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tomekkorbak

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[ "Q:\n\nAndroid NDK sourceSets.main coundn't find jni\n\nLike above, my build.gradle file cannot sync because it could not find property \"jni\" on source sets \"main\". ", "I'm using gradle-experimental:0.7.0.", "\nI wan't to use Android.mk file in compilation, but i cannot set srcDirs = [].", "\nMy build.gradle:\nmodel {\nandroid {\n def globalConfiguration = rootProject.extensions.getByName(\"ext\")\n\n compileSdkVersion = globalConfiguration.getAt(\"androidCompileSdkVersion\")\n buildToolsVersion = globalConfiguration.getAt(\"androidBuildToolsVersion\")\n\n defaultConfig {\n applicationId \"com.example.ndk\"\n minSdkVersion.apiLevel globalConfiguration.getAt(\"androidMinSdkVersion\")\n targetSdkVersion.apiLevel globalConfiguration.getAt(\"androidTargetSdkVersion\")\n versionCode globalConfiguration.getAt(\"androidVersionCode\")\n versionName globalConfiguration.getAt(\"androidVersionName\")\n }\n\n buildTypes {\n release {\n minifyEnabled false\n proguardFiles.add(file('proguard-android.txt'))\n// signingConfig signingConfigs.release\n }\n }\n\n sourceSets {\n def commonTestDir = 'src/commonTest/java'\n test {\n java.srcDir commonTestDir\n }\n androidTest {\n java.srcDir commonTestDir\n }\n main {\n jni.srcDirs = []\n }\n }\n}\n\n android.ndk {\n moduleName = 'mymodule'\n }\n}\n\nA:\n\nTake a look into the plugin Experimental Plugin User Guide, according to it, to specify the source directory, you have to do it like so:\nmodel {\n android {\n ...\n\n sources {\n main {\n jni {\n source {\n srcDir \"src\"\n }\n }\n }\n }\n }\n}\n\nIt's not the way you did it. ", "Take a look, here is the sources property used, but not the sourceSets\n\n" ]

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[ "(upbeat music)\n- It's week 28 and, from\nhere on out, there will start\nto be small differences\nin the rate of growth,\ndepending on whether your\nbaby-to-be is a boy or a girl.", "\nA bouncing blue bruiser\nis likely to grow bigger\nand heavier than a princess\nplaying on team pink.", "\nGenetics and other factors\nalso weigh on how fast\na baby grows and how big she\nwill ultimately be on arrival.", "\nSo while on average a 28-weeker\nis around two and a half pounds\nand almost 16 inches tall,\nyour little one may be\ncurrently longer, shorter,\nheavier or less tubby.", "\nAs long as she continues\nto get good reports\nat those prenatal checkups,\nyou can rest assured\nyour baby's on the right track\nand in the right range for growth.", "\nYour minute miracle\nhas added another trick\nto her repertoire: hiccuping.", "\nIf you haven't yet, you'll not\nonly be able to feel hiccups\non the inside as little rhythmic twitches,\nyou'll be seeing them on the outside too,\nmaking your belly shake\nlike a bowl of jelly.", "\nThese tiny spasms are thought to be caused\nby the sudden, irregular contraction\nof the immature diaphragm,\nwhich is still trying to\ngear up for life outside\nthe womb by practicing the\nins and outs of breathing.", "\nSome babies hiccup several\ntimes a day, every day,\nothers not so much.", "\nBut your bound to feel\nthose adorable twitches\nevery so often.", "\nAnd an ultrasound might\neven be able to pick up\nthat little chest heaving\nfrom the hiccups too.", "\nEntertaining for you,\nand happily not uncomfortable for baby.", "\nAnother activity that can be picked up\nis REM, or rapid eye movement.", "\nThose tiny flutters of baby's eyes suggest\nthat she's dreaming away,\nsince REM is considered\nthe dream phase of sleep.", "\nBut there's no way of knowing\nwhat's on your little ones mind or what,\nif anything, she might be dreaming of.", "\nWhat we do know is that sleep cycles\nare coming at more regular times,\nmeaning your sweet little sleepy head\nis developing a more\nregular pattern of sleeping\nand wakefulness.", "\nProblem is, your on-the-go\nmovements lull her to sleep\nduring the day, keeping\nher awake and raring to go,\njust when you're settling\ndown for the night.", "\nStill, there's nothing more\nsatisfying than feeling\nyour amazing miracle somersault\nand stretch inside of you.", "\nPlus, as they say, baby's keeping you up\nwith those antics now is good preparation\nfor after she's born,\nand when every night's the night to howl.", "\nWant more satisfaction?", "\nThough the bun in your oven\nis far from being fully baked,\nher chances of survival outside the womb\nare at least 90 percent at this point.", "\n" ]

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[ "Norwich City‘s fine form continued Saturday at home against Stoke City, though a result ultimately eluded the Canaries for the first time in quite a while. ", "A 35th-minute Timm Klose own goal proved their undoing in the 1-0 defeat. ", "The loss snapped Norwich’s unbeaten streak at eight across all competitions, with six of those results coming in league play.", "\n\nAfter a dismal start in which the Canaries appeared set to fend off relegation this season, they quickly righted the ship and now look closer to the part of promotion contender than bottom feeder. ", "What the squad truly is this season remains to be seen however, considering the recent run of sublime form only brought the club’s goal differential to zero following Saturday’s narrow setback. ", "That’s how bleakly the team’s 2018-19 campaign began.", "\n\nAgainst Stoke, Norwich manager Daniel Farke rolled out his oft-used 4-2-3-1 with veteran ‘keeper Tim Krul in net. ", "It marked the fifth-consecutive time Farke used the exact same 11 in Championship play. ", "Stoke, meanwhile, came out in a 4-1-4-1 featuring two alterations to its most recent lineup. ", "Peter Etebo and James McClean joined the 11 after not starting in Tuesday’s 2-0 win over Bolton.", "\n\nNorwich bossed several statistical categories, completing a staggering 398 more passes than the visitors while owning 69 percent of the possession. ", "But unable to solve a sneaky-good Potters back four of Bruno Martins Indi, Ashley Williams, Erik Pieters and Cuco Martina, the hosts never cancelled out Klose’s own goal with a strike of their own.", "\n\nThe Canaries honored a fallen supporter with a special tribute at Carrow Road in the 53rd minute. ", "Longtime season ticket holder Dawn Brown passed away this week from cancer at age 53, and her daughter took to Twitter to ask the club and supporters if they’d partake in a full minute of applause in memory of her mother. ", "The club obliged in a top-class gesture:\n\nA fan has asked that City supporters take part in a minute’s applause in the 53rd minute in memory of her mum, Dawn Brown, a season-ticket holder who passed away earlier this week after battling cancer. ", "Our thoughts are with Dawn’s family and friends. #", "ncfc https://t.co/K5WDw8cnv3 — Norwich City FC (@NorwichCityFC) October 6, 2018\n\nNext up for Norwich is an Oct. 20 away fixture against Nottingham Forest. ", "The Tricky Trees currently sit in fifth in the table with 19 points, just one above the Canaries.", "\n\nThough the unbeaten run came to a halt Saturday, Norwich produced another rather encouraging showing. ", "The last few weeks have served as portents of positivity after a doom-and-gloom start.", "\n\nFollow Kevin on Twitter: @KJboxing.", "\n\nSupport Soc Takes on Patreon for access to exclusive content and supporter benefits. ", "Click here to become a patron today." ]

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[ "Number of passengers\n\nAir Passenger Duty (APD) no longer applies to passengers aged between 12 and under 16 years old travelling in economy. ", "We need to know if anyone in this age range is travelling so we don't charge you APD for them." ]

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[ "Maria Novolodskaya\n\nMaria Yuryevna Novolodskaya (; born 28 July 1999) is a Russian racing cyclist, who currently rides for UCI Women's Continental Team . ", "She rode in the women's time trial event at the 2018 UCI Road World Championships.", "\n\nReferences\n\nExternal links\n\nCogeas–Mettler–Look team profile\n\nCategory:1999 births\nCategory:Living people\nCategory:Russian female cyclists\nCategory:People from Veliky Novgorod\nCategory:European Games competitors for Russia\nCategory:Cyclists at the 2019 European Games\nCategory:European Games medalists in cycling\nCategory:European Games bronze medalists for Russia\nCategory:Sportspeople from Novgorod Oblast" ]

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[ "/**\n * This file is part of the CernVM File System.", "\n */\n\n#ifndef CVMFS_SWISSKNIFE_HISTORY_H_\n#define CVMFS_SWISSKNIFE_HISTORY_H_\n\n#include <string>\n#include <vector>\n\n#include \"hash.h\"\n#include \"history_sqlite.h\"\n#include \"swissknife.h\"\n#include \"util_concurrency.h\"\n\nnamespace manifest {\nclass Manifest;\n}\n\nnamespace catalog {\nclass Catalog;\nclass WritableCatalog;\n}\n\nnamespace upload {\nstruct SpoolerDefinition;\nstruct SpoolerResult;\nclass Spooler;\n}\n\nnamespace swissknife {\n\nclass CommandTag : public Command {\n public:\n static const std::string kHeadTag;\n static const std::string kHeadTagDescription;\n static const std::string kPreviousHeadTag;\n static const std::string kPreviousHeadTagDescription;\n\n CommandTag() { }\n\n protected:\n typedef std::vector<history::History::Tag> TagList;\n typedef std::vector<history::History::Branch> BranchList;\n\n struct Environment {\n Environment(const std::string &repository_url,\n const std::string &tmp_path) :\n repository_url(repository_url), tmp_path(tmp_path) {}\n\n const std::string repository_url;\n const std::string tmp_path;\n\n UnlinkGuard manifest_path;\n UniquePtr<manifest::Manifest> manifest;\n UniquePtr<manifest::Manifest> previous_manifest;\n UniquePtr<history::History> history;\n UniquePtr<upload::Spooler> spooler;\n UnlinkGuard history_path;\n };\n\n\n Environment* InitializeEnvironment(const ArgumentList &args,\n const bool read_write);\n bool CloseAndPublishHistory(Environment *environment);\n bool UploadCatalogAndUpdateManifest(Environment *env,\n catalog::WritableCatalog *catalog);\n void UploadClosure(const upload::SpoolerResult &result,\n Future<shash::Any> *hash);\n\n bool UpdateUndoTags(Environment *env,\n const history::History::Tag &current_head_template,\n const bool undo_rollback = false);\n\n // TODO(jblomer): replace by swissknife::Assistant\n bool FetchObject(const std::string &repository_url,\n const shash::Any &object_hash,\n const std::string &destination_path) const;\n history::History* GetHistory(const manifest::Manifest *manifest,\n const std::string &repository_url,\n const std::string &history_path,\n const bool read_write) const;\n\n catalog::Catalog* GetCatalog(const std::string &repository_url,\n const shash::Any &catalog_hash,\n const std::string catalog_path,\n const bool read_write) const;\n\n void PrintTagMachineReadable(const history::History::Tag &tag) const;\n\n std::string AddPadding(const std::string &str,\n const size_t padding,\n const bool align_right = false,\n const std::string &fill_char = \" \") const;\n\n bool IsUndoTagName(const std::string &tag_name) const;\n};\n\n\n//------------------------------------------------------------------------------\n\n\n/**\n * If -a and -d are specified, removal of tags takes place before the new tag is\n * added.", "\n */\nclass CommandEditTag : public CommandTag {\n public:\n virtual std::string GetName() const { return \"tag_edit\"; }\n virtual std::string GetDescription() const {\n return \"Create a tag and/or remove tags.\";", "\n }\n\n virtual ParameterList GetParams() const;\n int Main(const ArgumentList &args);\n\n protected:\n int RemoveTags(const ArgumentList &args, Environment *env);\n int AddNewTag(const ArgumentList &args, Environment *env);\n\n shash::Any GetTagRootHash(Environment *env,\n const std::string &root_hash_string) const;\n bool ManipulateTag(Environment *env,\n const history::History::Tag &tag_template,\n const bool user_provided_hash);\n bool MoveTag(Environment *env,\n const history::History::Tag &tag_template);\n bool CreateTag(Environment *env,\n const history::History::Tag &new_tag);\n};\n\n\n//------------------------------------------------------------------------------\n\n\nclass CommandListTags : public CommandTag {\n public:\n virtual std::string GetName() const { return \"tag_list\"; }\n virtual std::string GetDescription() const {\n return \"List tags in the tag database.\";", "\n }\n\n virtual ParameterList GetParams() const;\n int Main(const ArgumentList &args);\n\n protected:\n struct BranchLevel {\n BranchLevel() : branch(), level(0) { }\n BranchLevel(const history::History::Branch &b, unsigned l)\n : branch(b), level(l) { }\n history::History::Branch branch;\n unsigned level;\n };\n typedef std::vector<BranchLevel> BranchHierarchy;\n\n void SortBranchesRecursively(unsigned level,\n const std::string &parent_branch,\n const BranchList &branches,\n BranchHierarchy *hierarchy) const;\n BranchHierarchy SortBranches(const BranchList &branches) const;\n\n void PrintHumanReadableTagList(const TagList &tags) const;\n void PrintMachineReadableTagList(const TagList &tags) const;\n void PrintHumanReadableBranchList(const BranchHierarchy &branches) const;\n void PrintMachineReadableBranchList(const BranchHierarchy &branches) const;\n};\n\n\n//------------------------------------------------------------------------------\n\n\nclass CommandInfoTag : public CommandTag {\n public:\n virtual std::string GetName() const { return \"tag_info\"; }\n virtual std::string GetDescription() const {\n return \"Obtain detailed information about a tag.\";", "\n }\n\n virtual ParameterList GetParams() const;\n int Main(const ArgumentList &args);\n\n protected:\n std::string HumanReadableFilesize(const size_t filesize) const;\n void PrintHumanReadableInfo(const history::History::Tag &tag) const;\n};\n\n\n//------------------------------------------------------------------------------\n\n\nclass CommandRollbackTag : public CommandTag {\n public:\n virtual std::string GetName() const { return \"tag_rollback\"; }\n virtual std::string GetDescription() const {\n return \"Rollback repository to a given tag.\";", "\n }\n\n virtual ParameterList GetParams() const;\n int Main(const ArgumentList &args);\n\n protected:\n void PrintDeletedTagList(const TagList &tags) const;\n};\n\n\n//------------------------------------------------------------------------------\n\n\nclass CommandEmptyRecycleBin : public CommandTag {\n public:\n virtual std::string GetName() const { return \"tag_empty_bin\"; }\n virtual std::string GetDescription() const {\n return \"Empty the internal recycle bin of the history database.\";", "\n }\n\n virtual ParameterList GetParams() const;\n int Main(const ArgumentList &args);\n};\n\n} // namespace swissknife\n\n#endif // CVMFS_SWISSKNIFE_HISTORY_H_\n" ]

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[ "2013 NRA Convention in Houston\n\nMay 3, 2013\n\nJohnny Hanson/Houston Chronicle\n\n52of129\n\nU.S. Senator Ted Cruz is introduced before speaking during the NRA-ILA Leadership Forum at the National Rifle Association's 142 Annual Meetings and Exhibits in the George R. Brown Convention Center Friday, May 3, 2013, in Houston.", "\n\nJohnny Hanson/Houston Chronicle\n\n52of129\n\nU.S. Senator Ted Cruz is introduced before speaking during the NRA-ILA Leadership Forum at the National Rifle Association's 142 Annual Meetings and Exhibits in the George R. Brown Convention Center Friday, May 3, 2013, in Houston." ]

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[ "Q:\n\nDates timeline on Recent activity\n\na little weird this morning\n\nshouldn't that have a different day?", "\n\nA:\n\nIf you look at the times you'll see it's 12:00:00AM to 11:59:59PM (UTC) on that same day, so the duration is in fact a full 24 hours, it just appears one second shorter until you think about it a bit :)\n\n" ]

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[ "Vani Ganapathy\n\nVani Ganapathy, also spelled as Vani Ganpati, is an Indian classical dancer. ", "In 1978, Vani married actor Kamal Haasan. ", "They got divorced 10 years later in 1988.", "\n\nShe started performing when she was seven, and has travelled across the world for her performances. ", "She lives in Bangalore, where she set up Sanchari, a dance academy.", "\n\nReferences\n\nCategory:Bharatanatyam exponents\nCategory:Living people\nCategory:Year of birth missing (living people)" ]

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[ "Q:\n\nJenkins Pipeline Checkout SVN to custom workspace\n\nI'm writing an Jenkins Pipeline script at the moment (declarative). ", "Basically like this:\npipeline {\n agent any\n environment {\n NLS_LANG = 'GERMAN_GERMANY.AL32UTF8'\n }\n stages {\n stage('Test') {\n steps {\n script {\n echo \"Test\"\n }\n }\n }\n }\n}\n\nThe script itself works fine. ", "But we now found out, that the jenkins checks out our SVN repository first to find the Jenkinsfile (Checkout in folder workspace@script in the job Folder > C:\\jenkins_home\\jobs\\<Projectname>\\jobs\\<Jobname>).", "\nThan the whole SVN is checked out again in an second step which I didn't wrote in the Jenkinsfile (Title: \"Declarative: SCM Checkout\").", "\nIt would be okay, if we could change the path of this checkout, because at the moment it checks out in a new created workspace folder in the job folder. ", "\nHere I have a screenshot from the console output of the pipeline job: \nHow can the checkout in a custom workspace be achieved? ", "\nPreferably it would only checkout the Jenkinsfile on it's own on the first checkout, not the whole repository. ", "\nI tried to change the repository url to the folder where the Jenkinsfile is saved (alone), but than the pipeline is also (only) checking out this folder on the second checkout.", "\nHere I have a screenshot of the console output trying this: \n\nA:\n\nTo whom it may concern when coming around this question: use a ws('/path/to/dir') to allocate a different directory (see Pipeline: Nodes and processes)\npipeline {\n agent any\n environment {\n NLS_LANG = 'GERMAN_GERMANY.AL32UTF8'\n }\nstages {\n stage('Test') {\n steps {\n script {\n echo \"Test\"\n ws('/path/to/dir'){\n //dosomething here, like \"checkout scm\"\n }\n }\n }\n }\n} \n\n" ]

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[ "Actions\n\nMom's a Genius: Detroit's first bridal boutique opened by celebrity consultant\n\nPosted: 4:00 PM, Aug 18, 2016\n\nUpdated:2016-08-24 21:29:58Z\n\nBy:\nJoAnne Purtan, Whitney Amann\n\nKeasha Rigsby has been dressing brides for over 20 years. ", "You may recognize her from TLC's \"Say Yes to the Dress\" or her own show \"Kaesha's Perfect Dress\".", "\n\n\"My time on say yes to the dress was just phenomenal. ", "I mean \"Say Yes to the Dress\"\nhas opened doors for me like I just can’t begin to tell you,\" says Keasha.", "\n\nIn February, she brought her charm to the Motor City.", "\n\n\"Well it has always been my dream to have my own bridal boutique. ", "I mean ever since I worked at Kleinfeld I always wanted to open my own bridal boutique,\" says Keasha.", "\n\nAlthough she is from Brooklyn, she decided to open up Beautiful Bridal\nin Detroit, making it the first bridal salon in the city.", "\n\n\"I love Detroit. ", "I feel that Detroit is on the up and up. ", "I'm so glad to be part of the revitalization of this great city. ", "I’m so grateful to be a part of the rebuilding of the community,\" says Keasha.", "\n\nShe has dressed brides from all over the world, and now brides from the Detroit area can find their dream wedding dress with her expertise.", "\n\nAshley Mack went to see Keasha at Beautiful Bridal\nthe first week it opened. ", "She said working with Keasha was a breath of fresh air and she made her dress hunting fun and exciting.", "\n\n\"To find out that Keasha Rigsby was going to be here promoting, selling dresses and helping girls out was awesome. ", "And then you walk into this beautiful mansion, and that’s breathtaking here in the city of Detroit,\" says Ashley.", "\n\nEarlier this year, Mayor Mike Duggan awarded Keasha and her business partner one of many small business grants. ", "They used the money to increase their inventory and provide more options for brides who have that perfect dress in mind.", "\n\n\"I need the best of the best. ", "So when I’m going into these showrooms and when I’m meeting with these designers, I look for like every little detail down to the itty bitty bead; just how it was placed on the dress, it shows me that the designer loves what he or she is creating,\" explains Keasha.", "\n\nThe dresses start at $3,000 and are beautifully displayed in the historic mansion on Jefferson Avenue. ", "Working with brides for as long as she has, does she have any \"bridezilla\" stories?", "\n\n\"Oh you know what? ", "I don't like calling them that... Because no one really knows what goes on with these young ladies and you know, any bride for that matter. ", "No one knows the stress, no one knows the pressure, so I don't like to refer to any bride as a bridezilla.\"", "\n\n\"I look at each and every one of my brides as they step into my store, they’re stepping into a new chapter in their lives,\" says Keasha. \"", "The most rewarding part is just seeing, I know it may sound corny but seeing the smiles of my brides.\"", "\n\nBeautiful Bridal\nis by appointment only but selling dresses isn't the only thing they do. ", "They also host fundraisers and events as well as \"try on\" parties where your group of friends can come in and try on as many dresses as you'd like." ]

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[ "// Foundation/URLSession/TaskRegistry.swift - URLSession & libcurl\n//\n// This source file is part of the Swift.org open source project\n//\n// Copyright (c) 2014 - 2016 Apple Inc. and the Swift project authors\n// Licensed under Apache License v2.0 with Runtime Library Exception\n//\n// See http://swift.org/LICENSE.txt for license information\n// See http://swift.org/CONTRIBUTORS.txt for the list of Swift project authors\n//\n// -----------------------------------------------------------------------------\n///\n/// These are libcurl helpers for the URLSession API code.", "\n/// - SeeAlso: https://curl.haxx.se/libcurl/c/\n/// - SeeAlso: URLSession.swift\n///\n// -----------------------------------------------------------------------------\n\n#if os(macOS) || os(iOS) || os(watchOS) || os(tvOS)\nimport SwiftFoundation\n#else\nimport Foundation\n#endif\n\n@_implementationOnly import CoreFoundation\nimport Dispatch\n\nextension URLSession {\n /// This helper class keeps track of all tasks, and their behaviours.", "\n ///\n /// Each `URLSession` has a `TaskRegistry` for its running tasks. ", "The\n /// *behaviour* defines what action is to be taken e.g. upon completion.", "\n /// The behaviour stores the completion handler for tasks that are\n /// completion handler based.", "\n ///\n /// - Note: This must **only** be accessed on the owning session's work queue.", "\n class _TaskRegistry {\n /// Completion handler for `URLSessionDataTask`, and `URLSessionUploadTask`.", "\n typealias DataTaskCompletion = (Data?, ", "URLResponse?, ", "Error?) -", "> Void\n /// Completion handler for `URLSessionDownloadTask`.", "\n typealias DownloadTaskCompletion = (URL?, ", "URLResponse?, ", "Error?) -", "> Void\n /// What to do upon events (such as completion) of a specific task.", "\n enum _Behaviour {\n /// Call the `URLSession`s delegate\n case callDelegate\n /// Default action for all events, except for completion.", "\n case dataCompletionHandler(DataTaskCompletion)\n /// Default action for all events, except for completion.", "\n case downloadCompletionHandler(DownloadTaskCompletion)\n }\n \n fileprivate var tasks: [Int: URLSessionTask] = [:]\n fileprivate var behaviours: [Int: _Behaviour] = [:]\n fileprivate var tasksFinishedCallback: (() -> Void)?", "\n }\n}\n\nextension URLSession._TaskRegistry {\n /// Add a task\n ///\n /// - Note: This must **only** be accessed on the owning session's work queue.", "\n func add(_ task: URLSessionTask, behaviour: _Behaviour) {\n let identifier = task.taskIdentifier\n guard identifier !", "= 0 else { fatalError(\"Invalid task identifier\") }\n guard tasks.index(forKey: identifier) == nil else {\n if tasks[identifier] === task {\n fatalError(\"Trying to re-insert a task that's already in the registry.\")", "\n } else {\n fatalError(\"Trying to insert a task, but a different task with the same identifier is already in the registry.\")", "\n }\n }\n tasks[identifier] = task\n behaviours[identifier] = behaviour\n }\n /// Remove a task\n ///\n /// - Note: This must **only** be accessed on the owning session's work queue.", "\n func remove(_ task: URLSessionTask) {\n let identifier = task.taskIdentifier\n guard identifier !", "= 0 else { fatalError(\"Invalid task identifier\") }\n guard let tasksIdx = tasks.index(forKey: identifier) else {\n fatalError(\"Trying to remove task, but it's not in the registry.\")", "\n }\n tasks.remove(at: tasksIdx)\n guard let behaviourIdx = behaviours.index(forKey: identifier) else {\n fatalError(\"Trying to remove task's behaviour, but it's not in the registry.\")", "\n }\n behaviours.remove(at: behaviourIdx)\n\n guard let allTasksFinished = tasksFinishedCallback else { return }\n if self.isEmpty {\n allTasksFinished()\n }\n }\n\n func notify(on tasksCompletion: @escaping () -> Void) {\n tasksFinishedCallback = tasksCompletion\n }\n\n var isEmpty: Bool {\n return tasks.isEmpty\n }\n \n var allTasks: [URLSessionTask] {\n return tasks.map { $0.value }\n }\n}\nextension URLSession._TaskRegistry {\n /// The behaviour that's registered for the given task.", "\n ///\n /// - Note: It is a programming error to pass a task that isn't registered.", "\n /// - Note: This must **only** be accessed on the owning session's work queue.", "\n func behaviour(for task: URLSessionTask) -> _Behaviour {\n guard let b = behaviours[task.taskIdentifier] else {\n fatalError(\"Trying to access a behaviour for a task that in not in the registry.\")", "\n }\n return b\n }\n}\n" ]

{ "pile_set_name": "Github" }

[ 0.0007126153795979917, 0.0011028411099687219, 0.0007826850633136928, 0.0006826284225098789, 0.0007272730581462383, 0.0008916215156204998, 0.000841388653498143, 0.0008297390304505825, 0.001955938758328557, 0.0009445316973142326, 0.0009395382949151099, 0.0009905531769618392, 0.001955938758328557, 0.0009445316973142326, 0.0007124938420020044, 0.0010711515787988901, 0.0006653303280472755, 0.0009937945287674665, 0.0008374142344109714, 0.0013276252429932356, 0.0010668935719877481, 0.0007223612046800554, 0.0008688030065968633, 0.0014394267927855253, 0.0011238373117521405, 0.000988166080787778, 0.00902626570314169, 0.0022431572433561087, 0.0007244368898682296, 0.001161067048087716, 0.002398610347881913 ]

[ "English & Spanish Medical Words & Phrases, Fourth Edition is a handy, pocket-sized reference covering thousands of key terms and phrases used in clinician-patient interactions. ", "It's the perfect resource for nurses and other health care professionals who care for Spanish-speaking patients or whose primary language is Spanish.", "\n\nThe book covers important terms related to every aspect of patient care, including systems assessment, patient teaching, discharge, medical equipment and supplies, diagnostic tests, treatments, nutrition and diet therapy, and complementary and alternative therapies. ", "Anatomical illustrations are included to facilitate communication. ", "This Fourth Edition includes an English-Spanish picture dictionary and Spanish pain-rating scales.", "\n\n.", "\n\nRead English & Spanish Medical Words & Phrases (LWW, English and Spanish Medical Words and Phrases) complete books online for free. ", "Reading English & Spanish Medical Words & Phrases (LWW, English and Spanish Medical Words and Phrases) full free books online without downloading.", "Looking up to the full article E-Books free download? ", "Here you can read\n\nEnglish & Spanish Medical Words & Phrases (LWW, English and Spanish Medical Words and Phrases) . ", "You can also read and download new and old full E-Books. ", "Enjoy and relax with full English & Spanish Medical Words & Phrases (LWW, English and Spanish Medical Words and Phrases) Books Online." ]

{ "pile_set_name": "Pile-CC" }

[ 0.0005805906257592142, 0.0009457830456085503, 0.000599755032453686, 0.0005641034222207963, 0.0007900819764472544, 0.0021375224459916353, 0.0006031814264133573, 0.0006137736490927637, 0.0006224449607543647, 0.0005717474268749356, 0.0007814014097675681, 0.0005660663591697812 ]

[ "KCFN\n\nKCFN (91.1 FM) is a radio station broadcasting a Christian format. ", "Licensed to Wichita, Kansas, United States, the station serves the Wichita area. ", "The station is owned by American Family Association and is an affiliate of American Family Radio.", "\n\nHistory\nThe station began broadcasting on April 23, 1978, holding the call sign KDSA, and was owned by the Defenders School of the Air. ", "In 1981, the station was sold to Friends University for $100,000. ", "Its call sign was changed to KSOF the following year. ", "KSOF aired a classical music/fine arts format.", "\n\nIn 1992, the station was sold to New Life Fellowship for $205,000, and it adopted a Christian contemporary format. ", "On June 15, 1992, its call sign was changed to KZZD and on July 12, 1993, its call sign was changed to KCFN. ", "In 1994, the station was sold to American Family Association for $275,000, and it became an affiliate of American Family Radio.", "\n\nReferences\n\nExternal links\n\nCFN\nCategory:Religious radio stations in the United States\nCategory:American Family Radio stations\nCategory:Moody Radio affiliate stations\nCategory:Radio stations established in 1978" ]

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

[ 0.001297596376389265, 0.0006072347168810666, 0.0009289397276006639, 0.0006553077255375683, 0.0007902857614681125, 0.0008032064069993794, 0.0007920223288238049, 0.0008290581754408777, 0.0008937733946368098, 0.0008770189597271383, 0.0006128909881226718 ]

[ "The ‘Vitalalm’ Spa in our Wellness Hotel\n\nExperience Wellness in the Front row seat in the Hohe Tauern National Park\n\nThe panoramic views of the Hohe Tauern National Park are fascinating and breathtaking. ", "Here I want to experience quiet, here I’m free and secure. ", "Rest, warmth, water, Christine's nature, healing hands, that’s what I want!", "\n\n• Beautiful views from the ‘Vital Alm’\n\nWellness in the Land hotel ‘gut Sonnberghof’.", "\n\nThe \"vitalalm\" is pleasantly quiet and comfortably warm, aromatically scented and relaxing. ", "Here, too, the view - from the quiet meadow or the snow-covered mountains of the National Park Hohe Tauern in Salzburgerland and around the Sonnberghof it is a dream.", "\n\nRelax & rejuvenate in our wellness hotel\n\nRELAXATION ROOMOur circular relaxation room inspired us to christen the new wellness area \"Vital Alm\". ", "The beautiful views of the pastures and the energy flowing round design guarantee relaxation. ", "Here, chat with friends, relax after a vitalising sauna or enjoy your day dreams immersed in the views of the mountains all around.", "\n\nSaunas & steam baths\n\n‘PINZGAUER’ SAUNA\n\nThe oldest and most well-known saunas: The classic sauna created by the Finns can be heated to approx. ", "90 ° C with relatively low humidity. ", "Let yourself be pampered by the smell of the natural, native wood from the mountains. ", "Natural flavor infusions help you to achieve complete relaxation." ]

{ "pile_set_name": "Pile-CC" }

[ 0.0006585549563169479, 0.0006624230300076306, 0.0006961334147490561, 0.0006383543368428946, 0.0006073582917451859, 0.0007675462402403355, 0.000696156348567456, 0.0005221262690611184, 0.001034882734529674, 0.0007406636723317206, 0.000640429905615747, 0.004457377828657627, 0.0005321317003108561 ]

[ "// Copyright 2009 The Go Authors. ", "All rights reserved.", "\n// Use of this source code is governed by a BSD-style\n// license that can be found in the LICENSE file.", "\n\n// +build aix darwin dragonfly freebsd linux netbsd openbsd solaris\n\npackage unix\n\nimport (\n\t\"bytes\"\n\t\"sort\"\n\t\"sync\"\n\t\"syscall\"\n\t\"unsafe\"\n)\n\nvar (\n\tStdin = 0\n\tStdout = 1\n\tStderr = 2\n)\n\n// Do the interface allocations only once for common\n// Errno values.", "\nvar (\n\terrEAGAIN error = syscall.", "EAGAIN\n\terrEINVAL error = syscall.", "EINVAL\n\terrENOENT error = syscall.", "ENOENT\n)\n\nvar (\n\tsignalNameMapOnce sync.", "Once\n\tsignalNameMap map[string]syscall.", "Signal\n)\n\n// errnoErr returns common boxed Errno values, to prevent\n// allocations at runtime.", "\nfunc errnoErr(e syscall.", "Errno) error {\n\tswitch e {\n\tcase 0:\n\t\treturn nil\n\tcase EAGAIN:\n\t\treturn errEAGAIN\n\tcase EINVAL:\n\t\treturn errEINVAL\n\tcase ENOENT:\n\t\treturn errENOENT\n\t}\n\treturn e\n}\n\n// ErrnoName returns the error name for error number e.\nfunc ErrnoName(e syscall.", "Errno) string {\n\ti := sort.", "Search(len(errorList), func(i int) bool {\n\t\treturn errorList[i].num >= e\n\t})\n\tif i < len(errorList) && errorList[i].num == e {\n\t\treturn errorList[i].name\n\t}\n\treturn \"\"\n}\n\n// SignalName returns the signal name for signal number s.\nfunc SignalName(s syscall.", "Signal) string {\n\ti := sort.", "Search(len(signalList), func(i int) bool {\n\t\treturn signalList[i].num >= s\n\t})\n\tif i < len(signalList) && signalList[i].num == s {\n\t\treturn signalList[i].name\n\t}\n\treturn \"\"\n}\n\n// SignalNum returns the syscall.", "Signal for signal named s,\n// or 0 if a signal with such name is not found.", "\n// The signal name should start with \"SIG\".", "\nfunc SignalNum(s string) syscall.", "Signal {\n\tsignalNameMapOnce.", "Do(func() {\n\t\tsignalNameMap = make(map[string]syscall.", "Signal)\n\t\tfor _, signal := range signalList {\n\t\t\tsignalNameMap[signal.name] = signal.num\n\t\t}\n\t})\n\treturn signalNameMap[s]\n}\n\n// clen returns the index of the first NULL byte in n or len(n) if n contains no NULL byte.", "\nfunc clen(n []byte) int {\n\ti := bytes.", "IndexByte(n, 0)\n\tif i == -1 {\n\t\ti = len(n)\n\t}\n\treturn i\n}\n\n// Mmap manager, for use by operating system-specific implementations.", "\n\ntype mmapper struct {\n\tsync.", "Mutex\n\tactive map[*byte][]byte // active mappings; key is last byte in mapping\n\tmmap func(addr, length uintptr, prot, flags, fd int, offset int64) (uintptr, error)\n\tmunmap func(addr uintptr, length uintptr) error\n}\n\nfunc (m *mmapper) Mmap(fd int, offset int64, length int, prot int, flags int) (data []byte, err error) {\n\tif length <= 0 {\n\t\treturn nil, EINVAL\n\t}\n\n\t// Map the requested memory.", "\n\taddr, errno := m.mmap(0, uintptr(length), prot, flags, fd, offset)\n\tif errno !", "= nil {\n\t\treturn nil, errno\n\t}\n\n\t// Slice memory layout\n\tvar sl = struct {\n\t\taddr uintptr\n\t\tlen int\n\t\tcap int\n\t}{addr, length, length}\n\n\t// Use unsafe to turn sl into a []byte.", "\n\tb := *(*[]byte)(unsafe.", "Pointer(&sl))\n\n\t// Register mapping in m and return it.", "\n\tp := &b[cap(b)-1]\n\tm.Lock()\n\tdefer m.Unlock()\n\tm.active[p] = b\n\treturn b, nil\n}\n\nfunc (m *mmapper) Munmap(data []byte) (err error) {\n\tif len(data) == 0 || len(data) !", "= cap(data) {\n\t\treturn EINVAL\n\t}\n\n\t// Find the base of the mapping.", "\n\tp := &data[cap(data)-1]\n\tm.Lock()\n\tdefer m.Unlock()\n\tb := m.active[p]\n\tif b == nil || &b[0] !", "= &data[0] {\n\t\treturn EINVAL\n\t}\n\n\t// Unmap the memory and update m.\n\tif errno := m.munmap(uintptr(unsafe.", "Pointer(&b[0])), uintptr(len(b))); errno !", "= nil {\n\t\treturn errno\n\t}\n\tdelete(m.active, p)\n\treturn nil\n}\n\nfunc Read(fd int, p []byte) (n int, err error) {\n\tn, err = read(fd, p)\n\tif raceenabled {\n\t\tif n > 0 {\n\t\t\traceWriteRange(unsafe.", "Pointer(&p[0]), n)\n\t\t}\n\t\tif err == nil {\n\t\t\traceAcquire(unsafe.", "Pointer(&ioSync))\n\t\t}\n\t}\n\treturn\n}\n\nfunc Write(fd int, p []byte) (n int, err error) {\n\tif raceenabled {\n\t\traceReleaseMerge(unsafe.", "Pointer(&ioSync))\n\t}\n\tn, err = write(fd, p)\n\tif raceenabled && n > 0 {\n\t\traceReadRange(unsafe.", "Pointer(&p[0]), n)\n\t}\n\treturn\n}\n\n// For testing: clients can set this flag to force\n// creation of IPv6 sockets to return EAFNOSUPPORT.", "\nvar SocketDisableIPv6 bool\n\n// Sockaddr represents a socket address.", "\ntype Sockaddr interface {\n\tsockaddr() (ptr unsafe.", "Pointer, len _Socklen, err error) // lowercase; only we can define Sockaddrs\n}\n\n// SockaddrInet4 implements the Sockaddr interface for AF_INET type sockets.", "\ntype SockaddrInet4 struct {\n\tPort int\n\tAddr [4]byte\n\traw RawSockaddrInet4\n}\n\n// SockaddrInet6 implements the Sockaddr interface for AF_INET6 type sockets.", "\ntype SockaddrInet6 struct {\n\tPort int\n\tZoneId uint32\n\tAddr [16]byte\n\traw RawSockaddrInet6\n}\n\n// SockaddrUnix implements the Sockaddr interface for AF_UNIX type sockets.", "\ntype SockaddrUnix struct {\n\tName string\n\traw RawSockaddrUnix\n}\n\nfunc Bind(fd int, sa Sockaddr) (err error) {\n\tptr, n, err := sa.sockaddr()\n\tif err !", "= nil {\n\t\treturn err\n\t}\n\treturn bind(fd, ptr, n)\n}\n\nfunc Connect(fd int, sa Sockaddr) (err error) {\n\tptr, n, err := sa.sockaddr()\n\tif err !", "= nil {\n\t\treturn err\n\t}\n\treturn connect(fd, ptr, n)\n}\n\nfunc Getpeername(fd int) (sa Sockaddr, err error) {\n\tvar rsa RawSockaddrAny\n\tvar len _Socklen = SizeofSockaddrAny\n\tif err = getpeername(fd, &rsa, &len); err !", "= nil {\n\t\treturn\n\t}\n\treturn anyToSockaddr(fd, &rsa)\n}\n\nfunc GetsockoptByte(fd, level, opt int) (value byte, err error) {\n\tvar n byte\n\tvallen := _Socklen(1)\n\terr = getsockopt(fd, level, opt, unsafe.", "Pointer(&n), &vallen)\n\treturn n, err\n}\n\nfunc GetsockoptInt(fd, level, opt int) (value int, err error) {\n\tvar n int32\n\tvallen := _Socklen(4)\n\terr = getsockopt(fd, level, opt, unsafe.", "Pointer(&n), &vallen)\n\treturn int(n), err\n}\n\nfunc GetsockoptInet4Addr(fd, level, opt int) (value [4]byte, err error) {\n\tvallen := _Socklen(4)\n\terr = getsockopt(fd, level, opt, unsafe.", "Pointer(&value[0]), &vallen)\n\treturn value, err\n}\n\nfunc GetsockoptIPMreq(fd, level, opt int) (*IPMreq, error) {\n\tvar value IPMreq\n\tvallen := _Socklen(SizeofIPMreq)\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&value), &vallen)\n\treturn &value, err\n}\n\nfunc GetsockoptIPv6Mreq(fd, level, opt int) (*IPv6Mreq, error) {\n\tvar value IPv6Mreq\n\tvallen := _Socklen(SizeofIPv6Mreq)\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&value), &vallen)\n\treturn &value, err\n}\n\nfunc GetsockoptIPv6MTUInfo(fd, level, opt int) (*IPv6MTUInfo, error) {\n\tvar value IPv6MTUInfo\n\tvallen := _Socklen(SizeofIPv6MTUInfo)\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&value), &vallen)\n\treturn &value, err\n}\n\nfunc GetsockoptICMPv6Filter(fd, level, opt int) (*ICMPv6Filter, error) {\n\tvar value ICMPv6Filter\n\tvallen := _Socklen(SizeofICMPv6Filter)\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&value), &vallen)\n\treturn &value, err\n}\n\nfunc GetsockoptLinger(fd, level, opt int) (*Linger, error) {\n\tvar linger Linger\n\tvallen := _Socklen(SizeofLinger)\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&linger), &vallen)\n\treturn &linger, err\n}\n\nfunc GetsockoptTimeval(fd, level, opt int) (*Timeval, error) {\n\tvar tv Timeval\n\tvallen := _Socklen(unsafe.", "Sizeof(tv))\n\terr := getsockopt(fd, level, opt, unsafe.", "Pointer(&tv), &vallen)\n\treturn &tv, err\n}\n\nfunc GetsockoptUint64(fd, level, opt int) (value uint64, err error) {\n\tvar n uint64\n\tvallen := _Socklen(8)\n\terr = getsockopt(fd, level, opt, unsafe.", "Pointer(&n), &vallen)\n\treturn n, err\n}\n\nfunc Recvfrom(fd int, p []byte, flags int) (n int, from Sockaddr, err error) {\n\tvar rsa RawSockaddrAny\n\tvar len _Socklen = SizeofSockaddrAny\n\tif n, err = recvfrom(fd, p, flags, &rsa, &len); err !", "= nil {\n\t\treturn\n\t}\n\tif rsa.", "Addr.", "Family !", "= AF_UNSPEC {\n\t\tfrom, err = anyToSockaddr(fd, &rsa)\n\t}\n\treturn\n}\n\nfunc Sendto(fd int, p []byte, flags int, to Sockaddr) (err error) {\n\tptr, n, err := to.sockaddr()\n\tif err !", "= nil {\n\t\treturn err\n\t}\n\treturn sendto(fd, p, flags, ptr, n)\n}\n\nfunc SetsockoptByte(fd, level, opt int, value byte) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(&value), 1)\n}\n\nfunc SetsockoptInt(fd, level, opt int, value int) (err error) {\n\tvar n = int32(value)\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(&n), 4)\n}\n\nfunc SetsockoptInet4Addr(fd, level, opt int, value [4]byte) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(&value[0]), 4)\n}\n\nfunc SetsockoptIPMreq(fd, level, opt int, mreq *IPMreq) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(mreq), SizeofIPMreq)\n}\n\nfunc SetsockoptIPv6Mreq(fd, level, opt int, mreq *IPv6Mreq) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(mreq), SizeofIPv6Mreq)\n}\n\nfunc SetsockoptICMPv6Filter(fd, level, opt int, filter *ICMPv6Filter) error {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(filter), SizeofICMPv6Filter)\n}\n\nfunc SetsockoptLinger(fd, level, opt int, l *Linger) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(l), SizeofLinger)\n}\n\nfunc SetsockoptString(fd, level, opt int, s string) (err error) {\n\tvar p unsafe.", "Pointer\n\tif len(s) > 0 {\n\t\tp = unsafe.", "Pointer(&[]byte(s)[0])\n\t}\n\treturn setsockopt(fd, level, opt, p, uintptr(len(s)))\n}\n\nfunc SetsockoptTimeval(fd, level, opt int, tv *Timeval) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(tv), unsafe.", "Sizeof(*tv))\n}\n\nfunc SetsockoptUint64(fd, level, opt int, value uint64) (err error) {\n\treturn setsockopt(fd, level, opt, unsafe.", "Pointer(&value), 8)\n}\n\nfunc Socket(domain, typ, proto int) (fd int, err error) {\n\tif domain == AF_INET6 && SocketDisableIPv6 {\n\t\treturn -1, EAFNOSUPPORT\n\t}\n\tfd, err = socket(domain, typ, proto)\n\treturn\n}\n\nfunc Socketpair(domain, typ, proto int) (fd [2]int, err error) {\n\tvar fdx [2]int32\n\terr = socketpair(domain, typ, proto, &fdx)\n\tif err == nil {\n\t\tfd[0] = int(fdx[0])\n\t\tfd[1] = int(fdx[1])\n\t}\n\treturn\n}\n\nvar ioSync int64\n\nfunc CloseOnExec(fd int) { fcntl(fd, F_SETFD, FD_CLOEXEC) }\n\nfunc SetNonblock(fd int, nonblocking bool) (err error) {\n\tflag, err := fcntl(fd, F_GETFL, 0)\n\tif err !", "= nil {\n\t\treturn err\n\t}\n\tif nonblocking {\n\t\tflag |= O_NONBLOCK\n\t} else {\n\t\tflag &= ^O_NONBLOCK\n\t}\n\t_, err = fcntl(fd, F_SETFL, flag)\n\treturn err\n}\n\n// Exec calls execve(2), which replaces the calling executable in the process\n// tree. ", "argv0 should be the full path to an executable (\"/bin/ls\") and the\n// executable name should also be the first argument in argv ([\"ls\", \"-l\"]).", "\n// envv are the environment variables that should be passed to the new\n// process ([\"USER=go\", \"PWD=/tmp\"]).", "\nfunc Exec(argv0 string, argv []string, envv []string) error {\n\treturn syscall.", "Exec(argv0, argv, envv)\n}\n\n// Lutimes sets the access and modification times tv on path. ", "If path refers to\n// a symlink, it is not dereferenced and the timestamps are set on the symlink.", "\n// If tv is nil, the access and modification times are set to the current time.", "\n// Otherwise tv must contain exactly 2 elements, with access time as the first\n// element and modification time as the second element.", "\nfunc Lutimes(path string, tv []Timeval) error {\n\tif tv == nil {\n\t\treturn UtimesNanoAt(AT_FDCWD, path, nil, AT_SYMLINK_NOFOLLOW)\n\t}\n\tif len(tv) !", "= 2 {\n\t\treturn EINVAL\n\t}\n\tts := []Timespec{\n\t\tNsecToTimespec(TimevalToNsec(tv[0])),\n\t\tNsecToTimespec(TimevalToNsec(tv[1])),\n\t}\n\treturn UtimesNanoAt(AT_FDCWD, path, ts, AT_SYMLINK_NOFOLLOW)\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Alastair Martin\n\nAlastair Bradley Martin (March 11, 1915 – January 12, 2010) was a U.S. National Championships title winner, Tennis Hall of Fame inductee, and president of the United States Lawn Tennis Association. ", "The New York Times attributes Martin with helping to \"forge the modern era of the Grand Slam-style game.\"", "\n\nMartin graduated from Princeton in 1938. ", "Martin was also an art collector and the holder of the Guennol Collection.", "\n\nReferences\n\nExternal links\nInternational Tennis Hall of Fame\n The Guennol collection of Mr. and Mrs. Alastair B. Martin, a fully digitized exhibition catalog from The Metropolitan Museum of Art Libraries\n\nCategory:1915 births\nCategory:2010 deaths\nCategory:American male tennis players\nCategory:Princeton Tigers men's tennis players\nCategory:International Tennis Hall of Fame inductees" ]

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

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[ "Fox News' host Sean Hannity defended former National Security Advisor Michael Flynn Thursday and advised him to withdraw his plea and \"fight.\"", "\n\n\"My advice to General Flynn is this: Get your new lawyers, move forward with your legal team. ", "Withdraw that plea and fight this in court. ", "You do not deserve the setup that was Comey and McCabe. ", "That is a national, despicable, disgusting disgrace what they did to him,\" Hannity said on his television show.", "\n\nDOJ DOESN'T NEED TO PROVIDE TRANSCRIPT OF KEY FLYNN PHONE CALL AFTER ALL, JUDGE RULES\n\nAccording to a motion filed in D.C. federal court on Thursday, Flynn is ending his relationship with the law firm Covington & Burling, and has already hired new legal representation.", "\n\nFlynn pleaded guilty to providing false statements to the FBI during a January 2017 interview. ", "He admitted to lying about his communications with Russian ambassador Sergey Kislyak in December 2016.", "\n\nFlynn has been cooperating for months with former Special Counsel Robert Mueller and federal prosecutors, and this move could signal he may be contesting his upcoming sentencing -- and perhaps may wish to change his plea.", "\n\nHannity contends that Flynn's plea \"was the result of a perjury trap\" laid out by Mueller, former FBI director James Comey and former FBI deputy director Andrew McCabe.", "\n\nThe host, in particular, went after Comey.", "\n\n\"James Comey bragged about how he would do something he'd never do in the Obama administration or the Bush administration. ", "And he's boasting about setting up a man who served this country for 33 years and put his life on the line in wartime,\" Hannity said, referring to Comey's comments to MSNBC's Nicole Wallace where he admitted he sent agents to the White House while they were unprepared.", "\n\n\"Something I probably wouldn't have done or maybe gotten away within a more organized investigation, a more organized administration in the George W. Bush administration for example or the Obama administration,\" Comey said December of last year. \"", "In both those administrations, there was a process. ", "And so if the FBI wanted to send agents into the White House itself to interview a senior official you would work through the White House counsel and there would be discussions and approvals and who would be there. ", "And I thought it's early enough, let's just send a couple of guys over.\"", "\n\nCLICK HERE TO GET THE FOX NEWS APP\n\nHannity reacting to those comments called out Comey for his treatment of Flynn.", "\n\n\"So you told him not to get a lawyer. ", "Then you set him up. ", "Then you brag about setting him up... What a jackass! ", "Who treats a 33-year veteran like this? ", "That's how we treat American heroes, we set them up we tell them not to have lawyers ... We pretty much say it's not an investigation and brag about it?\" ", "Hannity said." ]

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[ "Mechanisms of beta-lactam resistance in anaerobic bacteria.", "\nThe known mechanisms of beta-lactam resistance in anaerobic bacteria involve production of beta-lactamases, alteration of penicillin-binding proteins, and blocking of the penetration of beta-lactams through the outer membranes. ", "The most important factor in beta-lactam resistance is the production of beta-lactamase. ", "beta-Lactamases in various Bacteroides, Fusobacterium, and Clostridium species have been described. ", "beta-Lactam resistance in Bacteroides fragilis is most commonly mediated by the production of beta-lactamase, primarily of the cephalosporinase type. ", "Studies have also shown that B. fragilis can produce a penicillinase that inactivates piperacillin and carbenicillin. ", "Enzymes that inactivate cefoxitin and imipenem have also been found in B. fragilis. ", "The nonfragilis Bacteroides species produce beta-lactamases mainly of the penicillinase type. ", "Recently a penicillinase from Fusobacterium nucleatum has been characterized. ", "Among the clostridia, Clostridium butyricum, clostridium clostridiiforme and Clostridium ramosum have been shown to produce penicillinases." ]

