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tomekkorbak

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detoxify-pile-chunk3-4150000-4200000

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[ "Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience.", "\nRift Valley fever (RVF) virus causes serious and fatal disease in animals and man. ", "To protect personnel who work with RVF virus in the laboratory, or troops who may be exposed to this virus, the US Army successfully developed an improved version of inactivated RVF vaccine, TSI-GSD-200. ", "From early 1986 to late 1997, 598 at-risk workers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) were vaccinated as part of an occupational safety and health program. ", "The subjects of this study received three subcutaneous doses (0, 7 and 28 days) of 0.5 ml of TSI-GSD-200. ", "A total of 540 vaccinees (90.3%) initially responded (group A) with an 80% plaque-reduction neutralization antibody titer (PRNT80) of > or =1:40; whereas 58 subjects (9.7%) were initial nonresponders (group B) failing to achieve this titer. ", "Volunteers who either failed to respond or who achieved a titer of > or =1:40 but whose titer waned below 1:40 were boosted 1-4 times with the same vaccine. ", "Among 247 group A subjects who received the first recall injection, 242 (98%) were successfully boosted, achieving a PRNT80 > or =1:40. ", "Thirty-three of 44 (75%) initial nonresponders were converted to responder status after the first booster, which is a lower rate than that of group A (P < 0.001). ", "After the primary series and the first booster, Kaplan-Meier analysis showed 50% probability of group A members maintaining a titer of > or =1:40 for approximately eight years; whereas group B had a 50% probability of maintaining a titer for only 204 days. ", "Group A immune response rates to boosts 1-4 ranged from 87 to 100% with geometric mean titers (GMTs) ranging from 80 to 916. ", "Boosts 1-4 immune response rates of group B volunteers ranged from 67 to 79% with GMTs ranging from 90 to 177. ", "Minor side effects to TSI-GSD-200 were noted in 2.7% of all vaccinees after primaries and 3.5% of all vaccinees who had primaries and up to four boosters. ", "We conclude that the use of TSI-GSD-200 is safe and provides good long-term immunity in humans when the primary series and one boost are administered." ]

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[ "Marco Reus is ready to light up the World Cup By Rune Gjerulff\n\nAfter missing the World Cup in 2014 and Euro 2016 due to injuries, Marco Reus is ready to shine in Russia.", "\n\nMarco Reus. ", "Photo: Granada, CC-by-SA 4.0\n\nBorussia Dortmund’s Marco Reus is arguably one of the best players in the world at his position when he’s fully fit. ", "Unfortunately, during the past few years, the German international has suffered from an extreme amount of injuries, and each time he bounces back he seems to get hit by another injury.", "\n\n\n\n\n\nThe 29-year-old missed both the World Cup in 2014 and Euro 2016 due to injuries, but now it finally seems he will get the chance to show what he can do for Germany at the World Cup in Russia. ", "And German national team coach Joachim Löw is excited to have Reus at his disposal.", "\n\n\n\n\"He's an incredibly skilful and intelligent player, a real handful for the opposition,\" Löw recently said at a press conference and added:\n\n\n\n\"His timing is spot-on, even his passing. ", "He's clinical. ", "He's making a really good impression.\"", "\n\n\n\nFormer German international Cacau is even backing Reus to be the player of the tournament.", "\n\n\n\n\"Marco Reus. ", "For me, he is an absolute international top player. ", "A strong dribbler, extremely fast and a very strong finisher. ", "I'm excited that he will finally experience his first World Cup,\" Cacau said to t-online.de when he was asked who he thinks will be the player of the tournament.", "\n\n\n\n\n\nReus has fought his way back after he suffered his latest serious injury blow in the end of May last year when he was struck by a ruptured cruciate ligament - an injury that kept him out until February.", "\n\n\n\nThe injury was undoubtedly a tough blow for Reus who has been forced to spend time on the sidelines by various injuries more than 20 times during the last three seasons.", "\n\nIn an interview with GQ Magazine in October, Reus admitted that the many injuries have taken their toll on him.", "\n\n\n\n\"The tears came again two or three days later when I went through it again in my mind,\" Reus said when he was asked about the serious injury he sustained in May last year.", "\n\n\n\n\"To be alone, working your way back is the most demanding part. ", "I was really fed up after three weeks. ", "It's a brutal mental test because you always have to work on your own,\" the Dortmund star continued.", "\n\n\n\nIn February, Reus finally returned to the pitch, and he had a very good ending to the season. ", "The Dortmund star only missed a few matches because of minor muscular problems, and he made a huge difference for Dortmund on the pitch, scoring seven goals in 11 Bundesliga appearances.", "\n\n\n\nNow, Reus is ready to continue is good form at the World Cup. ", "And he better not get injured again in Russia.", "\n\n\n\n\n\n" ]

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[ "HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with an estimated 45-50 million people infected worldwide at the end of 2010. ", "The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. ", "In 2005, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. ", "Currently available drugs for the treatment of HIV include nucleoside reverse transcriptase (RT) inhibitors or approved single pill combinations: zidovudine (or AZT or RETROVIR®), didanosine (or VIDEX®), stavudine (or ZERIT®), lamivudine (or 3TC or EPIVIR®), zalcitabine (or DDC or HIVID®), abacavir succinate (or ZIAGEN®), Tenofovir disoproxil fumarate salt (or VIREAD®), emtricitabine (or FTC-EMTRIVA®), COMBIVIR® (contains-3TC plus AZT), TRIZIVIR® (contains abacavir, lamivudine, and zidovudine), EPZICOM® (contains abacavir and lamivudine), TRUVADA® (contains VIREAD® and) EMTRIVA®; non-nucleoside reverse transcriptase inhibitors: nevirapine (or VIRAMUNE®), delavirdine (or RESCRIPTOR®) and efavirenz (or SUSTIVA®), ATRIPLA® (TRUVADA®+SUSTIVA®), and etravirine, and peptidomimetic protease inhibitors or approved formulations: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir, KALETRA® (lopinavir and Ritonavir), darunavir, atazanavir)(REYATAZ®) and tipranavir (APTIVUS®) and cobicistat, and integrase inhibitors such as raltegravir (ISENTRESS®), and entry inhibitors such as enfuvirtide (T-20) (FUZEON®) and maraviroc (SELZENTRY®).", "\nEach of these drugs can only transiently restrain viral replication if used alone. ", "However, when used in combination, these drugs have a profound effect on viremia and disease progression. ", "In fact, significant reductions in death rates among AIDS patients have been recently documented as a consequence of the widespread application of combination therapy. ", "However, despite these impressive results, 30 to 50% of patients may ultimately fail combination drug therapies. ", "Insufficient drug potency, non-compliance, restricted tissue penetration and drug-specific limitations within certain cell types (e.g. most nucleoside analogs cannot be phosphorylated in resting cells) may account for the incomplete suppression of sensitive viruses. ", "Furthermore, the high replication rate and rapid turnover of HIV-1 combined with the frequent incorporation of mutations, leads to the appearance of drug-resistant variants and treatment failures when sub-optimal drug concentrations are present. ", "Therefore, novel anti-HIV agents exhibiting distinct resistance patterns, and favorable pharmacokinetic as well as safety profiles are needed to provide more treatment options. ", "Improved HIV fusion inhibitors and HIV entry coreceptor antagonists are two examples of new classes of anti-HIV agents further being studied by a number of investigators.", "\nHIV attachment inhibitors are a further subclass of antiviral compounds that bind to the HIV surface glycoprotein gp120, and interfere with the interaction between the surface protein gp120 and the host cell receptor CD4. ", "Thus, they prevent HIV from attaching to the human CD4 T-cell, and block HIV replication in the first stage of the HIV life cycle. ", "The properties of HIV attachment inhibitors have been improved in an effort to obtain compounds with maximized utility and efficacy as antiviral agents. ", "In particular, U.S. Pat. ", "Nos. ", "7,354,924 and 7,745,625 are illustrative of HIV attachment inhibitors.", "\nAnother emerging class of compounds for the treatment of HIV are called HIV maturation inhibitors. ", "Maturation is the last of as many as 10 or more steps in HIV replication or the HIV life cycle, in which HIV becomes infectious as a consequence of several HIV protease-mediated cleavage events in the gag protein that ultimately results in release of the capsid (CA) protein. ", "Maturation inhibitors prevent the HIV capsid from properly assembling and maturing, from forming a protective outer coat, or from emerging from human cells. ", "Instead, non-infectious viruses are produced, preventing subsequent cycles of HIV infection.", "\nCertain derivatives of betulinic acid have now been shown to exhibit potent anti-HIV activity as HIV maturation inhibitors. ", "For example, U.S. Pat. ", "No. ", "7,365,221 discloses monoacylated betulin and dihydrobetuline derivatives, and their use as anti-HIV agents. ", "As discussed in the '221 reference, esterification of betulinic acid (1) with certain substituted acyl groups, such as 3′,3′-dimethylglutaryl and 3′,3′-dimethylsuccinyl groups produced derivatives having enhanced activity (Kashiwada, Y., et al., ", "J. Med. ", "Chem. ", "39:1016-1017 (1996)). ", "Acylated betulinic acid and dihydrobetulinic acid derivatives that are potent anti-HIV agents are also described in U.S. Pat. ", "No. ", "5,679,828. ", "Esterification of the hydroxyl in the 3 carbon of betulin with succinic acid also produced a compound capable of inhibiting HIV-1 activity (Pokrovskii, A. G., et al., “", "Synthesis of derivatives of plant triterpenes and study of their antiviral and immunostimulating activity,” Khimiya y Interesakh Ustoichivogo Razvitiya, Vol. ", "9, No. ", "3, pp. ", "485-491 (2001) (English abstract).", "\nOther references to the use of treating HIV infection with compounds derived from betulinic acid include US 2005/0239748 and US 2008/0207573, as well as WO2006/053255, WO2009/100532 and WO2011/007230.", "\nOne HIV maturation compound that has been in development has been identified as Bevirimat or PA-457, with the chemical formula of C36H56O6 and the IUPAC name of 3β-(3-carboxy-3-methyl-butanoyloxy) lup-20 (29)-en-28-oic acid.", "\nReference is also made herein to the applications by Bristol-Myers Squibb entitled “MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS” U.S. Ser. ", "No. ", "13/151,706 filed on Jun. 2, 2011 (now U.S. Pat. ", "No. ", "8,754,068) and “C-28 AMIDES OF MODIFIED C-3 BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS” U.S. Ser. ", "No. ", "13/151,722, filed on Jun. 2, 2011 (now U.S. Pat. ", "No. ", "8,802,661). ", "Reference is also made to the application entitled “C-28 AMINES OF C-3 MODIFIED BETULINIC ACID DERIVATIVES AS HIV MATURATION INHIBITORS” U.S. Ser. ", "No. ", "13/359,680, filed on Jan. 27, 2012 (now U.S. Pat. ", "No. ", "8,748,415). ", "In addition, reference is made to the application entitled “C-17 AND C-3 MODIFIED TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY” U.S. Ser. ", "No. ", "13/359,727 filed on Jan. 27, 2012 (now U.S. Pat. ", "No. ", "8,846,647). ", "Further reference is also made to the application “C-3 CYCLOALKENYL TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY” filed U.S. Ser. ", "No. ", "13/760,726 on Feb. 6, 2013 (now U.S. Pat. ", "No. ", "8,906,889).", "\nWhat is now needed in the art are new compounds which are useful as HIV maturation inhibitors, as well as new pharmaceutical compositions containing these compounds." ]

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[ "BERKELEY (CBS SF) — Berkeley officials are evaluating how to respond to a small tent city of about 20 people that has been set up on a median in the middle of Adeline Street near the Berkeley Bowl grocery store, a city spokesman said Tuesday.", "\n\nCity of Berkeley spokesman Matthai Chakko said the city evaluates each situation on a case-by-case basis.", "\n\nMike Zint of the advocacy group First They Came for the Homeless said he and other homeless people set up the tent city because they are\n\nunhappy with the new system that was set up at the beginning of the year to allocate aid to people who live on the street.", "\n\nThose services are coordinated by the Berkeley Food & Housing Project, also known as The HUB, which is located nearby at 1901 Fairview St.\n\nZint said the center is disorganized, making it too hard for people to get help and homeless people are being sent out of the area for\n\nhousing.", "\n\nZint said he and other people set up a protest camp outside The HUB’s office last week but the city raided the camp.", "\n\nHe said the homeless camp is drug- and alcohol-free and people at the camp provide their own security to keep everyone safe.", "\n\nChakko said the city asked the protesters to move by last Friday and they complied and there weren’t any citations or arrests.", "\n\nZint alleged that the city brought “a crusher” to smash couches that the protesters were sleeping on.", "\n\nBut Chakko said when the city removes homeless people from sites it gives them time to take their belongings away and everything that is left over is bagged up and stored and people can retrieve those items without any cost.", "\n\nChakko said one reason the city asked people to leave the camp outside The HUB’s office is that it received “a number of complaints” by\n\nneighbors in the area.", "\n\nHe said the city has also received some complaints about the new camp on the median in the middle of Adeline Street between Ward and Stuart streets, which Zint said was set up on Sunday night.", "\n\nThe Berkeley Bowl and a Walgreen’s store are about a block away to the south and a Sports Basement store is about a block away to the north.", "\n\nThere are also several small businesses nearby, including a bakery and two pilates and yoga clinics.", "\n\nZint said protesters picked the site because it’s near The HUB and the Ashby BART station.", "\n\nThe protesters have set up a large sign that says, “Honk To Keep Affordable Housing in Berkeley” and Zint said they’ve been getting a lot of\n\ncommunity support.", "\n\nZint said, “Tents are a step in the process of getting people off the streets because otherwise they’ll be exposed to the elements and die.”", "\n\nHe said the homeless camp is drug- and alcohol-free and people at the camp provide their own security to keep everyone safe.", "\n\nHe said the next step would be to create “tiny homes” that would be like shacks, sheds or trailers and include a kitchen and a common area.", "\n\nZint said he wants to keep the protest small for now but it would be possible to expand tents to three adjacent medians in the middle of\n\nAdeline Street so that up to 1,000 homeless people could be accommodated.", "\n\nHe said the protesters are “mobile” and if the city moves them out of the Adeline Street site, they have “a target list” and will move on to\n\nMayor Tom Bates’ home and then to the homes of City Council members.", "\n\nSharon Hawkins Leyden, the director of client services for Berkeley Food & Housing, a non-profit group which has a contract with the\n\ncity to run the new system, said the program is aimed at finding long-term housing for homeless people.", "\n\nLeyden said homeless people who’ve been on the street the longest and have a disability are given the highest priority but the system tries to help other people as well.", "\n\nLeyden said the program has helped many people find housing but admitted that the process is slow.", "\n\n“The system is getting better every month and we’re finding more housing for people,” she said.", "\n\nLeyden said the protesters want affordable housing, tiny homes and a city-approved tent city but she said those priorities “are not in our\n\nportfolio.”", "\n\nShe said, “We can offer them services but most likely they would have to move out of Berkeley” because there’s more affordable housing in\n\noutlying communities than there is in Berkeley.", "\n\nLeyden said the protesters “have very legitimate concerns and we can help them if they’re willing to move into conventional housing but we\n\nhave no magic wands.”", "\n\nTM and © Copyright 2016 CBS Radio Inc. and its relevant subsidiaries. ", "CBS RADIO and EYE Logo TM and Copyright 2016 CBS Broadcasting Inc. Used under license. ", "All Rights Reserved. ", "This material may not be published, broadcast, rewritten, or redistributed. ", "Bay City News Service contributed to this report." ]

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[ "Jerry Boyes\n\nJerry Boyes is an American football coach and college athletics administrator. ", " He is the athletic director at Buffalo State College. ", "Boyes was the head coach of the Buffalo State Bengals football program from 1986 to 2000 and again from 2009 to 2018, compiling a record of 138–116. ", "He has been the athletic director at Buffalo State since 1999.", "\n\nHead coaching record\n\nReferences\n\nExternal links\n\n Buffalo State profile\n\nCategory:Year of birth missing (living people)\nCategory:Living people\nCategory:American football quarterbacks\nCategory:Buffalo State Bengals athletic directors\nCategory:Buffalo State Bengals football coaches\nCategory:Ithaca Bombers football coaches\nCategory:Ithaca Bombers football players" ]

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[ "Chyloptysis after ligation of the thoracic duct.", "\nChyloptysis is a very rare clinical finding. ", "We describe a 44-year-old man who presented with cough and milky-white sputum. ", "Fiberoptic bronchoscopy revealed white sputum, which originated from the right B(6) bronchus. ", "The finding of elevated triglyceride levels in his sputum led to the diagnosis of chyloptysis. ", "He had a surgical history of ligation of the thoracic duct for idiopathic chylopericarditis 7 years-previously. ", "He also suffered from postoperative bilateral empyema. ", "Since then, his pleural cavity has been adhered bilaterally. ", "It is thought that his abnormal postoperative lymphatic flow caused the chyloptysis." ]

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[ "Lung transplantation for severe pulmonary hypertension--awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling.", "\nBilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). ", "Ventilator weaning failure and death are more common as in BLTx for other indications. ", "We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO). ", "In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). ", "Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. ", "Early extubation after transplantation was attempted under continued ECMO. ", "Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). ", "On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. ", "On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. ", "Survival rates at 3 and 12 months were 100% and 96%, respectively. ", "Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH. ", "Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. ", "This can be effectively bridged with awake venoarterial ECMO." ]

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[ "The 7 Healthiest Things You Can Eat at McDonald's\n\nWhile saying the word McDonald's in the fitness world sometimes feels like saying an expletive in front of a priest, the truth of the matter is, there are times when you don't have other options. ", "Sometimes you're in a bind! ", "Whether you're on a road trip and there aren't rest stops for hundreds of miles or you simply don't have access to nutritious food on the go, the golden arches of gluttony may in fact be your only option. ", "Fortunately, if you take a conscious approach to ordering, there are a few options that can actually provide a somewhat nutritious snack or meal." ]

