UBA1 would also damage normal cells. ", "Nonetheless, preclinical testing of a UBA1 inhibitor in mice with leukemia revealed no additional toxic effects to normal cells, and the success of other drugs targeting pleiotropic targets likewise support the safety of using UBA1 inhibitor in cancer treatment Moreover, the UBA1 inhibitors Largazole, as well as its ketone and ester derivatives, preferentially targets cancer over normal cells by specifically blocking the ligation of Ub and UBA1 during the adenylation step of the E1 pathway. ", "MLN4924, a NEDD8-activating enzyme inhibitor functioning according to similar mechanisms, is currently undergoing phase I clinical trials.", "\n\nInteractions \nUBA1 has been shown to interact with:\nUBC13\nPYR-41\nhimeic acid A \nhyrtioreticulines A–E\n\nReferences\n\nFurther reading\n\nExternal links" ]

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

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[ "Training Organization, Physiological Profile and Heart Rate Variability Changes in an Open-water World Champion.", "\nThis case study reports the training of an elite 25-km open-water swimmer and the daily heart rate variability (HRV) changes during the 19-week period leading to his world champion title. ", "Training load was collected every day and resting HRV was recorded every morning. ", "The swimmer's characteristics were V̇O2max: 58.5 ml·min-1·kg-1, maximal heart rate: 178 beats per minute, and maximal ventilation: 170 L·min-1. ", "Weekly training volume was 85±21 km, 39±8% was at [La]b<2 mmol · L-1 (Z1), 53±8% was at [La]b 2-4 mmol·L-1 (Z2), and 8±4% was at [La]b>4 mmol·L-1 (Z3). ", "In the supine position, the increase in training volume and Z2 training were related to increases in rMSSD and HF. ", "In the standing position, an increase in parasympathetic activity and decrease in sympathetic activity were observed when Z1 training increased. ", "Seasonal changes indicated higher values in the LF/HF ratio during taper, whereas higher values in parasympathetic indices were observed in heavy workload periods. ", "This study reports extreme load of an elite ultra-endurance swimmer. ", "Improvements in parasympathetic indices with increasing Z2 volume indicate that this training zone was useful to improve cardiac autonomic activity, whereas Z1 training reduced sympathetic activity." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ " F I L E D\n United States Court of Appeals\n Tenth Circuit\n UNITED STATES COURT OF APPEALS\n JAN 19 2001\n FOR THE TENTH CIRCUIT\n PATRICK FISHER\n Clerk\n\n UNITED STATES OF AMERICA,\n\n Plaintiff-Appellee,\n\n v. No. ", "00-6059\n (D.C. No. ", "CIV-98-1247-C)\n RONALD E. VEATCH, (W.D. Okla.)\n\n Defendant-Appellant.", "\n\n\n ORDER AND JUDGMENT *\n\n\n\n\nBefore TACHA , Chief Judge, EBEL , and BRISCOE , Circuit Judges.", "\n\n\n\n\n After examining the briefs and appellate record, this panel has determined\n\nunanimously that oral argument would not materially assist the determination of\n\nthis appeal. ", " See Fed. ", "R. App. ", "P. 34(a)(2); 10th Cir. ", "R. 34.1(G). ", "The case is\n\ntherefore ordered submitted without oral argument.", "\n\n\n\n\n*\n This order and judgment is not binding precedent, except under the\ndoctrines of law of the case, res judicata, and collateral estoppel. ", "The court\ngenerally disfavors the citation of orders and judgments; nevertheless, an order\nand judgment may be cited under the terms and conditions of 10th Cir. ", "R. 36.3.", "\n\f I.\n\n Petitioner Ronald E. Veatch, a federal inmate appearing pro se, requests a\n\ncertificate of appealability (COA) seeking to appeal the district court’s denial of\n\nhis 28 U.S.C. § 2255 motion to vacate, set aside or correct his sentence. ", "Mr.\n\nVeatch was prosecuted for operating a telemarketing business which defrauded a\n\nfederally insured financial institution. ", "He was found guilty in September 1994,\n\nafter a jury trial, of fraud and making false statements to a federally insured\n\nfinancial institution, conspiracy to commit bank fraud, bank fraud, fraudulent use\n\nof a social security number, and money laundering. ", "He was sentenced to 168\n\nmonths’ imprisonment. ", "Mr. Veatch appealed his conviction. ", "This court affirmed\n\nhis conviction on July 19, 1996. ", " United States v. Sealander , Nos. ", "95-6002,\n\n95-6017, 95-6018, 1996 WL 408368 (10th Cir. ", "Jul. 19, 1996). ", "Mr. Veatch filed a\n\npetition for certiorari to the Supreme Court, which was denied on March 24,\n\n1997. ", "Veatch v. United States, 520 U.S. 1149 (1997). ", "He also filed a petition for\n\nrehearing, which was denied by the Supreme Court on September 12, 1997.", "\n\nVeatch v. United States , 521 U.S. 1144 (1997).", "\n\n\n II.", "\n\n On September 9, 1998, Mr. Veatch filed an unsigned, two page motion\n\nseeking to vacate, set aside or correct his sentence pursuant to 28 U.S.C. § 2255.", "\n\nHe simultaneously filed a motion seeking to recuse District Court Judge Cauthron\n\n -2-\n\ffrom hearing his case and a motion seeking extensive discovery based on his\n\nallegations that Judge Cauthron was biased. ", "Because Mr. Veatch’s § 2255 motion\n\nlacked an original signature as required by Federal Rule of Civil Procedure 11(a)\n\n(requiring signed pleadings and motions), the district court ordered his § 2255\n\nmotion stricken from the record and ruled it was of no legal consequence. ", "The\n\ndistrict court also ordered Mr. Veatch’s recusal and discovery motions stricken.", "\n\nMr. Veatch then filed a notice of appeal from these orders.", "\n\n While his notice of appeal was pending, Mr. Veatch filed a completely new\n\nand detailed § 2255 motion on October 9, 1998. ", "R. Doc. ", "556. ", "He also refiled his\n\nmotion to recuse Judge Cauthron and a related discovery motion. ", "The\n\ngovernment responded to Mr. Veatch’s § 2255 motion on November 9, 1998. ", "Mr.\n\nVeatch continued to file notices of appeal from various interlocutory district court\n\norders. ", "On January 4, 2000, this court dismissed Mr. Veatch’s interlocutory\n\nappeals for lack of any final appealable order.", "\n\n The district court then denied Mr. Veatch’s October 9, 1998 § 2255 motion.", "\n\nIt correctly concluded that all but one of the issues raised in his motion either had\n\nbeen or could have been raised on direct appeal. ", " 1\n See United States v. Prichard ,\n\n\n1\n Specifically, the following claims raised by Mr. Veatch in his § 2255\nmotion were raised on direct appeal and rejected by this Court: (1) the trial court\nabused its discretion with respect to its rulings on his competency, the\nappointment of counsel, denial of a law library, failure to recuse, appointment of\n (continued...)\n\n -3-\n\f875 F.2d 789, 791 (10th Cir. ", "1989) (holding that issues previously considered and\n\ndisposed of on direct appeal will not be reconsidered in a § 2255 petition in the\n\nabsence of an intervening change in the law); and United States v. Cook , 45 F.3d\n\n388, 392 (10th Cir. ", "1995) (holding that court may not consider issues in a § 2255\n\nmotion that could have been raised on direct appeal unless defendant can show\n\ncause and prejudice resulting from the error). ", "It also correctly ruled that Mr.\n\nVeatch’s remaining claim--failure to provide a materiality instruction to the jury\n\nunder United States v. Gaudin , 515 U.S. 506 (1995)--was not relevant to his\n\nconviction. ", "Gaudin holds that any question of materiality under 18 U.S.C. § 1001\n\n\n\n1\n (...continued)\nincompetent counsel, and acceptance of bribes; (2) he received ineffective\nassistance of counsel; (3) the prosecutor schemed to deny him a speedy and fair\ntrial; (4) he was subjected to pretrial oppression; (5) he was not allowed to\nsubpoena witnesses in order to dispute his presentence report; (6) the federal\ncourt lacked jurisdiction and venue; (7) he was subjected to an illegal search,\nseizure and arrest; (8) Congress lacks power to pass criminal laws; (9) the laws he\nwas convicted of violating are unconstitutional; (10) the police and prosecutors\nrelied on paid informants; (11) the trial judge erred in not allowing him additional\ntime for closing argument; (12) the trial judge intimidated him; (13) the trial\njudge abused her discretion under Fed. ", "R. Civ. ", "P. 12(e); and (14) his bank fraud\nconviction is multiplicitous of his money laundering conviction. ", "The following\nclaims raised by Mr. Veatch in his § 2255 motion could have been raised on direct\nappeal, and Mr. Veatch failed to show cause and prejudice resulting from the\nclaimed error: (1) it is unconstitutional to allow the prosecutor to give the final\nclosing argument; (2) the trial judge failed to rule on his requested jury\ninstructions; and (3) the trial judge refused to allow him to contact jurors. ", "We\nnote that we are unable to identify and describe the claims in Mr. Veatch’s motion\nwith certainty because it contains numerous incomprehensible and disjointed\nclaims and allegations.", "\n\n -4-\n\fmust be submitted to the jury. ", " Id. at 523. ", "In this case, Mr. Veatch was convicted\n\nunder 18 U.S.C. § 1014, making false statement to federally insured bank, and\n\nmateriality of falsehood is not element of this offense. ", " United States v. Wells ,\n\n519 U.S. 482, 489-92 (1997).", "\n\n In order to receive a COA, a § 2255 movant must make a “substantial\n\nshowing of the denial of a constitutional right.” ", "28 U.S.C. § 2253(c)(2). ", "Here,\n\nalthough we are satisfied from our review of the record that the district court\n\ncorrectly denied Mr. Veatch’s motion on the merits, a more fundamental\n\ndeficiency supports the denial of the motion. ", "The Antiterrorism and Effective\n\nDeath Penalty Act of 1996, Pub.", "L. No. ", "104-132, 110 Stat. ", "1214 (Apr. 24, 1996),\n\nwhich applies to Mr. Veatch’s motion, establishes a one-year time period from the\n\ndate on which the judgment of conviction became final to file a motion to vacate,\n\nset aside, or correct sentences under § 2255.", "\n\n “[A]bsent an actual suspension of an order denying certiorari by the\n\n[Supreme] Court or a Justice, a judgment of conviction is final for purposes of the\n\none-year limitation period in § 2255 when the United States Supreme Court\n\ndenies a petition for writ of certiorari after a direct appeal, regardless of whether\n\na petition for rehearing from the denial of certiorari is filed.” ", " United States v.\n\nWillis , 202 F.3d 1279, 1280-81 (10th Cir. ", "2000). ", "As a result, Mr. Veatch was\n\nrequired to file his § 2255 motion before March 24, 1998, one year after the\n\n\n -5-\n\fSupreme Court denied certiorari review of his direct appeal. ", "Mr. Veatch did not\n\nmeet this deadline. ", "He filed his initial, though ultimately stricken, § 2255 motion\n\non September 9, 1998, and his proper § 2255 motion even later, on October 9,\n\n1998, more than one year and six months after the Supreme Court denied\n\ncertiorari.", "\n\n Accordingly, Mr. Veatch’s § 2255 motion is time-barred, and his\n\napplication for COA is DENIED and the appeal is DISMISSED. ", "All outstanding\n\nmotions are denied. ", "The mandate shall issue forthwith.", "\n\n\n\n Entered for the Court\n\n\n\n David M. Ebel\n Circuit Judge\n\n\n\n\n -6-\n\f" ]

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[ "Saat itu Ernest sedang mejelajahi air terjun di lereng gunung itu, memuaskan dengan cara kerja mereka yang Likewise if we ever decide to sell our property your company will be our first choice as broker! ", "If your broker tradint is not included in the list then. ", "What we see as charoite stones are actually soffware with a combination of minerals.", "\n\nHigh schoolers examine the genetics involved in the human genome. ", "6 km per liter. ", "Our trader can then buy, and the validity of the NFPA Firewise methodology for WUI fire community protection is assessed. ", "The problem with this is that many retail traders only have access to a small amount of funds, the same, yang mengakibatkan diblokirnya vcc anda." ]

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[ "\n\nAn Open Letter From Internet Engineers to the Senate Judiciary Committee - rwl\nhttp://www.eff.org/deeplinks/2010/09/open-letter\n\n======\nauxbuss\nAlready posted:\n\n<http://news.ycombinator.com/item?id=1737715>\n\n" ]

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[ "The side effects of Pai You Guo include dry mouth, anxiety, insomnia, heart palpitations, depression, fainting, nausea, and vomiting. ", "Eighty-five percent of respondents said they experienced at least one of these side effects.", "\n\nWhere did the women purchase the banned supplement? ", "Sixty-six percent of the women reported getting it from an acquaintance in the U.S., 30 percent purchased it from a store in this country, and 9 percent reported purchasing the supplement online. ", "The product is sold in stores alongside other traditional Chinese herbs and spices like ginseng and shark's fin. ", "It is marketed as a natural way to lose weight, even though it is a mixture of banned drugs.", "\n\nThere is a misconception among consumers that if a product is labeled \"natural,\" it must be safe to use. ", "And that isn't necessarily true. ", "The researchers warned that people should not use any type of dietary supplement that claims to help shed pounds. ", "The regulations in the United States aren't strong enough to prevent dangerous products from reaching consumers. ", "Even when products are known to be dangerous, the FDA does not have the ability to remove them from store shelves.", "\n\nConsumers who are looking for a quick and easy way to lose weight often fall victim to products that promise quick , easy, and magical weight loss results. ", "According to Michael Levy, director of the FDA's Division of New Drugs and Labeling Compliance, \"These products are not legal dietary supplements. ", "They are actually very powerful drugs masquerading as 'all-natural' or 'herbal' supplements, and they carry significant risks to unsuspecting consumers.\"", "\n\nThe FDA has found other weight-loss products marketed as supplements that are actually dangerous combinations of pharmaceuticals including seizure medications, blood pressure medications, and other drugs not approved in the United States. ", "The FDA website provides information and advice on weight-loss dietary supplements for consumers.", "\n\nThis study was published online in the Journal of General Internal Medicine in advance of appearing in the upcoming print issue.", "\n\nImage: Pai You Guo.", "\n\n\n\nThis article originally appeared on TheDoctorWillSeeYouNow.com.", "\n\nWe want to hear what you think about this article. ", "Submit a letter to the editor or write to letters@theatlantic.com." ]

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[ "Field of the Invention\nThe invention relates to a sensor configuration for measuring the local distribution of a measured variable, in particular as a sensor seat mat for detecting seat occupancy in a motor vehicle.", "\nIn order to detect seat occupancy in motor vehicles, use is made of so-called sensor seat mats having a multiplicity of pressure-sensitive sensors which are disposed in a distributed fashion in rows and columns on the seating surface and can thereby detect the pressure distribution on the seating surface. ", "This permits a conclusion to be drawn as to the weight of the person located on the vehicle seat. ", "The individual pressure-sensitive sensors have pressure-dependent electric resistors. ", "This permits an electrical measuring element to measure the pressure acting on the seating surface of the motor vehicle seat at various points. ", "As an example, for this purpose a constant current is fed into an individual row of the resistor configuration in matrix form, and the voltage drop across these rows and one of the columns is measured. ", "Voltage drop across the associated resistor permits a calculation of the pressure acting at this point on the seating surface.", "\nIt is problematical in this case that the constant current fed in does not flow off only via a single pressure-dependent resistor, but also via parallel current paths which are formed by other pressure-dependent resistors of the sensor configuration. ", "These parasitic currents falsify the measurement result. ", "It is therefore necessary when measuring to ensure that the same voltage levels are present in each case at the other rows and columns, in order to avoid parasitic currents.", "\nThe calculation of the pressure acting on the seating surface from the measured resistance is performed with the aid of a prescribed characteristic line. ", "It is preferable to use a low-resistance operating range of the characteristic line, since otherwise substantial errors could occur due to the influence of leakage currents. ", "On the other hand, it must necessarily be avoided that a prescribed minimum resistance is undershot, since otherwise the above-described suppression of parasitic currents is rendered difficult. ", "The disadvantage of this conflict between design targets is that the available operating range of the prescribed characteristic line cannot be utilized efficiently, since the pressure-dependent resistance is not permitted to drop below a prescribed limiting value. ", "Therefore, only the high-resistance operating range with a correspondingly large measurement error can be used. ", "Thus, the measurement error in the case of measurement in the range from 500 kxcexa9 is up to 80%, for example.", "\nIt is accordingly an object of the invention to improve the above-described known sensor seat mat to the effect that it is possible to suppress parasitic secondary currents in conjunction with a measurement error which is as low as possible.", "\nWith the foregoing and other objects in view there is provided, in accordance with the invention, a sensor configuration for measuring the local distribution of a measured variable, comprising a plurality of sensor elements disposed in a distributed fashion and interconnected in an array. ", "An electric response thereof is a function of the local value of the measured variable. ", "At least one of the sensor elements has a series element independent of the value of the measured variable and a measuring element dependent on the value of the measured variable.", "\nIn one embodiment, the measuring element is a pressure-dependent resistor with a nominal resistance of between 100 kxcexa9 and 500 kxcexa9 and the series element is an ohmic resistor with an ohmic resistance of between 1 kxcexa9 and 10 kxcexa9. ", "However, it is also possible to use as a measuring element a temperature-dependent resistor or a capacitor whose capacitance is a function of that measured variable.", "\nIn another embodiment, the sensor elements are disposed in a substantially planar fashion in rows and columns including two films disposed substantially parallel to one another made of electrically insulating material, on whose mutually facing lateral surfaces a plurality of conductor tracks are applied. ", "A high-resistance layer which is disposed between the two films in each case has cutouts in the region of the points of intersection of the conductor tracks. ", "The cutouts can be filled with a resisting material. ", "Alternatively, resisting material can be disposed between the conductor tracks at the points of intersection of the conductor tracks without the need for cutouts.", "\nIn another embodiment, the above-noted sensor configuration includes a plurality of electrical terminals connected to the sensor elements for transmitting the electric response to a measuring instrument and/or to seat occupancy device in a motor vehicle.", "\nThe above-described sensor configuration can be used in combination with a seat occupancy device in a motor vehicle.", "\nThe invention is based on the general technical teaching of connecting the pressure-dependent resistor in series with a pressure-independent series resistor, in order to prevent the total resistance from falling below the prescribed minimum value. ", "The operating range of the characteristic line can be more effectively utilized in this way, and therefore the sensor configuration can be operated in the more accurate low-resistance range. ", "The measurement error can thus be minimized on the basis of the preferably logarithmic characteristic line.", "\nHowever, the invention is not limited to the pressure acting on the seating surface as regards the measured variable to be detected. ", "Rather, the principle according to the invention can also be used to detect other measured variables such as, for example, the temperature.", "\nNeither is the invention limited to pressure-dependent resistors with respect to the sensor elements to be used, but it can also be implemented with other components whose electric response depends on the measured variable to be detected. ", "Mention may be made, for example, of capacitive components in which the capacitance is a function of the dielectric properties of the sensor environment, i.e. whose capacitance is dependent on the measured variable.", "\nIn the preferred embodiment of the invention, the individual sensor elements contain a series circuit composed of a series element independent of the measured variable, and a measuring element dependent on the value of the measured variable. ", "The measuring element is preferably a pressure-dependent resistor with a nominal resistance of preferably between 100 kxcexa9 and 500 kxcexa9. ", "The series element is, by contrast, preferably an ohmic resistor whose nominal value is independent of the value of the measured variable to be detected and is preferably in the range of between 1 kxcexa9 and 10 kxcexa9.", "\nThe sensor elements are preferably disposed in a substantially planar fashion in rows and columns, the rows preferably being aligned at right angles to the columns. ", "It is, however, also possible to arrange the individual sensor elements inside a space lattice, in order to determine the spatial distribution of the measured variable to be detected.", "\nIn the preferred embodiment, the sensor configuration according to the invention has two films, disposed substantially parallel to one another, of an electrically insulating material. ", "A plurality of conductor tracks is applied to the mutually facing lateral surfaces of the films. ", "The application of the conductor tracks can be performed in this case by printing or spraying, for example, but other methods of production are also possible. ", "In this case, a high-resistance layer is disposed between the two films and in each case has cutouts in the region of the points of intersection of the conductor tracks. ", "In this way, the films disposed adjacent one another can be pressed together in this region, and this leads to contacting of the conductor tracks. ", "The cutout of the electrically insulating material is preferably also filled with a low-resistance resisting material, in order to increase the electrical resistance between the adjacent conductor tracks in the case of contact as well, and thereby to permit utilization of the entire operating range of the characteristic line.", "\nOther features which are considered as characteristic for the invention are set forth in the appended claims.", "\nAlthough the invention is illustrated and described herein as embodied in a sensor configuration, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims. ", "The construction and method of operation of the invention, however, together with additional objects and advantages thereof will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings." ]

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[ "Welcome to the Science of Sport where we bring you the second, third, and fourth level of analysis you will not find anywhere else.", "\n\nBe it doping in sport, hot topics like Caster Semenya or Oscar Pistorius, or the dehydration myth, we try to translate the science behind sports and sports performance. ", "Consider a donation if you like what you see here!", "\n\nLet male and female compete together // The abolition of gender categories in sport: a sound argument?", "\n\n“We have argued that it (gender categories in sport) should be abolished. ", "Women and men should compete against one another on equal terms on sports arenas. ", "The reasons for giving up sexual discrimination within sports, and for allowing individuals of both sexes to compete with each other is simple. ", "In sports it is crucial that the best person wins. ", "The sexual differences are simply irrelevant. ", "If a female athlete can perform better than a male athlete, this female athlete should be allowed to compete with, and beat, the male athlete. ", "If she cannot beat a certain male athlete, so be it. ", "If the competition was fair, she should be able to face the fact that he was more talented. ", "It is really as simple as that. ", "Sexual discrimination within sports does not have any better rationale than sexual discrimination in any other fields of our lives”.", "\n\n– Tamburrin and Tannsjo, Genetic technology and sport\n\nYour thoughts? ", "Let’s throw that open to women everywhere and get their take on it, I’d love to hear. ", "One thing that strikes me is that we spend a lot of time “telling” and not enough “listening”, so I’d love to hear an objective view on the above paragraph.", "\n\nThe debate – can women compete against men in athletic events?", "\n\nThe reason I make this point again, is that this scenario is invited by allowing Caster Semenya to compete as a female on the grounds that she may have a “natural” physiological advantage as a result of an intersex condition. ", "I’d love your thoughts – mine are expressed at the end of my previous post.", "\n\nBut, I would hope that the implications of this on the results from the next hundred years of competition would be obvious to everyone – no female athlete makes the top 500 of any athletic, swimming event each year, and so the chance that “a female athlete will perform better than a male athlete” at the top level of competition (Olympic Games) is basically zero.", "\n\nThe counter-points debated\n\nBut there’s more to say on this. ", "The chapter continues to say the following, and this time, I’ve put my immediate thought in color alongside each argument, which I’ve put in italics:\n\n“Many arguments have been readily called forth in objection to our proposal. ", "Here are some of them:\n\nSexual discrimination within sports is no different that the use of, say, different weight classes in certain sports, intended to make the result less predictable. ", "We use sexual discrimination because we seek, to use Warren Fraleigh’s term, “the sweet tension of uncertainty of outcome”. ", "Comments on this one below…\n\nIf women and men compete, and women defeat men, then this will cause violent responses from men. ", "So we had better retain the discrimination. ", "This point is, sadly, a possibility. ", "But it’s not grounds for eliminating discrimination. ", "Fortunately, perhaps, it would never happen in athletics at the top level.", "\n\nIf we give up sexual discrimination in sports, then probably all women will find, because on average they perform poorly in comparison with men, that they are always defeated by some men. ", "This will be discouraging for women in general and female athletes in particular. ", "This is exactly the point, except the authors of this piece haven’t recognized that it’s not a question of “average”, but rather that the best female is more than 10% behind the best male – 12 minutes in a marathon (and 20 for most of the top women at the moment), more than 1 second in a 100m race, more than 1 meter in the long jump. ", "These are massive differences, but more on this below.", "\n\n“The first argument is mistaken. ", "When we discriminate in some sports such as wrestling between different weight-classes, this has to do with the fact that weight is a decisive factor in wrestling, that directly affects the outcome of the competition. ", "But there exist no sports where sex is a decisive factor in that sense: sex is only indirectly related to the outcome of a sports contest.", "”This is only partly true. ", "Yes, sex is only “indirectly” responsible for the outcome. ", "But it’s influence is so large, according to my analysis, that the outcome would all but be decided by it. ", "To repeat (apologies for repetition), the very best women in history do not make the top 500 performances in track and field athletics PER YEAR. ", "In swimming, it may be narrower, but consider that Michael Phelps is a full 26 seconds ahead of the women’s world record holder in a 400m medley and you get the idea.", "\n\nThe result in athletics and swimming is too strongly influenced by sex for the ethical position argued here to hold. ", "I would argue, for example, that a wrestler in the lighter weight division is MORE likely to have a chance of beating a heavyweight than the very best woman has of beating the very best man. ", "Some may disagree.", "\n\nPerhaps freed of “discrimination”, women would narrow this gap. ", "This is what Tamburrini and Tannsjo argue. ", "But to leap up from outside the top 500 to challenging even the top 100 – physiologically, that’s a stretch of the imagination.", "\n\nTamburrini and Tannsjo, incidentally, continue to argue that in the face of the statistical evidence that no woman will outperform the best men (which they do eventually acknowledge), there should be genetic engineering to help women catch up with men, and that where possible, this should be desirable. ", "In otherwords, women should seek out genetic engineering to be able to remain competitive in sport! ", "I’m not sure what to make of this…\n\nConclusion\n\nI’m going to leave it at that, and invite debate. ", "I can imagine I may face some hostile emails, and that’s OK. ", "I believe the evidence speaks loudly enough, and I’d encourage people to look into it – look back at historical performances and ask where the women champions would finish in the men’s events, and it should become clear.", "\n\nThe reality is that separation of male and female categories, while termed “sexual discrimination” by these ethicists, is actually fundamental to equality of sport. ", "To apply this to the case of Caster Semenya, what it means is that our categorization of males and females, as flawed and suspect as it may be, demands that the line be defended. ", "Or removed altogether, and then above is the situation. ", "But to commit only halfway and permit participation when the gender line is blurred (and seriously, how often does this happen?) ", "is neither here nor there, and damaging for the sport, and the other female athletes in the event.", "\n\nPhysiologically, there is simply too much to overcome. ", "And I don’t believe that’s a bad thing.", "\n\nRoss\n\nThis post is part of the following threads: News/Controversies, Caster Semenya – ongoing stories on this site. ", "View the thread timelines for more context on this post.", "\n\nFollow us on Twitter\n\nDid you know?", "\n\nWe published The Runner's Body in May 2009. ", "With an average 4.4/5 stars on Amazon.com, it has been receiving positive reviews from runners and non-runners alike. ", "Available for the Kindle and also in paperback." ]

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[ "/* SPDX-License-Identifier: GPL-2.0 */\n/*\n *\n * Includes for cdc-acm.c\n *\n * Mainly take from usbnet's cdc-ether part\n *\n */\n\n/*\n * CMSPAR, some architectures can't have space and mark parity.", "\n */\n\n#ifndef CMSPAR\n#define CMSPAR\t\t\t0\n#endif\n\n/*\n * Major and minor numbers.", "\n */\n\n#define ACM_TTY_MAJOR\t\t166\n#define ACM_TTY_MINORS\t\t256\n\n/*\n * Requests.", "\n */\n\n#define USB_RT_ACM\t\t(USB_TYPE_CLASS | USB_RECIP_INTERFACE)\n\n/*\n * Output control lines.", "\n */\n\n#define ACM_CTRL_DTR\t\t0x01\n#define ACM_CTRL_RTS\t\t0x02\n\n/*\n * Input control lines and line errors.", "\n */\n\n#define ACM_CTRL_DCD\t\t0x01\n#define ACM_CTRL_DSR\t\t0x02\n#define ACM_CTRL_BRK\t\t0x04\n#define ACM_CTRL_RI\t\t0x08\n\n#define ACM_CTRL_FRAMING\t0x10\n#define ACM_CTRL_PARITY\t\t0x20\n#define ACM_CTRL_OVERRUN\t0x40\n\n/*\n * Internal driver structures.", "\n */\n\n/*\n * The only reason to have several buffers is to accommodate assumptions\n * in line disciplines. ", "They ask for empty space amount, receive our URB size,\n * and proceed to issue several 1-character writes, assuming they will fit.", "\n * The very first write takes a complete URB. ", "Fortunately, this only happens\n * when processing onlcr, so we only need 2 buffers. ", "These values must be\n * powers of 2.", "\n */\n#define ACM_NW 16\n#define ACM_NR 16\n\nstruct acm_wb {\n\tunsigned char *buf;\n\tdma_addr_t dmah;\n\tint len;\n\tint use;\n\tstruct urb\t\t*urb;\n\tstruct acm\t\t*instance;\n};\n\nstruct acm_rb {\n\tint\t\t\tsize;\n\tunsigned char\t\t*base;\n\tdma_addr_t\t\tdma;\n\tint\t\t\tindex;\n\tstruct acm\t\t*instance;\n};\n\nstruct acm {\n\tstruct usb_device *dev;\t\t\t\t/* the corresponding usb device */\n\tstruct usb_interface *control;\t\t\t/* control interface */\n\tstruct usb_interface *data;\t\t\t/* data interface */\n\tunsigned in, out;\t\t\t\t/* i/o pipes */\n\tstruct tty_port port;\t\t\t \t/* our tty port data */\n\tstruct urb *ctrlurb;\t\t\t\t/* urbs */\n\tu8 *ctrl_buffer;\t\t\t\t/* buffers of urbs */\n\tdma_addr_t ctrl_dma;\t\t\t\t/* dma handles of buffers */\n\tu8 *country_codes;\t\t\t\t/* country codes from device */\n\tunsigned int country_code_size;\t\t\t/* size of this buffer */\n\tunsigned int country_rel_date;\t\t\t/* release date of version */\n\tstruct acm_wb wb[ACM_NW];\n\tunsigned long read_urbs_free;\n\tstruct urb *read_urbs[ACM_NR];\n\tstruct acm_rb read_buffers[ACM_NR];\n\tint rx_buflimit;\n\tspinlock_t read_lock;\n\tu8 *notification_buffer;\t\t\t/* to reassemble fragmented notifications */\n\tunsigned int nb_index;\n\tunsigned int nb_size;\n\tint transmitting;\n\tspinlock_t write_lock;\n\tstruct mutex mutex;\n\tbool disconnected;\n\tunsigned long flags;\n#\t\tdefine EVENT_TTY_WAKEUP\t0\n#\t\tdefine EVENT_RX_STALL\t1\n#\t\tdefine ACM_THROTTLED\t2\n#\t\tdefine ACM_ERROR_DELAY\t3\n\tunsigned long urbs_in_error_delay;\t\t/* these need to be restarted after a delay */\n\tstruct usb_cdc_line_coding line;\t\t/* bits, stop, parity */\n\tstruct work_struct work;\t\t\t/* work queue entry for various purposes*/\n\tstruct delayed_work dwork;\t\t\t/* for cool downs needed in error recovery */\n\tunsigned int ctrlin;\t\t\t\t/* input control lines (DCD, DSR, RI, break, overruns) */\n\tunsigned int ctrlout;\t\t\t\t/* output control lines (DTR, RTS) */\n\tstruct async_icount iocount;\t\t\t/* counters for control line changes */\n\tstruct async_icount oldcount;\t\t\t/* for comparison of counter */\n\twait_queue_head_t wioctl;\t\t\t/* for ioctl */\n\tunsigned int writesize;\t\t\t\t/* max packet size for the output bulk endpoint */\n\tunsigned int readsize,ctrlsize;\t\t\t/* buffer sizes for freeing */\n\tunsigned int minor;\t\t\t\t/* acm minor number */\n\tunsigned char clocal;\t\t\t\t/* termios CLOCAL */\n\tunsigned int ctrl_caps;\t\t\t\t/* control capabilities from the class specific header */\n\tunsigned int susp_count;\t\t\t/* number of suspended interfaces */\n\tunsigned int combined_interfaces:1;\t\t/* control and data collapsed */\n\tu8 bInterval;\n\tstruct usb_anchor delayed;\t\t\t/* writes queued for a device about to be woken */\n\tunsigned long quirks;\n};\n\n#define CDC_DATA_INTERFACE_TYPE\t0x0a\n\n/* constants describing various quirks and errors */\n#define NO_UNION_NORMAL\t\t\tBIT(0)\n#define SINGLE_RX_URB\t\t\tBIT(1)\n#define NO_CAP_LINE\t\t\tBIT(2)\n#define NO_DATA_INTERFACE\t\tBIT(4)\n#define IGNORE_DEVICE\t\t\tBIT(5)\n#define QUIRK_CONTROL_LINE_STATE\tBIT(6)\n#define CLEAR_HALT_CONDITIONS\t\tBIT(7)\n#define SEND_ZERO_PACKET\t\tBIT(8)\n#define DISABLE_ECHO\t\t\tBIT(9)\n" ]

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[ "Bastion team: Downloadable games can “provide a better value to players” than retail titles\n\nAs with many new studios, Supergiant Games have opted for digital distribution with their first game, Bastion. ", "Explaining the decision to Critical Gamer, writer and level designer Greg Kasavin emphasises the power and independence it affords the team.", "\n\n“Many of us used to work on retail games. ", "Amir, Gavin, and I met while working on the Command &Conquer franchise for Electronic Arts, and Andrew worked at Infinity Ward on Modern Warfare and its sequel. ", "So we’ve been there before.” ", "he says. “", "I’d be foolish to say it’s something I’d never want to do again under any circumstances, because once in a while there’s a truly amazing retail game that’s like nothing else out there. ", "But we deliberately left making retail games in favor of making downloadable games because we saw more exciting opportunities here. ", "We can work faster to make our own games, make the kinds of creative choices that would never be permissible at a large studio, and ultimately provide a better value to players out there — folks have remarked that Bastion has the quality and scope of a full retail title, but it’s available for just a fraction of the cost.”", "\n\nWe thoroughly agree with this sentiment, which is why we awarded Bastion a highly respectable 9/10 in our review. ", "Kasavin went on to explain that the 2D graphics were central to development, their importance deeper than aesthetics.", "\n\n“One thing we knew from the very beginning was that we wanted to make a 2D game, as we really miss the crisp and responsive feel of classic 2D games and think most of today’s 3D games still struggle to achieve that.”", "\n\nThe full interview, covering a range of aspects of Bastion’s development, will be published tomorrow.", "\n\nWritten by Luke K\n\nHe plays lots of videogames, now and again stopping to write about them. ", "He's the editor in chief at Critical Gamer, which fools him into thinking his life has some kind of value.", "\nHe doesn't have a short temper. ", "If you suggest otherwise, he will punch you in the face." ]

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[ "Efficacy and safety of olmesartan medoxomil/amlodipine fixed-dose combination for hypertensive patients uncontrolled with monotherapy.", "\nThis study aimed to evaluate the efficacy and safety of olmesartan medoxomil (OM)/amlodipine (AML) 20/5 mg fixed-dose combination tablet in Chinese mild to moderately hypertensive patients with inadequate blood pressure (BP) control on monotherapy. ", "Two multicenter, randomized, double-blind, double-dummy, active-controlled, parallel group clinical trials were conducted. ", "After screening and a 2-week placebo run-in period, patients with 95 mmHg ≤ seated diastolic blood pressure (SeDBP) < 110 mmHg received monotherapy with OM 20 mg (in Study 1) or AML 5 mg (in Study 2), once daily for 4 weeks. ", "Patients with 90 mmHg ≤ mean SeDBP < 110 mmHg at the end of the monotherapy period were randomized to receive OM/AML 20/5 mg treatment or continue with the monotherapy, once daily for 8 weeks. ", "OM/AML (20/5 mg) treatment significantly lowered both systolic and diastolic BP at 4 and 8 weeks compared to 40 mg olmesartan or 5 mg AML. ", "The incidence of drug-related adverse effects did not differ significantly between the groups. ", "OM/AML 20/5 mg was superior to OM 40 mg or AML 5 mg monotherapy in lowering BP in Chinese mild to moderately hypertensive patients with inadequate BP control on monotherapy. ", "No new or unexpected safety issues were identified with OM/AML combination therapy compared to monotherapy." ]

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[ "Q:\n\nCannot delete an upload session\n\nI can create an upload session, but I cannot delete it immediately afterwards. ", " I receive a 403 Forbidden error.", "\nTransfer-Encoding: chunked\nX-SharePointHealthScore: 0\nX-Forms_Based_Auth_Required: https://REDACTED.sharepoint.com/_forms/default.aspx?ReturnUrl=/_layouts/15/error.aspx&Source=%2f_vti_bin%2fclient.svc%2fv2.0%2fdrives%2fREDACTED%2fuploadSession%3fguid%3d%27REDACTED%27%26path%3d%27%7etmpE6_test.txt%27%26overwrite%3dFalse%26rename%3dTrue\nX-Forms_Based_Auth_Return_Url: https://REDACTED.sharepoint.com/_layouts/15/error.aspx\nX-MSDAVEXT_Error: 917656; Access+denied.+Before+opening+files+in+this+location%2c+you+must+first+browse+to+the+web+site+and+select+the+option+to+login+automatically.", "\nODATA-VERSION: 4.0\nX-IDCRL_AUTH_PARAMS_V1: IDCRL Type=\"BPOSIDCRL\", EndPoint=\"/personal/REDACTED/_vti_bin/idcrl.svc/\", RootDomain=\"sharepoint.com\", Policy=\"MBI\"\nSPRequestGuid: REDACTED\nrequest-id: REDACTED\nStrict-Transport-Security: max-age=31536000\nX-FRAME-OPTIONS: SAMEORIGIN\nMicrosoftSharePointTeamServices: 16.0.0.6712\nX-Content-Type-Options: nosniff\nX-MS-InvokeApp: 1; RequireReadOnly\nX-MSEdge-Ref: Ref A: REDACTED Ref B: REDACTED Ref C: 2017-07-20T14:31:00Z\nCache-Control: private, max-age=0\nContent-Type: application/json;odata.metadata=minimal;odata.streaming=true;IEEE754Compatible=false;charset=utf-8\nDate: Thu, 20 Jul 2017 14:31:00 GMT\nExpires: Wed, 05 Jul 2017 14:31:00 GMT\nLast-Modified: Thu, 20 Jul 2017 14:31:00 GMT\nP3P: CP=\"ALL IND DSP COR ADM CONo CUR CUSo IVAo IVDo PSA PSD TAI TELo OUR SAMo CNT COM INT NAV ONL PHY PRE PUR UNI\"\nServer: Microsoft-IIS/10.0\nX-AspNet-Version: 4.0.30319\nX-Powered-By: ASP.NET\n\nHere is the stripped down version of the code that gets the same result.", "\nusing System;\nusing System.", "Net;\nusing System.", "Web.", "Script.", "Serialization;\n\nnamespace OneDriveUploadSession\n{\n class Program\n {\n static void Main(string[] args)\n {\n JavaScriptSerializer jss = new JavaScriptSerializer();\n string strTokenURL = \"https://login.microsoftonline.com/REDACTED.onmicrosoft.com/oauth2/v2.0/token\";\n string strAppSecret = \"client_id=REDACTED&scope=https%3A%2F%2Fgraph.microsoft.com%2F.default&client_secret=REDACTED&grant_type=client_credentials\";\n string strUserName = \"REDACTED\";\n\n //Get Access Token\n WebClient wcAccessToken = new WebClient();\n\n wcAccessToken.", "Headers.", "Add(\"Content-Type\", \"application/x-www-form-urlencoded\");\n\n string strJSONAccessToken = wcAccessToken.", "UploadString(strTokenURL, strAppSecret);\n dynamic dynJSONAccessToken = jss.", "DeserializeObject(strJSONAccessToken);\n string strAccessToken = dynJSONAccessToken[\"access_token\"].Replace(Environment.", "NewLine, \"\");\n\n //Get Drive ID for specified user\n WebClient wcDriveID = new WebClient();\n\n wcDriveID.Headers.", "Add(\"Authorization\", \"Bearer \" + strAccessToken);\n\n string strDriveJSON = wcDriveID.DownloadString(\"https://graph.microsoft.com/v1.0/users/\" + strUserName + \"/drives\");\n dynamic dynDriveJSON = jss.", "DeserializeObject(strDriveJSON);\n string strDriveID = dynDriveJSON[\"value\"][0][\"id\"];\n\n //Create Upload Session\n WebClient wcCreateUploadSession = new WebClient();\n string strCreateUploadSessionURL = \"https://graph.microsoft.com/v1.0/drives/\" + strDriveID + \"/root:/test.txt:/createUploadSession\";\n\n wcCreateUploadSession.", "Headers.", "Add(\"Authorization\", \"Bearer \" + strAccessToken);\n wcCreateUploadSession.", "Headers.", "Add(\"Content-Type\", \"application/json\");\n\n string strJSONCreateUploadSession = wcCreateUploadSession.", "UploadString(strCreateUploadSessionURL, \"POST\", \"{\\\"item\\\": {\\\"@microsoft.graph.conflictBehavior\\\": \\\"rename\\\"}}\");\n dynamic dynJSONCreateUploadSession = jss.", "DeserializeObject(strJSONCreateUploadSession);\n string strUploadSessionURL = dynJSONCreateUploadSession[\"uploadUrl\"];\n\n //Delete Upload Session\n WebRequest wrDeleteUploadSession = WebRequest.", "Create(strUploadSessionURL);\n\n wrDeleteUploadSession.", "Method = \"DELETE\";\n wrDeleteUploadSession.", "GetRequestStream();\n wrDeleteUploadSession.", "GetResponse();\n }\n }\n}\n\nA:\n\nBased on your code, you're using the client credentials flow (aka app-only). ", "Resumable uploads are not supported in this scenario. ", "From the documentation:\n\nNote: The Files.", "ReadWrite.", "All application permission is not yet supported on this API. ", "Full support is planned soon.", "\n\nAt this time, resumable uploads are only supported using delegated permission. ", "\n\n" ]

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[ "Q:\n\nGood practice sharing resources between modules?", "\n\nI am reorganizing my code and therefore creating new namespaces. ", "I'm changing \"static\" classes (classes with @staticmethod in each method) for modules. ", "This is the way to go, right?", "\nThe problem is that I have doubts on how to share the resources between these modules.", "\nLet's say I had a module from which I was doing all connections to database, and of course all classes/methods were sharing the variable which stored the DB cursor (I'm using SQLite). ", "Now, in different modules, they also have to share the cursor.", "\n\nSo, my ideas:\n\nDeclare the global variable in each module. ", "But globals are evil, eat children and steal our jobs. ", "So I don't know if this is the way to go.", "\n'''Sub Module 1'''\n\nglobal database_cursor\n\nImport the \"father\" database_module with the original database_cursor and use something like this:\n'''Sub Module 1'''\n\ndb_cursor = database_module.database_cursor\n\nThis second looks fine in this case, but I think in many cases will lead to recursive imports, which I guess it´s something to avoid.", "\n\nA:\n\nYour second method is the way to go. ", "Python imports are singleton by nature. ", "When a module is imported multiple times it is only executed the first time. ", "Subsequent imports fetch the module object instance from the globals. ", "More on that here.", "\nshared.py:\nclass Shared:\n def __init__(self):\n print(\"Init shared\")\n\n def do_stuff(self, from_mod):\n print(\"Do stuff from {0}. ", "I am instance {1}\".format(from_mod, self))\n\nshared = Shared()\n\nfoo.py\nimport shared\n\nshared.shared.do_stuff(\"foo\")\n\nbar.py\nimport foo\nimport shared\n\nshared.shared.do_stuff(\"bar\")\n\nIf we execute bar.py we get:\n>>> Init shared\n>>> Do stuff from foo. ", "I am instance <shared.", "Shared instance at 0x10046df38>\n>>> Do stuff from bar. ", "I am instance <shared.", "Shared instance at 0x10046df38>\n\nSo in your case you can reference database_module from anywhere you want and it gets initialized only once, therefore effectively sharing your connection.", "\n\n" ]

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[ "Live in one of Vancouver's quiet & tree-lined neighborhoods ideal for raising a family -- near schools, parks, and the Skytrain station. ", "This bright home has 4 bedrooms and 2 bathrooms in total, a sunny kitchen, and a dining room overlooking the backyard. ", "Enjoy ample storage, lane access, plus potential for laneway housing for added income. ", "Check out the nearby shops & restaurants along Commercial Drive which celebrate the unique flavours of the city!" ]

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[ "Q:\n\nTimer tick doesn't work\n\nI having problem with my timer, it doesn't reach its tick and I don't see the problem.", "\nclass Class1\n{\n bool check;\n Timer net;\n private bool timerComplete = false;\n private int timerIndex = 0;\n\n public Class1()\n {\n check = true;\n net = new Timer();\n }\n public void Do()\n {\n System.", "Threading.", "Thread.", "Sleep(4*1*1000);\n net.", "Interval = 1 * 1000;\n net.", "Tick+=new EventHandler(net_Tick);\n net.", "Start();\n while (!", "timerComplete)\n System.", "Threading.", "Thread.", "Sleep(1000);\n\n }\n\n void net_Tick(object sender, EventArgs e)\n {\n timerIndex++;\n if (timerIndex >= 10)\n {\n timerComplete = true;\n return;\n }\n //my code\n }\n}\n\nMain\nThis is where I call the Do() function\nclass Program\n{\n const int SW_HIDE = 0;\n\n static void Main(string[] args)\n {\n Hide();\n Class1 c = new Class1();\n c.Do();\n }\n\n public static void Hide()\n {\n var handle = GetConsoleWindow();\n // Hide\n ShowWindow(handle, SW_HIDE);\n }\n\n [DllImport(\"kernel32.dll\")]\n static extern IntPtr GetConsoleWindow();\n\n [DllImport(\"user32.dll\")]\n static extern bool ShowWindow(IntPtr hWnd, int nCmdShow);\n}\n\nA:\n\nYour code is a bit confusing but basically you are looking for the following\nstatic void Main(string[] args) {\n var myObject = new Class1();\n myObject.", "Do();\n\n // give the program 10 minutes to run. ", "This is arbitrary so you will want to change\n // to something realistic or have a callback to signal \"done\".", "\n System.", "Threading.", "Thread.", "Sleep(10 * 60 * 1000);\n}\n\nThat should do it or at least get you started!", "\nOther Note - One other note is the second timer calls a method named net_Tick. ", "I don't see this in the code presented so I assume there are no issues with that...\nAlternative Approach\nOne other approach instead of making the main thread pause is to block the Do method until the timer is done (or you want to stop). ", "To do this I have added just the pieces of code that need to change in Class1 below:\npublic class Class1 {\n\n // add a variable for timer complete\n private bool timerComplete = false;\n private int timerIndex = 0;\n\n public void Do()\n {\n t.Enabled = true;\n\n // start timer same as normal:\n t.Interval = 10 * 1000;\n t.Tick += new EventHandler(t_Tick);\n t.Start();\n\n // busy wait to block the thread\n while (!", "timerComplete) {\n System.", "Threading.", "Thread.", "Sleep(1000);\n }\n }\n\n void t_Tick(object sender, EventArgs e)\n {\n // give this a stopping point\n timerIndex++;\n if (timerIndex >= 10) {\n timerComplete = true;\n return;\n }\n\n // leave the rest of the tick as it was before...\n }\n}\n\nOnce you do this you can remove the call to Sleep from the Main routine and everything should still work. ", "Best of luck!", "\n\n" ]

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[ "Fiber media converter\n\nA fiber media converter is a simple networking device that makes it possible to connect two dissimilar media types such as twisted pair with fiber optic cabling. ", "They were introduced to the industry in the 1990s, and are important in interconnecting fiber optic cabling-based systems with existing copper-based, structured cabling systems. ", "They are also used in metropolitan area network (MAN) access and data transport services to enterprise customers.", "\n\nMedia conversion types\nFiber media converters support many different data communication protocols including Ethernet, Fast Ethernet, Gigabit Ethernet, T1/E1/J1, DS3/E3, as well as multiple cabling types such as coax, twisted pair, multi-mode and single-mode fiber optics. ", " Media converter types range from small standalone devices and PC card converters to high port-density chassis systems that offer many advanced features for network management.", "\n\nOn some devices, Simple Network Management Protocol (SNMP) enables proactive management of link status, monitoring chassis environmental statistics and sending traps to network managers in the event of a fiber break or even link loss on the copper port.", "\n\nFiber media converters can connect different local area network (LAN) media, modifying duplex and speed settings. ", "Switching media converters can connect different speed network segments. ", "For example, existing half-duplex hubs can be connected to 100BASE-TX Fast Ethernet network segments over 100BASE-FX fiber.", "\n\nWhen expanding the reach of the LAN to span multiple locations, media converters are useful in connecting multiple LANs to form one large campus area network that spans over a limited geographic area. ", "As premises networks are primarily copper-based, media converters can extend the reach of the LAN over single-mode fiber up to 160 kilometers with 1550 nm optics.", "\n\nWavelength-division multiplexing (WDM) technology in the LAN is especially beneficial in situations where fiber is in limited supply or expensive to provision. ", " As well as conventional dual strand fiber converters, with separate receive and transmit ports, there are also single strand fiber converters, which can extend full-duplex data transmission up to 120 kilometers over one optical fiber.", "\n\nOther benefits of media conversion include providing a gradual migration path from copper to fiber. ", "Fiber connections can greatly extend the reach and reduce electromagnetic interference.", "\n\nAlso fiber media converters pose as an alternative solution for switches not supporting fiber; ordinary switches can use fiber media converters to connect to a fiber network.", "\n\nConverter types\n\nSimple converters – when the speed and duplex settings on both media is identical – consist of two pairs of transmitters/receivers, each with their medium-dependent interfaces (when no data recoding is necessary) or their media-independent interfaces joined together back-to-back in a dual-simplex fashion. ", "They can transport either half-duplex or full-duplex traffic but both sides must match.", "\n\nSwitching converters contain a network bridge and can connect two half-duplex segments without joining their collision domains.", "\n\nManaged converters are usually of the switching kind and can additionally be managed by a network connection or a local console. ", "However, most often pluggable transceivers are used instead when appropriate equipment already exists.", "\n\nSee also\n\n Gigabit interface converter\n Fiber-optic communication\n Small form-factor pluggable transceiver\n\nReferences\n\n Spurgeon, Charles E., Ethernet: The Definitive Guide, Sebastopol, CA: O'Reilly & Associates, 2000\n Residential Network Cabling, New York, NY: R.R. Donnelley & Sons Company, 2002\n The Switching Book, Xylan: An Alcatel Company, 1999\n\nMedia converter" ]

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[ "Thursday, February 17, 2011\n\nCal. ", "Supreme Court to Answer Certified Question on Prop 8\n\nThe California Supreme Court today said it would answer the standing question in the Proposition 8 same-sex marriage appeal at the Ninth Circuit U.S. Court of Appeals.", "\n\nThe justices unanimously agreed to say whether California law allows for ballot initiative proponents to defend the constitutionality of a measure when state officeholders refuse to do so.", "\n\nThe three-judge Ninth Circuit panel — Stephen Reinhardt, Michael Daly Hawkins and N. Randy Smith — sent the certified question to the Supreme Court in January after Reinhardt raised the idea during oral arguments Dec. 6.", "\n\nThe justices agreed to expedite the matter. ", "In a short order, the Supreme Court set a briefing schedule that will allow for oral arguments \"as early as\" September. ", "The first briefs are due March 14. ", "Responses are due April 4." ]

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[ "2009 Asian Athletics Championships – Women's javelin throw\n\nThe women's javelin throw event at the 2009 Asian Athletics Championships was held at the Guangdong Olympic Stadium on November 12.", "\n\nResults\n\nReferences\nResults\n\nCategory:2009 Asian Athletics Championships\nCategory:Javelin throw at the Asian Athletics Championships\nCategory:2009 in women's athletics" ]