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[ "Propelled by rocket fuel, ego and tunnel vision, Eugene Cernan was the last man to walk on the moon. ", "Now a new film tells his amazing story, from the crash that charred his helmet to the ‘spacewalk from hell’\n\nEugene Cernan has felt the white heat of re-entry three times. “", "The landing,” says the astronaut, understandably animated by the memory, “is like being immersed in a sheet of fire, a comet, a shooting star.” ", "Cernan, alongside crewmates Thomas Stafford and John Young, has also travelled faster than any human being in history: Apollo 10 at one point reached 24,791mph, earning it a mention in the Guinness Book of Records.", "\n\nCernan is talking about The Last Man on the Moon, a new documentary that gives the naturally reticent astronaut, now 82, a chance to tell his story. ", "The bare bones are thus: born in Chicago in 1934 to a Czech mother and Slovak father, he became a naval aviator before being selected by Nasa for astronaut training. ", "He went on to pilot Gemini 9A in June 1966 and Apollo 10 in May 1969, before being selected as commander of Apollo 17, which carried out the most recent moon landing in December 1972. ", "It was on this voyage that Cernan, the final astronaut to reboard the lunar module, became the 12th – and last – man to walk on the moon.", "\n\nFacebook Twitter Pinterest ‘If you think going to the moon is hard, try staying at home’ … Cernan with his family\n\nHe is, as Mark Craig’s film shows, a survivor of that great adventure: neither becoming capsized by it, as Buzz Aldrin was for a while, using alcohol; nor retreating from it, as the reclusive Neil Armstrong did. ", "Like many astronauts, he retains a quiet authority, a military matter-of-factness that manifests itself in certain recurring phrases, not least: “We were there to do a job.”", "\n\n\n\nOccasionally, though, this reticence gives way to a sense of wonder. ", "Some of the best moments in the documentary come when the still-dramatic images of Cernan’s missions are merged with his evocative reflections. “", "You can hear yourself breathe inside the suit,” he says of the long moments of stillness and expectation just before the launch of Apollo 10. “", "Everything intensifies – but the clock keeps going.”", "\n\nThe ground rumbled and the fish jumped out of the lake\n\nCernan’s first words in The Last Man on the Moon are: “I am the luckiest human being in the world.” ", "But as the film shows, he had his share of bad luck. ", "His first spacewalk from Gemini 9, dogged by technical difficulties, was surely an inspiration for Gravity. ", "Not given to overstatement, he later described it as “the spacewalk from hell”. ", "And although he had successfully carried out more than 200 landings as a navy pilot, he crashed a helicopter in 1971, just two weeks before Apollo 14 was launched, a mission for which he had been chosen as back-up flight commander.", "\n\nHe still has the helmet, most of which is charcoal black. “", "How can anyone do something so dumb?” ", "he says, still angry with himself. ", "Cernan thought he had “screwed up” his chance of ever being considered for another lunar mission, but a few weeks later he got a call saying: “The job’s still yours if you want it.” ", "The following year, Cernan led the final mission.", "\n\n“The ground rumbled and all the fish jumped out of the lake,” remembers his then wife, Barbara, of the night launch of Apollo 17. ", "She was one of 500,000 people who watched it from Kennedy Space Center, in Florida, while people as far away as Miami – 225 miles south – saw a red streak in the sky. “", "It was my personal moment of reckoning,” says Cernan. “", "This is what I had asked for.”", "\n\nHe and Harrison Schmitt spent three days on the moon’s surface. “", "People say, ‘What was it really like up there?’ ", "Or they’ll ask, ‘Did you find God?’ ", "What I remember was that I felt like I had shaped up.” ", "Was he able to have a break and at least try to take in the wonder of it all? “", "Well, you couldn’t not. ", "We saw some dazzling, extraordinary things, and you had to take time to appreciate them. ", "I mean, not too many people get to see an Earth-rise.” ", "He pauses for a long time. “", "When I was boarding the lunar module for the last time and I looked at my footprints, I knew I wouldn’t be coming back. ", "That was the one moment when I wanted to stop time.”", "\n\nFacebook Twitter Pinterest One last fitting … Cernan in training\n\nUnlike the first man to walk on the moon, the late Neil Armstrong, with whom he became friends, Cernan seems to have relished the celebrity the moon landing bestowed on him. ", "He still makes public appearances. “", "I enjoy meeting people,” he tells me, his voice still strong. “", "I feel like I’m thanking them for that faith they had in me.”", "\n\nLast Man on the Moon recalls US era of courage to do the impossible Read more\n\nThe documentary shows the human cost of that celebrity, however, particularly for his first wife, Barbara, who says: “If you think going to the moon is hard, try staying at home.” ", "Their marriage did not survive. ", "The Apollo astronauts were an elite group of alpha males, to which family often took second place. ", "Bound by the discipline and dedication of their calling, but also by their shared sense of destiny, they developed egos to match. “", "We were so tunnel-vision about going to the moon,” says Cernan regretfully in the film, “that we never had time to get off that big white horse we were riding until it was too late. ", "But sooner or later, you’ve got to come to grips with who you are and what’s important in life.”", "\n\nCernan now seems to have done that. ", "Does he keep in touch with his fellow astronauts? “", "Well, you don’t become best friends for the rest of your life in the way you might expect,” he says. “", "That was certainly not the case with my flights anyway.” ", "But there is one thing he is clear about: “All I ever wanted to do was fly. ", "For a long time, there was nothing else.”", "\n\n• The Last Man on the Moon is out now in the US and opens 8 April in the UK.", "\n\n\n\n" ]

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[ "2003 Quebec general election\n\nThe 2003 Quebec general election was held on April 14, 2003, to elect members of the National Assembly of Quebec (Canada). ", "The Parti libéral du Québec (PLQ), led by Jean Charest, defeated the incumbent Parti Québécois, led by Premier Bernard Landry.", "\n\nIn Champlain there was a tie between PQ candidate Noëlla Champagne and Liberal candidate Pierre-A. Brouillette; although the initial tally was 11,867 to 11,859, a judicial recount produced a tally of 11,852 each. ", "A new election was held on May 20 and was won by Champagne by a margin of 642 votes.", "\n\nUnfolding\n\nIn 2002, the Parti Québécois (PQ) government had been in power for two mandates. ", "It was seen as worn-out by some, and its poll numbers fell sharply. ", "It placed third at its lowest point. ", "An important part of its support was going to the Action Démocratique du Québec (ADQ) and its young leader, Mario Dumont. ", "Some PQ supporters had left for the Liberal party.", "\n\nLandry, leader of the PQ, undertook a revitalization of the party and its image. ", "As the ideas of the conservative nature of ADQ's platform became more apparent, that party's popularity declined. ", "Social democratic measures taken by the PQ government, like the passing of the \"Law against poverty\" helped improve the PQ's standing in the public opinion polls. ", "PLQ leader Jean Charest initially continued to be unpopular with voters.", "\n\nThe 2003 election happened against the backdrop of the war in Iraq. ", "The battles of that war took place during the first half of the campaign, diverting the attention of the media and the population. ", "Landry became known for his custom of wearing the white ribbon (which in 2003 was worn by people in favour of peace). ", "This custom was shortly followed by the two other main party leaders, Charest and Dumont. ", "Landry was the most outspoken critic of the war. ", "The other two were more discreet on the matter. ", "Charest once stated that it was an opportunity to reaffirm his \"belief in peace\". ", "Dumont acted in a similar way, while also addressing criticism to Landry, saying that Quebecers should refrain from criticizing Americans too harshly since Americans were historical friends of Quebecers.", "\n\nThe desire for change was considered an important factor of the campaign (see \"Change\", below). ", "However, while reminding voters that the fundamental change was at the core of its primary ideal, sovereignty, the PQ focused its message and publicity not on change, but on stability. ", "Its campaign slogan emphasized this (see the Campaign slogans below). ", "Landry also tried to portray the vote as being a choice between the left wing PQ and two parties of the right. ", "The PLQ portrayed itself as centrist. ", "The PLQ produced dynamic ads and material, and released a new, younger logo. ", "The ADQ put forward its young, underdog leader, and denied being too much to the right. ", "It first broadcast a negative advertisement (a bleak television spot speaking of deaths in the hospitals) that backfired substantially, with criticism from opponents and citizens. ", "It shortly released a brighter, more positive advertising.", "\n\nDespite the PQ's recovery of support, Charest appeared as a viable alternative for people in desire of change, especially during the Leaders' Debate. ", "Also, the Parizeau Affair sparked by Charest is said to have harmed Landry's campaign up to election day. ", "The PQ lead in the public opinion polls vanished by mid-campaign.", "\n\nThe Parti Libéral won the election, while Parti Québécois won a respectable number of seats. ", "The ADQ won four seats, which was a considerable improvement from previous general elections. ", "It was nonetheless a disappointment for the party since it had five sitting members as a result of by-election victories in the previous year. ", "It had also had a high standing in the polls of that same year. ", " This was the first general election for the new left-wing Union des forces progressistes.", "\n\nA documentary about Bernard Landry's point of view of the campaign was released in 2003 called À Hauteur d'homme. ", "It was directed by Jean-Claude Labrecque.", "\n\nIssues\n\nHealth care\nJean Charest and the PLQ focused their campaign upon the issue of health care and reducing waiting lists. ", "The other major parties criticized Charest for planning to invest only in health care and education, while freezing other budgets. ", "Landry argued that money for health care would be available when the fiscal imbalance was solved by sovereignty. ", "He vowed to fight for money from Ottawa until then, as he had done earlier that year (see the \"Fiscal Imbalance\", below). ", "Charest portrayed Landry as putting sovereignty ahead of health care, and presented his party as the one that would make health care its first priority. ", "He also accused Landry's government of using waiting lists as an administration procedure for hospitals.", "\n\nChange\nThe desire for change was considered by the media to be a major deciding factor of the vote. ", "The media were criticized by the PQ and some citizens as \"wanting change for the sake of change\", since the government had ended its term with an economy doing well and high satisfaction polls for an outgoing administration. ", "Landry reminded voters that, while voting for his party did not change the government right away, the first ideal of the PQ, sovereignty, was \"the greatest of changes\". ", "At the Leaders' Debate, Charest told viewers that those wanting change should vote for the PLQ since \"A vote for the ADQ is a vote for the PQ\". ", "At the time, the ADQ was considered to be too low in the polls to be a potential victor. ", "Charest's reminder of the spoiler effect is said to have been partly responsible for his victory on election day. ", "The results on election day appear to have demonstrated the voters' desire for change.", "\n\nIncome tax\nCharest presented a plan of major reduction of income tax, which Landry opposed. ", "Quebec's income taxes are the highest in North America, but its social programs are also relatively generous, and the gap between rich and poor is the lowest of the North American continent. ", "The ADQ presented a flat tax plan in 2002. ", "This proved to be highly unpopular, and contributed to the image of the party as being too conservative. ", "This plan, in its pure form, was dropped in the beginning of 2003. ", "The ADQ claimed that, after further examination, the Quebec government did not have the resources to implement it. ", "This, again, hurt the party further by giving it the image of flip flopping.", "\n\nState size and intervention\nThe PQ government was criticized by the two other major parties for being too interventionist, maintaining an overly large government, and for practising statism. ", "Dumont spoke of Landry and the PQ's \"Social bureaucracy\", a pun on the Social democracy the PQ defends. ", "Landry responded to Charest and Dumont that \"Quebecers do not want less state, they want better state\". ", " Dumont had previously proposed a drastic reduction in the size of the civil service, but this was also softened before the campaign.", "\n\nFamily-work conciliation\nThe conciliation famille-travail became an important issue of the campaign as a result of Landry's \"Four day work-week\" plan. ", "This proposal would have required Quebec employers to offer the option of a four-day work week to parents. ", "This was presented by the PQ as a way to enhance family life, lower the stress on parents, and of counteracting the fall in Quebec's birthrate since the Quiet Revolution. ", "The plan was attacked by the PLQ and ADQ as being \"improvised\" since it was only presented near the beginning of the election. ", "It attracted some interest and support from voters, enough for Charest to declare, days before voting day, that he could consider implementing a four-day week, although the PLQ has not mentioned this since the election.", "\n\nFiscal imbalance\nThe theory of a fiscal imbalance between Ottawa and Quebec City was maintained and denounced by all major parties. ", "Charest argued that the co-operative approach of a federalist party like the PLQ would be more effective solving the problem. ", "As proof that the PQ would be able to solve the fiscal imbalance, Landry pointed to his success of early 2003, when he, along with the English Canadian Premiers, managed to come to an agreement with Prime Minister of Canada Jean Chrétien for more money to finance health care. ", "He promised to continue the \"battle\" to solve the imbalance until independence is achieved.", "\n\nCity mergers\nThe PQ government, during the premiership of Landry's predecessor Lucien Bouchard, had merged the major cities of Quebec. ", "The government argued that the mergers would allow a better division of the wealth and responsibilities between richer suburban communities and poorer parts of the main cities. ", "The mergers occurred despite widespread opposition in some municipalities. ", "Many Quebecers were still disgruntled, especially in wealthier and anglophone communities. ", "The PLQ proposed to allow referendums on de-amalgamation in communities where there was sufficient support. ", "The PQ and the ADQ strongly opposed the idea.", "\n\nSovereignty and autonomy\nWhile the PQ continued to promote sovereignty for Quebec with its usual arguments (dignity, culture, globalization, etc.), ", "it was also presented by the PQ as a way to solve the fiscal imbalance problem. ", "The ADQ made great efforts to avoid taking a position on the subject of independence in order to attract both sides of the National Question spectrum. ", "The ADQ positioned itself as a \"third way\" to Quebecers between what Dumont called \"radical separation\" and \"knelt down federalism\". ", "The ADQ had worked in favour of sovereignty during the 1995 Quebec referendum, but had been equivocal on the subject since then.", "\n\nThe PLQ criticized the PQ for using the politics of confrontation because of its sovereignty position, and argued that a PLQ government would restore Quebec's \"leadership role\" in the federation. ", "Landry promised a third referendum on independence \"in 1000 days\", confirming the plan he had set out in the Declaration of Gatineau, with support for independence running very low and support for a referendum running even lower in opinion polls; this did not prove to be a popular position. ", "An argument of Landry for this timetable was that he wanted Quebec to be present at the Summit of the Americas in Buenos Aires in 2005. ", "Representation for Quebec had been denied by Ottawa at the previous summit held in Quebec City, an act that angered many Quebecers. ", "At the same time, Landry kept the door opened to federalist support for the PQ and stated that he would only hold a referendum if he had the \"moral assurance\" of winning it. ", "This lead Charest to accuse him of having a \"hidden agenda\", during the Leaders' Debate.", "\n\nParizeau Affair\nOn the day of the leaders' debate, Charest's advisors gave him an article from the website of the Trois-Rivières newspaper Le Nouvelliste that spoke of past PQ leader Jacques Parizeau restating his controversial remarks about \"money and the ethnic vote\" which he had made in his 1995 referendum concession speech. ", "The truth of the article was later disputed, yet despite the uncertainty surrounding this article, Charest surprised Landry with it during the leaders' debate on live television. ", "This created a new controversy that ran for some days following the debate, and was said to have hurt Landry's campaign. ", "The PQ denounced Charest for launching an \"immoral attack\" on Parizeau's reputation and dignity, saying that the article was incorrect in concluding that he had repeated his comments, but this method of response was not enough to defuse the controversy. ", "The aftermath of the leaders' debate is thoroughly treated in the À Hauteur d'homme documentary, and became known as the Parizeau Affair.", "\n\nDay care\nThe \"five dollar-a-day child care\" program implemented by the PQ government of Lucien Bouchard was one of the most appreciated achievements of the recent PQ administration. ", "Some parents still did not have access to it, however, because of a lack of sufficient places. ", " Landry, who had been Minister of Finance when the plan was implemented, vowed to continue creating more spaces. ", "Charest presented his team as the most capable for this task. ", "He also vowed to keep the price at $5 a day. ", "He broke this promise later that year. ", "See Opposition to the Charest government.", "\n\nPublic debt\nThe Action Démocratique insisted that the Government of Quebec should pay down the public debt. ", "The other major leaders did not see it as a priority.", "\n\nContenders\n\nMajor parties\n\nAction démocratique du Québec\n\nQuebec Liberal Party\n\nParti Québécois\n\nMinor parties\n\nGreen Party of Quebec\n\nBloc Pot\n\nUnion des forces progressistes\n\nCampaign slogans\nAction démocratique du Québec: L'avenir autrement (The future differently)\nQuebec Liberal Party: Nous sommes prêts (We are ready)\nParti Québécois: Restons forts (Let us stay strong)\n\nIncumbent MNAs not running for re-election\n\nOverall Results\nThe overall results were:\n\nResults by riding \nThe results in each riding (electoral division) were:\n\nBas-Saint-Laurent and Gaspésie–Îles-de-la-Madeleine\n\n|-\n|bgcolor=whitesmoke|Bonaventure\n||\n|Nathalie Normandeau 11,975\n|\n|Marc Tétreault 6,313\n|\n|Maurice Anglehart 1,101\n|\n|Michel Goudreau (Green) 542\n||\n|Nathalie Normandeau\n|-\n|bgcolor=whitesmoke|Gaspé\n|\n|Johnny Gérard 8,052\n||\n|Guy Lelièvre 9,033\n|\n|Denis Paradis 1,743\n|\n|Luc-Reno Fournier (Green) 227\n||\n|Guy Lelièvre\n|-\n|bgcolor=whitesmoke|Îles-de-la-Madeleine\n|\n|Simone LeBlanc 3,150\n||\n|Maxime Arseneau 4,606\n|\n|Évé Longuépée 92\n|\n|\n||\n|Maxime Arseneau\n|-\n|bgcolor=whitesmoke|Kamouraska-Témiscouata\n||\n|Claude Béchard 11,266\n|\n|Harold LeBel 6,326\n|\n|Pierre Lévesque 6,504\n|\n|Guy Duguay (Green) 293\nRobert Raymond (Ind.) 238\n||\n|Claude Béchard\n|-\n|bgcolor=whitesmoke|Matane\n||\n|Nancy Charest 7,602\n|\n|Pascal Bérubé 7,569\n|\n|Raynald Bernier 3,005\n|\n|Nelson Gauthier (Ind.) 178\nNestor Turcotte (Ind.) 135\nDavid Lejeune (Green) 124\n||\n|align=center|vacant\n|-\n|bgcolor=whitesmoke|Matapédia\n|\n|Gaston Pelletier 6,339\n||\n|Danielle Doyer 9,197\n|\n|Claude Fortin 4,686\n|\n|\n||\n|Danielle Doyer\n|-\n|bgcolor=whitesmoke|Rimouski\n|\n|Éric Forest 10,817\n||\n|Solange Charest 14,177\n|\n|Stéphane Laforest 4,719 \n|\n|\n||\n|Solange Charest\n|-\n|bgcolor=whitesmoke|Rivière-du-Loup\n|\n|Jacques Morin 5,585\n|\n|Carol Gilbert 4,155\n||\n|Mario Dumont 13,452\n|\n|Julie Morin (Green) 312\n||\n|Mario Dumont\n|-\n|}\n\nSaguenay-Lac-St-Jean, Côte-Nord and Nord-du-Québec\n\n|-\n|bgcolor=whitesmoke|Chicoutimi\n|\n|Jean-Guy Maltais 11,814\n||\n|Stéphane Bédard 14,471\n|\n|Carl Savard 5,841\n|\n|Pierre Dostie (UFP) 670Dominic Tremblay (BP) 314\n||\n|Stéphane Bédard\n|-\n|bgcolor=whitesmoke|Dubuc\n|\n|Johnny Simard 9,723\n||\n|Jacques Côté 9,767\n|\n|Claude Gauthier 5,162\n|\n|Marie Francine Bienvenue (UFP) 457\n||\n|Jacques Côté\n|-\n|bgcolor=whitesmoke|Duplessis\n|\n|Marc Proulx 8,018\n||\n|Lorraine Richard 10,926\n|\n|Steeve Trudel 2,530\n|\n|André Forbes (Ind.) 1,334\n||\n|Normand Duguay\n|-\n|bgcolor=whitesmoke|Jonquière\n||\n|Françoise Gauthier 13,826\n|\n|Myrtha Laflamme 11,386\n|\n|Réjean Laforest 5,216\n|\n|Batiste Foisy (BP) 368Michel Perron (UFP) 330\n||\n|Françoise Gauthier\n|-\n|bgcolor=whitesmoke|Lac-Saint-Jean\n|\n|Benoît Harvey 7,405\n||\n|Stéphan Tremblay 15,200\n|\n|Roger Filion 5,694\n|\n|\n||\n|Stéphan Tremblay\n|-\n|bgcolor=whitesmoke|Réne-Lévesque\n|\n|François Désy 5,215\n||\n|Marjolain Dufour 8,997\n|\n|François Corriveau 7,356\n|\n|Jean-Pierre Brison (Ind.) 449\n||\n|François Corriveau\n|-\n|bgcolor=whitesmoke|Roberval\n||\n|Karl Blackburn 11,930\n|\n|Réjean Lalancette 11,686\n|\n|Bernard Généreaux 6,388\n|\n|Francis Breton (UFP) 453\n||\n|Benoît Laprise\n|-\n|bgcolor=whitesmoke|Ungava\n|\n|Don Bubar 4,258\n||\n|Michel Létourneau 5,744\n|\n|Gloria Trudeau 1,460\n|\n|\n||\n|Michel Létourneau\n|}\n\nCapitale-Nationale\n\n|-\n|bgcolor=whitesmoke|Charlesbourg\n||\n|Éric Mercier 17,169\n|\n|Sylvie Tremblay 9,741\n|\n|Jonatan Julien 10,936\n|\n|Yonnel Bonaventure (Green) 438Simon Carreau (UFP) 329\n||\n|Jean Rochon\n|-\n|-\n|bgcolor=whitesmoke|Charlevoix\n|\n|Denis Lavoie 8,758\n||\n|Rosaire Bertrand 10,131\n|\n|Daniel Bouchard 3,998\n|\n|Éric Tremblay (UFP) 168Gabriel Tremblay (Ind.) 105Phillippe Thivierge (DCQ) 62\n||\n|Rosaire Bertrand\n|-\n|bgcolor=whitesmoke|Chauveau\n||\n|Sarah Perreault 14,774\n|\n|Nathalie Samson 8,506\n|\n|Hélène Napert 12,555\n|\n|Christian Légaré (Ind.) 624Marie-Noëlle Béland (UFP) 387\n||\n|Raymond Brouillet\n|-\n|bgcolor=whitesmoke|Jean-Lesage\n||\n|Michel Després 15,547\n|\n|Robert Caron 9,408\n|\n|Aurel Bélanger 8,912\n|\n|Jean-Yves Desgagnés (Ind.) 714Nicolas Frichot (BP) 390Jean Bédard (M-L) 185\n||\n|Michel Després\n|-\n|bgcolor=whitesmoke|Jean-Talon\n||\n|Margaret Delisle 15,475\n|\n|Daniel-Mercier Gouin 11,999\n|\n|Simon Lauzon 5,149\n|\n|Sacha Calixte (UFP) 515Antonine Yaccarini (Green) 477Sabrina Falardeau (BP) 197Robert Bonenfant (Ind.) 126\n||\n|Margaret Delisle\n|-\n|bgcolor=whitesmoke|La Peltrie\n||\n|France Hamel 16,462\n|\n|Claude Gendreau 8,711\n|\n|Éric Caire 13,421\n|\n|Dany Hamel (Ind.) 586Guillaume Boivin (UFP) 515\n||\n|Michel Côté\n|-\n|bgcolor=whitesmoke|Louis-Hébert\n||\n|Sam Hamad 17,938\n|\n|Line-Sylvie Perron 11,688\n|\n|Guy Laforest 9,505\n|\n|Jean-Pierre Guay (Green) 493Jean-Phillipe Lessard-Beaupré (UFP) 402Pierre Laliberté (BP) 281\n||\n|Paul Bégin\n|-\n|bgcolor=whitesmoke|Montmorency\n||\n|Raymond Bernier 13,708\n|\n|Jean-François Simard 11,226\n|\n|Jean-François Paquet 11,821\n|\n|Magali Paquin (UFP) 517\n||\n|Jean-François Simard\n|-\n|bgcolor=whitesmoke|Portneuf\n||\n|Jean-Pierre Soucy 12,729\n|\n|Roger Bertrand 8,352\n|\n|Deny Lépine 10,781\n|\n|François Paradis-Caron (UFP) 413\n||\n|Roger Bertrand\n|-\n|bgcolor=whitesmoke|Taschereau\n|\n|Michel Beaudoin 11,240\n||\n|Agnès Maltais 12,930\n|\n|Jean-Guy Lemieux 6,537\n|\n|Alain Marcoux (UFP) 1,136Dominic Lapointe (Green) 731Benjamin Kasapoglu (BP) 389Patrice Fortin (Ind.) 102Alain Cyr (Ind.) 95\n||\n|Agnès Maltais\n|-\n|bgcolor=whitesmoke|Vanier\n||\n|Marc Bellemare 16,182\n|\n|Nicole Madore 9,385\n|\n|Normand Morin 11,646\n|\n|Sébastien Bouchard (UFP) 573\n||\n|Diane Barbeau\n|}\n\nMauricie\n\n|-\n|bgcolor=whitesmoke|Champlain (May 20, 2003)\n|\n|Pierre Brouillette 9,431\n||\n|Noëlla Champagne 10,073\n|\n|Rock Laviolette 6,459\n|\n|Lucie Favreau (UFP) 103 Gilles Noel (DCQ) 73\n||\n|Yves Beaumier\n|-\n|bgcolor=whitesmoke|Laviolette\n||\n|Julie Boulet 12,806\n|\n|Patrick Lahaie 7,730\n|\n|Sébastien Proulx 3,453\n|\n|Yves Demers (UFP) 182\nJosée Lafontaine (DCQ) 144\n||\n|Julie Boulet\n|-\n|bgcolor=whitesmoke|Maskinongé\n||\n|Francine Gaudet 13,240\n|\n|Rémy Désilets 12,334\n|\n|Louise-Andrée Garant 9,118\n|\n|\n||\n|Rémy Désilets\n|-\n|-\n|bgcolor=whitesmoke|Saint-Maurice\n|\n|Bob Vallières 8,232\n||\n|Claude Pinard 8,860\n|\n|Luc Arvisais 8,201\n|\n|Kevin Trudel (UFP) 225\n||\n|Claude Pinard\n|-\n|bgcolor=whitesmoke|Trois-Rivières\n||\n|André Gabias 11,034\n|\n|Guy Julien 10,154\n|\n|Jean-Claude Ayotte 5,181\n|\n|Rachel Sauvageau (BP) 274David Lanneville (UFP) 214Marcel Fugère (Ind.) 110Stéphane Robert (DCQ) 76\n||\n|Guy Julien\n|}\n\nChaudière-Appalaches and Centre-du-Québec\n\n|-\n|bgcolor=whitesmoke|Arthabaska\n||\n|Claude Bachand 12,663\n|\n|Danièle Caron 9,657\n|\n|Alain Rayes 11,389\n|\n|François Houle (Green) 379 Katrine Cyr (BP) 353\n||\n|Jacques Baril\n|-\n|bgcolor=whitesmoke|Beauce-Nord\n|\n|Normand Poulin 11,104\n|\n|Aline Carrier 4,160\n||\n|Janvier Grondin 13,275\n|\n|Julie Roy (BP) 223 Richard Fecteau (UFP) 175\n||\n|Normand Poulin\n|-\n|bgcolor=whitesmoke|Beauce-Sud\n||\n|Diane Leblanc 14,170\n|\n|Stéphane Pouliot 5,115\n|\n|Claude Lemieux 12,852\n|\n|Ginette Lewis (UFP) 216\n||\n|Diane Leblanc\n|-\n|bgcolor=whitesmoke|Bellechasse\n||\n|Dominique Vien 9,658\n|\n|Claude Lachance 7,084\n|\n|Serge Carbonneau 8,507\n|\n|Sylvain Castonguay (Green) 314\nMario Ouellette (UFP) 134\n||\n|Claude Lachance\n|-\n|bgcolor=whitesmoke|Chutes-de-la-Chaudière\n|\n|Pauline Houde-Landry 12,601\n|\n|Antoine Dubé 10,007\n||\n|Marc Picard 14,759\n|\n|Jean Bernatchez (UFP) 649\n||\n|Denise Carrier-Perreault\n|-\n|bgcolor=whitesmoke|Drummond\n|\n|Jean Courchesne 13,479\n||\n|Normand Jutras 15,200\n|\n|Patrick Leblanc 7,577\n|\n|Pascal Allard (Ind.) 393 Gilles Martineau (UFP) 301Robert Dufour (DCQ) 199\n||\n|Normand Jutras\n|-\n|bgcolor=whitesmoke|Frontenac\n||\n|Laurent Lessard 11,251\n|\n|Marc Boulianne 7,281\n|\n|Daniel Lamouth 6,888\n|\n|Bruno Vézina (Green) 231 Marie-Josée Vachon (UFP) 145\n||\n|Marc Bouliane\n|-\n|bgcolor=whitesmoke|Johnson\n|\n|Nicole Brouillette 10,700\n||\n|Claude Boucher 12,232\n|\n|Isabelle Marquis 6,612\n|\n|Martin Marois (UFP) 343 Michel Bélanger (DCQ) 224\n||\n|Claude Boucher\n|-\n|bgcolor=whitesmoke|Lévis\n||\n|Carole Théberge 12,891\n|\n|Linda Goupil 12,485\n|\n|Joël Bernier 10,670\n|\n|Madeleine Provencher (UFP) 442\nRichard Larivée (Ind.) 220\n||\n|Linda Goupil\n|-\n|bgcolor=whitesmoke|Lotbinière\n|\n|Monique Drolet-Glazier 8,773\n|\n|Jean-Guy Paré 6,502\n||\n|Sylvie Roy 9,522\n|\n|Marc Allard (Green) 306Étienne Hallé (UFP) 175Paul Biron (DCQ) 150\n||\n|Jean-Guy Paré\n|-\n|bgcolor=whitesmoke|Montmagny-L'Islet\n||\n|Norbert Morin 9,518\n|\n|Louise Soucy 4,683\n|\n|Mario Dolan 8,513\n|\n|Fernand Dorval (UFP) 225\n||\n|Réal Gauvin\n|-\n|bgcolor=whitesmoke|Nicolet-Yamaska\n|\n|Jean Rousseau 8,927\n||\n|Michel Morin 10,783\n|\n|Lise Blanchette 5,899\n|\n|Blak D. Blackburn (BP) 417\nSimonne Lizotte (Ind.) 141\n||\n|Michel Morin\n|-\n|}\n\nEstrie (Eastern Townships)\n\n|-\n|bgcolor=whitesmoke|Mégantic-Compton\n||\n|Daniel Bouchard 11,135\n|\n|Suzanne Durivage 7,347\n|\n|Alain Boisvert 4,901\n|\n|Christian Poulin (UFP) 193 Frank Moller (Equ.) ", "71\n||\n|Madeleine Bélanger\n|-\n|bgcolor=whitesmoke|Orford\n||\n|Pierre Reid 17,314\n|\n|Yvon Bélair 11,037\n|\n|Steve Bourassa 6,145\n|\n|Véronique Grenier (UFP) 498\n||\n|Robert Benoît\n|-\n|bgcolor=whitesmoke|Richmond\n||\n|Yvon Vallières 14,767\n|\n|André Blais 6,149\n|\n|Pierre Hébert 4,899\n|\n|\n||\n|Yvon Vallières\n|-\n|bgcolor=whitesmoke|Saint-François\n||\n|Monique Gagnon-Tremblay 16,562\n|\n|Guillaume Breault-Duncan 9,926\n|\n|Michel-André Samson 4,541\n|\n|Suzanne Thériault (UFP) 314 François Boudreau (BP) 310\n||\n|Monique Gagnon-Tremblay\n|-\n|bgcolor=whitesmoke|Sherbrooke\n||\n|Jean Charest 16,403\n|\n|Marie Malavoy 13,806\n|\n|Peter Downey 4,169\n|\n|Normand Gilbert (UFP) 496 Serge Lachapelle (M-L) 64\n||\n|Jean Charest\n|}\n\nMontérégie\n\n|-\n|bgcolor=whitesmoke|Beauharnois\n|\n|Mario Faubert 13,265\n||\n|Serge Deslières 13,904\n|\n|Michael Betts 3,338\n|\n|Rémi Pelletier (Green) 506\n||\n|Serge Deslières\n|-\n|bgcolor=whitesmoke|Borduas\n|\n|Daniel Doucet 9,981\n||\n|Jean-Pierre Charbonneau 13,840\n|\n|Patricia St-Jacques 5,282\n|\n|Raynald St-Onge (BP) 459\n||\n|Jean-Pierre Charbonneau\n|-\n|bgcolor=whitesmoke|Brome-Missisquoi\n||\n|Pierre Paradis 18,546\n|\n|Lina Le Blanc 8,093\n|\n|Pierre Plante 6,018\n|\n|Simon Gnocchini (UFP) 509 Lionel Albert (Equ.) ", "167\n||\n|Pierre Paradis\n|-\n|bgcolor=whitesmoke|Chambly\n||\n|Diane Legault 17,656\n|\n|Louise Beaudoin 16,857\n|\n|Denis Lavoie 6,935\n|\n|Sébastien Duclos (BP) 744\n||\n|Louise Beaudoin\n|-\n|bgcolor=whitesmoke|Châteauguay\n||\n|Jean-Marc Fournier 20,434\n|\n|Éric Cardinal 13,751\n|\n|Daniel Lapointe 4,399\n|\n|Gilles Lalumière (BP) 547 Guylaine Sirard (UFP) 222 Robert Jason Morgan (Equ.) ", "93\n||\n|Jean-Marc Fournier\n|-\n|bgcolor=whitesmoke|Huntingdon\n||\n|André Chenail 15,512\n|\n|François Boileau 8,302\n|\n|Michel Lavoie 5,261\n|\n|Kenneth Rimmer (BP) 452\n||\n|André Chenail\n|-\n|bgcolor=whitesmoke|Iberville\n||\n|Jean Rioux 12,106\n|\n|Jean-Paul Bergeron 11,185\n|\n|Lucille Méthé 6,731\n|\n|Michel Thiffeault (BP) 376 Benoit Lapointe (Green) 298 Guillaume Tremblay (UFP) 229\n||\n|Jean-Paul Bergeron\n|-\n|bgcolor=whitesmoke|La Pinière\n||\n|Fatima Houda-Pepin 22,474\n|\n|Marcel Lussier 7,934\n|\n|Gérard Lachance 4,026\n|\n|Inti Ortega (BP) 487\n||\n|Fatima Houda-Pepin\n|-\n|bgcolor=whitesmoke|Laporte\n||\n|Michel Audet 18,673\n|\n|Clément Arcand 10,178\n|\n|Judy Fay 3,885\n|\n|Christian Montmarquette (UFP) 489 Patrick Fiset (BP) 487 Mary Bevan-Ouellette (Equ.) ", "106\n||\n|André Bourbeau\n|-\n|bgcolor=whitesmoke|La Prairie\n||\n|Jean Dubuc 15,805\n|\n|Serge Geoffrion 14,868\n|\n|Yves-André Ferland 6,478\n|\n|Marc Bissonnette (BP) 547Danielle Maire (UFP) 229Sylvain Lesage (DCQ) 84\n||\n|Serge Geoffrion\n|-\n|bgcolor=whitesmoke|Marguerite-D'Youville\n||\n|Pierre Moreau 16,368\n|\n|François Beaulne 15,501\n|\n|Luc Pommainville 6,596\n|\n|Yan Lacombe (BP) 550Maxime Babeu (UFP) 536\n||\n|François Beaulne\n|-\n|bgcolor=whitesmoke|Marie-Victorin\n|\n|Jean-Marc Pelletier 9,799\n||\n|Cécile Vermette 12,736\n|\n|Michel Lalonde 4,374\n|\n|Pierre Losier-Côté (BP) 462Marc Lambert (UFP) 452Daniel Tavéra (Ind.) 134\n||\n|Cécile Vermette\n|-\n|bgcolor=whitesmoke|Richelieu\n|\n|Benoît Lefebvre 10,927\n||\n|Sylvain Simard 13,286\n|\n|Micheline Ulrich 3,756\n|\n|Marie-Hélène Charbonneau (BP) 407Nidal Joad (Ind.) 109Steve Ritter (Ind.) 100Florette Villemure-Larochelle (DCQ) 74\n||\n|Sylvain Simard\n|-\n|bgcolor=whitesmoke|Saint-Jean\n||\n|Jean-Pierre Paquin 14,758\n|\n|Roger Paquin 13,423\n|\n|Marc-André Legault 6,856\n|\n|Alexandre Boulerice (UFP) 535Eric Bédard (BP) 462Jean Robert (Ind.) 112Raymond Martin (Ind.) 73\n||\n|Roger Paquin\n|-\n|bgcolor=whitesmoke|Saint-Hyacinthe\n|\n|Pierre Solis 13,137\n||\n|Léandre Dion 13,870\n|\n|Bernard Barré 7,855\n|\n|François Choquette (UFP) 401\n||\n|Léandre Dion\n|-\n|bgcolor=whitesmoke|Shefford\n||\n|Bernard Brodeur 16,391\n|\n|Jean-François de la Chevrotière 10,073\n|\n|Sylvain Barré 8,114\n|\n|Dominic Thibeault (BP) 502 Gilles Dumoulin (UFP) 334\n||\n|Bernard Brodeur\n|-\n|bgcolor=whitesmoke|Soulanges\n||\n|Lucie Charlebois 13,473\n|\n|Gaëtane Legault 8,753\n|\n|Pierre Éloi Talbot 3,549\n|\n|Gloria Sawyer (BP) 327Sandra Stephenson (Green) 320\n|\n|\n|-\n|bgcolor=whitesmoke|Taillon\n|\n|Annie Evrard 13,120\n||\n|Pauline Marois 17,603\n|\n|Katrine Simard 6,353\n|\n|David Fiset (BP) 556Gabriel Landry (UFP) 545Xavier Rochon (Ind.) 216\n||\n|Pauline Marois\n|-\n|bgcolor=whitesmoke|Vachon\n|\n|Brigitte Mercier 12,741\n||\n|Camil Bouchard 12,960\n|\n|Joëlle Lescop 5,540\n|\n|Denis Durand (BP) 519Richard St-Onge (UFP) 279\n||\n|David Payne\n|-\n|bgcolor=whitesmoke|Vaudreuil\n||\n|Yvon Marcoux 18,490\n|\n|Carole Cardinal 9,474\n|\n|Luc Tison 3,487\n|\n|Kathleen Mary Mangin (BP) 488Ernest Semple (Equ.) ", "120\n||\n|Yvon Marcoux\n|-\n|bgcolor=whitesmoke|Verchères\n|\n|Mario Lebrun 8,720\n||\n|Bernard Landry 16,963\n|\n|François Pratte 4,585\n|\n|Sébastien Drouin (BP) 505Marc-André Morvan (UFP) 195\n||\n|Bernard Landry\n|}\n\nMontreal\n\nEast\n\n|-\n|bgcolor=whitesmoke|Anjou\n||\n|Lise Thériault 17,572\n|\n|France Bachand 10,573\n|\n|Martin Janson 4,319\n|\n|Hélène Héroux (M-L) 266\n||\n|Lise Thériault\n|-\n|bgcolor=whitesmoke|Bourassa-Sauvé\n||\n|Line Beauchamp 20,175\n|\n|Kettly Beauregard 8,243\n|\n|Michelle Allaire 3,771\n|\n|Francis Mallette (Green) 327 Sylvain Archambault (Ind.) 261 Denis Gagné (DCQ) 119 Claude Brunelle (M-L) 94 Boris Mospan (Equ.) ", "44\n||\n|Michèle Lamquin-Éthier Line Beauchamp\n|-\n|bgcolor=whitesmoke|Bourget\n|\n|Claude Paquette 11,290\n||\n|Diane Lemieux 15,074\n|\n|Pierre Bourque 5,747\n|\n|Steve Boudrias (BP) 469 Rosanne Labelle (UFP) 418 Claudette Deschamps (DCQ) 193\n||\n|Diane Lemieux\n|-\n|bgcolor=whitesmoke|Crémazie\n||\n|Michèle Lamquin-Éthier 15,498\n|\n|Hugues Cormier 13,979\n|\n|Manon St-Louis 4,057\n|\n|Jocelyne Desautels (UFP) 686 Claude Trudel (Green) 399 Phillippe Beauvais (BP) 306 Marsha Fine (M-L) 90\n||\n|Manon Blanchet\n|-\n|bgcolor=whitesmoke|Gouin\n|\n|William Aguilar 8,996\n||\n|André Boisclair 15,890\n|\n|Stéphane Deschênes 2,456\n|\n|Colette Provost (UFP) 1,397 Pierrette Chevalier (Green) 584 Hugô St-Onge (BP) 465\n||\n|André Boisclair\n|-\n|bgcolor=whitesmoke|Hochelaga-Maisonneuve\n|\n|Richer Dompierre 6,210\n||\n|Louise Harel 13,138\n|\n|Louise Blackburn 2,449\n|\n|Lise Alarie (UFP) 788 Alex Néron (BP) 476 Daniel Breton (Green) 367 Christine Dandenault (M-L) 79 Mario Richard (DCQ) 52\n||\n|Louise Harel\n|-\n|bgcolor=whitesmoke|Jeanne-Mance–Viger\n||\n|Michel Bissonnet 26,801\n|\n|Robert La Rose 4,303\n|\n|Carole Giroux 2,080\n|\n|Eddy Guarino (BP) 365\n||\n|Michel Bissonnet Anna Mancuso\n|-\n|bgcolor=whitesmoke|LaFontaine\n||\n|Tony Tomassi 18,164\n|\n|Line Pelletier 4,939\n|\n|Josée Anello 2,697\n|\n|Patrick Forcier (BP) 323\n||\n|Jean-Claude Gobé\n|-\n|bgcolor=whitesmoke|Laurier-Dorion\n||\n|Christos Sirros 16,052\n|\n|Tomas Arbieto 9,775\n|\n|Mario Spina 1,996\n|\n|William Sloan (UFP) 922 Phillippe Morlighem (Green) 595 Sylvain Mainville (BP) 375 Peter Macrisopoulos (M-L) 165 Charles Robidoux (Ind.) 131 Sylvie Charbin (Ind.) 117 Yang Zhang (Equ.) ", "78\n||\n|Christos Sirros\n|-\n|bgcolor=whitesmoke|Mercier\n|\n|Nathalie Rochefort 8,414\n||\n|Daniel Turp 13,334\n|\n|Vivian Goulder 1,855\n|\n|Amir Khadir (UFP) 5,278 Lyne Rivard (BP) 579\n||\n|Nathalie Rochefort\n|-\n|bgcolor=whitesmoke|Pointe-aux-Trembles\n|\n|Daniel Fournier 9,427\n||\n|Nicole Léger 14,261\n|\n|André Cordeau 4,050\n|\n|Xavier Daxhelet (Green) 457 Julien Ferron (DCQ) 137 Geneviève Royer (M-L) 80\n||\n|Nicole Léger\n|-\n|bgcolor=whitesmoke|Rosemont\n|\n|Marylin Thomas 14,721\n||\n|Rita Dionne-Marsolais 16,143\n|\n|Denise Larouche 4,248\n|\n|Omar Aktouf (UFP) 1,132 Huguette Plourde (BP) 493 Suzelle Gill (DCQ) 147\n||\n|Rita Dionne-Marsolais\n|-\n|bgcolor=whitesmoke|Sainte-Marie–Saint-Jacques\n|\n|Richard Brosseau 7,989\n||\n|André Boulerice 13,066\n|\n|Annick Brousseau 2,183\n|\n|Gaétan Breton (UFP) 1,699 Robert Ruffo (Green) 690 Antoine Théorêt-Poupart (BP) 444 Ginette Boutet (M-L) 87 Maria da Luz dos Santos Inacio (DCQ) 59\n||\n|André Boulerice\n|-\n|bgcolor=whitesmoke|Viau\n||\n|William Cusano 17,703\n|\n|Maka Kotto 6,142\n|\n|Paolo Tamburello 2,406\n|\n|Guillaume Blouin-Beaudoin (BP) 426 Jocelyne Dupuis (UFP) 324 Yannick Duguay (Ind.) 121\n||\n|William Cusano\n|}\n\nWest\n\n|-\n|bgcolor=whitesmoke|Acadie\n||\n|Yvan Bordeleau 23,211\n|\n|Maria Mourani 6,702\n|\n|Jean-Pierre Chamoun 2,253\n|\n|Johnathan Bérubé (BP) 440 André Parizeau (Ind.) 161 Linda Sullivan (M-L) 111 Marina Paümann (Equ.) ", "95\n||\n|Yvan Bordeleau\n|-\n|bgcolor=whitesmoke|D'Arcy-McGee\n||\n|Lawrence Bergman 23,968\n|\n|Mathieu Breault 1,087\n|\n|Sylvain James Bowes 520\n|\n|William Shaw (Equ.) ", "406 Blair Longley (BP) 274\n||\n|Lawrence Bergman\n|-\n|bgcolor=whitesmoke|Jacques-Cartier\n||\n|Geoffrey Kelley 30,035\n|\n|Guy Amyot 1,894\n|\n|Jeffrey Penney 1,253\n|\n|Ryan Young (Green) 727 Keith Henderson (Equ.) ", "650 Daniel Cormier-Roach (Ind.) 49\n||\n|Geoffrey Kelley\n|-\n|bgcolor=whitesmoke|Marguerite-Bourgeoys\n||\n|Monique Jérôme-Forget 22,807\n|\n|Suzanne Groulx 6,327\n|\n|Brigitte De Laroche 2,524\n|\n|Adam Jastrzebski (Green) 415 Paul Domagala (Equ.) ", "142 Marc Veilleux (DCQ) 94 Yves le Seigle (M-L) 68\n||\n|Monique Jérôme-Forget\n|-\n|bgcolor=whitesmoke|Marquette\n||\n|François Ouimet 21,232\n|\n|Yves Beauregard 7,672\n|\n|Denise Décoste 3,260\n|\n|Bruce Hulley (Equ.) ", "289 Garnet Colly (M-L) 179\n||\n|François Ouimet\n|-\n|bgcolor=whitesmoke|Mont-Royal\n||\n|Philippe Couillard 21,021\n|\n|Vincent Gagnon 3,465\n|\n|Nour-Eddine Hajibi 1,240\n|\n|Frank Kiss (Equ.) ", "256\n||\n|André Tranchemontagne\n|-\n|bgcolor=whitesmoke|Nelligan\n||\n|Russell Williams 27,934\n|\n|Micaël Poirier 4,611\n|\n|Sabrina Duguay 2,680\n|\n|Peter Graham (Green) 541 Giuliana Pendenza (Equ.) ", "233\n||\n|Russell Williams\n|-\n|bgcolor=whitesmoke|Notre-Dame-de-Grâce\n||\n|Russell Copeman 18,911\n|\n|Laurent Malépart 3,460\n|\n|Allan Patrick 1,225\n|\n|Jessica Gal (Green) 1,084 Helene Jutras (BP) 261 Peter Sauvé (Equ.) ", "246 Thomas Kernan (DCQ) 96 Rachel Hoffman (M-L) 71\n||\n|Russell Copeman\n|-\n|bgcolor=whitesmoke|Outremont\n||\n|Yves Séguin 14,278\n|\n|Marilyse Lapierre 8,218\n|\n|Christian de Serres 1,712\n|\n|Jill Hanley (UFP) 1,818 Maryève Daigle (BP) 345 Louise Charron (M-L) 119\n||\n|Pierre-Étienne Laporte\n|-\n|bgcolor=whitesmoke|Robert-Baldwin\n||\n|Pierre Marsan 28,892\n|\n|Alphonse Boisrond 2,637\n|\n|Alladin Abou Sharbin 1,705\n|\n|Jimmy Kalafatidis (Equ.) ", "411\n||\n|Pierre Marsan\n|-\n|bgcolor=whitesmoke|Saint-Henri–Sainte-Anne\n||\n|Nicole Loiselle 16,004\n|\n|Raymond Munger 9,830\n|\n|Claudette Marullo 2,645\n|\n|Marc-André Payette (UFP) 595 Suzanne Moussette (Green) 439 Nicky Tanguay (BP) 424 Andrzej Jastrzebski (DCQ) 142 Jean-Paul Bédard (M-L) 116 Larry Vitas (Equ.) ", "52\n||\n|Nicole Loiselle\n|-\n|bgcolor=whitesmoke|Saint-Laurent\n||\n|Jacques Dupuis 24,745\n|\n|William Fayad 4,556\n|\n|Sophie Theoharopoulos 1,834\n|\n|Alain Pérusse (UFP) 325 Fernand Deschamps (M-L) 206 Louis Ottoni (Equ.) ", "199\n||\n|Jacques Dupuis\n|-\n|bgcolor=whitesmoke|Verdun\n||\n|Henri-François Gautrin 15,185\n|\n|Denis Martel 8,782\n|\n|Sébastien Guérin 3,269\n|\n|Claude Genest (Green) 658 Pascal Durand (UFP) 368 Vincent Aubry (BP) 357 Gilles Noël (DCQ) 104 Normand Chouinard (M-L) 71 Bernard King (Equ.) ", "63 Robert Lindblad (Ind.) 54\n||\n|Henri-François Gautrin\n|-\n|bgcolor=whitesmoke|Westmount–Saint-Louis\n||\n|Jacques Chagnon 18,330\n|\n|Denise Laroche 2,372\n|\n|Nathalie Beaupré 959\n|\n|David Fennario (UFP) 718 David John Proctor (BP) 223 Don Donderi (Equ.) ", "182 Diane Johnston (M-L) 64\n||\n|Jacques Chagnon\n|}\n\nLaval\n\n|-\n|bgcolor=whitesmoke|Chomedey\n||\n|Thomas Mulcair 25,363\n|\n|Coline Chhay 6,568\n|\n|Vicken Darakdijian 3,384\n|\n|Polyvios Tsakanikas (M-L) 210 Robert Tamilia (Equ.) ", "148\n||\n|Thomas Mulcair\n|-\n|bgcolor=whitesmoke|Fabre\n||\n|Michelle Courchesne 18,689\n|\n|Nathalie Saint-Pierre 14,428\n|\n|Claude Dugas 6,370\n|\n|Pierre Bibeau (Ind.) 402\n||\n|Joseph Facal\n|-\n|bgcolor=whitesmoke|Laval-des-Rapides\n||\n|Alain Paquet 15,190\n|\n|Serge Ménard 13,209\n|\n|Philippe Laurin 4,693\n|\n|Louis-Philippe Verenka (Green) 366 Vincent Pelletier (BP) 339 Michelle Marleau (DCQ) 162\n||\n|Serge Ménard\n|-\n|bgcolor=whitesmoke|Mille-Îles\n||\n|Maurice Clermont 19,924\n|\n|Maude Delangis 14,333\n|\n|Gerry La Rocca 5,093\n|\n|Christian Lajoie (Ind.) 244 Régent Millette (DCQ) 113\n||\n|Lyse Leduc\n|-\n|bgcolor=whitesmoke|Vimont\n||\n|Vincent Auclair 17,908\n|\n|Normand Dupont 12,865\n|\n|François Gaudreau 7,227\n|\n|Serge Légaré (Green) 403 André Pigeon (UFP) 269\n||\n|François Gaudreau\n|-\n|}\n\nLaurentides\n\n|-\n|bgcolor=whitesmoke|Argenteuil\n||\n|David Whissell 12,645\n|\n|Georges Lapointe 5,906\n|\n|Sylvain Demers 4,372\n|\n|Claude Sabourin (Green) 496 Yannick Charpentier (BP) 292\n||\n|David Whissell\n|-\n|bgcolor=whitesmoke|Bertrand\n|\n|Michelle Montpetit 13,502\n||\n|Claude Cousineau 14,704\n|\n|Danielle Tremblay 4,834\n|\n|Richard Savignac (Green) 664 Serge Haroun (DCQ) 490 David Rovins (Ind.) 41\n||\n|Claude Cousineau\n|-\n|bgcolor=whitesmoke|Blainville\n|\n|Jocelyne Roch 12,689\n||\n|Richard Legendre 15,288\n|\n|Diane Bellemare 7,407\n|\n|Thérèse Hamel (UFP) 394\n||\n|Richard Legendre\n|-\n|bgcolor=whitesmoke|Deux-Montagnes\n|\n|Marc Lauzon 12,099\n||\n|Hélène Robert 12,432\n|\n|Éric Duhaime 6,907\n|\n|Julien Demers (UFP) 408\n||\n|Hélène Robert\n|-\n|bgcolor=whitesmoke|Groulx\n||\n|Pierre Descoteaux 13,763\n|\n|Robert Kieffer 13,460\n|\n|Sophie Cardinal 6,746\n|\n|Denis Letourneux (UFP) 436 Julien Boisvert (BP) 402\n||\n|Robert Kieffer\n|-\n|bgcolor=whitesmoke|Labelle\n|\n|Jean-Pierre Miljours 10,501\n||\n|Sylvain Pagé 13,530\n|\n|Pascal De Bellefeuille 4,283\n|\n|Anne Léger (Green) 468 André Haché (BP) 274\n||\n|Sylvain Pagé\n|-\n|bgcolor=whitesmoke|Mirabel\n|\n|Réal Proulx 7,529\n||\n|Denise Beaudoin 10,577\n|\n|Hubert Meilleur 9,486\n|\n|\n|colspan=2 align=center bgcolor=whitesmoke|new district\n|-\n|bgcolor=whitesmoke|Prévost\n|\n|Marie-Josée Gouin 11,855\n||\n|Lucie Papineau 16,159\n|\n|Martin Camirand 7,087\n|\n|Alexandre Émond (BP) 499 Reine Dubeau (DCQ) 179\n||\n|Lucie Papineau\n|-\n|}\n\nLanaudière\n\n|-\n|bgcolor=whitesmoke|Berthier\n|\n|Carole Majeau 10,828\n||\n|Alexandre Bourdeau 12,101\n|\n|Marie Grégoire 11,014\n|\n|Pierre Gravel (UFP) 632\n||\n|Marie Grégoire\n|-\n|bgcolor=whitesmoke|Joliette\n|\n|Robert Groulx 11,161\n||\n|Jonathan Valois 13,103\n|\n|Sylvie Lespérance 7,114\n|\n|Mathieu Lessard (UFP) 1,149\nMarco Geoffroy (BP) 667 \n||\n|Sylvie Lespérance\n|-\n|bgcolor=whitesmoke|L'Assomption\n|\n|Sylvie Thouin 14,111\n||\n|Jean-Claude St-André 16,965\n|\n|Daniel Labrecque 7,053\n|\n|Bob Aubin (Green) 602\nGilbert Morin (UFP) 356\n||\n|Jean-Claude St-André\n|-\n|bgcolor=whitesmoke|Masson\n|\n|Richard Marcotte 11,371\n||\n|Luc Thériault 15,445\n|\n|Nathalie Filion 7,637\n|\n|\n||\n|Gilles Labbé\n|-\n|bgcolor=whitesmoke|Rousseau\n|\n|Michel F. Brunet 9,127\n||\n|François Legault 14,079\n|\n|François Girouard 5,645\n|\n|Alex Boisdequin-Lefort (UFP) 324Gérard Gauthier (DCQ) 249\n||\n|François Legault\n|-\n|bgcolor=whitesmoke|Terrebonne\n|\n|Marcel Théorêt 11,353\n||\n|Jocelyne Caron 17,327\n|\n|Jean-Pierre Parrot 6,463\n|\n|Marco Legrand (UFP) 440\n||\n|Jocelyne Caron\n|-\n|}\n\nOutaouais and Abitibi-Témiscamingue \n\n|-\n|bgcolor=whitesmoke|Abitibi-Est\n||\n|Pierre Corbeil 9,056\n|\n|Lorraine Morissette 7,110\n|\n|Serge Allard 4,477\n|\n|Guy Cloutier (BP) 286 Samuel Dupras-Doroftei (Ind.) 202\n||\n|André Pelletier\n|-\n|bgcolor=whitesmoke|Abitibi-Ouest\n|\n|Jean-Louis Carignan 7,960\n||\n|François Gendron 9,677\n|\n|Claude Morin 3,661\n|\n|\n||\n|François Gendron\n|-\n|bgcolor=whitesmoke|Rouyn-Noranda–Témiscamingue\n||\n|Daniel Bernard 10,347\n|\n|Rémy Trudel 9,673\n|\n|Pierre Brien 7,849\n|\n|Patrick Rancourt (UFP) 507\n||\n|Rémy Trudel\n|-\n|bgcolor=whitesmoke|Chapleau\n||\n|Benoît Pelletier 18,774\n|\n|Sylvie Simard 6,512\n|\n|Berthe Miron 3,949\n|\n|Daniel Leblanc-Poirier (BP) 402 Jean Marois (UFP) 331 Gabriel Girard-Bernier (M-L) 122 \n||\n|Benoît Pelletier\n|-\n|bgcolor=whitesmoke|Gatineau\n||\n|Réjean Lafrenière 16,481\n|\n|Dominique Bedwell 6,663\n|\n|Brian Gibb 3,494\n|\n|Julie Mercier (UFP) 423 Françoise Roy (M-L) 95\n||\n|Réjean Lafrenière\n|-\n|bgcolor=whitesmoke|Hull\n||\n|Roch Cholette 16,262\n|\n|Raphaël Déry 7,234\n|\n|Jean-François LaRue 3,663\n|\n|Denise Veilleux (UFP) 677 Stéphane Salko (BP) 305 Maxime Gauld (Ind.) 155 Benoit Legros (M-L) 72 Gheorghe Irimia (Ind.) 37\n||\n|Roch Cholette\n|-\n|bgcolor=whitesmoke|Papineau\n||\n|Norman MacMillan 17,933\n|\n|Gilles Hébert 8,279\n|\n|Serge Charette 3,833\n|\n|Nathalie Gratton (Green) 576 Dominique Marceau (UFP) 286\n||\n|Norman MacMillan\n|-\n|bgcolor=whitesmoke|Pontiac\n||\n|Charlotte L'Écuyer 17,885\n|\n|Luc Côté 3,133\n|\n|Victor Bilodeau 1,830\n|\n|Serge Tanguay (UFP) 392 Louis Lang (M-L) 132\n||\n|Robert Middlemiss\n|-\n|}\n\nSee also\n Politics of Quebec\n List of premiers of Quebec\n List of leaders of the Official Opposition (Quebec)\n National Assembly of Quebec\n 2007 Quebec general election\n Timeline of Quebec history\n Political parties in Quebec\n 37th National Assembly of Quebec\n\nReferences\n\nExternal links \n Results by party (total votes and seats won)\n Results for all ridings\n\nCategory:2003 elections in Canada\nCategory:Elections in Quebec\nCategory:2003 in Quebec\nCategory:April 2003 events in Canada" ]