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[ "Self-styled \"men's rights advocates\" used their Reddit forum yesterday to organize a spam campaign against Occidental College's online sexual assault reporting system, possibly complicating the already-fraught reporting process for actual victims at the university.", "\n\nThe campaign went down on r/MensRights, a subreddit for \"those who wish to discuss men's rights and the ways said rights are infringed upon.\" ", "In a post yesterday, user \"ShitlordDon\" linked to a \"sexual violence reporting form\" that the L.A.-based university made available to students as an anonymous way of tracking assault complaints. \"", "You just fill out a form and the person is called into the office on a rape charge,\" ShitlordDon complained. \"", "The 'victim' never has to prove anything or reveal their identity.\"", "\n\nSeveral redditors responded by encouraging each other to fill out the form with numerous false allegations. ", "Most of those responses were promptly deleted by Reddit moderators, but were screenshot and published by one diligent \"anti-misogyny\" blogger:\n\nMany commenters on r/MensRights were bitterly opposed to the spamming move. \"", "I can't believe y'all here are making false accusations to prove a point, and are getting upvoted for it,\" one commenter wrote. \"", "I thought the [men's rights movement] was vehemently opposed to false accusations?\"", "\n\n\"Before everyone goes all torchy, how do we know anyone at Occidental actually responds to this, or how it is responded to?\" ", "asked one top-rated commenter. \"", "Before harassing an institution over this, we should check our facts, or we become what we despise.\"", "\n\nIn fact, the form alone does not appear to be sufficient to bring a rape complaint against an Occidental student, although it does streamline university assault reporting methods—a problem that the school has struggled to solve after admitting last October that it had underreported sex assaults on campus in recent years.", "\n\nBut even that admission seriously underreported the school's alleged rapes, according to an investigation published earlier this month by the L.A. Times. ", "Occidental is now one of several universities that could potentially face federal penalties for mishandling campus rape allegations under Title IX of the U.S. Code. ", "Yesterday's spam campaign could complicate efforts to bring the college's assault procedures in line with those federal standards.", "\n\nAs of Wednesday morning, it was not yet clear how many reports were actually filed with the university as a result of ShitlordDon's posting, or whether it had succeeded in disrupting reporting procedures for victims of attacks. ", "A spokesman for Occidental told Gawker the university was in the process of gathering facts about the situation and would follow up with its findings in the afternoon; Gawker will update this post as details become available.", "\n\nUpdate: Occidental confirms to Gawker that it got jammed up by fake rape reports—not just from Reddit, but from 4chan, too. ", "The bizarre full story is here.", "\n\n[Photo credit: Occidental College]" ]

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[ "/*\n * Licensed to the Apache Software Foundation (ASF) under one\n * or more contributor license agreements. ", " See the NOTICE file\n * distributed with this work for additional information\n * regarding copyright ownership. ", " The ASF licenses this file\n * to you under the Apache License, Version 2.0 (the\n * \"License\"); you may not use this file except in compliance\n * with the License. ", " You may obtain a copy of the License at\n *\n * http://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing, software\n * distributed under the License is distributed on an \"AS IS\" BASIS,\n * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n * See the License for the specific language governing permissions and\n * limitations under the License.", "\n */\npackage org.apache.drill.exec.planner.logical;\n\nimport org.apache.calcite.plan.", "Convention;\nimport org.apache.calcite.plan.", "RelOptRule;\nimport org.apache.calcite.plan.", "RelOptRuleCall;\nimport org.apache.calcite.plan.", "RelTraitSet;\nimport org.apache.calcite.rel.core.", "Uncollect;\nimport org.apache.calcite.rel.logical.", "LogicalProject;\nimport org.apache.calcite.rel.logical.", "LogicalValues;\nimport org.apache.calcite.rex.", "RexNode;\nimport org.apache.calcite.sql.", "SqlKind;\n\npublic class DrillUnnestRule extends RelOptRule {\n public static final RelOptRule INSTANCE = new DrillUnnestRule();\n\n private DrillUnnestRule() {\n super(RelOptHelper.some(Uncollect.class,\n RelOptHelper.some(LogicalProject.class, RelOptHelper.any(LogicalValues.class, Convention.", "NONE))),\n DrillRelFactories.", "LOGICAL_BUILDER, \"DrillUnnestRule\");\n }\n\n @Override\n public void onMatch(RelOptRuleCall call) {\n final Uncollect uncollect = call.rel(0);\n final LogicalProject project = call.rel(1);\n\n RexNode projectedNode = project.getProjects().iterator().next();\n if (projectedNode.getKind() !", "= SqlKind.", "FIELD_ACCESS) {\n return;\n }\n final RelTraitSet traits = uncollect.getTraitSet().plus(DrillRel.", "DRILL_LOGICAL);\n DrillUnnestRel unnest = new DrillUnnestRel(uncollect.getCluster(),\n traits, uncollect.getRowType(), projectedNode);\n call.transformTo(unnest);\n }\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Evolution of bacterial ribosomal protein L1.", "\nSearch vectors composed of Gly, Ala, Arg, and Pro (GARP) residues retrieve 98% of each of the ribosomal proteins in prokaryotic species with no false hits. ", "Different combinations of G, A, R and P and insertions differentiate each ribosomal protein from all others. ", "Amino acids in two sequence positions separate Gram+ from Gram- bacteria. ", "Specific residues separate proteins of cyanobacteria and chloroplasts from all other species. ", "Structural information played an essential role in developing a GARP based technique to achieve perfect sequence alignment. ", "It is possible to understand why GARP residues are 100% conserved in specific positions in families of proteins present in all species." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "2019 UEFA European Under-21 Championship Final\n\nThe 2019 UEFA European Under-21 Championship Final was a football match that took place on 30 June 2019 at the Dacia Arena in Udine, Italy, to determine the winners of the 2019 UEFA European Under-21 Championship. ", "The match was contested by Spain and Germany, the defending champions of the competition, making the fixture a rematch of the previous final.", "\n\nSpain won the final 2–1 for their fifth UEFA European Under-21 Championship title, equalling Italy's record.", "\n\nRoute to the final\n\nMatch\n\nDetails\n\nReferences\n\nExternal links\n\nFinal\nCategory:UEFA European Under-21 Championship finals\nCategory:Spain national under-21 football team\nCategory:2018–19 in Spanish football\nCategory:Germany national under-21 football team\nCategory:2018–19 in German football\nCategory:Sport in Udine" ]

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

[ 0.0007378847221843898, 0.0008448734297417104, 0.0011954524088650942, 0.0006816353998146951 ]

[ "State dependent response of the locus caeruleus neurons to bladder distention.", "\nThe precise mechanism by which normal persons wake upon urinary sensation is unclear. ", "The locus caeruleus in the pons is suggested to be involved in the activating systems for arousal. ", "We evaluated the effects of bladder distention on the neural activity in the l. caeruleus under different states of anesthesia. ", "Experiments were performed on 20 male Sprague-Dawley rats. ", "The spontaneous discharge rate of single neurons in and around the l. caeruleus was recorded with the rat under urethane anesthesia administered intraperitoneally, while the electroencephalogram was monitored simultaneously. ", "The changes of the discharge rate of the neurons were observed during saline infusion into the bladder or during tail pinch stimulation. ", "After recording the location of the neurons was confirmed histologically. ", "Of 42 l. coeruleus neurons whose response was examined during deep anesthesia 31 showed an excitatory response to bladder distention, followed by a change in electroencephalogram pattern to a faster and smaller rate, while the remaining 11 showed no response. ", "Of 28 l. coeruleus neurons examined during light anesthesia only 1 neuron was excited and the remaining 27 showed no response. ", "Virtually all of the l. coeruleus neurons unresponsive to bladder distention were responsive to tail pinch stimulation. ", "Of the nonnoradrenergic neurons ventromedial to the l. coeruleus 4 of 7 during deep anesthesia and 5 of 8 during light anesthesia showed an excitatory response to distention. ", "The excitatory response of the l. coeruleus neurons to bladder distention was strongly affected by the state of anesthesia. ", "The response was observed only during deep anesthesia and was accompanied by lightening of the anesthesia. ", "L. coeruleus may be involved in arousal which is mediated by bladder distention." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Links\n\nImages\n\nClassifications\n\nA—HUMAN NECESSITIES\n\nA61—MEDICAL OR VETERINARY SCIENCE; HYGIENE\n\nA61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY\n\nA61H3/00—Appliances for aiding patients or disabled persons to walk about\n\nA—HUMAN NECESSITIES\n\nA61—MEDICAL OR VETERINARY SCIENCE; HYGIENE\n\nA61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY\n\nA61H3/00—Appliances for aiding patients or disabled persons to walk about\n\nA61H2003/002—Appliances for aiding patients or disabled persons to walk about with attached or incorporated article carrying means\n\nA61H2003/004—Trays\n\nY—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS\n\nAbstract\n\nAn apparatus for use with a walker of a type having four vertically disposed legs which are adapted to contact the floor at the bottom thereof. ", "Handles are provided on each side of the walker and first and second horizontal elongated members are disposed below each of the handles. ", "A rigid tray is provided for extending over and above the first and second horizontal elongated members, with each side of the tray having first and second downwardly extending flanges thereon for preventing the tray from falling off of the first and second horizontal elongated members. ", "The tray is not bolted or fastened to the walker itself so that it can be easily and quickly removed from or placed onto the first and second horizontal elongated members.", "\n\nDescription\n\nTECHNICAL FIELD\n\nThe present invention relates generally to a tray for use on a walker of a type that people use to help support themselves when walking from place to place, and more particularly to such a tray which is easily attached and detached from such walker.", "\n\nBACKGROUND ART\n\nThere are many handicapped people who must rely on the aid of a walker to move about from place to place. ", "When the walker is in use, both hands of the person are needed for using the walker and it is extremely difficult, if not impossible, to carry other things at the same time of using the walker without some special device.", "\n\nSince people generally prefer to do things for themselves, and further because many handicapped people using walkers do not always have other people around to help them, there is a need for a walker of a type which will permit the user to place a meal or other items on a tray for taking the tray and objects or food thereon to a place for it to be used or eaten as the case may be.", "\n\nCertain walkers have been made having things permanently attached to them for carrying objects, but a common problem is that these additions to the walker change the center of gravity and make them somewhat dangerous. ", "Furthermore, those trays permanently attached to a walker are not easily cleaned or sterilized, rendering them impractical. ", "Furthermore, permanently attached devices tend to be cumbersome and add additional weight at times when they are not needed. ", "Furthermore, permanently attached devices preclude having the convenience of using folding type walkers.", "\n\nDISCLOSURE OF THE INVENTION\n\nThe present invention relates to an apparatus for use with a walker of a type having four vertically disposed legs which are adapted to contact the floor at the bottom thereof. ", "Handles are provided on each side of the walker and first and second horizontal elongated members are disposed below each of the handles. ", "A rigid tray is provided for extending over and above the first and second horizontal elongated members, with each side of the tray having first and second downwardly extending flanges thereon for preventing the tray from falling off of the first and second horizontal elongated members. ", "The tray is not bolted or fastened to the walker itself so that it can be easily and quickly removed from or placed onto the first and second horizontal elongated members.", "\n\nAn object of the present invention is to provide a tray for a walker which is located at the walker's center of gravity directly beneath the hands of the person using the walker.", "\n\nA further object of the present invention is to provide a tray for a walker which facilitates greater control, greater safety, greater ease of use and practically eliminates the possibility of spillage of food disposed thereon.", "\n\nA still further object of the invention is to provide a tray for a walker which can easily be washed or sterilized.", "\n\nA further object of the present invention is to provide a tray of the aforementioned type whereby the user can actually dine directly from the tray.", "\n\nA still further object of the invention is to provide a tray useful for carrying a meal but which is also useful for sewing, writing, reading, or the like.", "\n\nOther objects, advantages, and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.", "\n\nBRIEF DESCRIPTION OF THE DRAWINGS\n\nFIG. ", "1 is a perspective view of the present invention shown as it would be used for carrying a meal from place to place;\n\nFIG. ", "2 is an exploded perspective view showing how the tray can be removed from or attached temporarily to a walker;\n\nFIG. ", "3 is a cross sectional view taken along line 3--3 of FIG. ", "1;\n\nFIG. ", "4 is a view taken along line 4--4 of FIG. ", "3;\n\nFIG. ", "5 is a cross sectional view taken along line 5--5 of FIG. ", "3; and\n\nFIG. ", "6 is an alternate form of the invention and showing it in cross section similar to the FIG. ", "5 embodiment.", "\n\nBEST MODES FOR CARRYING OUT THE INVENTION\n\nReferring now to the drawings, wherein like reference numerals designate identical or corresponding parts throughout the several views, FIG. ", "1. ", "shows a walker (10) having a tray apparatus (11) removably disposed thereon for use in carrying objects such as food or the like from place to place. ", "The walker includes front legs (12 and 13) and rear legs (14 and 15). ", "Handles (16 and 17) are attached around where the top of the front and rear legs (12 and 14 and 13 and 15), respectively, are connected together. ", "A brace (18), as shown in FIG. ", "2, connects the forward legs (12 and 13) and is also connected to another brace (19) for further bracing the front of the walker (10). ", "Additional braces (20 and 21) reinforce and make the bottom of the walker more rigid by interconnecting a lower portion of legs (12 and 14 and 13 and 15), respectively. ", "Conventional rubber caps (22) are disposed on the bottom of each of the legs for preventing slippage.", "\n\nThe tray (11) includes a flat central portion (23) with downwardly extending flanges (24 and 25) which can best be seen in FIG. ", "5. ", "A third downwardly extending flange (26) is somewhat U-shaped and forms a groove (27) in the top of the tray (11).", "\n\nUpwardly extending flanges (28, 29, 30 and 31) are provided for preventing objects disposed on the flat surface (23) from sliding off of the edge thereof. ", "A hole (32) is cut through the flat member (23) as can readily be seen in FIGS. ", "1, 2 and 3. ", "This hole (32) is for the purpose of holding a glass (33) which is of a frusto-conical type so that the bottom portion thereof will fit through the hole (32), but an upper portion of the container (33) will be too large to pass through the opening (32) and will support the container (33) so that it can be taken from place to place on the walker as shown in FIG. ", "1.", "\n\nReferring to FIGS. ", "2, 4 and 5, it is noted that a first horizontal elongated member (34) is ridigly attached at the ends thereof to the front leg (12) at one end thereof and to the rear leg (14) at the other end thereof. ", "Another second horizontal elongated member (35) is rigidly attached at one end to the front leg (13) and at the other end to the rear leg (15) just below the handle (17). ", "In order to use the tray (11) as shown in FIG. ", "2, one end thereof, for example the end with the flange (30) thereon can be slipped under the handle (16) and then the tray (11) can be moved to the right so that the flange (25) passes over the second horizontal elongated member (35) so that it can come to rest in the position shown in FIGS. ", "1, 3 and 5. ", "In this position, the first and second flanges (24 and 25) prevent the tray (11) from moving from one side to the other, and this is aided to some extent by the third flange (26). ", "Also, the tray is prevented from sliding off the front of the walker (10) because it would first come in contact with the front legs (12 and 13), and similarly, the tray (11) is prevented from sliding off of the rear of the walker because it would first come into contact with the rear legs (14 and 15).", "\n\nOnce the tray (11) is in the position shown in FIG. ", "1, then the person using it can place a container (33) full of liquid into the opening (32) and then place a plate of food, for example, onto the top of the flat surface (23). ", "Then the walker (10) can be used in a conventional fashion by having its user hold onto the handles (16) with the left hand and the handles (17) with the right hand taking a step or two forward, then picking up the walker (10) and placing it securely in front of them whereby they can take a step or two forwardly. ", "This process is of course repeated until the person gets to the desired place. ", "Once a person using the apparatus shown in FIG. ", "1 arrives at their destination, they can sit in a chair and the tray (11) will be in approximately the proper height for allowing them to eat therefrom as though they were eating from a dining room or kitchen table. ", "Then when the meal is complete, a reverse procedure can be used to get the dishes back to the place where they can be cleaned or disposed of. ", "After that is accomplished, then the tray can be removed from the walker (10) by merely picking it up and sliding it to one side or the other and then pulling it up through the center between the handles (16 and 17) where it can be stored and the walker can be used without the additional weight of the tray thereon.", "\n\nReferring now to FIG. ", "6, an alternate embodiment (41) is shown, but it is substantially identical to the tray of FIG. ", "5, except that the flange (26') does not have a groove in it like the groove (27) in projection (26) of FIG. ", "5. ", "The use of the FIG. ", "6 embodiment is substantially identical to the use described above of the embodiment shown in FIGS. ", "1-5.", "\n\nAccordingly, it will be appreciated that the preferred embodiments do indeed accomplish the aforementioned objects. ", "Obviously, many modifications and variations of the present invention are possible in light of the above teachings. ", "It is therefore to be understood, that within the scope of the appended claims, the invention may be practised otherwise than as specifically described.", "\n\nClaims (4)\n\nI claim:\n\n1. ", "An apparatus in combination with a walker of a type including four substantially vertically disposed legs adapted to contact the floor at the bottom thereof, brace means for interconnecting the four legs together, handle means connected to respective ones of said legs, one each side of the top of the walker for permitting a user to grasp one of said handle means with each hand, a first horizontal elongated member disposed below one of said handle means and extending from one of said legs toward another of said legs, and a second horizontal elongated member disposed below the other of said handle means and extending parallel to said first horizontal member and toward another of said legs, said apparatus consisting of:\n\na generally rectangular rigid tray means for extending over and above said first and second horizontal elongated member;\n\neach side of said tray means having first and second downwardly extending elongated flange means extending on the outside of respective ones of said first and second horizontal elongated members for preventing said rigid tray means from falling off said first and second horizontal elongated members;\n\na third downwardly depending elongated flange means attached to said rigid tray means and extending parallel and adjacent to but spaced from said first downwardly extending flange, said third flange being disposed between said first and second horizontal elongated members but closer to the first than to the second horizontal elongated member; and,\n\nsaid downwardly depending flange means permitting said rigid tray means to be easily and quickly removed from or placed on said first and second horizontal elongated members.", "\n\n2. ", "The apparatus of claim 1 including an upwardly extending flange on each upper and outer edge of said rigid tray means for preventing food from falling off of said rigid tray means.", "\n\n3. ", "The apparatus of claim 2 including a circular hole means extending through said rigid tray means for receiving a frusto-conically shaped container for holding liquids.", "\n\n4. ", "The apparatus of claim 3 including a groove disposed in the top of said rigid tray means just above said third downwardly depending flange means." ]