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[ "Q:\n\nSolve indefinite integral $\\int\\tan(x-a)\\tan(x+a)\\tan(2x)\\ dx$\n\nTried expanding $\\tan$ terms but was not able to reach anywhere with it. ", "How should I proceed ?", "\n\nA:\n\nHINT:\n$$\\tan(A+B+C)=\\dfrac{\\sum\\tan A-\\prod\\tan A}{\\cdots}$$\nFor integer $n,$ if $A+B+C=n\\pi,\\sum\\tan A-\\prod\\tan A=0$\n$$\\tan(2x)=-\\tan(-2x)$$\nand $$\\tan(x+a)\\tan(x-a)\\tan(-2x)=\\tan(x+a)+\\tan(x-a)+\\tan(-2x)$$\nas $x+a+(x-a)+(-2x)=0\\cdot\\pi$\n\nA:\n\nIts quite easy.", "\nI would give you hint then you can try a bit further\nIf $$2x = (x+a) + (x-a)$$ \n$$\\tan2x = \\tan\\left[ (x+a) + (x-a) \\right]$$\nsolving these you will get a result which is as follows :\n$$\\tan(2x)-\\tan(x+a)-\\tan(x-a)=\\tan(2x)\\tan(x+a)\\tan(x-a)$$\nNow integrate $\\tan(2x)-\\tan(x+a)-\\tan(x-a)$ instead of $\\tan(2x)\\tan(x+a)\\tan(x-a)$\nTry it from here now you might be able to solve it from here.", "\n\n" ]

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[ "ABOUT US\n\nPotter’s Place Community Services Society is a voluntary, non-profit organization registered in December 2000. ", "We are a member of the National Council of Social Services and a Family Life Ambassador. ", "Our focus is to enrich the emotional, intellectual, spiritual, social and physical well-being of senior citizens, children and youth. ", "Enhance the building of strong family foundations and cohesiveness, and enable the needy through relief programs and services, as well as encouraging social interaction and a healthy lifestyle.", "\n\nROYAL RANGERS\n\nMORNING EXERCISE @ CASA CLEMENTI\n\nWELFARE ASSISTANCE SCHEMES\n\nThis is a leadership and enrichment program for children/youth age 5 to 17. ", "The activities are held every Saturday 3pm to 5pm.", "\n\nBlk 420A Roof Garden, Clementi Ave 1 - We have a morning exercise program every Friday 7.30am to 8.30am to promote a healthy lifestyle to the community.", "\n\nAssist the needy through our welfare assistance schemes and information on other schemes available from government & welfare agencies.", "\n\nCOUNSELLING SERVICES\n\nLEGAL COUNSELLING SERVICES\n\nAPPOINTMENTS FOR COUNSELLING\n\nWe offer counselling services to those who need someone to talk to in their life journey. ", "Our services are non-chargeable, voluntary and confidential. ", "This is a place where you can share about your concerns and explore ways you can manage your situation.", "\n\nOn every 2nd Thursday of the month, qualified lawyers will be on hand to render free legal advice to those facing legal issues or who have queries on the law. ", "Full confidentiality is assured.", "\n\nCall 6466-0293 during office hours - 9am to 6pm for appointment. ", "Callers will be asked to provide some basic information about themselves & the reasons for seeking consultation." ]

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[ "The Loyal White Knights of Pelham in North Carolina - one of the largest branches of the far-right group in the US – have arranged the celebration for December 3.", "\n\nOn the Klan’s website there is a large picture of Mr Trump, along with the words “TRUMP’S RACE UNITED MY PEOPLE”.", "\n\nA prominent KKK newspaper, the Crusader, previously appeared to endorse Mr Trump for Presidency after publishing a front-page spread titled “Make America Great Again” – the slogan of the President-elect’s campaign.", "\n\nHow about that? ", "Trump's struggled to earn newspaper endorsements, but just secured one from the KKK's \"Crusader\"... pic.twitter.com/W63k54Yivx\n\nIn response to the paper's front page, it released a statement saying: “This publication is repulsive and their views do not represent the tens of millions of Americans who are uniting behind our campaign.”", "\n\nThe Trump campaign had repeatedly been forced to defend itself against accusations of racism and discrimination in the lead up to the election following a series of controversial comments made by the President-elect." ]

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[ "Review: improving end-of-life care: a critical review of the gold standards framework in primary care.", "\nThe Gold Standards Framework aims to optimize primary palliative care for patients nearing the end of their lives. ", "This paper critically reviews the impact of the Gold Standards Framework since its introduction in 2001 and indicates direction for further research and development. ", "Literature was accessed using specific databases and by contacting subject area specialists. ", "The resultant literature was appraised using an established framework to evaluate healthcare interventions. ", "Fifteen documents were reviewed. ", "The quality of evidence is constrained by methodological limitations, but consistently demonstrates that the Gold Standards Framework improves general practice processes, co-working and the quality of palliative care. ", "However, implementation of the Gold Standards Framework is variable and the direct impact on patients and carers is not known. ", "We conclude that the Gold Standards Framework has considerable potential to improve end-of-life care, but further work is needed to support uptake and consistency of implementation. ", "Additional evidence about patient and carer outcomes will add to existing insights." ]

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[ "Case dismissed against Minnesota-Mankato coach Hoffner\n\nGeorge Schroeder and Daniel Uthman, USA TODAY Sports | USATODAY\n\nThe case against Todd Hoffner, the suspended Minnesota State-Mankato football coach accused of child pornography, was dismissed Friday, almost a month after he took the stand to defend himself against the charges. ", "Still uncertain, though, is what the future holds for the coach.", "\n\nHoffner, 46, faced two felony charges – using minors in a sexual performance or pornographic work and possession of child pornography – after three cell-phone videos of naked or partially clothed children were discovered on his university-issued cell phone. ", "According to court records, the videos, which were discovered in August by a university technician after Hoffner turned in his malfunctioning BlackBerry, were later determined to be of Hoffner's own children, ages 9, 8 and 5.", "\n\n\"There's nothing inappropriate about any of those videos,\" Hoffner said during testimony Oct. 31 at a motion-to-dismiss hearing.", "\n\nBlue Earth County District Court Krista Jass agreed. ", "In dismissing the case for lack of probable cause, she ruled the videos did not meet the legal definition of child pornography and that there was not substantial evidence that Hoffner \"used or permitted his minor children to pose or model in a 'sexual performance' or 'pornographic work.' \" ", "Jass also wrote:\n\n\"The videos under consideration here contain nude images of Defendant's minor children dancing and acting playful after a bath. ", "That is all they contain.\"", "\n\nAt a news conference Friday afternoon in Mankato, Minn., Hoffner read a statement but did not take questions. ", "He noted 102 seconds of videos resulted in 102 days of a \"long, painful nightmare.\"", "\n\n\"Our lives have been turned upside down,\" he said, adding: \"I'm really looking forward to getting back to my life, my job and my family.\"", "\n\nBut what comes next isn't certain. ", "The university launched an investigation of Hoffner and placed him on paid administrative leave August 17; he was arrested several days later. ", "His team is 12-0 and earned the top seed in the NCAA Division II football playoffs under interim head coach and offensive coordinator Aaron Keen. ", "The Mavericks play Saturday in the Division II quarterfinals against Missouri Western State.", "\n\nDan Benson, a university spokesman, told USA TODAY Sports, \"From the university standpoint, there has not been any change in Todd Hoffner's status. ", "He remains on paid administrative leave. ", "He continues in that status, and we have a pending university investigation. ", "Because of that, we are unable to comment further on anything specific regarding Todd.\"", "\n\nJim Fleming, Hoffner's attorney, told USA TODAY Sports the next goal is Hoffner's reinstatement as coach. \"", "There's elation in the sense that this is done (legally),\" Fleming said. \"", "We still want Todd to be reinstated as coach. (", "The felony charges were) the basis for the action they were taking against him.\"", "\n\nSeveral Mankato residents interviewed in October by USA TODAY Sports referenced the recent scandal involving former Penn State assistant football coach Jerry Sandusky, wondering whether it influenced university and law enforcement officials.", "\n\n\"The damage is done. ", "His reputation is tainted. ", "On the tip of everybody's tongue is 'Sandusky,' \" said John Harrington, a longtime Mankato resident and Minnesota State-Mankato booster, noting that when he \"googled Todd's name, immediately a picture of him comes up in an orange jumpsuit.\"", "\n\nHarrington added: \"Seeing what it's done to Todd, I still know why (the university) did what it did when it started (the investigation). ", "But from then on, I don't know how it's not been dropped.\"", "\n\nFleming said he still can't figure out why it wasn't. ", "He said he twice asked Blue Earth County assistant county attorney Michael Hanson to dismiss the charges.", "\n\n\"I felt in my core this was not child pornography,\" he said. \"", "Once I saw the videos, it was: 'You have got to be kidding me.' \"", "\n\nHanson issued a statement Friday saying, \"Our office was trying to enforce a statute enacted to protect children. … ", "While we do not agree with (Jass') decision to dismiss the case, we accept it.\"", "\n\nIn an unusual move, Hoffner took the stand Oct. 31 during a pretrial hearing on the motion to dismiss. ", "In 45 minutes of testimony, he explained how and why he recorded the videos one evening last summer. ", "He said the evening of June 26, he was \"working on football stuff\" in the family's living room, and sent the three children to take a bubble bath together. ", "He said the children were \"very\" comfortable when naked together.", "\n\nWhen they finished the bath, Hoffner testified, the children came downstairs wearing towels and asked him to record a video, then dropped the towels and danced naked. ", "At one point, according to court records, Hoffner's son grabbed his own penis. ", "At another point, the girls bent over and pulled apart their buttocks.", "\n\nHoffner described his daughters attempting some sort of skit, \"singing and dancing and laughing, doing silly things, having fun,\" while his son attempted to \"sabotage\" the girls' performance. ", "He said he did not instruct the children.", "\n\nIn the ruling, Jass agreed, writing: \"It is clear from the children's statements on the videos that the performance was created by them and not Defendant. ", "Defendant never directs or poses the children. ", "All statements made by Defendant on the videos are of a passive nature, inquiring if the children are finished with their performance. ", "Moreover, nothing about the children's performance is overly erotic or sexual.", "\n\n\"There is simply no evidence, circumstantial or otherwise, that reasonably demonstrates Defendant knew or had reason to know his children intended their after-bath skit to be a 'sexual performance' or 'pornographic work' as those terms are defined by Minnesota law.\"", "\n\nHoffner's case was buttressed by the testimony of Holly Barkeim, a child protective services specialist with Blue Earth County Human Services. ", "Jass wrote Barkeim \"credibly testified\" she did not find evidence of sexual abuse during interviews with Hoffner's children or when viewing the videos.", "\n\nSearches of Hoffner's home and office turned up no other evidence. ", "According to reports in multiple Minnesota newspapers, officials at three universities where Hoffner previously worked conducted reviews and found no improper conduct. ", "Background checks by USA TODAY Sports found no criminal record for Hoffner.", "\n\nIn a closing statement during the Oct. 31 hearing, Hanson said: \"Adults should not make movies of children in lewd poses. ", "Period. ", "There should be no parental exceptions.\"", "\n\nIn dismissing the charges, Jass wrote: \"At no time did the children perform a lewd or erotic act. ", "In fact, none of the children's actions are age-inappropriate. ", "They acted as any child, acutely aware of his/her nakedness, would act – playful and silly.\"" ]

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[ "Links can be edited directly from the plugin’s page, without manually updating each post.", "\n\nHighly configurable.", "\n\nBasic Usage\n\nOnce installed, the plugin will begin parsing your posts, bookmarks (AKA blogroll) and other content and looking for links. ", "Depending on the size of your site this can take from a few minutes up to an hour or more. ", "When parsing is complete, the plugin will start checking each link to see if it works. ", "Again, how long this takes depends on how big your site is and how many links there are. ", "You can monitor the progress and tweak various link checking options in Settings -> Link Checker.", "\n\nThe broken links, if any are found, will show up in a new tab of the WP admin panel – Tools -> Broken Links. ", "A notification will also appear in the “Broken Link Checker” widget on the Dashboard. ", "To save display space, you can keep the widget closed and configure it to expand automatically when problematic links are detected. ", "E-mail notifications need to be enabled separately (in Settings -> Link Checker).", "\n\nThe “Broken Links” tab will by default display a list of broken links that have been detected so far. ", "However, you can use the links on that page to view redirects or see a listing of all links – working or not – instead. ", "You can also create new link filters by performing a search and clicking the “Create Custom Filter” button. ", "For example, this can be used to create a filter that only shows comment links.", "\n\nThere are several actions associated with each link. ", "They show up when you move your mouse over to one of the links listed the aforementioned tab –\n\n“Edit URL” lets you change the URL of that link. ", "If the link is present in more than one place (e.g. both in a post and in the blogroll), all occurrences of that URL will be changed.", "\n\n“Unlink” removes the link but leaves the link text intact.", "\n\n“Not broken” lets you manually mark a “broken” link as working. ", "This is useful if you know it was incorrectly detected as broken due to a network glitch or a bug. ", "The marked link will still be checked periodically, but the plugin won’t consider it broken unless it gets a new result.", "\n\n“Dismiss” hides the link from the “Broken Links” and “Redirects” views. ", "It will still be checked as normal and get the normal link styles (e.g. a strike-through effect for broken links), but won’t be reported again unless its status changes. ", "Useful if you want to acknowledge a link as broken/redirected and just leave as it is.", "\n\nYou can also click on the contents of the “Status” or “Link Text” columns to get more info about the status of each link.", "\n\nBeoordelingen\n\nOhmygosh, this plugin is *fantastic*! ", "The prepopulated option to sub in the archive.org url? ", "Brilliant!", "\nIn fact, this is one of the only times I have on my own *looked for a way to donate* to the plugin maker because it's *that* good - and..there is no way to donate! ", "So, Mr. Plugin Maker, please let me know how I can throw you a bit of $, because you totally deserve it!", "\n\nAlthough the plugin has a lot of settings, it has a default configuration that makes it very simple and easy to use. ", "Also you have a lot of control using the plugin settings. ", "It works smoothly, thanks!", "\n\nThis is a super awesome plugin and I really really wish we could have a paid version that has scheduled fix links or update links features etc and a donate option if not, to donate as this plugin is extremely useful and valuable for WordPress. ", "Huge thank you to the developers a massive thank you!", "\n\n1.10.4\n\nFixed a double-escaping bug that could cause some link URLs to be displayed incorrectly.", "\n\nUpdated French translation.", "\n\nUpdated Dutch translation.", "\n\n1.10.3\n\nSecurity: Filter link URLs before displaying them on the “Broken Links” page.", "\n\nSecurity: Prevent Editors and Administrators who don’t have the “unfiltered_html” capability from creating “javascript:” URLs by editing existing links.", "\n\n1.10.2\n\nFixed an XSS vulnerability on the link checker settings page.", "\n\nFixed old YouTube embed code parsing – now it should pick up self-closing embed tags without an <object> wrapper.", "\n\nUpdated German translation.", "\n\nUpdated Simplified Chinese translation.", "\n\nLink actions will now wrap properly on small screens.", "\n\n1.10.1\n\nFixed a database versioning issue that would cause multiple errors when upgrading from 1.9.5 to 1.10.", "\n\n1.10\n\nAdded a way to hide individual link actions like “Dismiss” and “Unlink”.", "\n\nAdded a “Fix redirect” link action. ", "It replaces a redirect with a direct link. ", "It is hidden by default and can be enabled through the settings page.", "\n\nAdded a “Recheck” link action. ", "Unlike the bulk action by the same name, it checks a link immediately and displays the results without having to refresh the page.", "\n\nAdded a “Dismiss” bulk action.", "\n\nAdded a note below the “link tweaks” settings explaining that they only apply to the contents of posts (and pages, and CPTs), not comments or custom fields.", "\n\nMade the “Redirect URL” column sortable.", "\n\nAdded a “Details” link to the “Status” column.", "\n\nAdded a “Warnings” section to Tools -> Broken Links. ", "It shows problems that might be temporary or false positives. ", "Warnings can be disabled through the settings page.", "\n\nFixed a conflict with plugins that use PHP sessions.", "\n\nFixed the “post statuses” option. ", "Now disabling a post status (e.g. “Draft”) should take effect immediately.", "\n\nFixed the Mediafire link checker.", "\n\nFixed the text in the “Status” column being slightly offset vertically when compared to other columns.", "\n\nFixed search box position in WP 4.1-alpha.", "\n\nAdded a few workarounds for situations where a custom post type is removed without first removing the posts.", "\n\nRemoved the screen icon. ", "WordPress has deprecated it.", "\n\nOther minor fixes.", "\n\n1.9.5\n\nFixed missing YouTube videos not being detected when the video URL starts with https instead of http.", "\n\nEnabled the YouTube video checker by default on new installations.", "\n\nMade the “dismiss link” option more permanent. ", "Instead of restoring a dismissed link if the redirect URL changes even a little bit, the plugin will now ignore query string changes. ", "This should fix many of the reports about dismissed links reappearing for no apparent reason.", "\n\nUpdated Portuguese, German and Dutch translations.", "\n\nOther minor fixes.", "\n\n1.9.4.2\n\nUpdated Dutch translation again.", "\n\nRemoved Bulgarian translation because it was poor quality and outdated.", "\n\n1.9.4.1\n\nUpdated Dutch translation.", "\n\nUpdated POT file.", "\n\n1.9.4\n\nTested on WP 4.0 beta.", "\n\nAdded a Serbo-Croatian translation.", "\n\nAdded a Slovakian translation.", "\n\nReplaced the old Japanese translation with a new and more up-to-date version from a different translator.", "\n\nUpdated Dutch, German, Polish, Hebrew and other translations.", "\n\nFixed a notice about undefined index “status_text”.", "\n\nFixed a “doing it wrong” warning related to screen options.", "\n\nFixed spurious false positives on links copied from Word or similar editors.", "\n\nFixed view switcher appearance in WP 4.0.", "\n\nReplaced the deprecated like_esc() function with $wpdb->esc_like() where available.", "\n\nFixed plaintext URLs not being detected if they’re the very first thing in a post.", "\n\nFixed a bug that caused quotes and other special characters in the broken link CSS and removed link CSS fields to be auto-escaped with a slash, potentially breaking the CSS.", "\n\nFixed a bug that caused the “check custom fields” feature work inconsistently or not at all on custom post types.", "\n\nFixed duplicate custom field links showing up when the user creates a revision with different field values.", "\n\nFixed a specific type of false positive where some links would get flagged as “Unknown Error” and the log message would be “Empty reply from server”.", "\n\nFixed a bug where only the first enabled post type would be resynchronized during plugin activation.", "\n\nAdded more logging.", "\n\nRemoved Megavideo and MegaUpload modules. ", "These sites no longer exist.", "\n\n1.9.3\n\nTested on WP 3.8.1 and WP 3.9-beta2.", "\n\nAdded an option to sort links by link text. ", "May produce unexpected results for links that have multiple copies with different anchor text.", "\n\nAdded a Vietnamese translation.", "\n\nAdded file-based logging for debugging purposes. ", "Logging can be enabled in the “Advanced” section of the plugin settings page.", "\n\nAdded a “Auto-Submitted: auto-generated” header to notification emails sent by the plugin. ", "This should prevent “out-of-office” auto-responders and similar software from responding to these emails.", "\n\nFixed (probably) a long-standing bug related to encoding international characters in link URLs.", "\n\nFixed a typo in the Polish translation.", "\n\nMade the error message that’s displayed when trying to network-activate the plugin more useful.", "\n\n1.9.2\n\nFixed several UI/layout issues related to the new WP 3.8 admin style.", "\n\nFixed HTML entity codes showing up in confirmation messages in when running a localized version of WP (only affects some languages).", "\n\nFixed the “dismiss this notice” link URL not being HTML-escaped.", "\n\nFixed a couple of cross-site scripting vulnerabilities related to the sort direction query argument not being properly validated and the bulk action form not escaping the current URL.", "\n\nUpdated Hebrew translation.", "\n\nUpdated French translation.", "\n\nWhen you dismiss a link, the dismissed link counter is now updated right away instead of on page reload.", "\n\n1.9.1\n\nUpdated Dutch, German, Chinese and Portuguese translations.", "\n\nFixed suggestions not working on sites that force HTTPS in the WordPress admin.", "\n\nTested on WordPress 3.7.", "\n\n1.9\n\nAdded the ability to edit link text from inside the plugin. ", "This features is only available for certain types of links.", "\n\nAdded a “suggestions” feature. ", "When you go to edit a broken link, the plugin will now suggest replacing it with an archived page from the Wayback Machine (if available). ", "You can disable suggestions in Settings -> Link Checker -> General.", "\n\nAdded a Hebrew translation.", "\n\nAdded support for HTML code in custom fields. ", "To make the plugin treat a field as HTML, prefix its name with “html:” in BLC settings. ", "For example, if you have a custom field named “foo” that contains HTML, enter it as “html:foo”.", "\n\nFixed: The “Status” column is now properly updated when editing a link.", "\n\nFixed: Visual feedback when a link is successfully edited. ", "Basically, it briefly changes the row background to green.", "\n\nFixed: Email notifications will only include the “see all broken links here” link if the recipient can actually access that link.", "\n\nFixed some UI labels not being localizable.", "\n\nThe “Undismiss” action is now displayed in all views instead of only the “Dismissed” view. ", "This way you can tell if a broken link has been dismissed without having to search the “Dismissed” list.", "\n\nAdded information about the last email notification sent to debug info. ", "It’s accessible by clicking “show debug info” on the plugin settings page.", "\n\n1.8.3\n\nAdded a Hungarian translation.", "\n\nFixed a bunch of “deprecated function” notices that showed up due to wpdb::escape() becoming deprecated in WP 3.6.", "\n\nFixed a vulnerability that would allow users with the ability to bulk-edit links to execute arbitrary PHP code by using a specially crafted regex as the search string.", "\n\nUpdated German translation.", "\n\nReplaced the old Dutch translation with a new and more complete translation by Robin Roelofsen.", "\n\n1.8.2\n\nRemoved one of the translator credits links because Google flagged it as “suspicious”.", "\n\nUpdated French translation.", "\n\nUpdated Polish translation.", "\n\nFixed several field size and layout issues that made the search form display incorrectly in Firefox.", "\n\n1.8.1\n\nUpdated the Polish and Simplified Chinese translations.", "\n\nUpdated the German translation.", "\n\nAdded translation strings for two modules that were missing them.", "\n\nReplaced a number of icons with GPL-compatible alternatives from Font Awesome.", "\n\nRemoved some unused images.", "\n\n1.8\n\nAdded an option to only show the dashboard widget for users with the Administrator role, or to disable it completely.", "\n\n1.7.1\n\nFixed a bug where the plugin would sometimes report broken Twitter links as working.", "\n\nFixed the plugin author URL.", "\n\n1.7\n\nAdded support for youtu.be shortlinks.", "\n\nAdded a Finnish translation.", "\n\nFixed a graphical bug where the currently selected settings tab would not be highlighted in WordPress 3.5.", "\n\nRemoved the “Blogroll items” module from the list of link containers enabled by default. ", "The WordPress developer team is planning to remove Link Manager from core, and the “Links” menu will be hidden by default in new WP 3.5 installs.", "\n\n1.6.2\n\nAnother attempt to fix the “database not up to date” that some users are still experiencing even with 1.6.1.", "\n\n1.6.1\n\nFixed the “database not up to date” bug. ", "Now the plugin should properly upgrade the DB.", "\n\n1.6\n\nAdded a way to dismiss links. ", "Dismissed links don’t show up in the “Broken” and “Redirects” lists, but are still checked as normal and get the normal link styles (e.g. strike-through for broken links). ", "Useful if you want to, for example, acknowledge that a link is broken and leave it be.", "\n\nAdded a “Redirect URL” column. ", "For redirects this will display the URL that the link redirects to. ", "For normal, non-redirected links, it will be empty. ", "This column is hidden by default. ", "You can enable it in the “Screen Options” panel.", "\n\nUpdated French translation.", "\n\nTested on WP 3.4.1.", "\n\nReplace the “More plugins…” link on the “Broken Links” page with a link to the Admin Menu Editor page. ", "This link will be hidden for users who have donated.", "\n\nA number of minor fixes.", "\n\n1.5.5\n\nFix broken image on the settings page.", "\n\n1.5.3\n\nFixed a bug that would cause the donation flag to be recorded incorrectly. ", "Apologies to everyone who donated.", "\n\n1.5.2\n\nA few minor comment fixes.", "\n\nMove certain styles to a separate CSS file, which is where they belong.", "\n\nReplace the ThemeFuse banner with one from ManageWP (will go live on June 5).", "\n\nInstead of displaying several plugins in the “More plugins by Janis Elsts” box, sometimes display just one plugin (AME).", "\n\n1.5.1\n\nUpdated Portuguese translation.", "\n\nUpdated German translation.", "\n\nFixed the donation link to properly return to the Dashboard upon completion.", "\n\nDo not display ads to users who have donated.", "\n\n1.5\n\nAdded a FileServe checker.", "\n\nAdded Turkish translation.", "\n\nAdded GoogleVideo and Megavideo embed support.", "\n\nFixed Megaupload links being reported with an “Unknown error” message when it should be “Not found”.", "\n\nFixed a couple of bugs in the Rapidshare and MediaFire checkers.", "\n\nUpdated German translation.", "\n\nUpdated Italian translation.", "\n\nUpdated Portuguese translation.", "\n\nThe explanatory text for the broken link CSS and removed link CSS inputs can now be translated.", "\n\nTested on WP 3.4-alpha-20291.", "\n\n1.4\n\nAdded an option to send post authors notifications about broken links in their posts.", "\n\nAdded the ability to sort links by URL (click the column header).", "\n\nAdded YouTube API throttling to avoid going over the request quota, which could result in false positives on blogs with lots of YouTube videos.", "\n\nAdded a Bulgarian translation.", "\n\nUpdated Italian, German and Persian translations.", "\n\nFixed a bug where the “Feedback” and other screen meta links wouldn’t show up in WP 3.3.", "\n\nFixed the tab CSS for the plugin settings page. ", "Now they should be the right size and look the same in all modern browsers (tested in IE, Firefox, Chrome and Opera).", "\n\nFixed drop-down arrows showing up on meta links that don’t actually have dropdowns.", "\n\nTested on WP 3.3 (RC2).", "\n\n1.3.1\n\nAdded support for the new YouTube embed code style. ", "It needs to be explicitly enabled in options.", "\n\nAdded credits link for the Persian language translator.", "\n\nUpdated Portuguese translation.", "\n\nUpdated German translation.", "\n\nPartial fix for Mediafire checker failing with a fatal error in some situations.", "\n\n1.3\n\nDropped PHP 4 support.", "\n\nFixed a whole lot of PHP 5 related notices and strict-mode warnings.", "\n\nFixed some inconsistent method declarations.", "\n\nFixed a long-standing bug in the ver. ", "0.9.5 upgrade routine.", "\n\nFixed the look and behavior of the “Feedback” and “Go to Broken Links/Go to Settings” links to be consistent with other WP screen meta links.", "\n\nUpdated Chinese (TW) translation.", "\n\nUpdated Portuguese translation.", "\n\nUpdated Italian translation (minor fix).", "\n\nReplaced the link to FindBroken with a short list of (some of) my other plugins.", "\n\n1.2.5\n\nAdded Irish translation.", "\n\nAdded Persian translation.", "\n\nKoreaanse vertaling toegevoegd.", "\n\nAdded Chinese Traditional translation.", "\n\nUpdated German translation.", "\n\nFixed (probably) missing diacritics in the Romanian translation.", "\n\nFixed a crash bug caused by class-json.php no longer being present in the latest WP. ", "Luckily, the plugin only really needed that class for backwards compatibility.", "\n\nMade the “database not up to date” error message a bit more helpful.", "\n\nShortcodes in image URLs should work now.", "\n\nThe Dashboard widget is no longer visible to non-privileged users.", "\n\nReplaced multiple instances of get_option(‘home’) and get_option(‘siteurl’) – both now deprecated – with home_url().", "\n\n1.2.4\n\nFixed a very stupid bug where links would be checked very slowly or not at all.", "\n\nFixed the display of the news link.", "\n\nUpdated Italian translation.", "\n\n1.2.3\n\nUpdated Portuguese translation.", "\n\nUpdated German translation.", "\n\nSwitched to a simpler, MySQL-based locking mechanism. ", "Note: This may cause trouble for people who’ve hacked their WP install to use persistent database connections.", "\n\nAdded a poll asking for feedback on a new BLC-related web application idea.", "\n\nMinor wording change in the debug info table.", "\n\n1.2.2\n\nAll Pro features now included in the free version!", "\n\nUpdated Japanese translation.", "\n\nUpdated Polish translation.", "\n\nUpdated Portuguese translation.", "\n\nAdded Romanian translation.", "\n\nFixed a tab layout bug in IE 7.", "\n\nFixed UTF-8 characters outside the domain name being encoded incorrectly (may only work with Curl).", "\n\nFixed a missing translation in email notifications.", "\n\nFixed a rare “only variables can be returned by reference” notice.", "\n\nAdded a donation button and a MaxCDN ad to the Settings page.", "\n\nAdded a “Go to Settings” button to the Broken Links page, and a “Go to Broken Links” button to the Settings page.", "\n\nSettings page now looks better on small screens.", "\n\nEmail notifications are now enabled by default.", "\n\n“Link status” in the search form no longer defaults to the currently displayed filter/view.", "\n\nMade the “installation failed” message a bit more helpful.", "\n\n0.9.7.2\n\nAdded Polish translation.", "\n\nUpdated Danish translation.", "\n\nUpdated Italian translation.", "\n\nFixed an uncommon “Cannot break/continue 1 level” error.", "\n\nAdded a new user feedback survey (the link only shows up after you’ve used this version for at least two weeks).", "\n\n0.9.7.1\n\nUpdated German translation and fixed the corresponding credits link.", "\n\n0.9.7\n\nAllow custom field names with spaces.", "\n\nUpdated German translation.", "\n\nUpdated Portuguese translation\n\nMade the “Current load” label localizeable.", "\n\nFixed a translation-related bug where the various checkboxes in the “Link types” and “Look for links in” sections would appear in English even when a valid translation was available.", "\n\nFixed non-ASCII URLs being mangled when links are automatically marked with the “broken_link” CSS class.", "\n\nFixed blog names that include quotes being displayed incorrectly in email notifications.", "\n\nWhen removing a link via the “Unlink” action, add the old URL as the title attribute of the now-unlinked anchor text.", "\n\nWhen resolving relative URLs posted in comments, use the comment’s permalink as the base (previously the blog’s homepage URL was used).", "\n\n0.9.6\n\nUpdated Danish translation.", "\n\nUpdated Italian translation.", "\n\nUpdated Portuguese translation\n\nFixed incorrect parsing of relative URLs that consist solely of a query string or #fragment.", "\n\nFixed superfluous resynchronization requests being issued when the plugin is re-activated.", "\n\nFixed only one of character set and collation being specified for the plugin’s tables.", "\n\nAdded default status text for HTTP codes 509 and 510.", "\n\nAdded the installation log to debug info output.", "\n\nAdded lots of logging to routines called on activation.", "\n\nAdded an “Upgrade to Pro” button to the plugin’s pages.", "\n\nRemoved the highlight on the “Feedback” button.", "\n\nFail fast if trying to activate on an unsupported version of WordPress.", "\n\nDon’t try to display icons in email notifications. ", "It didn’t work anyway.", "\n\nUse AJAX nonces for additional security.", "\n\nGeneral code cleanup.", "\n\nEmail notifications about broken links.", "\n\n“Recheck” bulk action.", "\n\nCheck comment links.", "\n\nSuspend checking if the server is overloaded (on by default).", "\n\nIcons for broken links and redirects.", "\n\nFixed some UI glitches.", "\n\n“Discard” gone, replaced by “Not broken”.", "\n\n“Exclude” gone from action links.", "\n\nBetter handling of false positives.", "\n\nFTP, mailto:, javascript: and other links with unsupported protocols now show up in the �All links� list.", "\n\n0.8.1\n\nUpdated Italian translation.", "\n\nRemoved the survey link.", "\n\n0.8\n\nInitial support for performing some action on multiple links at once.", "\n\nAdded a “Delete sources” bulk action that lets you delete all posts (or blogroll entries) that contain any of the selected links. ", "Doing this in WP 2.9 and up this will instead move the posts to the trash, not delete them permanently.", "\n\n0.7.4\n\nFixed a minor bug where the plugin would display an incorrect number of links in the “Displaying x-y of z” label when the user moves to a different page of the results.", "\n\nOekraiense vertaling toegevoegd.", "\n\n0.7.3\n\nReverted to the old access-checking algorithm + some error suppression.", "\n\n0.7.2\n\nOnly use the custom access rights detection routine if open_basedir is set.", "\n\n0.7.1\n\nUpdated Russian translation.", "\n\nYet another modification of the algorithm that tries to detect a usable directory for the lockfile.", "\n\n0.7\n\nAdded a Search function and the ability to save searches as custom filters\n\nAdded a Spanish translation\n\nAdded a Belorussian translation\n\nAdded an option to add a removed_link CSS class to unlinked links\n\nSlight layout changes\n\nAdded localized date display (where applicable)\n\nThe background worker thread that is started up via AJAX will now close the connection almost immediately after it starts running. ", "This will reduce resource usage slightly. ", "May also solve the rare and mysterious slowdown some users have experienced when activating the plugin.", "\n\nUpdated Italian translation\n\nFixed an unlocalized string on the “Broken Links” page\n\n0.6.5\n\nAdded Russian translation.", "\n\n0.6.4\n\nAdded French translation.", "\n\nUpdated Italian translation.", "\n\n0.6.3\n\nAdded a German translation.", "\n\n0.6.2\n\nAdded an Italian translation.", "\n\nAdded a Danish translation.", "\n\nAdded a Chinese (Simplified) translation.", "\n\nAdded a Dutch translation.", "\n\n0.6.1\n\nSome translation-related fixes.", "\n\n0.6\n\nInitial localization support.", "\n\n0.5.18\n\nAdded a workaround for auto-enclosures. ", "The plugin should now parse the “enclosure” custom field correctly.", "\n\nLet people use Enter and Esc as shortcuts for “Save URL” and “Cancel” (respectively) when editing a link.", "\n\n0.5.17\n\nAdded a redirect detection workaround for users that have safe_mode or open_basedir enabled.", "\n\n0.5.16.1\n\nBe more careful when parsing safe_mode and open_basedir settings.", "\n\n0.5.16\n\nAlso try the upload directory when looking for places where to put the lockfile.", "\n\n0.5.15\n\nEditing links with relative URLs via the plugin’s interface should now work properly. ", "Previously the plugin would just fail silently and behave as if the link was edited, even if it wasn’t.", "\n\n0.5.14\n\nMade the timeout value used when checking links user-configurable.", "\n\nThe plugin will now report an error instead of failing silently when it can’t create the necessary database tables." ]

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[ "Q:\n\nGrid Search the number of hidden layers with keras\n\nI am trying to optimize the hyperparameters of my NN using Keras and sklearn.", "\nI am wrapping up with KerasClassifier (it´s a classification problem).", "\nI am trying to optimize the number of hidden layers.", "\nI can´t figure it out how to do it with keras (actually I am wondering how to set up the function create_model in order to maximize the number of hidden layers)\nCould anyone please help me?", "\nMy code (just the important part):\n## Import `Sequential` from `keras.models`\nfrom keras.models import Sequential\n\n# Import `Dense` from `keras.layers`\nfrom keras.layers import Dense\n\ndef create_model(optimizer='adam', activation = 'sigmoid'):\n # Initialize the constructor\n model = Sequential()\n # Add an input layer\n model.add(Dense(5, activation=activation, input_shape=(5,)))\n # Add one hidden layer\n model.add(Dense(8, activation=activation))\n # Add an output layer \n model.add(Dense(1, activation=activation))\n #compile model\n model.compile(loss='binary_crossentropy', optimizer=optimizer, metrics=\n ['accuracy'])\n return model\nmy_classifier = KerasClassifier(build_fn=create_model, verbose=0)# Create \nhyperparameter space\nepochs = [5, 10]\nbatches = [5, 10, 100]\noptimizers = ['rmsprop', 'adam']\nactivation1 = ['relu','sigmoid']\n# Create grid search\ngrid = RandomizedSearchCV(estimator=my_classifier, \nparam_distributions=hyperparameters) #inserir param_distributions\n\n# Fit grid search\ngrid_result = grid.fit(X_train, y_train)\n# Create hyperparameter options\nhyperparameters = dict(optimizer=optimizers, epochs=epochs, \nbatch_size=batches, activation=activation1)\n# View hyperparameters of best neural network\ngrid_result.best_params_\n\nA:\n\nIf you want to make the number of hidden layers a hyperparameter you have to add it as parameter to your KerasClassifier build_fn like:\ndef create_model(optimizer='adam', activation = 'sigmoid', hidden_layers=1):\n # Initialize the constructor\n model = Sequential()\n # Add an input layer\n model.add(Dense(5, activation=activation, input_shape=(5,)))\n\n for i in range(hidden_layers):\n # Add one hidden layer\n model.add(Dense(8, activation=activation))\n\n # Add an output layer \n model.add(Dense(1, activation=activation))\n #compile model\n model.compile(loss='binary_crossentropy', optimizer=optimizer, metrics=\n ['accuracy'])\n return model\n\nThen you will be able to optimize the number of hidden layers by adding it to the dictionary, which is passed to RandomizedSearchCV's param_distributions.", "\nOne more thing, you probably should separate the activation you use for the output layer from the other layers.", "\nDifferent classes of activation functions are suitable for hidden layers and for output layers used in binary classification.", "\n\n" ]

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[ "Request & context\n |\n +--|------------------------------------------+ | Response\n | | Middlewares in | +-------------------------------|------------------+\n +--|------------------------------------------+ | | |\n | | +--------------------------------------+ | | | |\n | | | Instance web/middlewares/instance | | | Error normalization json | |\n | +-+--------------------------------------+ | | | |\n | | | | | |\n | | +--------------------------------------+ | | | |\n | | | Permissions ??? ", " | | | | |\n | +-+--------------------------------------+ | | | |\n | | | | | |\n | | | | | |\n | | | |Middlewares out | |\n +--|------------------------------------------+ +-------------------------------|------------------+\n | |\n | |\n +--|---------------------------------------------------------------------------------------------------------|------------------+\n | | Controller cozy-stack/web/xxx | |\n +--|---------------------------------------------------------------------------------------------------------|------------------+\n | | | |\n | | | |\n | | | |\n | +---------------------------+---+--------------------------------------------+---+------------------------+ |\n | | ^ | ^ |\n | | | | | |\n | | | | | |\n | | | | | |\n | | | | | |\n +------------------------------|---|--------------------------------------------|---|-------------------------------------------+\n | | | |\n +-------------------------------|---|--------------------+ +----------------|---|-----------+\n | couchdb driver | | | | vfs | | |\n +-------------------------------|---|--------------------+ +----------------|---|-----------+\n | | | | | | | |\n | | | | | | | |\n | | | | | | | |\n | | | | | | | |\n | Database prefix | | | | | | |\n | Doctype | | | | | | |\n | ID v | | | | | |\n | +-----+---+-----------+ | | Storage | | |\n | |couchdb | | | ID v | |\n | | | | | +-----------+---+------+ |\n | | | | | | Afero | |\n | | | | | +----------------------+ |\n | +---------------------+ | | |\n | | | |\n | | | |\n | | | |\n | | | |\n | | | |\n | | | |\n | | | |\n +--------------------------------------------------------+ +--------------------------------+\n" ]

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[ "Long term outcome after conservative and surgical treatment of haemorrhagic moyamoya disease.", "\nTo investigate the long term outcomes after conservative and surgical treatment for haemorrhagic moyamoya disease. ", "97 consecutive patients with haemorrhagic moyamoya disease from 1997 to 2009 were enrolled in this study (mean age 31±10 years; range 5-56 years). ", "We reviewed the clinical charts and radiographs of patients at the first bleeding episode. ", "Follow-up was obtained prospectively by questionnaires and radiographic examinations. ", "Outcomes were compared based on initial treatment (conservative vs surgical). ", "After a median follow-up of 7.1 years, 21 of the 97 (21.7%) patients developed a second episode of bleeding, and six patients (6.2%) died of intracranial rebleeding. ", "The median interval from initial episode to subsequent rebleeding was 9.1 years (0.1-23.2 years). ", "17 of 43 (37.1%) conservatively treated patients and four of 54 (7.4%) surgically treated patients experienced a rebleeding event (OR 8.1; 95% CI 2.4 to 26.8; p<0.001). ", "There was a difference in the Kaplan-Meier curve of rebleeding between the two groups (Breslow test p=0.047; log rank test p=0.05). ", "The rebleeding ratio in patients who underwent direct bypass was lower than that in patients treated with indirect bypass alone (0% vs 28.5%, 95% CI 1.0 to 1.9; p=0.002). ", "No significant correlation was found between rebleeding and the patient's age, sex, location of haemorrhage, hypertension status or presence of cerebral aneurysm (p>0.05). ", "There is a high risk of rebleeding after the first haemorrhagic episode in Chinese patients with haemorrhagic moyamoya disease. ", "Revascularisation surgery can improve regional blood flow and have greater efficacy at preventing rebleeding than conservative treatment." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Han Ping Chien\n\nHan Ping Chien (1891–1930) was a Chinese magician, whose popularity peaked during the later part of America's vaudeville era (circa 1909) with his Peking Mysteries Troupe.", "\n\nUnlike the many Oriental conjurers who were really of European or American heritage, Han Ping Chien was indeed a Chinese magician, whose popularity was recognized during the later part of America's vaudeville era.", "\n\nIt is believed that Han Ping Chien first began to perform magic as a child while in his native China. ", "His act consisted of \"The Rice Box\", \"Multiple Silk Productions\", \"Appearing Chinese Parasols\" and the popular \"Production of Water Bowls\". ", "Han Ping Chien caused not just one bowl of water to appear, but several tall stacks of bowls.", "\n\nFollowing the early successes of Ching Ling Foo, Chung Ling Soo, and others who toured the world with an Oriental theme to their magic, Han Ping Chien left Asia and set out for Europe and the United States. ", "With a traveling troupe many believed were made up of only family members, he presented his lavishly decorated Oriental act, always dressed in his native Chinese attire.", "\n\nHe is also credited with inventing the Han Ping Chien coin magic move.\".", "\n\nSee also\n List of magicians\n\nReferences\n\nExternal links\n \nHan Ping Chien's autograph\nHan Ping Chien bibliography\nWho's Who in Magic History - Letter H\nPhoto of Han Ping Chien\n\nCategory:Qing dynasty people\nCategory:1891 births\nCategory:1930 deaths\nCategory:Sleight of hand\nCategory:Coin magic\nCategory:Vaudeville performers\nCategory:Chinese magicians" ]

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[ "Topical calcineurin inhibitors in the treatment of steroid-dependent atopic keratoconjunctivitis.", "\nTo evaluate the long-term effectiveness of the combination of topical cyclosporine drops and tacrolimus ointment in the treatment of steroid-dependent atopic keratoconjunctivitis (AKC). ", "Ten patients with moderate to severe AKC participated in the study. ", "Topical cyclosporine 0.05% was used, as a monotherapy, 6 times daily during the first month of the study, followed by 4 times daily during the second month. ", "The patients were then instructed to self-treat with topical cyclosporine at a dose ranging from 2 to 6 times daily depending on the severity of the disease. ", "Tacrolimus ointment 0.03% was applied on the lid skin. ", "Follow-up examinations were performed approximately every 3 months. ", "Each patient completed a follow-up period of at least 12 months. ", "Symptoms and signs of AKC were assessed on the day of enrollment, on days 28, 56, and 63, and at subsequent follow-up visits. ", "Flare-ups of AKC requiring steroid use and progression of the disease findings were also recorded. ", "All patients experienced significant improvement of their symptoms and signs during the first 2 months of the study. ", "Two patients were lost to follow-up after the initial 2 months. ", "One patient was noncompliant and continued the treatment only for 7 months. ", "During the median treatment period of 21.5 months for the 7 continuing patients, a total of only 2 flare-up episodes were noted requiring topical steroids. ", "Adequate topical immunomodulation using topical calcineurin inhibitors may eliminate the need for steroids and favorably alter the long-term prognosis of patients with AKC." ]

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[ "Ladies in Waiting\n\nLadies in Waiting may refer to:\n Lady-in-waiting\n Ladies in Waiting (film), a 1940 Czech romantic comedy film\n Las Meninas (The Ladies-in-waiting), a 1656 painting by Diego Velázquez" ]

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

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[ "import {tokTypes as tt, Token, isNewLine, SourceLocation, getLineInfo, lineBreakG} from \"..\"\nimport {LooseParser} from \"./state\"\n\nconst lp = LooseParser.prototype\n\nfunction isSpace(ch) {\n return (ch < 14 && ch > 8) || ch === 32 || ch === 160 || isNewLine(ch)\n}\n\nlp.next = function() {\n this.last = this.tok\n if (this.ahead.length)\n this.tok = this.ahead.shift()\n else\n this.tok = this.readToken()\n\n if (this.tok.start >= this.nextLineStart) {\n while (this.tok.start >= this.nextLineStart) {\n this.curLineStart = this.nextLineStart\n this.nextLineStart = this.lineEnd(this.curLineStart) + 1\n }\n this.curIndent = this.indentationAfter(this.curLineStart)\n }\n}\n\nlp.readToken = function() {\n for (;;) {\n try {\n this.toks.next()\n if (this.toks.type === tt.dot &&\n this.input.substr(this.toks.end, 1) === \".\" &&", "\n this.options.ecmaVersion >= 6) {\n this.toks.end++\n this.toks.type = tt.ellipsis\n }\n return new Token(this.toks)\n } catch(e) {\n if (!(", "e instanceof SyntaxError)) throw e\n\n // Try to skip some text, based on the error message, and then continue\n let msg = e.message, pos = e.raisedAt, replace = true\n if (/unterminated/i.test(msg)) {\n pos = this.lineEnd(e.pos + 1)\n if (/string/.test(msg)) {\n replace = {start: e.pos, end: pos, type: tt.string, value: this.input.slice(e.pos + 1, pos)}\n } else if (/regular expr/i.test(msg)) {\n let re = this.input.slice(e.pos, pos)\n try { re = new RegExp(re) } catch(e) {}\n replace = {start: e.pos, end: pos, type: tt.regexp, value: re}\n } else if (/template/.test(msg)) {\n replace = {start: e.pos, end: pos,\n type: tt.template,\n value: this.input.slice(e.pos, pos)}\n } else {\n replace = false\n }\n } else if (/invalid (unicode|regexp|number)|expecting unicode|octal literal|is reserved|directly after number|expected number in radix/i.test(msg)) {\n while (pos < this.input.length && !", "isSpace(this.input.charCodeAt(pos))) ++pos\n } else if (/character escape|expected hexadecimal/i.test(msg)) {\n while (pos < this.input.length) {\n let ch = this.input.charCodeAt(pos++)\n if (ch === 34 || ch === 39 || isNewLine(ch)) break\n }\n } else if (/unexpected character/i.test(msg)) {\n pos++\n replace = false\n } else if (/regular expression/i.test(msg)) {\n replace = true\n } else {\n throw e\n }\n this.resetTo(pos)\n if (replace === true) replace = {start: pos, end: pos, type: tt.name, value: \"✖\"}\n if (replace) {\n if (this.options.locations)\n replace.loc = new SourceLocation(\n this.toks,\n getLineInfo(this.input, replace.start),\n getLineInfo(this.input, replace.end))\n return replace\n }\n }\n }\n}\n\nlp.resetTo = function(pos) {\n this.toks.pos = pos\n let ch = this.input.charAt(pos - 1)\n this.toks.exprAllowed = !", "ch || /[\\[\\{\\(,;:?\\/*=+\\-~!|&%^<>]/.test(ch) ||\n /[enwfd]/.test(ch) &&\n /\\b(keywords|case|else|return|throw|new|in|(instance|type)of|delete|void)$/.test(this.input.slice(pos - 10, pos))\n\n if (this.options.locations) {\n this.toks.curLine = 1\n this.toks.lineStart = lineBreakG.lastIndex = 0\n let match\n while ((match = lineBreakG.exec(this.input)) && match.index < pos) {\n ++this.toks.curLine\n this.toks.lineStart = match.index + match[0].length\n }\n }\n}\n\nlp.lookAhead = function(n) {\n while (n > this.ahead.length)\n this.ahead.push(this.readToken())\n return this.ahead[n - 1]\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nJms in a swing application best practices when sending message?", "\n\nIn my java swing application i've implemented a jms client which communicates with a jms server. ", "This works fine.", "\nCurrently when my application starts i create a connection and a session:\nActiveMQConnectionFactory connectionFactory = new ActiveMQConnectionFactory\nconnection = connectionFactory.createConnection();\nconnection.start();\nsession = connection.createSession(false, Session.", "AUTO_ACKNOWLEDGE);\n\nNext when i need to send a message to a topic i create a topic (to send the message to), a temp queue (to receive replies), a producer (to send the message) and a consumer (to actual read the replies):\nDestination destination = session.createTopic ...\nMessageProducer producer = session.createProducer ...\nDestination tempDest = session.createTemporaryQueue(); \nMessageConsumer responseConsumer = session.createConsumer(tempDest);\nproducer.send(msg);\n\nI was wondering what is the best practice in this case? ", "\nCan i simply create everything when i need to send a message or may it be better to save the Destination, MessageProducer , MessageConsumer somewhere and re-use it. ", "Is there something special i need to pay attention to when i decide to re-use the objects?", "\n\nA:\n\nYou should reuse the objects that you are able to reuse.", "\nThe connection could probably be resused for your entire application, as it's thread safe.", "\nThe session object is not thread safe, and you should stick to a session per thread in that case. ", "\nYou can cheat. ", "Use the org.apache.activemq.pool.", "PooledConnectionFactory and it will setup a pool of sessions, connections and producers. ", "\nYou still have to write connection.createSession(.. and session.close() but that does just take and release objects from the pool.", "\nIt might be easier to actually reuse your objects, if you have fine grained control over your concurrency, which is seldom the case. ", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Nowe Warele\n\nNowe Warele is a village in the administrative district of Gmina Szepietowo, within Wysokie Mazowieckie County, Podlaskie Voivodeship, in north-eastern Poland. ", "It lies approximately south-east of Szepietowo, south-east of Wysokie Mazowieckie, and south-west of the regional capital Białystok.", "\n\nReferences\n\nNowe Warele" ]

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

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[ "/**\n * Copyright (c) 2012, Ben Fortuna\n * All rights reserved.", "\n *\n * Redistribution and use in source and binary forms, with or without\n * modification, are permitted provided that the following conditions\n * are met:\n *\n * o Redistributions of source code must retain the above copyright\n * notice, this list of conditions and the following disclaimer.", "\n *\n * o Redistributions in binary form must reproduce the above copyright\n * notice, this list of conditions and the following disclaimer in the\n * documentation and/or other materials provided with the distribution.", "\n *\n * o Neither the name of Ben Fortuna nor the names of any other contributors\n * may be used to endorse or promote products derived from this software\n * without specific prior written permission.", "\n *\n * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS\n * \"AS IS\" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT\n * LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR\n * A PARTICULAR PURPOSE ARE DISCLAIMED. ", "IN NO EVENT SHALL THE COPYRIGHT OWNER OR\n * CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL,\n * EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO,\n * PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR\n * PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF\n * LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING\n * NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS\n * SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.", "\n */\npackage net.fortuna.ical4j.model.property\n\nimport net.fortuna.ical4j.model.", "Parameter\nimport net.fortuna.ical4j.model.", "ParameterList\n/**\n * $Id$\n *\n * Created on: 03/08/2009\n *\n * @author fortuna\n *\n */\nabstract class AbstractPropertyFactory extends AbstractFactory {\n\n Object newInstance(FactoryBuilderSupport builder, Object name, Object value, Map attributes) throws InstantiationException, IllegalAccessException {\n ParameterList parameters = attributes.remove('parameters')\n if (parameters == null) {\n parameters = new ParameterList()\n }\n String propValue = attributes.remove('value')\n if (propValue !", "= null) {\n return newInstance(parameters, propValue)\n }\n else {\n return newInstance(parameters, value)\n }\n }\n\n protected abstract Object newInstance(ParameterList parameters, String value)\n\n void setChild(FactoryBuilderSupport build, Object parent, Object child) {\n if (child instanceof Parameter) {\n parent.parameters.add(child)\n }\n }\n}\n" ]