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

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[ "Q:\n\nStatement in textbook: inhomogeneous wave equation has finite solutions only if RHS is orthogonal to homogeneous solutions\n\nSummary: Brillouin states that an inhomogeneous hyperbolic PDE has a finite solution only if the RHS is orthogonal to the homogenous solutions\n\nHi, I've been reading Brillouin's 'Wave Propagation in Periodic Structures'.", "\nAbout the following equation\n$$\\nabla^2u_1+\\frac{\\omega^2_0}{V_0^2}u_1 = R(r)$$\nBrillouin states that \"it is well known that such an equation possesses a finite solution only if the right-hand term is orthogonal to all solutions of the homogeneous equation:\"\n$$\\iint_{\\text{all space}} u_1^*R(r) dr = 0$$\nThis is not a property of hyperbolic PDEs I've come across before. ", "I wasn't able to find anything in my PDE textbooks. ", "Would anyone be able to suggest why this is the case? ", "I would be very appreciative.", "\n\nA:\n\nLet $v$ be a solution of the homogeneous equation:\n$$\\nabla^2v+\\frac{\\omega_0^2}{V_0^2}v=0 \\tag{1}$$\nLet's take the inhomogeneous equation\n$$\\nabla^2u_1+\\frac{\\omega_0^2}{V_0^2}u_1=R(r) \\tag{2}$$\nWe multiply both sides of $(2)$ by a solution $v$ of the homogeneous eq. ", "and take the integral over all space:\n$$\\int v\\nabla^2u_1 dr + \\int \\frac{\\omega_0^2}{V_0^2}vu_1dr=\\int v R(r) dr \\tag{3} $$\nWe concentrate on the term $\\int v\\nabla^2u_1 dr$. Expanding the nabla operator, it becomes\n$$ \\int \\left( v\\partial_x^2u_1+ v\\partial_y^2u_1 + v\\partial_z^2u_1 \\right) dr \\tag{4}$$\nIf $v$, $u_1$ and their derivatives go to zero at infinity, then two successive integrations by parts yield (I consider only the x-derivative term for simplicity): $$\\int v\\partial_x^2u_1 dr=-\\int (\\partial_xv) (\\partial_xu_1) dr=\\int (\\partial_x^2v)u_1 dr \\tag{5}$$\nSo we can write\n$$\\int v\\nabla^2u_1 dr = \\int u_1\\nabla^2v dr \\tag{6}$$\nNow equation $(3)$ can be rewritten by means of $(6)$ as\n$$\\int u_1\\nabla^2v dr + \\int \\frac{\\omega_0^2}{V_0^2}vu_1dr=\\int v R(r) dr \\tag{7} $$\nThe left side of $(7)$ can be written as\n$$\\int u_1 \\left( \\nabla^2v + \\frac{\\omega_0^2}{V_0^2}v \\right) dr \\tag{8} $$\nWe recognize in the expression in brackets in $(8)$ the left side of $(1)$. Then the expression in brackets is zero, and $(8)$ as a whole is consequently zero. ", "Then $(7)$ becomes\n$$0=\\int v R(r) dr \\tag{9} $$\nor, switching sides,\n$$\\int v R(r) dr=0 \\tag{10} $$\nwhich means that $R$ is orthogonal to the solutions $v$ of the homogeneous equation.", "\n\n" ]

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[ "Introduction {#Sec1}\n============\n\nThe ability of B-lymphocytes to create a polyclonal immunoglobulin repertoire with a diverse set of antigen-binding sites permits specific responses to a broad range of foreign and self-antigens. ", "Each nascent immunoglobulin is the product of a complex series of V (D) J gene rearrangement and terminal deoxynucleotidyl transferase (TdT) catalyzed N addition that created an exponential repertoire of diverse heavy (H) and light (L) chains (Hozumi and Tonegawa [@CR19]; Tonegawa [@CR53]). ", "Immunoglobulin rearrangement is a hierarchical process, with D~H~➔J~H~ rearrangement preceding V~H~➔DJ~H~ rearrangement, and followed by V~L~➔J~L~ rearrangement. ", "Each stage of rearrangement marks a separate developmental checkpoint with early checkpoints focusing on generation of a functional immunoglobulin and later ones testing the specificity of the antigen-binding site (Huetz et al. [", "@CR20]). ", "Of the six hypervariable loops that are juxtaposed to form the antigen-binding site, the third complementary determining region of the heavy chain (CDR-H3) is the most diverse (Alt and Baltimore [@CR2]; Rajewsky [@CR40]; Tonegawa [@CR53]; Yancopoulos et al. [", "@CR59]). ", "CDR-H3, which includes the carboxyl terminus of the V~H~, the amino terminus of the J~H~, and all of the D~H~ in its entirety, is the direct product of V(D)J joining and N addition. ", "Its location at the center of the antigen-binding site permits CDR-H3 to often play a critical role in antibody specificity (Kabat et al. [", "@CR26]; Padlan [@CR38]; Xu and Davis [@CR55]).", "\n\nIn humans, the ability to mount an effective humoral response to many antigens, including specific microorganisms and vaccines, is delayed until well after infancy (Stein [@CR51]). ", "This sequential acquisition of the ability to respond to particular antigens is a characteristic feature of the developing immune system in jawed vertebrates, humans and mice included (Silverstein [@CR50]). ", "These observations present a paradox in that they suggest an element of order to the development of the binding characteristics of the antibody repertoire even though the mechanisms that underlie the generation of the antibody were initially viewed as highly stochastic (Yancopoulos and Alt [@CR58]). ", "This paradox was resolved, at least in part, by the observation that the fetus does not make full use of all the mechanisms that are available for the generation of V domain diversity in general, and CDR-H3 diversity in particular (Feeney [@CR15]; Gu et al. [", "@CR17]; Schroeder et al. [", "@CR46]; Schroeder et al. [", "@CR47]; Yancopoulos and Alt [@CR58]; Yancopoulos et al. [", "@CR59]). ", "More recent studies have shown that even in the adult the composition of CDR-H3 continues to demonstrate constraints on amino acid composition, length, and charge distribution (Ippolito et al. [", "@CR22]; Ivanov et al. [", "@CR25]; Schelonka et al. [", "@CR43]; Schelonka et al. [", "@CR44]). ", "Manipulation of these constraints can lead to altered patterns of B cell development, antigen-specific antibody production, and immune responses to pathogens.", "\n\nGiven the importance of CDR-H3 to antigen recognition, we sought to re-evaluate the process of CDR-H3 content control during perinatal B cell development in the expressed functional repertoire in the mouse. ", "This information is essential for a better understanding of the mechanisms that regulate the development of the early repertoire, of the role of fetal repertoire restriction on perinatal B cell development and perinatal responses to antigen, to better understand the contribution of this fetal repertoire to the population of critical B cell niches in the adult, such as the peritoneal cavity and to facilitate evolutionary studies of repertoire development (Ivanov et al. [", "@CR24]).", "\n\nWe used surface expression of CD43, BP-1, CD19, IgM, and IgD to sort B lineage cells from BALB/c 18-days post conception and neonatal liver. ", "After polymerase chain reaction amplification of transcripts cloned into cDNA by reverse transcription of mRNA (RT-PCR) amplification, we sequenced V~H~7183-containing VDJCμ transcripts from these sorted cells and then compared the results to our previous studies of repertoire development in adult BALB/c mice (Ippolito et al. [", "@CR22]; Ivanov et al. [", "@CR25]; Schelonka et al. [", "@CR43]). ", "As in the case of the adult BALB/c mice, we found that perinatal CDR-H3 content was biased from its inception, and then further focused with development. ", "In contrast to a previous study using unsorted cells from the perinatal liver (Bangs et al. [", "@CR6]), we also found that the changes in D~H~ and J~H~ usage between fetus and adults exhibited striking parallels to the pattern of D~H~ and J~H~ usage observed in human ontogeny. ", "Therefore, these results reinforce the value of the mouse as a model for the ontogeny of the development of immune competence in human.", "\n\nMaterials and methods {#Sec2}\n=====================\n\nMice {#Sec3}\n----\n\nWe obtained 18-day post-conception fetal liver and neonatal liver from two separate mice each on two separate occasions, for a total of four samples. ", "The mice analyzed represent the progeny of BALB/c mice bred in the University of Alabama at Birmingham (UAB) vivarium. ", "The mice were maintained in a specific pathogen-free barrier facility. ", "All experiments with live mice were approved by and performed in compliance with the requirements of the UAB Institutional Animal Care and Use Committee.", "\n\nFlow cytometry and cell sorting {#Sec4}\n-------------------------------\n\nFlow cytometric analysis and cell sorting from mononuclear cells from the liver was performed as previously described on mononuclear cells from the bone marrow of 8-week-old BALB/c mice (Ippolito et al. [", "@CR22]; Ivanov et al. [", "@CR25]; Schelonka et al. [", "@CR43]). ", "A MoFlo instrument (Cytomation, Ft. ", "Collins, CO, USA) was used for cell sorting. ", "Developing B lineage cells in the liver were identified on the basis of the surface expression of CD19, CD43, IgM, BP-1, and/or IgD (Fig.", " [1](#Fig1){ref-type=\"fig\"}). ", "Fig.", " 1Flow cytometric gates for the collection of fetal B lineage cells from 18-days post-gestation and neonatal BALB/cJ mice. ", "Cells within the lymphocyte gate were first distinguished on the basis of the expression of CD19 and CD43. ", "Early B-cell progenitors (CD19+ CD43+) were divided into fractions B and C on the basis of the expression of BP-1. ", "Late pre-B, immature B, and mature B cells (CD19+ CD43−) were divided into fractions D, E, and F on the basis of the surface expression of IgM and IgD\n\nSorting, RNA preparation, RT-PCR, and sequence analysis {#Sec5}\n-------------------------------------------------------\n\nTotal RNA isolation, V~H~7183 specific VDJCμ RT-PCR amplification, cloning, sequencing, and sequence analysis was performed in the same way as previously described (Ippolito et al. [", "@CR22]; Ivanov et al. [", "@CR25]; Schelonka et al. [", "@CR43]), thus permitting a direct comparison between perinatal and adult *BALB/c* mice sequences. ", "The sequences reported in this paper have been placed in GenBank database (accession number GU975849-GU976285). ", "A listing of the 472 unique, in-frame perinatal sequences used for analysis in this work is provided in Supplemental Table (S[1](#AppESM1){ref-type=\"sec\"}).", "\n\nStatistical analysis {#Sec6}\n--------------------\n\nDifferences between populations were assessed, where appropriate, by two-tailed Student's *t* test, two-tailed Fisher's exact test, *χ*^2^, or Levene test for the homogeneity of variance. ", "Analysis was performed with JMP version 7.0 (SAS Institute). ", "The standard error of the mean accompanies means.", "\n\nResults {#Sec7}\n=======\n\nIsolation of B lineage cells and RT-PCR cloning of Ig transcripts from fetal and perinatal liver {#Sec8}\n------------------------------------------------------------------------------------------------\n\nWe identified and isolated B lineage cells from Hardy fractions B through E (Hardy and Hayakawa [@CR18]) from 18 days gestation fetal liver, but were unable to detect cells belonging to fraction F (Fig.", " [1](#Fig1){ref-type=\"fig\"}, left). ", "Subsequently, fraction F cells for our analysis were obtained from the livers of neonatal mice (Fig.", " [1](#Fig1){ref-type=\"fig\"}, right). ", "Following total RNA extraction, RT-PCR amplification was performed using 3′ Cμ and 5′ V~H~7183-specific primers. ", "The resulting cDNAs were cloned into pUC19 plasmids and then sequenced. ", "We obtained 472 unique, in-frame, and open reading frame V~H~7183-D-J-Cμ sequences. ", "Of these, 53 fraction B (pro-B cells), 55 fraction C (early pre-B cells), 90 fraction D (late pre-B), and 142 Fraction E (immature B cells) sequences were obtained from 18-day post-conception liver, and 132 fraction F (mature B cells) sequences were obtained from neonatal liver. ", "We compared these to 194, 373, 279, 255, and 254 previously published Fractions B through F unique, in-frame, open reading sequences from the bone marrows of 11 different 8-week-old adult BALB/c mice (Zemlin et al. [", "@CR60]).", "\n\nUsage of V~H~81X (V~H~7183.1) in fetal B lineage cells varies by developmental stage {#Sec9}\n------------------------------------------------------------------------------------\n\nConsistent with previous studies (Martin et al. [", "@CR35]; Yancopoulos et al. [", "@CR59]), we observed preferential use of D~H~-proximal V~H~81X (V~H~7183.1) in fetal liver B lineage cells (Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "When compared to adult bone marrow B lineage cells, the use of V~H~81X was greater in perinatal fractions B, D, E and F; but smaller in fraction C (*p* \\< 0.05). ", "In adult fraction C through fraction F, VH7183.10 proved the most heavily used V~H~. In the perinatal period, we observed a dramatic increase in the relative use of V~H~7183.10 in fractions C and D (*p* ≤ 0.0001), followed by a drop in fraction E (*p* ≤ 0.0001). ", "By fraction F, however, the use of V~H~7183.10 matched that of adult. ", "Fig.", " 2V~H~ 7183 gene segment usage during B cell development in the perinatal liver versus the bone marrow of adults. ", "V~H~ gene segments are arranged according to their position relative to the J~H~ locus in the genome, with V~H~7183.1 (V~H~81X), the most J~H~ proximal, at the right. *", "Top* Percent of unique, in-frame sequences using the V~H~ gene segment specified in the perinatal liver from Hardy fractions B (CD19^+^ CD43^+^ IgM^−^ BP-1), C (CD19^+^ CD43^+^ IgM^−^ BP-1^+^), D (CD19^+^ CD43^−^ IgM^−^ IgD−), E (CD19^+^ CD43^−^ IgM^+^ IgD^−^), and F (CD19^+^ CD43^−^ IgM^low^ IgD^high^) from BALB/c mice is displayed. *", "Middle* Percent of unique, in-frame sequences using the V~H~ gene segment specified in the bone marrow of 8-week-old BALB/c mice. *", "Bottom* Divergence in the percentage of V~H~ gene segment use between the perinatal liver and the young adult bone marrow is displayed\n\nThe effect of distance to D~H~ was also apparent in V~H~ gene segments other than V~H~81X. We grouped the V~H~ gene segments distal to V~H~7183.10 into one block (block 8--18); and the V~H~ gene segments proximal to V~H~7183.10 but distal to V~H~81X and V~H~7183.2 into a second block (block 3--6). ", "Although usage of the distal block in the perinatal period increased with development, it consistently lagged behind the usage observed in adult (Fig.", " [3](#Fig3){ref-type=\"fig\"}, left); whereas in fractions C, E, and F usage of the proximal block was similar between perinatal liver and adult bone marrow (Fig.", " [3](#Fig3){ref-type=\"fig\"}, right). ", "Although within each fraction the numbers of sequences were insufficient to achieve statistical significance, when compared as a population the differences in the proportion of usage between the two blocks of sequences between the perinatal period versus the adult achieved statistical significance at *p* = 0.005. ", "Fig.", " 3D~H~ distal and proximal V gene usage during B cell development in the perinatal liver versus the adult bone marrow. ", "We grouped the V~H~ gene segments upstream of V~H~7183.10 into one block (block 8--18); and the VH gene segments downstream of V~H~7183.10, but upstream of V~H~81X and V~H~7183.2, into a second block (block 3--6) of gene segments. ", "V~H~ block usage is reported as the percent of the sequenced population of unique, in-frame, open transcripts from BALB/c mice perinatal liver and adult bone marrow Hardy fractions B through F\n\nPreferential use of D~H~ DQ52 in fetal liver {#Sec10}\n--------------------------------------------\n\nThe relative use of the D~H~ gene families in the perinatal liver reflected proximity to the J~H~ locus. ", "When compared to adult bone marrow, we observed decreased use of J~H~-distal DFL gene segments and enhanced use of J~H~-proximal DQ52 (Fig.", " [4](#Fig4){ref-type=\"fig\"}, left panel). ", "While this pattern of preference based on physical location was observed throughout development, by Fraction F there was evidence of convergence with the overall pattern of D~H~ family usage nearly matching that of adult bone marrow fraction F. Fig.", " 4D~H~, J~H~, and D~H~ reading frame usage during B cell development in the perinatal liver versus the bone marrow of adults. *", "Top left to right* The percent of sequences using members of the specified D~H~ family; the percent of sequences using DSP or DFL D~H~ gene segment family members in reading frames 1, 2, or 3; and percent of sequences using J~H~1, 2, 3, or 4 among in-frame sequences cloned from the perinatal liver from Hardy fractions B through F is displayed. *", "Middle left to right* The percent of sequences using members of the specified D~H~ family; percent of sequences using DSP or DFL D~H~ gene segment family members in reading frames 1, 2, or 3; and percent of sequences using J~H~1, 2, 3, or 4 among in-frame sequences cloned from 8 week old BABL/cJ bone marrow from Hardy fractions B through F is displayed. *", "Bottom left to right* Divergence in the percentage of D~H~ gene family, DSP and DFL, reading frame, and J~H~ between the perinatal liver and the young adult bone marrow is displayed. *", "Arrows* point to features of particular interest\n\nPreferential use of J~H~2 in perinatal liver {#Sec11}\n--------------------------------------------\n\nJ~H~ utilization also followed proximity to DQ52. ", "While use of J~H~1 did not differ between the perinatal and adult periods, when compared to adult use of J~H~2 was favored over J~H~3 and J~H~4 (*p* ≤ 0.002) at all stages of development except for fraction E. In human, there is a similar shift with use of J~H~ 2 and 3 in first trimester fetal liver preferred over J~H~5 and 6, and use of J~H~5 and 6 in adult bone marrow preferred over use of J~H~2 and 3 (Baskin et al. [", "@CR7] Apr; Xue et al. [", "@CR56]; Yamada et al. [", "@CR57]).", "\n\nIncreased prevalence of D/J overlaps and use of reading frame 1 in perinatal liver {#Sec12}\n----------------------------------------------------------------------------------\n\nAs previously reported (Kepler et al. [", "@CR28]), CDR-H3 sequences with V/D and D/J overlaps were exceedingly common in the perinatal samples (Fig.", " [5](#Fig5){ref-type=\"fig\"}), which essentially lack N nucleotide addition. ", "The increased prevalence of sequences with V/D and D/J overlaps were associated with an increase in the use of reading frame 1 among CDR-H3s that used DSP or DFL gene segments (Fig.", " [4](#Fig4){ref-type=\"fig\"}, middle panels). ", "Fig.", " 5Deconstruction of the contributing components to CDR-H3 length in sequences containing identifiable D~H~ gene segments as a function of B cell development in the perinatal liver. ", "The potential distribution of the germline sequence of the V~H~ gene segment, P junctions, the D~H~ gene segment, V~H~-D~H~ and D~H~-J~H~ overlap, and the J~H~ gene segment to the CDR-H3 length is illustrated\n\nChanges in the distribution of CDR-H3 length with development {#Sec13}\n-------------------------------------------------------------\n\nThe average length of perinatal CDR-H3 was significantly shorter than adult at all stages examined (Fig.", " [6a](#Fig6){ref-type=\"fig\"}). ", "However, an increase in the average length of CDR-H3 from fraction B (9.2 ± 0.4 codons) to fraction F (10.2 ± 0.2, *p* \\< 0.002) was observed. ", "This change was progressive, but was most marked in the transition from fraction C (9.2 ± 0.4) to D (10.1 ± 0.2, *p* \\< 0.02). ", "Fig.", " 6Average CDR-H3 length and CDR-H3 loop charge as a function of B cell development in the perinatal liver as compared to that in the bone marrow of adult BALB/cJ mice. **", "a** Average CDR-H3 length and **b** average CDR-H3 loop hydrophobicity of the V~H~7183DJCμ transcripts from perinatal liver and adult bone marrow. ", "The standard error of the mean is shown\n\nA closer examination of the distribution of CDR-H3 lengths as a function of ontogeny and development (Fig.", " [7](#Fig7){ref-type=\"fig\"}) revealed that the perinatal samples were completely devoid of CDR-H3s of greater than 15 codons. ", "At the other end of the scale, we observed an increase in the prevalence of sequences of eight codons or less. ", "In part, the reason for the major shift in length between fractions C and D reflected the reduced prevalence of CDR-H3 sequences with less than seven codons, including sequences without a recognizable D~H~ element (Fig.", " [4](#Fig4){ref-type=\"fig\"}). ", "Fig.", " 7Distribution of CDR-H3 lengths as a function of B cell development in the perinatal liver as compared to that in the bone marrow of adult BALB/cJ mice. *", "Left* Distribution of CDR-H3 lengths in V~H~7183DJCμ transcripts from perinatal liver as a function of B cell development ([@CR11]). ", "Distribution of CDR-H3 lengths in V~H~7183DJCμ transcripts from adult bone marrow as a function of B cell development. *", "Right* Divergence in the distribution of CDR-H3 length between the perinatal liver and the young adult bone marrow is displayed. ", "To facilitate visualization of the change in variance of the distribution, the *vertical lines* mark the preferred range of lengths in the bone marrow fraction F. *Arrows* point to features of particular interest\n\nAltered patterns of amino acid usage in perinatal CDR-H3 loops {#Sec14}\n--------------------------------------------------------------\n\nIn the absence of N addition and with preferential use of reading frame 1, which is enriched for use of tyrosine, there was a striking divergence in the pattern of amino acid utilization in the CDR-H3 loops of the sequences obtained from fraction B, which is prior to the expression of the H chain in protein form (Fig.", " [8](#Fig8){ref-type=\"fig\"}). ", "When compared to adult, this early repertoire was enriched for use of tyrosine, histidine, and asparagine. ", "Conversely, the perinatal repertoire was virtually devoid of arginine, lysine, glutamine, glutamic acid, proline, and phenylalanine. ", "Use of leucine, valine, and isoleucine was also reduced. ", "Of the five amino acids where little or no change was observed between fetus and adult, two, methionine and cysteine, were remarkable for their absence at both stages of life. ", "The overall outline of amino acid usage remained relatively unchanged from fraction B to fraction F. However, closer inspection revealed subtle adjustments as the B cells passed through sequential development checkpoints. ", "For example, use of aspartic acid was enhanced in fractions B and C, but declined to adult levels in fractions D, E, and F. Fig.", " 8Amino acid usage as a function of B cell development in the perinatal liver as compared to that in the bone marrow of adult BALB/c mice. ", "The distribution of individual amino acids in the CDR-H3 loop of sequences as a function of B cell development in the perinatal liver. ", "The Hardy bone marrow B lineage designation of fractions B through F (Hardy and Hayakawa [@CR18]) was used throughout\n\nVariation of CDR-H3 hydrophobicity during fetal B cell development {#Sec15}\n------------------------------------------------------------------\n\nWe used a normalized Kyte--Doolittle scale to assess the relatively distribution of hydrophobicity in the CDR-H3 loop of perinatal versus adult CDR-H3 loops (Eisenberg [@CR14]; Kyte and Doolittle [@CR30]). ", "In the absence of N addition and with increased use of reading frame 1, there was a shift in average hydrophobicity towards the charged end of the spectrum (Fig.", " [6b](#Fig6){ref-type=\"fig\"}). ", "Closer inspection revealed that this shift primarily reflected a paucity of sequences in the more hydrophobic range of the normal repertoire (Fig.", " [9](#Fig9){ref-type=\"fig\"}). ", "Indeed, the vast majority of the CDR-H3 loop sequences remained within the range that is preferred for recirculating fraction F B cells in adult; although unlike the adult fraction F repertoire, a few sequences continued to carry excess charge or hydrophobicity. ", "Fig.", " 9Distribution of CDR-H3 loop charge as a function of B cell development in the perinatal liver as compared to that in the bone marrow of adult BALB/cJ mice. *", "Left* Distribution of average CDR-H3 hydrophobicities in VH7183DJCμ transcripts from perinatal liver as a function of B cell development ([@CR11]). ", "Distribution of average CDR-H3 hydrophobicities in VH7183DJCμ transcripts from adult bone marrow as a function of B cell development. *", "Right* Divergence in the distribution of CDR-H3 loop hydrophobicity between the perinatal liver and the young adult bone marrow is displayed. ", "The normalized Kyte--Doolittle hydrophobicity scale (Eisenberg [@CR14]) has been used to calculate average hydrophobicity. ", "Although this scale ranges from −1.3 to +1.7, only the range from −1.0 (charged) to +1.0 (hydrophobic) is shown. ", "Prevalence is reported as the percent of the sequenced population of unique, in-frame, open transcripts from each B lineage fraction. ", "To facilitate visualization of the change in variance of the distribution, the vertical lines mark the preferred range average hydrophobicity previously observed in wild-type fraction F (Ivanov et al. [", "@CR25]). *", "Arrows* point to features of particular interest\n\nDiscussion {#Sec16}\n==========\n\nIn the bone marrow of adult BALB/c mice, the composition of the expressed immunoglobulin CDR-H3 repertoire is marked by constraints on length, amino acid utilization, and charge (Ivanov et al. [", "@CR25]). ", "These constraints are first established in early B cell progenitors, and then focused as the B lineage cells progress through sequential developmental checkpoints. ", "Many of these constraints are dependent on the specific sequence of the contributing gene segments and vary during ontogeny (Asma et al. [", "@CR3]; Ippolito et al. [", "@CR22]; Logtenberg et al. [", "@CR34]; Schelonka et al. [", "@CR43]; Terrell et al. [", "@CR52]; Zemlin et al. [", "@CR61]). ", "In this work, we sought to re-examine the development of the expressed CDR-H3 repertoire in the perinatal liver in order to gain insight into the forces that shape the repertoire during its passage through developmental checkpoints at both a different stage of ontogeny and in a different tissue organ.", "\n\nFraction B is represents the developmental stage at which V➔DJ rearrangement begins. ", "In both fetus and adult, the transition from fraction B to C is characterized by increased use of V~H~ gene segments other than V~H~81X. For example, the use of V~H~ 7183.10 increases markedly, suggesting that by fraction C access to V~H~ gene segments other than V~H~81X may be enhanced (Fig.", " [2](#Fig2){ref-type=\"fig\"}). ", "The greatest differences between the adult and perinatal repertoires occurred in fraction B (Fig.", " [10](#Fig10){ref-type=\"fig\"}), which is the least likely to undergo selection on the basis of the H chain to bind to either endogenous or exogenous compounds. ", "This would suggest that the differences that were observed largely reflected the effects of genetically controlled differences between the fetal and adult B cell progenitors in terms of the patterns of rearrangement and gene segment access. ", "Fig.", " 10Summary of results. ", "The adult and perinatal repertoires differ most markedly in fraction B; however, in fraction F the repertoires have drawn closer to each other in terms of VH usage, DH usage, JH usage, length, and hydrophobicity and charge\n\nThe transition from fraction C to D requires a successful interaction between the nascent H chain and (l5/VpreB) the pre-B cell receptor, which produces an appropriate survival and cell replication signal. ", "The changes in average length and charge are most marked at this transition (Fig.", " [6](#Fig6){ref-type=\"fig\"}), which reflect the loss of the shortest and the most highly charged CDR-H3s. ", "The change in charge in adult bone marrow is also most marked at this transition; although in this case, there appears to be a greater reduction in the more hydrophobic rather than the most charged. ", "These results would suggest that either the binding of H chains with short, highly charged, or highly hydrophobic CDR-H3s to VpreB/λ5 the pre-B cell receptor is less efficient or the signal that is transduced by H chains with these types of CDR-H3s is qualitatively or quantitatively different than that of CDR-H3 sequences of the preferred length, charge, or hydrophobicity.", "\n\nThe transition from fraction D to E reflects successful expression of a complete surface IgM B cell receptor. ", "CDR-H3 length distribution, hydrophobicity, and charge are unchanged, supporting the view that the pre-B cell receptor has acted to select for acceptable physico-chemical CDR-H3 characteristics. ", "However at this stage, we see a marked change in the use of V~H~7183.10, which does not occur in the adult. ", "It is possible that the antigens to which immature B cells that use V~H~7183.10 are responding differ between fetus and adult or that the binding specificity of V~H~7183.10 N-less CDR-H3s is not conducive to further B cell development. ", "Examination of the pattern of V~H~ usage in sorted single cells would help distinguish between these possibilities, as would evaluation of repertoire diversification in the absence of TdT.\n\nThe transition from fraction E to F at this early stage of life comes in a setting where exposure to the external environment has been restricted to the womb. ", "Subtle differences were observed in terms of V~H~, D~H~, and J~H~ usage, suggesting further antigen receptor-mediated selection in response to endogenous antigens.", "\n\nBy the time the B cells achieve fraction F status, the perinatal liver and adult bone marrow repertoires have drawn closer to each other in terms of V~H~ usage, D~H~ usage, J~H~ usage, and CDR-H3 length hydrophobicity and charge. ", "The fetal repertoire is well known for its tendency to produce poly-reactive antibodies with self-specificities (Avrameas [@CR4]; Avrameas and Ternynck [@CR5]). ", "Selection of the repertoire through idiotype/anti-idiotype interactions has been shown to differ between fetus and adult (Benedict et al. [", "@CR9]; Benedict and Kearney [@CR8]; Kearney et al. [", "@CR27]). ", "However, given the fact that the antibody repertoire in the perinatal period has developed in an environment protected from exposure to exogenous antigens, it may be that both the fetal and adult repertoires are being shaped, at least in part, by interactions with the same self-antigens.", "\n\nIn agreement with previous studies, we observed preferential use of the most D~H~ proximal V~H~, V~H~81X, in the earliest B cell progenitor examined. ", "And we confirmed a progressive fall in the usage of this gene segment with development (Huetz et al. [", "@CR20]; Yancopoulos et al. [", "@CR59]). ", "We also observed diminished use of the group, or block, of 7183 V~H~ gene segments most distal to D~H~. These findings are in accordance with studies that report differential accessibility of portions of the V~H~ locus to rearrangement early in ontogeny (Perlmutter et al. [", "@CR39]; Sen and Oltz [@CR48]; Williams et al. [", "@CR54]; Yancopoulos et al. [", "@CR59]).", "\n\nThe importance of position to gene segment expression in the perinatal liver was underscored by the increased use of J~H~-proximal DQ52 and D~H~-proximal J~H~2 and 3. ", "This follows the positional pattern of usage that is observed in human (Sanz [@CR42]; Schroeder et al. [", "@CR46]) as well as in rhesus monkeys (Link et al. [", "@CR33]). ", "It has been shown that deletion of both DQ52 and the region immediately adjacent and its upstream promoter enriches use of D~H~-proximal J~H~ gene segments in adult bone marrow (Nitschke et al. [", "@CR36]; Schelonka et al. [", "@CR43]), whereas deletion of a portion of the promoter region upstream of DQ52 only had no effect (Afshar et al. [", "@CR1]). ", "Together, this would support the view that the DQ52 region as a whole, including DQ52, plays a critical, evolutionarily preserved role in the regulation of initial D➔J immunoglobulin rearrangements (Kottmann et al. [", "@CR29]).", "\n\nIn addition to restrictions in V~H~ usage, the perinatal H chain repertoire in mice is also marked by an absence of N nucleotides (Asma et al. [", "@CR3]; Delassus et al. [", "@CR13]; Li et al. [", "@CR31]; Rusquet et al. [", "@CR41]; Schroeder [@CR45]; Shiokawa et al. [", "@CR49]). ", "In the absence of these non-germline-encoded terminal modifications, rearrangement occurs preferentially at sites of germline microhomology between the rearranging sequences (Chukwuocha and Feeney [@CR12]; Feeney [@CR15]; Feeney [@CR16]; Huetz et al. [", "@CR21]; Lieber et al. [", "@CR32]). ", "This has the effect of directing rearrangement into RF1 and further reducing CDR-H3 length by eliminating shared D~H~ and J~H~ sequence. ", "Preferential use of RF1 diminishes access to the hydrophobic and charged amino acids encoded by reading frames other than RF1(Ivanov et al. [", "@CR23]). ", "The absence of N addition limits incorporation of lysine, glutamic acid, glutamine, and proline while enriching for tyrosine, histidine, and asparagine. ", "Together, these factors create a fetal pre-B cell H chain CDR-H3 repertoire that differs significantly from its adult counterpart in its distribution of CDR-H3 lengths, amino acid content, and charge. ", "The changes that we have observed in early repertoire development could thus reflect either differences in the cells and tissues in which these developmental processes are occurring or they could reflect the effects of the absence of N addition. ", "A similar analysis of repertoire development in a TdT deficient state would help clarify the extent, if any, to which N addition influences the changes that we have observed in repertoire development between fetus and adult.", "\n\nStudies of the anatomy of hot spots in protein interfaces (Bogan and Thorn [@CR10]) have shown that tryptophan, tyrosine, and arginine contribute disproportionately to binding energies. ", "All three of these amino acids share the ability to contribute multiple types of favorable interactions. ", "Tyrosine, the most commonly used amino acid in both adult and fetal CDR-H3 loops, offers a large hydrophobic surface, aromatic p-interactions, and the hydrogen bonding ability of its 4-hydroxyl group. ", "Tryptophan and arginine also offer these binding opportunities. ", "Tryptophan offers a large hydrophobic surface, aromatic p-interactions, and a hydrogen-binding donor. ", "Arginine offers the ability to form a hydrogen bond network with up to five H-bonds, a guanidinium motif that offers a pseudo-aromatic p system, and three methylene carbon groups, which are all hydrophobic in character. ", "In addition, arginine offers the ability to create salt bridges by means of its positively charged guanidinium motif.", "\n\nGiven the importance of these three amino acids, it is remarkable that the pattern of their usage between the fetus and the adult is so different. ", "Globally, the fetus is enriched for tyrosine and depleted of arginine. ", "DQ52 is an unusual D~H~ gene segment in that it lacks tyrosine in all six reading frames, encoding tryptophan in its place (Ivanov et al. [", "@CR23]). ", "The inclusion of DQ52 uniquely leads to enrichment for tryptophan-containing antigen-binding sites. ", "Indeed, in our studies, the increase in the inclusion of tryptophan achieved statistical significance in fraction F (*p* = 0.03). ", "The biologic consequences of the increased prevalence of tryptophan-enriched CDR-H3s amongst mature neonatal B cells remains unclear when compared to adult, but this pattern holds true for both human and mouse (Ohno et al. [", "@CR37]). ", "It seems likely that all of these differences could contribute to the differential control of immune responses that characterizes early development (Silverstein [@CR50]). ", "The extensive similarities that we have observed between the composition of the fetal versus adult repertoires in mice and humans would suggest that the mouse may be a better model for the evaluation of both the mechanistic and functional consequences of human fetal CDR-H3 repertoire restriction than previously appreciated.", "\n\nElectronic supplementary material {#AppESM1}\n---------------------------------\n\nBelow is the link to the electronic supplementary material.", "\n\n###### \n\nUnique and in-frame perinatal sequences used for analysis (DOC 1,833 kb)\n\nThe authors wish to thank P. Burrows, M. Cooper, J. Kearney, and R. F. Maier for their invaluable advice and support. ", "This work was supported in part by AI07051, AI42732, AI48115, AI078449, HD043327, Deutsche Forschungsgemeinschaft SFB/TR22-TPA17, and Alexander von Humboldt-Stiftung FLF1071857. ", "The authors declare that they have no competing financial interests.", "\n\n**Open Access** This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.", "\n\nThis work was supported in part by AI07051, AI42732, AI48115, AI078449, HD043327, Deutsche Forschungsgemeinschaft SFB/TR22-TPA17, and Alexander von Humboldt-Stiftung FLF1071857. ", "The authors declare that they have no competing financial interests.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Molecular modeling study of the opioid receptor interactions with series of cyclic deltorphin analogues.", "\nIn this study, ten tetra- and heptapeptide analogues of deltorphin containing the urea bridges between residues 2 and 4 have been docked into the δ- and µ-opioid receptors to explain their different biological activities. ", "The important factors explaining particular ligand activity such as free energy of binding, conformation of the ligand, its location inside the binding pocket as well as the number and strength of the receptor-ligand interactions have been discussed. ", "Several different binding modes for investigated ligands have been proposed. ", "It appears that the binding site is not identical even for very similar ligands. ", "Results of this study help to explain the differences in biological activity of the deltorphin analogues, their interaction with the opioid receptors at the molecular level and support designing a new generation of potent opioid drugs with improved selectivity." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Kids’ magazine Highlights for Children strongly condemned the Trump administration’s policy of separating migrant children from their families at the U.S.-Mexico border in a blistering statement shared online Tuesday.", "\n\nKent Johnson, CEO of the venerable publication, urged the government to “cease this activity,” which he called “unconscionable” and said “causes irreparable damage to young lives.” ", "He asked people to write to their elected representatives to express their outrage.", "\n\n“As a company that helps children become their best selves — curious, creative, caring, and confident — we want kids to understand the importance of having moral courage,” Johnson wrote. “", "Moral courage means standing up for what we believe is right, honest, and ethical — even when it is hard.”", "\n\nJohnson said the company’s core belief — that “children are the world’s most important people” — applied to “ALL children.”", "\n\n“This is not a political statement about immigration policy,” Johnson continued, but one “about human decency, plain and simple.”", "\n\n“Let our children draw strength and inspiration from our collective display of moral courage,” the statement concluded. “", "They are watching.”", "\n\nCheck out the statement here:" ]