{ "pile_set_name": "Pile-CC" }

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[ "Shenzhen Zhongsuwang Plastic Products Co,.", "Ltd is one of the top level China TPE, TPR, TPU, TPV manufacturers and suppliers, our factory is able to produce cheap and low price TPE, TPR, TPU, TPV at\n... Read more\n\nWelcome to browse the website for the high quality and flexible drum dryer, spray dryer, belt dryer, spin flash dryer, hot air oven here, which is of fast drying performance and strong durability. ", "As\n... Read more" ]

{ "pile_set_name": "Pile-CC" }

[ 0.0008625391637906432, 0.0007128483848646283, 0.0008214992703869939 ]

[ "Field of the Art\nThe disclosure relates to the field of electronic devices, and more particularly to the field of wireless handheld controllers for interacting with host devices.", "\nDiscussion of the State of the Art\nIn the field of electronic devices, separate handheld controllers are commonly used to enable a user to provide interaction or receive feedback from a host device, such as a personal computer or a video gaming console. ", "These controllers may be connected via a wired or a wireless connection, and generally are paired with only a single host device at any given time. ", "When a user wishes to utilize multiple controllers, they must be connected individually to the host device (for example, connecting both a keyboard and a mouse to a personal computer, using two separate ports on the computer). ", "This requires a number of separate communication connections between a host device and controllers, and if a host device or controller have mismatched communication hardware, they are incompatible and cannot be used. ", "Additionally, controllers generally are designed for a particular purpose (such as for a particular type of video game or computer application), and require a user to interact with them in a specific fashion, such as to hold the controller in a particular manner to have manual access to all of its functions. ", "This can be awkward or even unhealthy for the user, and restrictive of the manner with which they interact with the device.", "\nWhat is needed, is a means to enable users to connect a variety of controllers to a host device regardless of their communication means, that also addresses the need for controllers that a user may interact with in a customizable fashion to enhance ergonomics as well as improve the quality of interaction." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Q:\n\nHow do I combine the Command Pattern with a JavaFX GUI?", "\n\nMy current Controller class\npublic class Controller {\n @FXML\npublic javafx.scene.image.", "ImageView imageView;\n\n@FXML\nprivate MenuItem openItem;\n\n@FXML\npublic void openAction(ActionEvent event) {\n FileChooser fc = new FileChooser();\n File file = fc.showOpenDialog(null);\n try {\n BufferedImage bufferedImage = ImageIO.read(file);\n Image image = SwingFXUtils.toFXImage(bufferedImage, null);\n imageView.setImage(image);\n } catch (IOException e) {\n System.out.println(\"lol\");\n }\n\n}\n\nHow would I be able to place the openAction function logic in its own class? ", "I need to add about 10 - 20 functions with their own actionevent listeners for my UI and I dont want to have all of these functions existing in this one controller class.", "\n\nA:\n\nIt's not clear in what context you want to use the pattern, so I'm showing an example conversion that accepts the address of the window (that is, to submit it as the owner of the dialogs that are displayed).", "\nIt starts with an interface that describes the command (in this case I chose to return Optional)\npublic interface Command<R> {\n public Optional<R> execute();\n}\n\nThe implementation of the Command interface in an abstract class follows.", "\npublic abstract class AbstractCommand<R> implements Command<R> {\n\n private Window window;\n\n public AbstractCommand(Window window) {\n this.window = window;\n }\n\n public Window getWindow() {\n return window;\n }\n}\n\nFrom here on, we can do as much as we want implementations either by realizing Command or by extending AbstractCommand.", "\nThis is an example implementation of the load image command\npublic class LoadImageCommand extends AbstractCommand<Image> {\n\n public LoadImageCommand() {\n this(null);\n }\n\n public LoadImageCommand(Window window) {\n super(window);\n }\n\n @Override\n public Optional<Image> execute() {\n Image image = null;\n\n FileChooser fc = new FileChooser();\n File file = fc.showOpenDialog(getWindow());\n try {\n if(file !", "= null) {\n BufferedImage bufferedImage = ImageIO.read(file);\n image = SwingFXUtils.toFXImage(bufferedImage, null);\n }\n } catch (IOException e) {\n System.out.println(\"lol\");\n }\n\n return Optional.ofNullable(image);\n }\n}\n\nUsing the command:\n@FXML\nprivate void openAction(ActionEvent event) {\n new LoadImageCommand().execute().ifPresent(imageView::setImage);\n}\n\nIf you want to use openAction in different controllers and do not want to create separate instances of Command, inherit Controller.", "\n\n" ]