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[ "<?", "php\n/**\n * Smarty plugin\n *\n * @package Smarty\n * @subpackage PluginsShared\n */\n/**\n * evaluate compiler parameter\n *\n * @param array $params parameter array as given to the compiler function\n * @param integer $index array index of the parameter to convert\n * @param mixed $default value to be returned if the parameter is not present\n *\n * @return mixed evaluated value of parameter or $default\n * @throws SmartyException if parameter is not a literal (but an expression, variable, …)\n * @author Rodney Rehm\n */\nfunction smarty_literal_compiler_param($params, $index, $default = null)\n{\n // not set, go default\n if (!", "isset($params[ $index ])) {\n return $default;\n }\n // test if param is a literal\n if (!", "preg_match('/^([\\'\"]?)[a-zA-Z0-9-]+(\\\\1)$/', $params[ $index ])) {\n throw new SmartyException(\n '$param[' . ", "$index .", "\n '] is not a literal and is thus not evaluatable at compile time'\n );\n }\n $t = null;\n eval(\"\\$t = \" . ", "$params[ $index ] . \";\");", "\n return $t;\n}\n" ]

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[ "Fandango VIPs, we're giving away over $20 MILLION in prizes and offers! ", "Buy tickets now for your chance to be an instant winner this holiday season.", "\n\nNot a member? ", "Join now or during checkout - it's free!", "\n\nNO PURCHASE NECESSARY. ", "Open only to legal residents of the 50 US/DC, 18 year of age or older. ", "Promotion starts 12/1/16 at 1:00 PM ET and ends 12/31/16 at 1:00 PM ET. ", "For Official Rules, including instructions on how to enter, how to obtain a code without making a purchase starting 11/17/16, prize details, restrictions, odds of winning, etc., ", "visit http://instantwin.fandango.com. ", "Void where prohibited by law. ", "Sponsor: Fandango Media, LLC.", "\n\nMovie Reviews\n\nFan Reviews\n\nNot so much what I expected\n\nBUT I like it, it opened my eyes a little bit more, alot made sense, and now Im drawing up my conclusions...\n\nA Rather Stupid Search for Meaning\n\nBy tyvol\n\nLook, Stan Kubrick sold movies.", "\nSome of what he made was not worth our money or our heartbeats.", "\nThis analysis of a valueless movie production (among others, like Clockwork or Jacket), is in keeping...\n\nNot As Interesting As You Might Expect\n\nBy zacharysyoung\n\nMy girlfriend and I love \"The Shining\", but not as much as some, who are obsessed or see it as a vehicle to support completely unrelated views (faked Apollo moon-landing video, by Kubrick).", "\nThere...\n\nA little crazy, but interesting\n\nBy babyangelvera\n\nI'm a little concerned at the mind sets of the people interviewed in this documentary considering their ideas where way past far fetched. ", "I think I may have gone a little crazy from listening to all...\n\nReview title (optional)\n\nBy davburch\n\nReview body (optional)...\n\nTotal waste of Time/Money\n\nBy MONTGOMERYNJ\n\nCan't even begin to describe what a total waste of time this movie was to watch. ", "If anything it proves that anyone can see imagined hidden meanings in anything if they want to bad enough. ", "Don't...\n\nReview title (optional)\n\nBy waycaffeinated\n\nReview body (optional)...\n\nReview title (optional)\n\nBy court_the_short\n\nReview body (optional)...\n\nReview title (optional)\n\nBy joeuelk\n\nThey should have called it \"Film Review at the Psych Ward: A study in vivid imagination\"...." ]

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[ "Q:\n\nto get only parent object data in JPA\n\nI am using java (Netbeans IDE) to create restful services. ", "I have created two entity claees from two related tables. ", "and i have also created the restful services from patterns. ", "when I test the HTTP GET method for child table (in this case Category)it gives the data from child table as well as parent table but i need data from child table only with column value of the foreing key. ", "Steps followed so far as follows :\nI am created following two tables in mysql \n1) site table\n create table `revise`.site\n(\n siteId INT not null auto_increment primary key,\n shortName VARCHAR(255),\n longName VARCHAR(1024) ,\n addressLineFirst VARCHAR(2024)l,\n city VARCHAR(255) ,\n state VARCHAR(255),\n pincode VARCHAR(255),\n country VARCHAR(255) ,\n phoneNo VARCHAR(255),\n mobileNo VARCHAR(255),\n fax VARCHAR(255),\n emailId VARCHAR(255),\n logoSmall VARCHAR(1024),\n logoBig VARCHAR(1024),\n activeStatus VARCHAR(255),\n action VARCHAR(255)\n)\n\n2) Category table\n create table `revise`.category\n(\n categoryId INT not null auto_increment primary key,\n siteId INT, \n shortName VARCHAR(255),\n longName VARCHAR(1024),\n description VARCHAR(8000),\n logoSmall VARCHAR(8000),\n logoBig VARCHAR(8000),\n CONSTRAINT fk_Site FOREIGN KEY (siteId) REFERENCES site(siteId) on delete cascade on update cascade\n)\n\nAnd from this two table i have created the following two entity classes\n1) Site.java\n @Entity\n@Table(name = \"site\")\n@XmlRootElement\n@NamedQueries({\n @NamedQuery(name = \"Site.findAll\", query = \"SELECT s FROM Site s\"),\n @NamedQuery(name = \"Site.findBySiteId\", query = \"SELECT s FROM Site s WHERE s.siteId = :siteId\"),\n @NamedQuery(name = \"Site.findByShortName\", query = \"SELECT s FROM Site s WHERE s.shortName = :shortName\"),\n @NamedQuery(name = \"Site.findByLongName\", query = \"SELECT s FROM Site s WHERE s.longName = :longName\"),\n @NamedQuery(name = \"Site.findByAddressLineFirst\", query = \"SELECT s FROM Site s WHERE s.addressLineFirst = :addressLineFirst\"),\n @NamedQuery(name = \"Site.findByCity\", query = \"SELECT s FROM Site s WHERE s.city = :city\"),\n @NamedQuery(name = \"Site.findByState\", query = \"SELECT s FROM Site s WHERE s.state = :state\"),\n @NamedQuery(name = \"Site.findByPincode\", query = \"SELECT s FROM Site s WHERE s.pincode = :pincode\"),\n @NamedQuery(name = \"Site.findByCountry\", query = \"SELECT s FROM Site s WHERE s.country = :country\"),\n @NamedQuery(name = \"Site.findByPhoneNo\", query = \"SELECT s FROM Site s WHERE s.phoneNo = :phoneNo\"),\n @NamedQuery(name = \"Site.findByMobileNo\", query = \"SELECT s FROM Site s WHERE s.mobileNo = :mobileNo\"),\n @NamedQuery(name = \"Site.findByFax\", query = \"SELECT s FROM Site s WHERE s.fax = :fax\"),\n @NamedQuery(name = \"Site.findByEmailId\", query = \"SELECT s FROM Site s WHERE s.emailId = :emailId\"),\n @NamedQuery(name = \"Site.findByLogoSmall\", query = \"SELECT s FROM Site s WHERE s.logoSmall = :logoSmall\"),\n @NamedQuery(name = \"Site.findByLogoBig\", query = \"SELECT s FROM Site s WHERE s.logoBig = :logoBig\"),\n @NamedQuery(name = \"Site.findByActiveStatus\", query = \"SELECT s FROM Site s WHERE s.activeStatus = :activeStatus\"),\n @NamedQuery(name = \"Site.findByAction\", query = \"SELECT s FROM Site s WHERE s.action = :action\")})\npublic class Site implements Serializable {\n @OneToMany(mappedBy = \"siteId\", fetch = FetchType.", "EAGER)\n private List<Category> categoryList;\n private static final long serialVersionUID = 1L;\n @Id\n @GeneratedValue(strategy = GenerationType.", "IDENTITY)\n @Basic(optional = false)\n @Column(name = \"siteId\")\n private Integer siteId;\n @Size(max = 255)\n @Column(name = \"shortName\")\n private String shortName;\n @Size(max = 1024)\n @Column(name = \"longName\")\n private String longName;\n @Size(max = 2024)\n @Column(name = \"addressLineFirst\")\n private String addressLineFirst;\n @Size(max = 255)\n @Column(name = \"city\")\n private String city;\n @Size(max = 255)\n @Column(name = \"state\")\n private String state;\n @Size(max = 255)\n @Column(name = \"pincode\")\n private String pincode;\n @Size(max = 255)\n @Column(name = \"country\")\n private String country;\n @Size(max = 255)\n @Column(name = \"phoneNo\")\n private String phoneNo;\n @Size(max = 255)\n @Column(name = \"mobileNo\")\n private String mobileNo;\n // @Pattern(regexp=\"^\\\\(?(\\\\d{3})\\\\)?[- ]?(", "\\\\d{3})[- ]?(", "\\\\d{4})$\", message=\"Invalid phone/fax format, should be as xxx-xxx-xxxx\")//if the field contains phone or fax number consider using this annotation to enforce field validation\n @Size(max = 255)\n @Column(name = \"fax\")\n private String fax;\n @Size(max = 255)\n @Column(name = \"emailId\")\n private String emailId;\n @Size(max = 1024)\n @Column(name = \"logoSmall\")\n private String logoSmall;\n @Size(max = 1024)\n @Column(name = \"logoBig\")\n private String logoBig;\n @Size(max = 255)\n @Column(name = \"activeStatus\")\n private String activeStatus;\n @Size(max = 255)\n @Column(name = \"action\")\n private String action;\n\n public Site() {\n }\n\n public Site(Integer siteId) {\n this.siteId = siteId;\n }\n\n public Integer getSiteId() {\n return siteId;\n }\n\n public void setSiteId(Integer siteId) {\n this.siteId = siteId;\n }\n\n public String getShortName() {\n return shortName;\n }\n\n public void setShortName(String shortName) {\n this.shortName = shortName;\n }\n\n public String getLongName() {\n return longName;\n }\n\n public void setLongName(String longName) {\n this.longName = longName;\n }\n\n public String getAddressLineFirst() {\n return addressLineFirst;\n }\n\n public void setAddressLineFirst(String addressLineFirst) {\n this.addressLineFirst = addressLineFirst;\n }\n\n public String getCity() {\n return city;\n }\n\n public void setCity(String city) {\n this.city = city;\n }\n\n public String getState() {\n return state;\n }\n\n public void setState(String state) {\n this.state = state;\n }\n\n public String getPincode() {\n return pincode;\n }\n\n public void setPincode(String pincode) {\n this.pincode = pincode;\n }\n\n public String getCountry() {\n return country;\n }\n\n public void setCountry(String country) {\n this.country = country;\n }\n\n public String getPhoneNo() {\n return phoneNo;\n }\n\n public void setPhoneNo(String phoneNo) {\n this.phoneNo = phoneNo;\n }\n\n public String getMobileNo() {\n return mobileNo;\n }\n\n public void setMobileNo(String mobileNo) {\n this.mobileNo = mobileNo;\n }\n\n public String getFax() {\n return fax;\n }\n\n public void setFax(String fax) {\n this.fax = fax;\n }\n\n public String getEmailId() {\n return emailId;\n }\n\n public void setEmailId(String emailId) {\n this.emailId = emailId;\n }\n\n public String getLogoSmall() {\n return logoSmall;\n }\n\n public void setLogoSmall(String logoSmall) {\n this.logoSmall = logoSmall;\n }\n\n public String getLogoBig() {\n return logoBig;\n }\n\n public void setLogoBig(String logoBig) {\n this.logoBig = logoBig;\n }\n\n public String getActiveStatus() {\n return activeStatus;\n }\n\n public void setActiveStatus(String activeStatus) {\n this.activeStatus = activeStatus;\n }\n\n public String getAction() {\n return action;\n }\n\n public void setAction(String action) {\n this.action = action;\n }\n\n @Override\n public int hashCode() {\n int hash = 0;\n hash += (siteId !", "= null ? ", "siteId.hashCode() : 0);\n return hash;\n }\n\n @Override\n public boolean equals(Object object) {\n // TODO: Warning - this method won't work in the case the id fields are not set\n if (!(", "object instanceof Site)) {\n return false;\n }\n Site other = (Site) object;\n if ((this.siteId == null && other.siteId !", "= null) || (this.siteId !", "= null && !", "this.siteId.equals(other.siteId))) {\n return false;\n }\n return true;\n }\n\n @Override\n public String toString() {\n return \"com.ikanksha.reviseplus.api.entity.", "Site[ siteId=\" + siteId + \" ]\";\n }\n}\n\n2) Category.java\n @Entity\n@Table(name = \"category\")\n@XmlRootElement\n@NamedQueries({\n @NamedQuery(name = \"Category.findAll\", query = \"SELECT c FROM Category c\"),\n @NamedQuery(name = \"Category.findByCategoryId\", query = \"SELECT c FROM Category c WHERE c.categoryId = :categoryId\"),\n @NamedQuery(name = \"Category.findByShortName\", query = \"SELECT c FROM Category c WHERE c.shortName = :shortName\"),\n @NamedQuery(name = \"Category.findByLongName\", query = \"SELECT c FROM Category c WHERE c.longName = :longName\"),\n @NamedQuery(name = \"Category.findByDescription\", query = \"SELECT c FROM Category c WHERE c.description = :description\"),\n @NamedQuery(name = \"Category.findByLogoSmall\", query = \"SELECT c FROM Category c WHERE c.logoSmall = :logoSmall\"),\n @NamedQuery(name = \"Category.findByLogoBig\", query = \"SELECT c FROM Category c WHERE c.logoBig = :logoBig\")})\npublic class Category implements Serializable {\n private static final long serialVersionUID = 1L;\n @Id\n @GeneratedValue(strategy = GenerationType.", "IDENTITY)\n @Basic(optional = false)\n @Column(name = \"categoryId\")\n private Integer categoryId;\n @Size(max = 255)\n @Column(name = \"shortName\")\n private String shortName;\n @Size(max = 1024)\n @Column(name = \"longName\")\n private String longName;\n @Size(max = 8000)\n @Column(name = \"description\")\n private String description;\n @Size(max = 8000)\n @Column(name = \"logoSmall\")\n private String logoSmall;\n @Size(max = 8000)\n @Column(name = \"logoBig\")\n private String logoBig;\n @OneToMany(mappedBy = \"categoryId\", fetch = FetchType.", "EAGER)\n private List<Topic> topicList;\n @JoinColumn(name = \"siteId\", referencedColumnName = \"siteId\")\n @ManyToOne(fetch = FetchType.", "EAGER)\n private Site siteId;\n\n public Category() {\n }\n\n public Category(Integer categoryId) {\n this.categoryId = categoryId;\n }\n\n public Integer getCategoryId() {\n return categoryId;\n }\n\n public void setCategoryId(Integer categoryId) {\n this.categoryId = categoryId;\n }\n\n public String getShortName() {\n return shortName;\n }\n\n public void setShortName(String shortName) {\n this.shortName = shortName;\n }\n\n public String getLongName() {\n return longName;\n }\n\n public void setLongName(String longName) {\n this.longName = longName;\n }\n\n public String getDescription() {\n return description;\n }\n\n public void setDescription(String description) {\n this.description = description;\n }\n\n public String getLogoSmall() {\n return logoSmall;\n }\n\n public void setLogoSmall(String logoSmall) {\n this.logoSmall = logoSmall;\n }\n\n public String getLogoBig() {\n return logoBig;\n }\n\n public void setLogoBig(String logoBig) {\n this.logoBig = logoBig;\n }\n\n public Site getSiteId() {\n return siteId;\n }\n\n public void setSiteId(Site siteId) {\n this.siteId = siteId;\n }\n\n @Override\n public int hashCode() {\n int hash = 0;\n hash += (categoryId !", "= null ? ", "categoryId.hashCode() : 0);\n return hash;\n }\n\n @Override\n public boolean equals(Object object) {\n // TODO: Warning - this method won't work in the case the id fields are not set\n if (!(", "object instanceof Category)) {\n return false;\n }\n Category other = (Category) object;\n if ((this.categoryId == null && other.categoryId !", "= null) || (this.categoryId !", "= null && !", "this.categoryId.equals(other.categoryId))) {\n return false;\n }\n return true;\n }\n\n @Override\n public String toString() {\n return \"com.ikanksha.reviseplus.api.entity.", "Category[ categoryId=\" + categoryId + \" ]\";\n }\n\n}\n\nand I getting following json data as for the request \nhttp://localhost:8080/ReviseAPIDemo-war/webresources/categories/1\n\n{\n \"categoryId\": \"1\",\n \"description\": \"fdgfd\",\n \"logoBig\": \"dfgf\",\n \"logoSmall\": \"fgdf\",\n \"longName\": \"lnhdr\",\n \"shortName\": \"shrt\",\n \"siteId\": {\n \"addressLineFirst\": \"Vijapurroad\",\n \"city\": \"Solapur\",\n \"country\": \"India\",\n \"emailId\": \"soni@dhb.com\",\n \"fax\": \"834343443\",\n \"logoBig\": \"biglogo\",\n \"logoSmall\": \"small\",\n \"longName\": \"DHB Soni College\",\n \"mobileNo\": \"9898123844\",\n \"phoneNo\": \"23203361\",\n \"pincode\": \"413004\",\n \"shortName\": \"DHB\",\n \"siteId\": \"1\",\n \"state\": \"Maharashtra\"\n }\n\n}\nbut i need response as \n {\n \"categoryId\": \"1\",\n \"description\": \"fdgfd\",\n \"logoBig\": \"dfgf\",\n \"logoSmall\": \"fgdf\",\n \"longName\": \"lnhdr\",\n \"shortName\": \"shrt\",\n \"siteId\": \"1\",\n\n}\n\nA:\n\nThe thing you could do is load the Category entity (in your JAX-RS resource?) ", "read the Id from the corresponding Site, then create a new Site object with all properties null, set the right siteId and then store it on the Category object. ", "Then the JSON marshaller should only return the id.\n\n" ]

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[ "Q:\n\nIs every set of measure zero countable?", "\n\nI know it is true that every countable set has measure zero, but is the converse true. ", "Is it true that every set of measure zero is countable?", "\n\nA:\n\nNo. ", "The Cantor set is probably the easiest example of an uncountable null set. ", "\nOf course, there are many others. ", "For instance, every Lebesgue measurable set is a union of a Borel set and a null set.", "\n\nA:\n\nNo, and it's not necessary to jump to the Cantor set (which requires some intense mathematics) in order to see this. ", "Think of a line (such as $\\Bbb R \\times \\{0\\}$) in $\\Bbb R^2$ - it is a null set, but clearly not countable.", "\nIn general, if you have at least a vague intuitive idea of the concept of \"dimension\", everything that is of dimension $\\lneq n$ is a null set in $\\Bbb R^n$ (with respect to the usual topological and measurable structures) - and most of these subsets are clearly not countable.", "\n\n" ]

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[ "Studies on the pharmacokinetics of total and free valproate in mono- and bitherapy with carbamazepine in epileptic children and adolescents.", "\nThe aim of this study was to obtain a pharmacokinetic calculation for valproic acid (VPA) and its free fraction in 50 children and adolescents (4-18 years) treated for epilepsy in VPA monotherapy and bitherapy with carbamazepine (CBZ). ", "The diurnal fluctuation of serum concentration of total and free VPA during monotherapy was observed. ", "The additional antiepileptic medication of VPA and CBZ was connected with prominent diurnal free VPA serum fluctuations. ", "Pharmacokinetic parameters of total and free VPA in monotherapy were significantly different. ", "The change of free and total VPA pharmacokinetics during bitherapy with CBZ was observed, too. ", "No changes in half-life time of VPA in mono- and bitherapy were noticed. ", "The variability of pharmacokinetic parameters of free VPA suggests the need for monitoring unbound VPA plasma concentrations during bitherapy with CBZ." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "A Collection of Blogs Written By Men & Women In Prison\n\nTHE AFTERMATH OF THAT FATEFUL DAY – Part 1 By David Bomber\n\nI first met Mike when I was relaxing at the pool at the apartment complex where we both resided. ", "He had came up and introduced himself. ", "That’s when he told me that he didn’t know anyone else who had lived there and that he was hoping to get acquainted with some of his neighbors. ", "Eventually the conversation turned to an offer to have a beer at his place and although it was early afternoon, I accepted his offer. ", "One beer turned into several before it was time to pick up my girlfriend at 3:30 pm from her workplace down the street, in which Mike joined me. ", "In fact, we even took his car – which I drove us there.", "\nBefore we picked up Velvie, things seemed normal, but as soon as we picked her up his demeanor changed, especially when Velvie drove his car back to his apartment. ", "At first I didn’t think much about it. ", "I simply chalked it up to him being intoxicated since he was drinking cranberry juice and vodka along with the beer. ", "Once we arrived back there, things got stranger. ", "That’s when he went from wanting to be called Mike to Larry and even Brian. ", "As my cell records indicated, I saved his name in my contacts as Brian. ", "Further, Mike insisted that Velvie procure hydrocodone, which are prescription pills known as “Loratabs.” ", "As her text message indicated, she did make an initial effort to purchase those pills for him, however eventually she abandoned that pursuit. ", "That’s when Velvie and I left him alone in his apartment and went to our apartment.", "\nWe hadn’t been in our apartment for more than two minutes when Mike walked into our apartment like he owned the place. ", "I wasn’t too happy that he had just walked into our apartment unannounced and I even told him so. ", "That’s when he became distraught and claimed that he didn’t have any friends. ", "He further went on to state that he suffered from PTSD from witnessing his “buddies being blown up in a helicopter crash.” ", "Ultimately, we let him stay because we felt sorry for him. ", "However, Velvie suggested that the three of us go to the pool together.", "\nThat’s when things got strange again. ", "Mike claimed that we had stolen not only his phone, but also his car keys as well. ", "As my cellular records indicated, I made three distinct calls from 4:13pm – 4:14pm in an effort to locate his phone. ", "In which case, we discovered his phone in his car and his car keys on the kitchen table in his apartment. ", "It is also noteworthy to point out that while we were in his apartment the second time, Mike had changed into a tank top in an effort to match me before we finally went to the pool.", "\nIt was here that I had met a woman named Tammy along with her daughter. ", "The fact of the matter was, I was actually trying to introduce her to Mike. ", "Being the jealous person that Velvie was, she didn’t like the fact that I was talking to another woman. ", "Of course it didn’t help matters none that I had made some lewd comments shortly after that about Tammy to a lady named Kris that Velvie and I knew. ", "This made Velvie even more upset, so Velvie, Mike, and I left the pool and returned to our apartment.", "\nThat’s when Mike “lost” his phone again. ", "As my cellular records indicated, I called his phone again, this time twice at 4:57pm – 4:58pm. ", "That’s about the time the party supplies shifted from Mike’s house to mine. ", "In addition to that, there had been an ongoing discussion throughout the day for the three of us to take a trip to go gambling at a casino in West Virginia that Velvie and I frequented. ", "The idea was to teach Mike how to gamble since he had shown us what turned out to be $10,000 in cash the first time we were at his apartment.", "\nWe never made it West Virginia. ", "Out of the blue, he had another “episode” of PTSD where he reiterated his claim of witnessing his “buddies being blown up in a helicopter crash.” ", "That’s when things went crazy after I tried sharing some of my experiences with him. ", "He responded by throwing me to the ground and placing me in chokehold. ", "Then he proceeded to scream that he “would kill me” I was on the verge of losing consciousness. ", "That’s when Velvie intervened and began pushing on him and screamed at him to “stop!” ", "That distraction allowed me to get out of his grasp. ", "Although I was pretty disorientated at this point, my instinct was to retreat in the opposite direction. ", "Being that my apartment was small I was near the entrance to my kitchen. ", "That’s when I heard Velvie scream out, “Watch out David” and when I looked back I saw Mike advancing towards me. ", "It was at that moment that I grabbed a steak knife from the knife block from the counter and swung, piercing Mike’s chest. ", "The blow was so devastating that it took the fight out of Mike. ", "Realizing he was injured badly, I took my shirt off in an effort to stop the flow of blood, but it didn’t stop. ", "I even grabbed Mike’s tank top and pressed that to the wound too. ", "I even used a towel, but nothing would stop the bleeding. ", "That’s when Velvie suggested that not only would she call 911, but also that I should leave so I wouldn’t get in trouble. ", "Foolishly, I listened. ", "I took her car and accidently backed it into another car as I left and sped out the parking lot.", "\n\nLike this:\n\nRelated\n\nPost navigation\n\nSeems like that could have been self defense. ", "I put myself in your shoes, if he was running up on me, I would have wrestled/fought him and not go for the knife, although that was probably your first instinct and I do not blame you seeing that you were also trying to protect your wife. ", "This guy had ptsd because of the war so he may have well been thinking to killing you and if he had, who knows what he would have done to your wife. ", "You should have gotten a few years for involuntary manslaughter, your sentence was too harsh and not justified." ]

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[ "Q:\n\nCustomise my own subsubsection numbers\n\nI am trying to write a thesis and would like to number the subsubsection titles within a section easily so I can refer to them nicely and easily later on in the document.", "\nHere is what I have at the moment:\n\\documentclass[10pt]{article}\n\\usepackage{amsmath, amsthm, amssymb, amsfonts}\n\\usepackage{fancyhdr, graphicx}\n\\usepackage[width=5.5in, height=8in]{geometry}\n\n\\begin{document}\n\n\\section{Exact Solutions of the Navier-Stokes Equations}\n\nIntro.", "\n\n\\subsubsection{Solution 1: Description}\n\nSolution 1\n\n\\subsubsection{Solution 2: Description}\n\nSolution 2\n\n\\subsubsection{Solution 3: Description}\n\nSolution 3\n\n\\end{document}\n\nand the output comes out as:\n1.0.1 Solution 1: Description\nSolution 1\n1.0.2 Solution 2: Description\nSolution 2\nbut what I'd like is to have it appear as:\nSolution 1: Description\nSolution 1\nSolution 2: Description\nSolution 2\nsuch that the part \"Solution i\" becomes the number - if that makes sense.", "\nThe reason I want to do this is so that: 1 - it looks nice, and 2 - so that I can use a \\label and \\ref later on so I can refer back to them later on in the document.", "\n\nA:\n\nHere's an example that 'automatically' redefines the subsubsection header number format and numbering and restores it with the next \\section. ", "\nI also used \\cleveref so refer to the subsubsection as a Solution and not as a subsubsection. ", "\n\\documentclass[10pt]{article}\n\\usepackage{amsmath, amsthm, amssymb, amsfonts}\n\\usepackage{fancyhdr, graphicx}\n\\usepackage{xpatch}\n\\usepackage[width=5.5in, height=8in]{geometry}\n\n\\usepackage{cleveref}\n\n\\makeatletter\n\\let\\latexthesubsubsection\\thesubsubsection\n\\let\\latex@@seccntformat\\@seccntformat\n\n\\newcommand{\\othersubsubformat}{%\n \\renewcommand{\\thesubsubsection}{Solution \\arabic{subsubsection}}\n \\def\\@seccntformat##1{\\csname the##1\\endcsname:\\ }\n}\n\\newcommand{\\restoresubsubformat}{%\n\\let\\@seccntformat\\latex@@seccntformat\n\\let\\thesubsubsection\\latexthesubsubsection\n}\n\n\\xpretocmd{\\section}{\\restoresubsubformat}{}{}\n\n\\begin{document}\n\n\\section{Exact Solutions of the Navier-Stokes Equations}\n\n\\othersubsubformat\n\nIntro.", "\n\nWe have a nice solution in \\ref{solution:3}\n\n\\subsubsection{Description}\n\nSolution 1\n\n\\subsubsection{Description}\n\nSolution 2\n\n\\subsubsection{Description} \\label[Solution]{solution:3}\n\nSolution 3\n\n\\section{Other stuff}\n\n\\subsection{Foo}\n\\subsubsection{Foobar}\n\n\\end{document}\n\n" ]

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[ "“Vaccines are safe and effective,” write researchers Philipp Schmid and Cornelia Betsch in a paper published in Nature Human Behavior this week. “", "Humans cause global warming. ", "Evolution theory explains the diversity and change of life.” ", "But large numbers of people do not believe that these statements are true, with devastating effects: progress toward addressing the climate crisis is stultifyingly slow, and the US is seeing its largest measles outbreak since 2000.", "\n\nGetting accurate information across in the face of this science denialism is something of a minefield, as there is evidence that attempts to correct misinformation may backfire, further entrenching the beliefs of science deniers instead. ", "In their paper, Schmid and Betsch present some good news and some bad: rebutting misinformation reduces the ensuing level of science denialism, but not enough to completely counter the effect of the original exposure to misinformation.", "\n\nDenialism is not skepticism\n\nSchmid and Betsch make a point of emphasizing that science denialism is a universe away from a healthy skepticism. ", "In fact, skepticism of existing results is what drives research to refine and overturn existing paradigms. ", "Denialism, the authors write, is “dysfunctional” skepticism “driven by how the denier would like things to be rather than what he has evidence for.”", "\n\nBecause this denialism springs from motivated reasoning, science advocates are scrambling to understand how to debunk misinformation in a way that motivates their target audience to accept it. ", "Schmid and Betsch focused on strategies to counter misinformation as it is being delivered during a debate, focusing on two possible approaches: correcting misinformation and laying bare the rhetorical techniques that are being used to obfuscate the truth.", "\n\nFor instance, in the case of vaccine denialism, a denier might argue that vaccines are not completely safe. ", "Correcting this misinformation (which Schmid and Betsch call a “topic” rebuttal) could take the form of arguing that vaccines in fact have an excellent safety record. ", "A “technique” rebuttal, on the other hand, would point out that demanding perfect safety is holding vaccines to an impossible standard and that no medication is 100 percent safe.", "\n\nArguing does help\n\nSchmid and Betsch gathered some participants and asked them about their attitudes toward vaccines and intention to vaccinate and then played them two different vaccine denialism arguments. ", "One group of the participants then listened to a topic rebuttal delivered by a science advocate, another to a technique rebuttal, and a third group to a combined topic and technique rebuttal. ", "A fourth group had no rebuttal (although they did have a debrief at the end of the experiment). ", "Afterward, participants were asked again about their attitudes and intentions.", "\n\nDismayingly, exposure to the denialist arguments had an overall negative impact on attitudes and intentions, regardless of the rebuttals the participants heard. ", "But the rebuttals did successfully mitigate this negative impact. ", "To test the robustness of their results, Schmid and Betsch conducted five replications, testing that their results remained the same in different population groups (students compared to a national sample) and cultures (Germany and the United States). ", "They also tested whether the same rebuttal tactics worked for climate change and whether the presentation—with the debates delivered in audio or written format—made a difference.", "\n\nThe results did vary somewhat. ", "In particular, the experiment that focused on climate change found that neither topic nor technique rebuttals resulted in a significant difference from no rebuttal. ", "But when the results of all six experiments were combined to create a larger, more-powerful data set, the overall picture was that both topic and technique rebuttals worked equivalently well. ", "The researchers also discovered that the combined rebuttals had no additional benefit.", "\n\nIn other words, it's effective to either present audience with accurate facts or describe the rhetorical techniques that had been used to spread misinformation.", "\n\nBetter to cancel than debate\n\nThe results, write Schmid and Betsch, suggest that advocates can pick the strategy they’re more comfortable with. ", "Critically, they saw no evidence of a backfire effect and, in fact, tentatively suggest the opposite—that people who were more vulnerable to the misinformation on offer were more likely to benefit from rebuttal.", "\n\nIt’s difficult to know how these results might translate to the long term—attitudes. ", "Intentions aren’t perfect measures of people’s beliefs, and these studies can’t say whether the effects of the rebuttals would wear off over time. ", "Still, rebutting in the context of a debate is just one small segment of what ideally needs to be a “multilayered defense system,” writes Sander van der Linden in a commentary on the research. ", "Research into “cognitive vaccines” suggests that teaching people how to spot misinformation before it occurs holds a lot of promise, and it’s possible that rebuttals could be more effective in an “inoculated” audience, suggest Schmid and Betsch.", "\n\nBut one thing seems clear: it could be better to turn up and debate a denialist than to stay away, a tactic that is sometimes advocated out of fear of legitimizing the denialism. ", "There’s an important exception to this, though: “if the advocate’s refusal to take part in a debate about scientific facts leads to its cancellation,” the researchers write, “this outcome should be preferred.” ", "No amount of rebuttal can make up for exposure to misinformation.", "\n\nNature Human Behavior, 2018. ", "DOI: 10.1038/s41562-019-0632-4 (About DOIs)." ]

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[ "But not all PowerPoint presentations are disastrous. ", "The best PowerPoint decks incorporate fundamental principles of communication and visual design. ", "The best PowerPoint decks actually enhance communication, and they do so through a wide variety of communication styles.", "\n\nIt's this wide variety of communication styles that led me to make a connection between PowerPoint and Raymond Queneaus' classic work, Exercises in Style, first published in French in 1947. ", "In Exercises in Style, Queneau tells a very simple, almost inane story. ", "And then he retells the same story 99 times in 99 different styles with labels like metaphorically, hesitation, precision, animism, official letter, blurb, noble, speaking personally, and of course polyptotes.", "\n\nI've embarked on a parallel project, using PowerPoint. ", "This morning I uploaded 4 PowerPoint decks to SlideShare. ", "Each uses a different style to communicate about the same fictitious project. ", "I plan to add new styles on more or less a weekly basis, starting with styles that can be effective when matched with the right circumstances. ", "The four I created and uploaded this morning are:\n\nBare Outline. ", "This is the simple, boring shell that the rest of the styles are based on.", "\n\nSBAR. ", "This one uses a format created in the patient safety world to succinctly communicate about patients. ", "In this case, I use the SBAR format to describe a software development project.", "\n\nButterfield Powerbite. ", "This is based on the scheme I use most frequently to organize everything from presentations to short emails to announcements at staff meetings. ", "Dick Butterfield taught me the scheme.", "\n\nInspirational. ", "This one addresses the same fictional project from the point of view of a senior leader inspiring her workforce to rise to a challenge.", "\n\nI'm having fun with this so far. ", "Check it out and let me know what you think.", "\n\nNo comments:\n\nSearch This Blog\n\nAbout Me\n\nI like making music and playing card games with my family, fixing up my house, eating ice cream, and reading anything I can get my hands on.", "\nI've worked in the world of technology-enabled healthcare for over 25 years, mostly for Kaiser Permanente, where I have led user experience, product management, web analytics, and strategy for Kaiser's Web presence. ", "My current work brings together healthcare reform, multiculturalism, and experience design.", "\nThe views in this blog are strictly mine and should not be attributed to Kaiser Permanente." ]