{ "pile_set_name": "OpenWebText2" }

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[ "// Package lru provides three different LRU caches of varying sophistication.", "\n//\n// Cache is a simple LRU cache. ", "It is based on the\n// LRU implementation in groupcache:\n// https://github.com/golang/groupcache/tree/master/lru\n//\n// TwoQueueCache tracks frequently used and recently used entries separately.", "\n// This avoids a burst of accesses from taking out frequently used entries,\n// at the cost of about 2x computational overhead and some extra bookkeeping.", "\n//\n// ARCCache is an adaptive replacement cache. ", "It tracks recent evictions as\n// well as recent usage in both the frequent and recent caches. ", "Its\n// computational overhead is comparable to TwoQueueCache, but the memory\n// overhead is linear with the size of the cache.", "\n//\n// ARC has been patented by IBM, so do not use it if that is problematic for\n// your program.", "\n//\n// All caches in this package take locks while operating, and are therefore\n// thread-safe for consumers.", "\npackage lru\n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nupdate my join on temporary table\n\nI have a table called leaderboard \nwhich I create\n create temporary table leaderboard \n (\n rank integer primary key auto_increment, \n score_id integer, \n game varchar(65), \n user_id integer\n)\n\nselect \n id, \n highscore, \n playername \nfrom \n players \norder by \n highscore desc\n\nThis is fine but am now trying to update the table with a join in the id.\nUPDATE players \nSET players.rank = leaderboard.rank \nFROM players \nJOIN leaderboard ON players.id = leaderboard.id\n\nbut get an error in the mysql? ", "And pointers would be good\nerror is\n\n...the right syntax to use near 'FROM players JOIN leaderboard ON\n players.id = leaderboard.id' at line 1\n\nA:\n\nMaybe something like this:\nUPDATE players \nJOIN leaderboard ON players.id = leaderboard.id\nSET players.rank = leaderboard.rank\n\nMysql syntax is different from tsql. ", "That style would work on mssql\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "1. ", "Introduction\n===============\n\nMalaria is the single most important cause of ill health, death and poverty in sub-Saharan Africa \\[[@B1-molecules-19-21276],[@B2-molecules-19-21276]\\]. ", "Malaria vector control relies on insecticides for killing mosquitoes, thereby reducing man-mosquito contact and transmission \\[[@B3-molecules-19-21276]\\]. ", "Today, 14 insecticides from four major classes of synthetic chemical insecticides are recommended for indoor residual spraying (IRS) and six insecticides, all belonging to the pyrethroid group, are recommended for insecticide treated material (ITM) and long-lasting insecticide treated nets (LLIN) \\[[@B4-molecules-19-21276],[@B5-molecules-19-21276],[@B6-molecules-19-21276]\\]. ", "Constant exposure to insecticides invariably causes insecticide resistance \\[[@B7-molecules-19-21276]\\]. ", "A dramatic increase in pyrethroid resistance in malaria mosquitoes has been reported during the last decade and is now widespread throughout Africa \\[[@B8-molecules-19-21276]\\]. ", "Resistance is now considered a threat to current advances in malaria control \\[[@B9-molecules-19-21276],[@B10-molecules-19-21276]\\]. ", "One of the main challenges for vector control is, therefore, to preserve and improve current insecticide-based interventions, but also to develop a broader range of new insecticides with novel modes of action that can circumvent the current threat of insecticide resistance. ", "Few new insecticides have been developed for public health in the last 30 years \\[[@B9-molecules-19-21276]\\]. ", "However, alternative candidates for vector control have been tested with promising results, such as dinotefuran \\[[@B11-molecules-19-21276]\\], indoxacarb \\[[@B12-molecules-19-21276]\\], and clorfenapyr \\[[@B13-molecules-19-21276]\\]. ", "All showed no cross resistance with the common resistance mutations, *kdr* and *ace1*, but had late-acting effect and kill insects at higher doses than conventional insecticides. ", "As all recommended insecticides for vector control are nerve poisons being acetylcholinesterase (AChE) inhibitors or sodium channel modulators, excessive use may be harmful to humans and the environment, highlighting the need for safer and less expensive insecticides and repellents. ", "Many current research initiatives aim at exploring natural plant extracts and their derivatives as sources of developing new anti-insect compounds. ", "However, most such research has focused on larvicides and repellents, and relatively little work has been undertaken on adulticides \\[[@B14-molecules-19-21276]\\].", "\n\nThe genus *Zanthoxylum*, syn. *", "Fagara*, belongs to the Rutaceae family and is found in tropical and subtropical regions around the world. ", "It is a rich genus, with up to 250 identified species. ", "Many of these species are traditionally used for controlling pests, infectious and metabolic diseases \\[[@B15-molecules-19-21276],[@B16-molecules-19-21276]\\]. ", "A considerable amount of research has been directed towards chemical analyses and biological activity of extracts and constituents of different plant parts of various species in the *Zanthoxylum* genus. ", "Biological activity has been found against a wide range of organisms, including insects such as mosquitoes, beetles, cockroaches, and houseflies \\[[@B17-molecules-19-21276],[@B18-molecules-19-21276],[@B19-molecules-19-21276],[@B20-molecules-19-21276],[@B21-molecules-19-21276],[@B22-molecules-19-21276],[@B23-molecules-19-21276],[@B24-molecules-19-21276],[@B25-molecules-19-21276]\\]. ", "Alkaloids, amides, and terpenoids appear to be the substances most often implicated in anti-insect effects.", "\n\n*Zanthoxylum heitzii* (Aubrév. & ", "Pellegr.) ", "P.G. Waterman, locally known as olon in the Republic of Congo, commonly occurs in the region from southern Cameroon to the Democratic Republic of Congo \\[[@B26-molecules-19-21276]\\]. *", "Z. heitzii* has many traditional uses in Central and West Africa. ", "Preparations from this plant have been reported to be used against a variety of diseases including jaundice \\[[@B27-molecules-19-21276]\\], toothache \\[[@B28-molecules-19-21276]\\], gonorrhea \\[[@B29-molecules-19-21276]\\], and malaria \\[[@B26-molecules-19-21276]\\]. ", "It has also been reported to be used as fish poison \\[[@B26-molecules-19-21276]\\].", "\n\nOnly a few investigations on chemical constituents and biological activity of *Z. heitzii* have been carried out, but alkaloids, lignans, triterpenes, esters and amides have been reported \\[[@B30-molecules-19-21276],[@B31-molecules-19-21276],[@B32-molecules-19-21276],[@B33-molecules-19-21276]\\]. ", "Hexane extracts from *Z. heitzii* bark was shown to be toxic to two weevil species and the American cockroach \\[[@B34-molecules-19-21276]\\] and having antifilarial effect on the nematode *Loa loa* \\[[@B35-molecules-19-21276]\\]. ", "A preparation of *Z. heitzii* has been patented as an antiviral, antibacterial and immunostimulating remedy with possible anti-AIDS activity \\[[@B36-molecules-19-21276]\\]. ", "Methanol extracts (not further characterized) of bark of *Fagara heitzii* (a.k.a. *", "Z. heitzii*) induced \\>60% cell death in four out of five human cancer cell lines and also inhibited the growth of gram-positive bacteria \\[[@B37-molecules-19-21276]\\].", "\n\nHowever, no studies have been carried out so far on the adulticidal properties of *Z. heitzii* against malaria vector mosquitoes. ", "Based on this background, we investigated the intrinsic insecticidal effect of *Z. heitzii* stem bark, seed and leaf extracts on adult *Anopheles gambiae* s.s. ", "mosquitoes.", "\n\n2. ", "Results and Discussion\n=========================\n\n2.1. ", "Extraction and Characterization of Active Fractions\n--------------------------------------------------------\n\nThe extract yields achieved by the two extraction methods and for the different plant parts are shown in [Table 1](#molecules-19-21276-t001){ref-type=\"table\"}. ", "^1^H- and ^13^C-NMR spectra of these extracts showed the presence of signals from aromatic, olefinic, oxygenated and aliphatic compounds. ", "NMR spectra of Soxhlet and ASE hexane extracts were nearly identical (for NMR spectra, see [Supplementary material, Figures S1--S4](#app1-molecules-19-21276){ref-type=\"app\"}). ", "From initial screening of extracts with HPLC-DAD (wavelength range of 200--400 nm), 237 nm was chosen as the reference wavelength as it gave the best profile of the constituents. ", "The maximum wavelength at 237 nm could indicate that the major constituents of the bark hexane extracts are alkaloids (see below). ", "The HPLC chromatograms at 237 nm showed some structural differences between the samples extracted by ASE and Soxhlet. ", "The bark Soxhlet hexane extract gave a major peak (Rt 8.0 min) and three minor peaks (Rt 4.5, 6.7 and 7.6 min) ([Supplementary material, Figure S5](#app1-molecules-19-21276){ref-type=\"app\"}). ", "The corresponding ASE hexane extract had the same major peak but the proportions between the constituents observed were different ([Supplementary material, Figure S6](#app1-molecules-19-21276){ref-type=\"app\"}). ", "This could be explained by the different extraction yields of these two methods.", "\n\nmolecules-19-21276-t001_Table 1\n\n###### \n\nExtraction yields (w/w) of *Zanthoxylum heitzii* stem bark, seeds and leaves by Soxhlet and Accelerated Solvent Extraction (ASE) methods. ", "All extracts, except the Soxhlet hexane leaf extract, were used in the mosquito bioassays.", "\n\n \\# Extraction Method Solvent Bark Seed Leaf\n ---- ------------------- ------------------------- ------- ------- -------\n 1 Soxhlet Hexane 2.0% 29.0% 2.7%\n 2 ASE Hexane 0.75% 28.0% 2.3%\n 3 ASE Ethyl acetate 0.4% 1.9% 1.5%\n 4 ASE Ethanol (96%) 2.4% 7.9% 13.5%\n 5 ASE Ethanol/water (50%/50%) 4.6% 11.1% 1.9%\n 6 ASE Water (100%) 1.6% 2.3% 5.8%\n\n2.2. ", "Mosquito Bioassays\n-----------------------\n\n### 2.2.1. ", "General Toxicity\n\nThe stem bark extracts of *Z. heitzii* produced the highest mortalities in all mosquito strains and overall the hexane extracts were the most effective ([Figure 1](#molecules-19-21276-f001){ref-type=\"fig\"}, [Table 2](#molecules-19-21276-t002){ref-type=\"table\"}). ", "Mortality generally declined with increasing polarity of the solvent; water extracts producing the lowest mortalities. ", "In the susceptible strain, 1% concentration of each bark hexane extract achieved 100% mortality, whereas 0.1% of the Soxhlet hexane extract killed \\>90% of mosquitoes and 0.1% of the ASE hexane extract killed about 80% of mosquitoes. ", "In both resistant strains, the 0.1%-concentrations provided less than 80%, and 1%-bark hexane extract concentration was needed to achieve close to 100% mortality ([Figure 1](#molecules-19-21276-f001){ref-type=\"fig\"}). ", "Also the 1% bark ethyl acetate extracts produced \\>80% mortality in all mosquito strains. ", "The toxicity of seed and leaf extracts was generally less than 30%, regardless of solvent, extraction method, or concentration ([Figure 1](#molecules-19-21276-f001){ref-type=\"fig\"}). ", "However, the AcerKis strain was slightly more sensitive compared to the other strains when exposed to 1% of seed extracts from ASE ethyl acetate, ethanol and ethanol/water solvents, producing mortalities \\~50%.", "\n\n### 2.2.2. ", "Toxicity to Hexane Bark Extracts\n\nThe Pearson goodness-of-fit chi-square statistic showed an adequate fit of the factor data to the model (χ^2^ = 12.22, df = 10, *p* = 0.27). ", "The parallelism test of the two factors was not significant (χ^2^ = 1.40, df = 1, *p* = 0.24), indicating that there is no significant difference between the slopes of the two lines, *i.e*., ", "the relative responses of the two extracts are similar ([Figure 2](#molecules-19-21276-f002){ref-type=\"fig\"}). ", "However, the relative median potency of the ASE method is significantly higher than the Soxhlet method is (0.78, 95% CI 0.60--0.92) (confidence interval does not include 1). ", "The dose-mortality relationships indicate that the ASE extract was slightly more toxic (LD~50~) than the Soxhlet extract against mosquitoes ([Table 3](#molecules-19-21276-t003){ref-type=\"table\"}).", "\n\n{#molecules-19-21276-f001}\n\nmolecules-19-21276-t002_Table 2\n\n###### \n\nMean mortality rates from general toxicity trial analyzed by ANOVA. ", "The factor mortalities within each group reflect general mortalities which are influenced by other group factors. ", "Therefore, mortalities do not indicate true mortalities, but are presented to show the relationships between each factor. ", "For example, the real mortality of stem bark is much higher than 33.8% but is significantly different from seeds and leaves. ", "The mosquito strains used were *Anopheles gambiae* s.s. ", "susceptible (Kis), carbamate/organophosphate resistant (AcerKis), and pyrethroid resistant (kdrKis), and pyrethroid resistant (kdrKis).", "\n\n --------------------------------------------------------------------------------------------------------------------------\n Group Factors *n* Mortality ^a^ df F *p*-Value \n --------------------------- ---------------- ----------- --------------- ------------ ------------- ----------- ----------\n Mosquito strain Kis 51 18.4 ^§^ 10.8--26.0 df~1~ = 2\\ 0.24 0.784\n df~2~ = 150 \n\n AcerKis 51 19.9 ^§^ 12.1--27.8 \n\n kdrKis 51 16.2 ^§^ 9.3--23.2 \n\n Plant part Stem bark 54 33.8 ^†^ 23.6--44.0 df~1~ = 2\\ 17.99 \\<0.0001\n df~2~ = 150 \n\n Seed 54 11.1 ^‡^ 7.6--14.7 \n\n Leaf 45 7.9 ^‡^ 5.4--10.3 \n\n Extract concentration 0.01% 51 6.4 ^α^ 3.7--9.1 df~1~ = 2\\ 14.49 \\<0.0001\n df~2~ = 150 \n\n 0.10% 51 16.0 ^β^ 9.3--22.7 \n\n 1.00% 51 32.1 ^γ^ 22.7--41.6 \n\n Extraction method/solvent Soxhlet/hexane 18 35.3 ^a^ 15.5--55.2 df~1~ = 5\\ 3.91 0.002\n df~2~ = 147 \n\n ASE/hexane 27 26.2 ^ac^ 12.3--40.2 \n\n ASE/ethyl acetate 27 19.9 ^bc^ 9.0--30.8 \n\n ASE/96% ethanol 27 15.5 ^bc^ 7.4--23.6 \n\n ASE/50% ethanol-water 27 12.1 ^bd^ 7.9--16.3 \n\n ASE/100% water 27 5.7 ^bd^ 3.1--8.3 \n --------------------------------------------------------------------------------------------------------------------------\n\n^a^: Multiple comparisons by Duncan's posthoc test. ", "Within each factor, mortalities with different superscript symbols are significantly different from each other at the α = 0.05% level.", "\n\n2.3. ", "Discussion\n---------------\n\nWe showed that crude extracts of *Zanthoxylum heitzii* plant parts kill *Anopheles gambiae* s.s., ", "the primary vector of malaria in Sub-Saharan Africa. ", "Insecticidal activity varied according to plant part, extraction method, solvent, and mosquito strain. ", "Seed and leaf extracts produced very low mortalities, compared to the bark extracts, indicating that toxic compounds are mainly present in the bark. ", "This is consistent with previous reports \\[[@B34-molecules-19-21276]\\]. ", "In our study, mortalities ranged from 97% to 100% in the three mosquito strains (insecticide susceptible and resistant) when exposed to the highest test concentration (1%) of Soxhlet and Accelerated Solvent Extraction (ASE) hexane stem bark extracts. ", "The ASE bark extracts produced the highest mortality with an LD~50~ of 102 ng/mg female mosquito in the susceptible strain of *An. ", "gambiae* s.s. ", "In comparison, the Soxhlet extraction method gave an LD~50~ of 144 ng/mg female mosquito. ", "We found no significant difference in mortality between the insecticide susceptible, the pyrethroid resistant, (L1014F mutation present), and the carbamate/organophosphate resistant (*Ace1^R^* mutation present) strains, indicating no cross resistance with conventional insecticides.", "\n\n{#molecules-19-21276-f002}\n\nmolecules-19-21276-t003_Table 3\n\n###### \n\nEfficacy of *Z. heitzii* stem bark hexane extracts using Accelerated Solvent Extraction (ASE) and Soxhlet methods against susceptible (*kdr*) *An. ", "gambiae* s.s. ", "by topical application.", "\n\n Extraction Method Slope (±SD) LD~50~ ng/mg Female (95% CI) LD~95~ ng/mg Female (95% CI)\n ------------------- ------------- ------------------------------ ------------------------------\n ASE 4.55 (1.07) 101.86 (74.75--117.93) 234.05 (191.85--379.84)\n Soxhlet 6.50 (1.49) 144.45 (124.99--161.59) 258.71 (214.93--404.18)\n\nHexane proved to be the best solvent for extracting *Z. heitzii* compounds, thus showing that the active components are lipophilic. ", "The NMR spectra of Soxhlet and ASE hexane extracts were almost identical, showing the presence of aromatic, olefinic, oxygenated and aliphatic compounds. ", "The HPLC chromatograms indicated that the major constituents might be alkaloids. ", "Alkaloids are well known in *Zanthoxylum* species \\[[@B15-molecules-19-21276]\\].", "\n\nThe HPLC also showed some differences between the Soxhlet and ASE hexane extracts. ", "While the components present appeared to be mostly the same, the ratios between them differed. ", "This could potentially be explained by the different extraction yields (2% by Soxhlet and 0.75% by ASE). ", "It is not clear from the chemical analyses why the mosquito bioassays showed a higher potency of the ASE extract than the Soxhlet extract. ", "It could be that the higher extractive yield in the Soxhlet extraction gives more inactive material, thus diluting the active components. ", "In this study, we only report results from crude extracts, but our further research will focus on identifying the most active fractions and compounds in the hexane extracts and testing them in mosquito bioassays.", "\n\nAlthough *Z. heitzii* crude stem bark extract can kill adult female mosquitoes, it is not as effective as synthetic insecticides. ", "As a comparison, studies have shown very low median lethal doses in *An. ", "gambiae* exposed synthetic insecticides, e.g., 1.02 ng/mg female for permethrin, 0.018 ng/mg for deltamethrin, 0.14 ng/mg for bifenthrin, 0.04 ng/mg for fibronil, 0.34 ng/mg for dinetofuran, and 1.14--2.25 ng/mg for chlorpyrifos-methyl (depending on susceptible and *kdr* resistant strains) \\[[@B11-molecules-19-21276],[@B38-molecules-19-21276]\\]. ", "In another study, pyrethrum, also a natural product, had LD~50~'s of 1.9 ng/mg and 16.0 ng/mg in susceptible and pyrethroid resistant *An. ", "gambiae*, respectively \\[[@B39-molecules-19-21276]\\].", "\n\nApart from pyrethrum, it is not clear how well *Z. heitzii* performs as an adulticide compared to other botanical compounds. ", "There is an emphasis in the botanical insecticide literature on larvicidal effects against malaria vectors, and reports on toxicity against adult mosquitoes are rare \\[[@B14-molecules-19-21276]\\]. ", "The focus on larvicides is potentially because of the comparative easiness of working with larvae. ", "Larvicides have, however, so far not played a large role in malaria vector control. ", "In an interim position statement, the WHO recommends use of larvicides in Sub-Saharan Africa in areas where breeding sites are few, fixed and findable \\[[@B40-molecules-19-21276]\\]. ", "In those investigations where adults have been tested, differences in methodology (e.g., topical application, adult bioassays) and reporting units (ng per mg mosquito, g per cm^2^ impregnated paper area, ppm) make comparisons difficult (e.g., \\[[@B41-molecules-19-21276]\\]). ", "To assess true (intrinsic) toxicity the topical application method should be used to avoid confusion with potential repellent effects. ", "For example, in the WHO tube bioassays, mosquitoes may avoid treated paper surfaces by resting on the untreated areas on the tops and bottoms of tubes.", "\n\nTo our knowledge, this is the first study investigating the insecticidal activity of *Z. heitzii* against mosquitoes of public health importance. ", "However, despite the urgent need to find new effective botanical and synthetic insecticides in the fight against malaria, the relatively low toxicity of *Z. heitzii* crude bark extracts to malaria mosquitoes could be an obstacle for further development. ", "On the other hand, encouragingly, our findings point to no apparent cross resistance with conventional insecticides. ", "In light of the rising problem of insecticide resistance, new insecticides are needed, and prospecting botanical resources should continue. ", "Although crude plant extracts for insecticide control may have an important local role in control insect pests, the constituent compounds in potentially effective plants should be further investigated. ", "Chemical synthesis of botanical insecticide analogues may also provide useful end products. ", "Further research is required to elucidate details of the chemistry and biological activity of *Z. heitzii*. ", "In addition to stem bark, seeds, and leaves, insect toxicity of other plant parts, such as flowers and root bark, should be investigated and tested on different mosquito species. ", "Repellent and synergistic effects of constituent compounds should be analyzed and the mode of action of active compounds determined. ", "Anecdotal reports say that *Z. heitzii* is toxic to fish \\[[@B26-molecules-19-21276]\\]; therefore, the potential toxicity to non-target organisms as well as environmental persistence of *Z. heitzii* extracts need to be further investigated.", "\n\nFinally, we agree with Isman and Grieneisen, \\[[@B42-molecules-19-21276]\\] that much of the scientific literature on botanical insecticides is of limited use unless results can be reproduced and comparisons between studies made. ", "A general research study protocol must be developed outlining detailed methodologies and standard operating procedures for botanical insecticide testing. ", "The research community should agree on a common research agenda to advance botanical insecticide development and commercialization.", "\n\n3. ", "Experimental Section\n=======================\n\n3.1. ", "Plant Material\n-------------------\n\nStem bark, seed and leaves of *Zanthoxylum heitzii* (Aubrév. & ", "Pellegr.) ", "P.G. Waterman (accepted name according to \\[[@B43-molecules-19-21276]\\]) were collected near Douakani village in south-western Republic of Congo during the rainy season of 2011 (December). ", "The plant material was identified using published keys \\[[@B44-molecules-19-21276]\\] and voucher specimens were deposited at the National Herbarium, Centre of Study on Botanical Resources (CERVE), Brazzaville. ", "Samples of the plant material are also deposited in the School of Pharmacy, Section of Pharmacognosy, University of Oslo, Norway (voucher numbers ZH-L111201, ZH-B111202, ZH-S111203).", "\n\n3.2. ", "Plant Preparation\n----------------------\n\nPlant material was dried locally at room temperature for seven days and transported to the laboratory in the University of Oslo, Norway. ", "Bark was cut into small pieces (\\<4 cm) and milled in a knife mill (Brabender, Duisburg, Germany) to pass through a 4-mm sieve. ", "Seeds of *Z. heitzii* were milled in the same way as the bark.", "\n\n3.3. ", "Extraction\n---------------\n\nExtraction was conducted in May-June 2012 using two different methods, the classical Soxhlet method and the Accelerated Solvent Extraction (ASE) method, using an ASE350 Solvent Extractor (Dionex, Sunnyvale, CA, USA). ", "Hexane was the only solvent used for the Soxhlet method, whereas five different solvents with increasing polarity (hexane, ethyl acetate, 96% ethanol, 50% water/ethanol and water) were used in the ASE method ([Table 1](#molecules-19-21276-t001){ref-type=\"table\"}).", "\n\nPowdered plant material (250 g bark), was placed in a Soxhlet extractor and extracted with *n*-hexane (3.5 L) for 10 h. The extract was allowed to cool to room temperature and filtered using a Whatman No.1 filter paper. ", "The extractor flask and filter were washed with dichloromethane and the washings combined with the filtrate. ", "It was then taken to dryness on a rotary evaporator at 40--50 °C followed by 30 min on an oil vacuum pump.", "\n\nIn the ASE, powdered bark, seeds and leaves (100 g of each) were extracted successively with hexane, ethyl acetate, 96% ethanol, 50% water/ethanol and water (*ca.* ", "0.3 L of each). ", "The solvents from the organic extractions were removed in vacuum on a rotary evaporator at 40 °C followed by 30 min in an oil pump vacuum. ", "The extracts from 50% water/ethanol and water extractions were freeze-dried.", "\n\nThe Soxhlet and ASE hexane extracts (most active in bioassays) were characterized by nuclear magnetic resonance (NMR) spectroscopy and high performance liquid chromatography (HPLC). ", "^1^H- and ^13^C-NMR spectra were recorded at 300 and 75 MHz, respectively, in deuterochloroform on a Bruker DPX300 instrument (Bruker, Rheinstetten, Germany). ", "HPLC analysis was performed on a LaChrom Elite HPLC system (VWR-Hitachi, Tokyo, Japan) equipped with an L-2455 diode array detector. ", "A Chromolith Performance RP18e 100 × 4.6 mm column (Merck, Darmstadt, Germany) was used for separation. ", "Elution was performed using a gradient of mobile phase A (water) and mobile phase B (acetonitrile) with the following time schedule: 20% B, 0--1 min; 20%--95% B, 1--15 min; 95% B, 15--16 min. ", "The concentration of injected samples was 0.5 mg/mL, injection volume was 10 µL and flow rate was 3.0 mL/min. ", "The absorbance was recorded at 237 nm, and separation took place at 25 °C. ", "All samples were filtered (0.45 µm) prior to injection. ", "The NMR spectra and HPLC chromatograms are appended as [Supplementary material](#app1-molecules-19-21276){ref-type=\"app\"}.", "\n\n3.4. ", "Mosquitoes\n---------------\n\nThree strains of *Anopheles gambiae* s.s. ", "Giles were used in this study: Kis: The Kisumu strain, originating from Kenya, is free of any detectable insecticide resistance mechanisms.kdrKis: A pyrethroid and DDT resistant strain. ", "This strain was obtained by introgression of L1014 F (*kdr*) into the genome of the susceptible Kisumu strain through successive backcrosses and selection with permethrin (1 mg/L). ", "kdrKis has the same genetic background as the Kisumu strain but has the L1014F allele at the homozygous state.", "AcerKis: An organophosphate and carbamate resistant strain. ", "This strain was obtained by introgression of insensitive acetylcholinesterase (*Ace1^R^*) into the genome of the Kisumu strain through successive backcrosses and selection with propoxur (10 mg/L). ", "AcerKis has the same genetic background as the Kisumu strain but differs by the presence of *Ace1^R^* allele (G119S) at homozygous state \\[[@B45-molecules-19-21276]\\].", "\n\nMosquitoes were reared in a temperature-controlled space at 25 ± 5 °C, and 80% ± 10% relative humidity in the laboratory at the Institut de Recherche de Developpement (IRD), Montpellier, France. ", "Strains were kept separately to ensure no accidental cross-breeding (contamination) between populations.", "\n\n3.5. ", "Mosquito Bioassays\n-----------------------\n\nIntrinsic insecticidal activity was assessed by topical application according to standard WHO protocol \\[[@B3-molecules-19-21276]\\]. ", "Two steps were carried out. ", "In the first step, the general toxicity of bark, seed, and leaf extracts produced by the different extraction methods and solvents was evaluated against both susceptible and resistant mosquitoes. ", "In the second step the toxicity of the most effective extracts was further evaluated to assess dose-effect relationships against susceptible mosquitoes. ", "In each test twenty-five 2--5 days old non-blood fed female mosquitoes were anaesthetized with carbon dioxide and placed on a plate cooled at 4 °C.", "\n\nStock solutions were prepared at 1% by dissolving crude extracts in acetone (for hexane, ethyl acetate, and water extracts) and in ethanol (for ethanol and ethanol/water extracts). ", "From the stock solutions, different concentrations were prepared and used in bioassays. ", "A volume of 0.1 μL of stock solution was deposited on the upper part of the pronotum of each mosquito. ", "Each test was duplicated giving a total of 50 mosquitoes per strain and per dose. ", "After application of the solutions, females were transferred to plastic cups provided with honey-soaked cotton and maintained at controlled temperature (27 ± 2 °C) and humidity (80% ± 10%) conditions. ", "Mortality rates were recorded after 24 h following tests and corrected using Abbott's formula.", "\n\n### 3.5.1. ", "Step 1---General Toxicity\n\nFirst, an initial examination of the general level of toxicity was carried out. ", "All three mosquito strains were exposed to three concentrations (0.01%, 0.1% and 1%) of each of the Soxhlet and ASE crude extracts of bark, seed and leaf of *Z. heitzii* (except Soxhlet hexane leaf extract). ", "In addition, 2 × 50 females were treated with 0.1 μL of pure solvent to serve as controls.", "\n\n### 3.5.2. ", "Step 2---Toxicity to Hexane Bark Extracts\n\nSoxhlet and ASE hexane bark extracts, being most toxic ([Figure 1](#molecules-19-21276-f001){ref-type=\"fig\"}), were selected for further examination of dose and mortality relationships. ", "Only the susceptible *An. ", "gambiae* s.s. ", "Kis strain was used in this step. ", "Female mosquitoes (2 × 25) were treated with 0.1 μL of each of seven concentrations (0.01%, 0.02%, 0.03%, 0.05%, 0.08%, 0.1% and 0.2%) of the two extracts. ", "These concentrations produced a range of 0%--100% mortality. ", "Four batches of 25 females each were used as controls.", "\n\n3.6. ", "Data Analysis\n------------------\n\nThe comparison between each concentration of bark, seed and leaf extract from the initial examination (step 1) was analyzed by one-way ANOVA using SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). ", "Multiple comparisons between factor levels were done by Duncan's posthoc test. ", "In the second step the relationship between dose and mortality in the insecticide susceptible mosquito strain was analyzed by probit analysis using SPSS software (IBM SPSS Statistics for Windows, Version 21.0. ", "IBM Corp., Armonk, NY, USA), which provides an estimation of the median lethal doses for each of the two compounds compared (Soxhlet and ASE bark *Z. heitzii* extracts). ", "Median lethal doses (LD~50~ and LD~95~ with 95% confidence intervals) are expressed in nanograms of active ingredient per mg of average mosquito body weight (calculated from 50 live mosquitoes). ", "The probit procedure further estimates the natural response rates, common slope and separate intercepts for each factor level. ", "The Pearson goodness-of-fit chi-square statistic was used to test the null hypothesis that the model adequately fits the data. ", "The relative median potency between the two compounds was compared and the parallelism was used to test if the assumption of equal slopes across factor levels is reasonable.", "\n\n4. ", "Conclusions\n==============\n\nThe olon tree, *Zanthoxylum* *heitzii*, is a traditional medicinal plant in Central and West Africa which also has insecticidal properties. ", "Our research indicates that crude bark extracts of *Z. heitzii* is toxic to *Anopheles gambiae*, the main malaria vector in Africa. ", "Although the insecticidal effect was lower than synthetic insecticides there was no apparent cross resistance with conventional insecticides. ", "Further research is warranted to determine insecticidal efficacy and synergistic effects of the chemical constituents in the bark of *Z. heitzii*. ", "We also encourage further studies on antiplasmodial activity of this species as it has been reported as being used as a malaria cure \\[[@B26-molecules-19-21276]\\]. ", "The toxicity to non-target organisms of various plant parts of this species also need to be investigated.", "\n\nThe Research Council of Norway funded this work (FUGE Bio prospecting, project establishment support, project No. ", "209508/S10). ", "For laboratory assistance we thank Suthajini Yogarajah and Ingvild Austarheim at the University of Oslo, Norway. ", "The NMR laboratory at the Department of Chemistry, University of Oslo, is acknowledged for use of NMR instruments.", "\n\n*Sample Availability*: Samples of the *Zanthoxylum heitzii* bark used are available from the authors.", "\n\nSupplementary materials (Figures S1--S6) can be accessed at: <http://www.mdpi.com/1420-3049/19/12/21276/s1>.", "\n\n###### \n\nClick here for additional data file.", "\n\nP.S., B.M. and Y.-F.Z. carried out the experimental work. ", "H.J.O., K.E.M., B.S.P., D.M., S.D., V.C. and F.C. designed the study, H.J.O., K.E.M. and H.W. prepared the manuscript, H.J.O. coordinated the project. ", "All authors read and approved the final manuscript.", "\n\nThe authors declare no conflict of interest.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Long-range and many-body effects in coagulation processes.", "\nWe study the problem of diffusing particles which coalesce upon contact. ", "With the aid of a nonperturbative renormalization group, we first analyze the dynamics emerging below the critical dimension two, where strong fluctuations imply anomalously slow decay. ", "Above two dimensions, the long-time, low-density behavior is known to conform with the law of mass action. ", "For this case, we establish an exact mapping between the physics at the microscopic scale (lattice structure, particle shape and size) and the macroscopic decay rate in the law of mass action. ", "In addition, we identify a term violating this classical law. ", "It originates in long-range and many-particle fluctuations and is a simple, universal function of the macroscopic decay rate." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "1. ", "Field of the Invention\nThe present invention relates to arc routing systems and methods thereof, and more particularly to an arc routing system and method that can route an area of a printed circuit board with high component density.", "\n2. ", "Description of Related Art\nRouting of printed circuit boards has ranged from hand layout to autorouting of all wires. ", "The need to complete routing rapidly and correctly with large numbers of nets and electrical constraints has driven the development and use of specialized autorouters. ", "However, for an area of a printed circuit board with high component density, hand layout is preferred to optimize the routing.", "\nFor an area of a printed circuit board with high component density, keepout regions are usually formed around each component in order to avoid signal crosstalk and short circuits. ", "As a result, signal lines should be taken round and kept away from many keepout regions. ", "Thus, a routing engineer needs to route a wire piece by piece by try and error method, which not only results in a low routing speed but also results in irregular wires. ", "The irregular wires will adversely affect the signal transferring. ", "Meanwhile, the irregular wires introduce electrical and signal resistances, thereby decreasing the electrical connection performance of printed circuit boards.", "\nAccordingly, there is a need to develop an arc routing system and method to simplify routing, increase routing efficiency and improving electrical connection performance of printed circuit boards." ]

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[ "Judges Need to Follow the Bible\n\nFour years after the Iowa State Supreme Court ruled in favor of marriage equality, the majority of the Hawkeye State’s Republican candidates for U.S. Senate have promised to block the appointment of any federal judge who doesn’t follow “natural law” or possess a “biblical view of justice.” ", "An organization called The Family Leader, one of the top financial supporters of the 2010 movement to oust the marriage-equality judges, hosted a forum for the Iowa candidates over the weekend. ", "The moderator, right-wing commentator Erik Erikson, asked the candidates what they look for in a federal judge. ", "Sam Clovis, who thinks the only reason Obama hasn’t been impeached yet is because he’s black, said judicial nominees must be able to “explain to me natural law and natural rights.” ", "Matt Whitaker said judges must be “people of faith” and have “a biblical view of justice.” ", "Not content to be outdone, State Sen. Joni Ernst said judges should have an “understanding [of] where the Constitution came from and our laws, and they all did come from God.”", "\n\nGlenn Beck: Hillary Clinton Is a Gay Copycat\n\nREAD MORE Outside Cash Floods N.C. Judicial Race\n\nGlenn Beck accused Hillary Clinton of being both a lesbian and one of those “coward” politicians who only back things like gay marriage once they’ve become popular. ", "One of his radio show co-hosts noted that Hillary Clinton came out in favor of same-sex marriage last year, to which he replied, “What I just heard you say is that Hillary came out last year? ", "Because I didn’t think that had officially…” His attempt at a joke trailed off as his co-host, not laughing, continued what he was saying. ", "But Beck wasn’t done. “", "I’m telling you, Hillary Clinton will be having sex with a woman on the White House desk if it becomes popular,” he said.", "\n\nDemocratic Rep. Plans to Hand Out KKK Hoods at GOP Convention\n\nREAD MORE Gay Republican vs. The LGBT Lobby\n\nWisconsin gubernatorial candidate Brett Hulsey, a Democratic state representative, announced Thursday that he will hand out Ku Klux Klan hoods at the state GOP convention this weekend. ", "Hulsey called the items “Republican Party hats.” ", "While his antics were quickly denounced by the state Democratic Party, Hulsey defended himself declaring, “What I find offensive is Gov. Walker and the Republicans’ racist record. ", "They’re the ones considering the resolution to leave the United States.” ", "Hulsey pointed to state Republicans ending record-keeping on racial profiling by police, cutting back on income-eligibility limits for Medicaid, and voting changes.", "\n\nStory continues\n\nCali Mayor: People Choose to Be Homeless\n\nREAD MORE Petraeus and the ACORN ‘Pimp’\n\nTemecula, Calif., Mayor Maryann Edwards says homeless people live on the street by choice. ", "She revealed this belief in the comments section of a blog post about her plan to “eliminate” homelessness by basically criminalizing it and discouraging people from giving money to the poor. “", "Homeless people panhandling on the off ramps are homeless by choice,” Edwards wrote in the comments section of a post on Nonprofit Quarterly’s website that questioned how the mayor plans to provide housing and services for her leafy city’s 80 homeless people without spending any taxpayer money. “", "They have rejected all forms of help and have chosen instead to play on the sympathy of generous residents.”", "\n\nRelated from The Daily Beast\n\nLike us on Facebook - Follow us on Twitter - Sign up for The Cheat Sheet Newsletter" ]

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[ "Tertiapin-Q removes a large and rapidly acting component of vagal slowing of the guinea-pig cardiac pacemaker.", "\nThe participation of acetylcholine-activated potassium current (I(K,ACh)) and hyperpolarization-activated pacemaker current (I(f)) in vagal bradycardia were examined using vagally-innervated preparations of guinea-pig atria. ", "Preparations were maintained in Krebs-Henseleit solution (36 degrees C). ", "Before treatment, trains of vagal stimuli (10 s at 2, 5 and 10 Hz) produced graded bradycardias displaying rapid onset and offset. ", "Tertiapin-Q (300 nM), which blocks I(K,ACh), had no effect on baseline atrial rate. ", "In tertiapin-Q, vagal bradycardia displayed a gradual onset and offset, with a peak response ~50% of that recorded in control conditions. ", "Cumulative addition of 1 mM ZD7288 (blocker of I(f)) caused atrial rate to fall by ~60%, but had no further effect on the amplitude of the vagal bradycardia, while response onset and offset became slightly faster. ", "From these observations, we argue that (i) vagal bradycardia was attributable primarily to activation of I(K,ACh), (ii) vagal modulation of I(f) had a minor influence on the rate of onset and offset of bradycardia, and (iii) removal of the influence of I(K,ACh) unmasked a slow response, of undetermined origin, to vagal stimulation. ", "In a separate set of experiments we compared the effects of 1 mM Ba(2+) and 300 nM tertiapin-Q on vagal bradycardia. ", "Ba(2+) reduced baseline atrial rate and the response to vagal stimulation. ", "Subsequent cumulative addition of tertiapin-Q had no additional effect on baseline atrial rate, but caused further reduction in the amplitude of vagal bradycardia, suggesting that 1 mM Ba(2+) did not achieve a complete block of I(K,ACh) in this preparation." ]

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[ "1. ", "Introduction {#sec1-cancers-11-00043}\n===============\n\nEstrogen receptor-α (ERα) is a nuclear receptor \\[[@B1-cancers-11-00043],[@B2-cancers-11-00043],[@B3-cancers-11-00043]\\] that responds to estrogen stimulation by translocating to the nucleus and regulating the transcription of target genes, including ERα and genes involved in regulating tumor progression \\[[@B4-cancers-11-00043]\\]. ", "Nearly 70% of breast cancers express ERα and rely on estrogen binding for growth and promotion of tumorigenesis \\[[@B4-cancers-11-00043]\\]. ", "Many ERα+ breast cancer patients are treated with the anti-estrogen tamoxifen, which binds to the receptor within the ligand-binding domain (LBD). ", "Mechanistically, binding of tamoxifen to the receptor results in a conformational change, initially decreasing the capacity of ERα to engage target genes. ", "Aside from the tamoxifen-ERα interaction, tamoxifen-induced oxidative damage was reported to be an integral component of its therapeutic efficacy \\[[@B5-cancers-11-00043],[@B6-cancers-11-00043],[@B7-cancers-11-00043]\\], through increased reactive oxygen species (ROS), and blocking ROS activity reduced anti-estrogen sensitivity \\[[@B8-cancers-11-00043]\\]. ", "Although highly effective in ER+ breast cancers, many of these patients develop resistance to tamoxifen, relapse and eventually succumb to the disease, despite continued ERα expression in their tumors \\[[@B9-cancers-11-00043]\\]. ", "In this regard, a better underlying mechanisms mediating tamoxifen resistance is of foremost clinical significance \\[[@B10-cancers-11-00043]\\].", "\n\nEndocrine resistance evolves from many mechanisms, including altered epigenetic regulation \\[[@B11-cancers-11-00043],[@B12-cancers-11-00043],[@B13-cancers-11-00043]\\], as well as post-translational modifications (PTMs) of ERα \\[[@B10-cancers-11-00043],[@B14-cancers-11-00043],[@B15-cancers-11-00043]\\]. ", "Many PTMs modify the ability of ERα to interact with transcriptional cofactors and engage target gene sequences in response to tamoxifen therapy, shifting tamoxifen from an antagonist to an ERα agonist \\[[@B15-cancers-11-00043]\\]. ", "In this context, additional understanding of ERα regulation may help identify novel approaches to overcome tamoxifen resistance in the presence of persistent ERα expression.", "\n\nPoly (ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme \\[[@B16-cancers-11-00043]\\] that regulates cell signaling and the DNA damage response by poly-ADP-ribosylating (PARylating) target proteins, including PARP1 itself \\[[@B17-cancers-11-00043],[@B18-cancers-11-00043]\\]. ", "A critical role for PARP1 in tumor progression through regulation of oxidative DNA damage has been demonstrated and indicated as a mechanism to overcome PARPi resistance \\[[@B19-cancers-11-00043],[@B20-cancers-11-00043]\\]. ", "Classically, clinical applications of PARP inhibitors (PARPi), such as talazoparib and veliparib, target BRCA-related cancers with defects in HR-mediated DNA repair pathways \\[[@B21-cancers-11-00043],[@B22-cancers-11-00043],[@B23-cancers-11-00043]\\]. ", "In addition to DNA damage, PARP1 regulates the activity of many nuclear receptors, including ERα \\[[@B24-cancers-11-00043]\\]. ", "It was revealed in a breast cancer model (MCF7, ERα-positive) that in response to estradiol, ERα and PARP1 co-localize to ERα-target genes to regulate their expression \\[[@B25-cancers-11-00043]\\]. ", "Furthermore, in vascular smooth muscle cells, ERα was demonstrated to be PARylated by PARP1 within the DNA binding domain (DBD), allowing for increased and maintained nuclear localization of ERα \\[[@B26-cancers-11-00043]\\]. ", "However, whether or not ERα is PARylated in breast cancer cells, and if PARylation correlates with tamoxifen response, is unknown.", "\n\nBased on previous reports demonstrating elevated oxidative stress in ERα-positive, tamoxifen resistant breast cancer \\[[@B5-cancers-11-00043],[@B8-cancers-11-00043],[@B27-cancers-11-00043]\\] and the role of PARP1 in responding to oxidative damage \\[[@B28-cancers-11-00043],[@B29-cancers-11-00043]\\], we hypothesized that combining the antiestrogen tamoxifen with a PARPi would sensitize tamoxifen resistant, ERα-positive breast cancer to tamoxifen therapy. ", "We tested our hypothesis in a MCF7-based breast cancer cell model systems. ", "Combining a PARPi with tamoxifen altered ERα PARylation and decreased ERα-PARylation, and this was sufficient to overcome tamoxifen resistance in hormone-refractory, ERα-positive breast cancer cells. ", "Our results demonstrate a novel mechanism of resistance to antiestrogen therapy and support a therapeutic approach for overcoming endocrine-resistant, ERα-positive breast cancer.", "\n\n2. ", "Results {#sec2-cancers-11-00043}\n==========\n\n2.1. ", "Survival of Tamoxifen-Sensitive and -Resistant Breast Cancer Cells Is Inhibited by Tamoxifen-Talazoparib Combination {#sec2dot1-cancers-11-00043}\n-------------------------------------------------------------------------------------------------------------------------\n\nWe observed that tamoxifen-resistant (MCF7-T) cells showed increased levels of oxidative damage ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}A), as indicated by immunofluorescence staining for the oxidative-damage marker 8-hydroxyguanosine (8-oxoG), consistent with previous studies \\[[@B27-cancers-11-00043]\\] and validated this observation by measuring basal levels of reactive oxygen species (ROS) in tamoxifen-sensitive versus -resistant cell lines. ", "As indicated by immunofluorescence, we observed increased (*p* \\< 0.05) levels of ROS in MCF7-T cells compared to the MCF7 parental cells ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}B). ", "We and others have demonstrated that oxidative damage caused by ROS promotes PARP1 activation \\[[@B28-cancers-11-00043],[@B29-cancers-11-00043]\\]. ", "We measured PARP1 levels and activity (indicated by poly-(ADP)-ribosylation (PARylation)), using western blot and ELISA assays and observed that basal PARP1 levels and activity were higher in MCF7-T cells compared to MCF7 cells ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}C and [Supplemental Figure S1A](#app1-cancers-11-00043){ref-type=\"app\"}), as well as active ERBB2 (pERBB2), a marker of tamoxifen resistance \\[[@B30-cancers-11-00043]\\]. ", "Furthermore, tamoxifen treatment increased (*p* \\< 0.05) PARP1 activity in both parental and resistant cell lines ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}D; ELISA assay).", "\n\nTo examine whether PARP1 inhibition altered cell sensitivity to tamoxifen, we treated MCF7 and MCF7-T cells with tamoxifen alone or in combination with talazoparib and performed colony formation assays. ", "As expected, tamoxifen alone decreased (*p* \\< 0.05) MCF7 clonogenic survival, and increased (*p* \\< 0.05) MCF7-T cell clonogenicity ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}E). ", "Despite differential response to tamoxifen, co-administration of tamoxifen and talazoparib decreased (*p* \\< 0.05) cell survival in both MCF7 and MCF7-T cells ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}E, [Supplemental Figure S1B,C](#app1-cancers-11-00043){ref-type=\"app\"}). ", "The observed decrease in colony formation was synergistic (CI \\< 1) ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}F, [Supplemental Figure S1B,C](#app1-cancers-11-00043){ref-type=\"app\"}), as determined by the Chou-Talalay method \\[[@B31-cancers-11-00043]\\]. ", "Similar combinatorial efficacy was observed upon co-administration of tamoxifen with the less potent PARPi veliparib (Velip; [Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}G) \\[[@B32-cancers-11-00043]\\].", "\n\nTo confirm the combinatorial efficacy of tamoxifen and talazoparib was not limited to the tamoxifen-resistant cells examined, we performed clonogenic survival assays in independently derived tamoxifen-resistant, ERα+ breast cancer cell lines (LCC2, LCC9; ref \\[[@B33-cancers-11-00043]\\]). ", "Treatment of LCC2 and LCC9 with tamoxifen-talazoparib decreased (*p* \\< 0.05) cell survival (CI \\< 1; [Supplemental Figure S1D,E](#app1-cancers-11-00043){ref-type=\"app\"}, respectively). ", "Furthermore, PARP1 activity was increased (*p* \\< 0.05) in LCC2 and LCC9 cell lines compared to MCF7 parental cells ([Supplemental Figure S1F](#app1-cancers-11-00043){ref-type=\"app\"}) and tamoxifen further increased (*p* \\< 0.05) PARP1 activity ([Supplemental Figure S1G](#app1-cancers-11-00043){ref-type=\"app\"}).", "\n\nTo validate the observed decrease in colony formation by MCF7 and MCF7-T cells in anchorage-dependent growth conditions, survival was also measured under anchorage-independent conditions. ", "Both MCF7 and MCF7-T cells were plated within an agarose substrate and treated with tamoxifen in the presence and absence of talazoparib. ", "Consistently, tamoxifen alone decreased (*p* \\< 0.05) MCF7 cell survival, while combination tamoxifen-talazoparib further decreased (*p* \\< 0.05) both MCF7 and MCF7-T survival compared to control or either single agent ([Supplemental Figure S2A](#app1-cancers-11-00043){ref-type=\"app\"}).", "\n\n2.2. ", "Tamoxifen-Talazoparib Combinatorial Efficacy Is ERα-Dependent {#sec2dot2-cancers-11-00043}\n------------------------------------------------------------------\n\nTo determine whether response to the combination was dependent on ERα, we treated MDA-MB-231 cells (TNBC; negative for ER, PR and HER2) and MCF7-F (clonally derived, fulvestrant resistant and lack ERα signaling; \\[[@B30-cancers-11-00043]\\]) with tamoxifen in the presence and absence of PARPi, and performed colony formation assays. ", "In response to tamoxifen alone, no effect on cell survival was observed in either cell line ([Supplemental Figure S2B--D](#app1-cancers-11-00043){ref-type=\"app\"}), as expected. ", "Similarly, following co-administration of tamoxifen with PARPi, no increase in cell response to tamoxifen treatment was observed. ", "Fulvestrant treatment with or without talazoparib had no effect on MCF7-F cell survival ([Supplemental Figure S2C,D](#app1-cancers-11-00043){ref-type=\"app\"}).", "\n\nIn response to tamoxifen treatment, ERα was shown to translocate to the nucleus in tamoxifen-resistant cells, with cytoplasmic localization being indicative of tamoxifen sensitivity \\[[@B34-cancers-11-00043]\\]. ", "In this regard, we observed tamoxifen treatment alone increased ERα nuclear localization ([Supplemental Figure S3](#app1-cancers-11-00043){ref-type=\"app\"}), consistent with previous reports \\[[@B34-cancers-11-00043]\\], and co-administration with talazoparib increased both PARP1 and ERα cytoplasmic subcellular localization (caveolin-1 (Cav1) was used to validate decreased ERα function; \\[[@B35-cancers-11-00043]\\]). ", "Based on these results, it was next of interest to further examine a role for PARP1 in mediating tamoxifen resistance.", "\n\n2.3. ", "Tamoxifen-Talazoparib Co-Administration Increases Cellular DNA Damage {#sec2dot3-cancers-11-00043}\n--------------------------------------------------------------------------\n\nInhibition of PARP1 using clinical PARPi increases DNA double strand break (DSB) repair in BRCA-proficient cells, which can be assessed by RAD51 foci formation \\[[@B36-cancers-11-00043]\\]. ", "To examine whether altered DSB repair contributed to talazoparib-mediated tamoxifen sensitivity, we measured RAD51 foci formation in both MCF7 and MCF7-T cells following treatment with talazoparib in the presence and absence of tamoxifen. ", "In response to talazoparib treatment alone, we observed increased (*p* \\< 0.05) RAD51 foci in both MCF7 and MCF7-T cell lines ([Figure 2](#cancers-11-00043-f002){ref-type=\"fig\"}A--C), consistent with the synthetic lethal relationship between PARP and BRCA-mediated DNA damage repair \\[[@B21-cancers-11-00043],[@B22-cancers-11-00043]\\]. ", "Interestingly, tamoxifen treatment alone did not alter RAD51 foci formation compared to control, and tamoxifen-talazoparib co-administration had no effect on RAD51 foci formation compared to talazoparib alone ([Figure 2](#cancers-11-00043-f002){ref-type=\"fig\"}A--C).", "\n\nBecause no specific effect on RAD51 was observed, we next examined DNA damage more generally. ", "MCF7 and MCF7-T cells were treated with tamoxifen in the presence and absence of talazoparib, and immunofluorescence staining for γH2Ax foci formation was performed. ", "In response to tamoxifen alone, we observed increased (*p* \\< 0.05) γH2Ax staining, which was further increased (*p* \\< 0.05) by co-administration with talazoparib ([Figure 2](#cancers-11-00043-f002){ref-type=\"fig\"}D--F). ", "These findings are consistent with a previous study by Qi et al. ", "showing that tamoxifen can impair homologous recombination repair, while promoting DNA damage accumulation \\[[@B37-cancers-11-00043]\\].", "\n\n2.4. ", "Tamoxifen Induces ROS, and ROS Promotes PARylaton of ERα {#sec2dot4-cancers-11-00043}\n-------------------------------------------------------------\n\nBecause co-administration of tamoxifen and PARPi increased both tamoxifen response and γH2AX foci, but not RAD51 foci formation, it was of interest to further investigate the mechanism of PARPi-mediated tamoxifen sensitivity. ", "We previously observed that basal ROS is increased in tamoxifen-resistant versus sensitive breast cancer cells ([Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}A,B). ", "Tamoxifen treatment increases intracellular ROS, and increased ROS is an important determinant of tamoxifen efficacy \\[[@B5-cancers-11-00043],[@B8-cancers-11-00043]\\]. ", "Based on these reports and our observations ([Figure 2](#cancers-11-00043-f002){ref-type=\"fig\"}D--F), we tested whether tamoxifen increased oxidative damage and if tamoxifen-mediated ROS increased PARP1 activity. ", "MCF7 and MCF7-T cells were treated with increasing concentrations of tamoxifen, and ROS levels were measured. ", "We observed that tamoxifen increased (*p* \\< 0.05) ROS in a dose-dependent manner ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}A), consistent with previous reports \\[[@B5-cancers-11-00043],[@B8-cancers-11-00043]\\]. ", "Furthermore, MCF7 and MCF7-T cells were treated with tamoxifen in the presence and absence of the ROS scavenger *N*-acetyl-[l]{.smallcaps}-cysteine (NAC) and cells were subjected to both immunofluorescence staining against 8-oxoG and western blot analysis. ", "In response to tamoxifen, increased 8-oxoG staining was observed, which diminished upon co-administration with NAC ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}B). ", "Western blot analysis revealed increased PAR levels following tamoxifen treatment ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}C and shown in [Figure 1](#cancers-11-00043-f001){ref-type=\"fig\"}D), and co-administration with NAC decreased (*p* \\< 0.05) PAR levels ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}C). ", "Taken together, these data suggest tamoxifen increases PARP1 activity in a ROS-dependent manner.", "\n\nUpon ROS-induced activation, PARP1 PARylates associated proteins to regulate cellular response to oxidative damage \\[[@B28-cancers-11-00043]\\]. ", "Moreover, in a vascular smooth muscle cell model \\[[@B26-cancers-11-00043]\\], it was demonstrated that PARP1 PARylated ERα, resulting in altered ERα nuclear translocation, response to ligand and transcriptional activity. ", "PARP1 activity has been shown to be an important regulator of ERα function \\[[@B26-cancers-11-00043]\\]; however, whether ERα PARylation is involved in breast cancer and furthermore tamoxifen resistance has not been examined. ", "To initially test if ERα was PARylated and whether ROS promoted ERα PARylation, we treated MCF7-T cells with H~2~O~2~ (2 mM for 3 h) and subsequently immunoprecipitated ERα. ", "Following addition of H~2~O~2~ (oxidative damage conditions), we observed increased ERα PARylation and an increased ERα-PARP1 interaction ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}D). ", "To examine whether ERα was differentially PARylated in tamoxifen-sensitive versus -resistant breast cancer cells, ERα was immunoprecipitated in untreated MCF7 and MCF7-T cells, and PAR accumulation was examined by western blot analysis. ", "Interestingly, we observed greater interaction between ERα and PAR in the tamoxifen-resistant MCF7-T cell line compared to the sensitive MCF7 cells ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}E). ", "These results demonstrate that oxidative damage is sufficient to promote ERα PARylation in breast cancer and correlate ERα PARylation with tamoxifen resistance.", "\n\n2.5. ", "Tamoxifen Promotes PARylation of ERα and PARylation Mediates ERα Response {#sec2dot5-cancers-11-00043}\n------------------------------------------------------------------------------\n\nWe next hypothesized that tamoxifen-dependent ROS accumulation would likewise promote ERα PARylation. ", "We treated both MCF7 and MCF7-T cells with tamoxifen, in the presence and absence of PARPi talazoparib and immunoprecipitated either ERα or PARP1 (MCF7-T cells). ", "In response to tamoxifen treatment, we observed increased ERα PARylation in both MCF7 ([Supplemental Figure S4A](#app1-cancers-11-00043){ref-type=\"app\"}) and MCF7-T ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}F) cells, and co-administration with talazoparib decreased the ERα PARylation, as well as the interaction with PARP1. ", "Based on these results, we suggest that loss of ERα PARylation by PARPi treatment correlates with ERα response to ligands and increased cell sensitivity to antiestrogen therapy.", "\n\nERα is rapidly degraded in response to estradiol (E2) in breast cancer cells that are tamoxifen-responsive \\[[@B30-cancers-11-00043]\\]. ", "However, in tamoxifen resistant cells, E2 does not induce ERα degradation \\[[@B30-cancers-11-00043],[@B33-cancers-11-00043]\\]. ", "To validate that loss of PARP1 activity could mediate ERα response to ligand, we treated cells with E2 and performed western blot analysis. ", "As a positive control, MCF7 cells were treated with E2 and reduced ERα levels were observed ([Supplemental Figure S4B](#app1-cancers-11-00043){ref-type=\"app\"}). ", "In contrast, E2 did not decrease ERα protein levels in MCF7-T cells ([Supplemental Figure S4C](#app1-cancers-11-00043){ref-type=\"app\"}), whereas addition of the pure anti-estrogen fulvestrant markedly downregulated ERα protein levels ([Supplemental Figure S4D](#app1-cancers-11-00043){ref-type=\"app\"}). ", "Next, MCF7-T cells were treated with talazoparib alone or in combination with E2, and under these conditions, a reduced level of ERα was observed ([Supplemental Figure S4C](#app1-cancers-11-00043){ref-type=\"app\"}). ", "These results suggest that PARPi is able to regulate ERα response to ligand as a function of PARP1 activity, consistent with previous observations \\[[@B25-cancers-11-00043],[@B26-cancers-11-00043]\\].", "\n\n2.6. ", "Talazoparib Reduces PARP1 and ERα Localization to ERα Target Genes {#sec2dot6-cancers-11-00043}\n-----------------------------------------------------------------------\n\nTamoxifen increased PARP1 activity, as well as ERα PARylation, and we observed that inhibition of PARP1 activity decreased nuclear ERα localization ([Supplemental Figure S3](#app1-cancers-11-00043){ref-type=\"app\"}). ", "We then explored the role of PARP1 activity in regulating the enrichment of ERα at the promoter of ERα target genes. ", "Based on ERα-binding sites of previously identified ERα target genes, described by Jin et al., ", "we performed PARP1 chromatin immunoprecipitation (ChIP) analysis against a panel of genes (RARα, MYC, GREB1, ERBB2, FOS, and XBP1) \\[[@B4-cancers-11-00043]\\]. ", "As a positive control, we also performed ERα ChIP against the same gene panel. ", "As predicted, treatment with talazoparib in both the tamoxifen-sensitive (MCF7) and -resistant (MCF7-T) cell lines resulted in decreased (*p* \\< 0.05) recruitment of PARP1 to ERα-binding sites in the majority of genes examined ([Figure 4](#cancers-11-00043-f004){ref-type=\"fig\"}A,B). ", "To a greater extent, ERα localization to ERα-binding sites was likewise decreased (*p* \\< 0.05) following tamoxifen-talazoparib treatment relative to tamoxifen treatment alone ([Figure 4](#cancers-11-00043-f004){ref-type=\"fig\"}C,D). ", "These results suggest that the ERα-PAR/PARP1 interaction is an important regulator of ERα-localization to ERα target genes.", "\n\n2.7. ", "Overexpression of miR-222 in Tamoxifen Resistant Cells Promotes PARP1 Activation {#sec2dot7-cancers-11-00043}\n-------------------------------------------------------------------------------------\n\nWhile we demonstrated that tamoxifen increased ERα PARylation, we also observed that the basal ERα PARylation was increased in tamoxifen resistant versus sensitive cells ([Figure 3](#cancers-11-00043-f003){ref-type=\"fig\"}E). ", "As such, it was of interest to investigate the mechanism by which PARP1 was overexpressed in tamoxifen resistant breast cancer cells. ", "It was recently demonstrated that microRNA-222 (miR-222) can both increase PARP1 activity, and promote PARPi sensitivity in ovarian cancer cells \\[[@B38-cancers-11-00043]\\]. ", "We and others demonstrated that miR-222 is overexpressed in tamoxifen resistant breast cancer cells compared to their sensitive counterparts \\[[@B39-cancers-11-00043],[@B40-cancers-11-00043],[@B41-cancers-11-00043]\\]. ", "To validate that miR-222 was overexpressed in tamoxifen resistant breast cancer, we measured basal miR-222 expression in parental MCF7 cells compared to MCF7-T by qRT-PCR analysis. ", "We observed increased (*p* \\< 0.05; \\~6.5-fold) miR-222 expression in tamoxifen resistant cells compared to the parental MCF7 cell line ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}A). ", "It was next of interest to determine whether tamoxifen could increase miR-222 expression and to test whether miR-222 overexpression was sufficient to promote tamoxifen resistance. ", "MCF7 cells were treated with tamoxifen and qRT-PCR analysis was performed. ", "As expected, tamoxifen treatment increased (*p* \\< 0.05) miR-222 expression in a dose-dependent manner ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}B). ", "We then treated MCF7 cells with tamoxifen in the presence and absence of miR-222 overexpression and subjected cells to clonogenic survival assays. ", "In the absence of miR-222 overexpression, a dose-dependent decrease (*p* \\< 0.05) in cell survival was observed, and subsequent addition of miR-222 prevented tamoxifen-mediated cell death ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}C). ", "Consistently, we observed decreased (*p* \\< 0.05) cell survival in MCF7-T cells upon inhibition of miR-222 and treatment with tamoxifen ([Supplemental Figure S5](#app1-cancers-11-00043){ref-type=\"app\"} and [Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}D).", "\n\nGiven that tamoxifen was sufficient to increase both PARP1 activity and miR-222 expression, we determined whether tamoxifen-mediated PARP1 activation was miR-222 dependent. ", "MCF7 cells were treated with tamoxifen in the presence and absence of miR-222 inhibitor and measured PAR levels. ", "We observed that tamoxifen treatment increased (*p* \\< 0.05) PARP1 activity, as previously demonstrated, and subsequent inhibition of miR-222 decreased tamoxifen-mediated PARP1 activation ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}E).", "\n\nRegulation of PARP1 by miR-222 has been studied in depth in ovarian cancer cells \\[[@B38-cancers-11-00043]\\]; however, whether miR-222 is sufficient to increase PARP1 activity in breast cancer is unknown. ", "Using a miR-222 mimic, we exogenously expressed miR-222 in MCF7 tamoxifen-sensitive cells and measured PARP1 and PAR levels by western blot analysis. ", "qRT-PCR validated overexpression of miR-222 (*p* \\< 0.05; \\~3-fold) ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}F). ", "Furthermore, overexpression of miR-222 increased both PARP1 and PAR levels ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}F).", "\n\n2.8. ", "miR-222 Regulates the Response to Tamoxifen-PARPi Co-Administration {#sec2dot8-cancers-11-00043}\n------------------------------------------------------------------------\n\nBecause miR-222 overexpression increased PARP1 activity ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}F), it was of interest to measure the effect on RAD51 foci formation. ", "Consistent with our observation ([Figure 2](#cancers-11-00043-f002){ref-type=\"fig\"}A--C), talazoparib treatment increased (*p* \\< 0.05) RAD51 foci in both MCF7 and MCF7-T cells ([Figure 6](#cancers-11-00043-f006){ref-type=\"fig\"}A,B). ", "Additionally, overexpression of miR-222 blocked formation of talazoparib-mediated RAD51 foci, irrespective of tamoxifen sensitivity ([Figure 6](#cancers-11-00043-f006){ref-type=\"fig\"}A,B). ", "We next investigated whether miR-222 mediated the PARPi response and, more importantly, the response to tamoxifen-talazoparib co-administration. ", "First, we treated MCF7 cells with PARPi alone or combination with tamoxifen, in the presence and absence of miR-222 overexpression, and subjected cells to colony formation assays. ", "In MCF7 cells overexpressing miR-222, we observed increased (*p* \\< 0.05) sensitivity to PARPi treatment ([Figure 6](#cancers-11-00043-f006){ref-type=\"fig\"}C). ", "Second, to determine whether miR-222 mediated the tamoxifen-talazoparib response, MCF7-T cells were treated with tamoxifen and increasing concentrations of talazoparib, with or without miR-222 expression. ", "As miR-222 loss promoted sensitivity to tamoxifen ([Figure 5](#cancers-11-00043-f005){ref-type=\"fig\"}D), tamoxifen-treated cells were used as the control ([Figure 6](#cancers-11-00043-f006){ref-type=\"fig\"}D). ", "In the presence of miR-222 (control), we observed a dose-dependent decrease in cell survival following tamoxifen-talazoparib co-administration; however, miR-222 inhibition diminished tamoxifen-talazoparib mediated cell death ([Figure 6](#cancers-11-00043-f006){ref-type=\"fig\"}D). ", "Taken together, our results support a role for talazoparib-mediated tamoxifen response in ER+, tamoxifen-resistant breast cancer.", "\n\n3. ", "Discussion {#sec3-cancers-11-00043}\n=============\n\nMost breast tumors express ERα, and stimulation of ERα by estradiol plays a significant role in breast tumor progression ERα-targeted therapies including tamoxifen demonstrate exceptional clinical efficacy in treating breast cancer \\[[@B42-cancers-11-00043]\\]. ", "However, due to long-term treatment, resistance to tamoxifen therapy is common, even though most resistant tumors continue to express ERα \\[[@B4-cancers-11-00043]\\]. ", "Mechanisms of resistance include epigenetic alterations \\[[@B11-cancers-11-00043],[@B41-cancers-11-00043]\\] and post-translational modifications \\[[@B14-cancers-11-00043]\\], which alter the antagonistic effects of tamoxifen on ERα function. ", "Attempts to overcome tamoxifen resistance through development of novel therapies that target estrogen synthesis \\[[@B15-cancers-11-00043],[@B43-cancers-11-00043],[@B44-cancers-11-00043]\\], and combination therapies have met with limited success, signifying a need to further explore therapeutic options to overcome tamoxifen resistance. ", "In this regard, our study reveals that both oxidative damage and PARP1 levels are elevated in ERα+ tamoxifen resistant breast cancer. ", "Addition of a PARPi increases cell response to tamoxifen therapy in an ERα-dependent manner. ", "Through in vitro analysis, we show that combining tamoxifen with talazoparib increases both DNA damage and PAR accumulation and decreases survival of tamoxifen-resistant breast cancer cells. ", "We identify miR-222 as a mediator of tamoxifen and PARPi response as well as the efficacy of tamoxifen-talazoparib combination. ", "The results of this study support further investigation into combining antiestrogen with PARPi as a potential therapeutic option to overcome tamoxifen resistance in ERα+ breast cancer.", "\n\nElevated levels of oxidative stress in tamoxifen resistant breast cancer have been previously reported \\[[@B27-cancers-11-00043]\\], which we postulate may correlate with increased PARP1 expression and activity, implicating PARP1 as a therapeutic target to overcome tamoxifen resistance \\[[@B19-cancers-11-00043],[@B20-cancers-11-00043]\\]. ", "With respect to our overall hypothesis, we demonstrate that intracellular ROS levels are elevated in tamoxifen resistant versus sensitive cells, as are PARP1 levels and activity. ", "Based on overexpression of PARP1, we show co-administration of PARPi with tamoxifen decreases cell survival in ER+ breast cancer cells. ", "However, in breast cancer cells that do not depend on estrogen signaling for the survival (MDA-MB-231, MCF7-F), the combination had no effect, demonstrating that ERα expression is integral in mediating tamoxifen-talazoparib induced cell death. ", "Additionally, treatment with the PARPi alone increases DSB break repair, as indicated by increased RAD51 foci formation. ", "However, tamoxifen alone or in combination with PARPi had no effect on RAD51 foci formation. ", "An increase in γH2AX following tamoxifen and tamoxifen-talazoparib treatment further supports the notion that tamoxifen-talazoparib induces DNA damage.", "\n\nIn addition to inhibiting ERα function, tamoxifen-induced intracellular ROS contributes to its therapeutic efficacy \\[[@B5-cancers-11-00043]\\]. ", "Interestingly, increased oxidative damage has been hypothesized to act as a mechanism to overcome PARPi resistance and a distinct therapeutic vulnerability in cancer cells \\[[@B19-cancers-11-00043],[@B45-cancers-11-00043]\\]. ", "In support of these studies, we demonstrate that tamoxifen treatment increases ROS accumulation in both MCF7 and MCF7-T cell lines, and tamoxifen-mediated ROS accumulation is sufficient to promote PARP1 activation. ", "Inversely, ROS depletion following tamoxifen treatment diminishes PARP1 activity. ", "We posit that tamoxifen treatment results in PARP1 activation and ultimately PARPi-tamoxifen response in a ROS-dependent manner.", "\n\nOur results relate ROS accumulation by tamoxifen to increase ERα PARylation. ", "PARP1 regulates cell signaling, including DNA damage response, through rapid PARylation of target proteins, including PARP1 itself \\[[@B24-cancers-11-00043]\\]. ", "In vascular smooth muscle cells, ERα is directly PARylated by PARP1, altering the ability of ERα to bind its target genes \\[[@B26-cancers-11-00043]\\]. ", "To our knowledge, this is the first demonstration that ERα is PARylated in breast cancer cells and that tamoxifen can induce ERα PARylation. ", "Moreover, treatment with talazoparib diminishes ERα PARylation, as well as the interaction between ERα and PARP1, which correlates with talazoparib-mediated tamoxifen response. ", "Differential ERα PARylation in tamoxifen sensitive versus resistant cells correlates with tamoxifen sensitivity. ", "As ERα functions as a nuclear receptor and a transcription factor, talazoparib treatment decreases both PARP1 and ERα localization to ERα-target genes, regardless of tamoxifen sensitivity. ", "However, this observation is also consistent with decreased ERα levels following talazoparib treatment. ", "Further experimentation will be necessary to understand the exact mechanism of talazoparib-mediated decrease in ERα localization to ERα-target genes.", "\n\nIn terms of a mediator of both tamoxifen and PARPi response, here we identify miR-222 as a potential negative regulator of tamoxifen-talazoparib mediated cell death. ", "Tamoxifen resistant breast cancers overexpress miR-222 \\[[@B39-cancers-11-00043],[@B40-cancers-11-00043]\\], and oxidative damage increases miR-222 expression. ", "Interestingly, through inhibition of DSB damage repair, miR-222 overexpression is sufficient to promote PARPi sensitivity in ovarian cancer cells \\[[@B38-cancers-11-00043]\\]. ", "Beyond validating miR-222 overexpression in tamoxifen resistant cells, this is the first demonstration that upregulation of miR-222 increases PARP1 activation and PARPi sensitivity and decreases RAD51 foci formation in breast cancer cells. ", "By inhibiting the oncomir (oncogenic miRNA), we further show the importance of miR-222 as a mediator of tamoxifen-talazoparib efficacy. ", "Collectively, the data support a critical role for miR-222 in mediating response to tamoxifen-talazoparib treatment, with both loss and gain of miR-222 expression regulating response to single agent tamoxifen or talazoparib.", "\n\nWhile the present study focuses on a proposed mechanism to overcome tamoxifen resistance through combination with PARPi, we do not believe this to be a mutually exclusive mechanism of induced cell death. ", "In addition to PARPi-mediated tamoxifen response, our results also demonstrate a novel mechanism to overcome PARPi resistance, regardless of BRCA status, as all cell lines examined are BRCA-proficient and do not respond to PARPi as a single agent. ", "Tamoxifen increases ROS and miR-222 expression but does not increase homologous recombination repair (RAD51 foci), all of which represent therapeutic avenues to increase sensitivity to PARPi \\[[@B19-cancers-11-00043],[@B38-cancers-11-00043],[@B45-cancers-11-00043]\\], suggesting a novel feedback loop such that both tamoxifen increases sensitivity to PARPi and PARPi to tamoxifen.", "\n\nAdditionally, work by our group and Muvarak et al. ", "demonstrate that addition of talazoparib to cells promotes PARP1 trapping to DNA, increases DNA damage and ultimately cell death in combination with DNMT inhibitors \\[[@B29-cancers-11-00043],[@B46-cancers-11-00043]\\]. ", "ROS induces several classes of DNA damage to which PARP1 may localize, and talazoparib is the most potent PARP1 trapper \\[[@B32-cancers-11-00043]\\]. ", "It is conceivable that tamoxifen-mediated ROS accumulation and co-administration with talazoparib promotes trapping of PARP1 to DNA, enhancing the efficacy of tamoxifen-talazoparib co-administration. ", "In support of this possibility, we demonstrate that tamoxifen co-administration with the PARPi veliparib, a less potent PARP-trapper, was able to induce cell death but not to the extent of the tamoxifen-talazoparib combination treatment \\[[@B32-cancers-11-00043]\\]. ", "Moreover, we show tamoxifen-talazoparib co-administration reduces nuclear localization of both ERα and PARP1, though some PARP1 remains in the nucleus ([Supplemental Figure S3](#app1-cancers-11-00043){ref-type=\"app\"}). ", "Talazoparib robustly reduces ERα at ERE sites and PARP1 but to a much lesser extent ([Figure 4](#cancers-11-00043-f004){ref-type=\"fig\"}), indicating that PARP1 may be more tightly bound to the DNA (albeit not directly explored in this study). ", "It is important to note that differences in ChIP enrichment at ERE sites may be due to either altered ERα and PARP1 nuclear localization, as demonstrated ([Supplemental Figure S3](#app1-cancers-11-00043){ref-type=\"app\"}), or decreased DNA affinity in the absence of PARP1 activity \\[[@B27-cancers-11-00043]\\]. ", "Further studies are needed to discriminate between these mechanisms. ", "Nonetheless, it seems reasonable to suggest that some of the enhanced response to tamoxifen-talazoparib co-administration is a result of tamoxifen-mediated ROS accumulation and PARP1 trapping.", "\n\nIn summary, using a model system based on the MCF7 breast cancer cell line, we show addition of a PARPi increases cell response to tamoxifen in tamoxifen-resistant ERα+ breast cancer. ", "We put forth a model of tamoxifen-mediated ROS accumulation, which increases miR-222 expression and subsequently PARP1 activity, priming the cell towards tamoxifen sensitivity, in an ERα-dependent manner ([Supplemental Figure S6](#app1-cancers-11-00043){ref-type=\"app\"}) and in the context of intact BRCA. ", "Collectively, these data support additional pre-clinical and clinical investigation of tamoxifen-talazoparib combination for patients with tamoxifen resistant ERα+ breast cancer. ", "Our future studies aimed at better understanding the significance of ERα PARylation and increasing the translational impact of the therapeutic combination will include multiple cell lines and in vivo model systems.", "\n\n4. ", "Materials and Methods {#sec4-cancers-11-00043}\n========================\n\n4.1. ", "Cell Lines, Culture Conditions and Reagents {#sec4dot1-cancers-11-00043}\n------------------------------------------------\n\nMCF7 and anti-estrogen resistant derivatives (MCF7-T and MCF7-F) were maintained and established as we have previously described \\[[@B30-cancers-11-00043]\\]. ", "Briefly, MCF7-T cells were maintained in tamoxifen-containing media, except prior to drug treatment. ", "The maintenance concentration of tamoxifen was 100 nM. MCF7/LCC2 and MCF7/LCC9 cells lines (anti-estrogen resistant) were derived and maintained as described by Brünner et al. ", "\\[[@B33-cancers-11-00043]\\]. ", "Cell lines were authenticated in 2017 by ATCC and tested for mycoplasma contamination (Manassas, VA, USA). ", "To ensure cell line integrity, all cell lines were thawed at frequent intervals and not used beyond 30 passages. ", "Additionally, cell morphology was monitored for each cell line, and proper media and growth conditions selected \\[[@B29-cancers-11-00043],[@B30-cancers-11-00043]\\]. ", "Hydrogen peroxide (H~2~O~2~) was purchased from EMD Millipore (Billerica, MA, USA). ", "Tamoxifen (Tamox or 4-OHT) was purchased from Sigma Aldrich (St. Louis, MO, USA). ", "Talazoparib (Talaz; PARPi) was provided by Pfizer/Medivation (San Francisco, CA, USA). ", "Primary antibody dilutions were as followed: PARP1 (Cell Signaling, Danvers, MA, USA; 1:3000), PAR (Trevigen, Gaithersburg, MD, USA; 1:2000) ERα (Santa Cruz, Dallas, TX, USA; 1:2000), pERBB2 (Cell Signaling; 1:2000), GAPDH (Santa Cruz; 1:2000), IgG (Santa Cruz; 1:5000), β-Tubulin (Santa Cruz; 1:5000).", "\n\n4.2. ", "Clonogenic Survival and MTT Assay {#sec4dot2-cancers-11-00043}\n--------------------------------------\n\nCells were seeded to 60--70% confluence in 10 cm plates and treated for the indicated times. ", "24 h following treatment, cells were washed, serially diluted, and plated in triplicate on 6-well plates (500--1000 cells/well). ", "6--14 days of cell growth were allowed for colony formation, followed by staining with 0.5% crystal violet. ", "Cell counts were normalized to untreated controls as previously described \\[[@B47-cancers-11-00043]\\]. ", "Combination treatment scheme is as followed: Co-administration ('Co-ad') with both 100 nM tamoxifen (Tamox) and 1 nM talazoparib (Talaz) on day 1, and 100 nM Tamox on days 2 and 3, unless otherwise indicated.", "\n\n4.3. ", "RNA Extraction, Quantitative RT-PCR and Cell Transfection {#sec4dot3-cancers-11-00043}\n--------------------------------------------------------------\n\nRNA was extracted via RNeasy kit (Qaigen, Venlo, Limburg, The Netherlands), and cDNA prepared with MMLV reverse transcriptase (Promega, Madison, WI, USA). ", "qRT-PCR was performed as we have previously described \\[[@B48-cancers-11-00043]\\], using EEF1A as the internal control. ", "Cells were treated with either miR-222 mimic (Ambion, Carlsbad, CA, USA; 4464066) or miR-222 inhibitor (Ambion; AM17000) within the indicated treatments conditions and according to the manufacturer's protocol using the Lipofectamine 3000 reagent (Thermo Fisher Scientific, Waltham, MA, USA; L3000008).", "\n\n4.4. ", "PAR-Capture ELISA {#sec4dot4-cancers-11-00043}\n----------------------\n\nConfluent (80%) 10 cm plates were treated as described in the text. ", "Following treatment, samples were harvested, 20% SDS was added (to a final concentration of 1%), protein concentration measured according to the manufacturer's protocol (Trevigen; 4520-096-K) and the lysate was snap-frozen and placed at −80 °C. ", "Preparation of the PAR standard curve and treated samples was performed according to the manufacturer's protocol, and as we have described \\[[@B29-cancers-11-00043]\\]. ", "In brief, 100 μL (20 μg protein) of each sample was added to a 96-well plate, pre-coated with PAR capture antibody and allowed to incubate overnight. ", "Wells were then washed with PBST (PBS + 0.1% Tween 20) and incubated with primary antibody (PAR Polyclonal antibody), washed with PBST and incubated in secondary antibody (Goat Anti-Rabbit IgG HRP). ", "Plates were washed with PBST, chemiluminescent substrate was added, and luminescence measured. ", "The data are reported as the relative change in PAR concentration compared to control.", "\n\n4.5. ", "ROS Assays {#sec4dot5-cancers-11-00043}\n---------------\n\nConfluent 10 cm plates were treated as indicated in the text. ", "Following treatment, 2 × 10^4^ cells/well were plated on 96-well plates. ", "24 h post plating, ROS assay, measuring H~2~O~2~ levels, (Promega) was performed as previously described \\[[@B47-cancers-11-00043]\\].", "\n\n4.6. ", "Immunofluorescence {#sec4dot6-cancers-11-00043}\n-----------------------\n\nCells were treated as described and plated on glass slides (50,000 cells/well), fixed and permeabilized as described by Sakai et al. ", "\\[[@B49-cancers-11-00043]\\]. ", "Following permeabilization, cells were incubated for 1 h with RAD51 antibody (1:1000), γH2Ax antibody (1:1000), or 8-hydroxyguanosine (8-oxoG) (1:1000). ", "Secondary antibody (Invitrogen, Carlsbad, CA, USA) was added and slides incubated for 45 min. ", "Nuclei were counterstained with Hoechst stain (1:5000; 33342, Invitrogen). ", "Images were captured using a Nikon NIE microscope, and processed using NIS Elements Viewer. ", "Cells with 5 or more RAD51 foci were considered positive (per ref \\[[@B49-cancers-11-00043]\\]) and cells with 20 or more γH2Ax foci were considered positive. ", "Results are representative of three independent experiments ± SEM.", "\n\n4.7. ", "Western Blot Analysis {#sec4dot7-cancers-11-00043}\n--------------------------\n\nTotal cell lysate was prepared with RIPA lysis buffer. ", "Western blot analysis was performed as we have described previously \\[[@B47-cancers-11-00043]\\].", "\n\n4.8. ", "Combination Index and Synergism {#sec4dot8-cancers-11-00043}\n------------------------------------\n\nCells were treated and plated as indicated for clonogenic survival assays (500 cells/well). ", "Following treatment, percent survival subtracted from 100% was indicative of the fraction affected (FA). ", "Subsequent combination indices, and synergism determination, were determined by the Chou-Talalay method (\\[[@B31-cancers-11-00043]\\]; with mutually non-exclusive assumption) using CompuSyn Software \\[[@B50-cancers-11-00043]\\].", "\n\n4.9. ", "Immunoprecipitation Assays {#sec4dot9-cancers-11-00043}\n-------------------------------\n\nMCF7 and MCF7-T cells were grown to confluence (90%) in 15 cm plates, and treated as described in the text. ", "24 h following treatment, cells were washed with PBS and harvested in immunoprecipitation (IP) lysis buffer and protease inhibitors. ", "The lysate was sonicated briefly and rotated at 4 °C, followed by centrifugation at 13,000 rpm for 10 min. ", "The lysates were added to 50--60 μL of pre-conjugated protein A/G beads with the indicated antibodies. ", "Beads were pelleted (1000 rpm, 4 °C) and washed in IP buffer. ", "The samples were run on SDS-PAGE gel and immunoblot analysis was performed against the indicated antibodies \\[[@B4-cancers-11-00043],[@B47-cancers-11-00043]\\].", "\n\n4.10. ", "Chromatin Immunoprecipitation (ChIP)-qPCR {#sec4dot10-cancers-11-00043}\n-----------------------------------------------\n\nMCF7 and MCF7-T cells were grown to confluency (90%) in 15 cm plates, and treated as described in the text. ", "24 h following treatment cells were washed with PBS, crosslinked with 10% formalin and harvested in immunoprecipitation (IP) lysis buffer. ", "Following IP (previously described, \\[[@B48-cancers-11-00043]\\]) with antibody pre-conjugated protein agarose beads, the crosslinks were reversed, and DNA was purified. ", "ChIP-qPCR primers targeting the estrogen response element (ERE) were designed as previously described by Jin et al. ", "\\[[@B4-cancers-11-00043]\\]. ", "A negative control region was used, as we have previously described \\[[@B48-cancers-11-00043]\\].", "\n\n4.11. ", "Statistical Analysis {#sec4dot11-cancers-11-00043}\n--------------------------\n\nAll data, unless noted otherwise, are represented as mean value ± SEM of at least three biological replicates. ", "IC~50~ data was determined by Prism 6 (GraphPad Software, San Diego, CA, USA), using logarithm normalized sigmoidal dose-curve fitting. ", "Tukey's test for multiple comparisons correction was used to analyze the significance among different groups in biological assays, unless otherwise stated. ", "For in vivo experiments, ANOVA/Mann-Whitney tests (GraphPad) were used to determine statistical significance, as described \\[[@B46-cancers-11-00043]\\].", "\n\n5. ", "Conclusions {#sec5-cancers-11-00043}\n==============\n\nTherapeutic targeting of ERα by tamoxifen is standard of care for premenopausal breast cancer. ", "While tamoxifen increases overall survival, tamoxifen resistance remains a major limitation, despite continued expression of ERα in resistant tumors. ", "Towards a better molecular understanding of endocrine resistance, we used clonally derived ERα-positive, antiestrogen-resistant breast cancer MCF7-cell models and demonstrated differential ERα PARylation in tamoxifen-resistant vs. --sensitive cells. ", "We further demonstrated that tamoxifen treatment was sufficient to activate PARP and increase ERα PARylation in an ROS-dependent manner. ", "Combination treatment of the PARP inhibitor talazoparib with tamoxifen effectively blocked ERα PARylation, markedly decreased ERα localization to ERα target genes and significantly enhanced response to tamoxifen in an ERα-dependent manner in models of acquired tamoxifen resistance. ", "We provide the first pre-clinical evidence that combining a PARP inhibitor with tamoxifen has significant activity against tamoxifen-resistant breast cancers which continue to express ERα, a therapeutic strategy that may warrant further investigation.", "\n\nWe thank Len Post (former: BioMarin Pharmaceutical Inc.).", "\n\nThe following are available online at <http://www.mdpi.com/2072-6694/11/1/43/s1>, Figure S1: Tamoxifen-talazoparib co-administration decrease cell survival and increase PARP activity, Figure S2: Tamoxifen-talazoparib efficacy is ERα-dependent, Figure S3: Tamoxifen and talazoparib alter ERα nuclear localization, Figure S4: Tamoxifen induces ER PARylation in tamoxifen-sensitive MCF7 cell line, Figure S5: miR-222 inhibition decreases expression of miR-222, Figure S6: Proposed model.", "\n\n###### \n\nClick here for additional data file.", "\n\nConceptualization, N.P., J.T. and K.P.N.; methodology, N.P., R.C. and K.P.N.; validation, N.P., J.T. and W.W.; formal analysis, N.P.; investigation, N.P., J.T., W.W. F.F. and R.S.; resources, R.C.; data curation, N.P., J.T. and W.W.; writing---original draft preparation, N.P., H.M.O., R.C. and K.P.N.; writing---review and editing, N.P., H.M.O., R.C. and K.P.N.; visualization, N.P. and K.P.N.; supervision, N.P. and K.P.N.; project administration, N.P., H.M.O., K.D.M., R.C. and K.P.N.; funding acquisition, N.P. and K.P.N.\n\nThis research was funded by NIH, grant number 5R01CA182832-05.", "\n\nThe authors declare no conflict of interest.", "\n\n{#cancers-11-00043-f001}\n\n{#cancers-11-00043-f002}\n\n![", "Tamoxifen-induced ROS accumulation promotes ERα PARylation. (**", "A**) MCF7 and MCF7-T cells were treated with the increasing concentrations of tamoxifen (Tamox) for 4 h, and subjected to ROS assay. (**", "B**) MCF7 and MCF7-T cells were treated with Tamox (1 μM) in the presence and absence of 1 mM *N*-acetyl-[l]{.smallcaps}-cysteine (NAC). ", "24 h post treatment immunofluorescence staining of 8-hydroxyguanosine (8-oxoG) was performed. ", "Results are representative of three independent experiments, and quantified below. ", "Scale bar: 20 µm. (**", "C**) MCF7 and MCF7-T cells were treated with 100 nM Tamox with or without 1 mM NAC (ROS scavenger). ", "24 h post treatment cell lysates were subjected to western blot analysis. (**", "D**) MCF7-T cells were treated with 2 mM H~2~O~2~ for 4 h. Treated cells were subjected to immunoprecipitation (ERα) and western blot analysis against the indicated antibodies. (**", "E**) MCF7 and MCF7-T subjected to immunoprecipitation (ERα) and western blot analysis against the indicated antibodies. (**", "F**) MCF7-T cells were treated for 4 h with 100 nM Tamox with or without 1 nM talazoparib (Talaz; pre-treat 24 h). ", "Post treatment cells subjected to immunoprecipitation and western blot analysis against the indicated antibodies. \\* *", "p* \\< 0.01, \\*\\* *p* \\< 0.001, \\*\\*\\* *p* \\< 0.0001 compared to control, \\# *p* \\< 0.01, \\#\\# *p* \\< 0.001 relative to bracketed treatment.](cancers-11-00043-g003){#cancers-11-00043-f003}\n\n{#cancers-11-00043-f004}\n\n{#cancers-11-00043-f005}\n\n{#cancers-11-00043-f006}\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Transcriptome profiling and in silico analysis of somatic embryos in Japanese larch (Larix leptolepis).", "\nJapanese larch (Larix leptolepis) is an ecologically and economically important species mainly grown in northeastern China, Japan and Europe. ", "However, erratic flowering and poor germplasm resources caused by high embryo abortion rates have hampered breeding of Larix species. ", "Somatic embryogenesis (SE) is an effective tool for the production of L. leptolepis with desirable characteristics, such as expression of totipotency, preparation of synthetic seeds, and genetic transformation. ", "However, public genomic resources for this species are limited. ", "We sequenced 591,759 raw expressed sequence tags (ESTs) from a 454 sequencing cDNA library of L. leptolepis somatic embryos, resulting in 572,403 high-quality reads. ", "These reads were assembled into 70,927 unique sequences (UniGenes), including 32,321 contigs and 38,606 singletons. ", "After removal of low-quality sequences, 65,115 UniGenes were annotated using the UniProtKB program. ", "Based on their sequence similarity with known proteins, the matched 30,372 sequences from 664 species were estimated to represent approximately 19,000 unique genes. ", "Gene ontology analysis revealed 21,324 UniGenes assigned to 51 categories. ", "By Kyoto Encyclopedia of Genes and Genomes mapping, 25,773 transcripts were associated with 160 biochemical pathways. ", "Further analysis screened four signal transduction pathways represented by 337 enzymes and 17 secondary metabolites. ", "In silico analysis reveals that 207 UniESTs in Larix are homologous to MAPKs genes identified from other model plants, which may be involved in regulating SE development. ", "This study provides an initial insight into the Larix transcriptomes of the pro-embryogenic mass and is a sound basis for future studies. ", "We constructed a large, full-length 454 sequencing cDNA library of Larix leptolepis during somatic embryogenesis. ", "More than 590,000 sequences were obtained and a deep-coverage EST database was constructed." ]