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[ "---\nabstract: 'Superconducting microwave circuits show great potential for practical quantum technological applications such as quantum information processing. ", "However, fast and on-demand initialization of the quantum degrees of freedom in these devices remains a challenge. ", "Here, we experimentally implement a tunable heat sink that is potentially suitable for the initialization of superconducting qubits. ", "Our device consists of two coupled resonators. ", "The first resonator has a high quality factor and a fixed frequency whereas the second resonator is designed to have a low quality factor and a tunable resonance frequency. ", "We engineer the low quality factor using an on-chip resistor and the frequency tunability using a superconducting quantum interference device. ", "When the two resonators are in resonance, the photons in the high-quality resonator can be efficiently dissipated. ", "We show that the corresponding loaded quality factor can be tuned from above $10^5$ down to a few thousand at 10 GHz in good quantitative agreement with our theoretical model.'", "\nauthor:\n- 'M. Partanen'\n- 'K. Y. Tan'\n- 'S. Masuda'\n- 'J. Govenius'\n- 'R. E. Lake'\n- 'M. Jenei'\n- 'L. Grönberg'\n- 'J. Hassel'\n- 'S. Simbierowicz'\n- 'V. Vesterinen'\n- 'J. Tuorila'\n- 'T. Ala-Nissila'\n- 'M. Möttönen'\ntitle: '[Flux-tunable heat sink for quantum electric circuits]{}'\n---\n\nIntroduction {#introduction .unnumbered}\n============\n\nOne of the most promising approaches to building a quantum computer is based on superconducting qubits in the framework of circuit quantum electrodynamics [@Ladd; @Clarke; @Blais; @Wallraff_Nature_2004; @Goppl; @Kelly2015]. ", "However, not all of the criteria for a functional quantum computer [@DiVincenzo2000] have been achieved simultaneously at the desired level. ", "In particular, computational errors need to be mitigated with quantum error correction [@Lidar_book_2013; @Terhal_2015]. ", "Many quantum error correction codes require frequent initialization of ancillary qubits during the computation. ", "Thus, fast and accurate qubit reset is a typical requirement in the efficient implementation of quantum algorithms. ", "To date, several approaches for qubit initialization have been studied [@Valenzuela_2006; @Johnson_2012; @Riste_2012; @Geerlings_2013; @Bultink_2016]. ", "Initialization to the ground state by waiting is a straightforward method but it becomes impractical in repeated measurements of qubits with long lifetimes. ", "Therefore, active initialization is advantageous. ", "Furthermore, it may be beneficial to design individual circuits for qubit control, readout, and initialization in order to avoid performance-limiting compromises in the optimization of the circuit parameters. ", "In this work we focus on a specialized initialization circuit, which remains to be implemented in superconducting quantum processors.", "\n\nRecently, a promising qubit initialization protocol based on dissipative environments was proposed in Refs.", " . ", "In this proposal, a resistor coupled to a frequency-tunable resonator quickly absorbs the excitation from the qubit when tuned in resonance. ", "In this paper, we experimentally realize such a tunable dissipative environment and study its effect on a superconducting resonator. ", "Tunable superconducting resonators have been demonstrated previously [@Palacios-Laloy2008; @Healey_2008; @Pierre_2014; @Wang_2013; @Vissers_2015; @Adamyan_2016] but without engineered dissipation arising from on-chip normal-metal components. ", "In addition to quantum computing, very sensitive cryogenic detectors [@Inomata_2016; @Govenius_2016; @Narla_2016] may benefit from tunable dissipation for calibration purposes. ", "Furthermore, tunable transmission lines are also useful in studying fundamental quantum phenomena [@Wilson_2011].", "\n\nAlthough dissipation is in some cases beneficial for quantum computing [@Verstraete2009], lossy materials are typically harmful for qubit lifetimes during computation. ", "Therefore, one needs to be able to switch the dissipation on and off deterministically. ", "In state-of-the-art experiments, quality factors, $Q$, above $10^6$ indicating very low dissipation have been achieved with coplanar-waveguide resonators [@Megrant_2012]. ", "Various materials and methods have been studied for fabricating high-$Q$ resonators [@Vissers_2010; @Sandberg_2012; @Bruno_2015; @Zmuidzinas_2012]. ", "Here we fabricate high-$Q$ resonators based on niobium on a silicon wafer. ", "In addition, we tune the $Q$ factor from above $10^5$ down to a few thousand by coupling the resonator relatively strongly to a dissipative element. ", "Importantly, the integrated resistive element we introduce does not inherently degrade the $Q$ factor when it is weakly coupled to the resonator compared with similarly fabricated resonators without any engineered resistive elements.", "\n\n{width=\"\\linewidth\"}\n\n ---------------- ---------------- ---------------- ---------------- ----------------- ----------------- ---------------- ------------ ------------ ---------------- ---------------------------- ------- ----------- -------------------- -------\n Parameter $C_\\textrm{C}$ $C_\\textrm{T}$ $C_\\textrm{L}$ $C_\\textrm{R1}$ $C_\\textrm{R2}$ $C_\\textrm{l}$ $R$ $Z_0$ $Z_\\textrm{L}$ $\\varepsilon_\\textrm{eff}$ $x_1$ $x_2$ $Q_\\textrm{int,1}$ $I_0$\n (fF) (fF) (pF) (pF) (pF) (pF/m) ($\\Omega$) ($\\Omega$) ($\\Omega$) (mm) (mm) (nA)\n \n \\[-1em\\] Value 1 5 2.8 4.0 28 180 375 50 50 6.35 12 7.5 (8.0) $1\\times10^{5}$ 255\n ---------------- ---------------- ---------------- ---------------- ----------------- ----------------- ---------------- ------------ ------------ ---------------- ---------------------------- ------- ----------- -------------------- -------\n\n\\[tab:simulation\\_parameters\\]\n\nResults {#results .unnumbered}\n=======\n\n**Experimental samples**\\\nThe structure of our device is presented in Fig.", " \\[fig:sample\\_structure\\] together with the corresponding electrical circuit diagram which defines the symbols used below. ", "The device consists of two coupled resonators, Resonator 1 with a fundamental frequency of 2.5 GHz, and Resonator 2 with a tunable frequency. ", "Both ends of Resonator 1 couple capacitively ($C_\\textrm{C}$) to external circuitry for scattering parameter measurements. ", "The even harmonics of Resonator 1 interact with Resonator 2 since there is a voltage antinode at the center of the half-wave Resonator 1, and hence, the capacitive ($C_\\textrm{T}$) coupling to Resonator 2 is significant.", "\n\nThe resonators are fabricated out of niobium in a coplanar-waveguide geometry. ", "The modes of Resonator 2 are tunable owing to a superconducting quantum interference device (SQUID) acting as a flux-tunable inductance, placed in the middle of the resonator. ", "The SQUID is integrated into the center pin of the waveguide and consists of two aluminium layers separated by an insulating aluminium oxide layer. ", "When the resonance frequencies of the two resonators meet, we expect a degradation of the Resonator 1 quality factor because Resonator 2 is terminated with a dissipative on-chip resistor made of copper. ", "Importantly, the device is designed to retain a high quality factor of Resonator 1 whenever Resonator 2 is far detuned.", "\n\nWe study two samples, Sample A and B, which are nominally identical, except for the length of Resonator 2. ", "We mostly focus on Sample A which has a wider tuning range of the quality factor of Resonator 1. ", "The samples are measured at a cryostat temperature of approximately 10 mK. The theoretical model described in Methods reveals all the essential features of the two samples with a single set of parameters given in Table \\[tab:simulation\\_parameters\\]. ", "See Methods for the details of the sample fabrication.", "\n\n{width=\"\\linewidth\"}\n\n{width=\"0.9\\linewidth\"}\n\n{width=\"0.85\\linewidth\"}\n\n**Flux dependence of the resonance frequencies**\\\nThe first four resonances of Resonator 1 in Sample A are shown in Fig.", " \\[fig:meas\\_sim\\_modes\\_i7\\] as a function of the magnetic flux through the SQUID. ", "The first and the third mode at approximately 2.5 and 7.5 GHz, respectively, do not depend on the flux due to a voltage node in the middle of Resonator 1, i.e., at the coupling capacitor $C_\\textrm{T}$. Thus, these modes are decoupled from those of Resonator 2. ", "In contrast, the second and the fourth mode at 5 and 10 GHz, respectively, show clear flux dependence owing to the changing SQUID inductance, which in turn changes the frequencies of the modes in Resonator 2. ", "If a dissipative mode in Resonator 2 approaches the frequency of a mode in Resonator 1, we observe two distinctive features: the resonance in Resonator 1 shifts and broadens owing to the coupling to the dissipative mode. ", "The experimental scattering parameter $S_{21}$ is normalized as explained in Methods. ", "The simulation based on the theoretical model (see Methods) shows excellent agreement with experimental data. ", "The slight discrepancy between the experiment and the simulation mainly arises from the uncertainty in the exact values of the parameters given in Table \\[tab:simulation\\_parameters\\].", "\n\nThe distinctively different flux dependence of modes 2 and 4 in Sample A is clarified by Fig.", " \\[fig:Qfactor\\_i7\\]b, which shows simulated $|S_{21}|$ with only Resonator 2, i.e., in the limit $C_\\textrm{C}\\rightarrow \\infty$. Resonator 2 has a flux dependent resonance near 4 GHz, which does not cross the second mode of Resonator 1 at 5 GHz. ", "Nevertheless, it comes sufficiently near 5 GHz, which explains the frequency shift of mode 2 of Resonator 1. ", "In contrast, Resonator 2 has a flux dependent resonance near 10 GHz, very close to mode 4 of Resonator 1. ", "The resonances intersect which results in dramatic changes in the fourth mode of Resonator 1. ", "The second mode of Resonator 2 near 8 GHz has a current node at the center of the resonator, where the SQUID is located; thus, it is only very weakly dependent on the flux.", "\n\nSupplementary Fig.", " \\[fig:meas\\_sim\\_modes\\_i8\\] shows results similar to those in Fig.", " \\[fig:meas\\_sim\\_modes\\_i7\\] for Sample A but for modes 2, 3, and 4 of Sample B. The simulations and experiments are also here in good agreement. ", "However, the simulated mode 2 is substantially narrower than the experimental one. ", "This broadening may arise from an unaccounted mode of the sample holder at a nearby frequency. ", "Furthermore, there is some discrepancy in the phase of mode 4 near integer flux quanta. ", "This discrepancy can be explained by uncertainty in the normalization procedure with very small amplitudes. ", "The first mode is outside the frequency range of the used microwave components, and hence we do not show data for it. ", "For a quantitative comparison of the measured and the simulated resonance frequencies in Samples A and B, Supplementary Fig.", " \\[fig:meas\\_sim\\_delta\\_f\\] shows the frequency shifts of modes 2 and 4 extracted from Fig.", " \\[fig:meas\\_sim\\_modes\\_i7\\] and Supplementary Fig.", " \\[fig:meas\\_sim\\_modes\\_i8\\]. ", "The flux dependence of the modes of Resonator 2 is similar in Sample B to that of Sample A as shown in Supplementary Fig.", " \\[fig:Qfactor\\_i8\\]b. ", "However, the resonances do not intersect at 10 GHz although they are very close to each other.", "\n\n**Quality factors**\\\nWe also analyze the quality factors as functions of flux, as shown for Sample A in Fig.", " \\[fig:Qfactor\\_i7\\]a, and for Sample B in Supplementary Fig.", " \\[fig:Qfactor\\_i8\\]a. ", "The $Q$ factors of the second and fourth mode are tunable unlike in the case of the first and third mode. ", "The second mode of Sample A shows only relatively small variation near $10^5$ whereas the fourth mode can be tuned from above $10^5$ down to a few thousand. ", "For Sample B, the flux dependence of the $Q$ factor is similar. ", "However, the second mode has a substantially lower experimental loaded quality factor, $Q_\\textrm{L}$, than the simulated value, i.e., a broader resonance peak as discussed above. ", "A better agreement between the simulation and the experiment can be obtained by introducing an additional loss mechanism as described in the caption of Supplementary Fig.", " \\[fig:Qfactor\\_i8\\].", "\n\nThe power dependence of the quality factors is analyzed in Fig.", " \\[fig:Qfactor\\_i7\\]c for the four lowest modes in Sample A. The $Q$ factors decrease with decreasing power as expected [@Zmuidzinas_2012]. ", "Nevertheless, they remain rather close to $10^5$ even at the single-photon level, around -140 dBm. ", "However, relatively high powers enable more accurate measurements of the losses caused by the resistor when the resonators are tuned into the weak coupling regime. ", "Figure \\[fig:Qfactor\\_i7\\]d shows the experimentally obtained loaded quality factor, $Q_\\textrm{L}$, and the theoretically predicted external quality factor, $Q_\\textrm{ext}$, corresponding to the losses through the coupling capacitors $C_\\textrm{C}$ as functions of the mode number $n$. Furthermore, the internal quality factor, $Q_\\textrm{int}$, corresponding to the internal losses in the system is calculated from the equation $Q_\\textrm{int}^{-1} = Q_\\textrm{L}^{-1} - Q_\\textrm{ext}^{-1}$. The internal quality factor slightly increases with the mode number and obtains values near $2.5\\times10^5$. The minimum value of $Q_\\textrm{L} \\lesssim 5\\times10^3$ in Fig.", " \\[fig:Qfactor\\_i7\\]a gives also the minimum value for $Q_\\textrm{int}$ since the internal losses of the system dominate when the resistor is strongly coupled to the fourth mode of Resonator 1.", "\n\nThe minimum and maximum $Q_\\textrm{int}$ correspond to photon lifetimes $\\tau_\\textrm{int}= Q_\\textrm{int}/\\omega_0$ of 80 ns and 4 $\\mu$s, respectively, at $\\omega_0 =2 \\pi \\times10$ GHz when other losses are neglected. ", "Furthermore, $Q_\\textrm{ext}$ corresponds to a photon lifetime of 6 $\\mu$s. ", "These photon lifetimes are long compared to the period of the coherent oscillations between the two resonators at resonance, $\\tau_\\textrm{T}=30$ ns (see Methods). ", "Thus, the internal or external losses of Resonator 1 are not dominating over the coupling strength between the resonators. ", "However, the simulated $Q$ factors of the lowest modes of Resonator 2 in Fig.", " \\[fig:Qfactor\\_i7\\]b are well below 40 at the zero flux bias and also at $\\Phi/\\Phi_0 \\approx 0.2$ which corresponds to the crossing of the modes at 10 GHz. ", "They obtain values above 100 only in the range $0.48 <\\Phi/\\Phi_0< 0.52$ due to the ideally diverging SQUID inductance. ", "Thus, the photon lifetime in Resonator 2 is below 0.6 ns at 10 GHz and at the relevant flux point. ", "Consequently, the photons in Resonator 2 are dissipated quickly compared to the period of the coherent oscillations between the resonators, which prevents the formation of well-separated modes hybridized between the resonators. ", "Importantly, Resonator 2 mostly functions as a tunable dissipative environment for Resonator 1, the dissipation of which is limited by the coupling strength between the resonators.", "\n\n**Simulations with different resistances**\\\nWe also simulate the effect of changing the termination resistance as shown in Fig.", " \\[fig:sim\\_i7\\_differentR\\]. ", "The other parameters in the simulations are from Sample A. Note the different frequency range and colour scale compared to Fig.", " \\[fig:meas\\_sim\\_modes\\_i7\\]. ", "In the case of a 100-$\\Omega$ termination resistance, there is very little shift in the resonance frequency as a function of the magnetic flux. ", "Nevertheless, the width of the peak varies since the ideal SQUID inductance diverges, $L \\rightarrow \\infty$ for $\\Phi/\\Phi_0 \\rightarrow 0.5$, and therefore, it decouples the resistor from Resonator 1. ", "At even lower resistances near 50 $\\Omega$ (not shown), the termination is well matched to the characteristic impedance, and hence the description of Resonator 2 as a resonator becomes obscure. ", "Instead, it appears as a broad-band dissipative environment for Resonator 1. ", "With increasing resistance, Resonator 2 obtains well-defined resonances, with zero-flux $Q$ factors becoming of the order of $10^3$ at $R=10$ k$\\Omega$. However, the maximum $Q_\\textrm{L}$ in Resonator 1 of $1.8\\times10^5$ does not vary due to the ideally infinite impedance of the SQUID at $\\Phi/\\Phi_0 \\rightarrow 0.5$. In contrast at zero flux, $Q_\\textrm{L}$ increases from $1.0\\times10^4$ to $1.3\\times10^5$ as the resistance increases from $100$ $\\Omega$ to $10$ k$\\Omega$. At $R=10$ k$\\Omega$, the two resonators show a clear avoided-crossing feature. ", "There is a continuous crossover from a single modulating resonance at low resistance values to two resonances with an avoided crossing at high resistances. ", "In the experiments, we have $R=375$ $\\Omega$, which results in a single modulating resonance with some avoided-crossing-like features.", "\n\nDiscussion {#discussion .unnumbered}\n==========\n\nWe have experimentally demonstrated tunable dissipation in a device consisting of two resonators in very good agreement with our theoretical model. ", "We have studied two samples with slightly different parameters. ", "Both of them allow us to substantially tune the loaded quality factors of the relevant resonances. ", "In addition, the internal quality factor of one of the modes can be tuned from approximately a quarter of a million down to a few thousand. ", "Importantly, we have designed the circuit such that the coupling strength between the resonators is somewhat weaker than the dissipation in Resonator 1 and stronger than the dissipation in Resonator 2. ", "Therefore, Resonator 2 operates as an efficient dissipative environment for Resonator 1. ", "Note that the spurious internal losses in the system are low as indicated by the high maximum quality factor. ", "Thus, the fabrication of the on-chip resistors is compatible with obtaining high quality factors using our fabrication process. ", "To our knowledge, these are the highest demonstrated quality factors in superconducting resonators with integrated on-chip resistors. ", "In the future, the remaining unwanted losses can be reduced by further improving the process.", "\n\nHere, we have demonstrated a tunable dissipative environment with a rather specific sample type. ", "Nevertheless, the geometry and parameters can be relatively freely chosen to optimize the heat sink for different applications. ", "For instance, it is possible to modify the losses by changing the resistance and capacitance values. ", "Furthermore, the geometry of the system can be changed in order to obtain different coupling strengths for different modes. ", "In addition, the resistor does not necessarily have to be directly coupled to Resonator 2. ", "Instead, it can be outside the resonator and coupled with a small capacitance and a section of a transmission line. ", "Furthermore, in case the resistance equals to the characteristic impedance of the transmission line resonator, the environment is effectively similar to a transmission line [@Pierre_2014].", "\n\nAlthough we consider the resistors only as sources of dissipation here, they may also be engineered to simultaneously function in photon-absorbing normal-metal–insulator–superconductor tunnel junctions [@Tan_2017], or quasiparticle traps in superconducting circuits [@Goldie_1990; @Ullom_2000; @Rajauria_2012; @Riwar_2016; @Patel_2017]. ", "Fast tuning of the quality factors can be obtained by introducing microwave flux bias lines. ", "A lower bound for the time scale of the flux tuning is given by the plasma frequency of the SQUID, which is of the order of 30 GHz in our samples. ", "In the future, qubits can be integrated into this system enabling the demonstration the protocol for fast and accurate initialization [@Tuorila_2017].", "\n\nMethods {#methods .unnumbered}\n=======\n\n**Theoretical model and simulations**\\\nWe analyze the electrical circuit shown in Fig \\[fig:sample\\_structure\\]f, which also defines the symbols employed below. ", "The input impedance of Resonator 2 can be obtained from standard microwave circuit analysis [@Pozar], and it is given by $$\\! ", " \\! ", " Z_\\textrm{r2} \\! ", "= \\! ", "\n \\frac{1}{i \\omega C_\\textrm{T}} + \n \\frac{Z_0 \\! ", " \\left\\{ \\! ", " Z_\\textrm{S} \\! ", "+ \\! ", " Z_0 \\! ", " \\tanh( \\! ", "\\gamma x_2 \\! ) ", " \\! ", " + \\frac{Z_0 \\left[ Z_\\textrm{term} \\! ", " + \\! ", " Z_0 \\tanh(\\gamma x_2) \\right]}{Z_0 + Z_\\textrm{term} \\tanh(\\gamma x_2)} \\! ", " \\right\\}\n}{\nZ_0 \\! ", "+ \\! ", " \\tanh(\\gamma x_2) \\left\\{ \\! ", " Z_\\textrm{S} \\! ", " + \\! ", " \\frac{Z_0 [ Z_\\textrm{term} + Z_0 \\tanh(\\gamma x_2) ]}{Z_0 + Z_\\textrm{term} \\tanh(\\gamma x_2)} \\! ", " \\right\\}\n},$$ where $Z_\\textrm{S}=i\\omega L + 2/(i\\omega C_\\textrm{L})$ is the impedance of the SQUID and the parallel plate capacitors connecting the SQUID to the center conductor, and $Z_\\textrm{term}=R+1/(i\\omega C_\\textrm{R1})+1/(i\\omega C_\\textrm{R2})$ is the impedance of the terminating resistor and the capacitances connecting it to the center conductor and the ground plane. ", "Here, $\\omega=2\\pi f$ is the angular frequency of the measurement tone, and $\\gamma$ is the wave propagation coefficient detailed below. ", "We consider the SQUID as a tunable classical inductor. ", "The inductance of the SQUID as a function of the magnetic flux $\\Phi$ is ideally given by $ L(\\Phi) = \\Phi_0 /[2 \\pi I_0 |\\cos(\\pi \\Phi / \\Phi_0)|],$ where $I_0$ is the maximum supercurrent through the SQUID, and $\\Phi_0 = h/(2e)$ is the magnetic flux quantum. ", "The losses in the SQUID are assumed to be substantially smaller than those induced by the resistor; thus, they are neglected. ", "One could also include a capacitance in parallel with the inductance in the model but it would have only a minor effect as discussed below.", "\n\nWe can calculate the scattering parameter from Port 1 to Port 2 using the ABCD matrix method [@Pozar] $$S_{21}=\\frac{2}{ A + B/Z_L + C Z_L + D},$$ where the coefficients are obtained from\n\n$$\\begin{pmatrix}\n A &B \\\\\n C &D\n \\end{pmatrix} \n=\n \\begin{pmatrix}\n 1 &\\frac{1}{i \\omega C_\\textrm{C}}\\\\\n0 &1\n \\end{pmatrix} \n \\begin{pmatrix}\n \\cosh(\\gamma x_1) & Z_0 \\sinh(\\gamma x_1) \\\\\n\\frac{1}{Z_0} \\sinh(\\gamma x_1) & \\cosh(\\gamma x_1) \n \\end{pmatrix} \n \\begin{pmatrix}\n 1 &0\\\\\n\\frac{1}{Z_\\textrm{r2}} &1\n \\end{pmatrix} \n \\begin{pmatrix}\n \\cosh(\\gamma x_1) & Z_0 \\sinh(\\gamma x_1) \\\\\n\\frac{1}{Z_0} \\sinh(\\gamma x_1) & \\cosh(\\gamma x_1) \n \\end{pmatrix} \n \\begin{pmatrix}\n 1 &\\frac{1}{i \\omega C_\\textrm{C}}\\\\\n0 &1\n \\end{pmatrix}.$$\n\nThese equations are solved numerically with Matlab.", "\n\nThe simulation parameters are given in Table \\[tab:simulation\\_parameters\\]. ", "We use identical parameters in the simulations for both samples except that the length $x_2$ is different. ", "The capacitances $C_\\textrm{C}$ and $C_\\textrm{T}$ are based on finite-element-method (FEM) calculations with design geometry and without native oxides, whereas $C_\\textrm{L}$, $C_\\textrm{R1}$, and $C_\\textrm{R2}$ are calculated using parallel-plate-capacitor model by deducing the areas from scanning electron microscope images, and assuming the niobium oxide to have a typical thickness [@Bach_thesis] of 5 nm and relative permittivity [@Graca_2015] of 6.5. ", "The capacitance per unit length of the coplanar waveguide $C_\\textrm{l}$ is also based on a FEM simulation. ", "The resistance $R$ is measured with a dc control sample in a four-probe setup at 10 mK. The test resistor is fabricated in the same process with the actual samples. ", "The effective permittivity of the waveguide $\\epsilon_\\textrm{eff}$ is obtained from the nominal widths of the centre conductor and the gap, 10 $\\mu$m and 5 $\\mu$m respectively, using an analytical formula [@Gevorgian_1995]. ", "The lengths $x_1$ and $x_2$ are design values. ", "The internal quality factor of the first mode of Resonator 1 alone, $Q_\\textrm{int,1}$, is based on measurements of control samples consisting of a single resonator, and it agrees well with the measured first mode of Sample A. The characteristic impedance of the external lines $Z_\\textrm{L}$ has a nominal value, and the characteristic impedance of the resonators $Z_0$ has a design value in good agreement with the experimental results. ", "The maximum supercurrent through the SQUID $I_0$ is used as the only fitting parameter since it cannot be directly measured in the actual sample. ", "Nevertheless, the critical current in the actual samples is relatively close to a switching current of approximately 180 nA measured with a dc setup in an essentially similar but separately fabricated control SQUID. ", "Due to noise from a high-temperature environment via the dc lines, the temperature of the control SQUID may be higher than in the actual sample, thus providing an explanation to the difference in the critical current and the switching current. ", "In addition, the difference may well be explained by unintentional differences in the fabrication. ", "We can write the wave propagation coefficient as $ \\gamma = \\omega_1 /(2 Q_\\textrm{int,1} v_\\textrm{ph}) + i\\omega / v_\\textrm{ph},$ where $v_\\textrm{ph} = c/\\sqrt{\\varepsilon_\\textrm{eff}}$ is the phase velocity, $\\omega_1 /(2 \\pi)= c/(4 x_1 \\sqrt{\\varepsilon_\\textrm{eff}})$ is the fundamental frequency, and $c$ is the speed of light in vacuum.", "\n\nThe loaded quality factor can be defined as $Q_\\textrm{L} = \\omega_0 E / P_\\textrm{loss}$, where $\\omega_0 = 2 \\pi f_0$ is the angular frequency of the resonance, $E$ the energy stored in the resonator, and $P_\\textrm{loss}=-\\textrm{d}E/\\textrm{d}t$ the power loss. ", "Without input power, the energy in the resonator evolves as a function of time $t$ as $E(t)=E_0 \\exp(-\\omega_0 t /Q_\\textrm{L})$, where $E_0$ is the initial energy. ", "Thus, the photon lifetime is given by $\\tau_\\textrm{L} = Q_\\textrm{L}/\\omega_0$, which corresponds to the total losses described by $Q_\\textrm{L}$. Since the number of photons in a resonator $n$ depends on the energy as $E=n \\hbar \\omega_0$, where $\\hbar$ is the reduced Planck constant, and the power loss is bounded from above by the input power $P_\\textrm{in}$ in the steady state, one obtains an upper bound for the photon number as $n < Q_\\textrm{L} P_\\textrm{in} /(\\omega_0^2 \\hbar)$. Therefore, the average photon number in a 10-GHz resonator is near unity or below if the $Q$ factor is $10^5$ and the input power is $-140$ dBm (c.f. ", "Fig.", " \\[fig:Qfactor\\_i7\\]). ", "The external quality factor corresponding to the leakage through the coupling capacitors can be calculated as[@Goppl] $Q_\\textrm{ext} = 2 x_1 C_\\textrm{l} /(4 Z_\\textrm{L} \\omega_0 C_\\textrm{C}^2)$. Although $Q_\\textrm{ext}$ calculated with this formula is quite sensitive to errors especially in $C_\\textrm{C}$, it can be considered at least as an order-of-magnitude estimate. ", "The external quality factor is related to the coupling strength describing the external ports, $\\kappa_\\textrm{ext}=\\omega_0/Q_\\textrm{ext}= 2\\pi \\times 30$ kHz at $\\omega_0 = 2\\pi \\times 10$ GHz. ", "In addition, one can write the photon lifetime without other loss mechanisms as $\\tau_\\textrm{ext} = Q_\\textrm{ext}/\\omega_0= 1 / \\kappa_\\textrm{ext} = 6$ $\\mu$s. ", "The coupling to the external ports can be compared with the coupling strength between the resonators at resonance calculated as [@Jones_4] $g_\\textrm{T} = C_\\textrm{T} V_1 V_2 / \\hbar = 2\\pi \\times 10$ MHz, where $V_{i} = \\sqrt{\\hbar \\omega_0/(2 x_{i} C_\\textrm{l})}$, $i=1,2$, and $\\omega_0 = 2\\pi \\times 10$ GHz. ", "Furthermore, the period for coherent oscillations between the resonators can be written as[@Blais] $\\tau_\\textrm{T} = \\pi / g_\\textrm{T} = 30$ ns, where we have neglected dissipation.", "\n\nThe junction capacitance can be estimated using a parallel-plate model with an approximate aluminium oxide thickness of 2 nm, a junction area of 0.25 $\\mu$m estimated from micrographs, and a typical relative permittivity [@Landry_2001] of 8.2, which yield 10 fF per junction. ", "At zero flux and 5 GHz (10 GHz), the inductive reactance of the SQUID is 40 $\\Omega$ (80 $\\Omega$) whereas the capacitor consisting of two junctions in parallel has a reactance of 2 k$\\Omega$ (0.9 k$\\Omega$). ", "If included in the model, the capacitive shunt of the inductance could result in a very small change of the scattering parameter $S_{21}$ at $\\Phi/\\Phi_0\\approx0.5$ where the inductance ideally diverges. ", "The change is small owing to the weak coupling of the resonators. ", "Consequently, we do not include it in the model. ", "Thus, the effect of the capacitance is effectively included in that of the inductance, which depends on the fitting parameter $I_0$. The plasma frequency of the SQUID can be obtained as $\\omega_\\textrm{p}/(2\\pi) = 1/(2\\pi\\sqrt{LC})$, where $L$ is the inductance and $C$ the capacitance of the junctions.", "\n\n**Sample fabrication**\\\nSamples A and B are fabricated in the same process. ", "The actual samples as well as the control samples are fabricated on 100-mm Si wafers. ", "First, native SiO$_2$ is removed with ion beam etching, and 200 nm of Nb is sputtered onto the waver without breaking the vacuum.", "\n\nSecond, the large patterns are defined using standard optical lithography. ", "The optical lithography begins with hexamethyldisilazane priming, followed by spin coating the resist AZ5214E at 4000 rpm. ", "The resist is exposed using a mask aligner in a hard-contact mode, and the exposed resist is removed with the developer AZ351B. In order to obtain a positive profile for the Nb edges, we apply a reflow bake at 140$^\\circ$C before reactive ion etching. ", "Once the large patterns are ready, we pre-dice the wafer half way from the back side.", "\n\nIn the third step, the nanostructures are defined using electron beam lithography (EBL). ", "After thorough cleaning of the wafer with a plasma stripper, a resist for EBL is spin-coated to the wafer. ", "The EBL resist consists of two layers: poly(methyl methacrylate) with 4% of anisole, and poly\\[(methyl methacrylate)-co-(methacrylic acid)\\] with 11% of ethyl lactate. ", "We fabricate all the nanostructures in a single EBL write. ", "For the development, we use a 1:3 solution of methyl isobutyl ketone and isopropanol. ", "The metallization for the nanostructures is carried out with an electron beam evaporator in two steps. ", "First, the Cu resistor is evaporated followed by the evaporation of the SQUID. ", "We evaporate Cu only on the area in the vicinity of the resistor on the chip and keep the rest of the chip covered by a metal mask. ", "Subsequently, we cover the resistor and evaporate the Al structures. ", "The SQUID consists of two Al layers evaporated at two angles ($\\pm15^\\circ$). ", "The oxide layer for the Josephson junctions is obtained by oxidizing Al in situ in the evaporation chamber at 1 mbar of O$_2$ for 5 min. ", "The lift-off process is carried out in acetone followed by cleaning with isopropanol. ", "The Cu resistor has a width of 250 nm, thickness of 30 nm, and length of 90 $\\mu$m. ", "The SQUID consists of two layers of Al with thicknesses of 40 nm each, and it has a loop area of approximately 50 $\\mu$m$^2$.\n\n**Measurement setup**\\\nThe measurement setup is shown in Supplementary Fig.", " \\[fig:meas\\_setup\\]. ", "The measurements are carried out in a dry dilution refrigerator with a base temperature of approximately 10 mK, and the scattering parameters are measured with a vector network analyzer (VNA). ", "We control the magnetic flux through the SQUID using an external coil attached to the sample holder, and the current through the coil is generated with a source-measure unit (SMU). ", "The sample is wire-bonded to a printed circuit board shielded by a sample holder that is fabricated out of Au-plated Cu. ", "The sample holder is placed inside a magnetic shield to mitigate magnetic-field noise.", "\n\n**Normalization of scattering parameters**\\\nAll raw experimental scattering parameters are normalized. ", "First, the winding of the phase as a function of frequency is cancelled for convenience by multiplying $S_{21}$ with $\\exp(i2\\pi f \\tau)$ where $\\tau\\approx 50$ ns. ", "Second, the circle in the complex plane drawn by $S_{21}$ when the frequency is swept through the resonance is shifted and rotated to its canonical position, where the circle intersects the origin and the maximum amplitude lies on the positive $x$ axis [@Petersan_1998]. ", "Any uncertainty in this shift causes relatively large errors near origin; hence, we use linear scale for experimental data as it emphasizes the large amplitudes with smaller relative error. ", "Consequently, one can extract the $Q$ factor using the phase–frequency fitting method discussed in Ref.", " . ", "In addition to the experimental $Q$ factors, we use the same method for obtaining the $Q$ factor also from the simulations, except that the very low $Q$ factor of Resonator 2 is obtained from the width of the dip. ", "In order to exclude uncertainty related to the cable losses, we normalize $S_{21}$ by dividing it with $\\max_{f,\\Phi} |S_{21}|$ separately for each mode. ", "The magnetic flux is extracted from the periodicity of the of modes 2 and 4, and there can be an irrelevant offset of an integer number of flux quanta. ", "One flux quantum corresponds to an electric current of approximately 2 mA in the coil used.", "\n\n[10]{} url \\#1[`#1`]{}urlprefix\\[2\\][\\#2]{} \\[2\\]\\[\\][[\\#2](#2)]{}\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/nature08812>.", "\n\n& . ** ****, (). ", "<http://dx.doi.org/10.1038/nature07128>.", "\n\n, , , & . ** ****, (). ", "<http://link.aps.org/doi/10.1103/PhysRevA.69.062320>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/nature02851>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.3010859>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/nature14270>.", "\n\n. ** ****, (). [", "http://dx.doi.org/10.1002/1521-3978(200009)48:9/11&lt;771::AID-PROP771&gt;3.0.CO;2-E](http://dx.doi.org/10.1002/1521-3978(200009)48:9/11<771::AID-PROP771>3.0.CO;2-E).", "\n\n& (eds.) ** (, ).", "\n\n. ** ****, (). ", "<https://link.aps.org/doi/10.1103/RevModPhys.87.307>.", "\n\n*et al.* . ** ****, (). ", "<http://science.sciencemag.org/content/314/5805/1589>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevLett.109.050506>.", "\n\n, , , & . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevLett.109.050507>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevLett.110.120501>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevApplied.6.034008>.", "\n\n, , , & . ** ****, (). ", "<http://dx.doi.org/10.1038/srep01987>.", "\n\n, , & . ** ****, (). ", "<https://doi.org/10.1038/s41534-017-0027-1>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1007/s10909-008-9774-x>.", "\n\n, , , & . ** ****, (). ", "<https://doi.org/10.1063/1.2959824>.", "\n\n, , , & . ** ****, (). ", "<https://doi.org/10.1063/1.4882646>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.4802893>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.4927444>.", "\n\n, & . ** ****, (). ", "<https://doi.org/10.1063/1.4947579>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/ncomms12303>.", "\n\n, , & . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevLett.117.030802>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevX.6.031036>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/nature10561>.", "\n\n, & . ** ****, (). ", "<http://dx.doi.org/10.1038/nphys1342>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.3693409>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.3517252>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1063/1.4729623>.", "\n\n*et al.* . ** ****, (). ", "<https://doi.org/10.1063/1.4919761>.", "\n\n. ** ****, (). ", "<https://doi.org/10.1146/annurev-conmatphys-020911-125022>.", "\n\n*et al.* . ** ****, (). ", "<http://dx.doi.org/10.1038/ncomms15189>.", "\n\n, , & . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevLett.64.954>.", "\n\n, & . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevB.61.14839>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevB.85.020505>.", "\n\n*et al.* . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevB.94.104516>.", "\n\n, , , & . ** ****, (). ", "<https://link.aps.org/doi/10.1103/PhysRevB.96.220501>.", "\n\n** (, , ), edn.", "\n\n**. ", "Ph.D. thesis, ().", "\n\n, , , & . ** ****, (). ", "<http://www.sciencedirect.com/science/article/pii/S0040609015001650>.", "\n\n, & . ** ****, (). ", "<https://doi.org/10.1109/22.375223>.", "\n\n, & . ** ****, (). ", "<http://dx.doi.org/10.1007/s10909-013-0889-3>.", "\n\n, , , & . ** ****, (). ", "<https://doi.org/10.1063/1.1336816>.", "\n\n& . ** ****, (). ", "<http://dx.doi.org/10.1063/1.368498>.", "\n\n**Acknowledgements** We acknowledge the provision of facilities and technical support by Aalto University at OtaNano - Micronova Nanofabrication Centre. ", "We thank H. Grabert, M. Silveri, A. Wallraff, J. Kelly, J. Goetz and D. Hazra for discussions, and R. Kokkoniemi and S. Patomäki for technical assistance. ", "We have received funding from the European Research Council under Starting Independent Researcher Grant No. ", "278117 (SINGLEOUT) and under Consolidator Grant No. ", "681311 (QUESS), the Academy of Finland through its Centres of Excellence Program (project nos 251748 and 284621) and grants (Nos. ", "265675, 286215, 276528, 305237, 305306, 308161 and 314302), the Vilho, Yrjö and Kalle Väisälä Foundation, the Technology Industries of Finland Centennial Foundation, and the Jane and Aatos Erkko Foundation.", "\n\n**Author Contributions** M.P. was responsible for sample design, fabrication, measurements, data analysis, and for the writing of the initial version of the manuscript. ", "K.Y.T and J.G. contributed to the sample design, fabrication, measurements, and analysis. ", "S.M. contributed to the analysis, and M.J. to the measurements and analysis. ", "L.G. deposited the Nb layer. ", "M.P., K.Y.T, J.G, R.E.L., L.G., J.H., S.S., V.V., and M.M. developed the fabrication process. ", "J.T. and T.A.-N. contributed to the theoretical understanding of the system. ", "M.M. provided initial ideas and supervised the project. ", "All authors commented on the manuscript.", "\n\n**Competing financial interests** The authors declare no competing financial interests.", "\n\n**Data availability** The data is available upon request from the authors.", "\n\n**Supplementary material** Supplementary Figures \\[fig:meas\\_sim\\_modes\\_i8\\], \\[fig:meas\\_sim\\_delta\\_f\\], \\[fig:Qfactor\\_i8\\], \\[fig:meas\\_setup\\].", "\n\n{width=\"\\linewidth\"}\n\n{width=\"0.85\\linewidth\"}\n\n{width=\"0.85\\linewidth\"}\n\n{width=\"0.5\\linewidth\"}\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Q:\n\nUsing a bookmarklet to click Gmail's \"Show original\" button\n\nWhen I have an email open in Gmail, I'm trying to click the \"Show original\" dropdown menu item programmatically. ", "The IDs of all the elements change dynamically with each email, so that's not a reliable way to find the menu item I'm trying to click. ", "To start, I'm just trying to make a piece of JavaScript that clicks it in Chrome's console. ", "After loading jQuery, I've tried this:\njQuery('div[role=menuitem]:contains(Show original)').click();\n\nWhile it seems to select the proper div and click it, it's not the expected behaviour and the click doesn't really do anything. ", "Here's a piece of a fully loaded email's menu containing the menu item I'd like to click with JavaScript:\n<div class=\"J-N\" role=\"menuitem\" aria-hidden=\"false\" id=\"so\" style=\"-webkit-user-select: none;\"><div class=\"J-N-Jz\"><div><div id=\":173\" class=\"cj\" act=\"32\"><img class=\"dS J-N-JX\" src=\"images/cleardot.gif\" alt=\"\">Show original</div></div></div></div>\n\nMy intention is to use a bookmarklet, but I'm having trouble loading jQuery in a bookmarklet because of a security warning, but that's another question/issue. ", "Also, should I try to open the dropdown before clicking the \"Show original\" button or is it likely that I am able to click this button without opening the menu first?", "\n\nA:\n\nYou must open menu at least once, so Gmail loads required menu elements.", "\nTo click on elements use dispatchEvent() straight on DOM elements (not jQuery collections)\nBasic example might look like this:\n// Create events\nvar mouseDownEvent = new MouseEvent('mousedown', { 'bubbles': true });\nvar mouseUpEvent = new MouseEvent('mouseup', { 'bubbles': true });\n\n// Get DOM elements\nvar menu = jQuery(\"div[role='button'][aria-label='More']\").get(0);\nvar button = jQuery(\"div[role='menuitem']:contains('Show original')\").get(0);\n\n// Open and close menu, to ensure button existence\nmenu.dispatchEvent(mouseDownEvent);\nmenu.dispatchEvent(mouseDownEvent);\n\n// Click menu item\nbutton.dispatchEvent(mouseDownEvent);\nbutton.dispatchEvent(mouseUpEvent);\n\nThat will work only in Chrome, Firefox and Opera.", "\n\n" ]