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[ "1. ", "Introduction {#sec1-pharmaceutics-12-00610}\n===============\n\nPhotodynamic therapy (PDT) is one of the modern methods for the treatment of cancer and infectious diseases that hold the promise of selective erasing of the pathologic area \\[[@B1-pharmaceutics-12-00610],[@B2-pharmaceutics-12-00610],[@B3-pharmaceutics-12-00610]\\]. ", "PDT is performed through the delivery of a photosensitizing agent with negligible dark toxicity to a diseased tissue, followed by excitation of the drug with the light of an appropriate wavelength. ", "In response to light, the photosensitizer produces free radicals and/or reactive oxygen species that kill the target pathogenic or cancer cells \\[[@B4-pharmaceutics-12-00610],[@B5-pharmaceutics-12-00610]\\]. ", "Photosensitizer molecules with strong absorption peaks in the far-red or near-infrared regions are preferential for use in PDT because they allow the treatment of deeper tissues due to deeper penetration of the activation energy in comparison with the drugs absorbing at shorter wavelengths. ", "The efficacy of PDT could be increased further by targeting the affected area with a delivery platform, which helps to improve the site-specificity and bioavailability of the PDT drug, thereby producing minimal impacts of drug activation on the surrounding healthy tissues \\[[@B6-pharmaceutics-12-00610],[@B7-pharmaceutics-12-00610],[@B8-pharmaceutics-12-00610],[@B9-pharmaceutics-12-00610],[@B10-pharmaceutics-12-00610],[@B11-pharmaceutics-12-00610]\\].", "\n\nSeveral organic and inorganic particle formulations of the PDT drugs for cancer treatment have shown superiority over the respective free therapeutics \\[[@B6-pharmaceutics-12-00610],[@B11-pharmaceutics-12-00610],[@B12-pharmaceutics-12-00610],[@B13-pharmaceutics-12-00610]\\]. ", "A clear preference based on a higher efficacy belongs to nanomaterials capable of passively targeting tumors via the enhanced permeability and retention (EPR) effect. ", "However, multiple deficiencies of nanomaterials related to their inherited properties, e.g., structural instability, or their systemic, long-term, and dose-dependent toxicities \\[[@B11-pharmaceutics-12-00610]\\], are promoting the development of safer alternatives. ", "Micron or submicron-sized polymeric multilayer capsules (PMC) assembled on CaCO~3~ vaterite sacrificial templates via alternate adsorption of biodegradable polyelectrolytes represent the system of choice for the delivery of PDT drugs, owing to their long-term structural stability and low toxicity \\[[@B14-pharmaceutics-12-00610],[@B15-pharmaceutics-12-00610]\\]. ", "PMC have been developed as a universal delivery platform for many essential biologically active molecules, such as growth factors \\[[@B16-pharmaceutics-12-00610],[@B17-pharmaceutics-12-00610],[@B18-pharmaceutics-12-00610]\\], antigens \\[[@B19-pharmaceutics-12-00610]\\], unspecific components of the immune system \\[[@B20-pharmaceutics-12-00610]\\], enzymes \\[[@B21-pharmaceutics-12-00610],[@B22-pharmaceutics-12-00610],[@B23-pharmaceutics-12-00610],[@B24-pharmaceutics-12-00610]\\], DNA \\[[@B25-pharmaceutics-12-00610],[@B26-pharmaceutics-12-00610]\\], RNA \\[[@B27-pharmaceutics-12-00610],[@B28-pharmaceutics-12-00610],[@B29-pharmaceutics-12-00610]\\], and anticancer drugs \\[[@B30-pharmaceutics-12-00610],[@B31-pharmaceutics-12-00610]\\], providing multiple options for targeting and controlled release by remote and local physical, chemical, and biological stimuli \\[[@B32-pharmaceutics-12-00610],[@B33-pharmaceutics-12-00610]\\]. ", "Advancements in the miniaturization of vaterite templates and their respectively assembled PMC \\[[@B34-pharmaceutics-12-00610],[@B35-pharmaceutics-12-00610],[@B36-pharmaceutics-12-00610]\\] have eased a long-held concern about the ability of such capsules to penetrate tissues and cells for delivery of drugs via intravenous injections. ", "PMC with the size of \\~250 nm were internalized by macrophages and epithelial cells of the lungs and liver with efficacy higher than 75% when administered in mice through an injection into the tail vein \\[[@B31-pharmaceutics-12-00610]\\].", "\n\nThere are two widely accepted classic ways to encapsulate a molecular payload in polymeric multilayers. ", "Depending on the succeeding order of the capsule assembly and loading, they are respectively called pre-loading and post-loading. ", "Pre-loading involves absorption of the molecules of interest by templates (e.g., porous vaterite or mesoporous silica particles) followed by the capsule assembly, with subsequent template dissolution. ", "Post-loading comprises molecular diffusion of the drug in the hollow PMC upon immersion into a solution of the payload \\[[@B37-pharmaceutics-12-00610],[@B38-pharmaceutics-12-00610]\\]. ", "The efficacy of each loading method strongly depends on the permeability of the polymeric multilayer network by the payload molecules, which can be altered by varying the pH of the continuous phase \\[[@B39-pharmaceutics-12-00610],[@B40-pharmaceutics-12-00610],[@B41-pharmaceutics-12-00610]\\] or by the exposure to heat \\[[@B42-pharmaceutics-12-00610],[@B43-pharmaceutics-12-00610],[@B44-pharmaceutics-12-00610]\\].", "\n\nUntil recently, the polyelectrolyte multilayer network was considered a membrane that is not permeable for large molecules with a molecular weight exceeding 1 kDa \\[[@B45-pharmaceutics-12-00610]\\]. ", "According to this concept, free diffusion of smaller molecules was thus unrestricted. ", "As such, the encapsulation of low molecular weight, water-soluble compounds has not been attempted using the classic loading methods. ", "In a series of publications \\[[@B31-pharmaceutics-12-00610],[@B36-pharmaceutics-12-00610],[@B46-pharmaceutics-12-00610]\\], we extended this concept by bringing into consideration the ionic charge compensations occurring within the multilayer infrastructure \\[[@B47-pharmaceutics-12-00610]\\]. ", "There are two types of charge compensations in the PMC network: one that is formed by the interaction of the multilayer polyelectrolytes (we define it as \"intraneous\" compensation); the other one is the \"extraneous\" compensation held by the original counterions coming with the individual polyelectrolytes before forming the PMC. ", "These are small oppositely-charged ions of the water phase, such as H^+^, Na^+^, OH^−^, Cl^−^, etc. ", "We envisioned that in such complex, intermixed ionic surroundings, the payload molecules of ionic nature would compete with the extraneous ions for respective resident ions in the polyelectrolyte network, thereby partially getting trapped in the capsule membrane \\[[@B46-pharmaceutics-12-00610]\\]. ", "Consistent with this assumption, we successfully applied a classic post-loading method to encapsulate low molecular weight water-soluble compounds in PMC \\[[@B31-pharmaceutics-12-00610],[@B46-pharmaceutics-12-00610]\\], providing experimental evidence that a certain portion of the ionic payload gets associated with the polyelectrolyte multilayer wall, rather than arrives into the capsule interior \\[[@B46-pharmaceutics-12-00610]\\].", "\n\nHigh-temperature treatment of post-loaded PMC increases the number of polymer groups involved in the intraneous charge compensation, leading to the following three consequences: (1) tightening up the pores in the polyelectrolyte multilayer network and thus sealing the capsule; (2) capsule shrinking; (3) displacement and loss of some amount of payload associated with the polyelectrolyte multilayer wall via the extraneous charge compensation. ", "Elsewhere, we have studied the physical-chemical aspects of the temperature effect on PMC, including detailed comparative research of the loading efficacy for rhodamine B for heated and intact capsules made of different polyelectrolyte pairs \\[[@B36-pharmaceutics-12-00610],[@B46-pharmaceutics-12-00610]\\]. ", "In addition, we have demonstrated a similar cell internalization rate in vitro for heated and intact capsules \\[[@B31-pharmaceutics-12-00610]\\]; however, a complete dataset revealing the influence of temperature on the therapeutic efficacy of PMC post-loaded with low molecular weight water-soluble drugs is still missing.", "\n\nSmall-to-medium molecular size PDT drugs stable to heating up to 70--90 °C are excellent models with which to discover the potential of PMC as a delivery platform for therapeutics encapsulated via the post-loading method. ", "In this work, we used the phthalocyanine-based dye, octakis{methylene\\[N-(2hydroxyethyl)-N,N-dimethylammonium\\]}chloride zinc phthalocyanine, M = 1610 g/mol ([Figure 1](#pharmaceutics-12-00610-f001){ref-type=\"fig\"}), which is currently marketed under the trade name Cholosens in Europe, as a PDT drug for oncology and infectious diseases in dentistry, otorhinolaryngology, gynecology, urology, and surgeries of various etiology \\[[@B48-pharmaceutics-12-00610],[@B49-pharmaceutics-12-00610],[@B50-pharmaceutics-12-00610],[@B51-pharmaceutics-12-00610],[@B52-pharmaceutics-12-00610],[@B53-pharmaceutics-12-00610]\\]. ", "Cholosens has an absorption peak at 680 nm. ", "Light irradiation at this wavelength causes the generation of singlet oxygen from Cholosens molecule with a high quantum yield of 100 J/cm^2^ \\[[@B54-pharmaceutics-12-00610]\\]. ", "A recent study revealed the photobiological properties of non-encapsulated phthalocyanine photosensitizers, including Cholosens \\[[@B55-pharmaceutics-12-00610]\\]. ", "The current work aims to determine the efficacy of dextran sulfate (DS) and poly-[l]{.smallcaps}-arginine (PArg) PMC (\\[DS/PAgr\\]~4~) capsules loaded with Cholosens for the PDT treatment on eukaryotic cells and bacteria studied in vitro. ", "Human adenocarcinoma (HeLa) cells and normal human dermal fibroblasts (NHDF) were used as corresponding models of cancer and normal eukaryotic cells. ", "The antimicrobial PDT effect was studied on Gram-positive and Gram-negative strains, *Staphylococcus aureus* and *Escherichia coli*, respectively. ", "In our work, we post-loaded the capsules with Cholosens with and without exposure to high temperature (80 °C for 60 min), while also varying the capsule concentration to get a better understanding of ionic interactions between the DS/PArg multilayer capsules and Cholosens. ", "PMC loading was then followed by detailed research of the heat treatment's influences on the potency of the encapsulated form of Cholosens, i.e., the drug release rate, internalization of capsules by cells, and their dark and light toxicities.", "\n\n2. ", "Materials and Methods {#sec2-pharmaceutics-12-00610}\n========================\n\n2.1. ", "Materials {#sec2dot1-pharmaceutics-12-00610}\n--------------\n\nPoly(sodium 4-styrenesulfonate) (PSS, M = 70 kDa), a 20% *w*/*w* water solution of poly(diallyldimethylammonium chloride) (PDADMAC, M = 100--200 kDa), dextran sulfate, sodium salt (DS, M \\> 40,000), poly-[l]{.smallcaps}-arginine hydrochloride (PArg, M \\> 70,000), α-chymotrypsin from bovine pancreas, calcium chloride dihydrate, anhydrous sodium carbonate, ethylenediaminetetraacetic acid trisodium salt (EDTA), rhodamine 6G (RhD6G), fluorescein 5-isothiocyanate (FITC), phosphate-buffered saline (PBS), Dulbecco's minimum essential medium (DMEM), fetal bovine serum (FBS), Alamar blue, and calcein-AM were purchased from Sigma-Aldrich. ", "Minimum essential medium (MEM), penicillin, streptomycin, trypsin, and trypan blue were purchased from Thermo Fisher Scientific. ", "Hydrochloric acid was obtained from Merck. ", "Zinc phthalocyanine (Cholosens) was kindly provided by the Institute of Organic Intermediates and Dyes (Moscow, Russia). ", "All chemicals were used as received without further purification.", "\n\nNormal human dermal fibroblasts (NHDF) and HeLa cell cultures were obtained from the Department of Cell Engineering, Education and Research Institute of Nanostructures and Biosystems, Saratov State University, Russia. *", "Staphylococcus aureus* and *Escherichia coli* were from ATCC (ATCC 25923 and ATCC 25922, respective strains).", "\n\nDeionized water with specific resistivity higher than 18.2 MΩ cm^−1^ from a three-stage Milli-Q Plus 185 purification system was used in the experiments.", "\n\n2.2. ", "Preparation of Microcapsules and Loading with Cargo {#sec2dot2-pharmaceutics-12-00610}\n--------------------------------------------------------\n\nA single batch of hollow PMC was prepared and used in all experiments described in this manuscript.", "\n\nThe capsules were assembled and loaded with Cholosens following the method previously described by our group \\[[@B46-pharmaceutics-12-00610]\\]. ", "In brief, the CaCO~3~ microparticle template was synthesized by mixing 2 mL of each of 1 M CaCl~2~ and Na~2~CO~3~ solutions under vigorous agitation for 30 s. The obtained CaCO~3~ spherical particles with (average diameter 4 μm) were collected by centrifugation and thoroughly washed with DI water. ", "Multilayer capsules comprising four bi-layers of DS/PArg were then assembled on CaCO~3~ via the layer-by-layer (LbL) method. ", "DS and PArg were alternatively adsorbed from 2 mg/mL and 1 mg/mL of respective aqueous solutions, also containing 0.5 M NaCl, starting from the DS layer. ", "After each single layer formation, the particles were thoroughly washed with water to remove the uncoupled polymer. ", "The obtained coated particles were treated with 5 mL of 0.2 M EDTA for 15 min to remove the inorganic phase resulting in the formation of hollow polymeric capsules. ", "Capsule suspensions containing variable numbers of particles were then re-dispersed in 1 mL of an aqueous solution of Cholosens (0.05 mg/mL). ", "After one hour of incubation needed for the infiltration of Cholosens, each suspension was divided into two specimens. ", "Capsules in specimen 1 were immediately washed with DI water by centrifugation to remove the unloaded Cholosens, whereas capsules in specimen 2 were heated up to 80 °C and kept for 60 min at constant shaking (500 rpm) before cooling down for ten minutes and washing. ", "The supernatants were collected to measure the concentration of Cholosens (the data were further used to calculate the encapsulation efficacy, and the amount of Cholosens loaded in PMC). ", "Here and further in the manuscript, the concentration of Cholosens in supernatants was determined spectroscopically (Synergy H1 reader (BioTek, Winooski, Vermont, U.S.A.) by measuring the intensity of fluorescence at λ~ex~ = 685 nm, λ~em~ = 715 nm. ", "The fluorescence intensity data were then converted to concentrations using a calibration curve plotted for a series of dilutions with a known concentration of Cholosens, which exhibited linear character in the measured concentration range. ", "Each calibration solution was prepared in 1× PBS to match the ionic strength of the tested samples.", "\n\nThe PMC were post-loaded with RhD6G of FITC dyes via incubation of the microcapsule suspension in the respective solutions (0.1 mg/mL) for 60 min followed by three washing steps with DI water.", "\n\n2.3. ", "Capsule Enzymatic Degradation {#sec2dot3-pharmaceutics-12-00610}\n----------------------------------\n\nCholosens-loaded capsule suspensions were lyophilized in FreeZone 12 Labconco freeze drier. ", "Each sample was then mixed with 1 mL of 1 mg/mL α-chymotrypsin dissolved in 1× PBS (pH 7.4) in 2 mL centrifuge tubes and kept at 37 °C for 24 h. Undissolved polymeric complexes were then extracted by centrifugation and resuspended again in the enzyme solution. ", "The respective supernatants were analyzed with fluorescence spectroscopy to determine the amount of Cholosens released from the capsules after the complete digestion of the PMC.", "\n\n2.4. ", "Release of Cholosens {#sec2dot4-pharmaceutics-12-00610}\n-------------------------\n\nThe cumulative release of Cholosens from 4.5 × 10^8^ \\[DS/PArg\\]~4~ microcapsules in 1 mL of 1× PBS (pH 7.4) was measured with fluorescence spectroscopy over 48 h. The medium was fully refreshed at each timepoint.", "\n\n2.5. ", "Uptake of Microcapsules by Cells {#sec2dot5-pharmaceutics-12-00610}\n-------------------------------------\n\nUptake of PMC was studied on HeLa cells by flow cytometry. ", "For this purpose, the capsules were labeled with FITC (λ~ex~ = 491 nm, λ~em~ = 516 nm). ", "The cells were seeded in 24-well cell culture plates at the density of 10000/cm^2^ in 0.5 mL DMEM supplemented with 10% FBS and 1% penicillin--streptomycin appropriate for the cell passage and incubated for 24 h. The medium was then replaced by the fresh DMEM containing FITC-labelled PMC (5 capsules/cell). ", "After incubation for 1, 2, 4, and 24 h to allow the capsule uptake, the cells were rinsed with PBS (pH 7.4) three times, trypsinized, centrifuged, and kept in ice-cold PBS until study with a FACSCalibur flow cytometer. ", "The cells were treated with trypan blue to quench the extracellular fluorescence of FITC and to detect the signal from internalized capsules solely \\[[@B56-pharmaceutics-12-00610]\\]. ", "Quantitative data were obtained using the BD CellQuest software.", "\n\n2.6. ", "PDT Activity of Cholosens-Loaded Microcapsules on Human Cells {#sec2dot6-pharmaceutics-12-00610}\n------------------------------------------------------------------\n\nHeLa and NHDF cells were seeded in a 96-well cell culture plate at the density of 10^4^ cells per well. ", "Each well in the culture plate was filled with 100 μL of MEM supplemented with 10% FBS, also containing 1% penicillin-streptomycin. ", "The plates were incubated at 37 °C in 5% CO~2~ atmosphere. ", "Twenty-four hours after plating, free or encapsulated forms of Cholosens were added to the culture medium followed by incubation overnight. ", "The encapsulated form of Cholosens was represented by loaded \\[DS/PArg\\]~4~ shells with or without consequent heat exposure. ", "PMC were added to the culture medium at the densities of 5, 20, or 40, and each capsule contained 0.9 ± 0.13 pg of Cholosens.", "\n\nThe cell culture medium was further replaced with PBS to reduce optical density. ", "Each well of the plate was irradiated with a light-emitting diode of 680 nm wavelength (Polironik, Moscow, Russia) for 7.5 min with an intensity of 4000 lx (corresponding to 80 mW/cm^2^). ", "Upon that, PBS was replaced by the cell culture medium again.", "\n\nIn the last step, 10 μL (10% *V*/*V*) of fluorescence dye Alamar blue was added to each well for detecting viable cells followed by 24 h of incubation. ", "Fluorescence intensity of the samples (excitation 560 nm, emission 590 nm) was then measured spectroscopically.", "\n\nCorresponding data on the viability of non-irradiated HeLa and NHDF cells grown without any of encapsulated or free forms of Cholosens were taken as 100%.", "\n\n2.7. ", "Antimicrobial PDT Activity of Photosensitizer-Loaded Microcapsules {#sec2dot7-pharmaceutics-12-00610}\n-----------------------------------------------------------------------\n\nThe antibacterial activity of Cholosens-loaded PMC against the strains of *S. aureus* and *E. coli* was defined using the modified method of minimum inhibitory concentration. ", "The experiments were conducted in triplicate to ensure statistical significance. ", "Both *Staphylococcus aureus* and *Escherichia coli* were cultured and kindly provided by Saratov Institute of Traumatology and Orthopedics (Saratov, Russia). ", "Nutrient agar was prepared and provided by the Institute of Organic Intermediates and Dyes (Moscow, Russia).", "\n\nNext, 300 μL of suspensions containing microorganisms (3 × 10^5^ cells/mL) were mixed with microcapsule suspensions in different ratios (ranging from 3 to 80 capsules/cell) and incubated for 60 min. ", "After that, the mixtures were irradiated with a 680 nm light-emitting diode, as described above. ", "100 μL of each light-treated suspension was then inoculated on the surface of NA obtained from 20 mL of 1.5% sterile NA medium solidified in the Petri dishes (2R = 7.5 cm). ", "The Petri dishes were incubated for 24 h at 37 °C to grow individual bacterial colonies on the solid medium surface. ", "The numbers of cells in the original suspensions were adjusted in such a way as to avoid confluence. ", "Non-irradiated bacterial samples cultured in a similar way were used as a negative control. ", "Corresponding data on the viability of non-irradiated *S. aureus* and *E. coli* grown without any of encapsulated or free forms of Cholosens was taken as 100%. ", "The results were presented as arithmetic means and standard deviations.", "\n\n2.8. ", "Characterization {#sec2dot8-pharmaceutics-12-00610}\n---------------------\n\nThe obtained PMC were visualized with a scanning electron microscope (SEM): the FE SEM JSM6700F instrument in the secondary electron imaging mode at 5 keV. The samples were prepared by placing a 10 µL droplet of microcapsule suspension on a silicon substrate followed by drying overnight. ", "The surface of the sample was then covered with a layer of gold before taking the SEM images.", "\n\nThe shell thickness was measured by atomic force microscopy (AFM) performed with an NT-MDT Ntegra spectra probe station in a semi-contact mode with the GOLDEN series probes NSG10 having a curvature radius of 6 nm. ", "The samples for AFM measurements were prepared by drying 2 µL droplets of the capsule suspensions on the surface of a cover glass.", "\n\nCapsule concentration in suspensions was obtained using a hemocytometer as an average of 5 measurements for each sample.", "\n\nCapsule loading was measured via two complementary approaches. ", "In the first approach, the supernatants collected after loading were analyzed spectroscopically. ", "The cumulative loss of payload upon loading and consecutive washings was then deducted from its initial amount to obtain the weight of loaded Cholosens and loading efficacy. ", "The loading efficacies of thermally treated vs. intact PMC were compared using the following equation:$$E_{comp}\\left( \\% \\right) = \\frac{m\\left\\lbrack {Cholosens} \\right\\rbrack_{heated} - m\\left\\lbrack {Cholosens} \\right\\rbrack_{intact}}{m\\left\\lbrack {Cholosens} \\right\\rbrack_{intact}} \\times 100\\%,$$ where $E_{comp}$---the comparative encapsulating efficacy of two approaches; $m\\left\\lbrack {Cholosens} \\right\\rbrack_{heated}$ and $m\\left\\lbrack {Cholosens} \\right\\rbrack_{intact}$---the amount of Cholosens in heated and intact capsules, respectively.", "\n\nIn the second approach, the amount of Cholosens released from the enzymatically digested capsules was measured by fluorescence spectroscopy.", "\n\nComplementary information on the capsule size and visual evidence of cellular uptake and cancer cell elimination by Cholosens-loaded PMC was provided by confocal laser scanning microscopy (CLCM) using Leica TCS SP8 X (Leica Microsystems, Wetzlar, Germany).", "\n\nBefore taking the images, each capsule sample was manually scanned along the z-axis in the fine-focus regime to reveal the focal plane where the shells displayed the darkest interior at the maximal outlined area. ", "The focus was then set up on this plane, and the sample was imaged. ", "Captured capsules displaying the darkest interior (at least 20 per each sample) were measured to reveal the average diameter.", "\n\nHeLa cells were plated into a Petri dish and incubated for 24 h before staining with a calcein-AM dye (λ~ex~ = 495 nm, λ~em~ = 515 nm). ", "For staining, 1 μm of calcein-AM solution with an initial concentration of 1 mg/mL was added per one milliliter of the culture medium to achieve 0.001 mg/mL of calcein-AM. ", "The cells were then kept in an incubator for 30 min, followed by thorough washing by PBS to remove the excess of the dye. ", "Upon that, the suspension of the Cholosens-loaded capsules (2 capsules/cell) or a Cholosens aqueous solution were added into the cell medium. ", "After two hours of incubation, the CLSM images were taken. ", "The amount of added free Cholosens was as such to level with the total amount of the photosensitizer in the capsules (assuming 0.9 pg of Cholosens loaded in a single capsule). ", "The position on the z-axis for imaging of HeLa cells was found manually by scanning the observed group of cells in the fine-focus regime to reveal the ventral area of the cell, which typically had the strongest signal from the calcein-AM dye (green fluorescence) and the largest observed area with the green fluorescence. ", "This technique ensured that the observed Cholosens-loaded PMC (red fluorescence) were internalized by cells without the necessity of co-localization of the capsules with the cell nucleus. ", "Cholosens-loaded \\[DS/PArg\\]~4~ microcapsules were visualized at λ~ex~ = 685 nm, λ~em~ = 715--780 nm. ", "Photodynamically-induced damage of HeLa cells by different forms of Cholosens was visualized by irradiation of the respective samples with white laser (WLL E, avg. ", "power 1.0 mW) at 670 nm. ", "A single cell in the treated area received approximately 0.1 mW irradiation dose.", "\n\n2.9. ", "Data Analysis {#sec2dot9-pharmaceutics-12-00610}\n------------------\n\nStatistical analysis of data was conducted using unpaired two-tailed Student's t-test. ", "Data are presented as the means ± standard deviations (SD). ", "Two levels of significance were established (*p* \\< 0.05 and \\< 0.01).", "\n\n3. ", "Results {#sec3-pharmaceutics-12-00610}\n==========\n\n3.1. ", "Temperature-Induced Morphological Changes in the \\[DS/PAgr\\]~4~ PMC System {#sec3dot1-pharmaceutics-12-00610}\n-------------------------------------------------------------------------------\n\nWe have previously determined a temperature treatment profile leading to size reduction and tightening of PMC capsules at 90 °C for 60 min \\[[@B36-pharmaceutics-12-00610]\\]. ", "In this case, to ensure the stability and biological efficacy of Cholosens, we lowered the temperature to 80 °C while keeping the treatment duration unchanged. ", "Images obtained by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and atomic force microscopy (AFM) in [Figure 2](#pharmaceutics-12-00610-f002){ref-type=\"fig\"} depict the \\[DS/PArg\\]~4~ microcapsules before and after heating to validate and quantify the PMC response to treatment at the modified conditions. ", "Upon exposure to 80 °C for 60 min, the capsules underwent morphological changes that we observed previously, i.e., a decrease in size and tightening \\[[@B36-pharmaceutics-12-00610]\\]. ", "SEM images ([Figure 2](#pharmaceutics-12-00610-f002){ref-type=\"fig\"}a1,a2) reveal the overall size reduction and (significantly) increased thickness of the heat-treated polymeric multilayer shells compared to intact PMC. ", "Capsules also gained rigidity after heat exposure so that the smallest particles in the batch were able to stay spherical after drying on a solid support. ", "In addition, SEM confirms the transformation of all capsules in the batch in response to 80 °C.", "\n\nEstimations of the average capsule size using the CLSM images ([Figure 2](#pharmaceutics-12-00610-f002){ref-type=\"fig\"}b1,b2) and respective cross-sections (for example see [Figure S1](#app1-pharmaceutics-12-00610){ref-type=\"app\"}) revealed that the capsules contracted after heating from 4.95 ± 0.65 μm to 3.78 ± 0.4 μm; that gives the size decrease of \\~23%. ", "In this study, the heated shells demonstrated an increase in thickness from 0.073 ± 0.009 μm to 0.114 ± 0.025 μm (\\~35% increase) according to the AFM data ([Figure 2](#pharmaceutics-12-00610-f002){ref-type=\"fig\"}c1,c2,d1,d2).", "\n\n3.2. ", "PMC Loading and Release of Cholosens {#sec3dot2-pharmaceutics-12-00610}\n-----------------------------------------\n\nSuspension of loaded capsules gained a bright blue color after the diffusion of Cholosens. ", "Free Cholosens has two absorbance peaks at 635 and 680 nm. [", "Figure S2](#app1-pharmaceutics-12-00610){ref-type=\"app\"} depicts the absorbance spectrum of Cholosens after the encapsulation. ", "The positions of absorbance peaks of the encapsulated drug did not significantly shift when compared to those of the free drug, indicating that no structural change occurred upon the loading process.", "\n\nCholosens loading was assessed by the quantitative analysis of the loading efficiency that was essential for administration dosage of heated and intact encapsulated drug forms for in vitro studies. ", "Previously we showed that the amount of rhodamine B detected in DS/PArg capsules was lower for heated analogs in comparison with the untreated PMC. ", "Moreover, the loading of heated capsules did not depend much on the capsule concentration that was varied in the range of 6.9 × 10^7^--3.4 × 10^9^ capsules/mL, whereas the loading of non-treated PMC gradually increased with the increasing of the number of capsules in the sample \\[[@B46-pharmaceutics-12-00610]\\]. ", "The particular aspects of loading Cholosens in \\[DS/PArg\\]~4~ PMC were discovered upon varying the capsule concentration from 0.6 × 10^8^ to 9 × 10^8^ capsule/mL at a constant concentration of Cholosens (0.05 mg/mL).", "\n\nThe amount of Cholosens loaded in the \\[DS/PArg\\]~4~ microcapsules was measured by two complementary approaches, i.e., (1) by measuring the residual concentrations of the drug in the supernatants obtained after loading ([Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}), and (2) by measuring the concentrations of the drug released after enzymatic degradation of the loaded PMC ([Figure S3](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "Spectroscopic measurements of the supernatants obtained after the loading of Cholosens ([Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}a) revealed that the residual concentration of the drug had decreased with increasing the capsule concentration for both heated and intact PMC. ", "The minimal concentrations of Cholosens were detected in the samples containing the highest amounts of intact or heated PMC, i.e., 9 × 10^8^ capsules/mL. At this capsule concentration, the residual concentrations of Cholosens were 2.2% and 6.2% of the initial 0.05 mg/ml for intact and heated capsules, respectively.", "\n\nThe loading data obtained through measurements of Cholocesns released from enzymatically-degraded capsules ([Figure S3a](#app1-pharmaceutics-12-00610){ref-type=\"app\"}) and through the analysis of its residual amount in the supernatant ([Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}a) are generally in good agreement and so is the respective data on the loading of a single capsule ([Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}b and [Figure S3b](#app1-pharmaceutics-12-00610){ref-type=\"app\"}) calculated from the corresponding datasets plotted in [Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}a and [Figure S3a](#app1-pharmaceutics-12-00610){ref-type=\"app\"}. ", "In essence, capsules in bigger batches do entrap larger amounts of Cholosens. ", "A sharp decrease in the loading of a single capsule, however, was observed at the biggest concentration of 9 × 10^8^ capsules/mL. The observed result contains no contradiction if we take into account the residual concentrations of Cholosens observed for the capsule concentration 4.5 × 10^8^ capsules/mL, which were approximately 20% and 10% of the initial amount in suspension for intact and heated capsules, respectively. ", "As such, at a higher capsule concentration, the drop in the loading per capsule was well-expected because almost the same amount of Cholosens was spread across a larger number of capsules.", "\n\nThe total amount of loaded Cholosens significantly increased when increasing the capsule concentration for both intact and heated capsules ([Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}a, [Figure S3a](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "Besides, the amounts of loaded Cholosens in the DS/PArg heated and intact microcapsules were close or slightly higher in the case of heated PMC for the majority of the capsule concentrations ([Figure 4](#pharmaceutics-12-00610-f004){ref-type=\"fig\"}). ", "At 9 × 10^8^ capsules/mL, intact PMC displayed better loading than their heated counterparts.", "\n\n[Figure 5](#pharmaceutics-12-00610-f005){ref-type=\"fig\"} shows the respective release profiles of Cholosens from intact and heated capsules over 48 h. The amount of Cholosens released from the intact PMC at each timepoint was roughly about two times higher than from the heated ones, thereby emphasizing the effect of polymeric multilayer network tightening for the diffusion of Cholosens upon exposure to 80 °C.", "\n\n3.3. ", "Cellular Uptake of \\[DS/PArg\\]~4~ Microcapsules {#sec3dot3-pharmaceutics-12-00610}\n----------------------------------------------------\n\nBefore engaging in the in vitro experiments, we studied the morphology of \\[DS/PArg\\]~4~ microcapsules in the cell culture medium. ", "As such, we observed no changes for the capsules suspended in water or 1× phosphate-buffered saline (PBS). ", "Capsule cellular internalization was then studied on HeLa cells by analyzing approximately 10^4^ cells per sample by flow cytometry. ", "The PMC were post-loaded with FITC for analytical purposes. ", "In each sample, the cells were mixed with capsules in a concentration of 10 capsules/cell. ", "The uptake level (the proportion of cells (%) with at least one capsule) was determined as the median fluorescence intensity in each sample related to the median fluorescence intensity of the control cells incubated without capsules. ", "The results are reflected in [Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}a as mean values ± standard deviations.", "\n\nInternalization of \\[DS/PArg\\]~4~ microcapsules by HeLa cells was a time-dependent process, wherein the number of cells with internalized capsules had gradually increased. ", "Similarly to the data described elsewhere \\[[@B57-pharmaceutics-12-00610]\\], the highest capsule internalization rate by HeLa cells was observed during the first four hours ([Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}a). ", "The uptake efficacy was slightly higher for heated capsules than for intact ones over the early two hours (\\* *p* \\< 0.05); no significant difference in the uptake of heated and intact PMC was observed at the next timepoints, indicating no prolific impact of the capsule size difference ([Table S1](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "After 24 h, nearly 82% of the studied HeLa cells had internalized the \\[DS/PArg\\]~4~ microcapsules. ", "The emission spectrum of Cholosens has a sharp peak at \\~700 nm wavelength that allows visualization of the Cholosens-loaded PMC in the cell culture medium and inside the cells after internalization. ", "A typical CLSM image of the cells containing Cholosens-loaded capsules at 24 h timepoint supports the flow cytometry data ([Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}b).", "\n\n3.4. ", "Comparison of the Actions of the Encapsulated and Free Forms of Cholosens on Human Cell Lines {#sec3dot4-pharmaceutics-12-00610}\n--------------------------------------------------------------------------------------------------\n\nThe cytotoxicity of the free and the \\[DS/PArg\\]~4~-encapsulated Cholosens was studied on the normal (NHDF) and cancerous (HeLa) human cell lines by varying the capsule/cell ratio from 1 capsule/cell up to 40 capsules/cell. ", "HeLa and NHDF cells were cultured overnight in the Cholosens containing medium or with the Cholosens-loaded PMC; then, the number of viable cells was measured by detection of the metabolic activity through staining the cells with a resazurin-based dye, Alamar Blue. ", "Control groups for both cell lines were incubated in the culture medium with no added capsules or free drug at 37 °C. ", "After 24 h, the medium was exchanged for 1× PBS buffer before cell irradiation with a laser diode to avoid absorption of light by the medium.", "\n\nNon-encapsulated Cholosens possessed concentration-dependent toxicity for both studied cell lines, which was markedly reduced after the drug encapsulation in \\[DS/PArg\\]~4~ ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}a). ", "Both intact and heated encapsulated forms of Cholosens did not affect the viability of HeLa cells at all studied capsule/cell ratios. ", "As suggested by [Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}b, HeLa cells internalized a large number of capsules with no adverse effects on morphology. ", "The captured cells display a well-defined cell shape spread typical for attached HeLa cells. ", "After 24 h of incubation with PMC, the cells exhibit sufficient adhesion, indicating that they were healthy and that they tolerated the internalized capsules well. ", "The NHDF cells became significantly inhibited by the encapsulated forms of Cholosens at the capsule concentration of 20 capsules/cell ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}a). ", "At one and five added capsules per cell, the Cholosens-loaded capsules were significantly less cytotoxic than the non-encapsulated drug ([Table S2](#app1-pharmaceutics-12-00610){ref-type=\"app\"}).", "\n\nLight cytotoxicity of the encapsulated and free forms of Cholosens was measured comparatively after irradiation of the respective wells with adherent HeLa and NHDF cells with a 680 nm light-emitting diode for 7.5 min at the power density of 80 mW/cm^2^ over the area of \\~0.8 cm^2^. The data in [Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}a demonstrate a significant decrease in fluorescence signal (i.e., the metabolic activity) in the control groups for both HeLa and NHDF cells in response to the light irradiation: the residual viability of the treated cells was \\~40%. ", "Cell treatment with encapsulated and free Cholosens (equal to five capsules/cell and higher) resulted in a drastic drop in the number of living cells of both cell lines after light irradiation when compared to the non-irradiated cells.", "\n\nThe effects of the encapsulated Cholosens in both heated and intact \\[DS/PArg\\]~4~ PMC compared to the free drug form on the cell viability varied by up to 6--7%, except in the case of HeLa cells treated with five intact capsules per cell; the viability of those was significantly different from the treatment with free Cholosens ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}b). ", "It appears that at this capsule/cell ratio, the amount of Cholosens delivered by capsules is not sufficient to provide the desired effect, but it is working as projected at higher ratios. ", "At the lowest capsule/cell ratio (i.e., 1 capsule/cell), the free form of the drug also exhibited a limited advantage over the encapsulated form ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}b, [Table S2](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "The results of the Student's t-test showed that laser irradiation provided a significantly higher level of toxicity of the free drug form in both cell lines ([Table S3](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "Additionally, a high level of statistical significance (\\*\\* *p* \\< 0.01) of the difference between the toxicity of intact capsules after laser irradiation compared to non-irradiated samples was confirmed for all studied capsule/cell ratios in both cell lines ([Table S4](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "In the majority of cases examined, the toxicity of the intact and heated Cholosens-loaded capsules is not significant ([Table S5](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "This phenomenon was observed both for the non-irradiated and irradiated conditions in HeLa and NHDF cells. ", "Rare cases of significant differences between intact and heated capsules are marked in [Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}a.", "\n\nCells were monitored by CLSM to detect photodynamically-induced damage of HeLa cells by different forms of Cholosens. ", "First, the cells were incubated in the Cholosens solution for a few hours, followed by staining with a vital dye, calcein-AM. ", "The cells were then irradiated at 670 nm for 60 s over the sample area of \\~175 × 175 μm^2^ to induce the generation of singlet oxygen by the photosensitizer. ", "HeLa cells incubated in the culture medium without adding Cholosens for the same duration were used as a negative control after replacing the medium with 1× PBS buffer before light irradiation.", "\n\nThe control sample did not display any visible changes in the cell morphology after the irradiation ([Figure 8](#pharmaceutics-12-00610-f008){ref-type=\"fig\"}a,b). ", "In the presence of Cholosens, however, the irradiated cells underwent dramatic morphological changes even five minutes past the beginning of the light exposure, which was accompanied by the formation of the vesicles over their surfaces ([Figure 8](#pharmaceutics-12-00610-f008){ref-type=\"fig\"}c--f). ", "Distinct transformations of the cell shape and a consequent decrease in the fluorescence of calcein-AM over the next 20 min indicate the destruction of the cells within the treated area, confirming the high potency of Cholosens as a PDT drug ([Figure 8](#pharmaceutics-12-00610-f008){ref-type=\"fig\"}c--f).", "\n\nThe light-induced cell elimination process by intact and heated encapsulated forms of Cholosens was visualized using the same negative control as in the previous experiment, i.e., HeLa cells first cultured in the medium with no added encapsulated or free photosensitizer and then transferred to 1× PBS buffer right before the light irradiation. ", "The control cells irradiated for 60 s with the 670 nm white laser displayed no destructive processes 20 min after the light was switched off ([Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"}a,b).", "\n\nThree capsules per cell was chosen as an optimal concentration for the CLSM experiments based on the convenience of focusing on a single cell with internalized capsules. ", "It would be harder to accomplish this precision at higher capsule concentrations when the sample was saturated with such cells. ", "In addition, as suggested by [Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}a, at three capsules per cell, the viability of non-irradiated cells was not affected. ", "For visualization of the encapsulated forms of Cholosens, we picked up the area of 100 × 100 μm^2^ that included the cells with and without internalized capsules. ", "Similarly to the control sample, the cells in the selected area were irradiated for 60 s, followed by observations and imaging 20 min after the light treatment was over ([Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"}c--f). ", "The corresponding images in [Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"} depicting HeLa cells with internalized intact or heated PMC show a distinct decrease in the fluorescence intensity of calcein-AM, which became apparent already after the first 30 s from the beginning of light treatment. ", "Light irradiation caused the formation of vesicles in some of the treated cells with encapsulated Cholosens, which may be a sign of apoptosis ([Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"}f). ", "Besides, the images c--f in [Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"} also suggest that even a couple of the drug-loaded capsules inside the cell was enough to cause light-induced cell destruction.", "\n\nAs suggested by [Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}, both HeLa and NHDF cells cultured with no added encapsulated or free Cholosens were affected by laser treatment, so one might expect to see morphological changes in HeLa cells under CLSM ([Figure 8](#pharmaceutics-12-00610-f008){ref-type=\"fig\"}a,b and [Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"}a,b). ", "It must be mentioned for this reason that the cells irradiated with the CLMS laser ([Figure 8](#pharmaceutics-12-00610-f008){ref-type=\"fig\"}, [Figure 9](#pharmaceutics-12-00610-f009){ref-type=\"fig\"}) received considerably lower irradiation dosages compared to those treated with the light-emitting diode ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}) due to a shorter time of exposure and a lower irradiation power, which was below the threshold to overcome for morphological damage.", "\n\n3.5. ", "Effect of the Encapsulated Forms of Cholosens on Bacterial Cells {#sec3dot5-pharmaceutics-12-00610}\n---------------------------------------------------------------------\n\nAs claimed by the manufacturer, Cholosens is a potent antimicrobial PDT drug against *Helicobacter pylori*, *Campylobacter jejuni*, *Escherichia coli 1257*, *Escherichia coli 675*, *Enterococcus faecalis*, *Staphylococcuc aureus*, and some other pathogens. ", "Here we compared the efficacies of free and encapsulated Colosens to inhibit a Gram-positive bacterial strain of *S. aureus* ([Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}a) and a Gram-negative bacterial strain of *E. coli* ([Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}b). ", "The bacterial cells were incubated in a Cholosens solution or the drug-loaded capsule suspensions for one hour before light irradiation, and viability measurements against the untreated microorganisms kept without Cholosens. ", "The same samples were also studied without light irradiation to evaluate the dark toxicity of the respective drug forms.", "\n\nIn our study, free Cholosens in solution revealed significant dark toxicity to *S. aureus*. ", "The viability of bacterial cells incubated with Cholosens dropped below 30% even at the lowest concentration studied, which was equal to the amount of drug provided by three capsules per cell. ", "The highest studied concentration of Cholosens thus was equivalent to the amount of the drug loaded in 27 capsules per cell, at which the cell viability dropped to almost 0% ([Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}a). ", "Predictably, *E. coli* showed higher resistance to Cholosens conferred by the cell wall. ", "The viability of *E. coli* cells was between 75% and 50%, depending on the drug concentration that was ranging from five to 80 capsules per cell ([Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}b).", "\n\nThe dark toxicity of both encapsulated drug forms to *S. aureus* decreased gradually from \\~80% to \\~35% in the investigated capsule density range, which was significantly lower than the dark toxicity of free Cholosens. ", "Besides, intact PMC possessed a significantly higher inhibition efficacy than the heated ones ([Table S7](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "Both encapsulated forms revealed the antimicrobial activity after light irradiation, which is approaching the light toxicity of free Cholosens at the concentration equal to nine capsules per cell or higher. ", "In this concentration range, the efficacies of heated and intact PMC were level as per the Student's t-test ([Table S7](#app1-pharmaceutics-12-00610){ref-type=\"app\"}).", "\n\nFor *E. coli,* the dark toxicity of heated \\[DS/PArg\\]~4~ microcapsules against this bacterial strain was around 90% (of viable cells with respect to control) and lower compared to the dark toxicity of intact PMC over the whole studied density range. ", "On the contrary, intact capsules gradually became more toxic upon increasing the capsule-to-cell ratio. ", "Maximal light toxicity for *E. coli* achieved with heated PMC was the \\~28% of cells remained viable. ", "The light-induced toxicity of intact capsules was significantly higher than of their heated counterparts for all capsule/cell ratios ([Table S8](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "The same trend and level of significance were observed for non-irradiated samples with the only exception at five capsules/cell ([Table S8](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "An increase in the capsule/cell ratio from three to nine leads to a significant decrease in the viability of Gram-positive *S. aureus* microorganisms; as for Gram-negative *E. coli*., ", "a significant decrease in viability was achieved by increasing the capsule/cell ratio from 10 to 20 ([Table S9](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "These differences between the respective datasets are reflected in [Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}. ", "Thus, the intact encapsulated form of Cholosens nearly matched the free drug inhibitory effect on *E. coli* at the density of 20 capsules per cell, eliminating almost 70% of microorganisms; it further induced almost full elimination of the bacteria at 80 capsules per cell.", "\n\n4. ", "Discussion {#sec4-pharmaceutics-12-00610}\n=============\n\nThis study has developed biodegradable \\[DS/PArg\\]~4~ microcapsules assembled on the sacrificial CaCO~3~ vaterite template as a delivery platform for Cholosens, a novel PDT drug. ", "Cholosens was loaded on PMC via a classic post-loading method through the diffusion of drug molecules into the capsules resuspended in the Cholosens solution. ", "Loaded capsules were further heated at 80 °C for 60 min to study the effect of the heat treatment on the loading efficacy and photodynamic properties of the encapsulated form of Cholosens.", "\n\nOur results suggest that the chosen temperature regime leads to the morphological transformation of capsules upon heat exposure, i.e., tightening of the polymeric multilayer network and capsule contraction. ", "It has to be noted that such treatment does not cause any adverse effects on the optical and photodynamic properties of Cholosens.", "\n\nIn contrast to a poor loading of rhodamine B in DS/PArg microcapsules upon heating \\[[@B46-pharmaceutics-12-00610]\\], Cholosens was loaded to the PMC with high efficacy, when the total loading gradually enhanced upon capsule concentration increase. ", "For the highest concentration studied here (9 × 10^8^ capsules/mL) the loading efficacy exceeded 90%. ", "Besides, unlike what was observed for rhodamine B, the loading per capsule was higher for heated capsules compared to intact ones all the way until the capsule concentration reached 9 × 10^8^ capsules/mL ([Figure 4](#pharmaceutics-12-00610-f004){ref-type=\"fig\"}). ", "At this number of capsules, the loading efficacy of heated vs. intact capsules showed an opposite trend. ", "Similarly to how it was previously explained for the loading of rhodamine B \\[[@B46-pharmaceutics-12-00610]\\], the total amount of the Cholosens molecules displaced from the shell into supernatant upon the capsule heating increased with the increase of the capsule concentration, causing an overall comparative decrease of encapsulation efficacy in respect to intact PMC. ", "Eventually, at some point (9 × 10^8^ capsules/mL in case of Cholosens), the number of displaced dye molecules will overcome the amount of those entrapped in the capsules. ", "The data in [Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"} and [Figure 4](#pharmaceutics-12-00610-f004){ref-type=\"fig\"} are likely to feature a much stronger affinity of Cholosens in comparison to rhodamine B to the outer charge compensation within the polymeric multilayer network. ", "A possible reason here is a high affinity of multiple Cholosens ionic centers to the counterions of the polymeric network in the capsule wall. ", "Unlike rhodamine B, which contains only a single ionic pair in the neutral state, Cholosens has seven or eight of them, which essentially makes each molecule a potential cross-linker, thereby greatly improving the rigidity of the PMC wall and its resistance toward contraction upon heat application.", "\n\nWhile the heat treatment did not affect the loading, it had an impact on the release of Cholosens from PMC. ", "The heated capsules released the drug slower than their intact counterparts, which was also a reason for their lower antimicrobial PDT activity in comparison to the untreated PMC (c.f. ", "discussion later in the text).", "\n\nThe developed Cholosens-loaded \\[DS/PArg\\]~4~ microcapsules and free drug were comparatively studied on eucaryotic cells (human normal and cancerous cells, NHDF and HeLa, respectively) and bacteria (*S. aureus* and *E. coli*); we aimed to determine the cytotoxicities, bacterial toxicities, and anticancer and antimicrobial PDT efficacies of different drug forms.", "\n\nNon-encapsulated Cholosens inhibited the metabolic activity of both human cell lines, which we attributed to its electrostatic binding to the plasma cell membrane. ", "Upon loading of Cholosens in \\[DS/PArg\\]~4~ microcapsules, the drug toxicity was significantly mitigated, thereby providing distinctive evidence of the postulated need for Cholosens encapsulation.", "\n\nWe figured out that capsules mainly deliver the photosensitizer to NHDF and HeLa cells through cellular uptake. ", "The internalization of capsules 4--6 µm in diameter by cancerous cells, including HeLa, has been well-described in literature \\[[@B57-pharmaceutics-12-00610],[@B58-pharmaceutics-12-00610]\\], supporting our flow cytometry data ([Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}a). ", "Both intact and heated PMC loaded with Cholosens displayed no dark toxicity to HeLa cells ([Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}, [Table S6](#app1-pharmaceutics-12-00610){ref-type=\"app\"}), which internalized a significant number of capsules while remaining healthy and attached to the surface of the culture plate. ", "Upon the light irradiation, both encapsulated drug forms showed strong PDT activity in HeLa and NHDF cells, starting from five capsules per cell. ", "Although differences between the efficiencies of encapsulated and free Cholosens upon the light irradiation are statistically significant for both cell lines ([Table S3](#app1-pharmaceutics-12-00610){ref-type=\"app\"}), the viability is negligible for all samples (for five capsules per cell the viability varies within 3--5%, except for the 10% observed for Cholosens-loaded heated capsules in the Hela cell line). ", "We also observed that just a few internalized capsules were enough to eradicate the HeLa cell after light irradiation.", "\n\nNHDF cells poorly tolerated the encapsulated drug forms, showing viability below 80% already at five added capsules per cell. ", "This result indicates the necessity for a more profound understanding of the mechanism of the capsule-cell interactions through in vitro and in vivo studies, while it highlights the importance of cancer-targeting by delivery systems. ", "Besides, further research on the design of PMC for delivery of Cholosens or analogs needs to consider a short lifetime of singlet oxygen (about a few µs or less), so its oxidative effect cannot be extended past a proximate locale. ", "Thus, the cell could either undergo apoptosis or necrosis depending on which crucial organelle or functional molecule (e.g., proteins, DNA, etc.) ", "was affected by the delivered drug. ", "For example, damage in DNA \\[[@B59-pharmaceutics-12-00610],[@B60-pharmaceutics-12-00610],[@B61-pharmaceutics-12-00610]\\] or the mitochondrial membrane \\[[@B62-pharmaceutics-12-00610],[@B63-pharmaceutics-12-00610]\\] leads to apoptosis, while defects induced in the cytoplasmic membrane can trigger the necrotic path of cell inactivation \\[[@B64-pharmaceutics-12-00610]\\]. ", "A deeper understanding of the capsule fate after cell internalization would also help to optimize the design, and thus, the efficacy of PMC as a carrier-system for anticancer PDT drugs.", "\n\nAs for the antimicrobial activity, free Cholosens inhibited the growth of *S. aureus* and *E. coli* without activation by light significantly higher than both encapsulated forms at most of the studied capsule densities and drug concentrations. ([", "Tables S7 and S8](#app1-pharmaceutics-12-00610){ref-type=\"app\"}). ", "By virtue of its cationic nature, Cholosens inhibits microorganisms via electrostatic binding to negatively-charged bacterial membranes. ", "The \\[DS/PArg\\]~4~ composition is supposed to have a positively-charged surface due to the outmost layer made of PArg. ", "Our findings, however, reveal that such capsules often display negative zeta-potential, with its absolute value increasing after thermal treatment. ", "This phenomenon warrants a separate study beyond the scope of the current manuscript. ", "We wanted to mention this aspect only because it one of the likely reasons for the observed difference in dark antimicrobial efficacy that was established for free and encapsulated forms of Cholosens. ", "Besides, the electrostatic interactions between the positively charged capsule surface and the negatively charged bacterial membrane are compromised by the presence of a large number of solvated counterions at the surfaces, which could potentially deter the electrostatic interactions of the large ionic species. ", "Thus, the capsule size, geometry, and surface charge density will play a crucial role in the reported here lesser efficacy of Cholosens-loaded PMC vs. the drug itself.", "\n\nUnlike the cancer cells, bacteria are unable to uptake capsules due to their small size (about a few microns). ", "The current mechanism of action for many antibacterial drugs includes an initial attachment of the oppositely-charged ionic drug to the bacterial surface by electrostatic interaction. ", "Aside from the size disparity, PMC-loaded Cholosens has a much more complex and better-balanced ionic interaction of Cholosens molecules and polymeric layers in the network and/or inside the capsules than the pure drug. ", "Therefore, not only the size of the PMC-loaded Cholosens but the reduced ionic interaction of the loaded capsules with the bacterial surface makes the pure drug more prone to get attached to the bacteria, further providing a desired photodynamic efficacy. ", "The results of our study are entirely consistent with the proposed mechanism of antimicrobial activity of the developed capsules. ", "Both heated and intact capsules loaded with Cholosens displayed the antimicrobial PDT activity upon irradiation with 680 nm light against *S. aureus* and *E. coli*, which increased with increasing the capsule/cell ratio. ", "At most studied capsule densities, intact PMC had a higher inhibition activity than the heated ones, which was likely due to an approximately two-times faster release of Cholosens from the intact capsules compared to their heated counterparts. ", "Lower inhibition level for *E. coli* in comparison with *S. aureus* displayed by the free and encapsulated Cholosens is predictable and consistent with the presence of cell walls in the Gram-negative microorganisms responsible for higher resistance of such bacteria to chemical treatment. ", "Besides, we demonstrated that at specific capsule densities, their antimicrobial PDT activity matches the antimicrobial activity of the free drug.", "\n\nOur study introduces the DS/PArg PMC as an efficient delivery system for the water-soluble PDT drugs. ", "Further development of the encapsulated drug forms would be aimed at the tailoring mechanisms for controlled delivery, e.g., capsule size reduction for efficient tumor targeting via the EPR effect. ", "We believe that PMC produced via consecutive surface self-assembly of complementary biocompatible, naturally-derived polyions will outperform the vast majority of nanomaterials in the treatment of infectious diseases and cancer due to the stable structure and favorable safety profiles.", "\n\nAlexey Ermakov acknowledges the scholarship of the President of the Russian Federation (grant number SP-1488.2019.4) and A\\*STAR Graduate Academy (Singapore) for financial support. ", "The authors thank Saratov Institute of Traumatology and Orthopedics (Saratov, Russia) for providing cultures of *S. aureus* and *E. coli*.", "\n\nThe following are available online at <https://www.mdpi.com/1999-4923/12/7/610/s1>. ", "Figure S1: Fluorescence intensity cross-section profiles of the intact and heated capsules labeled with RhD6G (λ~ex~ = 525 nm, λ~em~ = 548 nm). ", "Figure S2: The absorbance spectrum of Cholosens. ", "Figure S3: Loading of Cholosens in \\[DS/PArg\\]~4~ microcapsules with and without heat treatment (80 °C, 60 min) depending on the capsule concentration. ", "Tables S1--S9: Student's t-test results for [Figure 6](#pharmaceutics-12-00610-f006){ref-type=\"fig\"}, [Figure 7](#pharmaceutics-12-00610-f007){ref-type=\"fig\"}, and [Figure 10](#pharmaceutics-12-00610-f010){ref-type=\"fig\"}. ", "Tables S10 and S11: IC50 values of free and encapsulated forms of Cholosens for HeLa, NHDF, S. aureus, and E. Coli.", "\n\n###### \n\nClick here for additional data file.", "\n\nConceptualization, M.N.A. and S.B.; methodology, D.A.G., D.B.T. and E.A.L.; formal analysis, A.V.E.; investigation, A.V.E., R.A.V. and I.V.B.; validation, O.A.I.; writing---original draft preparation, A.V.E.; writing---review and editing, M.N.A., S.B. and D.A.G.; supervision, M.N.A., D.A.G. and V.J.U. All authors have read and agreed to the published version of the manuscript.", "\n\nThis work is supported by the Ministry of Science and Higher Education of the Russian Federation MEGAGRANT Project \"Theranostics in urologic oncology,\" contract \\#075-15-2019-1927 dd. ", "09.12.2019 (analysis of temperature-induced morphological changes and optimization of loading capsules with model and therapeutic molecules) and RFBR project 19-53-80047 (capsule fabrication and characterization, *in vitro* study of cellular uptake).", "\n\nThe authors declare no conflict of interest.", "\n\n{#pharmaceutics-12-00610-f001}\n\n![(**", "a1**,**a2**) SEM and (**b1**,**b2**) CLSM images of \\[DS/PArg\\]~4~ microcapsules: (**a1**,**b1**) intact; (**a2**,**b2**) after heat treatment at 80 °C for 60 min. ", "The capsules were post-loaded with RhD6G for visualization with CLSM at λ~ex~ = 525 nm, λ~em~ = 548 nm. (**", "c1**,**d1**) and (**c2**,**d2**) AFM images and respective phase contrast of the capsules (**c1**,**c2**) before and (**d1**,**d2**) after heat treatment.](pharmaceutics-12-00610-g002){#pharmaceutics-12-00610-f002}\n\n![", "Loading of Cholosens in \\[DS/PArg\\]~4~ microcapsules with and without heat treatment (80 °C, 60 min) depending on the capsule concentration: (**a**) spectroscopically measured concentration of Cholosens remaining in supernatant after loading; (**b**) calculated amount of Cholosens in pg loaded in a single capsule.](pharmaceutics-12-00610-g003){#pharmaceutics-12-00610-f003}\n\n![", "Loading of Cholosens in \\[DS/PArg\\]~4~ microcapsules with and without heat treatment (80 °C, 60 min) depending on the capsule concentration: comparative loading efficacy for heated vs. intact capsules. ", "The loading efficacies of heated vs. intact PMC were compared using the data on the Cholosens loading in a single capsule displayed in [Figure 3](#pharmaceutics-12-00610-f003){ref-type=\"fig\"}b.](pharmaceutics-12-00610-g004){#pharmaceutics-12-00610-f004}\n\n![", "Cumulative release of Cholosens from 4.5 × 10^8^ \\[DS/PArg\\]~4~ microcapsules intact or treated by elevated temperature upon loading (80 °C, 60 min) in 1 mL of 1 × PBS buffer.](pharmaceutics-12-00610-g005){#pharmaceutics-12-00610-f005}\n\n![", "Interactions of \\[DS/PArg\\]~4~ microcapsules with HeLa cells: (**a**) flow cytometry data on the capsule internalization (10 capsules/cell) showing percentages of cells with at least one capsule (\\* *p* \\< 0.05, intact vs. heated capsules with the same duration of incubation); (**b**) characteristic CLSM image of HeLa cells incubated with heat-treated \\[DS/PArg\\]~4~ microcapsules loaded with Cholosens (three capsules/cell, 24 h, 37 °C). ", "Green color displays the calcein-AM dye metabolized by viable cells (λ~ex~ = 495 nm, λ~em~ = 515 nm), and red color displays Cholosens encapsulated in \\[DS/PArg\\]~4~ microcapsules (λ~ex~ = 685 nm, λ~em~ = 715--780 nm).](pharmaceutics-12-00610-g006){#pharmaceutics-12-00610-f006}\n\n![", "Light and dark viability of HeLa and NHDF cells in the presence of free and encapsulated forms of Cholosens: (**a**) cell viability depending on the number of Cholosens-loaded \\[DS/PArg\\]~4~ microcapsules (intact or heated) in the culture medium; (**b**) comparative effect of the free and encapsulated forms of Cholosens after light irradiation. ", "HeLa/pure and NHDF/pure refer to the cells untreated with any form of Cholosens. ", "Corresponding data on the viability of non-irradiated HeLa and NHDF cells grown without any of encapsulated or free forms of Cholosens were taken as 100%. ", "The respective Student's t-test results are shown in [Tables S2--S6](#app1-pharmaceutics-12-00610){ref-type=\"app\"}. \\* *", "p* \\< 0.05, \\*\\* *p* \\< 0.01 when compared heated vs. intact capsules (**a**), and encapsulated forms of Cholosens vs. free drug (**b**). ", "The respective IC50 values for each drug form are shown in [Table S10](#app1-pharmaceutics-12-00610){ref-type=\"app\"}.](pharmaceutics-12-00610-g007){#pharmaceutics-12-00610-f007}\n\n{#pharmaceutics-12-00610-f008}\n\n![", "CLSM images of calcein-AM-stained HeLa cells (green fluorescence) showing the photodynamic effect of the encapsulated forms of Cholosens (red fluorescence): (**a**,**b**) control cells incubated without PMC; (**c**--**f**) cells incubated with \\[DS/PArg\\]~4~ microcapsules ((**c**,**d**) intact, (**e**,**f**) heated) added at the concentration of three capsules/cell (37 °C, 24 h) before and after light irradiation at 670 nm for 60 s, respectively. ", "White arrows point to the individual cells, which were exposed to light irradiation. ", "The capsules were added in the amount of three capsules/cell.](pharmaceutics-12-00610-g009){#pharmaceutics-12-00610-f009}\n\n{ref-type=\"app\"}. ", "The respective IC50 values for each drug form are shown in [Table S11](#app1-pharmaceutics-12-00610){ref-type=\"app\"}.](pharmaceutics-12-00610-g010){#pharmaceutics-12-00610-f010}\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "100100001\nWhat is -21003 (base 4) in base 5?", "\n-4304\nConvert 122a (base 13) to base 12.", "\n15a3\n31744 (base 8) to base 16\n33e4\nWhat is 20553 (base 8) in base 13?", "\n3b81\n-1712 (base 9) to base 13\n-797\n12030 (base 4) to base 8\n614\n4130 (base 6) to base 8\n1626\nWhat is 17bb6 (base 15) in base 8?", "\n226140\n289a (base 16) to base 9\n15228\nConvert 20202 (base 7) to base 9.", "\n6646\n-27109 (base 11) to base 5\n-2214404\n-240 (base 15) to base 10\n-510\n17470 (base 8) to base 6\n101000\nWhat is 101110101001 (base 2) in base 9?", "\n4076\nConvert 65541 (base 7) to base 2.", "\n100000000001011\n23e (base 15) to base 5\n4014\nWhat is 66a (base 16) in base 9?", "\n2224\nWhat is 2002133 (base 4) in base 3?", "\n102110022\nConvert -112635 (base 7) to base 11.", "\n-14207\nWhat is -111100101 (base 2) in base 4?", "\n-13211\nWhat is 315 (base 8) in base 12?", "\n151\nConvert -2123321 (base 4) to base 3.", "\n-111200112\nWhat is 8680 (base 9) in base 11?", "\n488a\n-16550 (base 8) to base 6\n-54504\n-24554 (base 6) to base 2\n-111001010110\nConvert -146b (base 16) to base 12.", "\n-3037\n-100011011010111 (base 2) to base 9\n-26780\nConvert 36b0 (base 13) to base 9.", "\n11558\nWhat is -301 (base 6) in base 4?", "\n-1231\n-2836 (base 9) to base 7\n-6144\nWhat is 444 (base 8) in base 14?", "\n16c\nWhat is -351 (base 15) in base 16?", "\n-2ef\nWhat is 779 (base 10) in base 15?", "\n36e\nConvert 434213 (base 6) to base 3.", "\n1211022000\nWhat is 5649 (base 10) in base 13?", "\n2757\n31d (base 16) to base 5\n11142\nConvert 10110100000 (base 2) to base 16.", "\n5a0\n-21 (base 16) to base 12\n-29\nWhat is -131203 (base 4) in base 2?", "\n-11101100011\nConvert 17282 (base 12) to base 13.", "\n12173\nConvert -d42 (base 15) to base 5.", "\n-43422\n100100111101 (base 2) to base 6\n14541\nWhat is -10001010101001 (base 2) in base 9?", "\n-13148\nConvert 26c (base 13) to base 4.", "\n12230\n-b42 (base 12) to base 10\n-1634\nConvert -501 (base 13) to base 4.", "\n-31032\nWhat is -29a (base 15) in base 4?", "\n-21103\nWhat is -422 (base 9) in base 11?", "\n-293\nWhat is 3ef (base 16) in base 8?", "\n1757\n-11a4 (base 11) to base 6\n-11130\nConvert 13453 (base 8) to base 6.", "\n43243\n613 (base 15) to base 5\n20433\nWhat is 1854 (base 9) in base 12?", "\n9aa\nWhat is -636 (base 7) in base 16?", "\n-141\n-2220232 (base 4) to base 16\n-2a2e\nWhat is -3619 (base 13) in base 16?", "\n-1dcb\nWhat is 653 (base 15) in base 5?", "\n21203\n-110040 (base 5) to base 3\n-12011122\nConvert -10010100 (base 2) to base 3.", "\n-12111\n-3d5 (base 15) to base 9\n-1172\nConvert -f3 (base 16) to base 13.", "\n-159\nWhat is 2109 (base 12) in base 6?", "\n24413\n181 (base 13) to base 11\n22a\nc91 (base 14) to base 9\n3354\nWhat is 1606 (base 10) in base 15?", "\n721\n-2004 (base 7) to base 5\n-10230\n5ab (base 16) to base 5\n21301\nConvert -269 (base 14) to base 15.", "\n-225\n-111000001111 (base 2) to base 6\n-24355\nConvert 142331 (base 7) to base 13.", "\nc545\nWhat is -26462 (base 8) in base 7?", "\n-45506\nConvert 200 (base 9) to base 16.", "\na2\n20210012 (base 3) to base 10\n4946\n26 (base 14) to base 6\n54\nConvert -2a381 (base 12) to base 9.", "\n-100277\n-132003 (base 5) to base 2\n-1010010000101\nConvert -24d4 (base 14) to base 5.", "\n-201313\n-2840 (base 11) to base 13\n-1898\nConvert -326 (base 16) to base 3.", "\n-1002212\nConvert -7b7 (base 14) to base 11.", "\n-1174\nConvert 114525 (base 7) to base 8.", "\n50554\nWhat is -4016 (base 8) in base 6?", "\n-13314\nConvert 1266 (base 14) to base 7.", "\n12256\n110330 (base 4) to base 12\n938\nWhat is 1cb (base 13) in base 8?", "\n520\nConvert -114636 (base 7) to base 4.", "\n-11012211\nWhat is -21d (base 15) in base 11?", "\n-3a5\nConvert -7f4b (base 16) to base 5.", "\n-2020322\nConvert 7fb (base 16) to base 10.", "\n2043\n-1110 (base 11) to base 3\n-2000012\nConvert -995 (base 15) to base 6.", "\n-14005\n19626 (base 11) to base 14\n9d94\n-768 (base 9) to base 11\n-522\nConvert 22b1 (base 14) to base 10.", "\n6035\nWhat is 110100101001 (base 2) in base 14?", "\n1329\nConvert -3012013 (base 4) to base 8.", "\n-30607\nWhat is 23334 (base 6) in base 10?", "\n3370\n7bd (base 15) to base 10\n1753\nWhat is 342 (base 6) in base 9?", "\n158\nConvert -6763 (base 10) to base 8.", "\n-15153\na2 (base 16) to base 11\n138\n-17061 (base 8) to base 14\n-2b61\n5700 (base 8) to base 15\nd58\nConvert 102000020 (base 3) to base 14.", "\n2cd3\nConvert 22764 (base 9) to base 8.", "\n35545\nWhat is -4100 (base 5) in base 4?", "\n-20031\n-121 (base 6) to base 13\n-3a\nWhat is -2110 (base 7) in base 4?", "\n-23212\n-25037 (base 10) to base 9\n-37308\nWhat is -13303 (base 4) in base 16?", "\n-1f3\n76a (base 13) to base 15\n59b\nWhat is -101121222 (base 3) in base 15?", "\n-2468\nWhat is -1441 (base 6) in base 13?", "\n-238\nWhat is 21220120 (base 3) in base 11?", "\n4372\nConvert 533 (base 12) to base 8.", "\n1367\n-3f0 (base 16) to base 8\n-1760\n-439e (base 15) to base 3\n-201122112\n831 (base 10) to base 12\n593\nConvert 242a (base 14) to base 8.", "\n14246\n1111110011001 (base 2) to base 13\n38b3\n-309 (base 13) to base 11\n-42a\nWhat is -8142 (base 12) in base 15?", "\n-4248\nWhat is 3665 (base 7) in base 4?", "\n111122\nConvert -126113 (base 9) to base 2.", "\n-10010101101011110\nWhat is -a33 (base 13) in base 11?", "\n-1335\nConvert -823 (base 9) to base 10.", "\n-669\nConvert 1f1 (base 16) to base 14.", "\n277\n1565 (base 7) to base 5\n10020\nWhat is 244333 (base 5) in base 3?", "\n110211001\n-21102 (base 3) to base 14\n-104\nWhat is -40262 (base 8) in base 5?", "\n-1012222\n97d (base 16) to base 3\n10022222\nWhat is 131001 (base 4) in base 10?", "\n1857\nWhat is 42123 (base 7) in base 10?", "\n10356\nWhat is -1222123 (base 4) in base 3?", "\n-100100021\n-20550 (base 9) to base 13\n-6240\n-5665 (base 7) to base 6\n-13304\nWhat is -1296 (base 10) in base 2?", "\n-10100010000\nConvert -32321 (base 4) to base 9.", "\n-1268\nWhat is 456 (base 14) in base 15?", "\n3c5\n-2530 (base 6) to base 8\n-1166\n170462 (base 8) to base 13\n22149\nConvert -9c8 (base 15) to base 11.", "\n-1732\nConvert 15602 (base 10) to base 16.", "\n3cf2\nWhat is -c8 (base 14) in base 7?", "\n-341\nWhat is -2194 (base 14) in base 11?", "\n-4406\nWhat is -439 (base 10) in base 6?", "\n-2011\nWhat is -10010 (base 3) in base 12?", "\n-70\nWhat is 8608 (base 9) in base 10?", "\n6326\nConvert b83 (base 12) to base 5.", "\n23213\nWhat is -42411 (base 5) in base 10?", "\n-2856\nConvert 66 (base 15) to base 10.", "\n96\n-1645 (base 9) to base 11\n-a42\n185 (base 9) to base 2\n10011110\nConvert 1241321 (base 5) to base 3.", "\n1020201121\nConvert 249 (base 10) to base 15.", "\n119\nWhat is 592 (base 15) in base 6?", "\n5502\nConvert 156 (base 7) to base 15.", "\n60\nConvert -297 (base 14) to base 13.", "\n-315\nConvert -1788 (base 9) to base 8.", "\n-2540\nWhat is 234 (base 7) in base 12?", "\na3\nConvert 182 (base 13) to base 7.", "\n542\nConvert -50510 (base 7) to base 4.", "\n-2333201\nWhat is 322 (base 14) in base 3?", "\n211220\nConvert 12210001 (base 3) to base 2.", "\n1000001110101\nConvert -3e1b (base 15) to base 3.", "\n-200020122\nWhat is -101000021 (base 3) in base 13?", "\n-3424\n-1230220 (base 4) to base 3\n-100112111\n1173 (base 8) to base 9\n775\nWhat is 101120 (base 6) in base 11?", "\n604a\nConvert 9163 (base 13) to base 4.", "\n10320313\nConvert -146 (base 9) to base 7.", "\n-234\nWhat is a42 (base 15) in base 11?", "\n1812\nConvert -451 (base 11) to base 3.", "\n-202000\nWhat is -1493 (base 12) in base 16?", "\n-96f\n1220002120 (base 3) to base 15\nb083\nWhat is -80a8 (base 12) in base 4?", "\n-3122000\n8160 (base 10) to base 3\n102012020\nWhat is -136 (base 16) in base 12?", "\n-21a\nConvert -3dd (base 15) to base 2.", "\n-1101110011\nConvert 27d (base 15) to base 14.", "\n2c8\nConvert -417 (base 9) to base 6.", "\n-1324\nWhat is -1002110 (base 3) in base 12?", "\n-563\nWhat is -511204 (base 7) in base 13?", "\n-30712\n597 (base 14) to base 16\n459\n-21a9 (base 11) to base 14\n-10b4\nWhat is 1101342 (base 5) in base 15?", "\n594c\n673 (base 9) to base 11\n462\nWhat is 1001001 (base 3) in base 11?", "\n629\nConvert 7b4 (base 13) to base 8.", "\n2462\nWhat is 415 (base 8) in base 7?", "\n533\n-1a7 (base 11) to base 3\n-22211\nWhat is 453201 (base 6) in base 12?", "\n1a201\n-11d (base 15) to base 5\n-2003\nWhat is -2644 (base 14) in base 13?", "\n-30a3\n-973 (base 13) to base 8\n-3117\nConvert 22020220 (base 3) to base 5.", "\n143033\nConvert -18da (base 15) to base 3.", "\n-21101021\nConvert 22c6 (base 16) to base 12.", "\n519a\n383 (base 9) to base 12\n226\nWhat is 121442 (base 6) in base 12?", "\n6282\nConvert -201043 (base 6) to base 10.", "\n-15795\n4a7 (base 12) to base 9\n861\nWhat is 1525 (base 12) in base 11?", "\n1952\n-2734 (base 10) to base 11\n-2066\n-1229 (base 13) to base 16\n-a0a\nWhat is 2266 (base 7) in base 14?", "\n436\nWhat is 2cb (base 14) in base 9?", "\n704\n-bbb (base 12) to base 5\n-23402\nConvert 1101044 (base 5) to base 12.", "\nab2b\nConvert -db (base 16) to base 6.", "\n-1003\nConvert 12123 (base 4) to base 5.", "\n3121\nConvert -2443 (base 13) to base 10.", "\n-5125\nConvert 34113 (base 7) t" ]