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[ "Dynamics of viscous liquid bridges inside microchannels subject to external oscillatory flow.", "\nWe report on two-dimensional simulations of liquid bridges' dynamics inside microchannels of uniform wettability and subject to an external oscillatory flow rate. ", "The oscillatory flow results in a zero net flow rate and its effects are compared to those of a stationary system. ", "To handle the three phase contact lines motion, Cahn-Hilliard diffuse-interface formulation was used and the flow equations were solved using the finite element method with adaptively refined unstructured grids. ", "The results indicate that the liquid bridge responds in three different ways depending on the substrate wettability properties and the frequency of the oscillatory flow. ", "In particular below a critical frequency, the liquid bridge will rupture when the channel walls are philic or detach from the surface when they are phobic. ", "However, at high frequencies, the liquid bridge shows a perpetual periodic oscillatory motion for both philic and phobic surfaces. ", "Furthermore, an increase in the frequency of the flow velocity results in stabilization effects and a behavior approaching that of the stationary system where no rupture or detachment can be observed. ", "This stable behavior is the direct result of less deformation of the liquid bridge due to the fast flow direction change and motion of contact lines on the solid substrate. ", "Moreover, it was found that the flow velocity is out of phase with the footprint and throat lengths and that the latter two also show a phase difference. ", "These differences were explained in terms of the motion of the two contact lines on the solid substrates and the deformation of the two fluid-fluid interfaces." ]

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[ "watermelon viagra\n\nДата подачи: 2015-08-04\n\nГород: Челябинск\n\nРайон:\n\nКонтактная информация: info@fast-isotretinoin.com\n\nNat.testicular MALE REPRODUCTIVE SYSTEM Fwhen wealthy Russianborn philanthropist Louisa Hubbard set up the Midwives Institute which aimed to raise the efficiency and improve the status of midwives and to petition parliament for their recognition. ", "Priligy No treatment necessaryprocess test or procedure in which something is measured or observed in a living organismIn Europe the number of strains of Neisseria gonorrhoeae the cause of the sexual infection gonorrheathat are resistant to the main antibiotic used to treat it doubled between and Priligy bursting forth of bloodSingle DNA molecule patterning for high throughput epigenetic mapping.", "Such experiments have shown that the average lifetime of a red blood cell is about four months..CIFor these reasons antibiotics may be prescribed at least initially even when a definitive diagnosis of bacterial prostatitis has not been made with the appropriate tests. ", "cialis from canada Conjugated bilirubin is then added to bile and enters the intestine duodenum.", "In addition exophthalmos protrusion of the eyeballs or proptosis occurs as a result of swelling of tissue behind the eyeball pushing it forward. ", "propecia abonos Some modern acupuncturists recognize more than double this number.", "Psychiatric causesdepression most common cause anxiety and somatization b.The initial goal should be to reduce the mean arterial pressure by approximately Accutane This is a item questionnaire that divides coping into eight different categories." ]

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[ "Image copyright Getty Images\n\nA German industry boss has said it would be \"very, very foolish\" if the EU imposes trade barriers on the UK in the event it votes to leave the EU.", "\n\nMarkus Kerber, the head of the influential BDI which represents German industry, said his organisation would make the case against such measures.", "\n\nHe said any introduction of tariffs would be \"regression to times we thought we'd left behind in the 1970s\".", "\n\nThe UK's referendum on whether to leave the EU will be held on Thursday.", "\n\n\"Imposing trade barriers, imposing protectionist measures between our two countries - or between the two political centres, the European Union on the one hand and the UK on the other - would be a very, very foolish thing in the 21st Century,\" Mr Kerber told the BBC's World Service.", "\n\n\"The BDI would urge politicians on both sides to come up with a trade regime that enables us to uphold and maintain the levels of trade we have, although it will become more difficult.\"", "\n\nMr Kerber added that any introduction of tariffs would lead to job losses in Germany and the UK.", "\n\nHe said a vote to leave the EU would lead to a \"serious disruption\" to the German-UK economic relationship, describing it \"as if a relative had left the family\".", "\n\nThe German government has taken a tougher line on a future trade arrangement, should the UK vote to leave. ", "Germany's finance minister Wolfgang Schaeuble has said a leave vote would mean Britain leaving the European single market - \"out is out\".", "\n\nLeave campaigners say the UK does not need to be part of the single market.", "\n\nShould the UK request a trade deal, a senior MP in Angela Merkel's Christian Democratic Union, Juergen Hardt, says the EU would not be able to negotiate a trade pact with the UK quickly.", "\n\n\"I'm sure we'll find ways again to link Britain to Europe, but it will be tougher for Britain,\" he said.", "\n\nHe said the EU was busy trying to do a deal with the US. ", "On a UK deal - should one be requested - he said \"there will be negotiations but (it is) not a priority\".", "\n\nGermany - an architect of the European Union - is gripped by the possibility of a British exit from the EU, with wall-to-wall TV coverage of the referendum campaign." ]