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[ "princesslacy doesn't have any Goodies to view right now.", "\n\n\"Her perfect ass was like a magnet drawing in love-sick men wherever she went - through the dark streets of Dublin or the cosmopolitan capitals she frequently travelled to. ", "All, of course,paid on the dime of the wanking hordes she dommed, wallet-raped andmind-fucked.", "She was Queen Bitch and she knew it.\"", "\nThis is an extract from an essay I had written for Me by one of my slaves, slave alan.", "\nI have owned him for 4 years now he is one of many. ", "he tributedvme often, I got many items from his tribuyes like agent provocateur, la perla, louboutins, gucci, chanel. ", "I love my brands.", "\nPiggies love to keep me in luxury I am a spoilt bitch who deserve the best.", "\nI am accustomed to getting what I want all the time.", "\nI am a money mistress money turns me on, humiliating piggies turns me on, watching them become addicted to me turns me on.", "\nIts all about me piggies!", "\nBut my favourite thing at the moment is to ignore money piggies and to here them beg, you may hear me laughing with girlfriends or other money mistresses, you may here me relax to music as I ignore you as I lay on my bed, you maybe here me shop with piggies money as I throw the bags in his face. ", "I love ignoring piggies its the highest form of worship that you will give your hard earned cash to me your goddess, your muse princess of piggies. ", "Give your money to me, I am your addiction, beg to have me talk to you, loser boy! ", "You will just be ignored because your a loser!" ]

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[ "Search Documents\n\nThe Virginia Quit Claim Deed is a simple to use form that will legally release a Property from one individual (Grantor) to another (Grantee) according to the terms contained within it. ", "This form is a basic quitclaim statement, meaning whatever Claims, Interests, Ownership, or Rights the Grantor has in the Property will be forfeit to…\n\nThe Virginia notary acknowledgment form is a document used by a notary public when verifying signatures on official paperwork. ", "The individual requesting verification must appear before the notary public in person and present their documents. ", "After the notary has confirmed the identity of the individual and ensured that their signature has been given willfully, the notary will complete…\n\nThe Virginia revocable living trust is different from an irrevocable living trust in several respects. ", "First of all, the Grantor will continue to benefit from any assets placed in the trust during their lifetime. ", "Secondly, the Grantor retains the right to revoke or amend the trust as they see fit. ", "While an irrevocable living trust does…\n\nVirginia self-proving affidavit forms are legal instruments which may be attached to a last will and testament to make it self-proving and shorten probate. ", "A self-proving will, is a will that has been certified and acknowledged in advance of probate. ", "The affidavit contains sworn statements attesting that the testator signed their will freely and without…\n\nVirginia name change forms are provided by the State’s circuit courts for individuals who would like to legally change their name. ", "These forms are used by Virginia citizens who intend to change their name for political, religious, or other personal reasons. ", "Those intent on taking their spouse’s name after marriage or reverting to their maiden…\n\nThe Virginia do not resuscitate (DNR) order form is a statement letting emergency service personnel know that a patient does not want to receive life-saving treatment during a medical emergency where they are unable to breathe or do not have a heartbeat. ", "Life-saving treatments include cardiopulmonary resuscitation (CPR), endotracheal intubation, cardiac compression, and certain airway management procedures. ", "The order…\n\nThe Virginia security deposit demand letter is a document which is sent to a landlord who has failed to return a security deposit within the mandatory forty-five (45) day period from the lease termination date. ", "State law stipulates that the tenant must give their landlord a forwarding address in order to facilitate the security deposit refund….", "\n\nThe Virginia employment contract agreement is used to verify employment conditions when hiring a new employee (part-time and full-time). ", "An employer should implement an agreement during the hiring process to verify that the individual understands their responsibilities and that they agree to undertake the proposed duties. ", "Included in the contract may be a non-disclosure clause which, if violated…\n\nThe Virginia Independent Contractor Agreement binds two (2) individuals, the client and the contractor, to a set of terms and conditions by which they must operate throughout their business relationship. ", "An agreement such as this is used when a client needs to hire a temporary contractor to complete a task or render a service. ", "The contract enables…\n\nThe Virginia residential purchase and sale agreement is used by potential home buyers as a means of submitting an official offer to purchase. ", "The document outlines the buyer’s initial terms which the seller must respond to within a specific period or the offer will become invalid. ", "In addition to price, the parties may negotiate various conditions such…" ]

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[ "Q:\n\nModifying aspect ratio of a plot in R\n\nHere is my first plot\npar(bg=\"white\")\nimage(m, main = paste(\"generation: \",generation), ylab=\"\", col=heat.colors(100), xaxt=\"n\", yaxt=\"n\", xlab=\"\")\n\nIt is a square, and I'd like it to be a rectangle. ", "So I did\npar(bg=\"white\", mar=c(16,1,16,1))\n image(m, main = paste(\"generation: \",generation), ylab=\"\", col=heat.colors(100), xaxt=\"n\", yaxt=\"n\", xlab=\"\")\n\nBut then the title (main) is really far away from the plot. ", "So I did\npar(bg=\"white\", mar=c(16,1,16,1))\n image(m, ylab=\"\", col=heat.colors(100), xaxt=\"n\", yaxt=\"n\", xlab=\"\")\n legend(0.32, 3.5, paste(\"Generation: \", IntFormat(generation, 4)), border=\"white\", xpd=TRUE, box.col=\"white\", cex=1.5)\n\nWell.. I wouldn't say it is splendid, but I was satisfied. ", "So let's put that into a .png\npng(paste0(folder.images, \"pg_\",IntFormat(generation,4),\".png\"))\n par(bg=\"white\", mar=c(16,1,16,1))\n image(m, ylab=\"\", col=heat.colors(100), xaxt=\"n\", yaxt=\"n\", xlab=\"\")\n legend(0.32, 3.5, paste(\"Generation: \", IntFormat(generation, 4)), border=\"white\", xpd=TRUE, box.col=\"white\", cex=1.5)\n dev.off()\n\nand here is what the .png looks like!", "\n\nIs there a better solution to make a rectangle out of my square than using the parameter mar that force me to add a title with legend and to search by trial and error where the center to the picture is for the title.", "\nWhy is the .png different from what is shown in the R window?", "\n\nA:\n\nI could achieve this:\npng(\"test.png\", res = 150, width = 8, height = 1, units = \"in\")\npar(mar = c(1,1,1,1))\nimage(matrix(1:10, ncol=1), ylab=\"\", col=heat.colors(100), xaxt=\"n\", \n yaxt=\"n\", xlab=\"\", main=\"Generation: 0001\")\ndev.off()\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Brill Public Affairs\n\nLobbying, Public Relations, and Internet Publishing\n\nWhen your company or organization needs to enlist the support of government, the business community, the news media, or leaders in the world of trade associations and community organizations, let Brill Public Affairs help you to connect and deliver.", "\n\nFor more than 15 years, Brill Public Affairshas represented the interests of a wide variety of Fortune 500 companies and trade associations with skill and integrity.", "\n\nWe manage successful public affairs campaigns, providing lobbying, legislative and regulatory monitoring, and media advocacy support for business, trade associations and others whose interests are affected by the activities of the New Jersey Legislature, the Governor's Office and state regulatory departments and agencies.", "\n\nWe also are the publishers of EnviroPolitics, a daily compendium of environmental and political information. ", "This paid-subscription, daily electronic newsletter has become essential reading for government policy-makers and for professionals in environmental law, engineering, consulting, planning, utilities, real estate development and construction.", "\n\nOther subscribers to EnviroPoliticsinclude association executives and leaders in a wide variety of businesses whose operations are affected by environmental laws and regulations--and by the political decisions that drive them both." ]