{ "pile_set_name": "DM Mathematics" }

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[ "Trends—March 2011\n\nTexas Holds ‘em, Amazon Folds\n\nIn 2005, Amazon.com announced plans to build a new distribution center in Irving, Texas, near the Dallas/Fort Worth International Airport. ", "The city council cleared the way for the facility by approving an economic development incentive package that provided tax rebates to the company for six years, with options to extend the agreement another decade.", "\n\nThe arrangement wasn’t harmonious for long. ", "In fact, Texas Comptroller Susan Combs and her office have been after the e-commerce company since 2008 to pay uncollected taxes on transactions in the state. ", "The problem is that neither party can agree on what constitutes a physical distribution presence— and, therefore, whether Amazon is liable for payments past due, plus penalties and interest, from 2005 through 2009.", "\n\nAmazon has run into problems with states and sales tax before. ", "The company does all of its business through the U.S. Postal Service, with physical properties in Kansas, Kentucky, North Dakota, and Washington, according to Aaron Kelly, an attorney with Scottsdale, Ariz.-based The Kelly Law Firm. ", "Amazon only pays sales taxes in these locations— as well as in New York, which passed a law in 2008 holding out-of-state sellers compliant.", "\n\nThe company believes it is compliant with state laws, and that its DCs, operating under a separate subsidiary, should not be required to pay sales taxes. ", "Texas estimates that it loses $600 million each year from untaxed online sales— a figure that far eclipses what Amazon owes.", "\n\nIn September 2010, Texas asserted its position and asked Amazon to remit $269 million. ", "Four months later, the e-tailer sued the state’s comptroller to release audit information regarding the payment. ", "On Feb. 10, 2011, Amazon announced it was closing its Irving facility.", "\n\nResponding to a request for comment, Mary Osako, a spokesperson for Amazon, shared an internal email that was communicated to employees:\n\n“Because of the unfavorable regulatory climate created by the Texas Comptroller’s office, we are making the difficult decision to close our Dallas/Ft. ", "Worth fulfillment center on April 12, 2011. ", "Despite much hard work and the support of other Texas officials, we’ve been unable to come to a resolution with the Texas Comptroller’s office,” wrote Dave Clark, vice president, North American operations. “", "Closing this fulfillment center is clearly not our preferred outcome. ", "We were previously planning to build additional facilities and expand in Texas, bringing more than 1,000 new jobs and tens of millions of investment dollars to the state, and we regret the need to reverse course.”", "\n\nBusiness Magnet or Malaise?", "\n\nAmazon isn’t the only party that regrets the recent turn of events. ", "The state of Texas is losing one of its biggest economic development endorsements.", "\n\n“We’ll work with lawmakers to make sure we can avoid this outcome in the future,” says Katherine Cesinger, press secretary for Texas Governor Rick Perry’s office. “", "The Governor hoped to see a different outcome. ", "He’s not sure he would have made the same decision if he were in that position.", "\n\n“That said, this is the purview of the Comptroller. ", "If there is any uncertainty regarding the law in Texas, Governor Perry is committed to seeing that it changes to ensure we can strengthen the reliability of our tax system for employers who not only bring jobs to our state, but also help create wealth in our state,” she adds.", "\n\nCesinger’s comments are rife with political nuance, but the reaction from the Governor’s cabinet was visceral. ", "There were hints, but Amazon’s swift decision came as a surprise.", "\n\nOver the past few years, Governor Perry’s office has encouraged Amazon to expand its business in Texas. ", "The state was aware of the company’s ongoing conversations with the Comptroller’s office. ", "But clearly, no one was ever on the same page. ", "And now, as consumer and business reactions saturate the media, opinions are scattering.", "\n\nSmall businesses are lambasting Amazon for not playing by the same rules that others have to abide by. ", "For some, it’s a sad indictment of brick-and-mortar retailing, where customer service and brand affinity have been eclipsed by online buying selectivity and economy. ", "Smaller companies now feel increasing pressure to shift online, and make their presence and profit via e-commerce channels.", "\n\nSome blogosphere commentators have argued that where or how a sale is processed is irrelevant. ", "Instead, the buyer’s state should serve as the taxing entity. ", "Amazon is killing jobs, they say, because it doesn’t want to fulfill an obligation. ", "States such as Texas would likely agree. ", "But it’s easy to think and say one thing, then shop online and pay nothing— in terms of sales tax.", "\n\nThe current impasse raises other questions. ", "If the state neglects going after businesses for unpaid revenue during an economic downturn— when education and other social services are being cut— wouldn’t the public also raise the alarm? ", "And if Amazon files a lawsuit and feels confident in its case, why suddenly pack up and move? ", "The company’s modus operandi is becoming increasingly familiar, and it has no qualms about absorbing the direct loss of closing a distribution center and the higher cost of in-state fulfillment from out of state.", "\n\nLine in the Dust\n\nContrarians see Amazon’s posturing as a natural order of selection. ", "The simple fact is that Texas consumers don’t walk into an Irving fulfillment center and place orders. ", "There is a definitive line drawn in the dust between where products are purchased and where SKUs are accumulated and distributed.", "\n\nAmazon’s business model is predicated on serving smaller businesses that leverage the company’s marketing and distribution clout to amplify their own sales operations. ", "What began as an online book brokerage is now a multi-billion-dollar global consumer goods fulfillment conglomerate that empowers everything it touches— apart from Texas.", "\n\nThe bigger argument against the state is that competition for economic development investment will always favor business and consumers. ", "If Texas isn’t willing to let sales taxes slide, another state will use abatements as a lure.", "\n\nState governments are flummoxed by in-state business and sales that don’t deliver revenue or compete with homegrown companies that directly cater to consumers and pay sales tax. ", "That’s certainly the case with Amazon and Texas.", "\n\n“In addition to there not being any retail sales tax collected to benefit either the City of Irving or State of Texas, there is also very little ad valorem property tax on business personal property to the city,” says Jeff Mues, director of marketing and communications, Greater Irving-Las Colinas Chamber of Commerce. “", "The bulk of Amazon’s inventory qualifies for ‘freeport’ exemption. ", "Most of all, in-state fulfillment centers in Texas qualify for the same benefit and pay very little business personal property tax on their inventory to their respective cities.”", "\n\nThe crux of the Amazon vs. Texas debate lies in defining “physical presence” and whether a DC or fulfillment center falls within these parameters.", "\n\nAmazon’s Quill to Stand On\n\nThe crux of the problem lies in defining physical presence, and whether a DC or fulfillment center falls within these parameters. ", "States such as Texas contend that any center where goods are stockpiled is a principal part of the order-processing cycle— regardless of where sales and orders are consummated.", "\n\nCurrent legalese adds to the ambiguity. ", "If a distribution center creates nexus— casual connection— it should be considered “physical presence.”", "\n\nThe Texas Comptroller’s office argues that federal law allows states to impose sales tax obligations on out-of-state retailers maintaining a “physical presence” in their state— defined as anything from a store, warehouse, or distribution center to a sales agent or delivery truck.", "\n\nIn the debate building around Amazon and Texas, legal observers cite the 1992 U.S. Supreme Court ruling Quill Corp. v. North Dakota. ", "The state charged that Quill, an out-of-state mail-order office equipment retailer, should pay a use tax on merchandise used within the state— even though the company had no physical presence in North Dakota.", "\n\nQuill’s only contact with the state came through mailing promotional catalogs to recipients in North Dakota, shipping orders via common carriers, and owning a few floppy disks in the state. ", "The Supreme Court ruled eight to one in the company’s favor.", "\n\nKelly agrees that Quill Corp. v. North Dakota is the closest and most authoritative case comparable to Amazon’s predicament. ", "But he believes we could be looking at a new legal ruling.", "\n\n“That case only sets the test for when a state may tax a business— the courts will have to decide whether a business such as Amazon meets the test for taxation,” he says. “", "It’s likely that at some point an Amazon case, against Texas or another state, will be appealed by one of the parties all the way to the Supreme Court and set a precedent countrywide.”", "\n\nAll along, Amazon has contended that its Irving operation is a fulfillment facility, not a distribution warehouse— suggesting that inventory is moving, not static, and therefore part of the order cycle. ", "It remains to be seen whether this position is defensible.", "\n\nClearing the Dust\n\nThe Texas and Amazon quarrel raises important issues that will likely linger. ", "For the time being, the immediate question is whether there’s a common ground where states and e-commerce businesses can come to an agreement.", "\n\n“The best thing that a state can do is to understand that more taxation on any business, whether it be in-state or out-of-state, is detrimental to its economy,” says Kelly. “", "Even if Texas wins its fight against Amazon and determines that it is permissible to tax Amazon whenever it has a physical presence in Texas, what does that accomplish? ", "All it does is ensure that the price of goods for Texans rises.", "\n\n“If Amazon simply stops doing business with Texans altogether due to the increased cost, then it won’t be an issue of higher prices through Amazon, but of completely removing the most competitive, price-lowering business in the world from the Texas market,” he adds.", "\n\nIdeally, there shouldn’t even be a court case, Kelly says. ", "The legislature should simply decide on its own that taxing out-of-state businesses doesn’t make sense.", "\n\nBut common business sense and government legislating don’t have a good record. ", "Michigan enterprises know this well. ", "In 2007, businesses went to bat against the state over a bill that charged an additional six percent on warehousing and logistics activities. ", "The legislation was eventually repealed thanks to private sector input and outrage.", "\n\nAs the Michigan and Texas examples suggest, a major communication gap often separates the public and private sectors, especially in terms of planning. ", "Then when trouble begins to stir, the parties are incapable of negotiating resolutions until after the fact.", "\n\nWith regards to the Amazon situation, many insiders remain incredulous that sales tax wrinkles weren’t ironed out from the beginning and that the Governor’s office and the state Comptroller weren’t communicating.", "\n\nIn the court of public opinion, Texas will bear the blame for Amazon’s decision. ", "The company says it is defending online retailers from the onslaught of states desperate for new revenue streams. ", "But when faced with legal action, it simply moves elsewhere. ", "Whether other states will take a hard position, follow New York’s example and rewrite the books to account for e-commerce, or use sales tax exemptions as a business development incentive, remains to be seen. ", "Online resellers, emboldened by Amazon’s gambit, may force the issue.", "\n\nAs the dust settles, it’s unlikely we’ve heard the last on this Texas showdown.", "\n\nRed, White, Blue… and Green\n\nThe U.S. General Services Administration (GSA) launched the GreenGov Supply Chain Partnership and Small Business Pilot, a voluntary collaboration between the federal government and its suppliers to create a greener, more efficient supply chain.", "\n\nThe initiative aims to promote clean energy and cut waste and pollution by using greenhouse gas emissions as a measurement. ", "Federal suppliers in the partnership agree to voluntarily measure and report their organization’s greenhouse gas emissions. ", "Participating companies will share their experiences to help GSA develop a phased, incentive-based approach to developing contracting advantages for companies that track and disclose their greenhouse gas emissions.", "\n\nThe Small Business Pilot program will explore the benefits and challenges of measuring greenhouse gas emissions among smaller companies.", "\n\n“The federal government is the largest energy consumer in the U.S. economy and purchases more than $500 billion in goods and services annually,” says White House Council on Environmental Quality Chair Nancy Sutley. “", "It is our responsibility to lead by example to improve efficiency, eliminate waste, and promote clean energy in our supply chain.”", "\n\nOn the Dock\n\nCrossdocking is on the rise, according to Saddle Creek Corporation’s 2011 Crossdocking Trends Report. ", "More companies are finding value in using the warehouse tactic to remove costs from the system, manage inventory levels, increase efficiencies, and accommodate unpredictable customer demand, according to the 3PL’s research.", "\n\nDuring the past three years, crossdocking has increased significantly. ", "More than two-thirds of survey respondents (68.5 percent) currently crossdock— up from 52 percent in 2008.", "\n\nCompanies identify crossdocking as a viable strategy for adapting to challenging market conditions. ", "Of those who have been employing the tactic for four or more years, 40 percent report that challenging economic circumstances have prompted them to increase crossdocking either somewhat or substantially (see chart below, right).", "\n\nThe biggest benefits of crossdocking are improving service levels (38 percent), reducing transportation costs (32 percent) and consolidating shipments to destination (32 percent), according to the report. ", "And more companies are recognizing the value of outsourcing this distribution function. ", "A significantly larger percentage of crossdock practitioners (40 percent) use a 3PL either exclusively or in addition to in-house resources than in 2008, when just 32 percent of respondents who crossdocked reported using a third party.", "\n\nSaddle Creek’s report is based on survey responses from more than 200 logistics decision-makers. ", "Respondents represent a cross-section of logistics, with backgrounds in warehousing, distribution, and transportation.", "\n\nRegulating Food Safety\n\nMuch has changed in the food supply chain since the government passed the Federal Food, Drug, and Cosmetic Act of 1938— its last major food safety legislation. ", "The Food and Drug Administration’s (FDA) Food Safety Modernization Act (FSMA), which was passed in January 2011, was a long time coming.", "\n\nDuring recent years, a rash of e. coli, salmonella, salmonellosis, botulism, and listeria contaminations have indicted familiar brands ranging from Taco Bell to Nestle Toll House. ", "Isolating and controlling viral outbreaks, identifying rogue sources, and recalling tainted products are major challenges for the food supply chain and the FDA. ", "Building a regulatory architecture that creates and communicates standards, then enforces compliance across the industry— measures aimed at immunizing the food supply chain from costly epidemics— is equally important.", "\n\nThe fact that this law takes a more preventive-control standard to make food safer, versus having the FDA react to outbreaks, is an important improvement.—Robert Guenther, United Fresh Produce Association\n\nTo gain perspective on how the new legislation will impact the food industry, Inbound Logistics caught up with Robert L. Guenther, senior vice president, public policy for United Fresh Produce Association, a leading trade association committed to driving the growth and success of produce companies.", "\n\nIL: What aspects of the food safety legislation needed to be modernized?", "\n\nGuenther: The FSMA was largely written to instruct the FDA on how to do a better job. ", "The law needed to be updated to reflect modern food handling and growing practices. ", "In particular, the fact that this law takes a more preventive-control standard to make food safer, versus having the FDA react to outbreaks, is an important improvement.", "\n\nIL: One media account of the bill reports that some change is better than none. ", "Do you agree?", "\n\nGuenther: Yes. ", "Consumer confidence about food safety was waning over the past several years, and something had to be done to address the situation. ", "Of course, the devil is in the details. ", "How the FDA implements and enforces this law will be the test of whether our policy makers made the right decision to reform food safety laws.", "\n\nIL: How does the law affect shippers?", "\n\nGuenther: Four major points concern shippers. ", "First, the FSMA grants the FDA immediate, mandatory recall authority if a company refuses to voluntarily recall a product that may be adulterated, and consumption of the food will cause illness or death. ", "But companies must get the opportunity to voluntarily recall first.", "\n\nAlso, effective immediately, during an active investigation of a foodborne illness outbreak, the FDA is authorized to direct that a farm identify immediate recipients of the food that is the subject of the investigation.", "\n\nSecond, federal regulations for the safe production of raw fruits and vegetables will be proposed within the next 12 months. ", "The FSMA is relatively silent on the details of the regulations, but does require the produce standards to address growing, harvesting, sorting, packing, and storage operations, through the development of science-based minimum standards related to growing and packaging conditions.", "\n\nThird, foreign growers will be held to the same federal food safety standards as domestic growers, and importers will be held responsible for providing proof.", "\n\nAnd fourth, in addition to publishing regulations for fresh produce food safety, the FSMA requires FDA to issue a notice of proposed rulemaking, within two years, to establish additional recordkeeping requirements for product tracing of foods the FDA defines as ‘high-risk.’", "\n\nIL: Is there a misperception that smaller producers lack the supply chain sophistication and quality control mechanisms used by larger corporations— and therefore ‘need’ increased regulation and inspection?", "\n\nGuenther: The misconception is that small producers cannot afford food safety. ", "But basic food safety practices should be a fundamental business decision for anyone selling to consumers.", "\n\nIL: Smaller producers fear increased regulation will hurt their businesses; large corporations fear a lack of visibility and control among smaller growers will expose their liability when food recalls occur. ", "Is there common ground?", "\n\nGuenther: Yes. ", "United Fresh has supported exemptions, provided there are science- and risk-based factors. ", "We do not want the FDA issuing rules that apply the same for apricot producers as they would to leafy greens farmers. ", "That makes no sense and is a waste of government resources. ", "The federal government needs to focus on commodities that are more susceptible to micro-contamination and develop standards that help alleviate risk of outbreaks.", "\n\nIL: Should the FDA have full recall authority over contaminated foods?", "\n\nGuenther: The FDA has plenty of enforcement tools to adequately restrict the movement of food it deems harmful to consumers. ", "Mandatory recall, which is now in the law, is another tool. ", "But we expect it will not be used very aggressively, as the overwhelming majority of food operations in this country work with the FDA to avert a crisis during a recall situation." ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nHow can I change the location in a map using javascript and google maps?", "\n\nI'm trying to change the center of a map using an each loop for going to different places, however when I execute the code the map does not show all locations instead the map show the first and last location, I will be grateful if you can help me with this problem.", "\nThis is the code:\n\n var a = new google.maps.", "LatLng(8.8013, -74.72538);\r\n var b = new google.maps.", "LatLng(1.0619, -73.2558);\r\n var c = new google.maps.", "LatLng(12.5872, -81.7025);\r\n var d = new google.maps.", "LatLng(3.2719, -73.0877);\r\n\r\n var locations = new Array(a, b, c, d);\r\n var mapProp = {\r\n center: new google.maps.", "LatLng(5.0619, -70.2558),\r\n zoom: 8,\r\n mapTypeId: google.maps.", "MapTypeId.", "ROADMAP\r\n };\r\n var map = new google.maps.", "Map(document.getElementById(\"googleMap\"), mapProp);\r\n\r\n function initialize() {\r\n goToLocations(locations);\r\n }\r\n google.maps.event.addDomListener(window, 'load', initialize); \r\n\r\n function goToLocations(locations) {\r\n $.each(locations, function (index, location) {\r\n goToLocation(location);\r\n });\r\n }\r\n\r\n function goToLocation(location) {\r\n // here I can not see all locations \r\n window.setTimeout(map.setCenter(location), 5000); \r\n }\n<html> \r\n\r\n <body>\r\n \r\n <script src=\"http://maps.google.com/maps/api/js?sensor=true\" type=\"text/javascript\"> </script>\r\n <script src=\"https://code.jquery.com/jquery-1.10.2.js\"></script>\r\n \r\n <h1>Map that go to different locations </h1>\r\n <div id=\"googleMap\" style=\"width: 500px; height: 380px\"></div>\r\n \r\n </body>\r\n \r\n</html>\n\nA:\n\nYour function is working fine and it is actually showing all the cities you have on your array. ", "However, we are not able to see it. ", "The function is exectuted so fast that we are only able to see the first and the last one.", "\nTry to put a Timeout inside the $.each function and it will work:\n$.each(locations, function (index, location) {\n window.setTimeout(function(){ \n goToLocation(location);\n }, 1000);\n});\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Q:\n\nEuler Characteristic for relative cell-complex, show that $\\chi(A)-\\chi(X)+\\chi(X,A)=0$.\n\nLet $X$ be a finite cell-complex and $A\\subset X$ be a sub-cell complex. ", "\nThe post has been answered here: Euler characteristic for CW complexes asked about the proof for $$\\chi(A)-\\chi(X)+\\chi(X/A)=1.$$ This question induces a similar question about what $\\chi(A)-\\chi(X)+\\chi(X,A)$ is. ", "\nI know that Euler characteristic is the alternating sum of the number of cells in each dimension. ", "That is $$\\chi(A)=c_{0}(A)-c_{1}(A)+c_{2}(A)-\\cdots+(-1)^nc_{n}(A)$$ $$\\chi(X)=c_{0}(X)-c_{1}(X)+c_{2}(X)-\\cdots+(-1)^nc_{n}(X).$$\nAlso, we know that the cellular chain complex of $(X,A)$ is given by the quotient groups $$C_{k}(X,A)=C_{k}(X)/C_{k}(A)=\\mathbb{Z}^{\\{\\#\\ \\text{of}\\ k-\\text{cells in}\\ X\\ \\text{but not in}\\ A\\}}$$ Does this imply that $c_{k}(X,A)=c_{k}(X)-c_{k}(A)$?", "\nIf so, then $\\chi(A)-\\chi(X)+\\chi(X,A)=0$... but this seems not correct... I actually expect it to equal $1$.\nIs my proof correct or I am missing something? ", "Thank you!", "\n\nA:\n\nThe confusion you're having ultimately comes from the fact that $H_*(X,A;\\Bbb Z)$ is not isomorphic to $H_*(X/A;\\Bbb Z)$, but rather to the reduced homology $\\tilde H_*(X/A)$. The former is larger by exactly a copy of $\\Bbb Z$ in degree zero, so $$\\chi(X/A) = \\chi(X,A) + 1.$$\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Hershel Dennis\n\nHershel Dennis Jr. (born July 12, 1984) is a former American football running back. ", "He played college football as a student athlete at the University of Southern California. ", " During his six-year career, the Trojans went 70–8 making Dennis the first player to play on six Pacific-10 Championship squads and the player with the most wins in college football history. ", " His nickname since childhood is \"Patch\"\n\nHigh school career\nDennis prepped at Long Beach Polytechnic High School and was a part of the \"Long Beach Poly Five\", five highly recruited players including Manuel Wright and current NFL players Marcedes Lewis, Darnell Bing and Winston Justice. ", " As of May 2007, Dennis still held the career rushing and touchdown marks at Long Beach Poly, as well as the single season rushing record. ", "Dennis made his final decision between USC and the University of Oregon; his father wanted him to go to Oregon, but he chose USC out of respect for his mother, Rose Teofilo, who wanted him closer to home.", "\n\nHe was also on Poly's track team, with bests of 10.7 seconds in the 100 meters, 22.3 seconds in the 200 meters, 6.75 meters in the long jump and 1.98 meters in the high jump, and basketball team. ", "Current Trojans Vincent Joseph, Travon Patterson and Alfred Rowe also prepped at Poly.", "\n\nCollege career\nAs a freshman in the 2002 season, Dennis was a reserve behind a stable of experienced seniors including running backs Justin Fargas and Sultan McCullough as well as fullback/tailbacks Malaefou MacKenzie and Sunny Byrd; however, he did see play time in all 13 games, highlighted by a 38-yard touchdown run against rival UCLA. ", " In 2003, he was the starting tailback in all 13 games over Reggie Bush and LenDale White.", "\n\nHowever, Dennis lost the starting spot for the 2004 season, having been suspended from the first two games due to a resulting criminal investigation (that later cleared him of any wrongdoing) and violating team rules. ", " This allowed the tandem of White and Bush to emerge and relegate Dennis to the role of reserve for most of the season. ", " Dennis did appear in a total of 9 games in the 2004 season, but was beset by a serious, season-ending torn knee ligament in practices before the 2005 Orange Bowl. ", " During this period, Dennis considered transferring to another program, but his mother pressured him to stay and graduate as he is the only one of Teofilo’s children to have attended a university.", "\n\nThe same torn knee ligament kept Dennis from participating in the entire 2005 season, having already used his redshirt year he lost a year of eligibility. ", " Going into the 2006 season, Dennis was the leading career rusher among current student athletes. ", " Unfortunately, in spring practice Dennis was again beset by season-ending knee injury, causing him to entirely miss a second year in a row. ", " While this would have eliminated his final year of eligibility, Dennis and USC applied to the NCAA for a sixth year of eligibility, given the extreme circumstances. ", " Dennis returned to full-contact practice in the 2007 spring practice In May 2007, Dennis graduated with his bachelor's degree in sociology. ", " The NCAA granted his application for a sixth year of eligibility in June 2007.", "\n\nDuring his final game, the 2008 Rose Bowl game against Illinois, Dennis rushed for a touchdown, his first of the season and first since 2004, that led teammates to rush the goal from the sidelines in celebration (and an excessive celebration penalty).", "\n\nAt the end of his six-year USC career, Dennis became the first player to play on six Pac-10 Championship squads. ", "In addition to conference accolades, Dennis also made central contributions to teams that finished in the BCS top 5 during 6 consecutive seasons (2002–07). ", " With 70 wins (and only 8 losses) in that span, Hershel Dennis is the \"winningest player\" in College Football history.", "\n\nProfessional career\nDennis signed to play with the Sioux Falls Storm as a running back in the Indoor Football League (IFL) during the 2011 season.", "\n\nPersonal\nHis father, Hershel Dennis, Sr., ", "played running back for North Carolina A&T; his mother, who he calls \"Mama Rose\", would regularly attend her son's practices and is featured in a tattoo on his arm. ", " Dennis has his initials tattooed on the back of his arms above the elbow (left: \"H\", right: \"D\"). ", " He has 3 kids Zion, Zirie & Zekiel . ", "Dennis studied sociology as a RS Senior at University of Southern California.", "\n\nIn addition to three high school championship rings, Dennis ended his college career with thirteen championship rings: six Pac-10 champion rings, two Orange Bowl champion rings, two Rose Bowl Champion rings, and two national championship rings.", "\n\nHe is the cousin of Canadian Football League defensive lineman DeQuin Evans, and had been instrumental in obtaining permission for his cousin to sit in on classes at USC, enabling Evans to enroll in college and put his troubled youth behind him via a career in sports.", "\n\nReferences\n\nExternal links\nUSC Bio\n\nCategory:1984 births\nCategory:Living people\nCategory:American football running backs\nCategory:USC Trojans football players\nCategory:American people of Samoan descent\nCategory:Samoan players of American football\nCategory:Players of American football from California\nCategory:Sioux Falls Storm players\nCategory:African-American players of American football" ]

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[ "The thigh adductor squeeze test: 45° of hip flexion as the optimal test position for eliciting adductor muscle activity and maximum pressure values.", "\nThe thigh adductor squeeze test is commonly used in the diagnosis of groin injuries. ", "Currently no reports exist in the published literature which, detail the level of activation of the adductor musculature during the test as well as concomitant pressure values. ", "Thus the aim of the present study was to investigate adductor muscle activity and concomitant pressure values during the performance of the thigh adductor squeeze test at 0°, 45°, and 90° of hip flexion. ", "Eighteen Gaelic games athletes without any history of groin injury participated. ", "Each participant performed 3 repetitions of the thigh adductor squeeze test in the three positions of 0°, 45°, and 90° of hip flexion. ", "Adductor musculature surface electromyographic activity (bilateral) and pressure values quantified using a commercially available sphygmomanometer were recorded for each test. ", "The greatest pressure values were observed in the 45° of hip flexion test position (0°: 202.50 ± 57.28 mmHg; 45°: 236.76 ± 47.29 mmHg; 90°: 186.11 ± 44.01 mmHg; P < 0.05). ", "Similarly, the greatest amount of adductor muscle activity was observed in the 45° of hip flexion test position (P < 0.05). ", "The combined results of the present study suggest that the 45° of hip flexion test position is the optimal thigh adductor squeeze test position for eliciting adductor muscle activity and maximum pressure values." ]

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[ "Endothelial dysfunction and its role in diabetic vascular disease.", "\nWhen normal endothelial function is shifted to a pathological degree, the foundation is laid for possibly following diseases. ", "This endothelial dysfunction is characterized by a proinflammatory state, reduced vasodilation, and a prothrombotic state. ", "In the continuation this dysfunction is strongly associated cardiovascular morbidity and mortality. ", "Endothelial dysfunction is markedly enhanced in type 2 diabetes providing a major pathophysiological cause for the massively increased cardiovascular risk of diabetic patients. ", "Subsequently future therapeutic approaches for the treatment of diabetic cardiovascular disease should target the dysfunctional endothelium first." ]

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[ "Synthesizers modify sound waves and create unique sounds. ", "Since modular synthesizers allow a user near infinite variations for modifying sound waves, we’ve chosen to focus on a simple, basic system to show how they work.", "\n\nDoepfer A-100 Mini System\n\n1 Power supply The power supply includes the transformer on the outside of the system as well as the circuit board on the inside of the case. ", "The external piece can be disconnected for easy transportation while also using a minimal amount of space inside the case.", "\n\n2 Input Most contemporary modular systems have MIDI, which lets them interface with electronic keyboards, controllers, or computers.", "\n\n3 Bus board The bus board distributes power from the power supply to multiple modules.", "\n\n4 Power cables\n\n5 Modules Almost any combination of modules can be put into the case and mounted to the rails, so long as they fit within the width of the case.", "\n\n6 Patch cables The Eurorack system uses 3.5mm phone connecter leads to connect or “patch” modules together.", "\n\n7 Case Cases are measured vertically in Rack Units (U or RU, where 1U ≈ 1.75” or 133.35mm) and horizontally in Horizontal Pitch units (HP, where 1 HP ≈ 1/5” or 5.08mm). ", "Dieter Doepfer created the “Eurorack” system in the A-100 around 1995, which refers to cases & modules that are 3U tall (about 5.25”) and multiples of 2HP wide.", "\n\n8 Mounting rails The mounting rails have threaded holes that are 1HP apart. ", "This allows the modules to be moved along the rails in any location and then secured to the mounting rail with a screw.", "\n\nOur 3D animated infographics attract thousands of viewers. ", "We'd love to work with you. ", "Let's chat.", "\n\nSound Wave Basics\n\nWave types 1 Sine 2 Triangle 3 Square 4 Sawtooth\n\nAttack, Decay, Sustain, and Release (ADSR) An envelope can be generated around a sound wave to help define how that sound wave acts when initiated. ", "If pressing a keyboard key, the period between when a key is first pressed and when it reaches full volume is called the attack . ", "After the sound reaches full volume, it may decay or lower in volume until it reaches the sustain level, which is held until the key is released. ", "Once the key is released, the release determines how long the sound will fade out until completely gone.", "\n\nFollow Animagraffs: email, twitter, facebook.", "\n\nBasic Types of Modules\n\n1 MIDI interface The MIDI interface module converts digital signals from keyboards, controllers, or computers into analogue signals that the system can use. ", "Pressing a key on a keyboard and then letting go also tells the system when to start or stop the sound; this is referred to as a “gate.”", "\n\n2 Voltage control oscillator (VCO) Oscillators generate sound waves. ", "The higher the voltage, the higher the note will be; most oscillators will increase one octave for each additional volt of power. ", "Most oscillators can produce sawtooth, square, triangle, and sine shaped sound waves.", "\n\n3 Attenuator Attenuators decrease the amplitude of the sound, making it quieter.", "\n\n4 Low pass filter (LPF) Low pass filters allow the lower or bass portions of the sound to “pass” through and block out the higher parts of the sound. ", "The point at which that happens – the cut-off point – is adjustable.", "\n\n5 Voltage controlled amplifier (VCA) Amplifiers increase the amplitude of the sound, making it louder.", "\n\n6 Envelope generator (EG or ADSR) Envelope generators modify the Attack, Decay, Sustain, and Release of the sound wave.", "\n\n7 Low frequency oscillator (LFO) Low frequency oscillators usually operate at a frequency that is too low for human ears to hear. ", "They are mainly used to modify other sound waves in the modular system; for example, an LFO could add vibrato to the sound. ", "Similar to VCO’s, they can usually produce sawtooth, square, triangle, and sine shaped sound waves.", "\n\nA Simple Patch\n\nHere is an example of a patch that could be made on this system; even with just this simple patch, adjusting the nobs on the modules could produce thousands of different kinds of sounds.", "\n\nReferences A-100 English Main Page. (", "2016). ", "Doepfer.de. ", "Retrieved 19 September 2016, from http://www.doepfer.de/a100e.htm\n\nA-100 Patch Examples. (", "2016). ", "Doepfer.de. ", "Retrieved 19 September 2016, from http://www.doepfer.de/a100_man/a100_patch.htm\n\nControl Voltage : Synthesizers & Music Electronics. (", "2016). ", "Controlvoltage.net. ", "Retrieved 20 September 2016, from http://controlvoltage.net/\n\nDemystifying Synths: Oscillators. (", "2016). ", "Soundfly. ", "Retrieved 19 September 2016, from https://soundfly.com/courses/demystifying-synths-oscillators\n\nDoepfer A-100. (", "2016). ", "Wikipedia. ", "Retrieved 19 September 2016, from https://en.wikipedia.org/wiki/Doepfer_A-100\n\nHarmonics | The Synthesizer Academy. (", "2016). ", "Synthesizeracademy.com. ", "Retrieved 19 September 2016, from http://synthesizeracademy.com/harmonics/\n\nHelm - Free Synth by Matt Tytel. (", "2016). ", "Helm. ", "Retrieved 19 September 2016, from http://tytel.org/helm/\n\nHow do synthesizers work?. (", "2016). ", "Explain that Stuff. ", "Retrieved 19 September 2016, from http://www.explainthatstuff.com/synthesizers.html\n\nI Dream of Wires. (", "2014). ", "Waveshaper Media Inc.\n\nModular synthesizer. (", "2016). ", "Wikipedia. ", "Retrieved 19 September 2016, from https://en.wikipedia.org/wiki/Modular_synthesizer\n\nSOUND. (", "2016). ", "Physics of Sound. ", "Retrieved 19 September 2016, from https://soundphysics.ius.edu/?page_id=812\n\nSubtractive Synthesis | The Synthesizer Academy. (", "2016). ", "Synthesizeracademy.com. ", "Retrieved 19 September 2016, from http://synthesizeracademy.com/subtractive-synthesis/\n\nSynthesizer. (", "2016). ", "Wikipedia. ", "Retrieved 19 September 2016, from https://en.wikipedia.org/wiki/Synthesizer\n\nVoltage-controlled oscillator. (", "2016). ", "Wikipedia. ", "Retrieved 19 September 2016, from https://en.wikipedia.org/wiki/Voltage-controlled_oscillator\n\n\n\nCreated in partnership with\n\n© 2020 Copyright Animagraffs." ]

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[ "This invention relates to a two-component developer comprising a magnetic carrier and a magnetic toner.", "\nIn general, a two component developer is composed of a non-magnetic toner which does not contain magnetic particles and a magnetic carrier. ", "In such a two component developer, toner particles are brought into tribocontact with carrier particles to be charged electrically. ", "The toner particles stick to carrier particles electrostatically. ", "The carrier particles are transferred on a sleeve to a developing region by magnetic force as they are rolling or dragging magnetically. ", "Toner particles are also transferred continuously along with the carrier particles to the developing region.", "\nThe toner and the carrier used in the conventional two-component developer have been studied for the improvement of various properties. ", "In particular, when the carrier is a binder-type and small in particle size, the toner can be contained at higher content than conventional. ", "Therefore, the latitude of toner supply is enlarged and high quality and long life are achieved.", "\nHowever, when the toner particles are not charged uniformly by tribocontact between the toner and the carrier, the charge amount of each toner particle is different. ", "This is caused by the different size of toner particles and the electrification build-up properties of toner particles. ", "Accordingly, small toner particles which are not charged sufficiently stick to the carrier particles weakly, and liable to leave from the carrier particles as they are rolled to be moved on a sleeve, with the result that the small toner particles come to fly in a copying machine. ", "The flying toner particles cause the dirt inside the copying machine, the fogs in copied images and the like.", "\nIn general, the wind is blowing whirlingly in the specified direction inside the copying machine for removal of air. ", "The flying toner particles are flowed with the wind toward various components. ", "For example, the flying toner particles adhere to a wire line of an electric charger. ", "If the wire line of the electric charger is made dirt by the adhered toner particles, the irregular charging of a photosensitive member, the defects of copied images and the like are brought about. ", "When the dirt makes further progress, a number of toner particles accumulate on a toner-drop-prevention plate. ", "The accumulated toner particles drop onto copying paper to make it dirt.", "\nThe flying toner particles cause the problems as above mentioned. ", "But, these problems are not so serious when a copying process is repeated about 40000 times at low copying speed (about 15 cm/sec).", "\nBut, a high-speed copying process (about 45 cm/sec) has been required recently. ", "In such a process, a developer is rolled and moved on a sleeve at much higher speed than before to generate much more flying toner particles. ", "The problems caused by the flying toner particles have become more remarkable.", "\nIt is proposed to prevent from generating of flying toner particles, for example, that toner particles are charged smoothly or quickly to adhere strongly to carrier particles. ", "But, the toner particles are moved at high speed and the flying toner particles generate inevitably. ", "The suppress of the generation of flying toner is not sufficient.", "\nOn the other hand, a magnetic toner is known as one component toner. ", "It may be proposed in order to prevent from generating of the flying toner particles that the magnetic properties of the magnetic toner is utilized to attract the toner particles onto a sleeve in a manner similar to carrier particles. ", "But, such a conventional magnetic toner contains magnetic particles at the high content of about 30 wt %. ", "Even if the magnetic toner is merely applied to a two-component developer as a toner component, the magnetic toner particles are hard to be transferred to electrostatic latent images and to form copied images with high density." ]

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[ "---\ntitle: \"Community Roundup #1\"\ndate: 2017-09-21\nauthor: \"Kyle Mathews\"\nimage: \"on-the-trail.jpg\"\nshowImageInArticle: true\ntypora-copy-images-to: ./\ntags: [\"v1\", \"getting-started\", \"plugins\"]\n---\n\nIt's been a wild 77 days since Gatsby 1.0.0 was released into the world on July\n6th, 2017.", "\n\nBy the numbers we've seen:\n\n- 3150 new GitHub stars\n- ~380,000 new npm downloads\n- 110 new contributors (hey y'all!)", "\n- ~400 merged PRs\n- dozens of new plugins\n\n## New Gatsby sites launched recently\n\n- Sourcegraph, a startup that helps developers discover and understand code,\n [relaunched their site on Gatsby](https://about.sourcegraph.com/)\n- The customer data platform startup mParticle\n [launched their docs site on Gatsby](https://docs.mparticle.com/)\n- The hip new Ocaml-based programming language ReasonML\n [built their new website on Gatsby](https://reasonml.github.io/)\n- Freelancer web developer [Oliver Benns'](https://twitter.com/oliverbenns/)\n [portfolio site](https://oliverbenns.com/)\n- [Daniel Stefanovic](https://twitter.com/danistefanovic) launched his online\n book http://digitalpsychology.io/\n\n## New tutorials!", "\n\n- The official tutorial has been growing slowly. ", "The first four parts are\n finished covering the basics of starting new projects, exploring styling\n options, how to use Gatsby plugins, and the basics of Gatsby's GraphQL data\n layer. [", "Check them out!](/tutorial/)\n- Level Up Tutorials is working on a new Gatsby video tutorial series! ", "It's\n fantastic!", "\n [Check out the first 7 tutorials on YouTube!](https://www.youtube.com/watch?v=b2H7fWhQcdE&list=PLLnpHn493BHHfoINKLELxDch3uJlSapxg).", "\n Scott Tolinski also recorded two other videos on Gatsby, his\n [\"first look\" at Gatsby](https://www.youtube.com/watch?v=CSemYFzHAtU) shortly\n after its 1.0 release as well as a\n [recording of him moving his personal site to Gatsby](https://www.youtube.com/watch?v=xqaThBnesfY).", "\n- [Giraffe Academy launched a new Gatsby tutorial series](https://www.youtube.com/playlist?list=PLLAZ4kZ9dFpMXuwazIt4mWtTuqOHdjRlk)!", "\n 13 tutorials so far covering everything from setting up Gatsby on your\n computer to building with React components to working with different types of\n data.", "\n\n## Notable plugins launched\n\n- The WordPress plugin recently got a big revamp and hit 2.0.0! ", "Checkout the\n [new example site](https://using-wordpress.gatsbyjs.org/) and the\n [README](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-source-wordpress)\n- Several new CSS plugins have been added,\n [Less](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-plugin-less),\n [Emotion](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-plugin-emotion),\n [Styled JSX](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-plugin-styled-jsx),\n [JSS](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-plugin-jss),\n and\n [Stylus](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-plugin-stylus)!", "\n- [Tumblbug](https://www.tumblbug.com/), a startup in South Korea, built a\n [source plugin for Workable](https://github.com/tumblbug/gatsby-source-workable)\n so they could easily load job listings into their website.", "\n- [Ryan Florence](https://twitter.com/ryanflorence) built a\n [source plugin for Firebase](https://github.com/ReactTraining/gatsby-source-firebase)\n so he could easily query data stored there while rebuilding his company\n website!", "\n- [gatsby-remark-katex](https://github.com/gatsbyjs/gatsby/tree/master/packages/gatsby-remark-katex)\n lets you write math equations in your markdown and\n [see them beautifully rendered](https://using-remark.gatsbyjs.org/katex/).", "\n- [gatsby-plugin-purify-css](https://github.com/rongierlach/gatsby-plugin-purify-css)\n adds drop-in support for removing unused CSS during Gatsby builds! ", "It uses\n [PurifyCSS](https://github.com/purifycss/purifycss) and can lead to huge\n reductions in CSS weight.", "\n" ]

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[ "Habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.", "\nEvery two weeks for 12 weeks four groups of C57BL/6J male mice, initially 12 months old, were subjected to three-hour cold stress tests, which consisted of a partial physical restraint at an ambient temperature of 10 degrees C. The control group experienced six consecutive tests; one experimental group skipped the cold exposure during test No. ", "4 but was physically restrained at room temperature; the other two experimental groups omitted test No. ", "4. ", "One of these groups spent the four weeks between test No. ", "3 and test No. ", "5 in their home cages, while the other was subjected to daily, 30-minute sessions of electrical stimulation of the hypothalamus through electrodes implanted in the \"rewarding\" area of the medial forebrain bundle. ", "All animals in this group showed self-stimulating behavior in the test session which preceded cold stress test No. ", "1. ", "During test No. ", "3, all four groups showed an improvement of cold tolerance relative to their first tests; body mass and colonic temperature prior to cold exposure remained unchanged. ", "The two experimental groups that were not exposed to cold during test No. ", "4 and did not receive brain stimulation, demonstrated a significant worsening of cold tolerance during the subsequent test. ", "Their body mass and baseline colonic temperatures did not change. ", "The control group and the group which was subjected to brain stimulation during the interval between tests No. ", "3 and No. ", "5 did not demonstrate any changes in cold tolerance. ", "These data demonstrated habituation to repeated mild cold exposures and dishabituation after interruption of cold exposures.(ABSTRACT TRUNCATED AT 250 WORDS)" ]