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[ "---\nabstract: 'We study the problem of robustly learning multi-dimensional histograms. ", "A $d$-dimensional function $h: D \\to \\R$ is called a $k$-histogram if there exists a partition of the domain $D \\subseteq \\R^d$ into $k$ axis-aligned rectangles such that $h$ is constant within each such rectangle. ", "Let $f: D \\to \\R$ be a $d$-dimensional probability density function and suppose that $f$ is $\\mathrm{OPT}$-close, in $L_1$-distance, to an unknown $k$-histogram (with unknown partition). ", "Our goal is to output a hypothesis that is $O(\\mathrm{OPT}) + \\epsilon$ close to $f$, in $L_1$-distance. ", "We give an algorithm for this learning problem that uses $n = \\tilde{O}_d(k/{\\varepsilon}^2)$ samples and runs in time $\\tilde{O}_d(n)$. For any fixed dimension, our algorithm has optimal sample complexity, up to logarithmic factors, and runs in near-linear time. ", "Prior to our work, the time complexity of the $d=1$ case was well-understood, but significant gaps in our understanding remained even for $d=2$.'\nauthor:\n- |\n Ilias Diakonikolas[^1]\\\n USC\\\n `diakonik@usc.edu`\n- |\n Jerry Li [^2]\\\n MIT\\\n `jerryzli@mit.edu`\\\n- |\n Ludwig Schmidt[^3]\\\n MIT\\\n `ludwigs@mit.edu`\nbibliography:\n- 'allrefs.bib'\ntitle: |\n Fast and Sample Near-Optimal Algorithms\\\n for Learning Multidimensional Histograms\n---\n\nIntroduction {#sec:intro}\n============\n\n[*Density Estimation*]{} or [*Distribution Learning*]{} refers to the following unsupervised learning task: Given i.i.d.", " samples from an unknown target probability distribution, output a hypothesis that is a good approximation to the target distribution with high probability. ", "Density estimation is a classical and paradigmatic statistical problem with a history of more than a century, starting with [@Pearson] (see, e.g., [@BBBB:72; @DG85; @Silverman:86; @Scott:92; @DL:01] for textbook introductions). ", "Despite this long and rich history, core computational aspects of density estimation are wide-open in a variety of settings. ", "Starting with the pioneering work of [@KMR+:94short], computer scientists have been working on this broad fundamental question for more than two decades.", "\n\nThe recent distribution learning literature usually studies *structured* settings in which the target distribution belongs to a given distribution family ${\\cal D}$ or is well-approximated by a member of this family with respect to a global loss function. ", "The complexity of distribution learning often depends heavily on the structure of the underlying family. ", "The performance of a distribution learning algorithm is typically evaluated by the following criteria:\n\n- [*Sample Complexity:*]{} For a given error tolerance, the algorithm should require a small number of samples, ideally matching the information-theoretic minimum.", "\n\n- [*Computational Complexity:*]{} The algorithm should run in time polynomial (or, ideally, linear) in the number of samples provided as input.", "\n\n- [*Robustness:*]{} The algorithm should provide error guarantees under model misspecification, i.e., even if the target distribution does not belong in the target family ${\\cal D}$. The goal here is to be competitive with the best approximation of the unknown distribution by any distribution in the family ${\\cal D}$.\n\nThere are two main strands of research in distribution learning. ", "The first one concerns the learnability of [*high-dimensional parametric*]{} distribution families, e.g., mixtures of Gaussians. ", "The sample complexity of learning parametric families is typically polynomial in the dimension and the goal is to design computationally efficient algorithms.", "\n\nThe second research strand — which is the focus of this paper — studies the learnability of [*low-dimensional nonparametric*]{} distribution families under various assumptions on the shape of the underlying density. ", "There has been a long line of work on this strand within statistics since the 1950s and, more recently, in theoretical computer science. ", "The reader is referred to [@BBBB:72] for a summary of the early work and to [@GJ:14] for a recent book on the subject. ", "The majority of this literature has studied the univariate (one-dimensional) setting which is by now fairly well-understood for a wide range of distributions. ", "On the other hand, the [*multivariate*]{} setting and specifically the regime of [*fixed dimension*]{} is significantly more challenging and poorly understood for many natural distribution families.", "\n\nOur Results: Learning Multivariate Histograms {#ssec:results}\n---------------------------------------------\n\nIn this work, we study the problem of density estimation for the family of histogram distributions on $d$-dimensional domains. ", "Throughout this paper, let $[m] = \\{1, \\ldots, m\\}$ denote an ordered discrete domain of size $m$. A distribution on $[0, 1]^d$ or $[m]^d$ with probability density function $h$ is a $k$-histogram if there exists a partition of the domain into $k$ axis-aligned hyper-rectangles $R_1, \\ldots, R_k$ such that $h$ is constant within each of the $R_i$’s.", "\n\nHistograms constitute one of the most basic nonparametric distribution families. ", "The algorithmic difficulty in learning such distributions lies in the fact that the location and size of these rectangles is unknown to the algorithm. ", "Histograms have been extensively studied in statistics and computer science. ", "Many methods have been proposed to estimate histogram distributions  [@Scott79; @FreedmanD1981; @Scott:92; @LN96; @Devroye2004; @WillettN07; @Klem09] that are of a heuristic nature or have a strongly exponential dependence on the dimension. ", "In the database community, histograms [@JPK+98; @CMN98; @TGIK02; @GGI+02; @GKS06; @ILR12; @ADHLS15] constitute the most common tool for the succinct approximation of data.", "\n\nThe time complexity of learning [*univariate*]{} histograms is well-understood: prior work [@CDSS13; @CDSS14; @CDSS14b; @ADLS17] gives sample-optimal learning algorithms with near-linear running time. [[", "Perhaps surprisingly, no nearly-linear time learning algorithm is known for arbitrary histograms even in [*two*]{} dimensions. ", "Motivated by this gap in our understanding]{}]{}, we study the following question:\n\n[*Is there a computationally and statistically efficient algorithm\\\nto learn arbitrary histograms on $\\R^d$, up to $\\ell_1$ distance ${\\varepsilon}$?*]{}", "\n\n[[ Our main result answers this question in the affirmative for any constant dimension: ]{}]{}\n\nFix ${\\varepsilon}> 0$ and $k \\in \\mathbb{Z}_+$. Let $f$ be an arbitrary distribution over $[m]^d$ or $[0, 1]^d$. There is an algorithm which draws $n = \\tilde{O}_d(k/{\\varepsilon}^2)$ samples from $f$, runs in time $\\tilde{O}_d(n)$, and outputs a hypothesis $h$ that with high probability satisfies $\\| f - h \\|_1 \\; \\leq \\; O(\\OPT_k) + {\\varepsilon}$, where $\\OPT_k = \\min_{h'} \\| f - h' \\|_1$ is the best $\\ell_1$-distance achievable by any $k$-histogram.", "\n\nIt is well-known (see, e.g., [@ADLS17]) that $\\Omega (k / {\\varepsilon}^2)$ samples are necessary for any histogram learning algorithm, even for $d=1$. Hence, for any fixed dimension $d$, our algorithm is sample near-optimal (within logarithmic factors) and runs in sample nearly-linear time. ", "Even for $d=2$ and $\\OPT_k = 0$, no non-trivial algorithm was previously known for this problem.", "\n\nA few additional remarks are in order. ", "First, we would like to stress that the focus of our work is on the case where the parameters $m, k$ are [*much larger*]{} than the dimension $d$, i.e., $m, k \\gg d$. For example, this condition is automatically satisfied when $d$ is bounded from above by a fixed constant. ", "This is arguably the most natural setting for several applications of multidimensional histograms. ", "Second, our proof establishes that the hidden multiplicative constant in the $O(\\OPT_k)$ of the RHS is at most $11$. While we do not know the value of the optimal constant, a lower bound of $2$ is known even in one dimension [@CDSS14b].", "\n\nThird, the dependence on $d$ in the sample complexity of our algorithm is (weakly) exponential. ", "Such a dependence in the sample size is not necessary. ", "Standard information-theoretic arguments give that $\\tilde{O}(k d/{\\varepsilon}^2)$ samples suffice — albeit with a $(1/{\\varepsilon})^{\\Omega(k d)}$ time learning algorithm, which is clearly unacceptable even in one dimension. ", "Obtaining a learning algorithm with running time $\\poly(d, k, 1/{\\varepsilon})$ is left as a challenging open problem. ", "As observed in [@DDS15], the existence of such an algorithm may be unlikely as it would imply a $\\poly(d, k, 1/{\\varepsilon})$ time algorithm for PAC learning $k$-leaf decision trees over $\\{0, 1\\}^d$.\n\n[[As a corollary of our algorithmic techniques, we also obtain an efficient “semi-proper”[^4] learning algorithm for discrete histograms with respect to the $\\ell_2$-distance. ", "Specifically, we show:]{}]{}\n\n\\[thm:l2-informal\\] Fix ${\\varepsilon}> 0$ and $k, m, d \\in \\mathbb{Z}_+$. Let $f: [m]^d \\to \\R$ be an arbitrary distribution. ", "There is an algorithm which draws $n = O(1 / {\\varepsilon})$ samples from $f$, runs in $O_d(n \\log^2 n)$ time, and outputs an $O_d(k \\log^{d + 1} 1 / {\\varepsilon})$-histogram $h$ so that with high probability $\\| f - h \\|_2^2 \\leq 2 \\cdot \\OPT_k + {\\varepsilon}$, where $\\OPT_k = \\min_{h'} \\| f - h' \\|_2^2$ is the best $\\ell_2$-squared error achievable by any $k$-histogram.", "\n\n[[ It is a folklore fact (see, e.g., [@ADHLS15]) that $\\Theta(1/{\\varepsilon})$ samples are necessary and sufficient for this problem and that the empirical distribution is an accurate hypothesis. ", "Our algorithm is sample-optimal, runs in near-linear time for constant dimension $d$, and importantly provides a succinct “semi-proper” hypothesis distribution. ", "Succinct data representations by multivariate histograms are well-motivated in several data analysis applications in databases, where randomness is used to sub-sample a large dataset [@CGHJ12].]{}]{}", "\n\nOur Techniques and Comparison to Prior Work\n-------------------------------------------\n\n[[ In this section, we provide an overview of our techniques in tandem with a comparison to prior work. ", "Standard metric entropy arguments (see, e.g., [@DL:01]) yield an inefficient method that uses $\\tilde{O}(kd/{\\varepsilon}^2)$ samples and runs in time $(1/{\\varepsilon})^{\\Omega(kd)}$. To avoid the exponential dependence on $k$ in the runtime, one can first partition the domain into $\\poly(k/{\\varepsilon})^{\\Theta(d)}$ “light” rectangles and then learn the induced probability distribution on these rectangles. ", "This naive learning algorithm inherently incurs sample complexity and running time of $\\poly(k/{\\varepsilon})^{\\Theta(d)}$, which makes it unsatisfying even for $2$ dimensions. ]{}]{}", "\n\nOur algorithms rely on two main ideas. ", "The first ingredient is a *greedy splitting* scheme that enables us to approximate multi-dimensional histograms efficiently. ", "In contrast to one-dimensional histograms, the partitions induced by multi-dimensional histograms are too complicated for a direct dynamic programming approach. ", "Similarly, the approximate [*iterative merging*]{} strategy analyzed in [@ADLS17] does not seem to generalize to the multi-dimensional setting: merging two adjacent rectangles does not necessarily yield another rectangle (as opposed to adjacent intervals). ", "We circumvent the difficulties introduced by the complex structure of arbitrary histogram partitions by going through hierarchical histograms, which yield a more structured space of partitions that is amenable to efficient algorithms. [[[", "@WillettN07] used a related decomposition to learn smooth classes of continuous densities. ", "First, we note that our algorithm and its analysis are significantly different from theirs. ", "Second, [@WillettN07] do not obtain a near-linear time algorithm even in one dimension. ", "In the univariate setting, [@DiakonikolasG0N17] used a similar algorithm to learn discrete distributions in the distributed setting with respect to the $\\ell_2$-norm.]{}]{}", "\n\nHierarchical histograms have appeared before in histogram approximation, especially in the setting of wavelet-based approaches (for instance, see [@GKMS01; @GGI+02]) but also in approximate dynamic programs such as [@MPS99]. ", "However, these approaches do not handle the $\\ell_1$-setting that is standard in distribution learning. ", "Instead, we propose a top-down splitting algorithm that expands leaf nodes in a growing hierarchical histogram according to a special error metric that we call the *${\\mathcal{D}}$-distance*. ", "The ${\\mathcal{D}}$-distance is closely related to VC theory and allows us to make good splitting decisions not only for the empirical distribution but also for the unknown distribtion we aim to recover.", "\n\nThe basic version of our greedy splitting scheme relies on hierarchical partitions of the distribution domain $[m]^d$, which incurs a logarithmic dependence on the domain size and does not apply to the continuous setting. ", "The second ingredient in our paper is an *adaptive* variant of our splitting algorithm. ", "This variant makes splitting decisions not on the dyadic boundaries of a data-independent hierarchical partition, but instead relies on the empirical distribution to build a data-dependent grid of coordinate points. ", "By restricting our attention to the relevant coordinates, we can remove the logarithmic dependence on $m$ and also apply our algorithm to distributions defined on $[0,1]^d$. The adaptive approach requires a more careful analysis of our splitting algorithms and relies on the notion of a *partial* hierarchical histogram. ", "In a partial hierarchical histogram, each partition can “shrink” to the bounding box of the samples in the partition, leaving a region on which the partition assigns value 0. ", "Our final adaptive splitting algorithm runs in time that is nearly-linear in the number of samples with no dependence on the domain size. ", "This is in contrast to prior wavelet-based approaches, which usually have a logarithmic dependence on the domain size and often process the entire domain $[m]^d$ as opposed to only the non-zero sample points.", "\n\n[0.3]{} ![", "One iteration of our adaptive partitioning scheme. ", "The left sub-figure (a) displays the hierarchical partitioning of $\\R^2$ after two iterations of the algorithm. ", "It is derived from two levels of splits: first the green split, then the blue splits. ", "The center sub-figure (b) shows the candidate leaf splits that the algorithm considers as next refinements. ", "The algorithm chooses the splits that most reduce a certain error metric (see the right sub-figure (c)). ](", "hist1.pdf \"fig:\"){width=\"\\textwidth\"}\n\n[0.3]{} ![", "One iteration of our adaptive partitioning scheme. ", "The left sub-figure (a) displays the hierarchical partitioning of $\\R^2$ after two iterations of the algorithm. ", "It is derived from two levels of splits: first the green split, then the blue splits. ", "The center sub-figure (b) shows the candidate leaf splits that the algorithm considers as next refinements. ", "The algorithm chooses the splits that most reduce a certain error metric (see the right sub-figure (c)). ](", "hist2.pdf \"fig:\"){width=\"\\textwidth\"}\n\n[0.3]{} ![", "One iteration of our adaptive partitioning scheme. ", "The left sub-figure (a) displays the hierarchical partitioning of $\\R^2$ after two iterations of the algorithm. ", "It is derived from two levels of splits: first the green split, then the blue splits. ", "The center sub-figure (b) shows the candidate leaf splits that the algorithm considers as next refinements. ", "The algorithm chooses the splits that most reduce a certain error metric (see the right sub-figure (c)). ](", "hist3.pdf \"fig:\"){width=\"\\textwidth\"}\n\nPreliminaries\n=============\n\nWe define the $\\ell_p$-norm of a measurable function $f: [m]^d \\to \\R$ or $f: [0, 1]^d \\to \\R$ to be $\\| f \\|_p = \\left( \\sum_{x \\in [m]^d} |f(x)|^p \\right)^{1 / p}$ or $\\| f \\|_p = \\left( \\int |f (x)|^p dx \\right)^{1 / p}$, for $[m]^d$ and $[0, 1]^d$ respectively. ", "For any subset $R \\subseteq [m]^d \\to \\R$ (similarly for $[0, 1]^d$), we let $\\| f \\|_{p, R}$ be the $\\ell_p$-norm of $f$ restricted to $R$. Given $X_1, \\ldots, X_n$ samples from a distribution $f$ supported over $[m]^d$ (resp $[0, 1]^d$), we let the empirical distribution induced by these samples be ${\\widehat{f}}= \\frac{1}{n} \\sum_{i = 1}^n \\delta_{X_i}$, where $\\delta_X$ is the delta distribution supported at $X$.\n\nHistograms and Problem Definition\n---------------------------------\n\nWe first define the notion of histograms. ", "Throughout this paper, we will assume w.l.o.g. ", "that $m$ is a power of $2$.\n\nA distribution $h: {{A}} \\to \\R$, [[where $A$ is either $[m]^d$, for $m \\in \\Z_+$, or $[0, 1]^d$,]{}]{} is called a *$k$-histogram* if there exists a partition of [[$A$]{}]{} into $k$ axis aligned rectangles $R_1, \\ldots, R_k$ so that $h$ is constant on $R_i$, for all $i = 1,\\ldots, k$. We let ${\\mathcal{H}}_k$ denote the set of $k$-histograms.", "\n\nWe now can state the formal problem:\n\n#### Problem Statement\n\nGiven $0< {\\varepsilon}, \\delta <1$ and independent samples from some distribution $f: {{A}} \\to \\R$ [[where $A$ is either $[m]^d$ or $[0, 1]^d$]{}]{}, return ${\\widehat{h}}$ so that with probability $1 - \\delta$, we have $\\| {\\widehat{h}}- f \\|_1 \\leq C \\cdot \\OPT_k + {\\varepsilon}$, where $C$ is an absolute constant and $$\\OPT_k = \\min_{h \\in {\\mathcal{H}}_k} \\| h - f \\|_1 \\; .$$\n\nWe will also crucially make use of the following definition throughout the paper:\n\nLet $g$ be any function over $[m]^d$ (resp. ", "$[0, 1]^d$). ", "For any set $R \\subseteq [m]^d$ (resp. ", "$[0, 1]^d$), define the flattening of $g$ over $R$, denoted ${\\overline{g}}_R$, to be the constant function on $R$ which takes on value $g(R) / |R|$ at each point in $R$. For any collection of disjoint sets $\\mathcal{R}$, define the flattening of $g$ over $\\mathcal{R}$, denoted ${\\overline{g}}_R$, to be the function which is equal to the flattening of $g$ on each set $R \\in \\mathcal{R}$.\n\nHierarchical Histograms\n-----------------------\n\nWe also require the notion of a *hierarchical* histogram, which is a histogram that respects a fixed dyadic partition. ", "Formally:\n\nGiven a grid ${\\mathcal{G}}= P_1 \\times P_2 \\times \\ldots \\times P_d$, where each $P_i$ is a collection of elements $x^{(i)}_1 \\leq x^{(i)}_2 \\leq \\ldots \\leq x^{(i)}_M$ in $[m]$ (resp. ", "$[0, 1]$) and $M$ is a power of $2$, *the level-$\\ell$ rectangles* induced by ${\\mathcal{G}}$, denoted ${\\mathcal{R}}_\\ell$, is defined to be $${\\mathcal{R}}_\\ell = \\left\\{ \\otimes_{i = 1}^d [x^{(i)}_{2^\\ell j_i + 1}, x^{(i)}_{2^{\\ell} (j_{i} + 1) }] : j_i \\in \\{0, \\ldots, M / 2^\\ell - 1\\} \\right\\} \\; .$$ Moreover, the *dyadic decomposition* of ${\\mathcal{G}}$, denoted ${\\mathcal{D}}= {\\mathcal{D}}({\\mathcal{G}})$, is defined to be ${\\mathcal{D}}= \\bigcup_{\\ell = 1}^{\\log M} {\\mathcal{R}}_\\ell$. For any $k \\geq 1$, and a dyadic decomposition ${\\mathcal{D}}$ of a grid ${\\mathcal{G}}$ we let ${\\mathcal{D}}_k$ denote all disjoint unions of at most $k$ rectangles from ${\\mathcal{D}}$.\n\nFor instance, if the domain is $[m]^d$ and each $P_i = [m]$, then the induced dyadic decomposition is simply the set of squares $R$ with side-length $2^\\ell$ for some $\\ell = 1, \\ldots, \\log m$ and whose rightmost vertices are at a power of $2$. In general, any dyadic decomposition induces a natural tree structure, which we will utilize throughout the paper. ", "We can now define our notion of a hierarchical histogram:\n\nWe say a $k$-histogram $f: {{A}} \\to \\R$ [[where $A$ is either $[m]^d$ or $[0, 1]^d$]{}]{} is hierarchical with respect to a grid ${\\mathcal{G}}$ if there exists a partition of ${{A}}$ into rectangles $R_1, \\ldots, R_k \\in {\\mathcal{D}}({\\mathcal{G}})$ so that $f$ is constant on each $R_i$. If ${\\mathcal{G}}$ is understood, we say $f$ is hierarchical for short.", "\n\nWe have the following simple lemma, which says that we may assume w.l.o.g. ", "that the histogram is hierarchical, with some loss:\n\n\\[lem:arbitrary-to-hierarchical\\] Fix a grid ${\\mathcal{G}}$ with side length $M$. Let $f: {{A}} \\to \\R$ [[where $A$ is either $[m]^d$ or $[0, 1]^d$]{}]{} be a $k$-histogram so that it is constant on $R_1, \\ldots, R_k$, where every vertex of every rectangle lies on ${\\mathcal{G}}$. Then $f$ is a $k \\log^d M$-hierarchical histogram.", "\n\nFor simplicity of exposition we will show this assuming ${\\mathcal{G}}= [m]^d$, so the side length is equal to $m$. [[The same proof easily extends to general grids, and so we omit the details for conciseness]{}]{}. ", "It suffices to show that any function which is supported within an axis-aligned rectangle $R$ and which is constant within this rectangle can be represented as a $\\log^d m$-hierarchical histogram. ", "Let $R = [a_1, b_1] \\times [a_2, b_2] \\times \\ldots \\times [a_d, b_d]$. Each interval $[a_i, b_i]$ can be written as a union of at most $\\log m$ disjoint dyadic intervals ${\\mathcal{I}}_i$, so $R$ can be decomposed as the disjoint union of all rectangles $R = \\otimes_{i = 1}^d I_i$ where each $I_i$ ranges over all intervals in ${\\mathcal{I}}_i$. By inspection, this requires $\\log^d m$ pieces.", "\n\nThus, we lose $\\log^d M$ factors going from arbitrary histograms to hierarchical histograms, where $M$ is the side length of our grid.", "\n\nVC Theory\n---------\n\nWe now need the following classical definition of ${\\mathrm{VC}}$-dimension:\n\nA collection of sets ${\\mathcal{A}}$ is said to *shatter* a set $S$ if for all $S' \\subseteq S$, there is an $A \\in {\\mathcal{A}}$ so that $A \\cap S = S'$. The VC dimension of ${\\mathcal{A}}$, denoted ${\\mathrm{VC}}({\\mathcal{A}})$, is the largest $n$ so that there exists a $S$ with $|S| = n$ so that ${\\mathcal{A}}$ shatters $S$.\n\nFor any collection $\\mathcal{A}$ of measurable subsets of $[m]^d$ or $[0, 1]^d$, define the $\\mathcal{A}$-norm, denoted $\\| \\cdot \\|_\\mathcal{A}$, on measurable real-valued functions on $\\R^d$ to be $$\\| f \\|_{\\mathcal{A}}= \\sup_{A \\in {\\mathcal{A}}} |f(A)| \\;.$$ For any measurable subset $R$ of $[m]^d$ or $[0, 1]$, we also define $\\| \\cdot \\|_{\\mathcal{A}, R}$ to be the ${\\mathcal{A}}$-norm of the function restricted to $R$. We now need the following form of the VC theorem, which follows by combining a classical form of the VC theorem along with standard uniform deviation arguments (e.g., McDiarmid’s inequality):\n\n\\[thm:vc\\] Let $f: [m]^d \\to \\R$ be a distribution, and let ${\\widehat{f}}_n$ denote the empirical distribution after $n$ independent draws from $f$. Then, for all $\\delta > 0$, $\n\\Pr \\left[ \\| f - {\\widehat{f}}_n \\|_{\\mathcal{A}}\\geq \\sqrt{\\frac{{\\mathrm{VC}}({\\mathcal{A}}) + \\log 1 / \\delta}{n}} \\right] \\leq \\delta\n$.", "\n\nLearning Histograms in $\\ell_1$-Distance {#sec:l1}\n========================================\n\nWe now consider the question of histogram approximation in $\\ell_1$. The main difficulty in learning in $\\ell_1$ (as opposed to, say, in $\\ell_2$), is that the statistical and algorithmic questions do not nicely decouple. ", "This is because the empirical distribution is not close to the true distribution until many samples are taken. ", "Instead, we will have to consider a different algorithmic objective inspired by VC theory.", "\n\nComputing ${\\mathcal{D}}$-distance and fitting in ${\\mathcal{D}}$-distance\n--------------------------------------------------------------------------\n\nRecall that ${\\mathcal{D}}$ is defined to be the set of dyadic rectangles over $[m]^d$ (resp. ", "$[0, 1]^d$). ", "By the theory developed above, this naturally induces a metric on functions from $[m]^d$ (resp. ", "$[0, 1]^d$) to $\\R$. In this section, we show that computing and fitting with respect to ${\\mathcal{D}}$ distance can be done in nearly input-sparsity time. ", "Throughout this section, fix any grid ${\\mathcal{G}}$ of side length $M$ for $[m]^d$ or $[0, 1]^d$. For any $a \\in \\R$ and $R \\in {\\mathcal{D}}$, let $\\phi_{a, R}: R \\to \\R$ denote the function on $R$ which is constantly $a$. We show:\n\n\\[lem:compute-A1\\] Given an empirical distribution ${\\widehat{f}}$, a rectangle $R \\in \\mathcal{D}$ so that ${\\widehat{f}}$ is supported on $s$ points in $R$, and a $a \\in \\R$, there is an algorithm <span style=\"font-variant:small-caps;\">ComputeD1</span> that runs in time $O(2^d s \\log M)$ and outputs $\\| {\\widehat{f}}- \\phi_{a, R} \\|_{{\\mathcal{D}}, R}$ together with a rectangle in ${\\mathcal{D}}$ achieving this maximum.", "\n\nFor conciseness we defer the proof of Lemma \\[lem:compute-A1\\] to Appendix \\[sec:l1-app\\]. ", "We now show that as a simple consequence of this, we can (approximately) find the constant fit to ${\\widehat{f}}$ on any rectangle $R$ in $\\| \\cdot \\|_{{\\mathcal{D}}, R}$-norm in nearly linear time:\n\nGiven $\\gamma > 0$, an empirical distribution ${\\widehat{f}}$, a rectangle $R \\in \\mathcal{D}$ so that ${\\widehat{f}}$ is supported on $s$ points in $R$, there is an algorithm <span style=\"font-variant:small-caps;\">FitD1</span> which outputs an $a \\in \\R$ so that $\n\\| {\\widehat{f}}- \\phi_{a, R} \\|_{{\\mathcal{D}}, R} \\leq \\min_{a' \\in \\R} \\| {\\widehat{f}}- \\phi_{a', R} \\|_{{\\mathcal{D}}, R} + \\gamma\n$ in time ${\\widetilde{O}}(\\poly(d) \\cdot s \\log M \\log 1 / \\gamma)$.\n\nThe algorithm is simple: we reduce the optimization problem with binary searching over feasibility problems, then solve each feasibility problem using <span style=\"font-variant:small-caps;\">ComputeD1</span> as a separation oracle. ", "The details are subsumed by the calculations for Theorem 31 of [@ADLS17], so we omit them.", "\n\nFor simplicity, we shall assume for the rest of the paper that <span style=\"font-variant:small-caps;\">FitD1</span> produces an exact fit in ${\\mathcal{A}}_1$-distance. ", "Because the dependence on $\\gamma$ in the runtime is logarithmic, it is not hard to see that by taking $\\gamma = \\poly (k, 1 / {\\varepsilon}, \\log 1 / \\delta)^d$ in the remainder, we only increase the approximation errors throughout by at most additive ${\\varepsilon}$ factors, and this keeps the runtime unchanged, up to log factors.", "\n\nThe Greedy Splitting Algorithm for $\\ell_1$-Distance\n----------------------------------------------------\n\nIn this section, we give an efficient algorithm for constructing hierarchical histograms for fitting a known empirical distribution in the norm induced by the hierarchical decomposition. ", "Throughout this section, fix a grid ${\\mathcal{G}}$ with side length $M$ over either $[m]^d$ or $[0,1]^d$, and let ${\\mathcal{D}}= {\\mathcal{D}}({\\mathcal{G}})$ be the induced dyadic decomposition.", "\n\nWe will prove that our output, despite being a hierarchical histogram, is actually competitive with the best error achievable by a slightly more general class of functions, which we call partial hierarchical histograms. ", "Formally:\n\nA partial $k$-histogram $h: [m]^d \\to \\R$ (or $h: [0, 1]^d \\to \\R$) is a distribution [[satisfying the following:]{}]{} there exist $k$ disjoint rectangles $R_1, \\ldots, R_k$ such that $h$ is supported on $\\bigcup_{i = 1}^k R_i$, and on each $R_i$, $h$ is constant. ", "We say that $h$ is a partial $k$-hierarchical histogram with respect to a grid ${\\mathcal{G}}$ if in addition we have $R_i \\in {\\mathcal{D}}({\\mathcal{G}})$ for all $i$.\n\nOur main algorithmic theorem is:\n\n\\[thm:splitting\\] Fix $k \\in \\mathbb{Z}_+$, and let $\\gamma > 0$ be a tuning parameter. ", "Let ${\\widehat{f}}$ be an empirical distribution on $s$ points. ", "There is an algorithm <span style=\"font-variant:small-caps;\">GreedySplit</span> which outputs a $O((1 + \\xi) 2^d k \\log M)$-hierarchical histogram $h$ so that $\\| h - {\\widehat{f}}\\|_{{\\mathcal{D}}_k} \\leq \\left( 3 + \\frac{6}{\\xi^2} \\right) \\cdot {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} + {\\varepsilon}$, where ${\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} = \\min_{h} \\| h - {\\widehat{f}}\\|_{{{{\\mathcal{D}}_k}}}$, where the minimum is taken over all partial hierarchical $k$-histograms $h$. Moreover, the algorithm runs in time ${\\widetilde{O}}(2^d s \\log^2 M)$.\n\nOur algorithm, given formally in Algorithm \\[alg:hist-l1\\], is quite simple. ", "We construct a tree of nested dyadic rectangles. ", "Initially, this tree contains only $[m]^d$. Iteratively, we find the leaves of this tree with largest ${{{\\mathcal{D}}}}$-distance error to $g$, and we split these into all of its children, and we repeat this for $\\log M$ iterations. ", "At the end, we return the flattening of $g$ over all the leaves in the final tree. ", "For conciseness, we defer the proof of Theorem \\[thm:splitting\\] to Appendix \\[sec:l1-app\\].", "\n\nLet ${\\mathcal{T}}$ be a subtree of the hierarchical tree, initially containing only the root. ", "Let $a_R = \\textsc{FitD1} ({\\widehat{f}}, {\\mathcal{D}}, R)$ Let $e_R = \\textsc{ComputeD1} ({\\widehat{f}}, R, a_R)$ Let ${\\mathcal{J}}$ be the set of $(1 + \\xi) k$ leaves $R \\in {\\mathcal{T}}$ with largest $e_R$. \\[line:J\\] Add all children of $R$ to ${\\mathcal{T}}$ **return** The function which is constantly $a_R$ for every leaf $R$ of ${\\mathcal{T}}$\n\nWarm-up: an Algorithm for Hierarchical Histograms on $[m]^d$\n------------------------------------------------------------\n\nIn this section, we will take ${\\mathcal{G}}= [m]^d$. Assume for simplicity that $m$ is a power of $2$. Then, we may take ${\\mathcal{D}}$ to be the dyadic partition of $[m]^d$, i.e., ${\\mathcal{D}}= \\{ {\\mathcal{R}}_i \\}_{i = 1}^{\\log m}$ where $${\\mathcal{R}}_i = \\left\\{ \\otimes_{i = 1}^d [j_i m 2^{-i} + 1, (j_i + 1) m 2^{-i}] : j_i \\in \\{0, \\ldots, 2^{i} - 1\\} \\right\\}$$ are all rectangles on a $m 2^{-i}$-spaced grid. ", "The following are standard facts from VC theory and we defer their proof to Appendix \\[sec:l1-app\\].", "\n\n\\[cor:difference-of-histograms\\] Let $f, g$ be two $k$-hierarchical histograms. ", "Then $2 \\| f - g \\|_{{\\mathcal{D}}_{2k}} = \\| f - g \\|_1$.\n\n\\[cor:VC-hierk\\] For all $k, d \\geq 1$, we have ${\\mathrm{VC}}({\\mathcal{D}}_k) = O(k d)$.\n\nThese corollaries together imply:\n\n\\[cor:hierarchical-main\\] Fix ${\\varepsilon}, \\delta > 0$, and let $\\gamma > 0$. Let $f: [m]^d \\to \\R$ be an arbitrary distribution. ", "Then, the algorithm $\\textsc{GreedySplit}({\\widehat{f}}, {\\mathcal{D}}([m]^d), \\xi)$, given ${\\widehat{f}}= {\\widehat{f}}_n$ which is the empirical distribution of $f$ after $\nn = \\Omega \\left( \\frac{(1 + \\xi) 2^d k \\log^{d + 1} m + \\log 1 / \\delta}{{\\varepsilon}^2} \\right)\n$ samples, outputs a $(1 + \\xi) 2^d d k \\log^{d +1} m$-hierarchical histogram $h$ so that with probability $1 - \\delta$, we have $\n\\| f - h \\|_1 \\leq \\left( 3 + \\frac{6}{\\xi^2} \\right) \\cdot \\OPT_k + {\\varepsilon}$. Moreover, this algorithm runs in time $O(2^d n \\log^2 m)$.\n\nThe bound on the number of pieces and the runtime of the algorithm follow from Lemmas \\[lem:pieces\\] and \\[lem:runtime\\] immediately. ", "Thus, it suffices to argue about correctness. ", "By Lemma \\[lem:arbitrary-to-hierarchical\\], we know that if we let $\\OPT'_{k \\log^d m}$ be the optimal $\\ell_1$-error to $f$ achievable by a hierarchical $k \\log^d m$-histogram, then $\\OPT'_{k \\log^d m} \\leq \\OPT_k$. Let $h^*_{{\\mathcal{D}}}$ be the hierarchical $k$-histogram which achieves the optimum.", "\n\nCondition on the event that $\\| f - {\\widehat{f}}\\|_{{\\mathcal{D}}_\\kappa} \\leq c {\\varepsilon}$, where $\\kappa = 2 (1 + \\xi) 2^d k \\log^{d + 1} m$, for some universal constant $c$ sufficiently small. ", "By Theorem \\[thm:vc\\], this happens with probability $1 - \\delta$ if we take $\nn = \\Omega \\left( \\frac{(1 + \\xi) 2^d k \\log^{d + 1} m + \\log 1 / \\delta}{{\\varepsilon}^2} \\right)\n$ samples. ", "Then, we have $$\\begin{aligned}\n\\| {\\widehat{f}}- h^*_{\\mathcal{D}}\\|_{{\\mathcal{D}}_\\kappa} &\\leq \\| f - {\\widehat{f}}\\|_{{\\mathcal{D}}_\\kappa} + \\| f - h^*_{\\mathcal{D}}\\|_{{\\mathcal{D}}_\\kappa} \\leq \\OPT'_{k \\log^d m} + c {\\varepsilon}\\; .\\end{aligned}$$ Therefore, we have ${\\widetilde{\\OPT}}_{k \\log^d m} \\leq \\OPT'_{k \\log^d m} + c {\\varepsilon}$. Combining this with the guarantee from Theorem \\[thm:splitting\\] then immediately yields the statement, for $c'$ chosen to be sufficiently small.", "\n\nGeneral Histograms via Adaptive Gridding\n----------------------------------------\n\nThe framework presented above is very clean, however, it has one major drawback. ", "Namely, the conversion from arbitrary to hierarchical histograms on the grid $[m]^d$ loses $\\log^d m$ factors. ", "In particular, these factors prevent the algorithm from being useful when the support size is large or infinite. ", "In this section, we show that a modification of the techniques presented above can remove these factors. ", "The algorithm in this section will work even when the support size is infinite. ", "Throughout the section, we will state our results for $[m]^d$, however, they generalize trivially to $[0, 1]^d$, and we omit the details for simplicity. ", "Our main result in this section is:\n\n\\[thm:adaptive-main\\] Fix ${\\varepsilon}, \\delta > 0$, and let $\\gamma > 0$. Let $f: [m]^d \\to \\R$ be an arbitrary distribution. ", "There is an algorithm <span style=\"font-variant:small-caps;\">AdaptiveGreedySplit</span>, which, given $n$ independent samples from $f$, where $\nn = O \\left( \\frac{(1 + \\xi) d 2^d k \\log^{d + 2} (k / {\\varepsilon}) + \\log 1 / \\delta}{{\\varepsilon}^2} \\right)\n$, outputs a $O((1 + \\xi) d 2^d k \\log^{d + 1} (k / {\\varepsilon}))$-hierarchical histogram $h$ so that with probability $1 - \\delta$, we have $\\| f - h \\|_1 \\leq \\left( 10 + \\frac{12}{\\xi^2} \\right) \\cdot \\OPT_k + {\\varepsilon}$. Moreover, this algorithm runs in time $O(2^d n \\log^2 n)$.\n\n#### The VC dimension of (Partial) Histograms\n\nIn this section, we bound the VC dimension of set systems induced by differences between $k$-histograms and partial histograms. ", "We first need the following fact, which is a direct implication of the respective definitions:\n\n\\[fact:difference-of-partials\\] Given two $k$-partial histograms $h, g: [m]^d \\to \\R$, the set $\\{x: h(x) > g(x) \\}$ is of the form $\\bigcup_{i = 1}^{k'} A_i - \\bigcup_{j = 1}^{k''} B_j$, for some axis aligned rectangles $A_i, B_j$ so that the $A_i$ are mutually disjoint and $B_j$ are mutually disjoint, and $k', k'' \\leq k$.\n\nMotivated by this fact, we let $${\\mathcal{A}}_k = \\left\\{ \\bigcup_{i = 1}^{k'} A_i - \\bigcup_{j = 1}^{k''} B_j : ~\\mbox{$\\{ A_i \\}_{i = 1}^{k'}, \\{ B_j \\}_{j = 1}^{k''}\n$ are collections of disjoint rectangles, $k', k'' \\leq k$}~ \\right\\} \\;$$ be the set system that captures sign difference between $k$-partial histograms. ", "By Fact \\[fact:difference-of-partials\\], we have:\n\nFor any two $k$-partial histograms $h, g: [m]^d \\to \\R$ (or over $[0, 1]^d$), we have $\n\\| h - g \\|_1 = 2 \\| h - g \\|_{{\\mathcal{A}}_k}.$\n\nWe now require a bound on the VC dimension of ${\\mathcal{A}}_k$, whose proof we defer to the appendix:\n\n\\[lem:VC-histograms\\] For all $k \\geq 1$, we have ${\\mathrm{VC}}({\\mathcal{A}}_k) = O(k d \\log (k d))$.\n\nAs an immediate corollary of Theorem \\[thm:vc\\] and Lemma \\[lem:VC-histograms\\], we have:\n\n\\[cor:VC-histograms\\] Fix ${\\varepsilon}, \\delta > 0$. Let $f:[m]^d \\to \\R$ be an arbitrary distribution. ", "Let ${\\widehat{f}}= {\\widehat{f}}_n$ be the empirical distribution given $n$ independent samples from $f$, where $\nn = O \\left( \\frac{k d \\log (k d) + \\log 1 / \\delta}{{\\varepsilon}^2} \\right)$. Then, with probability $1 - \\delta$, we have $\\| {\\widehat{f}}- f \\|_{{\\mathcal{A}}_k} \\leq {\\varepsilon}$.\n\nFor the rest of the section, we let $f$ denote the unknown distribution, and we let ${\\widehat{f}}= {\\widehat{f}}_n$ denote the empirical distribution after $n$ draws from $f$, where $$n = C \\frac{(1 + \\xi) d 2^d k \\log^{d + 2} (k / {\\varepsilon}) + \\log 1 / \\delta}{{\\varepsilon}^2} \\; ,$$ for some universal constant $C$ sufficiently large. ", "We let ${\\mathcal{X}}$ denote the (multi-)set of samples, i.e., ${\\mathcal{X}}= {\\mathrm{supp}}({\\widehat{f}})$, and we will, in a slight abuse of notation, let ${\\mathcal{D}}= {\\mathcal{D}}({\\mathrm{grid}}({\\mathcal{X}}))$.\n\nWe will condition on the event that $$\\label{eq:deterministic-cond}\n\\| {\\widehat{f}}- f \\|_{{\\mathcal{A}}_{\\kappa}} \\leq c' {\\varepsilon}\\; ,$$ for some universal constant $c'$ sufficiently small, where $\\kappa = C' (1 + \\xi) 2^d k \\log^{d + 1} (k / {\\varepsilon})$ for some universal constant $C'$ sufficiently large. ", "Observe that since ${\\mathcal{D}}_k \\subseteq {\\mathcal{A}}_k$, this immediately implies that $\n\\| {\\widehat{f}}- f \\|_{{\\mathcal{D}}_k} \\leq c' {\\varepsilon}$. By Corollary \\[cor:VC-histograms\\], this holds with probability $1 - \\delta$ as long as we take at least $$n = \\Omega \\left( \\frac{d \\kappa \\log (d \\kappa) + \\log 1 / \\delta}{{\\varepsilon}^2} \\right) \\; .$$ In particular, this holds for our choice of $n$, for $C$ sufficiently large.", "\n\n#### Rounding Histograms to Partial Hierarchical Histograms\n\nOur algorithm is straightforward: we simply grid over all points where the samples land, that is, we take the grid to be ${\\mathcal{G}}= {\\mathrm{grid}}({\\mathcal{X}})$, then find the best fit hierarchical histogram with respect to this grid, and the norm it induces, using the same algorithm as above. ", "Our algorithm will then be very similar to the algorithm presented previously, with some crucial but subtle changes, however, the analysis requires some additional steps.", "\n\nIn particular, now it is not a priori clear that the optimal histogram fit to the true density will have vertices on the grid, and in general, it is not too hard to show that it will not. ", "However, we show that by only losing constant factors in the approximation ratio, we may as well assume that it does, with some important caveats. ", "Specifically, we show that we may approximate the optimal fit $k$-histogram to $f$ with a $k$-partial histogram with vertices on the grid. ", "Formally:\n\n\\[lem:arbitrary-to-hierarchical-rounding\\] Fix ${\\varepsilon}> 0$, and assume that (\\[eq:deterministic-cond\\]) holds. ", "Then, there is a $\\kappa' = O(k \\log^d (k / {\\varepsilon}))$-partial histogram $h_p^*$ that is hierarchical with respect to ${\\mathcal{X}}$ so that $$\\label{eq:arbitrary-to-hierarchical}\n\\| f - h^*_p \\|_1 \\leq 2 \\cdot \\OPT_k + 4 c' {\\varepsilon}\\; .$$\n\nWe defer the proof of Lemma \\[lem:arbitrary-to-hierarchical-rounding\\] to Appendix \\[sec:l1-app\\]. ", "We also need the following lemma, which states that the ${\\mathcal{D}}_k$-distance still captures the $\\ell_1$-distance between a partial hierarchical histogram and a (regular) hierarchical histogram.", "\n\n\\[lem:partial-minus-full\\] Fix a grid ${\\mathcal{G}}$, and let $h$ be a partial hierarchical $k$-histogram, and let $g$ be a hierarchical $k$-histogram, both with respect to ${\\mathcal{G}}$. Then, $\\{x: h(x) > g(x)\\} \\in {\\mathcal{D}}_k ({\\mathcal{G}})$. In particular, this implies that $\\| h - g \\|_1 = 2 \\| h - g \\|_{{\\mathcal{D}}_{2k}}$.\n\nFor conciseness we defer the proof to Appendix \\[sec:l1-app\\].", "\n\n#### Putting Everything Together\n\nWe now have the tools to prove Theorem \\[thm:adaptive-main\\]. ", "The algorithm is fairly simple: we take the grid induced by our samples, and run <span style=\"font-variant:small-caps;\">GreedySplit</span> on this grid on the empirical distribution. ", "The formal pseudocode is given in Algorithm \\[alg:ada-hist-l1\\] in Appendix \\[sec:l1-app\\].", "\n\nThe runtime guarantee and the guarantee on the number of pieces easily follow from Theorem \\[thm:splitting\\]. ", "Thus, it suffices to prove correctness. ", "Let ${\\mathcal{X}}$ denote the set of samples, let ${\\mathcal{G}}= {\\mathrm{grid}}({\\mathcal{X}})$, and ${\\mathcal{D}}= {\\mathcal{D}}({\\mathcal{G}})$. Recall $h$ is the output of our algorithm, and let $h^*$ be the optimal $k$-histogram fit to $f$ in $\\ell_1$. By Lemma \\[lem:arbitrary-to-hierarchical-rounding\\], we know that there is some partial hierarchical $O(k \\log^d (k / {\\varepsilon}))$-histogram $h^*_p$ so that $$\\label{eq:OPT-partial}\n\\| f - h^*_p \\|_1 \\leq 2 \\OPT_k + 2 c' {\\varepsilon}\\; .$$ In particular, this implies that $$\\begin{aligned}\n\\| {\\widehat{f}}- h^*_p \\|_{{\\mathcal{D}}_{\\kappa}} &\\leq \\| {\\widehat{f}}- f \\|_{{\\mathcal{D}}_{\\kappa}} + \\| f - h^*_p \\|_{{\\mathcal{D}}_{\\kappa}} \n\\\\\n&\\leq {\\varepsilon}+ 2 \\OPT_k + 2 c' {\\varepsilon}\\\\\n&= 2 \\OPT_k + 3 c' {\\varepsilon}\\; ,\\end{aligned}$$ and hence ${\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\leq 2 \\OPT_k + 3 c' {\\varepsilon}$. We thus have $$\\begin{aligned}\n\\| f - h \\|_1 &\\leq \\| f - h^*_p \\|_1 + \\| h^*_p - h \\|_1 \\\\\n&\\stackrel{(a)}{\\leq} 2 \\cdot \\OPT_k + 2 c' {\\varepsilon}+ \\| h^*_p - h \\|_{{\\mathcal{D}}_{\\kappa}} \\\\\n&\\stackrel{(b)}{\\leq} 2 \\cdot \\OPT_k + 2 c' {\\varepsilon}+ \\| h^*_p - {\\widehat{f}}\\|_{{\\mathcal{D}}_{\\kappa}} + \\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_{\\kappa}} \\\\\n&\\stackrel{(c)}{\\leq} 2 \\cdot \\OPT_k + 2 c' {\\varepsilon}+ \\| h^*_p - f \\|_1 + \\| f - {\\widehat{f}}\\|_{{\\mathcal{D}}_{\\kappa}} + \\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_{\\kappa}} \\\\\n&\\stackrel{(d)}{\\leq} 4 \\OPT_k + 5 c' {\\varepsilon}+ \\left( 3 + \\frac{6}{\\xi^2} \\right) {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\\\\n&\\leq \\left( 10 + \\frac{12}{\\xi^2} \\right) \\OPT_k + O(c' {\\varepsilon}) \\; ,\\end{aligned}$$ where (a) follows from a triangle inequality, (\\[eq:OPT-partial\\]), and Lemma \\[lem:partial-minus-full\\], (b) and (c) follow from the triangle inequality, and (d) follows from (\\[eq:OPT-partial\\]), (\\[eq:deterministic-cond\\]) and Theorem \\[thm:splitting\\]. ", "By choosing $c'$ sufficiently small, this completes the proof.", "\n\nOmitted Proofs from Section \\[sec:l1\\] {#sec:l1-app}\n======================================\n\nVC Theory for Hierarchical Histograms\n-------------------------------------\n\nWe first characterize exactly the structure of the difference between two hierarchical histograms that respect the dyadic decomposition on $[m]^d$:\n\n\\[lem:difference-of-histograms\\] Let $f, g$ be two $k$-hierarchical histograms with respect to a grid ${\\mathcal{G}}$. Then $f - g$ is a $2k$-hierarchical histogram.", "\n\nLet $R_1, \\ldots, R_k$ and $R_1', \\ldots, R_k'$ be rectangles in the hierarchical structure so that $f$ is flat on each rectangle $R_i$ and $g$ is flat on each rectangle $R_i'$. For each pair of rectangles $R_i$ and $R_j'$, we have that either $R_i \\subseteq R_j'$ (or vice versa), or $R_i \\cap R_j' = \\emptyset$. Thus, if we choose a maximal subset $\\mathcal{S}$ of $\\{R_1, \\ldots, R_k, R_1', \\ldots, R_k'\\}$ so that (1) there do not exist $R, R' \\in \\mathcal{S}$ so that $R \\subseteq R'$, and moreover, (2) there does not exist a $R \\in \\mathcal{S}$ and $R' \\in \\{R_1, \\ldots, R_k, R_1', \\ldots, R_k'\\}$ so that $R' \\subset R$, then it is a partition of $[m]^d$ that consists of at most $2k$ rectangles that respect the hierarchical structure. ", "Moreover, it is easy to see that $f - g$ is flat on every rectangle in $\\mathcal{S}$. This completes the proof.", "\n\nLemma \\[lem:difference-of-histograms\\] immediately implies Corollary \\[cor:difference-of-histograms\\].", "\n\nWe also wish to instantiate these bounds for rectangles, and unions of at most $k$ rectangles. ", "Fortunately, the VC dimension of rectangles and unions is well-understood:\n\nIf ${\\mathcal{R}}$ is the set of axis-aligned rectangles in $\\R^d$, then ${\\mathrm{VC}}({\\mathcal{R}}) = 2d$.\n\nFor any two sets of sets $\\mathcal{A}_1, \\mathcal{A}_2$, we have ${\\mathrm{VC}}(\\mathcal{A}_1 \\cup \\mathcal{A}_2) \\leq {\\mathrm{VC}}(\\mathcal{A}_1) + {\\mathrm{VC}}(\\mathcal{A}_2) + 1$, where $$\\mathcal{A}_1 \\cup \\mathcal{A}_2 = \\{A_1 \\cup A_2 : A_1 \\in \\mathcal{A}_1, A_2 \\in \\mathcal{A}_2 \\} \\; .$$\n\nTogether, these two lemmas imply Corollary \\[cor:VC-hierk\\].", "\n\nLet ${\\mathcal{R}}$ denote the set of all axis aligned rectangles in $[m]^d$. The above two lemmas immediately imply that the class ${\\mathcal{R}}_k = \\bigcup_{i = 1}^k {\\mathcal{R}}$ has ${\\mathrm{VC}}({\\mathcal{R}}_k) \\leq 2 d k + k$. Since ${\\mathcal{D}}_k \\subseteq {\\mathcal{R}}_k$, the result follows immediately.", "\n\nProof of Lemma \\[lem:compute-A1\\]\n---------------------------------\n\nOur algorithm is given in Algorithm \\[alg:compute-A1\\]. ", "For any rectangle $R \\subseteq [m]^d$ (resp. ", "$[m]^d$), we let ${\\mathrm{vol}}(R)$ denote its measure in $[m]^d$ (resp. ", "$[0, 1]^d$).", "\n\nLet ${\\mathcal{T}}$ be the tree of rectangles in ${\\mathcal{D}}$ containing points in ${\\mathrm{supp}}({\\widehat{f}}) \\cap R$. For every rectangle $R'$ in ${\\mathcal{T}}$, let $c(R') = |{\\mathrm{supp}}({\\widehat{f}}) \\cap R'|$ \\[line:1\\] Let $b_1 = \\max_{R' \\in {\\mathcal{T}}} | c(R') - a \\cdot {\\mathrm{vol}}(R') |$, and let $R_1$ be the rectangle which achieves this maxima. ", "Let $b_2 = a \\cdot {\\mathrm{vol}}(R')$, where $R'$ is the rectangle with maximum volume not in ${\\mathcal{T}}$, and let $R_2$ be the rectangle which achieves this maxima. ", "\\[line:2\\] **return** $\\max (b_1, b_2)$ and the corresponding $R_1$ or $R_2$\n\nWe first prove the claimed runtime bound. ", "Observe that ${\\mathcal{T}}$ has size at most $O(2^d s \\log m)$, and by a simple recursive splitting procedure, can be generated in $O(2^d s \\log m)$ time. ", "Similarly $c(v)$ can be computed for every node in ${\\mathcal{T}}$ in $O(s \\log m)$ time overall. ", "Therefore $b_1$ can be computed in $O(2^d s \\log m)$ time overall. ", "To compute $b_2$, it suffices to find the largest rectangle $R'$ in ${\\mathcal{T}}$ which does not have $2^d$ children in ${\\mathcal{T}}$, and to return ${\\mathrm{vol}}(R') / 2^d$. This again can be done by iterating over the tree once, so this takes time $O(2^d s \\log m)$. Therefore overall the algorithm runs in time $O(2^d s \\log m)$.\n\nWe now show correctness of the algorithm. ", "Let $R'$ be the rectangle which achieves the maxima for the ${\\mathcal{D}}$-distance. ", "There are two cases. ", "if $R' \\cap {\\mathrm{supp}}({\\widehat{f}}) \\neq \\emptyset$, then clearly it is considered in Line \\[line:1\\] of <span style=\"font-variant:small-caps;\">ComputeA1</span>, and its contribution is considered in the distance computation. ", "Otherwise, $R'$ must be a rectangle with maximum volume not in ${\\mathcal{T}}$, as otherwise we may increase the value of the maxima by taking such a rectangle. ", "Therefore it is considered in Line \\[line:2\\]. ", "In either case, its contribution is considered, and thus the algorithm is correct.", "\n\nProof of Theorem \\[thm:splitting\\]\n----------------------------------\n\nFor any set $R$, let $\\OPT_{k} (R) = \\| h^* - f \\|_{1, R}$ be the $\\ell_1$-error incurred by $h^*$ to $f$ on $R$. Similarly, let ${\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} (R)$ be the ${\\mathcal{D}}_k$-error incurred by the best fit hierarchical $k$-histogram to ${\\widehat{f}}$ on $R$. For any collection of sets ${\\mathcal{S}}$, let $\\OPT_{k} ({\\mathcal{S}}) = \\OPT_{k} (\\cup_{S \\in {\\mathcal{S}}} S)$ and let ${\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{S}})$ be defined similarly. ", "We now have all definitions we need for the proof.", "\n\nThe proof of the bounds on the number of pieces and runtime are nearly identical to the proofs of Lemmas \\[lem:pieces\\] and \\[lem:runtime\\], so we omit them. ", "Thus it suffices to prove correctness. ", "This is also quite similar to the proof of correctness for $\\ell_2$. Let $h^*$ be an optimal partial hierarchical $k$-histogram fit to ${\\widehat{f}}$ in ${\\mathcal{D}}_k$ norm, and let $h$ be the output of our algorithm. ", "Let ${\\mathcal{T}}$ be the tree associated with $h$. Let ${\\mathcal{R}}^*$ be the set of $k$ disjoint dyadic rectangles on which $h^*$ is supported, and let ${\\mathcal{R}}$ be the leaves of ${\\mathcal{T}}$. Partition ${\\mathcal{R}}$ into three sets: $$\\begin{aligned}\n{\\mathcal{F}}&= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is constant on $R$}~\\} \\\\\n{\\mathcal{J}}_1 &= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is non-constant on $R$ and $e_R = 0$}~\\} \\\\\n{\\mathcal{J}}_2 &= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is non-constant on $R$ and $e_R > 0$}~\\} \\; .\\end{aligned}$$\n\nWe will prove that the error is low on all three sets separately.", "\n\n#### Error on $\\cal{F}$\n\nFirst, we will prove that the error is low in ${\\mathcal{F}}$. In fact, we will prove a more general lemma which will be useful later:\n\n\\[lem:flat-err\\] Let ${\\widehat{f}}$ be an empirical distribution, and let $\\kappa$ be arbitrary. ", "Let ${\\mathcal{R}}\\in {\\mathcal{D}}_k$ be any collection of at most $\\kappa$ disjoint rectangles in ${\\mathcal{D}}$, and let $g$ be the function which is, on every $R \\in {\\mathcal{R}}$, equal to the constant function $\\phi_{a, R}$ which minimizes $\\| {\\widehat{f}}- \\phi_{a, R} \\|_{{\\mathcal{D}}, R}$. Then, if $h^*$ is constant on every rectangle in ${\\mathcal{R}}$, we have $$\\| {\\widehat{f}}- g \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}} \\leq 3 \\| {\\widehat{f}}- h^* \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}}$$\n\nBy a triangle inequality, we have $$\\| {\\widehat{f}}- g \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}} \\leq \\| {\\widehat{f}}- h^* \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}} + \\| h^* - g \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}} \\; .$$ Observe that on every rectangle $R \\in {\\mathcal{R}}$, both functions are constant. ", "Hence $$\\begin{aligned}\n\\| h^* - g \\|_{{\\mathcal{D}}_{\\kappa}, {\\mathcal{R}}} &= \\sum_{R \\in {\\mathcal{R}}} |h^* (R) - g (R)| \\\\\n&= \\sum_{R \\in {\\mathcal{R}}} \\| h^* - g \\|_{{\\mathcal{D}}, R} \\\\\n&\\leq \\sum_{R \\in {\\mathcal{R}}} \\| h^* - {\\widehat{f}}\\|_{{\\mathcal{D}}, R} + \\sum_{R \\in {\\mathcal{R}}} \\| g - {\\widehat{f}}\\|_{{\\mathcal{D}}, R} \\\\\n&\\leq 2 \\sum_{R \\in {\\mathcal{R}}} \\| h^* - {\\widehat{f}}\\|_{{\\mathcal{D}}, R} \\\\\n&\\leq 2 \\| {\\widehat{f}}- h^* \\|_{{\\mathcal{D}}_k, {\\mathcal{R}}} \\; .\\end{aligned}$$ Putting these two inequalities together yields the desired estimate.", "\n\nAs an immediate corollary of this lemma, we get that $$\\label{eq:err-F}\n\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_k, {\\mathcal{F}}} \\leq 3 \\cdot {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{F}}) \\; .$$\n\n#### Error on ${\\mathcal{J}}_1$\n\nWe next consider the error on ${\\mathcal{J}}_1$. We will require the following elementary fact, which follows immediately from the definition of $\\| \\cdot \\|_{{\\mathcal{D}}_k}$:\n\n\\[fact:A1-to-Ak\\] For any $k \\geq 1$, and for any ${\\mathcal{R}}$, we have $\\| f \\|_{{\\mathcal{D}}_k, {\\mathcal{R}}} \\leq k \\| f \\|_{{\\mathcal{D}}, {\\mathcal{R}}}$.\n\nThis immediately implies that $$\\label{eq:err-J1}\n\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_k, {\\mathcal{J}}_1} = 0 \\; .$$\n\n#### Error on ${\\mathcal{J}}_2$\n\nThus it suffices to bound the error on ${\\mathcal{J}}_2$. By a triangle inequality, we have $$\\begin{aligned}\n\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_k, {\\mathcal{J}}_2} &\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\| h^* - h \\|_{{\\mathcal{D}}_k, {\\mathcal{J}}_2} \\\\\n&\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\| h^* - h \\|_{1, {\\mathcal{J}}_2} \\\\\n&= {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\sum_{R \\in {\\mathcal{J}}_2} \\| h^* - h \\|_{1, R} \\; .\\end{aligned}$$ For any $R \\in {\\mathcal{J}}_2$, let $\\Gamma (R) + 1$ denote the number of values that $h^*$ takes on $R$. Note that $$\\begin{aligned}\n\\| h^* - h \\|_{1, R} &= \\| h^* - h \\|_{{\\mathcal{D}}_{\\Gamma (R) + 1}, R} \\\\\n&\\leq \\| h^* - {\\widehat{f}}\\|_{{\\mathcal{D}}_{\\Gamma (R) + 1}, R} + \\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_{\\Gamma (R) + 1}, R} \\\\\n&\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} (R) + (\\Gamma (R) + 1) \\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}, R} \\; .\\end{aligned}$$\n\nObserve that $R$ cannot be an indivisible rectangle, as then otherwise $e_R = 0$ and so $R \\in {\\mathcal{J}}_1$ or $R \\in {\\mathcal{F}}$. Therefore, in some iteration, there must be some $R'$ so that $R \\subseteq R'$ so that $R'$ was not split in this iteration. ", "Let $\\phi_{a, R'}$ be the optimal constant fit in ${\\mathcal{D}}$ distance to ${\\widehat{f}}$ on $R'$. Let $A_1, \\ldots, A_{(1 + \\xi) k}$ be the rectangles which were split in this iteration. ", "Since these rectangles are disjoint, this means that $h^*$ can be non-constant on at most $k$ of them. ", "WLOG assume that $h^*$ is constant on $A_1, \\ldots, A_{\\xi k}$. Let $g$ be the optimal fit in ${\\mathcal{D}}$ to ${\\widehat{f}}$ over each rectangle in $\\mathcal{A} = \\{ A_1, \\ldots, A_{\\xi k} \\}$. We then have $$\\begin{aligned}\n\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}, R} &\\stackrel{(a)}{\\leq} \\| {\\widehat{f}}- \\phi_{a, R'} \\|_{{\\mathcal{D}}, R} \\\\\n&\\leq \\| {\\widehat{f}}- \\phi_{a, R'} \\|_{{\\mathcal{D}}, R'} \\\\\n&\\leq \\frac{1}{\\xi k} \\sum_{i = 1}^{\\xi k} \\| {\\widehat{f}}- g \\|_{{\\mathcal{D}}, A_i} \\\\\n&\\stackrel{(b)}{\\leq} \\frac{1}{\\xi k} \\| {\\widehat{f}}- g \\|_{{\\mathcal{D}}_{\\xi k}, \\mathcal{A}} \\\\\n&\\stackrel{(c)}{\\leq} \\frac{3}{\\xi k} \\| {\\widehat{f}}- h^* \\|_{{\\mathcal{D}}_{\\xi k}, \\mathcal{A}} \\\\\n&\\stackrel{(d)}{\\leq} \\frac{3}{\\xi^2 k} {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\; .\\end{aligned}$$ where (a) follows from the fact that $h$ is the optimal ${\\mathcal{D}}$ fit to ${\\widehat{f}}$ on $R$, (b) follows from the definition of $\\| \\cdot \\|_{{\\mathcal{D}}_k}$, (c) follows from Lemma \\[lem:flat-err\\], and (d) follows from Fact \\[fact:A1-to-Ak\\]. ", "Hence, overall we have $$\\begin{aligned}\n\\| h^* - h \\|_{1, R} &\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} (R) + \\frac{3}{\\xi^2 k} {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\; .\\end{aligned}$$ Summing over the elements in ${\\mathcal{J}}_2$, we obtain that $$\\begin{aligned}\n\\| h^* - h \\|_{1, {\\mathcal{J}}_2} &\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\frac{3}{\\xi^2 k} {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\sum_{R \\in {\\mathcal{J}}_2} (\\Gamma (R) + 1) \\\\\n&\\leq {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\frac{6}{\\xi^2} {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\; .\\end{aligned}$$ Hence overall, we have $$\\label{eq:err-J2}\n\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_k, {\\mathcal{J}}_2} \\leq 2 {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} ({\\mathcal{J}}_2) + \\frac{6}{\\xi^2} {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\; .$$ Combining (\\[eq:err-F\\]), (\\[eq:err-J1\\]), and (\\[eq:err-J2\\]) and simplifying yields that $$\\| {\\widehat{f}}- h \\|_{{\\mathcal{D}}_k} \\leq \\left( 3 + \\frac{6}{\\xi^2} \\right) {\\widetilde{\\OPT}}_{{\\mathcal{D}}, k} \\; ,$$ as claimed.", "\n\nProof of Lemma \\[lem:VC-histograms\\]\n------------------------------------\n\nLet $T$ be a finite set of size $r$. If our family can shatter $T$, then all $2^r$ subsets of $T$ must be expressible in the form\n\n$$\\label{eq:shattering}\nT \\cap \\left( \\bigcup_{i = 1}^{k'} A_i - \\bigcup_{j = 1}^{k''} B_j \\right) = \\left( \\bigcup_{j = 1}^{k'} A_j \\cap T \\right) - \\left( \\bigcup_{j = 1}^{k''} B_j \\cap T \\right)$$\n\nWe now count the number of possible sets of the form $R \\cap T$ for rectangles $R$. Observe that each face has a fixed normal, and for halfspaces $H$ with a fixed normal there are clearly at most $r$ possible sets $H \\cap T$. $R$ has $2d$ faces and so the number of possible sets of the form $R \\cap T$ is at most $r^{2d}$. Hence, the number of sets of the form in (\\[eq:shattering\\]) is at most $r^{4dk}$. This is smaller than $2^r$ when $r$ is a sufficiently large multiple of $kd \\log (kd)$. Thus, the VC dimension is $O(kd \\log (kd))$.\n\nProof of Lemma \\[lem:arbitrary-to-hierarchical-rounding\\]\n---------------------------------------------------------\n\nLet $R_1, \\ldots, R_k$ be a partition of $[m]^d$ into $k$ disjoint rectangles so that $h^*$ is constant on each $R_i$. For each $i$, let $R_i'$ be the smallest rectangle so that $R_i' \\subseteq R$ and so that $R_i'$ contains every point in ${\\mathrm{grid}}({\\mathcal{X}}) \\cap R_i$. Let $h^*_p$ be the $k$-partial histogram so that for each $i$, $h^*_p (x) = h^* (x)$ for all $x \\in R_i'$, and $h^*_p (x) = 0$ outside of $\\bigcup_{i = 1}^k R_i'$. We claim this function satisfies $$\\| f - h^*_p \\|_1 \\leq \\OPT_k + c' {\\varepsilon}\\; .$$ Let $R = \\bigcup_{i = 1}^{k} R_i'$. Then, we have $$\\begin{aligned}\n\\| f - h^*_p \\|_1 &= \\| f - h^*_p \\|_{1, R} + \\| f - h^*_p \\|_{1, R^c} \\stackrel{(a)}{=} \\| f - h^* \\|_{1, R} + \\| f \\|_{1, R^c} \\\\\n&\\stackrel{(b)}{=} \\OPT_k + 2 \\| f \\|_{{\\mathcal{A}}_k, R^c} \\stackrel{(c)}{=} \\OPT_k + 2 \\| f - {\\widehat{f}}\\|_{{\\mathcal{A}}_k, R^c} \\stackrel{(d)}{\\leq} \\OPT_k + 2 c' {\\varepsilon}\\; ,\\end{aligned}$$ where (a) follows from the decomposibility of $\\ell_1$, (b) follows from the definition of $h^*_p$, (c) follows since $R \\in {\\mathcal{A}}_{\\kappa}$ and since ${\\widehat{f}}= 0$ on $R^c$, and (d) follows from (\\[eq:deterministic-cond\\]).", "\n\nThe only remaining problem with this function is that it is not a distribution, namely, it does not integrate to $1$. However, we know that $\\left| \\| h^*_p \\|_1 - 1 \\right| \\leq \\| h^*_p - f \\|_1 \\leq \\OPT_k + 2 c' {\\varepsilon}$. Hence, if we renormalize $h^*_p$ to make it integrate to $1$ (say, by adding mass uniformly to one rectangle), we lose at most an additional $\\OPT_k + 2 c' {\\varepsilon}$ factor. ", "The claim follows then from an easy generalization of Lemma \\[lem:arbitrary-to-hierarchical\\], since the side length of ${\\mathrm{grid}}({\\mathcal{X}})$ is $\\poly (k, 1 / {\\varepsilon})$.\n\nProof of Lemma \\[lem:partial-minus-full\\]\n-----------------------------------------\n\nLet $Z = \\{h(x) > g(x)\\}$. Let $R_1, \\ldots, R_k$ be $k$ disjoint rectangles so that $h$ is constant on every $R_i$, and $h$ is supported on their union. ", "Let $R_1', \\ldots, R_k'$ be the same for $g$, except that these sets form a partition of $[m]^d$. Reminiscent of the proof of Lemma \\[lem:correctness-l2\\], partition ${\\mathcal{R}}= \\{R_1, \\ldots, R_k \\}$ into two sets: ${\\mathcal{F}}$, the set of $R \\in {\\mathcal{R}}$ so that $g$ is constant on $R$, and ${\\mathcal{J}}$, the set of $R \\in {\\mathcal{R}}$ so that $g$ has a jump on $R$. Clearly $Z$ is the disjoint union of $Z_1 = Z \\cap \\cup_{R \\in {\\mathcal{F}}} R$ and $Z_2 = Z \\cap \\cup_{R \\in {\\mathcal{J}}}$. Moreover, $Z_1$ is immediately expressible as the disjoint union of at most $k$ dyadic rectangles: namely, the rectangles in ${\\mathcal{F}}$ on which $h(x) > g(x)$. Thus, it suffices to show that $Z_2$ can be written as a disjoint union of at most $k$ disjoint rectangles. ", "But if $R \\in {\\mathcal{J}}$ then this means that $g$ partitions the rectangle. ", "Thus, $Z_2$ is exactly the set of $R_j'$ so that $h(x) > g(x)$ on $R_j'$, and $R_j' \\subset R_i$ for some $i \\in [k]$. Hence $Z_2$ can also be written as the union of at most $k$ rectangles, and so $Z$ can be written as a union of at most $2k$ rectangles, which completes the proof.", "\n\nAlgorithm \\[alg:ada-hist-l1\\]\n-----------------------------\n\nLet ${\\mathcal{X}}$ be the (multi-)set of points in the support of ${\\widehat{f}}$ **return** $\\textsc{GreedySplit}({\\widehat{f}}, {\\mathcal{D}}({\\mathrm{grid}}({\\mathcal{X}})), \\xi)$\n\nLearning Histograms in $\\ell_2$-Distance\n========================================\n\nIn this section, we consider the problem of learning the best fit $k$-histogram in $\\ell_2$-distance to a unknown distribution over $[m]^d$ given sample access to the distribution. ", "The main result of this section is the following:\n\n\\[thm:l2-main\\] Fix ${\\varepsilon}, \\delta > 0$, $k \\in \\mathbb{Z}_+$, and let $\\gamma > 0$ be a tuning parameter. ", "Let $f: [m]^d \\to R$ be an arbitrary distribution. ", "There is an algorithm <span style=\"font-variant:small-caps;\">GreedySplitL2</span> which takes $n = O(\\log (1 / \\delta) / {\\varepsilon})$ samples from $f$ and outputs a hierarchical $(1 + \\xi) 2^d k \\log^{d + 1} m$-histogram $h$ so that with probability at least $1-\\delta$ $$\\| h - g \\|_2^2 \\leq \\left( 1 + \\frac{1}{\\xi} \\right) \\OPT_k + {\\varepsilon}\\; ,$$ where $\\OPT_{k} = \\min_{h} \\| h - g \\|_{2}^2$ and the minimum is taken over all $k$-histograms $h$. Moreover, the algorithm runs in time $O (2^d n \\log^2 m)$.\n\nWhile the statement of this theorem does not quite obtain the guarantees in Theorem \\[thm:l2-informal\\], in that we have $\\log m$ factors instead of $\\log 1 / {\\varepsilon}$ factors, it is straightforward to use the same adaptive gridding techniques as we did for $\\ell_1$ to replace these $\\log m$ factors with $\\log 1 / {\\varepsilon}$ factors. ", "Since the ideas are subsumed by those described for $\\ell_1$, we omit these details for simplicity.", "\n\nOur starting point is the following well-known statistical guarantee, which states that the empirical distribution is ${\\varepsilon}$-close to the true distribution in $\\ell_2$-norm after roughly $O(1 / {\\varepsilon}^2)$ samples.", "\n\n\\[fact:l2-estimate\\] Fix ${\\varepsilon}, \\delta > 0$. Let $f: [m]^d \\to \\R$ be an arbitrary distribution, and let ${\\widehat{f}}= {\\widehat{f}}_n$ be the empirical distribution after $n = O (\\log (1 / \\delta) / {\\varepsilon})$ independent samples from $f$. Then, with probability $1 - \\delta$, we have $\\| {\\widehat{f}}- f \\|_2^2 \\leq {\\varepsilon}$.\n\nThis fact states that the $\\ell_2$ learning problem is purely algorithmic: it suffices to, given ${\\widehat{f}}$, find the best fit $k$-histogram approximation to ${\\widehat{f}}$ in $\\ell_2$. Then by a simple application of the triangle inequality, this will be an almost optimal fit to $f$ in $\\ell_2$ as well. ", "The main challenge is to devise algorithms for this problem which exploit the sparsity of ${\\widehat{f}}$.\n\nWe will also make crucial use of the following fact, which follows from basic calculus. ", "Then, we have:\n\n\\[fact:mean\\] Let ${\\widehat{f}}$ be an empirical distribution over $[m]^d$, and let $R \\subseteq [m]^d$ be any set. ", "Then, the best constant fit to ${\\widehat{f}}$ in $\\ell_2$ on $R$ is the flattening of ${\\widehat{f}}$ over $R$.\n\nGreedy Splitting for Hierarchical Histograms in $\\ell_2$-Distance\n-----------------------------------------------------------------\n\nOur main algorithmic result for the $\\ell_2$-norm is a greedy splitting routine which finds a nearly optimal hierarchical histogram fit to a sparse function efficiently. ", "Throughout this section, we will let ${\\mathcal{D}}= {\\mathcal{D}}([m]^d)$ be the full dyadic decomposition of the domain. ", "While it is not hard to adapt the techniques in this section to work with an adaptive grid, as we did for the $\\ell_1$-distance, we will not do this here for simplicity of the presentation, as this is not the main focus of our paper.", "\n\nOur main theorem is:\n\n\\[thm:splitting-l2\\] Fix $k \\in \\mathbb{Z}_+$, and let $\\gamma > 0$ be a tuning parameter. ", "Let $g: [m]^d \\to R$ be an arbitrary function supported on at most $s$ points. ", "There is an algorithm <span style=\"font-variant:small-caps;\">GreedySplitL2</span> which outputs a $(1 + \\xi) 2^d k \\log m$-hierarchical histogram $h$ so that $$\\| h - g \\|_2^2 \\leq \\left( 1 + \\frac{1}{\\xi} \\right) \\OPT_{{\\mathcal{D}}, k} \\; ,$$ where $\n\\OPT_{{\\mathcal{D}}, k} = \\min_{h} \\| h - g \\|_{2}^2,\n$ where the minimum is taken over all hierarchical $k$-histograms $h$. Moreover, the algorithm runs in time $O (2^d s \\log^2 m)$.\n\nCombining this with Lemma \\[lem:arbitrary-to-hierarchical\\] and Fact \\[fact:l2-estimate\\] immediately yields Theorem \\[thm:l2-main\\]. ", "Thus, it suffices to prove this theorem.", "\n\nOur algorithm, given formally in Algorithm \\[alg:hist-l2\\], is quite similar to Algorithm \\[alg:hist-l1\\]. ", "We construct a tree of nested dyadic rectangles. ", "Initially, this tree contains only $[m]^d$. Iteratively, we find the leaves of this tree with largest $\\ell_2^2$ error to $g$, and we split these into all of its children, and we repeat this for $\\log m$ iterations. ", "At the end, we return the flattening of $g$ over all the leaves in the final tree.", "\n\nLet ${\\mathcal{T}}$ be a subtree of the hierarchical tree, initially containing only the root. ", "Let $a_R = g(R) / |R|$ Let $e_R = \\sum_{x \\in R} (g(x) - a_R)^2$ Let ${\\mathcal{J}}$ be the set of $(1 + \\xi) k$ leaves $R \\in {\\mathcal{T}}$ with largest $e_R$. \\[line:J-l2\\] Add all children of $R$ to ${\\mathcal{T}}$ **return** The flattening of $g$ for every leaf $R$ of ${\\mathcal{T}}$\n\nWe will prove this theorem in three parts. ", "First, we will prove a bound on the number of pieces of the output histogram (Lemma \\[lem:pieces\\]). ", "Then, we will bound the runtime of the algorithm (Lemma \\[lem:runtime\\]). ", "Finally, we will bound the error of the algorithm (Lemma \\[lem:correctness-l2\\]).", "\n\nWe first bound the number of pieces in our output:\n\n\\[lem:pieces\\] The output of <span style=\"font-variant:small-caps;\">GreedySplitL2</span> has at most $(1 + \\xi) 2^d k \\log M$ pieces.", "\n\nIn each iteration, we split at most $(1 + \\xi) k$ rectangles each into $2^d$ pieces, so we increase the number of pieces by at most $(1 + \\xi) 2^d k$. Since there are $\\log M$ iterations, this immediately proves the bound.", "\n\nWe now prove a bound on the runtime:\n\n\\[lem:runtime\\] <span style=\"font-variant:small-caps;\">GreedySplitL2</span> runs in time $O(2^d s \\log^2 M)$.\n\nIn each iteration, we iterate over the number of rectangles currently in the tree, and we take $O(2^d s_R \\log M)$ time per rectangle $R$, if $R$ contains $s_R$ points in the support of $g$. Thus per iteration we do at most $O ((1 + \\xi) 2^d s \\log M)$ work, and there are $\\log M$ iterations. ", "Multiplying these two terms yields the desired claim.", "\n\nFinally, we turn our attention to correctness:\n\n\\[lem:correctness-l2\\] $\\| h - g \\|_2^2 \\leq \\left( 1 + \\frac{1}{\\xi} \\right) \\OPT_k$.\n\nLet $h^*$ be an optimal hierarchical $k$-histogram fit to $g$ in $\\ell_2$ norm, and let $h$ be the output of our algorithm. ", "For any set $S \\subseteq [m]^d$, let $\\OPT_{{\\mathcal{D}}, k} (S) = \\sum_{x \\in S} (h^* (x) - g(x))^2$ be the $\\ell_2$-squared error incurred by $h^*$ on $S$. For any collection of sets ${\\mathcal{S}}$, let $\\OPT_{{\\mathcal{D}}, k} ({\\mathcal{S}}) = \\OPT_{{\\mathcal{D}}, k} (\\cup_{S \\in {\\mathcal{S}}} S)$.\n\nLet ${\\mathcal{T}}$ be the tree associated with $h$. Let ${\\mathcal{R}}^*$ be the set of $k$ disjoint dyadic rectangles on which $h^*$ is supported, and let ${\\mathcal{R}}$ be the leaves of ${\\mathcal{T}}$. Partition ${\\mathcal{R}}$ into three sets: $$\\begin{aligned}\n{\\mathcal{F}}&= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is constant on $R$}~\\} \\\\\n{\\mathcal{J}}_1 &= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is non-constant on $R$ and $e_R = 0$}~\\} \\\\\n{\\mathcal{J}}_2 &= \\{ R \\in {\\mathcal{R}}: ~\\mbox{$h^*$ is non-constant on $R$ and $e_R > 0$}~\\} \\; .\\end{aligned}$$\n\nWe will prove that the error is low on all three sets separately.", "\n\n#### Error on $\\cal{F}$\n\nFirst, we will prove that the error is low in ${\\mathcal{F}}$. In fact, we will prove a more general lemma which will be useful later:\n\n\\[lem:flat-err-l2\\] Let $g$ be arbitrary. ", "Let ${\\mathcal{R}}\\in {\\mathcal{D}}_k$ be any union of at most $k$ disjoint rectangles in ${\\mathcal{D}}$, and let ${\\overline{g}}$ be the flattening of $g$ over the rectangles in ${\\mathcal{R}}$. Then, if $h^*$ is constant on every rectangle in ${\\mathcal{R}}$, we have $$\\| g - {\\overline{g}} \\|_{2, {\\mathcal{R}}}^2 \\leq \\| g - h^* \\|_{2, {\\mathcal{R}}}^2$$\n\nThis follows immediately from Fact \\[fact:mean\\].", "\n\nAs an immediate corollary of this lemma, we get that $$\\label{eq:err-F-l2}\n\\| g - h \\|_{2, {\\mathcal{F}}}^2 \\leq \\OPT_{{\\mathcal{D}}, k} ({\\mathcal{F}}) \\; .$$\n\n#### Error on ${\\mathcal{J}}_1$\n\nBy definition, we have $$\\label{eq:err-J1-l2}\n\\| g - h \\|_{2, {\\mathcal{J}}_1}^2 = 0 \\; .$$\n\n#### Error on ${\\mathcal{J}}_2$\n\nFinally, we bound the error ${\\mathcal{J}}_2$. Fix any $R \\in {\\mathcal{J}}_2$. Observe that $R$ cannot be an indivisible rectangle, as then otherwise $e_R = 0$ and so $R \\in {\\mathcal{J}}_1$ or $R \\in {\\mathcal{F}}$. Therefore, in some iteration, there must be some $R'$ so that $R \\subseteq R'$ so that $R'$ was not split in this iteration. ", "Let $A_1, \\ldots, A_{(1 + \\xi) k}$ be the rectangles which were split in this iteration. ", "Because the rectangles are dyadic, they are disjoint. ", "Thus, $h^*$ can be non-constant on at most $k$ of them. ", "WLOG assume that $h^*$ is constant on $A_1, \\ldots, A_{\\xi k}$. Let $q$ be the flattening of $g$ over $\\mathcal{A} = \\{ A_1, \\ldots, A_{\\xi k} \\}$. We then have $$\\begin{aligned}\n\\| g - h \\|_{2, R}^2 &\\stackrel{(a)}{\\leq} \\| q - {\\overline{g_{R'}}} \\|_{2, R'}^2 \\\\\n&\\leq \\frac{1}{\\xi k} \\sum_{i = 1}^{\\xi k} \\| g - {\\overline{g_{A_i}}} \\|_{2, A_i}^2 \\\\\n&\\stackrel{(b)}{\\leq} \\frac{1}{\\xi k} \\OPT_{{\\mathcal{D}}, k} \\; .\\end{aligned}$$ where (a) follows from the fact that $h$ is the optimal $\\ell_2$ fit to $g$ on $R$, and (b) follows from Lemma \\[lem:flat-err-l2\\].", "\n\nSumming over the elements in ${\\mathcal{J}}_2$, we obtain that $$\\label{eq:err-J2-l2}\n\\| g - h \\|_{2, {\\mathcal{J}}_2}^2 \\leq \\frac{1}{\\xi} \\OPT_{{\\mathcal{D}}, k} \\; .$$\n\nCombining (\\[eq:err-F-l2\\]), (\\[eq:err-J1-l2\\]), and (\\[eq:err-J2-l2\\]) and simplifying yields that $$\\| g - h \\|_{2}^2 \\leq \\left( 1 + \\frac{1}{\\xi} \\right) \\OPT_{{\\mathcal{D}}, k} \\; ,$$ as claimed.", "\n\nLemmas \\[lem:pieces\\], \\[lem:runtime\\], and \\[lem:correctness-l2\\] together immediately imply Theorem \\[thm:splitting-l2\\].", "\n\n[^1]: Supported by NSF Award CCF-1652862 (CAREER) and a Sloan Research Fellowship.", "\n\n[^2]: Supported by NSF grant CCF-1217921, DOE grant de-sc0008923, NSF CAREER Award CCF-145326, and a NSF Graduate Research Fellowship\n\n[^3]: Supported by a Google PhD Fellowship.", "\n\n[^4]: We call our algorithm semi-proper because it produces a hypothesis that is also a histogram but with more than $k$ pieces. ", "For our algorithm, the increase in the number of histogram pieces is a polylogarithmic factor.", "\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Extraintestinal oxyuriasis - report of three cases and review of literature.", "\nExtraintestinal oxyuriasis, in our experience with three affected women of fertile age, presented itself as a solitary fibrotic nodular lesion, with a varying location. ", "The sites of location were: parietal peritoneum, serous surface of the uterus and wall of the uterine tube. ", "The size of the nodules was 5 to 10 mm. ", "Histologically, the lesions were hypocellular fibrotic nodules with a variable amount of neutrophils and amorphous eosinophilic material in the center, harbouring eggs of the parasite and remnants of pinworm cuticle. ", "All three lesions were asymptomatic, only being discovered incidentally during the operations for unrelated conditions. ", "Their peroperative recovery by a surgeon did not alter the course of surgery. ", "These findings document the ability of pinworms to migrate into the abdominal cavity via the female genital tract." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Ireland is an EU member country with a knowledge-based economy and strong industries in services and technology. ", "With attractive corporate tax rates, Ireland has been ideal destination for multinational corporations.", "\n\nIreland’s Main Industries\n\nIreland is economically known for its strength in:\n\nAgriculture Sector\n\nCattle\n\nBeef\n\nDairy\n\nServices Sector\n\nFinancial\n\nBanking\n\nAsset Management\n\nTourism\n\nMining and Metals Sector\n\nZinc\n\nLead concentrates\n\nAlumina\n\nCoal\n\nGypsum\n\nLimestone\n\nIndustrial and Manufacturing Sector\n\nConstruction Sector\n\nResidential property\n\nPharmaceuticals and Chemicals\n\nTechnology Sector\n\nHardware\n\nSoftware related goods and services\n\nEnergy Sector\n\nSupply and distribution of natural gas\n\nElectricity\n\nCoal\n\nIreland’s Main Stock Exchanges\n\nThe main stock exchange in Ireland is:\n\n1. ", "Irish Stock Exchange\n\nFounded in 1793 and is Ireland’s sole independently-owned exchange\n\nHas an established and extensive debt securities trading market\n\nOperates three principal markets\n\ni. Securities of established domestic and global Irish companies\n\nii. ", "Growth-oriented companies\n\niii. ", "Debt market\n\nIndices\n\ni. ISEQ Overall Index\n\nGlimpse into Ireland’s Equity Market\n\nIrish equities experienced negative returns following the 2008 economic crisis. ", "With the Irish banking sector have a heavily credit exposure to a deteriorating and crashing property market, the economy underwent significant problems.", "\n\nThe 3-year return on the ISEQ overall index was -48%. ", "The index has somewhat recovered however, with the last 9 months yielding 4.5%" ]