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[ "Relationship of E1 and E3 regions of human adenovirus 35 to those of human adenovirus subgroups A, C and D.\nCloned PstI fragments of human adenovirus 35 (AV35) genome were compared with the DNA of representatives of human adenovirus subgroups A (type 12), B (type 7), C (types 1, and 5), D (type 8), and E (type 4), using blot hybridization techniques. ", "The E1b region of AV35 was found to be more distantly related to those of other subgroups than E1a regions sequences and examined by others. ", "DNA hybridization was observed only between E1b of AV35 and the DNA of AV4, thus the recombinant constructed might be applied as B-subgroup-specific diagnostic probe. ", "Common nucleotide sequences were detected within the E3 regions of serotypes 1, 4, 5, 7, 8, and 35. ", "On the basis of inter-subgroup homology, and PstI-fragments it may be concluded, that the structure of E3 sequences of AV7 and AV35 DNA are closely related to those of AV3 DNA sequenced by Signäs et al. [", "18]. ", "E4 regions were compared only of serotypes representing subgroups B, C, and D. These sequences were subgroup specific, similarly to E1b regions." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "@VoiceOfVegeta Was great meeting you today Chris, thanks again for taking the time to sign some stuff for me.", "\nIf you ever need additional support with your site let me know. ", "Would love to lend resources to help if I can. ", "pic.twitter.com/fXqQZ5OROu\n\n@VoiceOfVegeta Hey Chris! ", "I didn’t win the lottery but am going to buy a Majin Vegeta Pop from some greedy folks tomorrow who want to resell. ", "Can I swing by and have you sign it at your 2:00 signing session?", "\nTrying to add my favorite character to my signed DBZ pop collection!", "\n\nMany truly believe they are owed something by those who have built the foundations of success they have the security of working within. ", "They are too short sighted to see the value in the risk and effort taken to create the comfort they feel entitled too. ", "Leading to their greed.", "\n\nPlease be advised that we are still continuing with our legal campaign until ALL coins are available to withdraw. ", "This is a show of good will, and we wish to demonstrate our belief of just how important it is for the crypto community to unite. ", "pic.twitter.com/HB7Ove7mgg\n\nDid you know:\nElectra ECA uses Proof of Stake, which offers 50% returns on the ECA you store in your wallet. ", "You are rewarded **FREE ECA** simply for holding them in your wallet over time.", "\nAre you taking advantage of this???", "\n$ECA#ECA#electra#electraeca#PoS#NIST5#altcoins\n\nWe did it! ", "We hit #1 on Cobinhood.", "\nAs promised here is a new preview for some of our functional screens.", "\nIt isn’t over yet, Now we need to drastically increase the gap between ECA and the #2 coin, don’t let anyone take our lead! ", "Let’s go Electrans!", "\ncobinhood.canny.io/token-listing?…pic.twitter.com/Bdeu3sCU6X\n\nHelp Electra ECA get listed on Cobinhood! ", "Every single vote matters - let's continue showing the strength of the Electra community!", "\nMake sure you're logged into Google, Twitter, Facebook, etc:\ncobinhood.canny.io/token-listing/…" ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nHow much does function alignment actually matter on modern processors?", "\n\nWhen I compile C code with a recent compiler on an amd64 or x86 system, functions are aligned to a multiple of 16 bytes. ", "How much does this alignment actually matter on modern processors? ", "Is there a huge performance penalty associated with calling an unaligned function?", "\nBenchmark\nI ran the following microbenchmark (call.", "S):\n// benchmarking performance penalty of function alignment.", "\n#include <sys/syscall.h>\n\n#ifndef SKIP\n# error \"SKIP undefined\"\n#endif\n\n#define COUNT 1073741824\n\n .globl _start\n .type _start,@function\n_start: mov $COUNT,%rcx\n0: call test\n dec %rcx\n jnz 0b\n mov $SYS_exit,%rax\n xor %edi,%edi\n syscall\n .size _start,.-_start\n\n .align 16\n .space SKIP\ntest: nop\n rep\n ret\n .size test,.-test\n\nwith the following shell script:\n#!", "/bin/sh\n\nfor i in `seq 0 15` ; do\n echo SKIP=$i\n cc -c -DSKIP=$i call.", "S\n ld -o call call.o\n time -p ./call\ndone\n\nOn a CPU that identifies itself as Intel(R) Core(TM) i7-2760QM CPU @ 2.40GHz according to /proc/cpuinfo. ", "The offset didn't make a difference for me, the benchmark took constant 1.9 seconds to run.", "\nOn the other hand, on another system with a CPU that reports itself as a Intel(R) Core(TM) i7 CPU L 640 @ 2.13GHz, the benchmark takes 6.3 seconds, except if you have a offset of 14 or 15, where the code takes 7.2 seconds. ", "I think that's because the function starts to span multiple cache lines.", "\n\nA:\n\nTL;DR: Cache alignment matters. ", "You don't want bytes that you won't execute.", "\nYou would, at least, want to avoid fetching instructions before the first one you will execute. ", "Since this is a micro-benchmark, you most likely don't see any difference, but imagine on a full program, if you have an extra cache-miss on a bunch of functions because the first byte wasn't aligned to a cache-line and you eventually had to fetch a new cache line for the last N bytes of the function (where N <= the number of bytes before the function that you cached but didn't use).", "\nIntel's optimization manual says this:\n\n3.4.1.5 Code Alignment\nCareful arrangement of code can enhance cache and memory locality. ", "Likely sequences of basic blocks should be laid out contiguously in memory. ", "This may involve removing unlikely code, such as code to handle error conditions, from the sequence. ", "See\n Section 3.7, “Prefetching,” on optimizing the instruction prefetcher.", "\n3-8 Assembly/Compiler Coding Rule 12. (", "M impact, H generality) All branch targets should be 16- byte aligned.", "\nAssembly/Compiler Coding Rule 13. (", "M impact, H generality) If the body of a conditional is not likely to be executed, it should be placed in another part of the program. ", "If it is highly unlikely to be executed and code locality is an issue, it should be placed on a different code page.", "\n\nIt also helps in explaining why you don't notice any difference in your program. ", "All the code gets cached once and never leaves the cache (modulo context-switches, of course).", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Q:\n\nIs the right-shift operator in Objective C on OSX/iOS an arithmetic or logical right shift?", "\n\nIs the right-shift operator in Objective C on OSX/iOS an arithmetic or logical right shift?", "\nI can't find any references that specify whether the right-shift is arithmetic or logical, or if it varies depending on the data type (signed/unsigned) and/or architecture (x86/PPC/x64/ARM).", "\n\"Programming in Objective-C 2.0\" states that this is effectively undefined, but that conflicts with information I've seen elsewhere that compilers attempt to \"do the right thing\" based on signed-ness of types.", "\n\nA:\n\nObjective-C does not define the behavior for the right-shift operator. ", "That operator is defined in C. Here's the relevant part of the ANSI C spec:\n\nThe result of E1 >> E2 is E1 right-shifted E2 bit positions. ", "If E1 has an unsigned type or if E1 has a signed type and a nonnegative value, the value of the result is the integral part of the quotient of E1 / 2^E2. ", "If E1 has a signed type and a negative value, the resulting value is implementation-defined.", "\n\nSo yes, right-shift operator on a negative number is implementation-defined according to the spec.", "\n\nA:\n\nI did a quick experiment in the iOS simulator, with the following fragment:\n\nint i = -600;\n\nfor (int j = 0; j < 68; j++)\n{\n NSLog(@\"j: %d i: %d\", j, i);\n i = i >> 1;\n}\n\nWhich yielded the result:\n\nj: 0 i: -600\nj: 1 i: -300\nj: 2 i: -150\nj: 3 i: -75\nj: 4 i: -38\nj: 5 i: -19\nj: 6 i: -10\nj: 7 i: -5\nj: 8 i: -3\nj: 9 i: -2\nj: 10 i: -1\nj: 11 i: -1\n...\n\nThis would seem to indicate that the shift is arithmetic, not logical, because the sign of the answer is preserved.", "\n\n" ]

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[ "Hemoadsorption in critical care.", "\nThis paper concerns the results of endotoxin hemoadsorption therapy using a PMX column in patients with perforative peritonitis complicated by multiple organ failure. ", "The subjects were 31 patients aged 68 +/- 12 years. ", "When systolic arterial pressure decreased to less than 90 mm Hg, endotoxin hemoadsorption was initiated and continued for 2 h. At the completion of endotoxin hemoadsorption, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure were significantly increased. ", "Platelet count decreased to less than 50,000/mm(3) in 30% of patients. ", "As for cytokines and vascular endothelial cell function markers, interleukin-6 and plasminogen activator inhibitor-1 significantly decreased. ", "These results suggest favorable effects of endotoxin hemoadsorption on the hemodynamic and pathophysiological conditions in patients with septic shock although attention should be given to the decrease in platelet count." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Slipknot\n\nSlipknot and Marilyn Manson will be taking over DTE on July 29th and we have tickets for you. ", "Be sure to tune in to find out where you can get yours! ", "You owe it to yourself to see Slipknot live! ", "In the meantime, check out the top 10 Corey Taylor moments here.", "\n\nFinally a video that shows how much of a badass Santa is. ", "Check out this guys house for Christmas. ", "The lights are set to 'Psychosocial' and Corey Taylor is just an angry little tree. ", "We need more displays like this in our area. ", "Anyone know of good light shows in the area?" ]

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[ "Eternity Brewing Company, LLC\n\nAbout\n\nHi! ", "We are Mike and Dayna Tran, Co-Founders and Co-Brewers at Eternity Brewing!", "\n\nBefore we were business partners, we were lab partners at the University of Michigan. ", "We both graduated with masters in mechanical engineering. ", "To celebrate our graduation we went on a road trip with a couple of our buddies to tour several of Michigan’s microbreweries. ", "Memories from that trip will last with us forever.", "\n\nThat trip got us into craft beer which eventually led to homebrewing our own recipes. ", "Dayna quit her stable engineering job and and pursued her passion in the brewing industry as an assistant brewer with Witch’s Hat Brewing in South Lyon. ", "Her ''claim to fame'' is a gluten free IPA recipe that has gone over well with many customers (even those that don't need to stay away from gluten!).", "\n\nThe craft beer industry is where we belong. ", "After years of planning, we are finally set for an opening on September 23, 2014. ", "Stay stuned and please follow our progress on Twitter, Facebook, and on our Blog. ", "We want you to be a part of this journey with us!" ]