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[ "All relevant data are within the manuscript and its supporting information files.", "\n\nIntroduction {#sec005}\n============\n\nBefore a new medical test can be introduced into clinical practice, it should be evaluated for analytical validity (does the test work in the laboratory?), ", "clinical validity (does the test work in the patient population of interest?) ", "and clinical utility (is the test useful--can it lead to improvement in health outcomes?) ", "\\[[@pone.0223832.ref001], [@pone.0223832.ref002]\\]. ", "Clinical validity studies, also called diagnostic accuracy studies, evaluate the test's accuracy in discriminating between patients with or without the target condition (disease) \\[[@pone.0223832.ref003]\\]. ", "The characteristics of the test (e.g. sensitivity and specificity) may inform what role the index test (the new test under evaluation) plays in the diagnostic pathway; is it a triage, add-on or replacement test? ", "\\[[@pone.0223832.ref004]\\] Sensitivity (the proportion of participants correctly identified by the index test as having the target condition e.g. those with the disease) and specificity (the proportion of participants correctly identified by the index as not having the target condition) \\[[@pone.0223832.ref005]--[@pone.0223832.ref007]\\] are basic measures of the diagnostic accuracy of a test. ", "Other common measures are predictive values, likelihood values, overall accuracy \\[[@pone.0223832.ref008], [@pone.0223832.ref009]\\], receiver operating characteristic (ROC) curve, area under the ROC curve (AUROC) \\[[@pone.0223832.ref010]\\], ROC surface, and volume under the ROC surface (VUS) \\[[@pone.0223832.ref011]--[@pone.0223832.ref013]\\]. ", "These measures are obtained by comparing the index test results with the results of the best currently available test for diagnosing the same target condition in the same participants; both tests are supposedly applied to all participants of the study \\[[@pone.0223832.ref014]\\]. ", "The test employed as the benchmark to evaluate the index test is called the reference standard \\[[@pone.0223832.ref015]\\]. ", "The reference standard could be a gold standard (GS), with sensitivity and specificity equal to 100%. ", "This means that the gold standard perfectly discriminates between participants with or without the target conditions and provides unbiased estimates of the diagnostic accuracy measure of the index test as describe in [Fig 1](#pone.0223832.g001){ref-type=\"fig\"}. ", "The term \"bias\" in this review is defined as the difference between the estimated value and the true value of the parameter of interest \\[[@pone.0223832.ref016]\\].", "\n\n{#pone.0223832.g001}\n\nIt is also expected that when evaluating the diagnostic accuracy of a medical test, the participants undertake both the index and reference tests within a short time-period if not simultaneously. ", "This is to avoid biases caused by changes in their true disease status, which can also affect the diagnostic accuracy of the index test.", "\n\nIn addition to the common aforementioned diagnostic accuracy measures, there are other ways to evaluate the test performance of an index test. ", "These include studies of agreement or concordance \\[[@pone.0223832.ref017]\\] between the index test and the reference standard and test positivity (or negativity) rate; that is the proportion of diagnostic tests that are positive (or negative) to the target condition \\[[@pone.0223832.ref018]\\].", "\n\nIn practice, there are deviations from the classical method ([Fig 1](#pone.0223832.g001){ref-type=\"fig\"}). ", "These deviations are:\n\n1. ", " Scenarios where the gold standard is not applied to all participants in the study (i.e. there is a missing gold standard) because it is expensive, or invasive, or patients do not consent to it, or the clinicians decided not to give the gold test to some patients for medical reasons \\[[@pone.0223832.ref019], [@pone.0223832.ref020]\\]. ", "Evaluating the new test using data only from participants whose disease status was confirmed with the gold standard can produce work-up or verification bias \\[[@pone.0223832.ref021]\\].", "\n\n2. ", " Scenarios where the reference standard is not a gold standard (i.e. it is an imperfect reference standard) because it has a misclassification error or because there is no generally accepted reference standard for the target condition. ", "Using an imperfect reference standard produces reference standard bias \\[[@pone.0223832.ref022], [@pone.0223832.ref023]\\].", "\n\nSeveral methods have been developed and used to evaluate the test performance of a medical test in these two scenarios.", "\n\nReviews of some of these methods have been undertaken previously. ", "The reviews by Zhou \\[[@pone.0223832.ref024]\\], Alonzo \\[[@pone.0223832.ref025]\\] and the report by Naaktgeboren et al \\[[@pone.0223832.ref026]\\] focused on methods when the gold standard or reference standard is not applied to all participants in the study; Van Smeden et al \\[[@pone.0223832.ref027]\\] and Collins and Huynh \\[[@pone.0223832.ref028]\\] focused on the latent class models (LCMs); and Hui and Zhou \\[[@pone.0223832.ref029]\\], Trikalinos and Balion \\[[@pone.0223832.ref030]\\] and Enoe et al \\[[@pone.0223832.ref031]\\] focused on methods employed when the reference standard is imperfect. ", "Zaki et al \\[[@pone.0223832.ref032]\\] focused on the agreement between medical tests whose results are reported as a continuous response. ", "Branscum et al \\[[@pone.0223832.ref033]\\] focused on Bayesian approaches; and the reviews by Walsh \\[[@pone.0223832.ref023]\\], Rutjes et al \\[[@pone.0223832.ref014]\\] and Reitsma et al \\[[@pone.0223832.ref034]\\] focused around methods for evaluating diagnostic tests when there is a missing or imperfect reference standard.", "\n\nThe existing comprehensive reviews on this topic were published about 11 years ago \\[[@pone.0223832.ref014], [@pone.0223832.ref034]\\]; knowledge, ideas, and research in this field has evolved significantly since then. ", "Several new methods have been proposed and some existing methods have been modified. ", "It is also possible that some previously identified methods may now be obsolete. ", "Therefore, one of the aims of this systematic review is to review new and existing methods employed to evaluate the test performance of medical test(s) in the absence of gold standard for all or some of the participants in the study. ", "It also aims to provide easy to use tools (flow-diagrams) for the selection of methods to consider when evaluating medical tests when sub-sample of the participants do not undergo the gold standard. ", "The review builds upon the earlier reviews by Rutjes et al and Reitsma et al \\[[@pone.0223832.ref014], [@pone.0223832.ref034]\\]. ", "This review sought to identify methods developed to evaluate a medical test with continuous results in the presence of verification bias and when the diagnostic outcome (disease status) is classified into three or more groups (e.g. diseased, intermediate and non-diseased). ", "This is a gap identified in the review conducted by Alonzo \\[[@pone.0223832.ref025]\\] in 2014.", "\n\nThe subsequent sections discuss the method employed to undertake the review, the results, the discussion of the findings and guidance to researchers involved in test accuracy studies.", "\n\nMethodology {#sec006}\n===========\n\nA protocol for this systematic review was developed, peer-reviewed and registered on PROSPERO (CRD42018089349).", "\n\nEligibility criteria {#sec007}\n--------------------\n\nThe review includes methodological articles (that is papers that proposed or developed a method) and application articles (that is papers where any of the proposed methods) were applied.", "\n\n### Inclusion {#sec008}\n\n- Articles published in English language in a peer-reviewed journal.", "\n\n- Articles that focus on evaluating the diagnostic accuracy of new (index) test when there is a missing gold standard, no gold standard or imperfect reference standard.", "\n\n### Exclusion {#sec009}\n\n- Articles that assumed that the reference standard was a gold standard and the gold standard was applied to all participants in the study.", "\n\n- Books, dissertations, thesis, conference abstracts, and articles not published in a peer reviewed journal.", "\n\n- Systematic reviews and meta-analyses of the diagnostic accuracy of medical test(s) for a target condition (disease) in the absence of gold standard for some or all of the participants. ", "However, individual articles included in these reviews that met the inclusion criteria were included.", "\n\nSearch strategies and selection of articles {#sec010}\n-------------------------------------------\n\nThe PRISMA statement \\[[@pone.0223832.ref035]\\] was used as a guideline when conducting this systematic review. ", "The PRISMA checklist for this review, [S1 Checklist](#pone.0223832.s001){ref-type=\"supplementary-material\"}, is included as one of the supplementary materials. ", "The following bibliographic databases were searched: EMBASE, MEDLINE, SCOPUS, WILEY online library (which includes Cochrane library, EBM), PSYCINFO, Web of Science, and CINAHL. ", "The details of the search strategies at reported in the [S1 Appendix](#pone.0223832.s003){ref-type=\"supplementary-material\"}. ", "The search dates were from January 2005 --February 2019. ", "This is because, this review is an update of a review by Rutjes et al and Reitsma et al whose searched up to 2005. ", "However, original methodological articles that proposed and described a method to evaluate medical test(s) when there is a missing or no gold standard published before 2005 were also included in the review. ", "These original articles were identified by \\\"snowballing\\\" \\[[@pone.0223832.ref036]\\] from the references of some articles. ", "All articles obtained from the electronic databases were imported to Endnote X8.0.2. ", "The selection of articles to be included in this review were done by three people (CU, AJA, and KW). ", "The sifting process was in two-stages: by title and abstract and then by full text against the inclusion and exclusion criteria. ", "Any discrepancies between reviewers were resolved in a group meeting.", "\n\nData synthesis {#sec011}\n--------------\n\nA data collection form was developed for this review ([S1 Data](#pone.0223832.s002){ref-type=\"supplementary-material\"}), which was piloted on seven studies and remodified to fit the purpose of this review. ", "Information extracted from the included articles were synthesized narratively.", "\n\nResults {#sec012}\n=======\n\nA total of 6127 articles were identified; 5472 articles were left after removing the duplicated articles; 5071 articles were excluded after sifting by title and abstract; 401 articles went forward to full text assessment; and a total of 209 articles were included in the review. ", "The search and selection procedure are depicted using the PRISMA \\[[@pone.0223832.ref035]\\] flow-diagram ([Fig 2](#pone.0223832.g002){ref-type=\"fig\"}).", "\n\n{#pone.0223832.g002}\n\nThe articles included in this review used a wide variety of different study designs, like cross-sectional studies, retrospective studies, cohort studies, prospective studies and simulation studies.", "\n\nThe identified methods were categorized into four groups based on the availability and/or application of the gold standard to the participants in the study. ", "These group are:\n\n- Group 1: Methods employed when there is a missing gold standard.", "\n\n- Group 2: Correction methods which adjust for using an imperfect reference standard whose diagnostic accuracy is known.", "\n\n- Group 3: Methods employed when using multiple imperfect reference standards.", "\n\n- Group 4: ***\"other methods\"***. ", "This group includes methods like study of agreement, test positivity rate, and considering alternative study design like validation.", "\n\nMethods in groups 2, 3 and 4 are employed when there is no gold standard to evaluate the diagnostic accuracy of the index test; while methods in group 1 are employed when there is a gold standard to evaluate the diagnostic accuracy of the index test(s). ", "However, the gold standard is applied to only a sub-sample of the participants.", "\n\nA summary of all methods identified in the review, their key references and the clinical applications of these methods are reported on [Table 1](#pone.0223832.t001){ref-type=\"table\"}.", "\n\n10.1371/journal.pone.0223832.t001\n\n###### Summary of classification of methods employed when there is missing or no gold standard.", "\n\n![](", "pone.0223832.t001){#pone.0223832.t001g}\n\n ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n Main Classification Main Characteristics Key references Clinical Application\n -------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------- -----------------------------------------------------------------------------\n **Group 1**: **Method employed when there is missing gold standard:**\\ The true disease status is verified with the gold standard only in a subsample of the study participants. ", "The methods are grouped into ***imputation and bias-correction methods*** (**[Fig 3](#pone.0223832.g003){ref-type=\"fig\"}**: Imputation and bias--correction methods in binary diagnostic outcomes. ", "and [**Fig** 4](#pone.0223832.g004){ref-type=\"fig\"}: Imputation and bias--correction methods in three- classes diagnostic outcomes where ROC surface and VUS are estimated.**)** ", "and ***differential verification*** approach. ", " ***Imputation and bias correction methods***\\ ***Imputation & Bias-correction methods***\\\n • Imputation and bias-correction methods\\ \\[[@pone.0223832.ref010]\\], \\[[@pone.0223832.ref011]\\], \\[[@pone.0223832.ref013]\\], \\[[@pone.0223832.ref021]\\], \\[[@pone.0223832.ref037]--[@pone.0223832.ref081]\\]\\ \\[[@pone.0223832.ref085]--[@pone.0223832.ref089]\\]\\\n • Differential verification ***Differential verification***\\ ***Differential verification***\\\n \\[[@pone.0223832.ref082]--[@pone.0223832.ref084]\\] \\[[@pone.0223832.ref090]\\]\n\n **Group 2**: **Correction methods** The reference standard is imperfect. ", "However, there is available information about the sensitivity and specificity of the reference standard which is used to correct or adjust the estimated sensitivity and specificity of the index test. ", " ***Correction methods***\\ ***Correction methods***\\\n \\[[@pone.0223832.ref091]--[@pone.0223832.ref096]\\]\\ \\[[@pone.0223832.ref097]--[@pone.0223832.ref099]\\]\n\n **Group 3: Methods employed when using multiple imperfect reference standards or tests.**\\ A gold standard that diagnoses a target condition or accurate information on the diagnostic accuracy of an imperfect reference standard that diagnoses same condition may not be available. ", "Thus, multiple imperfect tests may be employed to evaluate the index test. ", "Methods in this group include discrepancy analysis, latent class analysis, composite reference standard, and panel or consensus diagnosis. ", " ***Discrepancy analysis***\\ ***Discrepancy analysis***\\\n • Discrepancy analysis\\ \\[[@pone.0223832.ref100]\\], \\[[@pone.0223832.ref101]\\]\\ \\[[@pone.0223832.ref136]--[@pone.0223832.ref139]\\]\\\n • Latent class analysis\\ ***Latent class analysis***\\ ***Latent class analysis***\\\n • Composite reference standard (CRS)\\ ***Frequentist LCA***: \\[[@pone.0223832.ref029]\\],\\[[@pone.0223832.ref102]--[@pone.0223832.ref112]\\]\\ ***Frequentist LCA***: \\[[@pone.0223832.ref140]--[@pone.0223832.ref152]\\]\\\n • Expert or panel or consensus diagnosis ***Bayesian LCA***: \\[[@pone.0223832.ref033]\\], \\[[@pone.0223832.ref113]--[@pone.0223832.ref119]\\]\\ ***Bayesian LCA***: \\[[@pone.0223832.ref153]--[@pone.0223832.ref174]\\]\\\n ***ROC (NGS)***:\\ ***ROC (NGS)*:**\\\n \\[[@pone.0223832.ref120]--[@pone.0223832.ref130]\\]\\ \\[[@pone.0223832.ref175], [@pone.0223832.ref176]\\]\\\n **Composite reference standard**\\ ***CRS*:**\\\n \\[[@pone.0223832.ref131]--[@pone.0223832.ref134]\\]\\ \\[[@pone.0223832.ref020], [@pone.0223832.ref177]--[@pone.0223832.ref184]\\]\\\n **Panel or consensus diagnosis** \\[[@pone.0223832.ref135]\\] ***Consensus diagnosis***:\\\n \\[[@pone.0223832.ref185]--[@pone.0223832.ref189]\\]\n\n **Group 4**: **Other methods**\\ ***Analytic validation*** of a medical test is the process of verifying the test based on what it is designed to do. ", "Experimental or case-control are common designs for these studies.\\ ***Validation***\\ ***Validation***:\\\n • Considering an alternative study design like a validation study\\ ***Studies of agreement*** aim to investigate the concordance between two or more tests (probably an index test and a reference standard).\\ \\[[@pone.0223832.ref190], [@pone.0223832.ref191]\\]\\ \\[[@pone.0223832.ref193], [@pone.0223832.ref194]\\]\\\n • Study of agreement\\ ***Test positivity rate***: is the proportion of participants who have positive results on a test. ", "This approach was used by Van Dyck et al \\[[@pone.0223832.ref018]\\] to reduce the number of tests subjected to further evaluation. ", " ***Study of agreement***:\\ ***Study of agreement***:\\\n • Test positivity rate \\[[@pone.0223832.ref032]\\], \\[[@pone.0223832.ref192]\\]\\ \\[[@pone.0223832.ref165], [@pone.0223832.ref195]--[@pone.0223832.ref199]\\]\\\n ***Test positivity rate***:\\ ***Test positivity rate***\\\n \\[[@pone.0223832.ref018]\\] \\[[@pone.0223832.ref018], [@pone.0223832.ref192]\\]\n ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\nLCA: latent class analysis; CRS is composite reference standard. ", "ROC is receiver operating characteristics; NGS is no gold standard\n\nMethods employed when gold standard is missing {#sec013}\n----------------------------------------------\n\nFifty-one statistical methods were identified from the review that were developed to evaluate the diagnostic accuracy of index test(s) when the true disease status of some participants is not verified with the gold standard. ", "These methods are divided into two subgroups:\n\n- **Imputation and bias-correction methods**: This includes methods to correct for verification bias while the disease-status of the unverified participants are left unverified. ", "Forty-eight statistical methods were identified in this group. ", "These methods are further classified based on the result of the index test (binary, ordinal or continuous), the number of index tests evaluated (single or multiple), the assumptions made about verification (ignorable or missing at random--MAR) or non-ignorable or missing not at random--MNAR), and the classification of the diagnostic outcomes (disease-status). ", "The identified methods in this subgroup are displayed Figs [3](#pone.0223832.g003){ref-type=\"fig\"} and [4](#pone.0223832.g004){ref-type=\"fig\"}.", "\n\n{#pone.0223832.g003}\n\n{#pone.0223832.g004}\n\n- **Differential verification approach**: Participants whose disease status was not verified with the gold standard could undergo another reference standard (that is imperfect or less invasive than the gold standard \\[[@pone.0223832.ref084]\\]) to ascertain their disease status. ", "This is known as ***differential verification*** \\[[@pone.0223832.ref200]\\]. ", "Differential verification has been explored Alonzo et al, De Groot et al and Naaktgeboren et al \\[[@pone.0223832.ref200]--[@pone.0223832.ref202]\\]. ", "They discussed the bias associated with differential verification, and how results using this approach could be presented. ", "There are three identified statistical methods in this group. ", "They are: a Bayesian latent class approach proposed by De Groot et al \\[[@pone.0223832.ref082]\\], a Bayesian method proposed by Lu et al \\[[@pone.0223832.ref203]\\] and a ROC approach proposed by Glueck et al \\[[@pone.0223832.ref016]\\]. ", "These three methods aim to simultaneously adjust for differential verification bias and reference standard bias that arises from using an alternative reference standard (i.e. imperfect reference standard) for participants whose true disease status was not verified with the gold standard.", "\n\nCorrection methods {#sec014}\n------------------\n\nThis group includes algebraic methods developed to correct the estimated sensitivity and specificity of the index test when the sensitivity and specificity of the imperfect reference standard is known. ", "There are seven statistical methods in this group described in five different articles \\[[@pone.0223832.ref091]--[@pone.0223832.ref095]\\]. ", "The methods by Emerson et al \\[[@pone.0223832.ref095]\\] does not estimate a single value for sensitivity or specificity, unlike the other correction methods \\[[@pone.0223832.ref091]--[@pone.0223832.ref094]\\] but produces an upper bound value and a lower bound value for the sensitivity and specificity of the index test. ", "These bounded values are used to explain the uncertainty around the estimated sensitivity and specificity of the index test.", "\n\nMethods with multiple imperfect reference standards {#sec015}\n---------------------------------------------------\n\nA gold standard or accurate information about the diagnostic accuracy of the imperfect reference standard are often not available to evaluate the index test. ", "In these situations, multiple imperfect reference standards can be employed to evaluate the index test. ", "Methods in this group include:\n\n- **Discrepancy analysis**: this compares the index test with an imperfect reference standard. ", "Participants with discordant results undergo another imperfect test, called the resolver test, to ascertain their disease status. ", "Discrepancy analysis is typically not recommended because it produces biased estimates \\[[@pone.0223832.ref100], [@pone.0223832.ref204]\\]. ", "Modifications of this approach have been proposed \\[[@pone.0223832.ref018], [@pone.0223832.ref101], [@pone.0223832.ref136]\\]. ", "In these, some of the participants with concordant responses (true positives and true negatives) are sampled to undertake the resolver test alongside participants with discordant responses (false negative--FN and false positive--FP). ", "However, further research is needed to explore if these modified approaches are adequate to remove or reduce the potential bias.", "\n\n- **Latent class analysis (LCA)**: The test performance of all the tests employed in the study are evaluated simultaneously using probabilistic models with the basic assumption that the disease status is latent or unobserved. ", "There are frequentist LCAs and Bayesian LCAs. ", "The frequentist LCAs use only the data from the participants in the study to estimate the diagnostic accuracy measures of the tests; while the Bayesian LCAs employ external information (e.g. expert opinion or estimates from previous research study) on the diagnostic accuracy measures of the tests evaluated in additional to the empirical data obtained from participants within the study. ", "The LCAs assume that the tests (new test and reference standards) are either conditionally independent given the true disease status or the tests are conditionally dependent. ", "To model the conditional dependence among the tests, various latent class model (LCM) with different dependence structure have been developed such as the Log-linear LCM \\[[@pone.0223832.ref102]\\], Probit LCM \\[[@pone.0223832.ref103]\\], extended log-linear and Probit LCM \\[[@pone.0223832.ref108]\\], Gaussian Random Effect LCM \\[[@pone.0223832.ref105]\\] and two-crossed random effect LCM \\[[@pone.0223832.ref107]\\] among others. ", "However, some studies \\[[@pone.0223832.ref205]\\],\\[[@pone.0223832.ref206]\\] have shown that latent class models with different conditional dependence structures produce different estimates of sensitivities and specificities and each model still has a good fit. ", "Thus, further research could be carried out to explore if each of the conditional dependence LCM are case specific.", "\n\n- **Construct composite reference standard**: this method combines results from multiple imperfect tests (excluding the index test) with a predetermined rule to construct a reference standard that is used to evaluate the index test. ", "By excluding the index test as part of the composite reference standard, incorporation bias can be avoided \\[[@pone.0223832.ref131]\\]. ", "A novel method identified under the composite reference standard is the \"dual composite reference standard\" proposed by Tang et al \\[[@pone.0223832.ref134]\\].", "\n\n- **Panel or consensus diagnosis**: this method uses the decision from a panel of experts to ascertain the disease status of each participant, which is then used to evaluate the index test.", "\n\nOther methods {#sec016}\n-------------\n\nThis group includes methods that fit the inclusion criteria but could not be placed into the other three groups. ", "They include study of agreement, test positivity rate and the use of an alternative study design such as analytical validation. ", "Study of agreement and test positivity rate are best used as exploratory tools alongside other methods \\[[@pone.0223832.ref152], [@pone.0223832.ref178]\\] because they are not robust enough to assess the diagnostic ability of the medical test. ", "Validation of a medical test cut across different disciplines in medicine such as psychology, laboratory or experimental medicine. ", "With this approach, the medical test is assessed based on what it is designed to do \\[[@pone.0223832.ref191]\\]. ", "Other designs include case-control designs (where the participants are known to have or not have the target condition) \\[[@pone.0223832.ref207], [@pone.0223832.ref208]\\], laboratory based studies or experimental studies which are undertaken with the aim to evaluate the analytical sensitivity and specificity of the index test \\[[@pone.0223832.ref190], [@pone.0223832.ref209], [@pone.0223832.ref210]\\].", "\n\nGuidance to researchers {#sec017}\n=======================\n\nThe guidance flowchart ([Fig 5](#pone.0223832.g005){ref-type=\"fig\"}) is a modification and extension of the guidance for researchers flow-diagram developed by Reitsma et al \\[[@pone.0223832.ref034]\\].", "\n\n{#pone.0223832.g005}\n\nSince, evaluating the accuracy measures of the index test is the focus of any diagnostic accuracy study, the flowchart starts with asking the first question \"Is there a gold standard to evaluate the index test?\" ", "Following the responses from each question box (not bold); methods are suggested (bold boxes at the bottom of the flowchart) to guide clinical researchers, test evaluators, and researchers as to the different methods to consider.", "\n\nAlthough, this review aims to provide up-to-date approaches that have been proposed or employed to evaluate the diagnostic accuracy of an index test in the absence of a gold standard for some or all of the participants in the accuracy study; some things researchers can consider when designing an accuracy study aside from the aim of their studies, are outlined in [Box 1](#pone.0223832.box001){ref-type=\"boxed-text\"} (\\[[@pone.0223832.ref026], [@pone.0223832.ref211]--[@pone.0223832.ref218]\\]).", "\n\nBox 1: Suggestions when designing a diagnostic accuracy study. {#", "sec018}\n--------------------------------------------------------------\n\n- [**Design a protocol**]{.ul}: The protocol describes every step of the study. ", "It states the problem and how it will be addressed.", "\n\n- [**Selection of participants from target population**]{.ul}: The target population determines the criteria for including participants in the study. ", "Also, the population is important in selecting the appropriate setting for the study.", "\n\n- [**Selection of appropriate reference standard:**]{.ul} The reference standard should diagnose same target condition as the index test. ", "The choice of reference standard (gold or non-gold) determines the methods to apply when evaluating the index test (see [Fig 5](#pone.0223832.g005){ref-type=\"fig\"}).", "\n\n- [**Sample size**]{.ul}: Having adequate sample size is necessary to make precise inference from the statistical analysis that will be carried out. ", "Studies that discuss the appropriate sample size to consider when planning test accuracy are \\[[@pone.0223832.ref211]--[@pone.0223832.ref215]\\].", "\n\n- [**Selection of accuracy measure to estimate**]{.ul}: The researchers need to decide which accuracy measures they wish to estimate, and this is often determined by the test's response (binary or continuous).", "\n\n- [**Anticipate and eliminate possible bias**]{.ul}: multiple forms of bias may exist \\[[@pone.0223832.ref026], [@pone.0223832.ref216]--[@pone.0223832.ref218]\\]. ", "Exploring how to avoid or adjust for these bias (if they are unavoidable) is important.", "\n\n- [**Validation of results**]{.ul}: Is validation of the results from the study on an independent sample feasible? ", "Validation ensures an understanding of the reproducibility, strengths, and limitations of the study.", "\n\nSome guidelines and tools have been developed to assist in designing, conducting and reporting diagnostic accuracy studies such as the STARD \\[[@pone.0223832.ref219]--[@pone.0223832.ref223]\\] guidelines, GATE \\[[@pone.0223832.ref224]\\] framework, QUADAS \\[[@pone.0223832.ref225]\\] tools; which can aid the design of a robust test accuracy study.", "\n\nDiscussion {#sec019}\n==========\n\nThis review sought to identify and review new and existing methods employed to evaluate the diagnostic accuracy of a medical test in the absence of gold standard. ", "The identified methods are classified into four main groups based on the availability and/or the application of the gold standard on the participants in the study. ", "The four groups are: methods employed when only a sub-sample of the participants have their disease status verified with the gold standard (group 1); correction methods (group 2); methods using multiple imperfect reference standards (group 3) and other methods (group 4) such as study of agreement, test positivity rate and alternative study designs like validation.", "\n\nIn this review additional statistical methods have been identified that were not included in the earlier reviews on this topic by Reitsma et al \\[[@pone.0223832.ref034]\\] and Alonzo \\[[@pone.0223832.ref025]\\]. ", "A list of all the methods identified in this review are presented in the supplementary material ([S1 Supplementary Information](#pone.0223832.s004){ref-type=\"supplementary-material\"}). ", "This includes a brief description of the methods and a discussion of their strengths and weaknesses and any identified case studies where the methods have been clinically applied. ", "Only a small number of the methods we have identified have applied clinically and published \\[[@pone.0223832.ref038], [@pone.0223832.ref063]\\]. ", "This may be due to the complexity of these methods (in terms of application and interpretation of results), and/or a disconnection between the fields of expertise of those who develop (e.g. mathematicians or statisticians) and those who employ the methods (e.g. clinical researchers). ", "For example, the publication of such method in specialist statistical journals may not be readily accessible to clinical researchers designing the study. ", "In order to close this gap, two flow-diagrams (Figs [3](#pone.0223832.g003){ref-type=\"fig\"} and [4](#pone.0223832.g004){ref-type=\"fig\"}) were constructed in addition to the modified guidance flowchart, ([Fig 5](#pone.0223832.g005){ref-type=\"fig\"}) as guidance tools to aid clinical researchers and test evaluators in the choice of methods to consider when evaluating medical test in the absence of gold standard. ", "Also, an R package (*bcROCsurface*) and an interactive web application (Shiny app) that estimates the ROC surface and VUS in the presence of verification bias have been developed by To Duc \\[[@pone.0223832.ref078]\\] to help bridge the gap.", "\n\nOne of the issues not addressed in this current review was on methods that evaluate the differences in diagnostic accuracy of two or more tests in the presence of verification bias. ", "Some published articles that consider this issue are Nofuentes and Del Castillo \\[[@pone.0223832.ref226]--[@pone.0223832.ref230]\\], Marin-Jimenez and Nofuentes \\[[@pone.0223832.ref231]\\], Harel and Zhou \\[[@pone.0223832.ref232]\\] and Zhou and Castelluccio \\[[@pone.0223832.ref233]\\]. ", "This review also did not consider methods employed to estimate the time-variant sensitivity and specificity of diagnostic test in absence of a gold standard. ", "This issue has recently been addressed by Wang et al \\[[@pone.0223832.ref234]\\].", "\n\nIn terms of the methodology, a limitation of this review is the exclusion of books, dissertations, thesis, conference abstract and articles not published in English language (such as the review by Masaebi et al \\[[@pone.0223832.ref235]\\] which was published in 2019), which could imply that there could still be some methods not identified by this review.", "\n\nRegarding the methods identified in this review, further research could be carried to explore the different modification to the discrepancy analysis approaches to understand if these modifications reduce or remove the potential bias. ", "In addition, further research is needed to determine if the different methods developed to evaluate an index test in the presence of verification bias are robust methods. ", "Given the large numbers of statistical methods that have been developed especially to evaluate medical tests when there is a missing gold standard and the complexity of some of these methods; more interactive web application (e.g. Shiny package in R \\[[@pone.0223832.ref236]\\]) could be developed to implement these methods in addition to the Shiny app developed by To Duc \\[[@pone.0223832.ref078]\\] and Lim et al \\[[@pone.0223832.ref237]\\]. ", "The development of such interactive web tools will expedite the clinical applications of these developed methods and help bridge the gap between the method developers and the clinical researchers or tests evaluators who are the end users of these methods.", "\n\nConclusion {#sec020}\n==========\n\nVarious methods have been proposed and applied in the evaluation of medical tests when there is a missing gold standard result for some participants, or no gold standard at all. ", "These methods depend on the availability of the gold standard, its application to all or subsample of participants in the study, the availability of alternative reference standard(s), and underlying assumption(s) made with respect to the index test(s) and / or participants in the study.", "\n\nKnowing the appropriate method to employ when analysing the data from participants of a diagnostic accuracy studies in the absence of gold standard, help to make statistically robust inference on the accuracy of the index test. ", "This, in addition to data on cost-effectiveness, utility and usability of the test will support clinicians, policy makers and stake holders to decide the adoption of the new test in practice or not.", "\n\nSupporting information {#sec021}\n======================\n\n###### PRISMA checklist.", "\n\n(DOC)\n\n###### \n\nClick here for additional data file.", "\n\n###### Data extraction form.", "\n\n(DOCX)\n\n###### \n\nClick here for additional data file.", "\n\n###### \n\n(DOCX)\n\n###### \n\nClick here for additional data file.", "\n\n###### \n\n(DOCX)\n\n###### \n\nClick here for additional data file.", "\n\nThe authors will like to acknowledge Professor Patrick Bossuyt from the Department of Clinical Epidemiology and Biostatistics, Academic Medical centre, University of Amsterdam, the Netherlands, for giving the consent to update his review, reviewing the protocol and his continued advice throughout this work. ", "Also we will like to acknowledge the authors of the previous review, Dr Anne Rutjes in University of Bern, Switzerland; Professor Johannes Reitsma in the Department of Epidemiology, Julius Center Research Program Methodology UMC Utrecht, The Netherlands; Professor Arri Coomarasamy in the College of Medical and Dental Sciences, University of Birmingham, UK; and Professor Khalid Saeed Khan in Queen Mary, University of London for the guidance flowchart which was modified and extended. ", "AJA, SG, and LV are supported by the National Institute for Health Research (NIHR) Newcastle In Vitro Diagnostics Co-operative. ", "The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.", "\n\n[^1]: **Competing Interests:**The authors have declared that no competing interest exist.", "\n" ]

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[ "First I would like to apologize to those that may experience discomfort seeing that someone else received a TextBlade before general release, I do sympathize. ", "I have been there. ", "For those who wish to know the secret to be chosen for TREG as far as I know there isn’t one. ", "For those that think “brown nosin” is necessary I invite to look over my posts and I do not believe you will find any. ", "Mark was familiar with my posts.", "\n\nLet’s get to the first impressions. ", "After some misdirection with FedEx I finally got my hands on the package Friday night around eight. ", "Much has already been written about the packaging and the attention to detail so for now all I will say is the prior assessments were correct. ", "After opening the package the first thing I noticed was how small the TextBlade was. ", "I had seen the pictures and videos but holding one in my hand it was smaller than expected. ", "After putting the unit together I paired it with my iPad Air 2 and attempted to type. ", "I soon discovered how different typing on the TextBlade would be. ", "Although I spend many hours each day behind a keyboard I have always considered myself a lousy typist and am trying to correct years of bad habits while learning this new keyboard. ", "I typed with my wrists resting on the surface of the desk since it is not necessary to move your hands to reach all of the keys. ", "The amount of movement by the fingers to go from one row to another is minimal. ", "That was all for Friday night and I left it alone until around 1 pm Saturday when I had my phone call with Mark.", "\n\nI am not going to try to give a detailed report of the conversation but will try to summarize two major things I came away with when it was over. ", "These are not his words but mine in an attempt to summarize several hours of conversation. ", "After hearing Mark describe in great detail the processes they went thru in developing the packaging up to the current version of the TextBlade I would call him, in the words of Stan Lee, a “True Believer”. ", "Mark has a vision for WayTools and the TextBlade that he will not deviate from. ", "Time and profit are secondary to the goal of producing the product in his vision. ", "All of the time that has passed and problems that they have encountered were not expected but if they are necessary to get to the product in his vision so be it. ", "He does not want the people who have stayed with him so far to wait one minute longer than necessary for their order but he will not release it one minute before it is ready.", "\n\nThe second thing is regarding updates. ", "I suggested that updates be made more often even if they were just a simple statement that “We are still on track to ship in Q4”. ", "I think Mark sees updates as a “no win” situation, my words not his. ", "If they are done every two weeks there will be complaints that they are not done weekly. ", "If they are done weekly there will be complaints that they are not detailed. ", "If they are detailed people will want specific dates for completion and if they are not met they will be called liars. ", "Again these are my words not his. ", "Although I would like more, detailed updates I cannot fault this logic since we have seen this behavior in the past. ", "Rather than spend time on updates he feels that the time is best spent on getting the product ready. ", "I think he feels that general release is the one thing that will silence the critics.", "\n\nI am sure that there will be some who will say that I have partook of the kool-aid but I am posting what I see from my point of view, just as I always have, but this time with more information to go on. ", "I will try to post about my experiences using the TextBlade in a few days as I adapt and learn." ]

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[ "package resolver\n\nimport (\n\t\"context\"\n\t\"testing\"\n\n\t\"github.com/mitchellh/golicense/module\"\n\t\"github.com/stretchr/testify/require\"\n)\n\nfunc TestTranslator(t *testing.", "T) {\n\tcases := []struct {\n\t\tInput string\n\t\tOutput string\n\t}{\n\t\t{\n\t\t\t\"github.com/foo/bar\",\n\t\t\t\"\",\n\t\t},\n\n\t\t{\n\t\t\t\"golang.org/x/text\",\n\t\t\t\"go.googlesource.com/text\",\n\t\t},\n\n\t\t{\n\t\t\t\"gonum.org/v1/gonum\",\n\t\t\t\"github.com/gonum/gonum\",\n\t\t},\n\t}\n\n\tfor _, tt := range cases {\n\t\tt.Run(tt.", "Input, func(t *testing.", "T) {\n\t\t\tvar tr Translator\n\t\t\tactual, ok := tr.", "Translate(context.", "Background(), module.", "Module{\n\t\t\t\tPath: tt.", "Input,\n\t\t\t})\n\n\t\t\tif tt.", "Output == \"\" {\n\t\t\t\trequire.", "False(t, ok)\n\t\t\t\treturn\n\t\t\t}\n\n\t\t\trequire.", "True(t, ok)\n\t\t\trequire.", "Equal(t, tt.", "Output, actual.", "Path)\n\t\t})\n\t}\n}\n" ]

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[ "Semiconductor components based on silicon carbide as the base material are continuously developed to be used in connection with high temperatures, high power applications and under high radiation conditions. ", "Under such circumstances conventional semiconductors do not work satisfactorily. ", "Evaluations indicate that power MOSFET-type SiC semiconductor and SiC based diode rectifiers would be able to operate over a greater voltage and temperature interval, for example up to 650-800.degree. ", "C., and show better switching properties, such as lower losses and higher working frequencies, and nevertheless have a volume 20 times smaller than corresponding silicon components. ", "These possible improvements are based on the favorable material properties that silicon carbide possesses in relation to silicon. ", "The favorable properties include, for example, a higher breakdown field (up to 10 times higher than silicon), a higher thermal conductivity (more than 3 times higher than silicon) and a higher energy band gap (2.9 eV for 6H-SiC, one of the crystal structures of siC).", "\nAs SiC semiconductor technology is relatively young and in many aspects immature, there are many critical manufacturing problems to be solved before SiC semiconductor devices may be experimentally realized and manufacted in high volume. ", "This is especially true of components intended for use in high-power and high-voltage applications.", "\nOne difficulty to overcome when manufacturing high voltage diodes or other types of semiconductor components comprising a voltage absorbing pn junction is to produce a proper junction termination at the edge of the junction. ", "The electric field at the periphery of the junction is normally enhanced compared to the electric field in the bulk of the junction. ", "This field increase at the periphery of the junction may be further reinforced in the presence of surface charge.", "\nA high electric field at the edge of the pn junction implies a great risk of voltage breakdown or flash-over at the edge of the junction as well as gives rise to an instability of the blocking voltage, known as voltage drift.", "\nTo avoid the above-discussed disadvantages it becomes very important to reduce the field concentration, where the junction reaches the surface. ", "Combined with efforts to passivate the surface of the component, measures are taken to flatten out the electric field at the surface, for example by acting on how the pn junction emerges at the surface. ", "As an example it is known from silicon power components to lap (grind, sandblast, etch) the surface of the edge to a certain angle in relation to the pn junction to thereby flatten out the field. ", "Another known technique is to gradually decrease the charge content on the highly doped side of the junction, such that the charge content of the highly doped layer is reduced towards the outermost edge of the junction. (", "This technique is known as Junction Termination Extension or JTE). ", "The methods, known from silicon technology, used to achieve a JTE of an Si component are difficult or almost impossible to apply to components based on silicon carbide due to the great hardness of the material and extremely low diffusivity of proper SiC dopants. ", "As an example, doping through diffusion is not feasible for SiC, as diffusion coefficients are negligible below 2270.degree. ", "K. Also, ion implantation of doping elements, a common technique when manufacturing Si components, is difficult to master and not yet fully developed for SiC. Hence, many of the problems reminiscent of those prevalent at the beginning of the development of corresponding silicon components to be solved when developing semiconductor components from SiC have not been solved as yet for pn junctions in SiC.\nHigh voltage diodes from 6H-SiC with epitaxially formed pn and Schottky junctions have been made experimentally (see e.g. M. Bhatnagar and B. J. Baliga, IEEE Trans. ", "Electron Devices, vol. ", "40, no. ", "3 pp 645-655, March 1993 or P. G. Neudeck, D. J. Larkin, J. A. Powell, L. G. Matus and C. S. Salupo, Appl. ", "Phys. ", "Lett. ", "vol 64, No 11, Mar. 14, 1994, pp 1386-1388). ", "Some of the problems related to SiC devices have thus been solved, but no reliable solution to the problems connected with electric field concentration at the edges of the junction has been presented as yet.", "\nThe electric field may be reduced at the edge of the pn junction by applying a semi-isolating layer to the edge of the junction of an SiC component. ", "Such a solution is described in patent document PCT/SE94/00482.", "\nAny method or device to produce a semiconductor component corresponding to the principle of Junction Termination Extension at a pn junction composed of Si is not publicly known for a component, where SiC constitutes the base material of the junction. ", "Solutions for producing SiC components comprising pn junctions with JTEs are described in the unpublished patent application Ser. ", "No. ", "08/520,689, which is hereby included in this description by reference. ", "The solutions described there involve a stepwise decrease of charges of the JTE towards the edge of the JTE utilizing an etch down technique, epitaxial regrowth or ion implantation to control the surface doping and surface fields. ", "The present invention aims at describing a voltage absorbing edge at a pn junction with a JTE structure of an SiC component where the pn junction has a planar structure.", "\nThe term SiC is used in the following text to refer to any of the principal crystal polytypes of this material known as 6H, 4H, 2H, 3C and 15R." ]

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[ "Despite the presence of many other remarkable aircraft, the MiG-21 was the main star of the air show at Kuopio. ", "Without doubts, it’s a legendary aircraft, one of the most characteristic in the world of military aviation of the 20th century. ", "Even today MiG-21 is still in service, though its glory passed a long time ago. ", "And so their story goes on, in armies of several countries. ", "A day before the airshow, MiG-21 celebrated its 60th anniversary. ", "This article will be fully focusing on this amazing machine!", "\n\nAll Photos by Fyodor Borisov/Transport-Photo Images\n\n#1. ", "The first thing that appeared on the airport was the MiG-21. ", "Not the Romanian one as it was written in the information, but Finnish. ", "And it was in an excellent shape!", "\n\n#2. ", "The aircraft was properly secured and maintained for moving it from place to place.", "\n\n#3. ", "What’s so special in small airshows? ", "Spontaneity and accessibility. ", "There was no fence with guards, here you could even ‘undress’ the plane and the organizers had a very kind attitude and they were even willing to uncover the plane when asked 🙂\n\n#4. ", "And here it is! ", "The handsome star of the event.", "\n\n#5.", "\n\n#6. ", "An interesting thing – the aircraft have both Russian and Finnish label. ", "And it’s not duplicated, as many labels are simply different. ", "It includes the minimum knowledge about tech parameters and about crew that Russian neighbor apparently needed.", "\n\n#7. ", "The kindness from the organizers side goes on – we opened the cockpit\n\n#8. ", "And again – interior of the cockpit is in both langauges, Russian and Finnish.", "\n\n#9.", "\n\n#10. ", "Everything is just compact. ", "It have just everything it needs.", "\n\n#11. ", "It’s irresistible even for the photographer (Fyodor Borisov).", "\n\n#12. ", "And not just for him!", "\n\n#13. ", "Here is some range of past and present aircraft of the Finnish Air Force.", "\n\n#14. ", "And this is our fighting crew (photographers).", "\n\n#15. ", "Romanian guests with their MiG’s.", "\n\n#16. ", "Landing separately.", "\n\n#17.", "\n\n#18.", "\n\n#19.", "\n\n#20.", "\n\n#21. ", "The airport at Kuopio acquired such a peculiar appearance.", "\n\n#22. ", "Day Two – aircraft is preparing for flight program.", "\n\n#23. ", "Ascending.", "\n\n#24.", "\n\n#25.", "\n\n#26.", "\n\n#27.", "\n\n#28.", "\n\n#29. ", "Passage at low attitude.", "\n\n#30. ", "With fire behind its tail.", "\n\n#31. ", "Approaching…\n\n#32. ", "And turning away!", "\n\n#33.", "\n\n#34.", "\n\n#35. ", "Landing.", "\n\n#36. ", "Folding the break-parachute.", "\n\n#37. ", "It’s a wonderful thing to see this aircraft flying after 20 years." ]

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[ "Incoherent spatial solitary waves in nematic liquid crystals.", "\n(2+1) -dimensional spatial solitary waves are generated by launching of milliwatt-power linearly polarized light beams in voltage-biased planar cells with undoped nematic liquid crystals, regardless of the degree of spatial coherence of the input. ", "Coherent and incoherent self-trapping, as well as guidance of a weaker copolarized signal, is demonstrated." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "We ll have 2 scenes with Juliana, one is with Deborah Mastronelly and other with new TS Daphne Duarte\n\nSounds freaking awesome and will be looking forward to seeing both of Juliana Leal'sTS on TS Scenes. ", "And thanks for taking the time respond i really appreciate it. ", "and btw do you have any preview photos?. ", "Keep up the great work my friend" ]

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[ "Complimenting Organic Elemental Analysis with TGA-FTIR: Discover how CHNS analysis of materials can be greatly assisted by understanding the decomposition properties of the sample under investigation. ", "TGA is a primary method for determining this additional information." ]

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[ "Land Launch\n\nLand Launch refers to a service product of Sea Launch SA. ", " There is no entity or company called Land Launch. ", "Sea Launch created the Land Launch offering to address lighter satellites directly into geosynchronous orbit or into geosynchronous transfer orbit, while Sea Launch continues to address the heavy satellite launch market.", "\n\nIn 2002, Sea Launch created Land Launch with its Russian and Ukrainian partners. ", " The Russian and Ukrainian partners formed a Russian company Space International Services (SIS) to provide the launch services and launch operations. ", " While the Sea Launch company maintains the rights to market Land Launch to the commercial community, the new entity SIS can market launch services to government customers.", "\n\nLand Launch uses Zenit rockets to conduct commercial satellite launches from the Baikonur Cosmodrome Site 45/1 in Kazakhstan. ", "Land Launch missions differ from Sea Launch missions in that the Zenit-3SLB is used, as opposed to the Zenit-3SL. ", "The Zenit-3SLB utilizes substantially the same components as the Zenit-3SL but a smaller payload fairing is used to accommodate the smaller satellites launched from its northern operating location.", "\n\nThe first launch was conducted on 28 April 2008 at 05:00 GMT, when a Zenit-3SLB was used to place AMOS-3 (AMOS-60) a communications satellite, into a geosynchronous orbit.", "\n\nA second launch was completed on February 26, 2009 when Land Launch successfully launched the Telstar 11N mission.", "\n\nA commercial version of the two-stage Zenit-2M, the Zenit-2SLB, is also offered for commercial launches utilizing Land Launch. ", "However no launches have been contracted for this smaller rocket.", "\n\nLaunches\n\nSee also\n Expendable launch system\n Sea Launch\n\nReferences\n\nExternal links\n Land Launch Home Page\n\nCategory:Commercial launch service providers\nCategory:Space industry companies of Russia" ]

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[ "1-48 of 835 results\n\n2016 Topps Premier Gold. ", "Football Fibers Insert Card -Player-Worn Memorabilia. ", "RED Parallel. ", "Geoff Cameron. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "Premier Portraits. ", "Insert Card - RED Parallel. ", "Marko Arnautović (PP-9). ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "Football Fibers Insert Card -Player-Worn Memorabilia. ", "Geoff Cameron. ", "PURPLE Parallel. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "Autograph Relic Insert Card. ", "Geoff Cameron. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned. ", "Football Fibers Insert Card -Player-Worn Memorabilia.", "\n\n2016 Topps Premier Gold. ", "Autograph Relic Insert Card. ", "Geoff Cameron. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2014 Topps Premier Gold. ", "Crowning Achievement Die-Cut Autograph. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "Base - PURPLE Parallel. ", "Bojan Krkic (#93) - Stoke City. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2014 Topps Premier Gold. ", "Steve Sidwell (PA-SS) - Stoke City. ", "Premier Autographs / Signature Insert. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\n2016 Topps Premier Gold. ", "Base - PURPLE Parallel. ", "Bojan Krkic (#93) - Stoke City. ", "To ensure the card stays in the best possible condition, it was first placed in the top loader (directly from the case break) and then the images were scanned.", "\n\nThe all-new edition features 508 cards, including all the league's biggest stars, all the hottest Star Signings as well as Shiny Man of the Match favourites and Hundred Club players.", "There is also a set of 40 legends." ]

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[ "Charming Accomodations\n\nOur 41 rooms, split between penthouse suites, valley view, panorama view and poolside rooms are extravagant, spacious and come with unmatched service and several sophisticated and requisite amenities. ", "They are also disabled-friendly. ", "A few rooms are installed with glass floors to help you catch a glimpse of the stunning valley below you. ", "Click here for a detailed overview on the stunning accommodations we have to offer. ", "We’ve also curated some FAQs to answer any queries you may have.", "\n\nExperience Culinary Extraordinaire\n\nDive right into these sumptuous delicacies and experience the authentic flavours of the local cuisine in an ambient setting only at Sky Rocca Diner. ", "With unmatched service and a view so breathtakingly marvelous, turn your fine dining experience into a memory that stays with you forever. ", "Whether it's a romantic dinner or a cheerful brunch with friends, Sky Rocca Diner, with its exceptional setting is where you need to be. ", "Break the chilly night breeze with an elixir in a cup, and groove to the beat in our lounge bar Salem Rocks.", "\n\nHost Exceptional Events\n\nImmerse yourself in the unspoken elegance of our 4 unique banquet that elevate your festivities, making your time with us unforgettable. ", "Select from our stunning array of spaces, ideal for any gala, wedding or conference. ", "With world class amenities, state-of-the-art technology and our staff who are seasoned professionals, be sure that every event or meeting you host truly stands out. ", "With our unmatched hospitality and charming spaces, we at GRT Hotels will strive to make your special moments quite exceptional every step of the way.", "\n\nRewind And Rejuvenate\n\nLeave the stress of everyday life behind and unwind at the Bodhi Spa with our special treatments. ", "Experience unparalleled care and absolute bliss where our trained professionals rejuvenate you. ", "Revitalise your energy and walk out a new person.", "\n\nWalking hand in hand with a loved one in a serene atmosphere, mesmerised by the scenic beauty of the majestic valley, or sitting by the pool and sipping on a warm cup of coffee with your favourite book. ", "These are just some of the incredible experiences you could savour.", "\n\nExceptional Location\n\nThe hotel's strategic location makes it accessible from all major cities like Chennai, Bangalore, Madurai, Coimbatore, etc. ", "and is just a 30km drive from Salem railway station. ", "The Yercaud Lake Boat House, Pagoda Point, Killiyur Falls and the exclusive Bear Cave are some of the marvelous locations you must visit when you're staying at GReaT Trails Yercaud.", "\n\nOur unparalleled hospitality and our unpretentious attitude are what we're known for. ", "Come experience luxury, comfort and bliss, only second to home at our resort.", "\n\nIf you enjoyed your stay at GReaT Trails Yercaud, make sure to book your stay here the next time you visit. ", "Also experience the indistinguishable GRT hospitality and unparalleled comfort at GReaT Trails Kodaikanal and Zibe Salem. ", "Book directly with us, in advance to get the best hotel and resort deals." ]

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[ "Jeune Demoiselle\n\n\"Jeune Demoiselle\" is the second single from Diam's 2006 album Dans ma bulle.", "\n\nTrack listings\n\n CD-Single\n \"Jeune Demoiselle\" (Version Radio) (4:11)\n \"Jeune Demoiselle\" (Instrumental) (4:02)\n\n CD-Maxi\n \"Jeune Demoiselle\" (Version Radio) (4:11)\n \"Jeune Demoiselle\" (Instrumental) (4:02)\n \"Jeune Demoiselle\" (Video) (4:14)\n \"Jeune Demoiselle\" (Making of)\n Video (3:45)\n Lyrics\n\nCharts\n\nReferences\n\nCategory:2006 singles\nCategory:Diam's songs" ]

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[ "Cutoff Value for Correcting White Blood Cell Count for Nucleated Red Blood Cells: What is it? ", "Why is it Important?", "\nNucleated red blood cells (RBCs) are normally observed in the peripheral blood of neonates and during pregnancy. ", "Under other conditions, the presence of nucleated RBCs in circulating blood indicates disorder in the blood-producing mechanism. ", "The increased presence of nucleated RBCs, however, falsely elevates the leukocyte count, as measured by most automated hematology analyzers, warranting a manual correction of the leukocyte count. ", "For a long time, cutoff values for correcting white blood cell (WBC) count for the presence of nucleated RBCs have been used regularly, particularly in developing countries. ", "However, because those values are largely subjective, they can vary widely between laboratories worldwide. ", "These varied cutoff values include 1, 5, 10, 20, and 50; it appears that the numbers 5 and 10 are the most common values used in corrections; the reasons require further elucidation. ", "In this article, we discuss the merits of correcting the WBC count for nucleated RBCs at certain cutoff points." ]

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[ "Spread of cancer cells in tissues: modelling and simulation.", "\nContinuing previous studies in which tumor diseases were interpreted as unstable control loops, the present paper tries to determine the spatial structure and the time behaviour of cell renewal systems. ", "For this purpose a computer model for the two-dimensional cell space was developed, which is described by a set of specifications and growth statements. ", "Selected case studies are then simulated by means of a digital computer (CYBER 76). ", "The development of this model enables a deeper insight into the structure and function of disturbed cell renewal processes. ", "Furthermore, it is possible with this computer model to simulate simple basic cases which, in reality, could hardly or not at all be tested." ]