{ "pile_set_name": "Pile-CC" }

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[ "Alias(\"INTEGER\",symlimit)\n" ]

{ "pile_set_name": "Github" }

[ 0.0006256158812902868 ]

[ "Variants of NOS1, NOS2, and NOS3 genes in asthmatics.", "\nNitric oxide (NO) gas concentrations are higher in expired air in asthmatics. ", "NO is synthesized by three isoforms of NO synthase (NOS) encoded by three distinct genes, NOS1, NOS2, and NOS3. ", "Genome-wide searches have identified linkages to asthma on chromosomes 7, 12, and 17 where these three genes are localized. ", "No association study, however, has been reported to date. ", "To test whether variants of NOS1, NOS2, and NOS3 relate to asthma, a genetic association study was conducted in a British population (n = 300). ", "Intragenic microsatellite variants of NOS1 were significantly associated with asthma [odds ratio (OR) = 2.08, 95% CI: 1.20-3.57 (95% CI), P = 0.008 (Pc = 0.048)], but not with IgE levels. ", "Neither NOS2 nor NOS3 variants showed any association with asthma nor IgE levels. ", "These findings suggest that NOS1 variants may be a significant contributor to asthma in a British population." ]

{ "pile_set_name": "PubMed Abstracts" }

[ 0.000656719843391329, 0.0014438879443332553, 0.0006229785503819585, 0.0005595466936938465, 0.0005829086294397712, 0.0005612396053038538, 0.0006985435029491782, 0.0007480169297195971, 0.000574713631067425 ]

[ "\n245 B.R. 77 (2000)\nIn re Peter Wister REA, Debtor.", "\nChristopher and April McCoun, Plaintiffs,\nv.\nPeter Wister Rea, Defendant.", "\nBankruptcy No. ", "99-32142-SAF-7. ", "Adversary No. ", "99-3327.", "\nUnited States Bankruptcy Court, N.D. Texas, Dallas Division.", "\nFebruary 7, 2000.", "\n*78 *79 *80 *81 John T. Palter, Novakov Davis, P.C., Dallas, Counsel for Plaintiffs.", "\nWm. ", "Chris Wolffarth, Johnson & Wolffarth, L.L.P., Dallas, Counsel for Defendant.", "\n\nMEMORANDUM OPINION AND ORDER\nSTEVEN A. FELSENTHAL, Bankruptcy Judge.", "\nPeter W. Rea, the debtor, traded stocks for Christopher and April McCoun. ", "Between July 7, 1998, and July 31, 1998, Rea lost $69,340.00 of the $100,000.00 that the McCouns gave him for day trading. ", "In this adversary proceeding, the McCouns object to the discharge of that loss under 11 U.S.C. §§ 523(a)(2) and (a)(4). ", "The court tried this matter on December 10 and 13, 1999.", "\nThe determination of the dischargeability of debts under § 523 constitutes a core matter over which this court has jurisdiction to enter a final judgment. ", "28 U.S.C. §§ 157(b)(2)(I) and 1334. ", "This memorandum opinion contains the court's findings of fact and conclusions of law. ", "Bankruptcy Rule 7052.", "\nHaving been in the securities business for 30 years, in 1998 Rea ventured into the practice of day trading of stocks. ", "The National Association of Securities Dealers (NASD) defines day trading strategy as \"[a]n overall trading strategy characterized by the regular transmission by a customer of intra-day orders to effect both purchase and sale transactions in the same security or securities.\" ", "See Testimony of Arthur Levitt, Chairman, United States Securities and Exchange Commission, Concerning Day Trading Before the Permanent Subcommittee on Investigations, United States Senate, n. 25, p. 22 (Sept. 16, 1999)(quoting NASD proposed rule SRNASD-99-41 submitted to the SEC on August 20, 1999)(page references are to typed transcript). ", "Levitt explained to the Senate committee that the level of individual trading activity varied across a wide spectrum making it difficult to clearly define \"day trading\" or \"day trader.\" ", "Levitt testified:\nOn one end of the spectrum lie investors who trade occasionally — sometimes online — and hold their investments for the longer term. ", "Moving along the spectrum, an increasing number of individuals use their on-line accounts both to invest longer term and to trade short term on momentum or small changes in the price of a stock. ", "On the far end of the spectrum are so-called `day traders,' who exclusively buy and sell stock rapidly throughout the day trying to make money on short-term market moves.", "\nId. at 3.", "\nRea structured his business at that far end of the spectrum. ", "Mary L. Schapiro, the president of NASD Regulation, Inc., told the Senate committee on September *82 16, 1999, that day trading at that end of the spectrum referred to\na trading strategy where an individual buys and sells the same security in an attempt to profit from very small movements in the price of a security over a short period of time. ", "Although the term [day trading] is commonly used to refer to aggressively buying and selling a group of securities in a single day . . ., ", "there are varying degrees of day trading currently being employed. . . .", "\nHowever, the term `day trading,' as commonly used within the [securities] industry, generally refers to the trading activities of the `professional day trader,' that is, an individual who conducts intra-day trading in a focused and consistent manner, with the primary goal of earning a living through the profits derived from this trading strategy. ", "This form of day trading requires aggressive and frequent securities trading, and as a result, generally requires a significant amount of capital, a sophisticated understanding of securities markets and trading techniques, and a high risk tolerance. ", "Day traders typically have a relationship with a brokerage firm that provides them with more direct access to markets, as well as access to real-time trading and related information.\"", "\nTestimony of Mary L. Schapiro, President of NASD Regulation, Inc., Concerning Day Trading Before the Permanent Subcommittee on Investigations, United States Senate, p. 6-7 (Sept. 16, 1999)(page references are to typed transcript).", "\nRea held a securities brokers license. ", "He affiliated with an entity in Dallas, Texas, known as 1-800-DAY-TRADE, which provided access to markets and to realtime trading, with on-site trading facilities. ", "Rea paid 1-800-DAY-TRADE a fee for each transaction. ", "He developed a strategy to day trade for investors with $100,000.00 to commit as capital.", "\nRea solicited investments from his dentist, Jimmy Miller, and Miller's dental hygienist, Robin Parrent. ", "Parrent told Rea that she invested $100,000.00 with a day trader who assured her that he would stop trading should the value of her portfolio drop below $90,000.00, and who would split profits with her. ", "Rea said he would do better. ", "Parrent said Rea guaranteed $1,000.00 per month return on a $100,000.00 investment, but Rea said he only represented that if he did not make a profit in one month, he would pay $1,000.00 the next month before he received a fee or a share of the profits. ", "Miller had the impression that Rea had been doing quite well with his day trading. ", "Miller referred Rea to Christopher McCoun, a fellow dentist and friend.", "\nIn June 1998 Rea contacted McCoun. ", "Rea asked McCoun to invest $100,000.00 in day trading. ", "Rea represented that he had experience in day trading, had traded several accounts and would personally trade and supervise McCoun's account.", "\nMcCoun had virtually no experience in the stock market. ", "But he had accumulated $100,000.00 and sought a vehicle for investment and growth. ", "Rea proposed to McCoun that Rea would accumulate daily profits and losses in McCoun's account and that they would split profits at the end of each month, on a fifty-fifty basis. ", "In the event that the account lost money in a month, Rea proposed that McCoun would realize $1,000.00 from the next month's profits before they split the remaining profit. ", "Profits would not be paid to Rea until previous losses had been recovered. ", "Profits would be determined after payout of all associated commissions. ", "McCoun understood Rea to be guaranteeing a return. ", "Rea would not himself charge a commission, but rather looked to the profits of the venture with McCoun for compensation.", "\nAfter their initial telephone conversation, McCoun met Rea at Rea's office. ", "They discussed Rea's background. ", "Rea explained that he had completed a course in day trading. ", "McCoun asked Rea about his experience with other accounts. ", "Rea *83 told McCoun that he had been trading three accounts averaging $750.00 profit per day. ", "Rea claims that McCoun misunderstood his response. ", "Rea asserts that he told McCoun that he had an objective of a $750.00 daily profit on average. ", "In reality, Rea had been losing money on the other accounts.", "\nMcCoun and Rea discussed the philosophy of day trading. ", "Rea explained the objective to buy and sell stock each day, with no holdings at the end of the day. ", "McCoun testified that Rea assured him there would be no open positions at the end of each day. ", "McCoun insisted that Rea provide daily reports showing the daily transactions. ", "Rea agreed to provide those reports. ", "Rea would fax a report to McCoun daily showing daily actual profits and losses and the current daily value of the account. ", "Rea agreed that McCoun reasonably requested daily reports. ", "Rea also agreed that the account could be liquidated at any time.", "\nRea showed McCoun his operations, including computers, and introduced McCoun to his son, Robert. ", "McCoun understood that Rea would be personally trading and supervising the account. ", "McCoun also understood that Robert would assist Rea. ", "Rea did not tell McCoun that Robert would be doing the actual trades nor that Robert had previously sustained losses trading another Rea account. ", "Rea testified that he did inform McCoun about Robert's actual role, but McCoun's testimony to the contrary is credible. ", "Rea had the experience. ", "Rea solicited the business. ", "Rea would hold the funds and provide the accounting. ", "Rea described the strategy and relationship. ", "Robert did not hold a license to trade securities. ", "All factors in the conversation support McCoun's understanding of how Rea portrayed Robert's role.", "\nMcCoun had no desire to put his $100,000.00 savings at risk. ", "McCoun testified that Rea assured McCoun that he could minimize the risk by utilizing stop loss sales instructions should the portfolio value fall by 10%. ", "Rea testified that he never told McCoun that he would limit losses. ", "Rea does not recall discussing stop loss projections with Miller and Parrent, but Parrent's testimony supports McCoun's testimony. ", "With McCoun's lack of securities trading experience and his desire to protect his savings in any investments, McCoun's testimony is credible. ", "Rea testified that a stop loss protection mechanism would not be typical for a traditional stock broker practice. ", "But Rea recognizes that day trading is atypical; it is not traditional broker services. ", "See Levitt Testimony. ", "The court finds that Rea included a representation of stop loss protection mechanisms in his solicitation of the McCouns' $100,000.00. ", "With the belief that Rea could implement this stop loss protection, that Rea had been realizing profits of $750.00 per day per $100,000.00 account, and that he would receive daily reports, McCoun and his wife agreed to the investment.", "\nOn June 28 and June 29, 1998, the McCouns executed several written agreements including a trading authorization for Rea that provided in part that Rea could not withdraw from their account cash or securities. ", "McCoun completed a new account questionnaire checking his investment objective as \"short term growth with high risk.\" ", "He signed a form customer letter of understanding stating \"[I] understand that active day trading is highly speculative. ", "The capital in my trading account is capital not needed by me for my necessary expenses and is capital which I can afford to lose in its entirety.\" ", "The written agreements do not include provisions for sharing the profits or other compensation terms, do not provide for the daily reports, and do not include instructions to stop trading should the value of the portfolio drop 10% from the initial investment. ", "McCoun testified that he requested written agreements including those terms on several occasions but Rea never drafted nor submitted them. ", "The form customer letter of understanding provides *84 that \"as a general policy positions should be flat by the close of each business day.\" ", "McCoun understood by that provision Rea would not hold open accounts at the end of a day.", "\nOn June 29, 1998, McCoun provided Rea $100,000.00. ", "Rather than trade himself, Rea turned the funds over to his son, Robert, who did the trading. ", "While Robert handled the McCouns' trading, Rea traded his own account, funded by his wife's retirement funds. ", "Rea testified that he used that account for experimentation and training. ", "While Robert traded the McCouns' account, Rea lost $166,000.00 on his own account.", "\nEach day 1-800-DAY-TRADE provided Rea with reports of the previous day's transactions. ", "The confirmation reports reflected open positions at the end of each day. ", "Rea did not question the accuracy of those reports. ", "Robert prepared the daily report for McCoun and faxed the report to McCoun. ", "Rea did not review the report prepared by Robert nor did Rea verify Robert's report with the 1-800-DAY-TRADE statements. ", "The daily reports faxed to McCoun listed the stock purchase, the number of shares, the purchase price and the sales price. ", "The report then reflected whether the transactions resulted in a gain or loss for each stock, with a daily total gain or loss and the portfolio value. ", "None of the daily reports reflected stock positions still held at the end of a day. ", "The report dated July 31, 1998, reflected an account value of $107,488.59, suggesting profit in the first month of $7,488.00. ", "The daily reports were false.", "\nRobert kept open positions on days when particular holdings had a loss. ", "The daily reports faxed to McCoun did not reflect these open positions and consequently did not reveal the losses. ", "The daily reports falsely stated the current value of the account. ", "By the end of the month, McCoun's account had lost $69,340.00. ", "At trial, Rea conceded that he was responsible to the McCouns for timely and accurate daily trade reports. ", "Rea conceded that he failed to perform in accordance with that responsibility. ", "Rea recognized that he neglected the McCouns' account and failed to supervise and instruct Robert during this period. ", "He also testified that a brokerage business had to be based on trust between the customer and the broker. ", "He recognized that the trust relationship applied to his role as a day trader with the McCouns' money.", "\nRea recognized the situation at the end of July 1998. ", "Rea and McCoun set a meeting for August 7, 1998. ", "McCoun expected to receive his half of the $7,488.00 profit. ", "Instead, Rea told him that he had lost about $69,000.00. ", "On Rea's advice, McCoun directed Rea to sell his outstanding holdings, which Rea did. ", "After applying the proceeds, the parties agree that the McCouns lost $69,340.00.", "\nRea offered to invest $20,000.00 into the McCouns' account and attempt to regrow the account. ", "Later, Rea offered to purchase life insurance on Rea's life. ", "Rea admitted liability and agreed to pay the McCouns back in full. ", "But Rea soon learned that his other accounts had the same problem. ", "He revised his settlement offer to have his accounts share in a fund. ", "Ultimately Rea filed his petition for relief under Chapter 7 of the Bankruptcy Code. ", "With the filing of the bankruptcy petition, Rea has forfeited his securities license. ", "He now works as a salesman with hourly wages. ", "He has not talked to Robert for 18 months.", "\nRea agrees that he owes the McCouns $69,340.00, the difference between the value of the holdings liquidated in early August 1998 and the $100,000.00 investment. ", "The McCouns contend that the debt must be excepted from Rea's discharge under § 523(a)(2)(A) and (a)(4).", "\n\nSection 523 (a)(2)(A)\nExceptions to discharge should be construed in favor of debtors since the Bankruptcy Code provides a fresh start to debtors unhampered by pre-existing financial *85 burdens. ", "In re Davis, 194 F.3d 570, 574 (5th Cir.1999). ", "But the Code does not create a haven for wrongdoers. ", "Rather the Code gives the \"honest but unfortunate debtor who surrenders his [non-exempt] property a new opportunity in life unhampered by pre-existing debt.\" ", "Id. The creditor objecting to the discharge of a debt has the burden of establishing the exception by a preponderance of the evidence. ", "Grogan v. Garner, 498 U.S. 279, 286-88, 111 S.Ct. ", "654, 112 L.Ed.2d 755 (1991).", "\nUnder § 523(a)(2)(A), the court may not discharge a debt for money obtained by false pretenses, a false representation or actual fraud, other than a statement respecting the debtor's financial condition. ", "Fraud may include fraud in the inducement and actual fraud in the transaction. ", "To except a debt under this section, the McCouns must establish by a preponderance of the evidence that, either in the inducement or in the actual transaction, Rea made false representations, with the intent and purpose of deceiving the McCouns, and that the McCouns justifiably relied on the representations, and that they sustained a loss as a result of the representations. ", "RecoverEdge L.P. v. Pentecost, 44 F.3d 1284, 1292 (5th Cir. ", "1995); In re Allison, 960 F.2d 481, 484-85 (5th Cir.1992)(reliance must be justified); In re Smith, 113 B.R. 297, 304 (Bankr. ", "N.D.Tex.1990).", "\nThe McCouns contend that Rea fraudulently induced them into making the $100,000.00 investment. ", "They contend that Rea falsely represented that he was successfully trading four accounts of $100,000.00 each, realizing $750.00 per day average profits. ", "They contend that Rea guaranteed a $1,000.00 per month return and that he would minimize risk with a 10% stop loss protection.", "\nRea did solicit the McCouns' business. ", "He induced them to make their investment, by falsely representing that his experience with other accounts had been profitable. ", "The court also finds that Rea represented that he could minimize risk with a 10% stop loss protection. ", "Without that protection, the McCouns would not have made the investment.", "\nThe McCouns lacked stock market experience. ", "They agreed to the investment with the understanding that they would be exposed to no more than a $10,000.00 loss in the first month. ", "They also knew that they would receive daily statements reflecting their precise positions at the end of each day. ", "The McCouns thereby could terminate their investments should the risks be too great or should profits not be realized.", "\nBut the court does not find that Rea guaranteed a monthly return. ", "Rea had substantial experience in securities trading. ", "He knew he could not guarantee a return. ", "Indeed he had the McCouns sign a written statement acknowledging the high risk in day trading and recognizing that they did not need the invested funds for sustenance. ", "The McCouns confused Rea's proposal that the McCouns receive the first $1,000.00 of profits in a month following a loss with a guarantee of $1,000.00 per month.", "\nThe court further finds that Rea provided the McCouns with goals and objectives, including that holdings would be flat each day and that he sought a $750.00 daily profit on a $100,000.00 portfolio. ", "Yet, he falsely represented his success with other accounts. ", "And, by omission, he failed to inform the McCouns that his son, and not he, would actually be doing the daily trades. ", "Robert had previously traded accounts for Rea but had failed to sell accounts by the end of each day.", "\nRea made false representations to induce the McCouns to invest $100,000.00 with him. ", "He falsely represented that he had been profitably managing accounts and that he would minimize risks with stop loss protections. ", "He falsely represented that he would trade the McCouns' money with his experience when he intended that his son would do the trading. ", "He did not, however, represent that he guaranteed the *86 McCouns a profit. ", "Rather, he represented his objectives and agreed that in the event a profit had not been realized in any one month, the McCouns would recover the first $1,000.00 of profits the following month. ", "The McCouns acknowledged in writing that they were making high risk investments.", "\nThe McCouns justifiably relied on all of Rea's representations, including the false ones. ", "But for those representations, the McCouns would not have made their investment and thus would not have lost the $69,340.00.", "\nBeyond the inducement problems, Rea agreed to provide accurate daily reports showing the actual results of all transactions. ", "Rea provided that report. ", "But the reports were false. ", "They did not show open positions. ", "The open positions represented paper losses. ", "Had the open positions been included, the McCouns would have seen that they were losing money throughout the month.", "\nRea blames his son for the false daily reports. ", "But Rea had the agreement with the McCouns. ", "Rea was responsible for the account. ", "As the compliance officer for 1-800-DAY-TRADE testified, Rea personally received actual daily reports from 1-800-DAY-TRADE showing all activities from the previous day, including open accounts. ", "Rea had the obligation to supervise his son. ", "Rea had the duty to verify the accuracy of the reports sent to the McCouns, which he could have done from the 1-800-DAY-TRADE reports, even with Robert doing the actual trading. ", "Rea knew or was recklessly indifferent that the reports sent to the McCouns were false. ", "The court may infer an intent to deceive from Rea's actual knowledge of the daily positions and the false reports or his reckless indifference to the accuracy of the reports. ", "In re Samani, 192 B.R. 877, 880 (Bankr.", "S.D.Tex.1996).", "\nThe daily reports sent to the McCouns constitute false representations. ", "Rea allowed Robert to send the reports with the intent that the McCouns believe that positions were flat each day, with profits growing during the month. ", "Both were false. ", "Rea intended to deceive the McCouns. ", "The McCouns justifiably relied on the reports, believing that Rea was performing according to his stated objectives and that they were making money. ", "But they were not. ", "But for the false reports, the McCouns would have stopped trading once they suffered a 10% loss. ", "As a result of the representation, they suffered losses of $69,340.00.", "\nThe McCouns have established by a preponderance of the evidence that Rea obtained money initially and daily during the month of the transaction by false representations. ", "Rea concedes he is liable for the McCouns' loss of $69,340.00. ", "Accordingly, under § 523(a)(2)(A), that debt is excepted from Rea's discharge.", "\nRea contends, nevertheless, that he did not \"obtain\" money. ", "Section 523(a)(2)(A) excepts from discharge a debt for money \"obtained by\" false pretenses, a false representation or actual fraud. ", "The McCouns retained legal and equitable title to their $100,000.00 or the securities purchased by Rea from that fund. ", "The McCouns did not pay Rea a commission; the only commissions being paid went to 1-800-DAY-TRADE. ", "The venture never resulted in a profit to share.", "\nCourts have split on whether the debtor must actually receive the money or derive a benefit from the money. ", "See In re Naimo, 175 B.R. 878, 880-881 (Bankr.", "E.D.Pa.1994)(listing the cases with the competing reading of the provision). ", "This court agrees with the courts that hold the term \"obtained by\" limits nondischargeable debts for money to fraud instances as opposed to money obtained by honest means. ", "In re Mones, 169 B.R. 246, 252 (Bankr.", "D.Dist.", "Colo.1994). ", "The statute does not otherwise require or address for whose benefit the debtor obtained the money.", "\n*87 But, in any event, Webster's Third New International Dictionary Unabridged (1986) defines \"obtain\" as \"to gain or attain possession or disposal of usually by some planned action or method.\" ", "Rea gained possession of the McCouns' money by their planned agreement. ", "Rea accordingly obtained money. ", "Rea had the daily use of the money to invest with the opportunity to profit pursuant to his agreement with the McCouns. ", "Accordingly, Rea derived benefit.", "\nThe case presents an unusual set of circumstances. ", "Rea and his son bought securities with the McCouns' money. ", "The McCouns owned the securities. ", "When Rea informed the McCouns of the loss of value of their investments, the McCouns nevertheless owned the equity positions. ", "After learning that Rea had misrepresented that he would minimize their risk with a 10% stop loss protection, would trade their accounts himself and would provide accurate daily reports, they nevertheless accepted Rea's advice to immediately liquidate their holdings. ", "The court would have expected under these circumstances that the McCouns would have sought the advice of security houses before deciding to liquidate their holdings. ", "Ironically, had the McCouns held their holdings until the day of trial, as best as the court can determine from daily stock quotes, their $100,000.00 investment portfolio would have been worth at least $271,083.00 on December 10, 1999, and at least $350,876.00 on January 31, 2000 (the court could not obtain a value for two companies). ", "But that highlights the risks with and inadvisability of day trading.", "\n\nSection 523(a)(4)\nThe McCouns next contend that Rea committed the fraud or an act of defalcation while acting in a fiduciary capacity thereby excepting the debt from discharge under 11 U.S.C. § 523(a)(4). ", "To show non-dischargeability under § 523(a)(4), a creditor must prove by a preponderance of the evidence that (1) the debt was caused by fraud or defalcation, and (2) there was a fiduciary relationship between the parties at the time the debt was created. ", "In re Chavez, 140 B.R. 413, 422 (Bankr.", "W.D.Tex.1992).", "\nA fiduciary under § 523(a)(4) does not refer to any relationship involving confidence, trust or good faith, rather § 523(a)(4) concerns a relationship arising out of a technical or express trust. ", "In re Tran, 151 F.3d 339, 342 (5th Cir.1998); Davis v. Aetna Acceptance Co., 293 U.S. 328, 333, 55 S.Ct. ", "151, 79 L.Ed. ", "393 (1934). ", "An express trust traditionally includes (1) an explicit declaration of a trust, (2) a defined trust res, and (3) an intent to create a trust relationship. ", "Chavez, 140 B.R. at 423. ", "To create an express trust, the legal and equitable title to the trust res must be separate, the former being vested in a trustee and the latter in a beneficiary. ", "But the express trust may be created by an express agreement, the direct acts of the parties or a written instrument. ", "In re Berry, 174 B.R. 449, 454 (Bankr.", "N.D.Tex. ", "1994). ", "A technical trust, on the other hand, may be imposed by law. ", "In re Angelle, 610 F.2d 1335, 1341 (5th Cir.1980). ", "The trust must exist before the transactions that give rise to the claim. ", "Id.\nRea and the McCouns operated like a joint venture. ", "The McCouns provided the capital for the investments, but vested full discretion in Rea on the daily investment decisions, provided that he not permit their losses to exceed 10%. ", "Rea managed the capital. ", "Rea bought and sold securities in the McCouns' name and on their behalf. ", "Rea maintained the McCouns' funds in a segregated account and provided a daily accounting to the McCouns. ", "At month's end, if Rea achieved a profit, he and the McCouns would share the profit equally. ", "If he did not receive a profit, the McCouns would receive the first $1,000.00 of profit from the next profitable month before the parties shared the remaining profits. ", "The McCouns had virtually no experience in securities trading. ", "They relied on and deferred to Rea's experience. *", "88 Rea recognized that he and the McCouns had a relationship based on trust.", "\nTexas common law recognizes that a fiduciary relationship may arise from moral, social, domestic or purely personal relationships of trust and confidence. ", "41 TX Jur.3d Fraud and Deceit § 6 (1988). ", "But the test for § 523(a)(4) does not turn on whether Texas law would recognize a fiduciary relationship for equitable reasons but rather whether Texas law would recognize a fiduciary relationship based on an express or technical trust. ", "Here, the parties had a relationship of trust and confidence. ", "Indeed, they stood as principal and agent or as parties in a venture. ", "By their acts, they established that relationship. ", "But, the res, the McCouns' $100,000.00 and the equities it bought, remained at all times in the McCouns' name. ", "The McCouns retained both legal and equitable title. ", "Consequently, Texas law would not recognize an express trust.", "\nThe law may, nevertheless, impose a technical trust on the relationship. ", "For example, a managing partner in a Texas partnership owes a fiduciary duty imposed by law to his partners. ", "See In re Bennett, 989 F.2d 779 (5th Cir.1993); Huffington v. Upchurch, 532 S.W.2d 576 (Tex.1976). ", "A director of a corporation owes a fiduciary duty to the corporation's shareholders. ", "Dunagan v. Bushey, 152 Tex. ", "630, 263 S.W.2d 148, 152 (1953). ", "A statute may impose a technical trust on a relationship providing it includes a res and trust-like duties. ", "Tran, 151 F.3d at 342-43.", "\nEven though not performing traditional broker strategies, Rea acted as a securities broker as defined by the Securities and Exchange Act, 15 U.S.C. § 78c(a)(4), which defines a broker as an individual who is \"engaged in the business of effecting transactions in securities for the account of others.\" ", "Rea engaged in effecting daily transactions in securities for the McCouns' account.", "\nRea effected securities transactions for the McCouns with total discretion, using a defined res, provided he stopped trading if he experienced a 10% loss. ", "Title to the securities bought and sold by Rea remained in the customer, the McCouns.", "\nRea contends that he should not be viewed as a broker, observing that he had not been paid by commission. ", "Rea's activities fall squarely within the securities' law definition of a broker. ", "As Chairman Levitt testified before the Senate committee, day trading differs from traditional broker strategies, but the difference amounts only to strategy, not to the parties' legal relationship.", "\nThe broker, by virtue of his position, owes a fiduciary duty to his customer. ", "Armstrong v. McAlpin, 461 F.Supp. ", "622 (S.D.N.Y.1978); People v. Mercer Hicks Corp., 4 Misc.2d 55, 155 N.Y.S.2d 740, 744 (1956), aff'd 3 A.D.2d 708, 160 N.Y.S.2d 806 (1st Dept.1957); 11 N.Y. Jur. ", "Brokers § 74 (1996). ", "Although some jurisdictions do not recognize a fiduciary duty for brokers who merely execute a customer's orders without any discretion on the broker's part, In re Oberweis Securities, Inc., 1992 WL 119272 (Bankr. ", "N.D.Ill.1992), when the broker has the discretion to determine which purchases and sales to make and when, the law imposes a fiduciary duty on the broker. ", "Leib v. Merrill Lynch, Pierce, Fenner & Smith, Inc., 461 F.Supp. ", "951, 953 (E.D.Mich.1978); Commodity Futures Trading Commission v. Heritage Capital Advisory Services, Ltd., 823 F.2d 171, 173 (7th Cir.1987). \"", "Unlike the broker who handles a non-discretionary account, the broker handling a discretionary account becomes the fiduciary of his customer in a broad sense.\" ", "Leib, 461 F.Supp. ", "at 953. ", "The court has not found any Texas authority addressing the issue; but the court cannot discern any teaching from the Texas courts that would not follow this precedent.", "\nRea relies on In re Michel, 74 B.R. 80 (Bankr.", "N.D.Ohio 1985), and In re Buhay, 77 B.R. 561 (Bankr.", "W.D.Tex.1987), for the *89 proposition that a broker is not a fiduciary under an express or technical trust existing prior to the transaction from which the debt arises. ", "Both cases, however, recognize that a securities broker may hold money for an investor in trust. ", "Both courts found that the creditor failed to meet its burden of proof. ", "Although here the McCouns failed to establish an express trust because they retained legal and equitable title to the res, the law imposes a technical trust on their relationship with Rea. ", "They have met their burden of proof by establishing a res and trust-like duties. ", "The McCouns transferred the $100,000.00 to Rea before Rea began trading. ", "The transactions that give rise to the debt occurred in the daily trading after the establishment of the technical trust relationship.", "\nThe case law does not expressly address the fiduciary capacity of day traders. ", "Since Rea acted as a broker over a discretionary account, the law would impose a fiduciary relationship without the need to explore the day trading practice.", "\nMarketplace developments concerning day trading support that result. ", "Chairman Levitt testified before the Senate Committee that recent technological advances fostered the development of day trading. ", "While the SEC does not believe that day trading currently presents systemic problems for the securities markets, Levitt testified about the potential for individuals to be seduced by promises of easy profits by day trading without fully understanding the risks. ", "Day trading involves significant risks of loss. ", "Levitt observed: \"While technology provides innumerable benefits to investors by making trading easier and faster, new and relatively inexperienced investors may be using this technology to trade in ways that do not match their goals and risk tolerance.\" ", "Levitt Testimony at 6. ", "The NASD has concluded that day trading brokers must disclose the \"unique risks\" posed by day trading and have reasonable grounds for believing that a day trading strategy is appropriate for the customer. ", "The NASD has promulgated a rule to that effect, which has been submitted to the SEC for consideration. ", "See SR-NASD-99-41 (August 20, 1999). ", "Chairman Levitt explains that the rule would require firms that promote day trading activities to disclose to customers, prior to opening accounts, the risks associated with that type of trading. ", "The customer must be prepared to lose all of the funds used for day trading. ", "The rule would also require day trading firms to make a threshold determination that day trading is appropriate for the particular customer. ", "A day trading firm, in approving an account for day trading, would need reasonable grounds for believing that a day trading strategy is appropriate for the customer by gathering essential facts about the customer. ", "SR-NASD-99-41 (August 20, 1999).", "\nThis recent rule-making responds to the unique risks generated by the technological innovation that makes day trading possible. ", "If anything, those risks strengthen the public policy reasons for the common law's imposition of a technical trust on brokers. ", "The court, therefore, concludes that the law imposes a trust on Rea acting as a securities broker for the McCouns. ", "Rea was \"acting in a fiduciary capacity.\"", "\nThe court has already found that Rea actively misrepresented and that the McCouns justifiably relied on the misrepresentations in allowing Rea to invest the money throughout their one month's relationship. ", "Rea has therefore incurred a debt for fraud while acting in the fiduciary capacity.", "\nUnder § 523(a)(4), a defalcation is a willful neglect of a fiduciary duty even if not accompanied by fraud or embezzlement. ", "Matter of Moreno, 892 F.2d 417, 421 (5th Cir.1990). ", "For a broker generally, the fiduciary obligation imposes a duty to recommend securities suitable for the customer. ", "The broker has a duty to provide the customer with all information relevant to the affairs the customer instructed to the broker. ", "When the broker's services include providing investment advice, *90 the broker has the duty of making recommendations in the best interest of the customer. ", "The broker must execute orders fairly, with a duty to disclose markups and markdowns and other pricing events. ", "Dan Brecher and Jeffrey S. Rosen, Securities Arbitration of Customer Claims Alleging Unsuitability, Improper Markups/Markdowns or Breach of Fiduciary Duties, 950 PLI/Corp. 469, 473, 494-95 (1996). ", "The broker has a duty to segregate the customer's funds, including proceeds of sales and to provide an accounting to the customer. ", "Mercer Hicks, 155 N.Y.S.2d at 744. ", "For brokers handling discretionary accounts, while not needing prior authorization for each transaction, the broker has a duty to manage the account in a manner directly comporting with the needs and objectives of the customer as stated in the authorization papers or as apparent from the customer's investment and trading history; to keep informed regarding the changes in the market which affect his customer's interest and act responsively to protect those interests; to keep his customer informed as to each completed transaction; and to explain forthrightly the practical impact and potential risks of the course of dealing in which the broker is engaged. ", "Leib, 461 F.Supp. ", "at 953.", "\nRea did not provide accurate daily accountings of transactions to the McCouns. ", "Indeed, he provided false and misleading accountings of transactions. ", "Rea did not keep the McCouns informed as to all completed transactions. ", "Rea did not disclose that their partnership-like profit sharing agreement did not comport with the traditional manner of payment by commission under the securities regulations. ", "Rea did not manage the account based on the articulated needs and objectives of the McCouns, since he did not liquidate the holdings nor stop trading when the value of the equities ended a day below $90,000.00. ", "Rea did not explain the practical impact and potential risks to the McCouns even though he had them acknowledge risks. ", "The court finds that Rea committed acts of defalcation while acting in a fiduciary capacity. ", "He committed these acts after the trust had been imposed on June 29, 1998.", "\nThe McCouns have established by a preponderance of the evidence that Rea's debt to the McCouns must be excepted from his discharge under § 523(a)(4).", "\nThe McCouns move the court for leave to file a second supplemental trial brief. ", "The brief discusses violations of NASD rules of conduct and the Texas Securities Act. ", "Although an analysis of these matters may have been informative, the parties did not try this adversary proceeding based on state or federal securities laws and regulations. ", "Except for the definitions of brokers and day trading and the regulatory developments concerning day trading, the court has not considered whether any securities laws or regulations have been violated by the parties' course of dealing. ", "The motion is denied.", "\n\nAttorney's Fees\nThe McCouns contend they should recover their attorney's fees for prosecuting this matter. ", "The McCouns may recover reasonable attorney's fees necessary to establish their claim, to the extent authorized by non-bankruptcy law. ", "In re Jordan, 927 F.2d 221, 226-228 (5th Cir.1991). ", "However, Rea conceded that debt, including the damages. ", "Consequently, this litigation concerned only the dischargeability of that debt. ", "The Bankruptcy Code does not provide for the recovery of attorney's fees for dischargeability litigation. ", "See Alyeska Pipeline Serv. ", "Co. v. Wilderness Soc'y, 421 U.S. 240, 249-50, 95 S.Ct. ", "1612, 44 L.Ed.2d 141 (1975)(absent specific fee-shifting statutory or contractual authorization, each side bears its attorney's fees under the so-called \"America Rule\"). ", "The McCouns may not recover their attorney's fees for prosecuting this adversary proceeding.", "\n\n\n*91 Conclusion\nA court must adjudicate disputes not settled by the parties. ", "But this case continues to compel a pragmatic resolution by the McCouns and Rea. ", "The McCouns claimed risk aversion yet they agreed in writing to the riskiness of the investments. ", "They relied on Rea's representation they could cut their losses at $10,000.00. ", "The McCouns do not contend that Rea willfully and maliciously injured them. ", "Indeed, had they held their equity positions long term, they could have netted an impressive return. ", "Meanwhile, Rea has appropriately lost his securities license. ", "He struggles on an hourly wage while his wife has returned to the work force after retirement. ", "Neither Rea nor his wife have spoken to Robert since August 1998.", "\n\nOrder\nBased on the foregoing,\nIT IS ORDERED that Christopher and April McCoun have a judgment against Peter Wister Rea declaring the debt of $69,340.00 not discharged under § 523(a)(2)(A) and (a)(4). ", "Counsel for the McCouns shall prepare a final judgment consistent with this order.", "\n" ]

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[ "There was cause for \"shell-ebration\" after the owner of a tortoise was reunited with their pet - nine months after it crawled away from home.", "\n\nPippa, a 12-year-old Hermann's tortoise, is believed to have escaped from the front garden of a property on Milne Drive, Bircotes, Nottinghamshire, on June 18 last year.", "\n\nShe was found by dog walker Jessica Walker about 200 metres away. ", "Owner Laura Tissington said Pippa has now been \"grounded\"." ]

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[ "It was just around the time that Mike Reilly mentioned Odell Willis that his teammate appeared, wearing nothing but a gold-coloured towel.", "\n\n“Odell’s loud, boisterous and likes to have a good time,” Reilly says. ", "On cue, Willis walks by.", "\n\n“There he is right there, going to his media wrapped in a towel.”", "\n\nA layer of terrycloth is all that’s between him and a room full of reporters. ", "Willis barely glances away as he hears his name and enters the room.", "\n\n“If he wasn’t doing that, if Odell wasn’t doing what we just saw, I’d think there was something wrong,” Reilly says.", "\n\nThe way Reilly explains it, there’s very much a come-as-you-are feel to this Esks team.", "\n\n“To me, there are many different types of leaders,” the MOP candidate says on Wednesday afternoon, after a relatively quick but cold practice at Commonwealth Stadium.", "\n\n“I coach the game with emotion. ", "I played the game with emotion and you either like it or you don’t.” – ", "Edmonton Eskimos head coach Jason Maas\n\nThe saying that pundits love to slap on a team with an interesting coach is that it takes on his personality. ", "If it’s suggested here that this team has taken on Jason Maas’ personality, what’s the first thing that comes to mind? ", "Is it the anger that you’ve seen on the sidelines from week to week the last two seasons? ", "Is it a verbal wrath that seemingly no one is safe from? ", "Is it a headset meeting its untimely demise on a challenge lost?", "\n\n“I coach the game with emotion. ", "I played the game with emotion and you either like it or you don’t,” Maas says when he’s asked about the perception of him that might be out there.", "\n\nHe’s seen himself at times this season on TSN when he’s watching games, CFL and otherwise. ", "He catches idle chatter here and there. ", "He knows his sideline presence has been a recurring topic.", "\n\n“Everyone’s entitled to their opinion about me. ", "I’m in the public eye,” he says. “", "I chose a profession that people get to criticize you for everything you do. ", "Good and bad. ", "It doesn’t bother me. ", "If it did, I wouldn’t do this. ", "I’m going to always do this how I feel it needs to be done.”", "\n\nIt’s fascinating to stand in this narrow hallway at the stadium with Maas and listen to him. ", "He can’t explain his coaching philosophy because he doesn’t specifically have one.", "\n\n“I didn’t read a book on how to coach. ", "I basically coach the way I feel it’s meant to be done,” he half-explains. “", "I’m not one of those guys that has a library of how-to. ", "I just do it.”", "\n\nHe stands there unflinching, completely comfortable in his skin. ", "The more he talks, the more it dawns on you that this is a man that, as a football coach, is completely honest and true to himself. ", "When you realize that, it’s hard not to be jealous of him. ", "Can you imagine how freeing that is? ", "How much simple, unnecessary day-to-day stress would leave our lives if we could all live like this at least some of the time? ", "There are movies made about people that get opportunities like that.", "\n\nRELATED\n\n“I know what type of person, football player that Jason Maas was and I know what type of coach that he is,” Reilly says. “", "I know the passion that he has for the game and I know if he were to handle himself any differently on the sidelines that would throw us off our game. ", "We’d wonder what was up, we’d know it was not genuine, we’d know it’s not real.”", "\n\nTwo seasons together now, a combined 22-14 and at the helm of an offensive machine, Reilly and Maas are entering into their second of what they hope is another deep playoff run. ", "They seem like the perfect QB-as-extension-of-the-coach that you hope for. ", "More than anything, both men appreciate people being who they are, saying what they need to say and doing what needs to be done to win. ", "They spoke separately on Wednesday, but said the word “fake” with the same intonations and same disdain. ", "They need honesty if their pairing is going to work. ", "The team needs it if it’s going to be successful.", "\n\n“I don’t want anybody to be in charge of my team that’s fake,” Reilly says. “", "I think that everybody knows what it’s like to be around someone that’s fake. ", "When they’re trying to be a rah-rah guy and they’re not. ", "Or they’re trying to sit there and have a conversation with you about something that they don’t really care about and they’re just saying things that you want to hear. ", "That’s not what you want to hear. ", "That’s not somebody that people are going to follow.”", "\n\nReilly learned first-hand what Maas was about in early 2016, shortly after he was hired as coach. ", "Maas took whoever was on the roster and in town out for a night of bowling.", "\n\n“There were probably 30 or 40 of us and I could just see it. ", "He didn’t want to lose, bowling,” Reilly says.", "\n\n“We’re all just together having a good time and he was super focused and intense bowling. ", "I was like, ’I like that. ", "He wants to win at everything he does.’ ", "I know he cares about being competitive and being successful and I’m drawn to that type of stuff. ", "It’s not for everybody and that’s fine, that’s OK, it’s not a problem. ", "But it’s not an act. ", "it’s just how he is in every day life.”", "\n\nMaas knows there are limits in the Esks organization. ", "He saw his GM, Ed Hervey, relieved of his duties late in the off-season this year. ", "He knows that if you push in the wrong way, for the wrong things, there can be push back. ", "He hasn’t gotten that.", "\n\n“Trust me. ", "If I was not of,” the hint of a smile starts to emerge here, “of sound mind — maybe it appears that I’m not at times — but if I wasn’t I’d be told to be different and that’s not what my employer wants. ", "I don’t get that from my employer.”", "\n\nHe’s gotten one phone call this season. ", "He said commissioner Randy Ambrosie was in touch with him over throwing his headset on the field.", "\n\n“I’ve seen headsets thrown. ", "I’ve seen a lot of other things thrown on the sideline, but not on the field, I get that. ", "I understand that part,” he says.", "\n\n“But when I’m sitting there and I’m yelling at an official or yelling at a player or yelling at a coach, to me that’s part of football, it’s what football is. ", "It’s a game of emotions and high pressure situations. ", "Not everyone’s going to be even keel. ", "Do people take it over the line at times? ", "Yeah, it happens.", "\n\n“I coach a certain way, I am a certain way and all of it’s real. ", "There’s nothing fake about that,” he says, sounding so much like Reilly. “", "I enjoy and love my job and I love the CFL and am very thankful and grateful for it.”" ]