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[ "1. ", "Current licensed HPV prophylactic vaccines {#s0005}\n=============================================\n\nThere are currently three licensed HPV prophylactic vaccines: Cervarix®, a bivalent HPV-16/18 product from GlaxoSmithKline; Gardasil®, a quadrivalent HPV-6/11/16/18 product and Gardasil®9, a nonavalent HPV-6/11/16/18/31/33/45/52/58 vaccine, both from Merck & Co., Inc. [@b0005], [@b0010], [@b0015], [@b0020]. ", "These products were licensed following highly encouraging efficacy data from large phase III vaccine trials and have the potential (nonavalent vaccine) to prevent up to 90% of cervical cancer cases. ", "The first two products to be licensed, Cervarix® and Gardasil®, used a placebo arm and relied on cervical disease as the primary endpoints [@b0025], [@b0030], [@b0035]. ", "The Gardasil®9 trial used the previously licensed Gardasil® vaccine as the control arm [@b0040]. ", "For the 4 HPV types targeted by both vaccines, the primary endpoint was non-inferiority in antibody response, while cervical disease endpoints were used for the 5 additional types in Gardasil®9. ", "All the vaccine trials have demonstrated outstanding long-term efficacy. ", "This remarkable vaccine efficacy is now starting to be seen as effectiveness at the population level following introduction of HPV vaccines into national immunization programs [@b0045].", "\n\nAll three vaccines are based on non-infectious recombinant type-specific L1 capsid proteins assembled into viral-like particles (VLPs) as immunogens. ", "The expressed recombinant L1 capsids self-assemble in arrays of 72 pentamers that present an exterior surface closely mimicking HPV virions and it is this multiplicity of L1 domains that bestows the VLP antigen with significant immunogenicity, even in the absence of concomitant immune modulators (adjuvants) [@b0050], [@b0055].", "\n\nThe vaccines differ in the antigen expression system used, antigen composition and adjuvants included ([Table 1](#t0005){ref-type=\"table\"}) [@b0060], [@b0065], [@b0070]. ", "Both Gardasil® and Gardasil®9 products are produced in yeast and formulated with amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvant, which has an increased capacity to bind to L1 VLPs compared with other aluminum salts [@b0075]. ", "In contrast, Cervarix® is produced in insect cells using a baculovirus expression vector system and adjuvanted with AS04 which contains aluminum hydroxide plus an additional immunostimulant, the toll-like receptor 4 agonist monophosphoryl lipid A [@b0080]. ", "AS04 has been shown to enhance innate as well as humoral and cell-mediated immune responses [@b0085], and may be responsible for differences in the overall immunogenicity described in head-to-head studies of the two vaccines [@b0090], [@b0095], [@b0100], [@b0105]. ", "Other differences between the vaccines include the concentration of each of the L1 VLPs, and the ratio of antigen to adjuvant. ", "Gardasil® has two-fold higher concentrations of HPV-16 L1 VLP and an equal concentration of HPV-18 L1 VLP compared with Cervarix®. ", "Gardasil®9 contains twice the amount of HPV-18 L1 VLP, 50% more HPV-16 antigen and more than twice the level of adjuvant contained in Gardasil®.Table 1Main characteristics of the licensed HPV prophylactic vaccines.", "Cervarix®Gardasil®Gardasil9®ManufacturerGlaxoSmithKlineMerck and Co, Inc.Merck and Co, Inc.VLP Types IncludedHPV-16/18HPV-6/11/16/18HPV-6/11/16/18/31/33/45/52/58Dose of L1 VLP (μg)20/2020/40/40/2030/40/60/40/20/20/20/20/20Expression system*Trichoplusia ni* (Hi 5) insect cell line infected with L1 recombinant baculovirus*Saccharomyces cerevisiae* expressing L1*Saccharomyces cerevisiae* expressing L1Adjuvant500 μg aluminum hydroxide salt and 50 μg 3-O- Desacyl-4′-monophosphoryl lipid (MPL) A225 μg amorphous aluminum hydroxyphosphate sulfate500 μg amorphous aluminum hydroxyphosphate sulfateInitially approved injection schedule0, 1 and 6 months0, 2, and 6 months0, 2, and 6 monthsManufacturing components4.4 mg NaCl, 0.624 mg sodium dihydrogen phosphate dihydrate9.56 mg NaCl, 0.78 mg L-Histidine, 50 μg Polysorbate 80, 35 μg Sodium borate9.56 mg NaCl, 0.78 mg L-Histidine, 50 μg Polysorbate 80, 35 μg Sodium borateRoute of administrationIntramuscularIntramuscularIntramuscular\n\nThe vaccines were originally licensed for use as a three-dose regimen, administered intramuscularly. ", "The licensed HPV vaccines have demonstrated remarkable efficacy in phase III clinical trials in HPV-naïve young women, providing nearly complete protection against incident infection and cervical disease caused by the HPV types that they specifically target [@b0025], [@b0030], [@b0035], [@b0040], [@b0110]. ", "This is coincident with the induction of a high level, high affinity polyclonal anti-L1 IgG antibody response to the HPV types included in the vaccine, and essentially 100% seroconversion to all targeted HPV types [@b0115], [@b0120], [@b0125], [@b0130], [@b0135], [@b0140]. ", "The robust immunogenicity of the HPV vaccines contrasts with the immune responses observed after natural infection, in which seroconversion is found in only a proportion of individuals following incident infection [@b0145]. ", "Vaccine antibodies persist for several years after vaccination at levels that are orders of magnitude higher than those observed in natural infection [@b0120], [@b0150], [@b0155], [@b0160]. ", "Antibodies generated during natural infection do not appear to consistently protect against subsequent infection. ", "In addition, some studies suggest that protection may be limited to individuals with relatively high levels of naturally-acquired antibody [@b0165], [@b0170]. ", "These findings are consistent with a recent study indicating that antibodies cloned from naturally elicited memory B cells were generally non-neutralizing while those isolated after vaccination had strong neutralization activity [@b0175].", "\n\nA degree of efficacy against some non-vaccine types (i.e. cross-protection) has been demonstrated in vaccine trials, particularly for HPV-31 and HPV-45 [@b0180], [@b0185]. ", "Cervarix® appears to confer greater cross-protection than Gardasil® and this difference is reflected in antibody levels against these non-vaccine types [@b0190]. ", "For the purposes of this review, however, only antibody responses against vaccine-targeted types are considered.", "\n\nCorrelates of protection against infection afforded by HPV vaccines have not been formally identified and are difficult to study because of the exceptional efficacy of the vaccines. ", "There have been very few cases of breakthrough infection or disease with the current vaccines to identify the threshold of antibody level that confers immunity among vaccinated subjects. ", "Most studies attempting to address this question have analyzed the protective levels of naturally acquired antibodies in the placebo arm of vaccine trials [@b0165], [@b0170] or in cohort studies of infection [@b0145]. ", "Evaluation of different immunogenicity measures in reduced dose schedule trials, in which virological failures may be more likely to occur, could make it possible to establish immune correlates of protection.", "\n\nImmunogenicity testing of prophylactic HPV vaccines in clinical trials has focused primarily on antibody responses because neutralizing antibodies are thought to be the principal effectors of protection against HPV infection. ", "This is primarily based on experimental evidence in animal models demonstrating that protection against papillomavirus infection can be passively transferred in serum or purified immunoglobulin (Ig) G from VLP-vaccinated animals [@b0195]. ", "It has also been shown that very low levels of HPV antibodies are able to neutralize HPV-16; the 50% inhibitory concentration being estimated to range from 1.9 picomolar to 5.4 nM for three monoclonal antibodies [@b0200]. ", "Vaccine-induced antibodies against vaccine types are detectable not only in serum but also at mucosal sites of infection, such as the cervix and oral cavity [@b0205], [@b0210], [@b0215], [@b0220]. ", "These antibodies are believed to reach the site of infection through transudation from serum and by exudation at sites of potential trauma that expose the basement membrane to infection [@b0215], [@b0225].", "\n\n2. ", "Review of immunogenicity of licensed HPV vaccines and duration of responses {#s0010}\n==============================================================================\n\n2.1. ", "Immunogenicity of three-dose schedules {#s0015}\n-------------------------------------------\n\nA number of recent publications have thoroughly reviewed the immunogenicity and efficacy of licensed HPV vaccines in the context of the standard three-dose and reduced dose regimens [@b0230], [@b0235]. ", "While all three licensed vaccines have similar efficacy against HPV infection and precancer lesions in clinical trials, the products do differ in immunogenicity, as demonstrated in a variety of assays. ", "Head-to-head trials of three doses of Cervarix® and Gardasil® in 18--45 year-old women and in 12--15 year-old girls have found that HPV-16 antibody levels were significantly lower for Gardasil® when compared with Cervarix® [@b0095], [@b0100], [@b0105], [@b0240], although they had similar patterns of peak and decay over time. ", "HPV-18 antibody levels and seropositivity were significantly lower for Gardasil® than Cervarix®. ", "Furthermore, Gardasil® induced lower HPV-16 and HPV-18 specific CD4^+^ T cell responses, as well as lower memory B cell responses, particularly for HPV-18 up to 24 months after vaccination [@b0095], [@b0100], [@b0105].", "\n\nHigh and durable HPV-16 and HPV-18 antibody levels, significantly above natural infection levels, have been reported after vaccination with Cervarix® for at least 9.4 years [@b0150]. ", "Stable HPV-16 antibody levels, above natural infection levels were described for Gardasil® for at least 9 years [@b0120]. ", "However, HPV-18 antibody levels appear to decline to levels closer to natural infection. ", "The observed seropositivity for HPV-18 is assay dependent (See Section 3) and was found to be 91% with a total IgG binding Luminex immunoassay and 60% with competitive Luminex immunoassays (cLIA) in women 9 years after vaccination.", "\n\nGardasil®9 has been reported to elicit comparable HPV-16 and HPV-18 antibody responses as Gardasil®. ", "HPV-18 antibody levels induced by three doses of Gardasil®9 measured with the cLIA also declined over time and 78% seropositivity was observed 5 years after vaccination [@b0245]. ", "A similar decline in HPV-45 seropositivity was described, while antibody seropositivity for other types was maintained.", "\n\nCovariates of immunogenicity have been evaluated both for Gardasil® and Gardasil®9 in three dose recipients [@b0250], [@b0255]. ", "Age at the time of immunization was inversely correlated with antibody levels at month 7 for all the 9 HPV types. ", "For all 9 HPV types, vaccine-induced antibody levels were higher in girls and boys than in young women. ", "Boys had slightly higher HPV antibody levels than girls of the same age. ", "Overall, immunogenicity was generally comparable across different races and different geographical regions. ", "Small differences in month 7 HPV antibody levels were observed in 16--26 year-old women of different races. ", "Black women had slightly higher HPV antibody levels than Asian or white women or women of other races. ", "Individuals in Africa, Latin America and North America tended to have higher HPV antibody levels than those in Asia, and Europe. ", "In addition, pre-existing HPV antibodies at the time of vaccination resulted in higher HPV responses to that type.", "\n\nCritical questions that will need to be addressed by ongoing and planned trials include whether higher vaccine-induced antibody levels would predict longer duration of protection and how to improve sensitivity and specificity of antibody assays so that reliable correlations can be made between protection against infection and detection of antibodies.", "\n\n2.2. ", "Immunogenicity of reduced dose schedules {#s0020}\n---------------------------------------------\n\nClinical studies evaluating reduced dose schedules and the interval between doses for both vaccines have demonstrated non-inferior antibody responses in girls younger than 15 years of age that received two doses, given six months apart, when compared with women who received the standard three doses of vaccine and had evidence of efficacy in clinical trials [@b0260], [@b0265], [@b0270]. ", "These findings have led to the recommendations and approval of two-dose schedules in 9--14 year-old girls [@b0275]. ", "Both Cervarix® and Gardasil® induced similar antibody levels following two and three vaccine doses, for their corresponding vaccine, when the doses were administered six months apart, in 18--25 year-old women as well as in 10--18 year-old girls, over 4 years of follow-up [@b0280], [@b0285]. ", "Administration of two doses of Cervarix® 1 month apart resulted in lower antibody levels than two doses (given 6 months apart) or three doses, but they were stable over a 4 year follow-up. ", "Increasing the interval to one year between the two doses of Gardasil® in 11--13 year-old girls has demonstrated similar levels of HPV-16 and HPV-18 antibodies to those observed in a three-dose Gardasil® regimen, one year after vaccination [@b0290], [@b0295].", "\n\nA head-to-head trial of two doses of Cervarix® or Gardasil® six months apart in 9--14 year-old girls demonstrated higher antibody levels for Cervarix® than Gardasil® at one year following initial vaccination [@b0300]. ", "Two doses of Cervarix® also induced higher antibody levels than three doses of Gardasil®. ", "These studies have demonstrated that dosing interval is an important determinant of immunogenicity.", "\n\nImmunogenicity data for a single vaccine dose are limited and to date has been examined in clinical trial participants who did not complete protocol or in trials that ended prematurely. ", "Although lower than the levels induced by two- and three-dose schedules, a single dose of Cervarix®, in 18--25 year-old women from the NCI-sponsored Costa Rican Vaccine Trial, induced detectable HPV-16 and HPV-18 ELISA antibody levels in all participants. ", "These remained approximately 9-fold and 5-fold higher than natural infection levels, respectively, 4 years after initial vaccination [@b0280]. ", "In a Gardasil® trial in adolescents in India that was ended prematurely, only a fraction of recipients had HPV-16 and HPV-18 seropositive responses following one-dose vaccination as assessed with multiplex bead assays (49% and 58%, respectively) twelve months post-vaccination, with levels around the assay seropositivity cut-off, but these were reported as stable over a 36 month follow-up [@b0285]. ", "These preliminary data suggest that one dose of HPV vaccine may be sufficient to confer protective immunity against HPV. ", "The clinical trials being conducted in Costa Rica (ClinicalTrials.gov Identifier: NCT03180034) and Tanzania (ClinicalTrials.gov Identifier: NCT02834637) will provide opportunities for a comprehensive head-to-head comparison of immune responses induced by Cervarix® and Gardasil®9, in the context of one- and two-dose regimens in young adolescents.", "\n\nWith the increasing number of trials relying on immunogenicity data to support new vaccine recommendations, evaluation of one-dose trials, and approval of new follow-on vaccines, there is a need for the critical assessment of the sensitivity, specificity, reproducibility and comparability of HPV immunogenicity assays. ", "These assays are briefly described in the next section along with the role for International Standards and steps being taken to address gaps in availability of these key reagents.", "\n\n3. ", "HPV vaccine immunogenicity assays and considerations for single dose studies {#s0025}\n===============================================================================\n\nMeasures of the type-specific immune response to HPV after vaccination include both cellular as well as humoral markers. ", "The HPV vaccines induce potent T and B cell responses both in animal models and in humans [@b0305]. ", "However, most attention has focused on the humoral responses given the proposed role that neutralizing antibodies have in protection against infection and subsequent disease [@b0310]. ", "Serology assays include those detecting antibodies (neutralizing assays and binding assays), as well as those measuring antibody binding strength (avidity). ", "The cellular assays include assays for evaluation of T cell (CD4 and CD8 T cell responses) and of memory B cell responses. ", "The remainder of this review will focus on the most commonly used serology assays in vaccine trials.", "\n\nThree main serological assays have been used to evaluate HPV L1 VLP antibody responses to HPV L1 VLP vaccines in clinical trials ([Fig. ", "1](#f0005){ref-type=\"fig\"}): (1) pseudovirus-neutralization assays [@b0315], (2) competitive (epitope-specific) immunoassays [@b0320], [@b0325], [@b0330], and (3) VLP-IgG binding assays [@b0335]. ", "Neutralization assays are considered the most relevant for measuring the biological activity of the antibodies and the WHO has suggested that such assays should be considered the reference standard for assessing protective antibodies induced by the vaccines [@b0340]. ", "Competitive immunoassays, such as the cLIA, estimate neutralizing activity by measuring competition of test serum with neutralizing monoclonal antibodies. ", "In contrast, ELISAs detect all antibodies, regardless of neutralization ability. ", "Most L1 VLP ELISAs detect IgG, but other immunoglobulin classes (such as IgA) or IgG subclasses can be targeted if the specificity of the secondary antibody is changed. ", "The glutathione S-transferase (GST) fusion L1 immunoassays are similar to L1 VLP ELISAs in that they detect all binding antibodies of particular immunoglobulin class that is determined by the secondary antibody. ", "However, GST fusion assays rely on an L1 protein target that is synthesized in bacteria and is not assembled into conformational VLPs [@b0345]. ", "The results of these assays generally correlate well, particularly in specimens with high antibody levels, suggesting that the dominant immune response to HPV vaccination is IgG against neutralizing epitopes [@b0210], [@b0335], [@b0350], [@b0355], [@b0360], [@b0365], [@b0370].Fig. ", "1Three main types of assays have been used in the evaluation of antibody responses to HPV vaccines. (", "A) Neutralization assays, (B) Competitive immunoassays and (C) ELISA.", "\n\nThe neutralization assays measure total immunoglobulins (IgM, IgA, and IgG) that exhibit *in vitro* neutralizing function ([Fig.", " 1](#f0005){ref-type=\"fig\"}A). ", "This assay, originally developed by Dr. Schiller's laboratory at the National Institutes of Health [@b0315], has been widely adopted. ", "The assay makes use of pseudovirions that incorporate the minor (L2) capsid protein, as well as the L1 protein and an encapsidated reporter gene, such as secreted alkaline phosphatase (SEAP) or luciferase [@b0315], [@b0375], [@b0380], [@b0385], [@b0390]. ", "Following pseudovirion binding to and entry into target cells, the reporter plasmid is translocated to the nucleus and expressed. ", "When neutralizing antibodies are present, pseudovirus infection is blocked with a concomitant reduction in reporter signal. ", "Antibody levels are generally expressed as the reciprocal of the sample dilution resulting in an *a priori* level of inhibition (usually 50%). ", "Since they are cell-based, neutralization assays tend to have a higher coefficient of variation than binding assays, are labor intensive, and costly. ", "Generally, these have been difficult to adapt to a high-throughput format, although a 384-well format has been described [@b0390]. ", "Most formats of the assay are not amenable to multiplexing, but a recent report achieved a three-plex assay using three different reporter genes expressing different fluorescent proteins [@b0385].", "\n\nThe cLIA assay requires labeled type-specific monoclonal antibodies and conformationally intact VLPs ([Fig.", " 1](#f0005){ref-type=\"fig\"}B). ", "Antibodies in the serum sample bind to VLPs and prevent binding of the labeled monoclonal antibody, thereby reducing signal. ", "Concentrations are generally based on a standard curve. ", "The assay measures antibodies of all immunoglobulin classes but, in principle, only to one epitope. ", "Thus, it has high specificity, but results may underestimate the total functional antibody levels. ", "The assay is epitope specific, rapid, readily multiplexed and amenable to high-throughput platforms. ", "Vaccine trials sponsored by Merck used a competitive multiplex bead array assay [@b0325], [@b0330].", "\n\nELISAs also require conformationally intact VLPs and they measure both neutralizing and non-neutralizing antibodies, recognizing both conformational and non-conformational epitopes ([Fig.", " 1](#f0005){ref-type=\"fig\"}C). ", "VLPs are bound to a solid surface (beads or wells) and antibodies in the sample bind directly. ", "Bound antibody is detected with labeled secondary antibodies directed against a specific Ig class, usually anti-IgG. The label can be an enzyme, an affinity label or a fluorescent molecule. ", "L1 VLP ELISAs for type-specific IgGs have been used by GlaxoSmithKline and several research labs as the main assay in a number of immunogenicity trials [@b0095], [@b0100], [@b0105], [@b0280], [@b0335], [@b0395]. ", "ELISAs for many other targets have been widely used, so the format is familiar to laboratories. ", "The format is adaptable to multiplexing with bead arrays [@b0350], [@b0360], [@b0400] or multi-spot wells [@b0365], fast and amenable to high-throughput testing. ", "However, only one immunoglobulin class is detected at a time and both neutralizing and non-neutralizing antibodies will generate a signal.", "\n\nThe overall advantages and disadvantages of the three broad classes of serology assays are summarized in [Table 2](#t0010){ref-type=\"table\"}. ", "Both qualitative (positive/negative) and quantitative results (magnitude of antibody levels) are important. ", "The quality of all these assays is dependent on the quality of the VLPs, pseudovirions and QC procedures [@b0340]. ", "Validated critical reagents and assay standards are not available commercially and therefore must be prepared and validated by the laboratory. ", "Strict adherence to standard operating procedures for production and quality control of these reagents is required, monitoring purity, concentration and type-specific conformation for each lot. ", "When the immunogenicity of two different vaccine formulations is being compared, the use of VLP antigens produced in an expression system that is different from that used to produce the vaccines would be preferable to avoid potentially favoring one formulation over another [@b0090], [@b0105]. ", "Assay reproducibility should be monitored with the use of high- and low-antibody titer control sera in every run and trends monitored. ", "Cut-off values can be challenging to determine, and although most laboratories base the value using a panel of virginal sera, such as children's sera, there are critical differences between cut-off determinations used in different laboratories and assays. ", "Currently there are no guidelines on methods to establish serostatus cut-offs which has a major influence on seropositivity rates. ", "Therefore, establishing uniform criteria for cut-off determinations of seropositivity will be particularly critical for one-dose trials where lower levels of antibodies are anticipated.", "Table 2Three main assay types used in monitoring HPV vaccine immunogenicity and their advantages and disadvantages.", "AdvantagesDisadvantagesNeutralization assay•Measures function closest to presumed mechanism of protection•All immunoglobulin classes are detected•Requires pseudovirions for each type•Requires cell culture and time for cells to grow•Time-consuming and labor intensive•Limited ability to multiplex•Higher coefficients of variation

Competitive immunoassay•Detects neutralizing antibodies•Easily multiplexed with bead arrays (e.g. Luminex)•Rapid, high throughput•All immunoglobulin classes detected•Only a subset of total neutralizing antibodies detected•Requires type-specific neutralizing monoclonal antibodies•Mulitplexing requires compromise between selecting dominant epitope and retaining type specificity

Enzyme linked immunosorbent assay•Fast, high throughput•Familiar assay format•Amenable to multiplexing (bead arrays or multispot wells)•Detects one immunoglobulin class (IgG or IgA), determined by secondary antibody•Non-neutralizing binding antibodies can be detected\n\nBecause different laboratories have used different assays for evaluation of immunogenicity to the HPV vaccines and key reagents are prepared differently in each laboratory, inter-laboratory assay standardization has been quite challenging. ", "In 2006, the Bill and Melinda Gates Foundation funded a WHO Global HPV Laboratory Network whose main activities were to work out systems for international comparability of HPV ELISA assays for HPV-16 and HPV-18 [@b0405], [@b0410], [@b0415]. ", "A series of international collaborative studies proved the basic principles of comparability [@b0410], [@b0415], [@b0420]. ", "The serology assays in use were found to generate sufficiently similar results, such that a simple use of the same international reference standard in all laboratories gave highly comparable data [@b0415]. ", "Such reference sera are formally established as International Standards (IS) that define the International Unit (IU) of HPV antibodies and can be ordered from the National Institute of Biological Standards and Controls (NIBSC, Potters Bar, UK). ", "A simple mathematical calculation called the parallel line method can be used to compare the crude results from a dilution series of the serum to be tested with the reference serum to find the antibody level [@b0415]. ", "Ideally, serology assay results should be reported in IU to facilitate direct comparison of results. ", "The laboratory step-by-step protocol for HPV-16 and HPV-18 assays is published in the WHO HPV Laboratory Manual, which also details the protocols of two common serology methods found to be robust and transferable (the pseudovirion neutralization assay and the VLP ELISA assay) [@b0340].", "\n\nIn addition to concentrations, antibody quality can be evaluated in terms of binding strength of antibodies to VLPs, or avidity. ", "Only a few studies have examined avidity in samples from HPV vaccine trials [@b0090], [@b0285], [@b0425], [@b0430]. ", "Avidity assays use the ELISA format but add a dissociating step with chaotropic agents such as ammonium thiocyanate, sodium thiocyanate or guanidine hydrochloride. ", "Generally, the ratio of antibodies detected after dissociation to those detected without dissociation is used to calculate an avidity index. ", "Care must be taken when selecting chaotropic agents and concentrations to ensure that the dissociation step does not introduce significant conformational change to the VLPs. ", "Several assay variations have been reported [@b0435], [@b0440], [@b0445], [@b0450] but no standard avidity assay or interlaboratory comparisons have been performed to date. ", "Affinity maturation and increases in avidity have been shown with increasing doses and time following vaccination [@b0090], [@b0285], [@b0445], [@b0450]. ", "Although lower than that observed in three-dose recipients, high avidity levels indicative of antibody affinity maturation have been observed in one-dose recipients of Cervarix® and Gardasil® [@b0285], [@b0425]. ", "The importance of antibody avidity in antiviral protection has been shown experimentally for some viruses, however, the significance of avidity in protection against HPV infection is not yet known [@b0455]. ", "In low antibody level situations, such as may be encountered with one-dose schedules, this could be an important parameter to monitor.", "\n\nRobust and standardized serological assays are critical for current and future HPV vaccine evaluation and may help identify immune correlate(s) of protection and provide early indications of potential efficacy of new vaccine products, such as biosimilars. ", "For closely related vaccines, immunogenicity data may support regulatory approval, accelerating vaccine implementation.", "\n\nBased on long-term efficacy data, HPV vaccines are expected to induce sufficiently high levels of immunity to protect against infection and subsequent disease. ", "However, low levels of antibodies are expected to be induced by single dose regimens, in particularly for HPV-18 in Gardasil® and Gardasil®9 recipients as well as for HPV-45 in Gardasil®9 recipients, based on long-term antibody persistence data and the data published in reduced dose schedules [@b0095], [@b0245], [@b0460], [@b0465]. ", "Thus, efforts to increase serology assay sensitivity at the lower end may be required to support immunobridging trials for single dose vaccines. ", "Results from mouse intravaginal challenge systems suggest that the levels required for *in vivo* protection are estimated to be orders of magnitude lower than levels detected *in vitro* by ELISA or neutralization assays [@b0375], [@b0470], suggesting that strategies for improvement in detectability of HPV antibody responses *in vitro* to match *in vivo* protection are warranted.", "\n\nIt is clear that immunogenicity assessment in one-dose vaccine studies will be challenging. ", "The importance of the immunologic data from these trials requires that the data from these assays be reliable and interpretable. ", "This means that testing must be done with methods that allow reporting results in terms of directly comparable International Units. ", "International Standards are still required for the additional 5 oncogenic types included in Gardasil®9. ", "A newly launched HPV Serology Standardization project, co-funded by the Bill and Melinda Gates foundation and the US National Cancer Institute, is addressing critical needs for global harmonization of HPV serology testing in clinical trials of HPV prophylactic vaccines. ", "The project plans to identify additional secondary standards for the types included in current vaccines, provide critical reference reagents (VLPs), and develop testing guidelines, all of which will be made available to the HPV serology community. ", "This builds on previous efforts of the WHO HPV LabNet and will be done in parallel with ongoing WHO and NIBSC efforts for production of International Standards for the additional HPV types included in Gardasil®9.", "\n\nThis project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. ", "HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US. ", "Government.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Abstract\n\nBackground Fibromyalgia (FM) is a prevalent musculoskeletal chronic pain condition. ", "Obesity is frequent in patients with FM. ", "Several studies suggests that body mass index (BMI) is related with pain intensity and quality of life.", "\n\nObjectives 1) To determine the prevalence of obesity in a sample of women with FM. ", "2) To determine the relationship between obesity and the following variables: pain intensity, functionality, psychological distress, quality of life, and sleep problems.", "\n\nResults The 30.9% (N=47) of the patients were normal weight, the 40.1% (N=61) overweight, and the remaining 28.9% (N=44) obese. ", "Groups were homogeneous regarding to age. ", "ANOVA analysis, with Bonferroni correction, showed no differences between groups in the assessed measures, except in pain intensity. ", "Patients with obesity had more pain than patients with overweight (p<.01).", "\n\nConclusions 1) As already stated in previous studies, obesity was a frequent comorbid condition in patients with FM. ", "2) Patients with obesity had more pain than overweight patients. ", "3) Weight didn’t determine differences in the other studied variables.", "\n\nStatistics from Altmetric.com\n\nNo Altmetric data available for this article.", "\n\nRequest permissions\n\nIf you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. ", "You will be able to get a quick price and instant permission to reuse the content in many different ways." ]