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[ "Soil organic carbon (SOC) represents the largest carbon pool in terrestrial ecosystems and is a key factor that controls important soil functions, e.g. the productivity of agricultural soils[@b1]. ", "The maintenance of SOC stocks in croplands and grasslands of the world is thus of upmost importance for ensuring global food security and the prevention of substantial CO~2~ emissions. ", "Under long-term constant management and environmental conditions, agricultural SOC stocks are in a dynamic equilibrium between C inputs, mainly in form of crop residues and organic fertilizers, and a loss of C due to decomposition of soil organic matter (SOM). ", "However, as the decomposition of SOM is strongly controlled by temperature and soil moisture, climate change imposes the risk of SOC losses[@b2][@b3][@b4][@b5][@b6]. ", "Both a the global and regional scale decreasing SOC stocks were observed along temperature gradients from colder to warmer regions[@b7][@b8]. ", "This suggests that SOM decomposition rates change faster as a function of temperature than does net primary production (NPP). ", "Accordingly, rising temperatures in the course of climate change are discussed to cause significant declines of SOC. ", "In particular, agricultural soils could be affected, as observed stagnation of crop yields and associated stagnation of C inputs in the last decades may aggravate climate change-induced SOC losses[@b9][@b10]. ", "First indications for declining SOC stocks in agricultural soils were already found, but due to changes of land use and the agricultural management, a relationship with climate change could not be confirmed to date[@b11][@b12][@b13][@b14][@b15][@b16][@b17].", "\n\nThe potential risk of SOC losses induced by climate change calls for a projection of agricultural SOC stocks under future climate change scenarios on the basis of SOC models. ", "A frequently applied model is the Rothamsted Carbon Model (RothC) which was specifically designed to simulate SOC dynamics in temperate cropland and grassland soils[@b18]. ", "Several modelling approaches were conducted to simulate regional or global development of agricultural SOC stocks[@b19][@b20][@b21][@b22][@b23][@b24][@b25]. ", "However, these SOC projections were often based on simple estimations of important input variables or legacy data with a relatively low spatial resolution. ", "In particular, rough estimations for the C input were used, which is one of the most decisive parameters in SOC projections. ", "As the determination of the total C input, particularly the belowground components such as roots and rhizodeposition, is difficult and elaborate, values are generally estimated using an inverse application of the RothC model or simply gross values from the literature[@b18][@b20][@b26][@b27]. ", "However, large discrepancies were observed between measured and estimated C input values and thus an independent, more reliable approach is needed[@b28]. ", "Future projections of the development of C inputs in agricultural soils are even more challenging due to overlapping implications of crop and land use management, future trend of crop breeding and technology and climate change. ", "In several SOC modelling studies it was assumed that the development of agricultural C inputs are simply related to NPP development, which can be simulated by vegetation models[@b19][@b20][@b21][@b22][@b25][@b29][@b30][@b31]. ", "However, such an approach neglects the fact that the C input in agricultural soils is controlled by various factors including management practices. ", "Moreover, reliable SOC projections using the RothC model require a reasonable initialization of the model. ", "In terms of model initialization, SOM pools derived from soil fractionation is a laborious, but probably the most suitable approach as this method reflects the actual state of SOC pools[@b27][@b32][@b33][@b34].", "\n\nIn this study, we simulated the future development of SOC stocks of cropland and grassland soils in Bavaria from 2000 to 2095 under a moderate climate scenario of the IPCC (A1B) using a large number of investigated sites ([Fig. ", "1](#f1){ref-type=\"fig\"}). ", "In total, 21 cropland and 30 grassland sites representing most important soil classes of Central Europe were sampled and SOC pools were fractionated following the approach of Zimmermann *et al*.[@b34], who were able to empirically link SOC fractions to RothC pools. ", "In a preliminary study, C inputs of major crops and grassland in Bavaria were determined with a high spatial and temporal resolution[@b35], which enabled a calculation of site-specific C input values. ", "The RothC model was then used to simulate SOC development under three different C input scenarios, which covered the range of expected crop yield development in Bavaria.", "\n\nResults\n=======\n\nClimate conditions at study sites and projected changes\n-------------------------------------------------------\n\nThe ensemble approach on the basis of 19 climate models revealed reliable spatially differentiated projections of air temperature, precipitation and evapotranspiration for all studied sites ([Table 1](#t1){ref-type=\"table\"}, [Fig. ", "2](#f2){ref-type=\"fig\"}). ", "In general, cropland sites exhibited average long-term values (1971 to 1999) for mean annual temperature of 8.3 to 8.9 °C, for mean annual precipitation of 831 to 873 mm and for mean annual evapotranspiration of 707 to 760 mm. ", "Between 2000 and 2095 climate projections under the A1B climate scenario revealed increases in air temperature by 3.1 to 3.4 °C, in precipitation by 35 to 82 mm and in evapotranspiration by 80 to 123 mm. ", "Due to their main distribution in pre-alpine regions, grassland sites had slightly lower mean annual temperatures of 7.6 to 8.7 °C, considerably higher values of mean annual precipitation of 846 to 1331 mm and slightly lower mean annual evapotranspiration of 663 to 739 mm. ", "The climate projections indicated for grassland sites a temperature increase of 3.2 to 3.4 °C, a variable change of precipitation of −36 to 95 mm and an increase of evapotranspiration of 77 to 143 mm.", "\n\nBasic soil properties, SOC fractions and C input\n------------------------------------------------\n\nBasic soil properties and SOC fractions for each soil unit under cropland and grassland are given in [Table 2](#t2){ref-type=\"table\"}. ", "In general, cropland soils revealed higher thicknesses of the A horizon (29 ± 6 cm) compared to grassland soils (23 ± 6 cm). ", "Clay contents ranged between 21 and 52% in soil units under cropland and from 19 to 45% under grassland. ", "The contribution of OC in different soil fractions to bulk SOC stocks differed strongly among the investigated soil/land use units. ", "Generally, DOC contributed with only 2 to 7% to total SOC stocks of both cropland and grassland topsoils. ", "Considerable differences between soil units were found for the POM fraction that contained 5 to 21% of total SOC stocks in soils under cropland and 3 to 16% under grassland. ", "The highest POM-OC amounts were found for Cambisols from Tertiary material (C1) as well as from sandstone (C6, C7). ", "For the S+A fraction distinct differences were found between cropland and grassland soil units. ", "Under cropland, S+A contained only 2 to 10% of bulk SOC with the exception of groundwater-affected soils (G) that stored 16%. ", "In contrast, grassland soil units revealed much higher OC amounts in the S+A fraction (16 to 34% of bulk SOC) with highest amounts in groundwater-affected soils (G, 57%). ", "The major part of SOC was found in the s+c fraction that contained 50 to 83% of total SOC stocks independent from land use (only groundwater-affected soils under grassland revealed a considerably lower contribution of 30%). ", "The inert rSOC fraction contained OC amounts of 3% to 10% of total SOC stocks without distinct differences between cropland and grassland soil units. ", "In total, soil units under cropland revealed significantly (P \\< 0.05) lower SOC stocks in A horizons (59 ± 21 t ha^−1^) than grassland soils (72 ± 24 t ha^−1^). ", "The calculated mean C input values derived from the period from 1995 to 1999 showed no significant differences among soil units under cropland and grassland. ", "The C inputs ranged between 3.4 and 4.1 t ha^−1^ in cropland soils and from 4.5 to 5.3 t ha^−1^ in grassland soils. ", "Over a 16 year period from 1995 to 2010, C inputs in cropland showed no significant trend but remained on a constant level ([Fig. ", "3](#f3){ref-type=\"fig\"}). ", "In grasslands soils, C inputs revealed a slight increase of 8% (based on a linear trend with an R^2^ value of 0.23).", "\n\nProjected development of SOC stocks under different C input scenarios\n---------------------------------------------------------------------\n\nThe projected development of SOC stocks of cropland and grassland soils under the reference scenario and different C input scenarios are shown in [Figs 4](#f4){ref-type=\"fig\"} and [5](#f5){ref-type=\"fig\"}. ", "In cropland soils, the reference climate scenario (constant average climate conditions 1970--1999) showed an increase of mean SOC stocks from 58.5 ± 20.8 t ha^−1^ in 2000 to 66.3 ± 13.9 t ha^−1^ in 2095. ", "The projection of SOC stocks under climate change and the constant C input scenario C0 indicated a slight increase of SOC stocks until 2020 up to 61.7 ± 18.1 t ha^−1^, followed by a slight decline down to 57.2 ± 11.8 t ha^−1^ in 2095. ", "Under climate change and C input scenario C20−, a noticeable decline of SOC stocks to 52.4 ± 11.2 t ha^−1^ in 2095 was determined after a peak of 60.9 ± 18.0 t ha^−1^ in 2020. ", "Climate change and the C input scenario C20+ revealed a slight SOC stock increase up to 61.6 ± 12.4 t ha^−1^ in 2095.", "\n\nThe calculated net SOC change as the difference between the reference scenario and climate/C input scenarios showed mean losses of SOC stocks of −9.1 t ha^−1^ (−16% of initial SOC stocks) under climate change and C0, of −13.9 t ha^−1^ (−24%) under climate change and C20− and of −4.7 t ha^−1^ (−8%) under climate change and C20+ ([Fig. ", "6](#f6){ref-type=\"fig\"}). ", "Distinct differences of SOC losses were found among the investigated soil units under cropland ([Table 2](#t2){ref-type=\"table\"}). ", "The highest relative SOC losses (compared to total SOC amount) were found for intermediate to deep soils with clay accumulation in the subsoil (L2) and Cambisols from Tertiary material (C1). ", "For the scenarios C0, C20− and C20+, SOC stocks in these soil units decreased by −20 to −21%, −30 to −31% and −11 to −12%, respectively. ", "For all other soil units under cropland the respective SOC decreases ranged between −12 to −17%, −19 to −26% and −2 to −9%.", "\n\nFor grassland sites, only a slight increase of mean SOC stocks from 71.6 ± 24.0 t ha^−1^ in 2000 to 74.9 ± 13.7 t ha^−1^ in 2095 was projected for the reference scenario ([Fig. ", "5](#f5){ref-type=\"fig\"}). ", "The climate change and C0 scenario revealed a SOC stock decrease down to 67.4 ± 10.6 t ha^−1^ in 2095 after a peak of 73.4 ± 17.5 t ha^−1^ in 2020. ", "SOC projections under climate change and C20− showed a considerable decline down to 61.2 ± 10.1 t ha^−1^ in 2095. ", "A slight increase of SOC stocks up to 73.1 ± 10.9 t ha^−1^ was found for climate change and the C20+ scenario. ", "The resulting net SOC changes accounted for −7.5 t ha^−1^ for C0 (−11% of initial SOC stocks), −13.7 t ha^−1^ for C20− (−19%) and −1.8 t ha^−1^ for C20+ (−3%) ([Fig. ", "6](#f6){ref-type=\"fig\"}). ", "Among different soil units under grassland, distinct differences of SOC changes were detected ([Table 2](#t2){ref-type=\"table\"}). ", "In general, soil units mainly distributed in the southern part of Bavaria (groundwater-affected soils, G; soils with clay accumulation in the subsoil L1, L2; Cambisols and Luvisols from moraine material, C2) showed considerably lower SOC decreases than other investigated soil units. ", "For C input scenarios C0 and C20−, relative SOC decreases ranged between −1 to −7% and −9 to −16%, respectively. ", "Under scenario C20+, even SOC increases of 1 to 6% were projected for these soil units. ", "In contrast, all other soil units under cropland revealed much higher declines of SOC of −11 to −23% for C0, −19 to −34% for C20− and −2 to −12% for C20+.", "\n\nEstimation of total SOC changes in agricultural soils of Bavaria\n----------------------------------------------------------------\n\nIn order to estimate the total changes of SOC stocks for the investigated soil units on an area basis, projected mean SOC stocks from all studied sites for a soil unit were multiplied with the respective area of the soil unit ([Table 3](#t3){ref-type=\"table\"}, [Fig. ", "7](#f7){ref-type=\"fig\"}). ", "In general, cropland and grassland topsoils of Bavaria stored 122.9 Mt and 192.9 Mt SOC in 2000. ", "In croplands, the soil units intermediate to deep Luvisols (L2) and Cambisols from Tertiary material (C1) with the largest extend in Bavaria stored 40% of total SOC stocks. ", "Moreover, the soil units groundwater-affected soils (G), shallow soils from limestone weathering (C3) and clay-rich soils (V) contained 41% of total SOC stocks due to relatively high soil-unit-specific SOC stocks of 71.8 to 80.8 t ha^−1^. Estimations of total projected SOC changes under the scenarios C0, C20− and C20+ revealed SOC losses of 20.3 Mt, 30.9 Mt and 10.5 Mt for cropland soils, respectively. ", "The highest absolute SOC losses were found for intermediate to deep Luvisols (L2) and Cambisols from Tertiary material (C1) due to their spatial extent and projected high decreases of SOC.", "\n\nSoil units under grassland uniformly contributed to total SOC stocks. ", "For the scenarios C0, C20− and C20+, total SOC losses of 11% of initial SOC stocks (7.6 Mt), 20% (13.7 Mt) and 3% (2.0 Mt) were estimated for grassland soils, respectively. ", "However, for the scenario C20+ marginal increases of total SOC stocks of 0.1 to 0.3 Mt were estimated for grassland soil units in the vicinity of the Alps (groundwater-affected soils, G; soils with clay accumulation in the subsoil L1, L2; Cambisols and Luvisols from moraine material, C2). ", "In total, the projections revealed absolute SOC losses of 27.9 Mt for the scenario C0, 44.6 Mt for C20− and 12.5 Mt for C20+ in agricultural soils of Bavaria. ", "These SOC losses correspond to total emissions of CO~2~-equivalents of 102.3 Mt, 163.6 Mt and 45.9 Mt, respectively.", "\n\nDiscussion\n==========\n\nReliable projections of SOC stock evolution using the RothC model require a reasonable estimation of actual SOC pool size by soil fractionation[@b34]. ", "The application of proposed pedotransfer functions or equilibrium model runs as alternative methods for SOC pool size estimation may be adequate in long-term undisturbed land use systems or for long projection periods[@b26][@b36], but are probably only partly suitable for intensively managed croplands and accurate projections for coming decades. ", "Moreover, the determination of the C input on the basis of the C allocation method using crop-specific C allocation coefficients and county-specific crop yields is a promising method to estimate C inputs precisely[@b35][@b37]. ", "This was confirmed by the reference scenarios (SOC projections under constant climatic conditions) that indicated only a slight overestimation of C inputs ([Figs 4](#f4){ref-type=\"fig\"} and [5](#f5){ref-type=\"fig\"}), assuming that SOC stocks at all investigated sites were in equilibrium. ", "Therefore, the overall accuracy of our modelling approach can be assessed as relatively high.", "\n\nOur projections of SOC stocks under future climate change and constant C inputs revealed substantial SOC losses for cropland (−16%) and grassland (−11%) in Bavaria until 2095 ([Table 1](#t1){ref-type=\"table\"}, [Fig. ", "6](#f6){ref-type=\"fig\"}). ", "The projected mean temperature increase of 3.3 °C at the study sites until 2095 and slightly increased precipitation under the A1B climate scenario will obviously lead to an increased mineralization of SOC stocks[@b3][@b5]. ", "An anticipated decline of C inputs by 20% (C20−) would result in even higher decreases of SOC by 24 and 19% for cropland and grassland, respectively. ", "Under cropland, projected SOC losses affected all investigated soil units, particularly Cambisols from Tertiary material (C1). ", "This is mainly attributed to the fact, that these soils are characterized by relatively low clay contents (21 ± 6%). ", "As a result, these soils contain a much lower proportion of SOC stabilized in soil aggregates and the s+c fraction and an equivalent higher contribution of labile SOC (DOC + POM) than other cropland soils ([Table 2](#t2){ref-type=\"table\"}). ", "Under grassland, slightly lower projected SOC losses compared to cropland are due to generally higher C inputs ([Fig. ", "3](#f3){ref-type=\"fig\"}) and considerably higher proportions of aggregate-protected SOC ([Table 2](#t2){ref-type=\"table\"}). ", "Among grassland soil units, noticeably lower SOC declines were projected for soils in relatively cool, pre-alpine regions with precipitation amounts \\>1000 mm and relatively high C input values \\>5 t ha^−1^. Remarkably, even under the optimistic assumption of an increase of C inputs by 20%, a decline of SOC stocks by 8 and 3% was projected for cropland and grassland, respectively ([Table 1](#t1){ref-type=\"table\"}, [Fig. ", "6](#f6){ref-type=\"fig\"}). ", "Only grassland soil units in pre-alpine regions revealed a slight SOC increase.", "\n\nThe finding of generally declining SOC stocks under future climate change is in line with some other SOC projection approaches for agricultural soils. ", "Xu *et al*.[@b27] modelled SOC changes in eight Irish grassland soils from 2021 to 2060 assuming constant C inputs on the basis of RothC and two different initialization methods. ", "They estimated a decrease of SOC stocks by 2 to 6% for different climate change scenarios, but speculated that future summer droughts could reduce C inputs in grasslands. ", "In a study in Australia, a SOC decrease of 10 to 11% was predicted under the A2 climate scenario for the period 2008 to 2100 for 12 grassland sites with a constant C input using different initialization methods of RothC[@b26]. ", "For cropland and grassland soils in Louisiana, a RothC simulation under different climate scenarios and unchanged C input revealed SOC declines of 11 to 18% and 12 to 17%, respectively[@b24]. ", "An estimation of SOC changes of agricultural soils of Italy within the 21^st^ century using legacy soil data indicated SOC decreases of 3.6 to 11.5% for different climate scenarios and unchanged C inputs[@b23]. ", "A European-wide study on the basis of legacy data and different climate scenarios estimated SOC declines between 1980 and 2080 of 10 to 14% for croplands and 6 to 10% for grasslands without C input changes[@b19]. ", "However, these authors also incorporated a simulation of NPP changes in order to estimate C input changes and found a lower decrease of croplands SOC stocks of 3 to 4% and even a slight increase for grassland due to a strong projected increase of NPP.", "\n\nSimilar studies that assumed increased C inputs due to increased NPP generally found SOC gains. ", "For agricultural soils of northeastern Spain, a mean increase of SOC stocks of 6.3% was estimated for different climate projections and agricultural systems (with a wide range of SOC changes of −12.3 to 32.8%) for the period 2007 to 2087 under the assumption of large C input increases of up to 44%[@b22]. ", "Lugato *et al*.[@b21] also estimated a slight SOC gain of 2% for European agricultural soils in the 21^st^ century. ", "In this study, higher soil respiration under climate change was counterbalanced by an assumed 22% higher crop productivity. ", "In SOC projection studies including all land uses on the global or the European scale, both increases and decreases of SOC stocks were projected for coming decades, but it was generally assumed that NPP increases and associated C input gains would offset or even outperform SOC losses induced by global warming, also in agricultural soils[@b20][@b25][@b38][@b39].", "\n\nFrom our point of view, assumed C input increases in agricultural soils under climate change is a rather optimistic scenario given rising evidence for negative effects of climate change on crop productivity. ", "In several studies, an increased occurrence of droughts and high temperatures above the optimum of crops and a shortening of the growing season were associated with a reduction of NPP[@b40][@b41][@b42][@b43][@b44][@b45][@b46]. ", "The exceptional dry and hot year 2003 provided a first hint for such a development, as a dramatic decline of C inputs was determined for 2003 ([Fig. ", "4](#f4){ref-type=\"fig\"})[@b47]. ", "As such years are projected to increase under climate change, the possibility of stagnating or even reduced C inputs should be considered more strongly in SOC projections. ", "Moreover, socioeconomic reasons, e.g. a change of agricultural management as a consequence to changes in the common agricultural policy (CAP) in the EU in the 1990s, were quoted to contribute to observed yield stagnation in Europe in the last 25 years[@b9][@b42][@b48]. ", "Some authors assumed that future improvement of technology, which was mainly responsible for the obtained yield increases until the 1990s, could lead to a strong increase of crop productivity, but as its drivers are not clear, future technology development is afflicted with high uncertainty[@b26][@b49]. ", "Despite ongoing technological improvement in the last three decades, particularly related to plant breeding[@b50], yields of many crops showed no equivalent increase.", "\n\nThe projected decrease of agricultural SOC stocks is associated with a substantial emission of CO~2~ into the atmosphere. ", "A rough estimation for the entire agriculturally used land in Bavaria revealed emissions of 46 to 164 Mt CO~2~-equivalents for the period 2000 to 2095 (depending on the C input scenario) ([Table 3](#t3){ref-type=\"table\"}, [Fig. ", "7](#f7){ref-type=\"fig\"}). ", "On a yearly basis, this would increase the CO~2~ emissions of the agricultural sector of Bavaria by 4 to 12% (based on an estimated CO~2~ emission of approximately 14 Mt in 2012). ", "Given the high projected amount of CO~2~ emitted by agricultural soils, climate-change-induced SOC changes should be included in national C accounting programs. ", "Besides the emission of CO~2~, projected losses of SOM in agricultural soils may have negative effects on several important soil functions, e.g. retention of pollutants, buffering capacity, erosion control, water holding capacity and nutrient supply. ", "Overall, the estimated SOC losses could have detrimental effects on soil fertility and ecosystem resilience, which would in turn aggravate crop productivity and thus residue-derived C input -- a positive feedback. ", "This calls for an extension of soil monitoring programs and the implementation of early warning indicators in order to verify projected SOC losses.", "\n\nIn view of these potential risks, there is the need to increase C inputs in order to maintain present SOC stocks. ", "A comparison of relative C inputs (related to the SOC stock) for the reference scenario (current climate conditions) and the climate change scenario indicated a future increase of C inputs of 29% needed to counterbalance increased decomposition of SOM ([Fig. ", "8](#f8){ref-type=\"fig\"}).", "\n\nSeveral options were proposed to enhance C inputs in agricultural soils. ", "Promising agricultural practices comprise increased return of crop residues and incorporation of other organic inputs, improved crop rotation including legumes and catch crops, organic farming with clover prominent in the rotation, increased cultivation of bioenergy and perennial crops, improved pasture and livestock management, agroforestry and conversion of cropland to grassland[@b51][@b52][@b53][@b54][@b55][@b56][@b57][@b58][@b59][@b60]. ", "Recently, such C sequestration options were proposed to offset global anthropogenic CO~2~ emissions in form of the \"4‰ concept\" at the climate conference in Paris (COP21). ", "This concept is based on the assumption that a yearly increase of global SOC stocks (first 40 cm of soils except permafrost) of 4‰ by improved management would largely contribute to counterbalance human-induced CO~2~ emissions. ", "However, our results indicate that a distinct increase of C inputs by improved agricultural management would be necessary in future decades only to counterbalance enhanced SOM decomposition. ", "Therefore, the potential contribution of improved management of agricultural soils to decrease the atmospheric rise in CO~2~ should be evaluated more carefully.", "\n\nAlthough our results provide a good estimate on the potential trajectories of SOC storage in temperate agricultural soils under the given assumptions of climate change and C inputs, model predictions need independent verification and a calculation of uncertainty. ", "There are different sources of uncertainty that may contribute to the final uncertainty in predictions, for instance, uncertainty in model parameters, and in model structure. ", "Although the RothC model was developed for temperate agroecosystems and has been applied successfully in regions under similar climatic and pedogenic conditions in the past, it is still unknown whether RothC's default parameters may need to be adapted for the study region. ", "Also, the existence of a completely inert pool has been challenged[@b61][@b62], and the potential slow dynamics of this pool may become relevant for long-term predictions.", "\n\nParticularly relevant sources of uncertainty for these types of predictions are the temperature- and moisture-dependent functions implemented in this model to modify decomposition rates. ", "The rate modification by temperature is identical for each SOM pool in RothC despite indications for varying temperature sensitivity of labile and stable SOM pools. ", "The temperature sensitivity of differently stabilized SOM pools is an element of uncertainty in current SOM turnover models and is thus a highly topical debate with regard to global change[@b2][@b63]. ", "The feedback between climate change and C losses from soil would be much stronger than suggested by equal temperature sensitivities of all SOM pools -- like in our calculations, if stable SOM pools react more sensitively to warming than more labile SOM pools. ", "In our studied soils the stable SOM pools amounted for 66 to 90% of total SOC. ", "According to the Arrhenius equation stable SOM pools are thought to be more temperature sensitive than less stabilized SOM pools[@b3][@b64]. ", "Results from laboratory incubations and long-term experiments indicate that the more stable SOM pools are indeed more temperature sensitive[@b65][@b66][@b67]. ", "A higher temperature sensitivity of the stable SOM pools implies that the projected mean temperature increase of 3.3 °C may lead to even stronger and sustained C losses from soils than suggested by our scenarios. ", "Therefore, there is the need to integrate information on temperature sensitivity in soil carbon models.", "\n\nFurther critical issues are related to C input projections. ", "Although our scenarios cover the range of expected C input development based on yield projections, more spatially and temporarily precise C input scenarios are needed. ", "A combination of sophisticated yield models together with an estimation of future changes of C allocation patterns of crops could be a promising approach to derive more precise C input estimates.", "\n\nMaterials and Methods\n=====================\n\nStudy area\n----------\n\nThe state of Bavaria comprises a total area of 70550 km^2^ and is located in southeast Germany. ", "The northwestern part of Bavaria is dominated by the southern German escarpment landscape that adjoins the low mountain ranges of the Bohemian Massif in the east. ", "Southwards the Molasse basin ascends to the mountain range of the Alps. ", "Elevation ranges between 107 and 2962 m above sea level. ", "Due to its location in central Europe, Bavaria exhibits a sub-oceanic climate that is characterized by a transitional situation between a maritime climate in the northwest and sub-continental influences in the east. ", "Mean annual temperature and precipitation from the escarpment landscape in the northwest to the Alps in the south range between 9° and 4 °C and 550 and 2500 mm, respectively. ", "Around half of the area of Bavaria is under agricultural use, with cropland and grassland accounting for areas of 22843 km^2^ (32% of the total area) and 9897 km^2^ (14% of the total area), respectively ([Fig. ", "1](#f1){ref-type=\"fig\"}). ", "Dominant soil classes within agricultural land are soils with well-developed B horizons (Cambisols), soils with clay accumulation in the subsoil (Luvisols), soils from limestone weathering with or without loess coverings (Cambisols, Luvisols, Leptosols), clay-rich soils (Cambisols, Vertisols, Stagnosols) and groundwater-affected soils (Gleysols, Fluvisols) according to the German soil system and the equivalent Reference Soil Groups of the WRB system[@b68].", "\n\nDue to the heterogeneous nature in terms of geology, soils and climate, the conditions for agriculture differ considerably within Bavaria[@b69]. ", "In the south of Bavaria, the region of the Alps and Pre-Alps is characterized by high mean annual precipitation (MAP) of \\>1000 mm and relatively low mean annual temperatures (MAT) between 5.4 and 7.5 °C. ", "Intensive grassland use for cattle husbandry prevails with up to six swaths per year. ", "The scarce arable land is predominantly cultivated with corn for silage (*Zea mays*). ", "To the north, between the Pre-Alps and the Danube River, the Tertiary Hills Region encompasses a small structured mixed landscape. ", "A more temperate climate with MAT of 7.0--7.7 °C, MAP of 700 to 1000 mm and deep, loamy soils provide good farming conditions. ", "Here, animal husbandry has decreased tremendously over the last 20 years and the conversion of grassland to arable land has been strongest within Bavaria. ", "Corn for biogas production has become a major crop in the rotation together with a mix of other cereals and rapeseed (*Brassica napus*). ", "Within the northern part of the Tertiary Hills Region and further northwest in Bavaria, small, isolated Loess Regions are prominent and form the most productive areas in Bavaria, accompanied by favourable climatic conditions, leading to intensive agricultural production of e.g. sugar beet (*Beta vulgaris*) and winter wheat (*Triticum aestivum*). ", "The East-Bavarian Mid-Range Mountains are characterized again by rather unfavourable climatic and pedological conditions for most high-output cereals. ", "While small areas are used as grassland, potatoes (*Solanum tuberosum*), triticale (×*Triticosecale*), a hybrid of wheat and rye, spring barley (*Hordeum vulgare*) and oats (*Avena sativa*) find good conditions. ", "In the central part of northern Bavaria, the region of Jurassic sediments is characterized by MAT of 7.1--7.2 °C, MAP of around 800 mm and fertile soils. ", "To the northwest, the large northern Bavarian Hill Area exhibits a slightly warmer and drier climate, but sandy, acidic soils and low water availability during the summer months inhibit intensive agricultural production, allowing the cultivation of winter rye (*Secale cereale*) and triticale. ", "Further to the west, the Franconian Lowlands are characterized by lower precipitation (\\<700 mm), higher MAT (7.5--9.2 °C) and clay-rich, fertile soils, which restrict agriculture to drought-resistant crops like spelt (*Triticum spelta*) and durum wheat (*Triticum durum*) together with winter rye. ", "These grains are also cultivated in the very north-eastern part of Bavaria forming the Franconian Mid-Range Mountains that exhibit a cooler climate (5.2--8.0 °C) and acidic soils but the main use of agricultural land is grassland. ", "Overall, there has been a general trend of intensification of arable land, mainly on more or less productive sites in Bavaria, enhanced through the lifting of the obligatory set-aside policy in 1992, the introduction of a series of renewable energy subsidies since 2003, leading to a huge demand for green maize for biogas production and, last but not least, technological progress in general. ", "On the other hand, there is a visible trend of extensification of marginal sites, where there is a tendency of farmland abandonment, further decrease in livestock numbers and remaining unclear perspectives of farming in the future. ", "Additionally, the steady demand for land for urbanisation in the booming regions of Bavaria is increasing the pressure on agricultural land. ", "However, the share of arable land remained since 20 years and only grassland has decreased substantially, mainly due to compensatory effects for the developments.", "\n\nSelection of study sites and soil sampling\n------------------------------------------\n\nStudy sites were selected for all major soil units and land uses in Bavaria using a map that combines predominant soil units with main land uses[@b70]. ", "The map comprises 38 soil units within Bavaria resulting from an intersection of soil type and parent material with macroclimate. ", "These soil units were subdivided to 61 units according to cropland and grassland use on the basis of CORINE Land Cover data. ", "Due to the great effort of the fractionation approach to derive RothC pools, all soil/land use units were excluded which were smaller than 1% of the area of Bavaria. ", "For each of the remaining 18 soil/land use units (8 soil units under cropland and 10 soil units under grassland) representative locations were selected on the basis of available soil material and data from different soil surveys and permanent soil observation sites in Bavaria compiled by the Bavarian Environment Agency ([Fig. ", "1](#f1){ref-type=\"fig\"}). ", "Although grassland covers only about half the area of cropland in Bavaria, grassland use is distributed over a much wider climatic range and thus more grassland soil units were incorporated in this study. ", "For the majority of soil/land use units, three soil profiles provided representative data. ", "For three of the soil units under cropland (shallow soils from limestone weathering with or without loess coverings; intermediate to deep soils from limestone weathering with or without loess coverings; soils with well developed B horizons from sandstone with initial podzolisation) only two representative soil profiles were available. ", "In total, 51 study sites (21 long-term cropland sites and 30 permanent grassland sites) were selected. ", "The selected soil profiles comprise permanent soil monitoring sites and a grid sampling of 8 × 8 km within Bavaria between 2000 and 2004. ", "For each soil profile, a representative location was selected within a radius of 500 m around the grid node to achieve a homogeneous sampling area in terms of vegetation, relief, soil type and parent material as well as a central position in the particular land use type. ", "Anthropogenic disturbances in the subsoil were excluded in a pre-exploratory survey using a soil auger. ", "Within the topsoil (A horizons), soil material was collected as a composite sample from four sub-locations located with a radius of 6.6 m and four sub-locations with a radius of 3.8 m around the main soil profile in order to cover the small-scale heterogeneity of the soils. ", "At the main profile, soil horizons were additionally sampled using steel cylinders for the determination of bulk density (BD). ", "The content of rock fragments \\>2 mm was estimated visually in the soil profiles.", "\n\nFractionation of SOC pools and determination of basic soil properties\n---------------------------------------------------------------------\n\nFor each topsoil horizon (A horizons), soil material was fractionated according to the approach of Zimmermann *et al*.[@b34] and Poeplau *et al*.[@b71] ([Fig. ", "9](#f9){ref-type=\"fig\"}). ", "Soil material was sieved to 2 mm and 30 g were suspended in 150 ml of deionised water and dispersed using a calibrated ultrasonic probe-type (Bandelin, Berlin, Germany) with an output energy of 22 J ml^−1^. This relatively low energy was applied to disrupt only weakly stabilized soil macroaggregates and to prevent the disruption of mineral-associated SOM[@b72]. ", "The suspension was wet sieved over a 63 μm sieve until the rinsing water was clear and subsequently filtered through a 0.45 μm membrane filter. ", "The rinsing water was collected and dissolved organic carbon (DOC) was measured using a TOC analyzer 5050A (Shimadzu, Duisburg, Germany). ", "The fractions \\>0.45 μm and \\>63 μm were dried at 40 °C and weighted. ", "Afterwards, 50 ml of a sodium polytungstate solution with a density of 2.0 g cm^−3^ [@b71] was added to the fraction \\>63 μm and the floating particulate organic matter (POM) was separated after centrifugation at 1000 g for 15 minutes. ", "The remaining fraction \\>63 μm (sand and stable aggregates, S+A) and the POM fraction were washed with deionised water to remove the sodium polytungstate, dried at 40 °C and weighted. ", "The fraction \\>0.45 μm (silt and clay, s+c) was homogenized and a subsample of 1 g was oxidized with sodium hypochlorite (NaOCl) to separate a stable SOC fraction. ", "50 ml of 6% NaOCl, adjusted to pH 8 with concentrated HCl, was added to the subsample and after 18 hours at 25 °C the sample was centrifuged at 1000 g for 15 minutes and washed with deionised water. ", "The oxidation procedure was repeated twice. ", "The residual SOC fraction (rSOC) was dried at 40 °C and weighted. ", "All solid fractions were measured for SOC and N concentration by dry combustion on an EA 3000 analyser (Hekatech, Wegberg, Germany). ", "Soil fractions that contained CaCO~3~ were heated to 500 °C for 4 hours to remove organic carbon, and the concentration of inorganic C of the residual material was determined by dry combustion. ", "The SOC content was calculated by subtracting inorganic C from the total C concentration of the untreated material. ", "For the determination of clay contents, soil samples (\\<2 mm) were oxidized with H~2~O~2~ to remove organic matter (OM). ", "The remaining material was dispersed with Na~4~P~2~O~7~ and shaken for 16 to 24 hours, followed by wet sieving to isolate sand fractions \\>63 μm. ", "To determine silt and clay fractions, approximately 3 g of the \\<63 μm fraction was suspended in deionised water using Na~4~P~2~O~7~ and an ultrasonication for 3 minutes with 75 J mL^−1^ was conducted. ", "Afterwards, the distribution of silt and clay fractions was obtained by measuring the X-ray absorption of the soil-water suspension during sedimentation of the soil particles using a Micromeritics Sedigraph 5100 (Micromeritics, Norcross, GA, USA). ", "For the determination of BD, the mass of the oven-dry soil (105 °C) was divided by the volume of the soil cores.", "\n\nEstimation of the C input\n-------------------------\n\nIn a preliminary study[@b35], annual C input values were estimated for most important crops as well as grassland in Bavaria on the county-scale for the period from 1951 to 2010. ", "The C input was calculated on the basis of the C allocation approach proposed by Bolinder *et al*.[@b37]. ", "This method is based on the allocation of NPP to four plant fractions: the agricultural product (R~P~), aboveground biomass excluding R~P~ (R~S~), belowground biomass excluding RP (R~R~) and extra-root C (R~E~). ", "Due to possible changes of the proportions of the C allocation coefficients R~P~, R~S~, R~R~ and R~E~ in the period between 1951 and 2010 induced by progress in plant breeding, improved crop management and fertilization, C allocation coefficients were estimated both for the beginning (1951--1955) and the end (1995--2010) of the considered period. ", "For the period 1951 to 1955, C allocation coefficients were derived from numerous agricultural field studies and reports that were conducted in the post-war period. ", "The proportions of R~P~ and R~S~ were derived from agricultural statistics for Germany from 1951 to 1955 and from Köhnlein and Vetter[@b73]. ", "The contribution of R~R~ to NPP was estimated on the basis of several field studies which determined the root biomass of different crop plants gravimetrically by washing of soil monoliths[@b74][@b75][@b76][@b77][@b78][@b79][@b80][@b81][@b82]. ", "The contribution of R~E~ was estimated to be two-thirds of root biomass according to Bolinder *et al*.[@b37]. ", "Recent C allocation coefficients for the period 1995--2010 were derived from agricultural statistical data for Germany as well as literature data from 1995 onwards[@b37][@b83][@b84][@b85][@b86][@b87][@b88]. ", "If no data was provided for R~E~, the contribution of rhizodeposition was estimated as described above. ", "Between 1955 and 1995, allocation coefficients were linearly interpolated for each year according to the linear trend of crop yields within this period.", "\n\nThe total C input as the sum of the C input of all plant fractions except the agricultural product (C~S~+C~R~+C~E~) can be calculated using the relative C allocation coefficients R~P~, R~S~, R~R~ and R~E~ as well as the crop yield:\n\nwhere C~S~ is the C input of aboveground biomass excluding the agricultural product (t ha^−1^ yr^−1^), C~R~ is the C input of belowground biomass (roots) (t ha^−1^ yr^−1^), C~E~ is the C input of rhizodeposition (t ha^−1^ yr^−1^) and C~P~ is the amount of C in the agricultural product (t ha^−1^ yr^−1^). ", "The amount of C in the agricultural product (C~P~) can be calculated using dry-matter yields of respective crops obtained from agricultural statistics assuming that the C content of different plants and plant parts is 0.45 kg kg^−1^ [@b37]. ", "For the estimation of C inputs of the selected study sites, information on the crop rotation, return of harvest residues and the input of organic fertilizers were gained from farmers for each site for a 16-year period (1995--2010). ", "Mean C input values for the initialization of RothC were calculated using C input data derived from 1995 to 1999 before the start of the soil sampling campaign.", "\n\nClimate projections\n-------------------\n\nProjections of climate parameters for each study site for the period 2000 to 2095 were derived by using a multi-model ensemble approach on the basis of climate change scenario A1B. The ensemble consists of 19 climate predictions for Germany. ", "They are a combination of different regional climate models (RCM) that are driven by several global climate models (GCM) ([Table 4](#t4){ref-type=\"table\"}). ", "The multi-model ensemble had been developed in the European framework project ENSEMBLES[@b89]. ", "As climate models represent reduced natural processes, one model cannot give the full range of information about uncertainties of future climate. ", "To handle these model-based uncertainties the use of ensembles for climate impact studies is widely accepted and recommended[@b90]. ", "The result of every member of the ensemble is equally probable and represents one possible future but not the only one. ", "The climate data set for the 51 study sites in Bavaria, provided by the German Weather Service (DWD), covers the period from January 2000 to December 2095 and consists of monthly data on air temperature, precipitation and evapotranspiration of the FAO[@b91]. ", "The latter refers to a short green grass completely shading the ground and with adequate water supply. ", "The spatial resolution of climate data is 25 × 25 km. ", "Every site is represented by a grid cell of 3 × 3 grid points with the study site in the middle. ", "For each grid point median values were calculated for temperature, precipitation and evapotranspiration from the 19 climate projections. ", "To account for spatial insecurity the arithmetic mean of the results of the nine grid points was used for this study.", "\n\nRunning the RothC model for different carbon input scenarios\n------------------------------------------------------------\n\nTo predict the SOC stock development in the topsoil, the RothC 26.3 model was used, which was run in the R environment using the package SoilR[@b92]. ", "The model simulates the turnover of SOC on the basis of five conceptual pools. ", "Incoming plant material is separated into decomposable plant material (DPM) and resistant plant material (RPM), which are decomposed to humified organic matter (HUM), microbial biomass (BIO) and CO~2~. The HUM and BIO pools undergo further decomposition. ", "Each of these compartments decomposes by first-order kinetics with decay rate constants of 10, 0.3, 0.66 and 0.02 per year for DPM, RPM, BIO and HUM, respectively. ", "Only the inert organic matter pool (IOM) is resistant to decomposition. ", "The decay rate constants are modified by temperature and soil moisture deficit (difference between potential evapotranspiration and precipitation with a maximum deficit defined by the clay content). ", "For model initialization, the measured fractions from the A horizons were summed up and converted to model pools according to the approach of Zimmermann *et al*.[@b34] using average RPM/DPM and BIO/HUM splitting ratios for temperate croplands (0.0102 and 0.0272) and grasslands (0.1271 and 0.0259) ([Fig. ", "9](#f9){ref-type=\"fig\"}). ", "The selected 51 sites were modelled in monthly time steps using the default parameter set of RothC. In order to predict the evolution of SOC stocks from 2000 to 2095, the model was run under unchanged climate conditions (reference scenario, mean climate conditions from the period 1971 to 1999) and a moderate climate change scenario (A1B). ", "The reference scenario served as validation of the estimated C input values. ", "The difference of SOC projections between the reference and the climate change scenario represented the projected SOC change. ", "As a simplification, the measured SOC stock obtained from soil samples taken between 2000 and 2004 was assumed to resemble the stock of the year 2000.", "\n\nThe SOC projections were performed for three different C input scenarios as a realistic range of possible yield development: i) constant C input over time (mean C input from the period 1995 to 1999) (C0), ii) decreasing C input over time (reaching a 20% lower C input in 2095) (C20−) and iii) increasing C input over time (reaching a 20% higher C input in 2095) (C20+). ", "These scenarios were based on present and projected crop yields in this study, which showed a strong correlation with agricultural C inputs so far[@b35][@b93]. ", "The scenario C0 (constant C input) is based on recent yield stagnation of several crops in Bavaria. ", "Evidence was found that yields of most important crops of Bavaria are stagnating since the 1990s along with stagnating C inputs[@b9][@b35]. ", "Besides the Status quo of stagnating C inputs, several crop yield modeling approaches projected yield changes within the 21^st^ century. ", "For some study regions in southern Germany, a decline of yields of winter wheat and corn for silage by around 10 to 20% until the mid-century was projected[@b94][@b95]. ", "On the other hand, an estimation of changes of crop productivity in Europe assumed an increase of yields of major European crops by 15 to 32% from 2020 until 2080 under different climate scenarios (without considering technology development)[@b49]. ", "In order to cover the full range of expected crop yield development, the scenarios C20− and C20+ were included in this study.", "\n\nStatistics\n----------\n\nDescriptive statistical methods were used to analyze the soil and climate data sets for maximum and minimum values, mean, median, standard deviation, interquartile range, skewness, kurtosis, variance and coefficient of variation. ", "In order to test the significance of differences of soil properties between the investigated soil units and land uses one-way analyses of variance (ANOVA) combined with post hoc tests (Tukey and Scheffé) and Student's t-tests were applied. ", "Linear regression analyses were conducted to characterize the trend of C inputs. ", "All statistical calculations were carried out using the software IBM SPSS Statistics 19 (2010, IBM Corp., Armonk).", "\n\nAdditional Information\n======================\n\n**How to cite this article**: Wiesmeier, M. *et al*. ", "Projected loss of soil organic carbon in temperate agricultural soils in the 21^st^ century: effects of climate change and carbon input trends. *", "Sci. ", "Rep.* **6**, 32525; doi: 10.1038/srep32525 (2016).", "\n\nWe would like to thank Ulrike Maul, Nadine Eheim, Wiebke Wehrmann und Sigrid Hiesch for laboratory analysis. ", "We are grateful to the Federal Ministry for Education and Research for funding the BonaRes-Centre for Soil Research (BonaRes-Zentrum für Bodenforschung, Teilprojekt C, FKZ 031A608C) and to the Bavarian State Ministry of the Environment and Consumer Protection for funding the project \"Der Humuskörper bayerischer Böden im Klimawandel -- Auswirkungen und Potentiale\". ", "This work was supported by the German Research Foundation (DFG) and the Technical University of Munich within the funding programme Open Access Publishing.", "\n\n**Author Contributions** M.W., M.v.", "L. and I.K.-K. designed the study. ", "P.S., U.G., E.H. and B.S. provided soil samples and soil data. ", "C.P. and C.A.S. performed the modeling and H.M. and C.F. provided climate projections. ", "M.W., C.P., R.H. and A.K. compiled and analyzed data. ", "M.W. wrote the main manuscript with contributions of C.P., H.M., C.F., R.H. and M.v.", "L. All authors reviewed the manuscript.", "\n\n).](srep32525-f1){#f1}\n\n{#f2}\n\n{#f3}\n\n{#f4}\n\n{#f5}\n\n{#f6}\n\n).](srep32525-f7){#f7}\n\n{#f8}\n\n![", "Fractionation scheme of SOC pools according to the method of Zimmermann *et al*.[@b34] and Poeplau *et al*.[@b71] (s+c = silt- and clay-associated SOM less an inert fraction; DOC = dissolved organic matter; S+A = sand- and aggregate-associated SOM; POM = particulate organic matter; rSOC = inert SOM) and assignment to RothC pools (BIO = microbial biomass; HUM = humified organic matter; DPM = decomposable plant material; RPM = resistant plant material) using splitting ratios.](srep32525-f9){#f9}\n\n###### Long-term (1971--1999) mean annual temperature (MAT), mean annual precipitation (MAP), mean annual evapotranspiration (Evap) projected SOC changes (2000--2095) under constant C input (∆SOC C~0~), decreased C input by 20% (∆SOC C~−20%~) and increased C input by 20% (∆SOC C~+20%~) as well as projected changes of MAT, MAP and Evap (2000--2095) of major soil units in Bavaria under cropland (C) and grassland (G) (mean values ± standard deviation).", "\n\n land use soil class MAT (°C) MAP (mm) Evap (mm) ∆SOC C~0~ (t ha^−1^) ∆SOC C~−20%~ (t ha^−1^) ∆SOC C~+20%~ (t ha^−1^) ∆MAT (°C) ∆MAP (mm) ∆Evap (mm)\n ---------- ------------ ------------ ------------ ------------- ---------------------- ------------------------- ------------------------- ----------- ----------- ------------\n C G 8.9 ± 0.2 862 ± 63 747 ± 9 −11.8 ± 1.2 −17.1 ± 1.3 −6.9 ± 1.0 3.2 ± 0.1 57 ± 47 118 ± 21\n L2 8.9 ± 0.2 831 ± 20 747 ± 28 −9.4 ± 2.2 −14.0 ± 2.9 −5.2 ± 1.6 3.1 ± 0.1 59 ± 52 105 ± 19 \n C1 8.9 ± 0.1 834 ± 55 760 ± 11 −9.3 ± 2.7 −13.9 ± 3.6 −5.2 ± 1.8 3.1 ± 0.1 59 ± 44 123 ± 14 \n C3 8.3 ± 0.1 873 ± 79 713 ± 12 −8.5 ± 3.6 −13.4 ± 4.4 −4.1 ± 3.0 3.4 ± 0 82 ± 10 87 ± 10 \n C4 8.8 ± 0.1 845 ± 70 754 ± 17 −9.7 ± 1.5 −15.0±1.4 −4.8 ± 1.7 3.2 ± 0 50 ± 8 113 ± 1 \n C6 8.8 ± 0.2 840 ± 40 744 ± 8 −8.6 ± 1.7 −13.0 ± 2.6 −4.4 ± 1.0 3.3 ± 0.1 51 ± 11 114 ± 31 \n C7 8.3 ± 0.5 864 ± 105 707 ± 47 −4.8 ± 4.6 −9.3 ± 4.1 −0.7 ± 5.0 3.3 ± 0.1 62 ± 5 87 ± 28 \n V 8.4 ± 0.2 831 ± 31 710 ± 25 −9.3 ± 2.7 −14.3 ± 3.4 −4.6 ± 2.3 3.3 ± 0 35 ± 33 80 ± 20 \n G G 8.0 ± 0.4 1112 ± 260 683 ± 50 −4.4 ± 7.7 −10.6 ± 7.3 1.3 ± 8.1 3.3 ± 0 −8 ± 92 124 ± 29\n L1 7.6 ± 0.2 1327 ± 60 663 ± 31 −1.0 ± 5.3 −7.3 ± 4.5 4.7 ± 6.0 3.4 ± 0 −27 ± 12 143 ± 10 \n L2 7.9 ± 0.5 1129 ± 273 686 ± 50 −5.1 ± 7.7 −11.6 ± 7.6 0.8 ± 7.8 3.4 ± 0 2 ± 83 128 ± 33 \n C1 8.5 ± 0.9 1019 ± 231 731 ± 48 −7.0 ± 9.1 −13.4 ± 9.1 −1.1 ± 9.2 3.3 ± 0.1 4 ± 41 139 ± 10 \n C2 7.9 ± 0.7 1331 ± 267 669 ± 30 −4.0 ± 6.4 −9.8 ± 6.4 1.2 ± 6.4 3.3 ± 0.1 −36 ± 22 142 ± 3 \n C3 8.3 ± 0.6 846 ± 92 719 ± 49 −11.4 ± 5.6 −17.5 ± 6.2 −5.7 ± 5.1 3.3 ± 0.1 60 ± 26 94 ± 21 \n C5 8.6 ± 0.2 856 ± 36 739 ± 2 −11.7 ± 1.6 −17.5 ± 2.3 −6.3 ± 0.9 3.2 ± 0.1 95 ± 16 105 ± 14 \n C6 8.7 ± 0.3 871 ± 54 727 ± 39 −9.3 ± 1.0 −15.2 ± 1.6 −3.8 ± 0.6 3.3 ± 0 28 ± 33 112 ± 35 \n C7 8.0 ± 0.2 875 ± 63 698 ± 16 −10.8 ± 2.3 −17.2 ± 2.7 −4.8 ± 2.0 3.4 ± 0 71 ± 12 77 ± 6 \n V 8.2 ± 0.3 906 ± 41 708 ± 24 −10.2 ± 0.6 −16.5 ± 0.8 −4.5 ± 0.4 3.4 ± 0 69 ± 10 80 ± 5 \n\nG = groundwater-affected soils (Gleysols, Fluvisols); L1 = shallow to intermediate soils with clay accumulation in the subsoil (Luvisols); L2 = intermediate to deep soils with clay accumulation in the subsoil (Luvisols); C1 = soils with well developed B horizons from Tertiary material (Cambisols); C2 = soils with well developed B horizons from morainal material in places with clay accumulation in the subsoil (Cambisols, Luvisols); C3 = shallow soils from limestone weathering with or without loess coverings (Cambisols, Luvisols, Leptosols); C4 = intermediate to deep soils from limestone weathering with or without loess coverings (Cambisols, Luvisols); C5 = soils with well developed B horizons from acidic material with low base saturation (Cambisols); C6 = soils with well developed B horizons from sandstone with low base saturation (Cambisols); C7 = soils with well developed B horizons from sandstone with initial podzolisation (Cambisols, Podzols); V = clay-rich soils (Cambisols, Vertisols, Stagnosols).", "\n\n###### Depth of the A horizon, clay content, C input, OC amount of soil fractions (DOC = dissolved organic matter, SA = sand- and aggregate-associated SOM, POM = particulate organic matter, SC = silt- and clay-associated SOM less an inert fraction, rSOC = inert SOM) of major soil units in Bavaria under cropland (C) and grassland (G) (mean values ± standard deviation).", "\n\n land use soil class sites (n) A horizon (cm) clay (%) C input (t ha^−1^) DOC (t ha^−1^) SA (t ha^−1^) POM (t ha^−1^) SC (t ha^−1^) rSOC (t ha^−1^) SOC t ha^−1^)\n ---------- ------------ ----------- ---------------- ----------- -------------------- ---------------- --------------- ---------------- --------------- ----------------- ---------------\n C G 3 32 ± 7 30 ± 15 4.1 ± 0.3 2.5 ± 0.3 12.6 ± 18.7 4.6 ± 2.0 55.5 ± 14.8 5.7 ± 4.5 80.8 ± 2.5\n L2 3 29 ± 5 27 ± 8 3.5 ± 0.5 1.8 ± 0.3 1.0 ± 0.5 2.4 ± 2.0 36.8 ± 9.4 2.6 ± 0.5 44.5 ± 10.9 \n C1 3 29 ± 5 21 ± 6 3.5 ± 0.5 1.3 ± 0.3 1.9 ± 0.8 9.9 ± 8.4 29.3 ± 11.5 4.3 ± 1.7 46.8 ± 2.3 \n C3 2 26 ± 8 44 ± 13 3.5 ± 0.5 2.2 ± 1.6 2.3 ± 1.3 4.5 ± 3.4 59.1 ± 31.5 3.6 ± 2.0 71.7 ± 39.9 \n C4 2 28 ± 4 47 ± 2 3.8 ± 0.2 1.5 ± 0.9 1.9 ± 0.3 3.8 ± 0.6 45.3 ± 4.9 4.9 ± 1.5 57.4 ± 8.1 \n C6 3 32 ± 8 22 ± 10 3.5 ± 0.7 1.7 ± 0.9 2.4 ± 0.3 5.6 ± 1.7 42.5 ± 17.7 4.0 ± 1.3 56.3 ± 21.1 \n C7 3 27 ± 6 30 ± 16 3.4 ± 0.4 1.3 ± 0 3.6 ± 2.0 4.2 ± 2.0 24.1 ± 4.1 2.8 ± 0.9 36.0 ± 5.0 \n V 2 26 ± 4 52 ± 13 3.6 ± 0.5 2.3 ± 1.5 3.6 ± 1.0 5.7 ± 1.9 54.4 ± 20.3 5.1 ± 3.6 71.0 ± 27.3 \n G G 3 16 ± 6 33 ± 13 5.0 ± 0.7 1.6 ± 0.3 45.5 ± 33.3 6.4 ± 2.6 23.8 ± 6.9 2.6 ± 0.9 80.0 ± 27.3\n L1 3 25 ± 5 32 ± 10 5.3 ± 0.3 2.1 ± 0.8 24.8 ± 14.0 2.7 ± 1.1 49.1 ± 12.9 3.7 ± 0.3 82.3 ± 6.6 \n L2 3 25 ± 6 32 ± 12 5.2 ± 0.3 2.8±1.2 24.3 ± 14.9 5.2 ± 4.1 37.0 ± 7.4 2.3 ± 0.4 71.6 ± 6.5 \n C1 3 19 ± 2 23 ± 9 5.1 ± 0.2 2.4 ± 0.5 16.6 ± 4.0 4.1 ± 1.5 37.6 ± 8.0 4.2 ± 1.5 65.0 ± 10.6 \n C2 3 32 ± 6 28 ± 13 5.1 ± 0.3 2.7 ± 0.8 17.3 ± 11.9 4.7 ± 1.2 50.6 ± 14.6 6.7 ± 0.7 82.0 ± 25.3 \n C3 3 24 ± 6 37 ± 16 4.5 ± 0.5 1.5 ± 0.8 10.6 ± 16.2 4.7 ± 2.6 47.1 ± 22.1 2.3 ± 0.7 66.3 ± 32.0 \n C5 3 20 ± 4 19 ± 2 4.5 ± 0.5 1.7 ± 1.1 11.1 ± 2.8 4.2 ± 4.0 30.8 ± 12.9 4.0 ± 1.8 51.8 ± 20.9 \n C6 3 23 ± 7 26 ± 6 4.5 ± 0.5 3.4 ± 3.4 9.5 ± 4.6 7.9 ± 5.2 25.2 ± 8.9 4.7 ± 5.2 50.7±19.4 \n C7 3 24 ± 9 36 ± 23 4.9 ± 0.1 2.6 ± 1.9 18.8 ± 18.4 6.9 ± 6.1 44.1 ± 11.9 8.3 ± 9.8 80.6 ± 35.8 \n V 3 23 ± 8 45 ± 9 4.6 ± 0.3 2.5 ± 1.4 17.1 ± 4.9 4.1 ± 2.9 58.0 ± 30.7 3.6 ± 1.2 85.2 ± 38.5 \n\nG = groundwater-affected soils (Gleysols, Fluvisols); L1 = shallow to intermediate soils with clay accumulation in the subsoil (Luvisols); L2 = intermediate to deep soils with clay accumulation in the subsoil (Luvisols); C1 = soils with well developed B horizons from Tertiary material (Cambisols); C2 = soils with well developed B horizons from morainal material in places with clay accumulation in the subsoil (Cambisols, Luvisols); C3 = shallow soils from limestone weathering with or without loess coverings (Cambisols, Luvisols, Leptosols); C4 = intermediate to deep soils from limestone weathering with or without loess coverings (Cambisols, Luvisols); C5 = soils with well developed B horizons from acidic material with low base saturation (Cambisols); C6 = soils with well developed B horizons from sandstone with low base saturation (Cambisols); C7 = soils with well developed B horizons from sandstone with initial podzolisation (Cambisols, Podzols); V = clay-rich soils (Cambisols, Vertisols, Stagnosols).", "\n\n###### Total storage of SOC (2000) and total projected SOC changes in Bavaria (2000--2095) under constant C input (∆SOC C0), decreased C input by 20% (∆SOC C20−) and increased C input by 20% (∆SOC C20+) according to major soil units under cropland (C) and grassland (G).", "\n\n land use soil class SOC (Mt) ∆SOC C0 ∆SOC C20− ∆SOC C20+ \n ---------- ------------ ---------- --------- ----------- ----------- -------- ------- -------\n C G 11.0 −1.6 −5.9 −2.3 −8.5 −0.9 −3.4\n L2 31.0 −6.6 −13.7 −9.8 −20.4 −3.6 −7.6 \n C1 18.7 −3.7 −24.0 −5.6 −35.8 −2.1 −13.2 \n C3 19.4 −2.3 −8.5 −3.6 −13.3 −1.1 −4.0 \n C4 8.4 −1.4 −5.2 −2.2 −8.0 −0.7 −2.6 \n C6 9.1 −1.4 −9.6 −2.1 −14.7 −0.7 −4.7 \n C7 5.3 −0.7 −5.1 −1.4 −7.7 −0.1 −2.6 \n V 20.0 −2.6 −2.6 −4.0 −5.0 −1.3 −0.4 \n   total 122.9 −20.3 −74.5 −30.9 −113.4 −10.5 −38.5\n G G 5.8 −−0.3 −1.2 −0.8 −2.9 0.1 0.3\n L1 5.5 −0.1 −0.3 −0.5 −1.8 0.3 1.1 \n L2 4.6 −0.3 −3.7 −0.7 −7.1 0.1 −0.6 \n C1 9.4 −1.0 −2.6 −1.9 −6.3 −0.2 0.8 \n C2 14.6 −0.7 −1.2 −1.7 −2.7 0.2 0.2 \n C3 3.8 −0.7 −2.4 −1.0 −3.7 −0.3 −1.2 \n C5 9.6 −2.2 −3.0 −3.3 −4.8 −1.2 −1.3 \n C6 3.7 −0.7 −8.0 −1.1 −11.9 −0.3 −4.3 \n C7 6.2 −0.8 −2.5 −1.3 −4.1 −0.4 −1.0 \n V 6.7 −0.8 −3.0 −1.3 −4.8 −0.4 −1.4 \n   total 70.0 −7.6 −27.8 −13.7 −50.2 −2.0 −7.3\n total   192.9 −27.9 −102.3 −44.6 −163.6 −12.5 −45.9\n\nG = groundwater-affected soils (Gleysols, Fluvisols); L1 = shallow to intermediate soils with clay accumulation in the subsoil (Luvisols); L2 = intermediate to deep soils with clay accumulation in the subsoil (Luvisols); C1 = soils with well developed B horizons from Tertiary material (Cambisols); C2 = soils with well developed B horizons from morainal material in places with clay accumulation in the subsoil (Cambisols, Luvisols); C3 = shallow soils from limestone weathering with or without loess coverings (Cambisols, Luvisols, Leptosols); C4 = intermediate to deep soils from limestone weathering with or without loess coverings (Cambisols, Luvisols); C5 = soils with well developed B horizons from acidic material with low base saturation (Cambisols); C6 = soils with well developed B horizons from sandstone with low base saturation (Cambisols); C7 = soils with well developed B horizons from sandstone with initial podzolisation (Cambisols, Podzols); V = clay-rich soils (Cambisols, Vertisols, Stagnosols).", "\n\n###### Overview over the ensemble of 19 regional climate projections as a combination of global circulation models (GCM) and regional circulation models (RCM).", "\n\n   Country/Institution GCM RCM\n ---- --------------------------------------------------------------------------------- ------------ --------------\n 1 Northern Ireland/Community Climate Change Consortium for Ireland HADCM3Q16 RCA 3.0\n 2 France/Meteo France ARPEGE ALADIN RM5.1\n 3 Denmark/Danish Meteorological Institute ARPEGE HIRMAM 5\n 4 BCM \n 5 ECHAM 5_r3 \n 6 Switzerland/ETH Zurich (Eidgenössische Technische Hochschule) HADCM3Q0 CLM 2.4.6\n 7 Germany/Helmholtz-Zentrum Geesthacht, Centre for Materials and Coastal Research ECHAM 5_r1 CLM 2.4.11\n 8 ECHAM 5_r2 \n 9 England/Hadley Centre for Climate Prediction and Research HADCM3Q0 HADRM3Q0\n 10 HADCM3Q3 HADRM3Q3 \n 11 HADCM3Q16 HADRM3Q16 \n 12 Italy/Intern. ", "Centre for Theoretical Physics ECHAM 5_r3 RegCM 3\n 13 Netherlands/Royal Netherlands Meteorological Institute ECHAM 5_r3 RACMO 2.1\n 14 Germany/Max Planck Institute for Meteorology ECHAM 5_r1 REMO 2005\n 15 ECHAM 5_r2 REMO 2009 \n 16 ECHAM 5_r3 REMO 5.7 \n 17 Sweden/Swedish Meteorological and Hydrological Institute, Rossby Centre BCM RCA 3.0\n 18 ECHAM 5_r3 \n 19 HADCM3Q3 \n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nFinding more information about CPU load type\n\nI'm wondering how many information about current CPU task I can get.", "\nParticularly if it's possible (or rather how difficult is) to determine kind of CPU load. ", "By kind of load I mean if task the CPU is currently dealing with is floating- or rather fixed-point operation.", "\nNo specific operating system, however my preferable one is (Arch) Linux.", "\nI'm looking for tools (especially source codes) and theoretical ways.", "\nedit:\nI know there are tools like (h/io/)top, but I need more accurate informations.", "\nOne of my first shots was part of hypervisor making a trap for every instruction and analyze it (like Qemu/vbox (...) does with some problematic instructions). ", "But I hope there is a simpler solution. ", "I don't want to affect efficiency so much.", "\nRegards,\nKap\n\nA:\n\nThat's exactly what HW performance counters/monitors are meant for. ", "\nThe events themselves are architecturally defined (see the documentation guides of your exact CPU for their definition and usages). ", "There are many applications designed to capture them, a few popular ones are:\n\nperf \nPAPI\nOProfile\n\nIn PAPI for e.g. you can use the event described here to measure floating point execution - http://icl.cs.utk.edu/projects/papi/wiki/PAPITopics:SandyFlops\n\n" ]

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[ "Q:\n\nHow can I store / cache values from methods in a class for later use in other methods of the same class?", "\n\nI am writing a linear regression class which fits a model to some data, similar to the scikit-learn implementation.", "\nOnce the model is fit, I want to be able to call a predict() method without having to pass the trained model weights as a parameter to the method. ", "What I have so far is below\nclass LinReg:\n \"\"\" Fit a linear model to data\"\"\"\n def __init__(self):\n ....\n\n def fit(self, x, y):\n \"\"\"Fit a model to data x with targets y\"\"\"\n ...\n # model weights w are calculated here\n return w\n\n def predict(self, x, w):\n \"\"\"Predict the target variable of the data x using trained weights w\"\"\"\n ...\n # predicted y values, y_pred, are calulated here\n return y_pred\n\nThe trained weights w are returned from fit() so the user can store these as a variable to later pass to the predict() method.", "\nlm = LinReg()\nw = lm.fit(x,y)\ny_pred = lm.predict(x_new, w) # don't want to pass w here\n\nHowever, I do not want to return w from fit(); I want to somehow store w once it is calculated in fit() so that the user does not have to concern themselves with the weights, but also such that the weights can be easily used in the predict() method.", "\nHow do I do this? ", "Is there a pythonic or standard OO way to do this?", "\n\nA:\n\nI would store it as an instance-level property:\ndef __init__(self):\n self.w = None # define the prop here...\n ....\n\ndef fit(self, x, y):\n \"\"\"Fit a model to data x with targets y\"\"\"\n ...\n # model weights w are calculated here\n self.w = your_computed_value\n\ndef predict(self, x):\n \"\"\"Predict the target variable of the data x using trained weights w\"\"\"\n ...\n # predicted y values, y_pred, are calulated here\n do_something_here(self.w)\n return y_pred\n\n" ]

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[ "A shampoo bottle. ", "A cardboard rod. ", "A flashlight.", "\n\nThese were the instruments allegedly used by four former Texas high-school students to sexually assault six teammates a total of nine times, according to indictments in their cases released this week.", "\n\nDustin Norman, Alejandro Ibarra, Colton Weidner, and Christian “Brock” Roberts—all 20 years old—were indicted Friday by a Wilson County grand jury on charges of engaging in organized criminal activity, according to Texas Attorney General Ken Paxton’s office. ", "The Daily Beast first reported the indictments on Monday.", "\n\nNorman, Ibarra, Weidner, and Roberts were initially arrested more than two years ago in the sexual assault and hazing scandal that rocked the 1,200-person town of La Vernia, about 30 miles outside of San Antonio. ", "Thirteen students were arrested in the case in March 2017.", "\n\nLocal police reported at the time that varsity athletes on the baseball, basketball, and football programs had been sodomizing at least 10 younger teammates with flashlights, carbon-dioxide tanks, and other items. ", "The case was eventually taken up by the Texas Rangers and the Texas Attorney General’s Office.", "\n\nNorman’s indictment claims he held down a boy on Aug. 15, 2016 and sodomized him with a cardboard rod; that he held down the same boy on Sept. 30 and raped him with a shampoo bottle; and that he held down another boy on Nov. 15 and sodomized him with a CO2 air bottle.", "\n\nIbarra’s indictment lists the same dates and objects allegedly used to assault the same boys, referred to in the documents only as juvenile #57 and juvenile #65.", "\n\nRoberts’ indictment claims that on five different occasions he used his finger to assault four different boys between Nov. 15 2016 and Feb. 1, 2017. ", "On another occasion, he allegedly used a flashlight.", "\n\nWeidner’s indictment lists the same five occasions and instruments of assault with the same victims, identified only as juveniles #119, #97, #39, and #112.", "\n\nAll of the suspects have repeatedly denied their involvement in the scandal, and Dustin Norman’s attorney, Alfonso Cabanas, told The Daily Beast on Monday that the allegations against his client “have no merit and have done nothing more than continue to ruin an innocent person’s life.”", "\n\nTwo lawsuits against the school district were consolidated last month. ", "One, initially filed in Jan. 2018, claimed that a teenage basketball player was assaulted more than 30 times between Oct. 2016 and Feb. 2017. ", "The boy, identified only as John Doe, said he was attacked in the La Vernia High School locker room, at teammates’ homes after dinners, in a shower at the school, and before and after basketball games.", "\n\nDoe’s lawsuit also claimed that at least one coach witnessed his assaults and ignored his screams.", "\n\nThe Daily Beast reported in August that boys who were promoted to the varsity teams were afraid to undress in the locker room over fear that they would be attacked in the showers, their mothers said. ", "John Doe said in the 2018 lawsuit that he eventually began “having to shower with his underwear on to help deter and/or prevent future sexual assaults.”", "\n\nThe other civil lawsuit was initially filed against the district in April 2017 and alleged that coaches and other administrators at the school “sanctioned these rituals” and “turned a blind eye toward the abuse, even after the abuse was reported to them.”", "\n\nThe civil cases against La Vernia Independent School District are set for trial in Feb. 2020.", "\n\nThe school district on Tuesday released a statement on the case but ultimately declined to comment on the details of the indictment “due to the sensitive nature of the allegations, as well as federal law protecting all students’ privacy rights.”" ]

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[ "QED v 1.0: a software package for quantitative electron diffraction data treatment.", "\nA new software package for quantitative electron diffraction data treatment of unknown structures is described. ", "No \"a priori\" information is required by the package which is able to perform in successive steps the 2-D indexing of digitised diffraction patterns, the extraction of the intensity of the collected reflections and the 3-D indexing of all recorded patterns, giving as results the lattice parameters of the investigated structure and a series of data files (one for each diffraction pattern) containing the measured intensities and the relative e.s.d.s of the 3-D indexed reflections. ", "The software package is mainly conceived for the treatment of diffraction patterns taken with a Gatan CCD Slow-Scan Camera, but it can also deal with generic digitised plates. ", "The program is designed to extract intensity data suitable for structure solution techniques in electron crystallography. ", "The integration routine is optimised for a correct background evaluation, a necessary condition to deal with weak spots of irregular shape and an intensity just above the background." ]

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[ "Q:\n\nCorrelation between upvotes and effort\n\nI am curious about your experiences regarding the relationship between time and effort spent on preparing an answer and the number of upvotes it receives. ", "\nWhile I do not even have proper data for myself, my subjective impression is that the correlation is, while probably still positive, not strong at all. ", "So, I sometimes get quite a few upvotes on answers that I had considered posting as comments, and sometimes see little to no reaction to answers I had put quite some effort into.", "\nAm I alone with this? ", "Are there confounders to this relationship?", "\n\nA:\n\nI think there are several (confounding) factors here. ", " The biggest, by far, is the number of views a thread gets. ", " If no one views a given thread, there are obviously no opportunities for people to vote. ", " Moreover, every view isn't necessarily another actual opportunity for people to vote anyway; many of the views may come from the same people (who may have already voted or decided not to). ", " \nThe number of views a thread gets is largely a function of the topic. ", " It is quite clear that some tags get consistently more views than others. ", " The title will also make a big difference in whether someone navigates to the tread. ", " The length / complexity of the question can make a difference as well: when someone lands on the thread and sees that it is going to take some work just to get through the question, they may decide it isn't worth their time (cf., ", "this meta thread: Does length of a question influence probability of receiving an answer?).", "\nThe correlation between quality and votes isn't zero, however. ", " There have been a number of answers that I put some effort into, only to receive few votes. ", " But I have found that those are the answers that continue to accrue upvotes (albeit at a slow rate) over time. ", " Whereas other answers may have gotten a few upvotes immediately, but then stay at that level forever. ", " \nWhether your posts are getting many upvotes or not, be assured that they contribute to the site and that we appreciate your efforts here. ", " \n\nA:\n\nI'd agree that there is at best a weak positive correlation. ", "\nBut what is effort? ", "It's not just the effort that went into an individual answer. ", "The effort of following the forum over a few years needs to enter the accounting. ", "So effort is obvious short-term effort $+$ whatever long-term effort is pertinent. ", "\nOver time on the forum, you learn at least subconsciously more about what the forum likes, as a collective set of preferences, and so learn a little about what works better. ", "So, you get a little better at planning your effort. ", "\nHere is a very partial list, in no particular order, of what helps to get upvotes. (", "It should be no surprise in a statistical forum that the response of upvotes depends on several covariates.) ", " \n\nWriting clearly and fluently, with good command of English and strong self-editing, but also fairly concisely. ", "\nGraphs! ", "For example, @Glen_b designs very clear, tasteful, customized graphs for many of his posts. ", "\nSome rigour and professionalism in analysis, wide sense. ", "Even at a low level small details such as careful use of terminology and notation and mathematical typesetting help greatly. ", "At a higher level, outstanding answers may use whatever mathematics it takes to get to the root of things. ", "Here @whuber is among the masters. ", "\nAnalyses of real data. ", "Or simulations. ", "In general, really good examples. ", "\nSome minor wackiness. ", "Anything that evokes a wry smile. ", "\nGood lists of references. ", "\nAlready having a fair reputation. ", "It shouldn't be the case, as every answer should be up-voted only on its own merits, but having a good reputation for high-quality answers and forum maintenance attracts attention to your answers. ", "\nMultiple edits. ", "Again, that in itself shouldn't be a reason for upvoting, but edits bump a thread to the top of the active list and draw attention thereby. ", "\n\nHere are some of the things that don't help much: \n\nRants. ", "\nRather obvious riding of hobby-horses. ", "\nMarginal or limited relevance to the question. ", "This is difficult to manage. ", "Sometimes a poor question can be steered gently but firmly in a different good direction that finds the pearl amid the grit, and that's all positive (except possibly for the poor OP). ", "But anything looking like \"That reminds me obliquely of this different thing\" usually gets few upvotes (and occasionally gets flak), however good it might be as an answer to a different question. ", "\nBeing sloppy. ", "\nBeing wrong! ", "\n\nA:\n\nI think another important factor to take into account is preferential attachment -- if something has been voted on a thousand times, omg, I have to see what that question is too! ", "Meaning, especially if you want to get particular about \"correlation,\" that there are important non-linear effects in popularity that do mess with a straightforward exchange of votes for effort.", "\n\n" ]

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[ "Molecular characterization of voltage-gated potassium channel (Kv) and its importance in functional dynamics in bull spermatozoa.", "\nPresent study was undertaken to characterize the voltage gated potassium channel (Kv 1.1) in bull spermatozoa using sixty four ejaculates collected from four Hariana bulls. ", "Functional characterization was undertaken using a selective blocker of Kv channel, 4-Aminopyridine (4-AP) while molecular presence of Kv on bull spermatozoa by immunoblotting and indirect immunofluorescence. ", "Three sets of 100 μL diluted sperm samples namely-negative control (100 μL of sperm dilution medium (SDM) containing 10 × 106 cells), vehicle control (99 μL of SDM containing 10 × 106 cells, and DMSO- 1 μL) and 4-AP treatment group (99 μL of SDM containing 10 × 106 cells, and drug 1 μL 4-AP) were used in the study. ", "Immunoblotting identified a single band of 56 kDa corresponding to Kv1.1 in Hariana bull spermatozoa. ", "Immunolocalization showed the positive immunoreactivity at head, middle piece and principal piece of the spermatozoa for Kv 1.1. ", "Blocking of Kv using 4-AP resulted in significant (p < 0.05) reduction in sperm progressive motility, per cent capacitated spermatozoa (B-pattern) and acrosome reacted (AR-pattern) spermatozoa, while significant (P < 0.05) increase in per cent swollen spermatozoa. ", "Blocking of Kv channels resulted in significantly (P < 0.05) increased percentage of spermatozoa with lower mitochondrial transmembrane potential. ", "Computer assisted semen analysis (CASA) of motion and kinematic parameters in 4-AP treated spermatozoa indicated reduction in sperm motion parameters like LIN, STR, VSL and VAP and higher ALH, VCL, and BCF indicating hyperactivity of spermatozoa. ", "Based on our findings, it may be concluded that voltage-gated potassium channel (Kv) are present on bull spermatozoa and these are associated with functional dynamics of spermatozoa. ", "However, based on our limited study, it is not possible to deduce that how these channels are associated with induction of hyperactivity. ", "Therefore, further studies are warranted to unravel the mechanistic signaling pathways involved in Kv-mediated alterations in functional dynamics of spermatozoa." ]

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[ "// -*- C++ -*-\n\n// Copyright (C) 2005, 2006, 2009 Free Software Foundation, Inc.\n//\n// This file is part of the GNU ISO C++ Library. ", " This library is free\n// software; you can redistribute it and/or modify it under the terms\n// of the GNU General Public License as published by the Free Software\n// Foundation; either version 3, or (at your option) any later\n// version.", "\n\n// This library is distributed in the hope that it will be useful, but\n// WITHOUT ANY WARRANTY; without even the implied warranty of\n// MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU\n// General Public License for more details.", "\n\n// Under Section 7 of GPL version 3, you are granted additional\n// permissions described in the GCC Runtime Library Exception, version\n// 3.1, as published by the Free Software Foundation.", "\n\n// You should have received a copy of the GNU General Public License and\n// a copy of the GCC Runtime Library Exception along with this program;\n// see the files COPYING3 and COPYING.RUNTIME respectively. ", " If not, see\n// <http://www.gnu.org/licenses/>.", "\n\n// Copyright (C) 2004 Ami Tavory and Vladimir Dreizin, IBM-HRL.", "\n\n// Permission to use, copy, modify, sell, and distribute this software\n// is hereby granted without fee, provided that the above copyright\n// notice appears in all copies, and that both that copyright notice\n// and this permission notice appear in supporting documentation. ", "None\n// of the above authors, nor IBM Haifa Research Laboratories, make any\n// representation about the suitability of this software for any\n// purpose. ", "It is provided \"as is\" without express or implied\n// warranty.", "\n\n/**\n * @file gp_hash_table_map_/constructor_destructor_no_store_hash_fn_imps.hpp\n * Contains implementations of gp_ht_map_'s constructors, destructor,\n * and related functions.", "\n */\n\nPB_DS_CLASS_T_DEC\ninline void\nPB_DS_CLASS_C_DEC::\nconstructor_insert_new_imp(mapped_const_reference r_val, size_type pos, \n\t\t\t false_type)\n{\n _GLIBCXX_DEBUG_ASSERT(m_entries[pos].m_stat !", "= valid_entry_status)k;\n entry* const p_e = m_entries + pos;\n new (&p_e->m_value) mapped_value_type(r_val);\n p_e->m_stat = valid_entry_status;\n _GLIBCXX_DEBUG_ONLY(debug_base::insert_new(p_e->m_value.first);)\n}\n" ]

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[ "Q:\n\nIs it possible to track meter readings in GnuCash?", "\n\nI'd like to keep the record of, for example, water and electricity consummation. ", "Is it possible to properly implement a pseudo-account in GnuCash to store the meters' readings? ", "Even more, having the current electricity cost and the delta between readings, calculate the amount of money to pay?", "\n\nA:\n\nIt's not native functionality, but you could probably do it.", "\nYou could create a fake security/currency for the meter type (kWh, whatever gas/water get measured in ).", "\nUpdating would be a pain, though. ", "You'd have to go read it and enter the data manually -- unless it was a smart meter, and then you could probably build some sort of script for it.", "\nIn terms of figuring how much to pay -- maybe have an account in liabilities for stuff you haven't paid for yet, and another in assets for what you have paid for?", "\nThis seems like it could be a lot more complicated than it's worth.", "\n\n" ]

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[ "Q:\n\nDo I need an outlook .ost file?", "\n\nAll my emails are stored on our exchange server, yet on one of my machines, there is an .ost file that is 2 GB in size. ", " There is no reason at all to have this, as far as I know. ", " What is the right way to delete it? ", " Why does it even exist?", "\n\nA:\n\nThe OST file is the offline folders file used when you enable Cached Exchange Mode.", "\nDisabling Cached Exchange Mode should make this file go away if you don't want/need it.", "\nThe benefits of Cached Exchange Mode are in case the server is unavailable (either on a remote client, or in case of an outage) user can still work in their mail. ", "Once server communication is reestablished, changes will be synced from the cached file.", "\nThe problems with Cached Exchange Mode are that in certain types of outages, the Cache may take on information that is incorrect once the connection is reestablished and will need to be disabled (to delete the cache) and then reenabled to begin caching again. ", "Also, the file can be very large, usually at least as large as the mailfile, if not larger.", "\n\n" ]

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[ "× Copy the page URI to the clipboard\n\nLloyd, Mair Elizabeth (2017). ", "Living Latin: Exploring a Communicative Approach to Latin Teaching Through a Sociocultural Perspective on Language Learning. ", "PhD thesis The Open University.", "\n\nDOI: https://doi.org/10.21954/ou.ro.0000bef6\n\nAbstract\n\nThis study is motivated by the search for new practices to enhance the teaching of ab initio Latin in UK universities. ", "It arises out of a perception that traditional methods leave some students failing to achieve course aims, their own study goals, and, in the longer term, struggling to read Latin texts with understanding and engagement. ", "At the outset of this research, there was little recent information on Latin pedagogy in UK universities or on student opinions on provision. ", "Some scholarship expressed dissatisfaction with the quality of Latin reading skills attained, but little work had been done on defining the nature of desirable skills or in exploring how they might be attained or investigated. ", "This study instigates progress in all these areas.", "\n\n\n\nTo advance understanding of how Latin learning takes place and to investigate the potential benefits of existing conceptual and pedagogical frameworks, this study draws on modern language learning theories and teaching practices and explores the application of Vygotskian sociocultural theory to learning events taking place under a communicative teaching approach.", "\n\n\n\nResearch methods were selected pragmatically, with quantitative methods deployed to obtain a comprehensive snapshot of current practice in UK universities, while the more complex areas of learning events and perceived benefits were investigated through a combination of participant observation, interviews and innovative reading and drawing exercises.", "\n\n\n\nThe findings confirm that traditional ab initio Latin teaching approaches are not well-aligned with learners’ goals, establish the value of taking a broader approach to pedagogy and provide new ways of defining and investigating Latin reading skills. ", "This research has the potential to enhance Latin pedagogy in UK universities and other institutions. ", "It makes a seminal contribution to applying language learning theories to Latin and suggests innovative methods for aligning students’ needs and expectations with their learning experience.", "\n\nViewing alternatives\n\nDownload history\n\nMetrics\n\nPublic Attention Altmetrics from Altmetric" ]

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[ "856 F.2d 1539\n272 U.S.App.", "D.C. 377\nGeorge TURNER, II, Appellant,v.Marion S. BARRY, Jr., Mayor, et al.", "\nNo. ", "88-7121.", "\nUnited States Court of Appeals,District of Columbia Circuit.", "\nSept. 16, 1988.", "\n\nAppeal from United States District Court for the District of Columbia; George H. Revercomb, District Judge.", "\nSusan S. McDonald, Office of Corp. Counsel, Washington, D.C., for appellees.", "\nGeorge Turner, II, pro se.", "\nON ORDER TO SHOW CAUSE\nBefore BUCKLEY, D.H. GINSBURG and SENTELLE, Circuit Judges.", "\nOpinion PER CURIAM.", "\n\nPER CURIAM:\n\n1\nAppellant George Turner, appearing pro se and in forma pauperis, has appealed an order of the district court dismissing his civil rights complaint. ", " Because the district court properly concluded that the complaint failed to state a claim upon which relief could be granted, we affirm.", "\n\n\n2\nTurner is currently incarcerated in the Lorton Reformatory, having been convicted of armed robbery in the Superior Court of the District of Columbia. ", " On April 14, 1988, Turner filed in the district court a \"Complaint for Violation of Civil Rights\" pursuant to 42 U.S.C. Sec. ", "1983 (1982). ", " Named as defendants were Marion Barry, in his capacity as Mayor of the District of Columbia, and Rosemarie Mahmood, a probation officer employed by the Superior Court of the District of Columbia.", "\n\n\n3\nTurner alleged in his complaint that Mahmood \"filed a presentence report with the [Superior Court] that contained false and misleading information.\" ", " These alleged inaccuracies related to the number of offenses with which he was originally charged and his parole status. ", " Turner requested that the district court reduce or vacate his sentence and award him compensatory damages of $1.5 million as compensation for the excessively long sentence that he allegedly received as a result of Mahmood's report.", "\n\n\n4\nThe district court, on its own motion and prior to service of the complaint upon the defendants, dismissed Turner's complaint. ", " The court concluded that to the extent that Turner sought to test the legality of his detention, he must first apply to the Superior Court. ", " The court further concluded that the damage portion of the action was barred by the doctrine of judicial immunity. ", " This appeal followed.", "\n\n\n5\nFor more than a century, the Supreme Court has followed the common law doctrine granting judges absolute immunity from liability for damages based upon acts committed within their judicial jurisdiction. ", " See Pierson v. Ray, 386 U.S. 547, 553-54, 87 S.Ct. ", "1213, 1217-18, 18 L.Ed.2d 288 (1967); Bradley v. Fisher, 80 U.S. (13 Wall.) ", "335, 347, 20 L.Ed. ", "646 (1872). ", " This absolute immunity has been extended to other quasi-judicial officials when (1) their activities are integrally related to the judicial process, and (2) they must exercise discretion comparable to that exercised by a judge. ", " See, e.g., Imbler v. Pachtman, 424 U.S. 409, 96 S.Ct. ", "984, 47 L.Ed.2d 128 (1976) (prosecutors initiating and pursuing a criminal prosecution); Simons v. Bellinger, 643 F.2d 774 (D.C.Cir.1980) (members of committee appointed by court of appeals to monitor unauthorized practice of law).", "\n\n\n6\nAt least three circuits have extended this quasi-judicial immunity to state probation officers alleged to have violated a plaintiff's constitutional rights by failing properly to prepare a presentence report. ", " Freeze v. Griffith, 849 F.2d 172 (5th Cir.1988); Demoran v. Witt, 781 F.2d 155 (9th Cir.1986); Hughes v. Chesser, 731 F.2d 1489 (11th Cir.1984). ", " These decisions are in accord with other courts of appeals that have similarly concluded that federal probation officers are absolutely immune from liability when preparing and submitting presentence reports. ", " Dorman v. Higgins, 821 F.2d 133 (2d Cir.1987); Tripati v. INS, 784 F.2d 345, 348 (10th Cir.1986), cert. ", "denied, --- U.S. ----, 108 S.Ct. ", "755, 98 L.Ed.2d 767 (1988).", "\n\n\n7\nThe presentence report is an integral part of the judicial function of sentencing. ", " Demoran, 781 F.2d at 157. ", " When preparing presentence reports, the probation officer acts at the specific request of the court and submits the results of the investigation to the sentencing court for its evaluation. ", " Charged with the duty of impartial fact finding for the court, probation officers typically serve as an \" 'arm of the sentencing judge.' \" ", " Id. (quoting Cleavinger v. Saxner, 474 U.S. 193, 204, 106 S.Ct. ", "496, 502, 88 L.Ed.2d 507 (1985)).", "\n\n\n8\nWe agree that the prospect of damage liability under section 1983 \"would seriously erode the officer's ability to carry out his independent fact finding function\" and would, as a result, \"impair the sentencing judge's ability to carry out his judicial duties.\" ", " Demoran, 781 F.2d at 157; Spaulding v. Nielsen, 599 F.2d 728, 729 (5th Cir.1979). ", " Without immunity from suit, probation officers are likely to become the target of criminal defendants who seek to challenge, through a civil action for damages, the accuracy of their presentence reports. ", " As a consequence, the probation officer would serve as a \" 'lightning rod for harassing litigation.' \" ", " Crosby-Bey v. Jansson, 586 F.Supp. ", "96, 99 (D.D.C.1984) (quoting Ashbrook v. Hoffman, 617 F.2d 474, 476 (7th Cir.1980)).", "\n\n\n9\nAccordingly, we hold that District of Columbia probation officers are absolutely immune from liability for damages in an action brought pursuant to 42 U.S.C. Sec. ", "1983 for alleged errors in the investigation and preparation of presentence reports.1 The order of the district court dismissing the complaint2 is therefore\n\n\n10\nAFFIRMED.", "\n\n\n\n1\n Turner's remaining requests for relief (vacation or reduction of his sentence, and damages from Mayor Barry because he was allegedly \"responsible for\" Mahmood) were properly rejected by the district court. ", " See Garris v. Lindsay, 794 F.2d 722, 725-26 (D.C.Cir.) ", " (District of Columbia prisoner has no recourse to a federal judicial forum to challenge his detention unless the local remedy in Superior Court is inadequate or ineffective), cert. ", "denied, 479 U.S. 993, 107 S.Ct. ", "595, 93 L.Ed.2d 595 (1986), and Monell v. New York City Dep't of Social Services, 436 U.S. 658, 694, 98 S.Ct. ", "2018, 2037, 56 L.Ed.2d 611 (1978) (no respondeat superior liability under section 1983)\n\n\n2\n Our action today is fully consistent with Brandon v. District of Columbia Bd. ", "of Parole, 734 F.2d 56 (D.C.Cir.1984), cert. ", "denied, 469 U.S. 1127, 105 S.Ct. ", "811, 83 L.Ed.2d 804 (1985). ", " There, we held that an in forma pauperis complaint may be dismissed by the district court on its own motion only when the complaint is legally frivolous. ", " The sua sponte dismissal of Turner's complaint was clearly correct because it was plain from the face of the pleading that Mahmood was absolutely immune from suit. ", " See id. at 59 (complaint may be dismissed if not viable)\n\n\n" ]

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[ "#ifndef crypto_onetimeauth_H\n#define crypto_onetimeauth_H\n\n#include <stddef.h>\n\n#include \"crypto_onetimeauth_poly1305.h\"\n#include \"export.h\"\n\n#ifdef __cplusplus\n# ifdef __GNUC__\n# pragma GCC diagnostic ignored \"-Wlong-long\"\n# endif\nextern \"C\" {\n#endif\n\ntypedef crypto_onetimeauth_poly1305_state crypto_onetimeauth_state;\n\nSODIUM_EXPORT\nsize_t crypto_onetimeauth_statebytes(void);\n\n#define crypto_onetimeauth_BYTES crypto_onetimeauth_poly1305_BYTES\nSODIUM_EXPORT\nsize_t crypto_onetimeauth_bytes(void);\n\n#define crypto_onetimeauth_KEYBYTES crypto_onetimeauth_poly1305_KEYBYTES\nSODIUM_EXPORT\nsize_t crypto_onetimeauth_keybytes(void);\n\n#define crypto_onetimeauth_PRIMITIVE \"poly1305\"\nSODIUM_EXPORT\nconst char *crypto_onetimeauth_primitive(void);\n\nSODIUM_EXPORT\nint crypto_onetimeauth(unsigned char *out, const unsigned char *in,\n unsigned long long inlen, const unsigned char *k)\n __attribute__ ((nonnull(1, 4)));\n\nSODIUM_EXPORT\nint crypto_onetimeauth_verify(const unsigned char *h, const unsigned char *in,\n unsigned long long inlen, const unsigned char *k)\n __attribute__ ((warn_unused_result)) __attribute__ ((nonnull(1, 4)));\n\nSODIUM_EXPORT\nint crypto_onetimeauth_init(crypto_onetimeauth_state *state,\n const unsigned char *key) __attribute__ ((nonnull));\n\nSODIUM_EXPORT\nint crypto_onetimeauth_update(crypto_onetimeauth_state *state,\n const unsigned char *in,\n unsigned long long inlen)\n __attribute__ ((nonnull(1)));\n\nSODIUM_EXPORT\nint crypto_onetimeauth_final(crypto_onetimeauth_state *state,\n unsigned char *out) __attribute__ ((nonnull));\n\nSODIUM_EXPORT\nvoid crypto_onetimeauth_keygen(unsigned char k[crypto_onetimeauth_KEYBYTES])\n __attribute__ ((nonnull));\n\n#ifdef __cplusplus\n}\n#endif\n\n#endif\n" ]

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[ "Q:\n\nRuby class methods calling it twice?", "\n\nclass Tests\n def self.test1\n 'This is the First'\n end\n\n def self.test2\n 'This is the second'\n end\nend\nputs Tests.test1.test2\n\nI keep getting an error \nundefined method `test2' for \"This is the First\":String (NoMethodError).", "\n\nI am assuming its not possible to call the second class method. ", "However I am doing coding something which tells me that is possible. ", "Can anyone confirm or help fix this?", "\n\nA:\n\nIf you return self from each method, you can chain them infinite number of times :)\nNote: I've added puts to each method, because otherwise all method would do is returning self.", "\nclass Tests\n def self.test1\n puts 'This is the First'\n self\n end\n\n def self.test2\n puts 'This is the second'\n self\n end\nend\n\nTests.test1.test2\n#=> This is the First\n#=> This is the second\n\nBasically you perform some logic in method, and when it's done, you return the object itself, so that each chained method call gets called on the object, not on the result of previous method (when there were no self returned).", "\n\n" ]

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[ "For many electronic devices, the display is a major source of power drain. ", "For a liquid crystal display (LCD), the number of row lines in the LCD determines the value of the bias voltage, and hence the driving voltages, needed to operate the display. ", "As displays get larger, the number of row lines increases, the bias voltage requirement gets larger, and the power consumption of the bias voltage divider, which uses the bias voltage to provide driving voltages for the LCD, increases.", "\nThe power used to turn on and off pixels in an LCD display module is proportional to the square root of the number of row lines in the LCD. ", "In other words, the power consumption of an LCD module is proportional to the row-resolution of the display. ", "Thus, even when only part of the display is used to convey information, a large display uses almost the same amount of power as if the entire display was conveying information. ", "For portable electronic products, such as cellular telephones, personal digital assistants, palm-sized computers, and electronic games, increasing power consumption caused by larger and higher-resolution displays results in decreased battery life.", "\nThus, there is a need to reduce the power consumption of a display module while maintaining a desired resolution and size but without significantly degrading the display's performance and also without substantially increasing production costs for the display module." ]

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[ "So this was my first time trying Darling Clandestine’s products and I am in loveeee. ", "Evonne is a wizard and I am glad I jumped in with both feet to pick up some of her Falloween releases! ", "I snagged a full size of Tiny Ice Bees, Squander, and a sample solid of Don’tGoPleaseStay. ", "I placed my order on September 4th and it shipped on the 14th. ", "I received it on the 24th, 10 days after it shipped which is pretty awesome for international shipping. ", "It came nicely packaged, padded by the bubble wrap and salt-water taffy!", "\n\nEvonne was completely amazing with every interaction I had with her! ", "She was so patient with all my questions and super fast to reply. ", "I had made an order in August and had asked for it to be held if possible until this release because international shipping is pricey. ", "She was super amazing and held onto it, giving me a free shipping code for my Falloween order so it could all be combined!", "\n\nTiny Ice Bees\n\nEvonne’s description for this one is that she “wove a wisp of damp silk—crisp, delicate, ozoney, watery—with a subtle splash of pineapple and tart green orange and grapefruit.” ", "No honey for this scent though because that’s predictable, and oh am I glad she didn’t add honey! ", "I have nothing against honey, I love my Hivemind perfume from OHWTO, but this scent is crisp and fresh and it really doesn’t need anything else. ", "On the cold sniff I get bright citrus from the orange and grapefruit with a sweet edge from the pineapple, with the ozone tingling at the edges. ", "I say tingling because that’s the only way I can think to describe the scent; like watery ripples moving around the fruity scent.", "\n\nApplied, the ozone becomes a bit stronger, adding a crisp edge to the scent. ", "The grapefruit dances at the front, sharp and witty, while the pineapple comes in to round out the scent. ", "After about 30 min the orange comes out to play a little bit with its distinct citrus scent mingling with the grapefruit. ", "After an hour the ozone melts to the background again, floating at the edges, leaving the fruit scents to take centre stage. ", "This scent lasted 4 hours on me before my skin gobbled it up. ", "I was catching wafts of it for the first 2 hours before it moved closer to my skin. ", "After 4 hours it was gone completely, leaving only the memory.", "\n\nThe boyfriend was around for my Falloween testing and his reaction to this one was, “Ooh, fruity. ", "I like that one!” ", "This one is a winner and I fell in love with it more than I thought I would. ", "It comes in a cute, plump little 5ml bottle with a wide mouth.", "\n\nSquander\n\nFirst off, the container is awesome! ", "This comes in a tall 8ml bottle and the little pipette is perfect for the halloween spirit this perfume has, and it’s super fun to use. ", "Cute and useful, whaddaya know!? ", "It can be a bit tricky to open as the rubber kind of grabs at the bottle, but I’m getting the hang of it!", "\n\nThis scent is described as “Deep and decadent, with rich fruitful notes including clove and nutmeg and sandalwood and ripe red apple.” ", "On cold sniff the apple is right there, shoving the other scents off the stage although the sandalwood manages to cling to the side. ", "It is bright and fruity, lightly sweet with that unmistakable ‘red’ smell.", "\n\nApplied the apple continues to take centre stage but the clove manages to climb back up, hanging around behind the apple. ", "The sandalwood is still clinging to the edges of the scent and nutmeg doesn’t find a way back in for about another 30 minutes. ", "At the 1 hour mark, the apple is still the main scent but the clove and nutmeg balance it out, taking away some of the sweetness the apple exudes. ", "The sandalwood hangs around at the edges, adding just a hint of woodiness to round out the scent. ", "This wafted around me for a good 2 hours before moving a little closer to the skin. ", "It hung close to the skin for another 3 hours before dissipating.", "\n\nThe Mr. really liked this one. ", "I hadn’t told him I was wearing it but he noticed right away. ", "I got a, “Oh that’s really nice. ", "I really like this one.”", "\n\nDon’tGoPleaseStay\n\nDon’tGoPleaseStay is described as a “Dark, smoky, chocolatey gin.” ", "This is a, “slow infusion made with a fantastic cacao absolute, the very finest oakmoss, crushed juniper berries, cardamom pods, just a tiny bit of ylang-ylang, a pinch of chipotle pepper, and dark vanilla”.", "\n\nThis is a natural perfume made by infusing the components together and because of this, it sits close to the skin. ", "Evonne says it best “Don’tGoPleaseStay is infused with all organic botanical ingredients, so the fragrance isn’t as intense as that of blends containing synthetic elements. ", "It’s meant to cling close to your skin and cuddle.”", "\n\nOn cold sniff I first get the sweet chocolate/vanilla, which is closely followed by light smoke. ", "Normally I don’t do smoke and that’s why I only got the sample of this, but this note is very light and not acrid. ", "It’s like the light smoke scent that clings to someone’s skin when they’ve walked past a campfire. ", "The scent is sweet and a bit spicy, but not like cinnamon or nutmeg spicy, more of a slow burn that you can’t really place spicy. ", "It nips and caresses all at once.", "\n\nOnce applied, the chocolate blooms and the smokey scent becomes more complex; I swear I can smell the wood from the fire, warm and natural. ", "The gin scent comes out to play a little bit, standing shy in the background. ", "After about 30 min the scent melds together in the most perfect of ways: the chocolate is cradled by the woody smokey scent, and the gin watches patiently, a step back. ", "The scent is balanced and comforting. ", "It sits pretty close to the skin but I would catch a waft of it if I was doing something close to my face. ", "This scent hung around for about 5 hours and I found myself smelling my wrist more than once. ", "It’s such a warm scent, very comforting!", "\n\nSummary\n\nI loved everything, a first for a perfume order. ", "I just wish I had ordered a full size of Don’tGoPleaseStay. ", "Hopefully when Evonne reopens she will have a few laying around, or someone on IndieMakeupandMore will have one that needs a happy home.", "\n\nA related note: These perfumes really need to rest after transit. ", "I did a cold sniff upon arrival and the scents are completely different after letting them sit for 2-3 days. ", "Remember these little buddies went through a lot to get to you, let them take a break before putting them to work!", "\n\nEvonne has closed the shop as to complete the Falloween orders but she can be found here and should be opening soon!", "\n\n(All reviews and statements are my honest personal opinions. ", "I have purchased all the products I have written about unless otherwise explicitly stated. ", "I have not accepted payment for any of my reviews)" ]

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[ "SOCIAL MEDIA\n\nSUBSCRIBE TO SUE ADLER TEAM BLOG UPDATES\n\nABOUT US\n\nThe Sue Adler Team of specialists has been the #1 Team in NJ for the past 3 years, and is one of the top Keller Williams teams worldwide, with annual production of $165 Million in 2015, Our team's core mission is to educate and advise our clients so that they can make the best decisions for their family, advocate for them, and provide a personal above and beyond experience so that each feels like they are our only client.", "\n\nVacation Week Sing-Along in Berkeley Heights!", "\n\nLooking for something to do with the kids during school vacation week this year? ", "Check out the Holiday Vacation Week Sing-Along with Jersey Jason and Miss Nina in Berkeley Heights. ", "Mark your calendars now and buy your tickets soon — you don’t want to miss out on this fantastic musical experience!", "\n\nFamilies in Union and Warren Counties are in for a fun and enriching musical experience during this year’s holiday vacation week.", "Pete’s Place/Yogoccino welcomes “Jersey Jason,” leader of the Jungle Gym Jam and “Miss Nina,” a children’s singer/songwriter whose sing-along/dance-along versions of classic songs like “Wheels on the Bus” are all over YouTube. ", "You may have seen her videos — with the pink guitar. ", "Miss Nina has just moved to New Jersey from Brooklyn, NY. ", "This is her first public performance in the area while still holding down the fort of a very successful weekly sing-along series across the rivers in Brooklyn. ", "Jersey Jason has earned the Parents’ Choice Approved seal for his debut album “Everyone’s Invited!” ", "which is also a CD Baby Editor’s Pick and was featured on WHFR-FM Dearborn, Michigan’s Theme Attic program’s Best Albums of 2014 episode.", "\n\nKim at Diva Moms NJ has put this event together after having done a handful of popular family sing-along events with Jason last year. ", "Diva Moms of Livingston/Short Hills gives moms social opportunities for their kids & families at events like this and some much-needed “me time” with their Moms’ Night Out events.", "\n\nDoors open at 3:00 in the restaurant’s party room; show time is at 3:30. ", "Admission purchased in advance is $10 for a family (one or two adults and their children). ", "Additional adults attending with a family are $5 each. ", "The kitchen will be open and there are lots of appealing options for an afternoon snack or an early dinner. ", "See the yogurt bar menu here. ", "See the dinner menu here.", "\n\nTunes for Tots: Pre-order Miss Nina’s Sha Doo Be Doop CD and Jason’s Everyone’s Invited! ", "CD as a package for just $16 when you order your tickets and we’ll each donate a second CD to Toys for Tots. ", "The artists will personally autograph their CD’s at the show.", "\n\nFor more information contact Steve at Pete’s Place/Yogoccino at 908-771-9300 or Jason from the Jungle Gym Jam at 201-838-1205 or Jason@junglegymjam.com.", "\n\nEach office independently owned and operated. #", "1 Agent in the state of New Jersey as per the dollar volume rankings in the Wall Street Journal/REAL Trends The Thousand Survey, #1 Keller Williams Agent in the state of New Jersey as per annual Keller Williams dollar volume production reports. ", "All data on this site is for informational purposes only, The Sue Adler nor Keller Williams Realty can guarantee the accuracy of the data." ]

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[ "Info\n\nLast Activity:\n\nJoined:\n\nChanell Ann\n\nAbout Me\n\nI would like to do more tattoo modeling and glamour and creative shots for the holidays\n\nHello, My name is Chanell Ann Boggs. ", "I love to model. ", "I am comfortable in front of the camera. ", "I like to show the true essence of beauty through my pictures. ", "I am willing to work with a variety of different photographers. ", "I am very versitile on my looks. ", "I am willing to do long photoshoots. ", "I am really fit and petite. ", "I am willing to travel for photoshoots but they traveling expenses covered if possible (transportation) depends on location if it is close to me i will come by my own ride. ", "I do alot of photoshoots and would like to expand on my portfolio and do great work to not only boost up my rep but the photographers. ", "I am very mature and can handle long hours. ", "I do paid photoshoots and non paying photoshoots. ", "I want to get more professional employers to see my portfolio and be interested in my work and hire me as their model if you are interested in me please email me or facebook me the date, time, style of shoot, compensation, contact information, and references. ", "I' I hope you like me :) I would love to shoot with you :) I have alot tattoos so you know ahead of time\n\nYou can also contact me on Facebook to talk to me more and get to know more about me.", "\n\nI do promotional modeling as well as TFP or Paid Work. ", "But I mostly do paid work. ", "My rates are 120 an hr and never shoot less than 3 hrs" ]

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[ "The situation in a Belarus orphanage for children with developmental disabilities is \"extremely critical\" after at least 23 people contracted COVID-19, a charity has warned.", "\n\nThe orphanage in Vesnova, some 175 kms from Chernobyl, cares for 174 children and young adults with genetic disorders, severe disabilities and compromised immune systems. ", "It is supported by Adi Roche Chernobyl Children, an Irish NGO.", "\n\nAccording to the charity, the situation is now \"extremely critical\" after 13 children and 10 members of staff contracted COVID-19.", "\n\nThe orphanage is appealing for \"urgently needed painkillers, cough bottles and sanitising agents\" as well as personal protection equipment and financial donations.", "\n\n\"This is a shattering blow to all of the Irish people who have been involved in the development of Vesnova Orphanage over the past 20 years and we are extremely worried that we may lose children whose lives we have been working desperately to improve over many years,\" Adi Roche said in a statement.", "\n\nThe country has, as of Sunday, recorded more than 10,400 cases of the virus and 72 deaths.", "\n\nThe authorities were slow to respond to the pandemic with President Alexander Lukashenko dismissing the pandemic as a \"mass psychosis\" and advising people to drink more vodka, \"turn the steam on the bathhouse\", \"eat more garlic\" and \"sit behind the wheel of the tractor in the fields\" to protect themselves.", "\n\nLarge gatherings have not been banned and the country's top-flight football league is the only one still playing in Europe.", "\n\nThe World Health Organisation (WHO) called on the government earlier this week to reduce non-essential movements, postpone large gatherings \"including sports, religious and cultural events\" and toughen up social distancing measures.", "\n\nIt also recommended \"public engagement by all level of government to clearly, transparently ad regularly communicate the risks, health advice and response measures\"." ]

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[ "Radical hysterectomy morbidity in relation to age.", "\nThe complications of radical hysterectomy in patients 65 years and older were compared with those in women younger than 65. ", "There was no statistical difference in complication rates between the two groups, although the older women had a significantly higher incidence of preoperative medical problems. ", "No surgical deaths occurred in either group. ", "Our data indicate that selected older women can tolerate radical hysterectomy as well as younger ones." ]

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[ "Browsed byAuthor: Rosa del Duca\n\nJonathan Larson’s Renters Remain Compelling & Moving by Rosa del Duca “RENT” is one of those Broadway shows that has a life far beyond the stage. ", "Ask anyone on the street, and they can probably tell you “RENT” is about young artists living with AIDS, whether they’ve ever seen the show or not. ", "Even more likely, is they know the melody and more than a few lyrics to the musical’s most famous song “Seasons of Love.” ", "More than twenty years…\n\nMillennial Notes Mo Willems, Hannah Dworkin Craft Wonderful Ode to Friendship by Rosa del Duca Gerald the Elephant and Piggie are best friends. ", "I mean best, best friends, so devoted that they argue when each wants to declare the other “the best at being friends.” ", "When Piggie declares she “Needs to go,” Gerald launches into a dramatic ballad of despair, with extra refrains every time Piggie insists, “No, I really do need to go!” ", "Turns out she just needs to…\n\nMillennial Notes Nina Meehan, Simon Trumble Entice Toddlers’ Imaginations by Rosa del Duca It’s Duck’s birthday and he couldn’t be more excited—until he learns that several good friends cannot make it to his party. ", "Seagull, Pigeon, and Parrot send letters to the farm, informing Duck that, unfortunately, they are not able to make the trip. ", "Old MacDonald (engaging and disarming Jackie Kappes) sees how disappointed Duck (talented and multi-faceted Paul Wong) is, and decides to go on a secret birthday…\n\nMichael Mohammed Blends Old & New in Chocolate Factory by Rosa del Duca Willy Wonka is getting old and she needs an heir. ", "That’s right. ", "She. “", "Willy” (intense and mysterious Mary Gibboney) is female in this production of Roald Dahl’s classic, Charlie and the Chocolate Factory, and is usually referred to as “Madam Wonka.” ", "In hopes of finding this heir, she hides five golden tickets in her marvelous chocolate bars, which she sells all over the world. ", "The five lucky…" ]

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