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[ "Lewis C. Cassidy School\n\nLewis C. Cassidy Academics Plus School is a historic elementary school located in the Morris Park neighborhood of Philadelphia, Pennsylvania. ", "It is part of the School District of Philadelphia. ", "The building was designed by Irwin T. Catharine and built in 1922–1924. ", "It is a three-story, nine bay by five bay, brick building on a raised basement in the Colonial Revival-style. ", "It features large stone arch surrounds on the first level, a projecting entrance pavilion, a double stone cornice, and brick parapet topped by stone coping.", "\n\nThe building was added to the National Register of Historic Places in 1988.", "\n\nReferences\n\nExternal links\n\nCategory:School buildings on the National Register of Historic Places in Philadelphia\nCategory:Colonial Revival architecture in Pennsylvania\nCategory:School buildings completed in 1924\nCategory:School District of Philadelphia\nCategory:Overbrook, Philadelphia\nCategory:Public elementary schools in Philadelphia" ]

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[ "Andrew Crichton\n\nAndrew Crichton (1790–1855) was a Scottish biographer and historian.", "\n\nCrichton, youngest son of a small landed proprietor, was born in the parish of Kirkmahoe, Dumfriesshire, December 1790, and educated at Dumfries Academy and at the university of Edinburgh.", "\n\nAfter becoming a licensed preacher he was for some time engaged in teaching in Edinburgh and North Berwick. ", "In 1823 he published his first work, the Life of the Rev. John Blackadder, which was followed by the Life of Colonel J. Blackadder, 1824, and Memoirs of the Rev. Thomas Scott, 1825. ", "To Constable's Miscellany he contributed five volumes, viz. ", "Converts from Infidelity, 2 vols. ", "1827, and a translation of Christoph Wilhelm von Koch's Revolutions in Europe, 3 vols. ", "1828.", "\n\nIn the Edinburgh Cabinet Library he wrote the History of Arabia, 2 vols. ", "1833, and Scandinavia, Ancient and Modern (written with Henry Wheaton), 2 vols. ", "1838. ", "He commenced his connection with the newspaper press in 1828 by editing (at first in conjunction with De Quincey) the Edinburgh Evening Post. ", "In 1830 he conducted the North Briton, and in 1832 he undertook the editorship of the Edinburgh Advertiser, in which employment he continued till June 1851.", "\n\nHe contributed extensively to periodicals, among others to the Westminster Review, Tait's Edinburgh Magazine, the Dublin University Magazine, Fraser's Magazine, the Church Review, and the Church of Scotland Magazine and Review.", "\n\nIn 1837 the university of St. Andrews conferred on him the degree of Doctor of Laws. ", "He was a member of the presbytery of Edinburgh, being ruling elder of the congregation of Trinity College Church, and sat in the general assembly of the Church of Scotland as elder for the burgh of Cullen for three years previous to his decease.", "\n\nHe died at 33 St. Bernard's Crescent, Edinburgh, 9 Jan. 1855.", "\n\nHe married first, in July 1835, Isabella Calvert, daughter of James Calvert, LL.D. of Montrose, she died in November 1837; and secondly, December 1844, Jane, daughter of the Rev. John Duguid, minister of Erie and Kendall.", "\n\nHe was a good friend of Leitch Ritchie, who was his neighbour at St Bernards Cresecent.", "\n\nNotes\n\nReferences\nAttribution\n\nExternal links\nWorks by Andrew Crichton at Google Books\n\nCategory:1790 births\nCategory:1855 deaths\nCategory:Scottish biographers\nCategory:Scottish historians\nCategory:Elders of the Church of Scotland\nCategory:People from Dumfries and Galloway\nCategory:Alumni of the University of Edinburgh\nCategory:Alumni of the University of St Andrews" ]

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[ "alue? ", " (a) r (b) 1 (c) 3 (d) 2/7\nc\nLet d = -0.21 - 1.39. ", "Let l = 2.6 + d. What is the biggest value in l, -4, -12?", "\nl\nLet n be (2/21)/((-5)/(-789330)). ", "Let f = n - 14960. ", "Let o = 75 - f. Which is the smallest value? ", " (a) o (b) 0.4 (c) -0.4\nc\nLet k = -9.4 - -11. ", "Let l = -0.9 + k. Let z = l + -0.6. ", "Which is the second smallest value? ", " (a) 2 (b) -2/9 (c) z\nc\nLet y be (2/(-24))/((-2)/(-4)). ", "Let s = 173 - -4. ", "Let d = s + -1067/6. ", "Which is the second smallest value? ", " (a) -1/3 (b) y (c) d\na\nSuppose 17*r = 12*r + 15. ", "Let p be (-39 + -1)*(-4)/10. ", "Suppose r*c - 8*c + 3*l = -p, 0 = -3*c + 5*l + 16. ", "What is the third smallest value in c, 3, -3?", "\n3\nSuppose -21*w + 13 = 55. ", "What is the third smallest value in w, 1/4, 4/55?", "\n1/4\nLet x(k) = -k**3 + 3*k**2 - 2*k - 3. ", "Let d be x(-1). ", "Suppose 2*y = -y + 9. ", "Let u be (-15)/42 - y/21. ", "Which is the second smallest value? ", " (a) u (b) d (c) 0.1\nc\nLet m = 182.1 - 182. ", "What is the smallest value in m, -3, -22/3?", "\n-22/3\nLet v = 278.9 + -277.9. ", "Let o = 6 - 8. ", "Let k be 1/(1/4*o). ", "Which is the third smallest value? ", " (a) v (b) k (c) 0.4\na\nLet m = 26.7 + -3.6. ", "Let r = m - 23. ", "Which is the biggest value? ", " (a) 4 (b) r (c) 2/5\na\nLet j = -0.8 + 3.8. ", "Let h = -10158 + 10163. ", "Which is the second biggest value? ", " (a) 2/5 (b) j (c) h (d) 2/11\nb\nLet w = 92 - 88. ", "Let s = 0.22 + -0.52. ", "Which is the fourth smallest value? ", " (a) 1 (b) 5/9 (c) s (d) w\nd\nLet v = 813/5 + -162. ", "Let x = 0.41 + 1.69. ", "Let f = -0.1 + x. Which is the smallest value? ", " (a) -6 (b) v (c) f\na\nLet i = -3 + 0. ", "Let u = -53.022 + 53. ", "Let v = u - -0.422. ", "Which is the third biggest value? ", " (a) v (b) i (c) -1/3\nb\nLet f be (1 - 2)/((-14)/(-126)). ", "Let g be (-30)/f - (-1)/(-3). ", "Which is the third biggest value? ", " (a) g (b) 0 (c) 44\nb\nLet a be 2/20*(-125)/(-100). ", "Let r = 0 + 3. ", "Let y = r + -2.5. ", "What is the third biggest value in y, -3, a?", "\n-3\nLet z be (-16)/28*(-3)/6. ", "Let m = -2.9 - 2.1. ", "Which is the smallest value? ", " (a) -3 (b) -2 (c) m (d) z\nc\nSuppose 0 = 4*m + 5*f - 12, -3*m + 10 = 275*f - 271*f. ", "Let r = 0.15 - -8.85. ", "Which is the second smallest value? ", " (a) r (b) m (c) -3 (d) -4\nc\nLet x = -108 + 111. ", "Which is the biggest value? ", " (a) -1 (b) 7 (c) -0.3 (d) x\nb\nLet n be (-9)/72 - 39/(-120). ", "Which is the second smallest value? ", " (a) n (b) -1/11 (c) 4\na\nLet d be (-1)/3 + (-43)/(-3). ", "Let p = -694 - -711. ", "Suppose 0 = -p*s + d*s - 9. ", "What is the biggest value in 8, s, -4?", "\n8\nLet j be (-4)/(-4) - 2/1. ", "What is the second biggest value in j, 1/3, -0.5, 0.3?", "\n0.3\nLet u = -19 - -1. ", "Let z = 22 + u. Let y = -0.6 - -1. ", "Which is the second smallest value? ", " (a) y (b) z (c) -2\na\nLet d be (-1 - -3) + 3 + -1. ", "Let j = 3 - d. Let o = 64/185 + 2/37. ", "What is the biggest value in 3, o, j?", "\n3\nLet y be (-24)/378 - (-4)/14. ", "Let p = -0.04 + 0.14. ", "Let l = -2.1 + p. Which is the third biggest value? ", " (a) 0.3 (b) y (c) l\nc\nLet o = -1.688 + 1.068. ", "Let i = -11 + 6. ", "Which is the third biggest value? ", " (a) o (b) 4 (c) i\nc\nLet p(m) = -m**3 + 8*m**2 + m - 3. ", "Let n be p(8). ", "Let z = n + 4. ", "Which is the biggest value? ", " (a) 1/3 (b) 1 (c) z\nc\nLet d(q) = 13*q - 7. ", "Let g be d(-7). ", "Let k = g - -880/9. ", "What is the biggest value in k, -1, -0.3?", "\nk\nLet v = -19.96 + 19.985. ", "Which is the third biggest value? ", " (a) -3 (b) -0.3 (c) v (d) -1/3\nd\nLet q = 15.53 + -15.83. ", "Let i = 0.04 - -4.96. ", "Which is the smallest value? ", " (a) -2/7 (b) q (c) i\nb\nLet v = -692 + 695. ", "Which is the second smallest value? ", " (a) 0.3 (b) 7 (c) v (d) 0.4\nd\nLet f = -26 - -24.4. ", "Which is the third biggest value? ", " (a) -4 (b) -0.1 (c) f\na\nLet q = -1 - -0.9. ", "Let p = -1 + 4. ", "Let v = 1475 + -1477. ", "Which is the third biggest value? ", " (a) q (b) v (c) p\nb\nLet h be (24/24)/((-1)/(-1)). ", "Let x = -4.4 + 5. ", "Let f = 0.3 - x. Which is the smallest value? ", " (a) f (b) h (c) -1/4\na\nLet v = -1114 - -1096. ", "Which is the third biggest value? ", " (a) -3 (b) v (c) -0.07 (d) -0.5\na\nLet s(j) = -j**2 + j + 1. ", "Let v be s(0). ", "Let z = -40.02 + 40.02. ", "Which is the second smallest value? ", " (a) 3 (b) z (c) v (d) 5\nc\nLet f = -0.046 + -4.754. ", "Let i = -7 - -12. ", "Let h = i + f. Which is the second biggest value? ", " (a) 0 (b) 2 (c) h\nc\nLet s = -15850/18359 + -1/3338. ", "Let v = -15/11 - s. Which is the biggest value? ", " (a) v (b) -2/11 (c) 1/5\nc\nSuppose -7*q + 89 = -4*t - 2*q, -2*t - 37 = -5*q. ", "Let x = 129/5 + t. Let o be (2 - 0)/(-2) + 4. ", "Which is the biggest value? ", " (a) x (b) o (c) 0.1\nb\nLet h(o) = -o**3 - 6*o**2 + 7*o - 5. ", "Let u be h(-7). ", "Suppose -2*r - 12 + 18 = 0. ", "Let w be -3 + r + (-1)/u. ", "What is the smallest value in -2/23, w, -0.5?", "\n-0.5\nLet j(v) = 0 - 2*v - v**2 + 1 - 6 + 2. ", "Let i be j(0). ", "Let n be (3/20)/(i/12). ", "Which is the second biggest value? ", " (a) n (b) -5 (c) -2/7\na\nLet o = -41 + 23. ", "Let y = -47 - -44. ", "Which is the third smallest value? ", " (a) y (b) o (c) -2/9\nc\nLet d(s) = -4*s - 42. ", "Let v be d(-12). ", "Let y(z) = z - 2. ", "Let p be y(v). ", "Let m = 9 - 4. ", "Which is the second biggest value? ", " (a) p (b) m (c) -2\na\nLet a(k) = -k**3 + 7*k**2 - 5*k - 1. ", "Let t be a(6). ", "Let y = -0.059 - 22.941. ", "Let x = y - -8. ", "What is the third smallest value in t, 4, x?", "\nt\nLet m = -6.3 + 2.8. ", "Let r = m + 3.2. ", "What is the third biggest value in -3/4, -3, r?", "\n-3\nLet g = 1761/2 + -879. ", "Let w be 1/2 + (-9)/6. ", "What is the smallest value in w, -2/23, 5, g?", "\nw\nLet f = -1934 - -1930. ", "Which is the third smallest value? ", " (a) -192/7 (b) f (c) 0.2\nc\nLet v be -6*((-12)/(-3))/(-8). ", "Let f be v/(-6) + (-98)/(-4). ", "Let r = f - 49/2. ", "What is the third biggest value in r, -0.1, 5?", "\nr\nSuppose -4*r = -5*l + 4*l + 22, 3*r + l = -13. ", "Let o = 9 + -8.9. ", "Let p = 1.9 + o. Which is the third biggest value? ", " (a) 5 (b) p (c) r\nc\nLet m = -0.63 - 0.37. ", "Let w = 1 - -2. ", "Which is the biggest value? ", " (a) -1/11 (b) w (c) -0.3 (d) m\nb\nLet s = -0.15 + -0.25. ", "Let h be -3 + -6*(-2)/6. ", "Which is the biggest value? ", " (a) -0.5 (b) s (c) h\nb\nLet v = 9 - 9.1. ", "Let o = 0.33 - 19.33. ", "What is the smallest value in v, o, 5?", "\no\nLet q = 1866 + -1870. ", "Let j = 4.9 + 0.1. ", "Which is the biggest value? ", " (a) j (b) 0.5 (c) q\na\nLet n be ((-16)/(-10))/(3/540). ", "Let f = n + -3746/13. ", "Which is the biggest value? ", " (a) f (b) -0.5 (c) -0.3\na\nSuppose 2*k + 2 = -0. ", "Let t be 2*(-1 + k/2). ", "Let q be 1/5 - 21/(-245). ", "Which is the smallest value? ", " (a) q (b) t (c) 3/5\nb\nLet s = -385 - -422.4. ", "Let t = s - 0.4. ", "What is the third smallest value in 0.1, t, 3/5?", "\nt\nLet s be 6/11 + 1541/(-506). ", "Let x = 10.8 - 11. ", "What is the third smallest value in s, 5, x, -2/17?", "\n-2/17\nLet i = -0.1 + -12.9. ", "Let y = 614 - 613. ", "Which is the third smallest value? ", " (a) y (b) i (c) -1/2\na\nLet p = -1241/4 - -310. ", "Which is the second smallest value? ", " (a) -4 (b) 4 (c) p (d) 0.0094\nc\nLet s = -1669 - -1661. ", "Which is the fourth smallest value? ", " (a) 3 (b) s (c) -2/3 (d) 0.06\na\nSuppose -x + 175 = y, 2*x = 5*y - 86 + 457. ", "Let q = x + -1956/11. ", "Suppose -2*j = -6*j + 12. ", "What is the second biggest value in j, -2/11, q?", "\nq\nLet l = -2 + 3. ", "Let i = 0 - 2. ", "Let p be (11/99)/((-2)/12). ", "What is the third smallest value in l, i, p?", "\nl\nSuppose -35 - 7 = -14*m. ", "Which is the third biggest value? ", " (a) 1 (b) 2 (c) m\na\nLet z be (161632/(-75990))/8 - -2. ", "Let o = z + -2/2533. ", "Let f = -12/5 + o. What is the third biggest value in 2/5, -0.5, f?", "\nf\nLet a = -308.1 + 308. ", "What is the smallest value in a, 0, -0.055?", "\na\nLet l be (3 - 7)*2/20. ", "Which is the smallest value? ", " (a) 4 (b) l (c) 0.4 (d) 0.2\nb\nLet h = 4118/9 + -458. ", "Which is the second biggest value? ", " (a) 1.7 (b) 1 (c) 0.5 (d) h\nb\nLet k = 0.8 + 6.2. ", "Let d = k - 4. ", "Let f be 30/(-18) - (0 - 1). ", "What is the smallest value in d, f, -2/7?", "\nf\nLet k = -0.1261 + -0.1739. ", "What is the second smallest value in k, 7/5, 8?", "\n7/5\nLet s = 2.2 - -2.8. ", "Which is the fourth smallest value? ", " (a) -1/7 (b) 4 (c) s (d) 0.8\nc\nLet g = 0.2 - 0.4. ", "Let i = 392 - 7446/19. ", "Suppose -11*y + 19*y = 8. ", "What is the second biggest value in i, y, g?", "\ni\nSuppose 0*i - 8 = -2*i. ", "Suppose i*q = 5*s + 6*q + 32, -3 = 3*q. ", "Which is the second smallest value? ", " (a) -2 (b) 0.2 (c) s\na\nLet g(c) = 4*c - 3*c**3 + 6 + 0 + 4*c**3 - 6*c**2. ", "Let r be g(5). ", "Let s = -70 + 69. ", "What is the third biggest value in -0.5, s, r?", "\ns\nLet r = -16 - -11. ", "Let n = -4 + 7.9. ", "Let w = 3.7 - n. What is the second smallest value in w, -4, r?", "\n-4\nLet q = -1.995 - -1.695. ", "What is the second biggest val" ]

{ "pile_set_name": "DM Mathematics" }

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