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[ "Successful candidates submit election expense details to ECP\n\nISLAMABAD: The Election Commission of Pakistan (ECP) has received details of election expenses of successful candidates in the national and provincial assemblies.", "\n\nAccording to the ECP, it has received details of 269 National Assembly candidates, 295 Punjab Assembly candidates, 129 from Sindh Assembly, 97 from Khyber Pakhtunkhwa and 49 from Balochistan.", "\n\nThe details will also be published on the election body’s website. ", "The ECP after receiving the details has started working on issuing a notification declaring successful candidates, except in those constituencies which have been challenged in courts.", "\n\nAll successful candidates were bound to submit their expenditure detail within 10 days of polling while non-successful candidates were required to submit expenditure detail within 30 days.", "\n\nIndependent candidates are either required to join any political party in the Parliament or retain their independent status within three days from the issuance of notification.", "\n\nIt is the constitutional obligation that the session of new assembly should be convened within 21 days after elections so that the election of new prime minister, speaker and deputy speaker might be carried out." ]

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[ "São Paulo\n\nO preço do tomate voltou a pressionar o orçamento das famílias. ", "Com uma alta de 31,84% somente no mês de março, segundo a inflação medida pelo IBGE (Instituto Brasileiro de Geografia e Es­tatística), o produto já passa de R$ 10 nos supermercados da capital e exige malabaris­mos do consumidor.", "\n\nA dona de casa Zenaide Ri­co Citadini, 58 anos, da Bela Vista (região central), conta que, há uma semana, che­gou a encontrar o quilo do tomate por R$ 4 em um su­permercado da região. ", "Ela aposta na pesquisa de preços para escapar da alta. “", "Hoje, está por R$ 10,99. ", "Eu pes­quiso até encontrar um bom preço.”", "\n\nNos restaurantes, a solução tem sido inovar: re­duzir a quantidade e oferecer alguma compensação. ", "No Arimbá, em Perdizes (zona oeste), a proprietária Angelita Gonzaga, 52, en­controu um jeito de não de­sagradar o cliente e nem ter prejuízo.", "\n\n“Diminuo um pou­co o tomate da receita e acrescento um outro vegetal. ", "Se fosse repassar o aumento\n\npara o consumidor final, os preços dos pratos estariam 10% mais caros. ", "Se você re­passa, perde o cliente”, diz.", "\n\nSegundo o coordenador do IPC, da Fipe (Fundação Insti­tuto de Pesquisas Econômi­cas), Guilherme Moreira, es­sas variações de preço no co­meço do ano são esperadas.", "\n\n“Verão e calor trazem muita chuva. ", "A boa notícia é que a tendência é de queda. ", "No mês que vem, o tomate deve chegar mais barato aos con­sumidores”, explica.", "\n\nO pesquisador João Paulo Deleo, do Cepea/USP, diz que o recuo nos preços começa em maio para o consumidor." ]

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[ "Low Cost Dumpster Rentals\n\nRoll Off For Rent in Fairhaven, MA\n\nFree Price Quote, Call Now!", "\n\nNeed a Dumpster Rental in Fairhaven?", "\n\nWe have the commercial and residential dumpster service you need in Fairhaven.", "\n\nAt WastePages, we strive to bring you the best service at the best price available. ", "We have a wide selection of dumpster sizes in stock in Fairhaven, MA, with flexible & timley pickup and delivery. ", "Give us a call today for all your dumpster rental and roll off needs.", "\n\nGive us a call today for a free dumpster quote. (", "508) 507-7946\n\nMore About Us\n\nWastePages has made it super fast and easy to rent a dumpster. ", "You only need 5 minutes!", "\n\nWhen you are renting a 5, 10, 15, 20, 30 or 40 yard dumpster, you want a company you can trust with prices that make you smile. 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", "It perhaps kills your time and efforts because all the trash is going to be handled personally.", "\n\nRequest a Call Back!", "\n\nStill need a quote but don't want to talk on the phone right now? ", "Fill out the form below and we will get back to you!", "\n\nPlease use the form below to contact us. ", "We look forward to working with you and will get back to you as soon as possible. ", "All fields are required" ]

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[ "Important: This destination may have COVID-19 travel restrictions in place, including specific restrictions for lodging. ", "Check any national, local, and health advisories for this destination before you book.", "\n\nFeatured Resort Hotels in Culion Island\n\nNestled on the beach, this Coron resort is within 25 mi (40 km) of Palawan State University - Coron, Mount Tapyas and San Nicolas Barangay Hall. ", "Iglesia ni Cristo ...…Nestled on the beach, this Coron resort is within 25 mi (40 km) of Palawan State University - Coron, Mount Tapyas and San Nicolas Barangay Hall. ", "Iglesia ni Cristo ...WWW…\n\n4.3/5Excellent! (", "130 reviews)\n\n\"The place is beautiful and the food was really good. ", "The staff was really friendly as well.\"…", "\"\"The place is beautiful and the food was really good. ", "The staff was really friendly as well.", "\"WWW…\"\n\nNestled on the beach, this Coron resort is just steps away from Malcapuya Island and Tanglaw Beach. ", "Mount Tapyas and Palawan State University - Coron are also ...…Nestled on the beach, this Coron resort is just steps away from Malcapuya Island and Tanglaw Beach. ", "Mount Tapyas and Palawan State University - Coron are also ...WWW…\n\n4.5/5Wonderful! (", "57 reviews)\n\n\"Loved this place! ", "Cannot beat the view! ", "Staff is so incredibly kind ❤️\"…\"\"Loved this place! ", "Cannot beat the view! ", "Staff is so incredibly kind ❤️\"WWW…\"\n\nNestled on the beach, this Coron resort is 1.3 mi (2.1 km) from Palawan State University - Coron and 1.6 mi (2.6 km) from Bayside Plaza. ", "Mount Tapyas and Coron ...…Nestled on the beach, this Coron resort is 1.3 mi (2.1 km) from Palawan State University - Coron and 1.6 mi (2.6 km) from Bayside Plaza. ", "Mount Tapyas and Coron ...WWW…\n\n3.5/5Good! (", "108 reviews)\n\nSmell the sea and feel the sky.", "\n\n\"Employees are customer focused and helpful. ", "Loved the location on water. ", "Serene place and great views.\"…", "\"\"Employees are customer focused and helpful. ", "Loved the location on water. ", "Serene place and great views.", "\"WWW…\"\n\nLocated in the mountains, this family-friendly resort is within 9 mi (15 km) of Palawan State University - Coron, Mount Tapyas and Bintuan Mangrove Park. ", "Iglesia ...…Located in the mountains, this family-friendly resort is within 9 mi (15 km) of Palawan State University - Coron, Mount Tapyas and Bintuan Mangrove Park. ", "Iglesia ...WWW…\n\n4.3/5Excellent! (", "84 reviews)\n\n\"General area is quiet. ", "There should be a designated area for smoking not in the restaurant. ", "It took 2 days for maintenance to check on hot water temperature on the shower. ", "Overall stay is good .\"…\"\"General area is quiet. ", "There should be a designated area for smoking not in the restaurant. ", "It took 2 days for maintenance to check on hot water temperature on the shower. ", "Overall stay is good .\"WWW…\"\n\n\"Beautiful serene place to call home for a few days. ", "We went diving and all of the shipwrecks were amazing. ", "We had one “ hiccup” with the resort but Kat made everything right.\"…", "\"\"Beautiful serene place to call home for a few days. ", "We went diving and all of the shipwrecks were amazing. ", "We had one “ hiccup” with the resort but Kat made everything right.", "\"WWW…\"\n\n\"Great destination. ", "Especially around 5pm sitting at a table listening to some great tunes with a beverage overlooking an amazing view. ", "The staff were fantastic and helpful, and the 2 singers at night serenading the restaurant was a highlight as well.\"…", "\"\"Great destination. ", "Especially around 5pm sitting at a table listening to some great tunes with a beverage overlooking an amazing view. ", "The staff were fantastic and helpful, and the 2 singers at night serenading the restaurant was a highlight as well.", "\"WWW…\"\n\nNestled on the beach, this Coron resort is within 6 mi (10 km) of Iglesia ni Cristo, Mount Tapyas and Palawan State University - Coron. ", "Coron Central Plaza and ...…Nestled on the beach, this Coron resort is within 6 mi (10 km) of Iglesia ni Cristo, Mount Tapyas and Palawan State University - Coron. ", "Coron Central Plaza and ...WWW…\n\n4.3/5Excellent! (", "23 reviews)\n\n\"The property is very quiet away from the town proper, view is very nice and relaxing, Beach front resort and staff are very accomodating\"…\"\"The property is very quiet away from the town proper, view is very nice and relaxing, Beach front resort and staff are very accomodating\"WWW…\"\n\n\"We loved this resort! ", "The views are fantastic! ", "Each unit has a terrace for sitting and enjoying the views. ", "They also have made several other places with comfortable chairs and hammocks to sit and enjoy the time. ", "All sorts of water sports are available: kayaks, snorkeling, island hopping, and of course ...\"…\"\"We loved this resort! ", "The views are fantastic! ", "Each unit has a terrace for sitting and enjoying the views. ", "They also have made several other places with comfortable chairs and hammocks to sit and enjoy the time. ", "All sorts of water sports are available: kayaks, snorkeling, island hopping, and of course ...\"WWW…\"\n\n\"Discovery island being away from the main town of Coron itself was unique. ", "The staff are very helpful and friendly. ", "There is a bookshelf where you can take a book and leave one (exchanging), if you are a reader on vacation. ", "The Town might have some expensive resaurants depending on where you go. ...\"…\"\"", "Discovery island being away from the main town of Coron itself was unique. ", "The staff are very helpful and friendly. ", "There is a bookshelf where you can take a book and leave one (exchanging), if you are a reader on vacation. ", "The Town might have some expensive resaurants depending on where you go. ...\"", "WWW…\"\n\nLocated in Coron Town Proper, this resort is 0.1 mi (0.1 km) from Iglesia ni Cristo and 1.9 mi (3.1 km) from Palawan State University - Coron. ", "San Agustin Parish ...…Located in Coron Town Proper, this resort is 0.1 mi (0.1 km) from Iglesia ni Cristo and 1.9 mi (3.1 km) from Palawan State University - Coron. ", "San Agustin Parish ...WWW…\n\n4.1/5Very Good! (", "46 reviews)\n\n\"Our room was a little outdated. ", "The power outlets were mostly round. ", "The room was spacious with lots of windows. ", "Internet was very weak.\"…", "\"\"Our room was a little outdated. ", "The power outlets were mostly round. ", "The room was spacious with lots of windows. ", "Internet was very weak.", "\"WWW…\"\n\nSituated near the airport, this resort is within 3 miles (5 km) of Concepcion Pier, Okikawa Maru Shipwreck and Concepcion Falls. ", "Huma Island Beach and Bintuan ...…Situated near the airport, this resort is within 3 miles (5 km) of Concepcion Pier, Okikawa Maru Shipwreck and Concepcion Falls. ", "Huma Island Beach and Bintuan ...WWW…\n\n4.6/5Wonderful! (", "52 reviews)\n\nOur 4th visit\n\n\"We have stayed Al Faro 4 times now and always found it to be excellent in every way. ", "The staff are all extremely friendly, welcoming and efficient. ", "The hilltop position is stunning and the pool fabulous. ", "Food is always very good and varied. ", "Being picked up and dropped off by speedboat always makes ...\"…\"\"We have stayed Al Faro 4 times now and always found it to be excellent in every way. ", "The staff are all extremely friendly, welcoming and efficient. ", "The hilltop position is stunning and the pool fabulous. ", "Food is always very good and varied. ", "Being picked up and dropped off by speedboat always makes ...\"WWW…\"\n\nThis family-friendly Coron resort is located near the airport, within 1 mi (2 km) of Iglesia ni Cristo and Palawan State University - Coron. ", "Mount Tapyas and ...…This family-friendly Coron resort is located near the airport, within 1 mi (2 km) of Iglesia ni Cristo and Palawan State University - Coron. ", "Mount Tapyas and ...WWW…\n\n3.6/5Good! (", "49 reviews)\n\nBudget Hotel\n\n\"Budget stay!!! ", "If you’re trying to save few quids. ", "The whole place needs upgrading especially the rooms and bathrooms. ", "We got shifted to 3 different rooms because things stopped working in the room. ", "Staff were friendly and nice and helpful. ", "10-15 mins walking distance to the town/Port.\"…", "\"\"Budget stay!!! ", "If you’re trying to save few quids. ", "The whole place needs upgrading especially the rooms and bathrooms. ", "We got shifted to 3 different rooms because things stopped working in the room. ", "Staff were friendly and nice and helpful. ", "10-15 mins walking distance to the town/Port.", "\"WWW…\"\n\nLowest nightly price found within the past 24 hours based on a 1 night stay for 2 adults. ", "Prices and availability subject to change. ", "Additional terms may apply.", "\n\nOther property types in Culion Island\n\nSave Sunlight Eco Tourism Island Resort to your lists\n\nSunlight Eco Tourism Island Resort\n\n3.5 out of 5\n\nThe price is CA $212 per nightCA $212\n\nper night\n\nJun 23 - Jun 24\n\n3.9/5Very Good! (", "18 reviews)\n\n\"We absolutely loved the efficiency and sensitivity of the staff. ", "Although there were other tourists there, the staff made us feel like it was just my wife and I. It was incredible the quality of everything there. ", "We would totally come again and are recommending it to others. ", "Loved it!\"…\"\"We absolutely loved the efficiency and sensitivity of the staff. ", "Although there were other tourists there, the staff made us feel like it was just my wife and I. It was incredible the quality of everything there. ", "We would totally come again and are recommending it to others. ", "Loved it!\"WWW…\"\n\n\"To reach the above island, we have to hire a boat from Coron Concepcion Port for peso 4,000. ", "When we reached the island at 1pm, we have noticed that the island has been deserted and not a single soul, only 2 dogs around. ", "We tried to reach the owner on his contact number but the number was no longer ...\"…\"\"To reach the above island, we have to hire a boat from Coron Concepcion Port for peso 4,000. ", "When we reached the island at 1pm, we have noticed that the island has been deserted and not a single soul, only 2 dogs around. ", "We tried to reach the owner on his contact number but the number was no longer ...\"WWW…\"\n\nLowest nightly price found within the past 24 hours based on a 1 night stay for 2 adults. ", "Prices and availability subject to change. ", "Additional terms may apply.", "\n\nResorts in Culion Island\n\nYou deserve a getaway, and a resort is the ideal place to find all the amenities and services you need for a relaxing time in Culion Island. ", "One of the comfortable resort hotels in the area could be just what you're looking for, whether you want an amazing pool, a state-of-the-art fitness center, or activities for the kids.", "\n\nApril-June: 93° F is the daytime average and 72° F is the nighttime average\n\nJuly-September: Daytime averages are around 89° F and nighttime averages are around 75° F\n\nOctober-December: The average temperatures are 88° F during the day and 69° F at night\n\nAverage rainfall is 2.91 inches in a year\n\nHow to Get to Culion Island and Around the Area\n\nCulion Island Transportation\n\nName\n\nType\n\nDistance\n\nBusuanga (USU-Francisco Reyes)\n\nAirport\n\n21.7 mi (34.9 km)\n\nFrequently asked questions\n\nWhat can I expect from a resort vacation in Culion Island?", "\n\nYou deserve some time off, and a resort is just the place to indulge in all the amenities and services you need for a relaxing stay in Culion Island. ", "One of the comfortable resorts in the area could be just what you’re looking for, whether you want great restaurants on site, shopping possibilities, or activities for the kids.", "\n\nMalcapuya Island, Huma Island Beach, and Coron Central Plaza are a few interesting places to visit nearby. ", "Other attractions in the area include Iglesia ni Cristo and Palawan State University - Coron.", "\n\nWhat's the seasonal weather like in Culion Island?", "\n\nThe hottest months are usually April and May with an average temp of 82°F, while the coldest months are January and February with an average of 79°F. ", "Average annual rainfall for Culion Island is 81 inches.", "\n\nWhat's the best way to get to and around Culion Island?", "\n\nFly into Busuanga (USU-Francisco Reyes), which is located 21.7 mi (34.9 km) away. ", "If you’d like to explore around the area, you may want to rent a car for your trip." ]

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[ "Third Star A'ahl, vision of the Church of the Third Star.", "A'kani's name is decent directly from A'ahl's, as she was born with their light. ", "A curse or blessing, it depends on how you use it.", "A'kani: iguanodragon.deviantart.com/ar…" ]

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[ "This Is Probably The Longest Killstreak In ‘Battlefield 1’ History\n\nWyatt\n\nJust like in real life, tanks in Battlefield 1 are absolutely devastating against infantry. ", "If you have a good tank player on your team, chances are that things are going to swing your way more often than not. ", "Hopefully, the tank helps you secure the objective, but that’s not always the case, especially when players like SamL97 are playing. ", "For about 30 minutes, not once did SamL97 try to capture the objective. ", "Instead, he managed to rack up a total of 105 kills without dying once.", "\n\nEveryone who’s played knows that the light tank is one of the sneakiest ways to get a ton of kills, but this is honestly insanity. ", "In 100+ kills, did none of his victims ever say “enough is enough” and try to take him out? ", "Because I know that after a few consecutive deaths by way of tank, I switch to assault and spend the rest of the round trying to turn the tank into a dutch oven.", "\n\nThe light tank works particularly well on St. Quentin’s Scar because visibility is poor and because there aren’t many other vehicles that can pose a danger. ", "It also helps in this round that all of SamL97’s teammates love to spam the spotting button, pointing out all the meatbag targets to hit." ]

{ "pile_set_name": "Pile-CC" }

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[ "Samsung announced a refreshed Gear VR headset at the MWC 2017 in Barcelona. ", "Even though the VR headset looks almost identical to the Gear VR 2016 model but there is a new addition to the package - a controller. ", "Now, with the inclusion of a controller, the VR headset attains a new level of immersive motion-controlled experience. ", "To emphasize the new addition, Samsung has named the new VR Headset as the Gear VR with Controller.", "\n\nThe Controller on the Gear VR is a nifty addition for sure as it enables users to point, shoot, drag and drop objects in the virtual ecosystem. ", "Not just that, users would no longer need to touch the headset for controlling volume or other tasks, everything could be controlled right from the controller in their hand.", "\n\nAt the event, Samsung also revealed that more than 70 apps are under development for the new Gear VR. ", "The controller uses motion sensors to offer better VR experience and it also has a touch pad and trigger input for enhanced control. ", "Home Button, Volume Buttons, and Back Buttons are also integrated in the contollers for quick access. ", "It is also compatible with all the existing Gear VR apps.", "\n\nNotably, the controller on the new Gear VR has stark similarities with the one that comes with Google's Daydream VR. ", "We think that with the inclusion of a controller, the Gear VR will now look like a more attractive prospect for the developers as they can create apps with support for motion sensors.", "\n\nThe Gear VR Controller adds a deeper level of immersion by giving you the power to interact with the virtual environment in an intuitive way. ", "The controller’s touchpad has been tuned to make it easy to navigate to your favorite videos and perform a number of actions within a game, while the trigger lets you select, grab, take aim, and fire. ", "Ergonomically designed for use with a single hand, the controller also has integrated home, volume, and back buttons, so you can easily move through a variety of content without breaking immersion.", "\n\nThe Gear VR with Controller also supports the devices that the 2016 variant did - the Galaxy S6, Galaxy S6 edge, Galaxy S7, Galaxy S7 edge, Galaxy S6 edge+ and the Galaxy Note 5. ", "The controller is powered by AAA batteries and it can run for 40 days with a 2 hours per day usage on one set of batteries. ", "For the old Gear VR Headset owners, you can easily add the new controller to your VR package without any problem. ", "You can buy the controller separately as well.", "\n\nFollow US\n\nSubscribe\n\nSome posts on Wccftech.com may contain affiliate links. ", "We are a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com" ]

{ "pile_set_name": "Pile-CC" }

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[ "Kino Lorber Studio Classics To Release ‘GOG’!", "\n\nKino Lorber Studio Classics is proud to announce the Blu-ray release of Herbert L. Strock’s 1954 3-D sci-fi classic GOG, presented in a new HD restoration by the 3-D Film Archive. ", "This Atomic Age cult favorite, starring Richard Egan, Constance Dowling, Herbert Marshall and William Schallert, tells the story of a special agent sent to investigate possible sabotage at a secret space research station, only to find it under the control of the Supercomputer NOVAC and two experimental robots, GOG and MAGOG, resulting in a terrifying battle between man and machine.", "\n\nLong unavailable in 3-D, GOG will finally be seen in its original format when it is released on 3-D Blu-ray by Kino Lorber on its Studio Classics label on March 1, 2016, in a painstaking new HD restoration by the 3-D Film Archive that returns the film to its original 3-D glory. ", "Kino Lorber has previously released the 3-D Film Archive’s restorations of The Bubble and The Mask on Blu-ray. ", "GOG comes to Blu-ray with the option to play the film in either 3-D or 2-D, and is packed with an array of special features including audio commentary by film historians Tom Weaver, Bob Furmanek and David Schecter, a 3-D restoration demo, a 2003 interview with director Herbert L. Strock, an archival interview with cinematographer Lothrop B. Worth, and a 3-D trailer gallery. ", "The SRP for the Blu-ray is $34.95.", "\n\nGOG was photographed in the Natural-Vision 3-D process and originally released in 1954, just as 3-D movies were quickly falling out of fashion at the box office. ", "As a result, it had only five theatrical screenings in 3-D before continuing its theatrical release in 2-D, and was subsequently sold to television in a black-and-white version. ", "Eventually, the 35mm left camera negatives were lost, and for nearly five decades, GOG has been completely unavailable in 3-D.\n\nIn 2001, 3-D Film Archive founder Bob Furmanek located the only surviving left 35mm element: an original 1954 Pathe color release print that was completely faded with no yellow or cyan information. ", "For the 2016 3-D Blu-ray release, Kino Lorber secured scans of the surviving 35mm left/right elements and Greg Kintz began the painstaking shot-by-shot restoration process.", "\n\n“Of all our restoration projects, GOG is the most rewarding to me personally,” said Furmanek. “", "When I began my search for lost 3-D elements in the early 1980s, GOG was at the top of my want list. ", "I knew director Herbert L. Strock quite well. ", "He was very proud of his work on the film and lamented the fact that it was lost in 3-D. After extensive research, I found the lost left side 35mm print in 2001. ", "I tell the full story of this exciting discovery in the commentary track on the Blu-ray. ", "After suffering through murky, black and white, flat and full-frame 16mm prints for decades, it’s a real thrill to finally see GOG finally restored as the filmmakers intended in vibrant 3-D, color and widescreen.”", "\n\nGreg Kintz, 3-D Film Archive Technical Director, added, “GOG was certainly our most challenging project to date. ", "Our usual timeline for a 3-D feature restoration is three months:GOG was on the operating table for five months. ", "The only surviving 35mm left side element was totally faded with no yellow or cyan information whatsoever. ", "Every single shot in the film required up to seven levels of correction, including color restoration, left/right panel matching, flicker reduction, image stabilization, detail extraction from the superior right side element, stereoscopic vertical alignment and dirt/damage clean-up. ", "We’re very proud of the final result in bringing this lost 3-D film back to life.”", "\n\nFor more information on the restoration of GOG, including stills and original promotional artwork, please visit the 3-D Film Archive website, or click here to watch a video with examples of the restoration process.", "\n\nSynopsis:\nNewly restored in HD and 3-D!", "\nIn a remote, underground research laboratory two scientists, engaged in space travel research, are frozen to death in a cold chamber when their instruments comes under the control of an unknown power.", "\n\nA security agent, Dr. David Sheppard (Richard Egan,The 300 Spartans) arrives at the secret space research base, home of two experimental robots to investigate the possible sabotage. ", "Early in his investigation, Sheppard finds that the underground laboratory under the control of the Supercomputer NOVAC and experimental robots GOG and MAGOG.", "\n\nHerbert L. Strock (The Crawling Hand) directed this sci-fi/horror classic with a stellar cast that includes Constance Dowling (Black Angel), Herbert Marshall (The Letter) and William Schallert (TV’s The Patty Duke Show).", "\n\nAbout Jess Landry\n\nJess Landry is an eccentric billionaire, the inventor of the hacky-sack and a compulsive liar. ", "She spends her time mentally preparing for the zombie apocalypse and playing with her cats. ", "You can find some of her work online at SpeckLit.com and EGM Shorts.", "\n\nRelated\n\n99designs\n\nDark Discoveries – Issue #36\n\n01 Publishing\n\nThe Shadow Over Portage and Main\n\nBedtime Horrors\n\nSpark\n\nSubscribe!", "\n\nSubscribe to the JournalStone mailing list\n\n* indicates required\n\nEmail Address *\n\nFirst Name *\n\nSwift to Chase\n\nFrom JournalStone\n\nThe JournalStone Network is your source for horror news and reviews. ", "Striving to bring you the latest and greatest of everything from the genre we love. ", "For contact information, review requests, or advertising questions please CLICK HERE." ]

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[ "Choose an account to switch subscription\n\nBroadband\n\nIreland’s fastest broadband network\n\nFLASH SALE!", "\n\nSign up by midnight March 27th & get €50 off your second bill.", "\n\nCrazy Fast WiFi\n\nAt Virgin Media we don’t do things by halves. ", "That’s why we’ve brought you Ireland’s fastest in-home WiFi, with broadband bundles built for an awesome entertainment experience. ", "So fast it should come with a warning.", "\n\nTerms & Conditions\n\nGeneral\n\nAll Broadband, TV and telephony products are subject to a 12 month contract, unless otherwise stated.", "\n\nWhen you purchase services from Virgin Media via our website or by telesales you have the right to cancel your contract within 14 days without giving any reason and without penalty, click here for more information.", "\n\n30 days written notice is required should you wish to cancel your service. ", "A cancellation fee will apply should you cancel during the contract period. ", "If you cancel & fail to facilitate the return of the equipment, you will be subject to an unrecoverable equipment charge of €150.", "\n\nFreedom Broadband and Anytime Mobile (30 Day Contract)\n\nFreedom Broadband and Anytime Mobile is available to New Virgin Media customers only, and is subject to a 30 day rolling contract period. ", "A €20 equipment activation fee applies. ", "In order to avail of this bundle, customers must sign up to Direct Debit at the point of sale. ", "To cancel your Freedom Broadband and Anytime Mobile subscription contract, you must provide 30 days’ notice in writing to Virgin Media. ", "If you cancel & fail to facilitate the return of the equipment, you will be subject to an unrecoverable equipment charge of €150.", "\n\n(In order to purchase a TV product from Virgin Media, Freedom Broadband and Anytime Mobile customers must sign up to one of our combined TV, Broadband and telephony bundles, which are subject to a 12 month contract.)", "\n\nInformation correct at 05/2017\n\nRed House Experience\n\nThe Red House Experience is available to all Virgin Media residential customers. ", "The Red House Experience will be offered at no additional charge if you are a new customer where self install is not available at your address or you are an existing customer who needs a maintenance visit to fix a fault. ", "If you request a Red House Experience there will be a charge of €50.", "\n\nSpecial Offers\n\nFree connection: Offer applies to new customers who self-install and new customers where self install is not available at your address. ", "If you choose not to self-install a €50 charge applies. ", "Existing customers can avail of free connection if ordering or upgrading to our Virgin TV service, or ordering any broadband and home phone bundle if they choose to self install. ", "Free connection offer ends April 30th 2018.", "\n\nAll of the offers listed below are available to new customers ordering our services online and choosing self-install. ", "After the offer period, normal monthly rate will apply thereafter. ", "A 12 month contract applies when you subscribe to any offer. ", "All Offers end April 30th 2018.", "\n\n€25 off a month for 12 months: This offer is only available to new customers ordering a new Virgin TV, Broadband and home phone pack.", "\n\n€15 off a month for 6 months: This offer is only available to new customers ordering a new Broadband and home phone pack.", "\n\n€36 off a month for 12 months: This offer is only available to new customers ordering a new Virgin TV, Broadband and home phone pack with Full House Sport and Movies.", "\n\nCustomers downgrading any element of their current package will not be eligible for advertised discount offers.", "\n\nVirgin Full House Sky Sports and Cinema:\n\nThe Full House Sky Sports and Cinema Bundle is priced at €99 for 12 months, the price thereafter will change to €135. ", "This offer is available to New Virgin Media Customers. ", "This offer is also available to existing Virgin Media customers purchasing either BB, HP or TV in addition to their existing package. ", "The Full House Sky Sports and Cinema Bundle is subject to a new subscription contract for 12 months. ", "Existing customer will lose any existing discounts associated to with old bundle. ", "You’ll see the monthly cost on your bill. ", "Offer end 30/04/2018\n\nVirgin Media TV & On Demand\n\nAn installation fee of €60 applies for each additional point ordered unless an active cable outlet point is already in place.", "\n\nA HD TV is required to enjoy the benefit of our HD service.", "\n\nTo avail of Sky Sports &/or Sky Movies HD you must first have a subscription to Virgin Media Ireland’s HD service or Virgin TV.", "\n\nVirgin Media On Demand You must have a compatible Virgin Media set top box. ", "If your box is not compatible you can order a new one by contacting us on 1908. ", "A charge may apply for the new box.", "\n\nIf you order a movie using On Demand a charge will apply. ", "We will confirm the cost of the movie before you buy it. ", "The charge will appear on your next bill.", "\n\nReplay TV available on selected channels\n\nVirgin TV Anywhere is subject to device registration on a maximum of 2 devices in addition to your set top box. ", "Virgin TV Anywhere service includes 80 channels available to watch Out of Home over 3G, 4G and public W-Fi networks. ", "Virgin TV Anywhere requires your device to have iOS7 or above for Apple products & OS.4.0.3 or above for Android, Windows 10 devices & is available to Virgin Media Ireland customers with Virgin Media Ireland TV.", "\n\nInformation correct at 01/2017.", "\n\nVirgin Media Broadband\n\nIreland’s ultra fast broadband: Offering speeds of 360Mb expected average speed during peak times of at least 300Mb on a wired connection.", "\n\nOther factors that may impact the actual speed experienced include the connection from your device(s) to the cable modem & the websites visited. ", "Wi-Free: When you sign up for Virgin Media’s Broadband service your modem will automatically offer a second signal for Wi-Free. ", "If you would prefer your modem was not available to other Virgin Media customers visiting your home you can opt out at any time by logging into My Virgin Media Ireland. ", "If you choose to opt out, your modem will not offer a Wi-Free service nor will you be able to connect to other Wi-Free networks. ", "You must be a Virgin Media Broadband customer & in the home of another participating Virgin Media Broadband customer to avail of the Wi-Free service. ", "All Virgin Media Broadband customers can connect to Wi-Free. ", "Wi-Free will give you speeds of 2.5Mb download & 0.5Mb upload. ", "Up to 3 members of a Virgin Media household can connect to Wi-Free at a time. ", "5 Virgin Media customers can connect to a single modem at a time. ", "The Wi-Free service is subject to our Acceptable Usage Policy. ", "These terms & conditions are in addition to Virgin Media Ireland’s General Terms & Conditions, a copy of which is available here\n\nLimited Broadband services: These services have a monthly usage allowance of 30GB. ", "If you exceed the usage allowance in any month we will automatically upgrade you to the nearest pack that best meets your needs. ", "Before upgrading we will:\n\n- Send you an email or text message notifying you the first time you exceed the allowance.", "\n\n- The next time you reach 70% of your allowance we’ll send you an email or text message letting you know that you are close to exceeding your limit again. ", "We won’t communicate with you thereafter about your usage. ", "We suggest you monitor your usage using the tool available in My Virgin Media.", "\n\n- In order to send you these notifications you must provide us with a valid email address or mobile phone number when buying this service. ", "For further details on how we may use your email address, or mobile phone number please refer to our Consumer Privacy Policy.", "\n\n- If you exceed your monthly allowance on two occasions we shall automatically upgrade you to the Broadband pack that best meets your needs.", "Additional information about our broadband\n\nAdditional information about our broadband\n\nOur Internet speeds\n\nMaximum speeds on our network: When we advertise a broadband speed we mean what we say, this will be the maximum download speed you can get on our network.", "\n\nNormal speeds on our network: As we promise in our advertising, the expected average download speed you typically get at peak times will be:\n\n- on our 240Mb product 180Mb\n\n- On our 360Mb product 300 Mb.", "\n\nUpload speeds will be 24Mb for our 240Mb product and 36Mb for our 360Mb product.", "\n\nMaximum and normal speeds assume all technologies are working at optimum speeds; in practice numerous factors beyond our control can cause speeds to vary. ", "Should you wish to contact us to get further information in relation to our speeds please call us on 1908.", "\n\nWe may as part of normal network performance carry out traffic management as part of general network maintenance including the management of any network congestion. ", "These activities do not impact on the quality of the internet service we provide to you and do not impact on your privacy or the protection of your personal data.", "\n\nWe may also be legally required to carry out traffic management when directed by any court, tribunal, regulatory body, police authority or other competent authority as part of any proceedings or investigation. ", "This may require us in these limited circumstances to disclose communications transmitted via our services to such authorities which may include personal data.", "\n\nFreetime mobile call pack provides free off-peak calls to Irish mobiles and fixed landlines as well as 400 off-peak minutes per month to fixed landline numbers in 22 international destinations including USA and Canadian mobile numbers. ", "Excludes calls to premium rate, SMS and non-geographic numbers. ", "Calls made outside of the call pack minutes are charged at our current call rates.", "\n\nMobile World: provides unlimited free calls to local, national and Irish mobile numbers and to mobile and fixed landline numbers in 22 international destinations. ", "Excludes calls to premium rate, SMS & non-geographic numbers. ", "A fair usage policy of 6,000 minutes a month applies. ", "Calls made above this limit are charged at our standard rates. ", "A fair usage policy of 6,000 minutes a month applies to local, national and Irish mobile number calls.", "\n\nA fair usage policy of 6,000 minutes a month applies to Anytime Mobile,Anytime World, Freetime Mobile and Mobile World packs.", "\n\nThere is a charge of €30 for each phone handset. ", "Virgin Media Ireland guarantees the handset for the first 6 months & faults thereafter are the responsibility of the customer.", "\n\nInformation correct at 06/2017.", "\n\nEquipment\n\nA €60 connection fee applies for each TV set top box & for each Broadband or Home Phone service ordered unless you qualify for free connection. ", "This will appear as an ‘equipment activation fee’ on your bill. ", "A €60 connection fee applies for each Digital+ box & a €90 connection fee for each Digital+ HD box used for multiroom viewing. ", "Equipment remains the property of Virgin Media Ireland so there is no charge for service technician visits when the fault is related to our network or equipment.", "\n\nFlash Sale Terms & Conditions\n\nOffer only available to new customers who subscribe to either Virgin TV, Broadband and Home Phone bundle or a Broadband and Home Phone bundle, on a 12 month contract during the period 16th – 28th March 2018.", "\n\nVirgin Media will apply a €50 credit to your second bill.", "\n\nOffer subject to availability and not applicable to any downgrades or cancellations of service.", "\n\nAvailability at your address:\n\nOur network’s always growing, so we’ll have your area covered soon enough. ", "Enter your contact information, and we’ll let you know when you can get connected to the fastest broadband network in Ireland." ]

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[ "Gmina Racławice\n\n__NOTOC__\nGmina Racławice is a rural gmina (administrative district) in Miechów County, Lesser Poland Voivodeship, in southern Poland. ", "Its seat is the village of Racławice, which lies approximately east of Miechów and north-east of the regional capital Kraków.", "\n\nThe gmina covers an area of , and as of 2006 its total population is 2,514.", "\n\nVillages\nGmina Racławice contains the villages and settlements of Dale, Dosłońce, Dziemierzyce, Głupczów, Górka Kościejowska, Góry Miechowskie, Janowiczki, Klonów, Kościejów, Marchocice, Miroszów and Racławice.", "\n\nNeighbouring gminas\nGmina Racławice is bordered by the gminas of Działoszyce, Miechów, Pałecznica, Radziemice, Skalbmierz and Słaboszów.", "\n\nReferences\nPolish official population figures 2006\n\nRaclawice\nCategory:Miechów County" ]

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

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[ "/*\n * GRUB -- GRand Unified Bootloader\n * Copyright (C) 2010 Free Software Foundation, Inc.\n *\n * GRUB is free software: you can redistribute it and/or modify\n * it under the terms of the GNU General Public License as published by\n * the Free Software Foundation, either version 3 of the License, or\n * (at your option) any later version.", "\n *\n * GRUB is distributed in the hope that it will be useful,\n * but WITHOUT ANY WARRANTY; without even the implied warranty of\n * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n * GNU General Public License for more details.", "\n *\n * You should have received a copy of the GNU General Public License\n * along with GRUB. ", " If not, see <http://www.gnu.org/licenses/>.", "\n */\n\n#include <config.h>\n#include <grub/dl.h>\n#include <grub/env.h>\n#include <grub/kernel.h>\n#include <grub/misc.h>\n#include <grub/emu/misc.h>\n#include <grub/disk.h>\n\nconst int grub_no_modules = 1;\n\nvoid\ngrub_register_exported_symbols (void)\n{\n}\n\ngrub_err_t\ngrub_arch_dl_check_header (void *ehdr)\n{\n (void) ehdr;\n return GRUB_ERR_BAD_MODULE;\n}\n\ngrub_err_t\ngrub_arch_dl_relocate_symbols (grub_dl_t mod, void *ehdr,\n\t\t\t Elf_Shdr *s, grub_dl_segment_t seg)\n{\n (void) mod;\n (void) ehdr;\n (void) s;\n (void) seg;\n return GRUB_ERR_BAD_MODULE;\n}\n\n#if !", "defined (__i386__) && !", "defined (__x86_64__)\ngrub_err_t\ngrub_arch_dl_get_tramp_got_size (const void *ehdr __attribute__ ((unused)),\n\t\t\t grub_size_t *tramp, grub_size_t *got)\n{\n *tramp = 0;\n *got = 0;\n return GRUB_ERR_BAD_MODULE;\n}\n#endif\n\n#ifdef GRUB_LINKER_HAVE_INIT\nvoid\ngrub_arch_dl_init_linker (void)\n{\n}\n#endif\n\n" ]

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[ "Living in the tension\n\n10/31/2014\n\n\"I, therefore, the prisoner in the Lord, beg you to lead a life worthy of the calling to which you have been called, with all humility and gentleness, with patience, bearing with one another in love, making every effort to maintain the unity of the Spirit in the bond of peace.\" (", "Ephesians 4:1-3)\n\nBy BISHOP ROBERT HAYES Jr.\n\nToday I feel compelled to address what I believe is the most volatile issue in U.S. culture and within our denomination: human sexuality. ", "More specifically: homosexuality and same-gender marriage.", "\n\nDebate has intensified since the recent Supreme Court decision that made it possible for same-gender couples to legally marry in five states, including here in Oklahoma.", "\n\nThis subject is so provocative that mere mention of the topic can trigger strong emotions and sides are chosen. ", "There seems little tolerance by people of any view for those who hold a different opinion, or for those who are neutral. ", "And silence on the subject is not a helpful response.", "\n\nWe know that our United Methodist Church says the practice of homosexuality is \"incompatible with Christian teaching,\" (paragraph 161.f, Book of Discipline) and that marriage is \"shared fidelity between a man and a woman\" (paragraph 161.b, Book of Discipline). ", "But the U.S. legal system and the voices that cry out for equality and justice from their perspective are saying something totally different.", "\n\nThe tension between these two stances literally has dominated our Church’s conversation for a long, long time. ", "Until we acknowledge and address the anger, pain, and passion generated by this subject, it will continue to divide us.", "\n\nYet a way forward remains unclear. ", "I admit that I have no easy answers. ", "I am not suggesting a fix-it-all solution within these few paragraphs.", "\n\nAs a bishop in the Church, I believe that I have an obligation to voice hope and reassurance in the midst of our differences.", "\n\nI feel there is wisdom available to us in the lessons woven into the fabric of our Christian history — lessons that will help us to see these issues from another perspective. ", "They may even teach us how to treat one another as we search for answers to our future.", "\n\nDivision and problems are not new\n\nWhen you look at the history of the Christian church, you will discover that controversy, disagreement, and discord were present from the very beginning. ", "From the moment the 12 were sent out by Jesus to \"make disciples\" (Matthew 28:19), there were problems.", "\n\nA primary hindrance was Rome itself. ", "The empire viewed the Christian movement with suspicion, believing it was an effort to overthrow that system of government. ", "So persecution was the way they dealt with this newfound faith.", "\n\nAnother great obstacle was the Jewish religion. ", "The Pharisees and rabbis saw an imminent threat to their authority in the masses of people who were following Jesus. ", "They sought to crush that perceived menace wherever it existed, giving rise to prosecutors such as Saul.", "\n\nEven the question of who was eligible to be a disciple sparked arguments.", "\n\nSome members in the early church insisted that only Jews could be followers of Christ, but Acts 8, 9, and 10 paint a different picture. ", "Stephen baptizes the Ethiopian; Paul is converted on the road to Damascus and chosen as the \"apostle to the Gentiles\"; Peter converts all the members of Cornelius’ household and preaches Good News to non-Jewish believers.", "\n\nAdditional problems in that first era included the role of women in the new movement, the practice of circumcising those who converted, eating food forbidden by Jewish law, and a host of other issues. ", "Yes, there was a multitude of problems that plagued the early church.", "\n\nMy point is this: Somehow those early Christians found a way to live together amid the tension of their differences!", "\n\nWhat did they have that enabled them to overcome their arguments and disputes? ", "What was the key to their success? ", "I often contemplate those questions.", "\n\nAnd precisely at that point, the passage Ephesians 4:1-3 comes to me!", "\n\nA plan of action\n\nThe author of the letter to the church at Ephesus makes sure his readers understand that unity is his theme. ", "But it is not a form of unity that declares everyone must think alike. ", "Rather, it is the unity demonstrated in the virtues befitting a person who follows Christ: humility, gentleness, and patience.", "\n\nThe writer goes on to say that we should make every effort to \"pour out ourselves for each other in acts of love, alert at noticing differences and quick at mending fences.\" (", "The Message)\n\nThis scripture has led me to action. ", "I will pursue a dialogue with individuals in our Conference, scheduling times to meet together and discuss this controversial subject that creates such discord among us.", "\n\nEarly next year I will invite both pastors and laity to talk with me and with each other, not in an effort to change anyone’s mind, but committed to find ways that we can be the Body of Christ, working together — ways we can live faithfully within the tension that exists within the Church and our society.", "\n\nWe must find the path that leads us to the unity that was present in the early church. ", "We owe it to the Church we love to do this.", "\n\nAnd for me personally, I intend to govern my ministry among you by trying to fulfill the duties set forth in paragraph 403.e of the Book of Discipline: A bishop should have … \"a passion for the unity of the church. ", "The role of the bishop is to be the shepherd of the whole flock and thereby provide leadership toward the goal of understanding, reconciliation, and unity within the church — The United Methodist Church and the church universal.\"" ]

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[ "La lesión de Samuel Umtiti estará dos meses después de haber sufrido un pinchazo muscular en la jugada del gol de Maxi Gómez en una carrera por la banda con Iago Aspas. ", "Así lo ha podido saber MD y así lo ha adelantado en primicia, haciéndose eco varios medios a los pocos minutos de esta información. ", "Las pruebas médicas y el comunicado oficial del FC Barcelona confirman las ocho semanas de baja del jugador francés, a causa de una lesión muscular en el bíceps femoral de la pierna derecha.", "\n\nCon esta mala noticia la situación del Barça en cuanto al eje de su defensa queda muy tocada ya que son solo dos los futbolistas sanos en la posición: Piqué y Vermaelen. ", "El tercero en cuestión, Javier Mascherano, se está recuperando de una lesión y todavía le quedan unas dos semanas de proceso. ", "Aunque el ‘jefecito’ podría llegar al Clásico del 23 de diciembre contra el Real Madrid, la papeleta que le queda a Valverde en el eje de la defensa no es nada positiva y tendrá que pensar en alternativas para superar esta adversidad." ]

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[ "Determination of N-nitrosodimethylamine levels in some Canadian 2,4-D amine formulations.", "\nLevels of N-nitrosodimethylamine (NDMA) were determined in 112 samples of 2,4-dichlorophenoxyacetic acid, (2,4-D), formulated as the dimethylamine salt, collected over a 2 year period from products on the Canadian market. ", "A sample aliquot is partitioned with dichloromethane, and the co-extracted dimethylamine is removed by cleanup on a silica gel column. ", "The eluates containing NDMA are concentrated, an internal standard of N-nitrosodipropylamine is added, and nitrosamine levels are determined using a gas chromatograph interfaced with a thermal energy analyzer. ", "Recoveries of NDMA and N-nitrosodiethylamine spiked into samples were 103 +/- 16 and 96.3 +/- 9.8%, respectively. ", "Of the 112 samples analyzed, 92 were below 1 part per million (ppm) relative to the amount of 2,4-D in the samples, 16 were between 1 and 5 ppm, and 4 were greater than 5 ppm. ", "The gas chromatographic column used is compared to a conventional packing material for volatile nitrosamine analysis. ", "Formation of NDMA during cleanup and analysis was shown not to occur." ]

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[ "The Speex RTP payload is defined as a header, followed by any number of\nrequests to the remote encoder and all encoded speech frames.", "\n\n+--------+----------+----------------+\n| Header | Requests | Speech data... |\n+--------+----------+----------------+\n\nThe header contains only the number of frames sent \nencoded in 6 bits\n\n 0 1 2 3 4 5 \n+-+-+-+-+-+-+\n| NB frames |\n+-+-+-+-+-+-+\n\nThere can be any number of requests of the form\n\n 0 1 2 3 4 5 6 7 0 1\n+-+-+-+-+-+-+-+-+-+-+\n|R| ReqID | ReqVal |\n+-+-+-+-+-+-+-+-+-+-+\n\nwhere R is 1 when a request is following and 0 when there is no more\nrequest. ", "Each request (if R=1) is composed of a 4-bit request ID (ReqID) and\na 5-bit value (ReqVal)\n\nPossible values for ReqID are:\n 0: REQ_PERSIST ReqVal=1 for persistent requests/mode selection, \n 0 otherwise\n 1: PERSIST_ACK Acknowledge a REQ_PERSIST from the other end, \n ReqVal equals the value received\n 2: MODE Choose the encoder mode directly\n 3: QUALITY Choose the encoder quality\n 4: VBR Set VBR on (ReqVal=1) or off (ReqVal=2)\n 5: VBR_QUALITY Set the encoder quality for VBR mode\n 6: LOW_MODE Set the encoder mode for low-band (wideband only)\n 7: HIGH_MODE Set the encoder mode for high-band (wideband only)\n\nAll requests should be considered at the receiver as a suggestion and\ncompliance is not mandatory. ", "The PERSIST_ACK should be sent upon receiving a\nREQ_PERSIST request to indicate that the request has been received.", "\n\nThe speech data part contains speech frames one after the other. ", "The size of\nthe encoded frames can be found since the mode is directly encoded into each\nframe.", "\n\nFor example, a frame where we request VBR to be on with quality 8 and we\ntransmit two frames encoded at 8.35 kbps (167 bits/frame) will be:\n\n 0 1 2 3\n 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| NB=2 |1|ReqID=2| ReqVal=0|1|ReqID=3|ReqVal=8 |0| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 1 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n|end| frame 2 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 2 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 2 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 2 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| frame 2 |\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n| end frame 2 |P|P|P|P|P|P|\n+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+\n" ]

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[ "A driver jumped a curb and struck a pedestrian, reportedly severing one of her legs, on 58th Street this morning. ", "Photos: Liz Patek\n\nReader Liz Patek sends this account from a crash scene in Midtown this morning:\n\nAs I was biking through Midtown, I came across this scene on West 58th Street between Seventh and Sixth Ave. ", "It happened before I got there, I am guessing about 9/9:30 a.m. A pedestrian, a woman, was hit by the car. ", "She was on the sidewalk when she was hit. ", "According to witnesses, she was sent flying through the glass door of the restaurant, and according to their accounts, she was in pretty bad shape (her leg was severed). ", "The driver was still on the scene. ", "There was also a camera person from CBS 2 and another reporter on the scene. ", "According to another witness account, the woman appeared to be about 55-60 years of age.", "\n\nAlso, according to witnesses, they are not sure if the driver was trying to execute a three-point turn or trying to parallel park and possibly lost control/accelerated in reverse into the woman. ", "The woman was alive when ambulances took her away. ", "Again, this is all accounts from people who either witnessed the accident or arrived just after it happened.", "\n\nStreetsblog will be following up with NYPD on the outcome of their investigation.", "\n\n[2]\n\nArticle printed from Streetsblog New York City: http://www.streetsblog.org" ]

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[ " United States Court of Appeals\n Fifth Circuit\n F I L E D\n REVISED OCTOBER 27, 2005\n August 15, 2005\n UNITED STATES COURT OF APPEALS\n For the Fifth Circuit Charles R. Fulbruge III\n Clerk\n\n\n No. ", "02-10190\n\n\n\n LUCINDA G. MILLER; ELAINE KING-MILLER,\n\n Plaintiffs-Appellees,\n\n VERSUS\n\n\nTEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER, ET AL\n\n Defendants-Appellants.", "\n\n\n Appeal from the United States District Court\n For the Northern District of Texas\n\n\n\n ____________________\n\n Consolidated with\n No. ", "02-30318\n No. ", "02-30369\n ___________________\n\n\n THEODORE JOHNSON,\n\n Plaintiff-Appellee,\n\n\n\n VERSUS\n\n\n\n LOUISIANA DEPARTMENT OF EDUCATION, ET AL\n\n Defendants,\n\f LOUISIANA DEPARTMENT OF EDUCATION; STATE OF LOUISIANA;\n PRESIDENT OF LOUISIANA STATE UNIVERSITY SYSTEM;\n BOARD OF REGENTS\n\n Defendants-Appellants,\n\n and\n\n LYNN AUGUST\n\n Plaintiff-Appellee\n VERSUS\n\n SUZANNE MITCHELL, ET AL\n\n Defendants-Appellants\n\n\n _________________________________________________\n\n Appeals from the United States District Court\n For the Eastern District of Louisiana\n ________________________________________________\n\n\nBefore KING, Chief Judge and JOLLY, HIGGINBOTHAM, DAVIS, JONES,\nSMITH, WIENER, BARKSDALE, GARZA, DeMOSS, BENAVIDES, STEWART,\nDENNIS, CLEMENT, and PRADO, Circuit Judges.*", "\n\nDAVIS AND WIENER, Circuit Judges:\n\n This consolidated appeal presents the same issue we recently\n\nresolved en banc in Pace v. Bogalusa City School Board:1 Does a\n\nstate waive its Eleventh Amendment immunity from suit in federal\n\ncourt under § 504 of the Rehabilitation Act of 19732 when it\n\naccepts federal funds that are granted by Congress under authority\n\n\n *\n Judge Owen was not a member of the court when this case was\nsubmitted to the court en banc and did not participate in this\ndecision.", "\n 1\n 403 F.3d 272 (5th Cir. ", "2005) (en banc).", "\n 2\n 29 U.S.C. § 794.", "\n\n 2\n\fof the Constitution’s Spending Clause and expressly conditioned on\n\nwaiver of immunity from § 504? ", " For reasons that follow, we find no\n\nmerit in appellants’ arguments and reaffirm our conclusions in Pace\n\nthat acceptance of such federal funds operates to waive a State’s\n\nEleventh Amendment immunity under the express conditions of 42\n\nU.S.C. § 2000d-7.3\n\n\n 3\n The factual and legal background of this consolidated appeal is\naccurately and succinctly presented in the panel opinions:\n\nA. Johnson/August v. Louisiana Dep’t of Education, 330 F.3d 362, 363-\n 64 (5th Cir. ", "2003).", "\n\n Appellee Johnson was a full time student at the University\n of New Orleans (“UNO”) on financial aid. ", "He is disabled by\n a partial paralysis of his left foot. ", "In February 2000, a\n medical emergency caused Johnson to withdraw from UNO. ", "Four\n months later, UNO revoked Johnson’s eligibility for financial\n aid. ", " Johnson successfully appealed the decision. ", " The\n appeals committee, however, did not inform Johnson of its\n decision until after the fall 2000 semester had begun; the\n committee also imposed academic requirements to maintain his\n eligibility for financial aid. ", "Johnson asserts that because\n of his late start in fall semester classes, he was unable to\n comply with the academic requirements. ", "In January 2001, UNO\n denied Johnson financial aid for the spring semester.", "\n Johnson filed suit against the Louisiana Department of\n Education, the State of Louisiana, the President of the\n Louisiana State University System, the Louisiana Board of\n Regents, and UNO under 42 U.S.C. § 1983, Title II of the\n Americans with Disabilities Act, and § 504 of the\n Rehabilitation Act, alleging discrimination against disabled\n students and failure to provide reasonable accommodations.", "\n\n [Lynn] August, a blind man, worked as a computer\n instructor for the Louisiana Department of Social Services\n (“DSS”). ", " In June 2000, DSS eliminated August’s teaching\n duties, averring that August failed to submit “manual\n materials” required for use in the computer course. ", "August\n contended...that he submitted the necessary material at the\n same time as a sighted instructor whose materials were\n approved. ", "August brought various claims for damages against\n the DSS and the three state employees in their official\n capacities, including claims under the ADA and the\n Rehabilitation Act ( § 504).", "\n\n 3\n\f I. BACKGROUND\n\n Louisiana’s Department of Education (“LADOE”) and Department\n\nof Social Services (“DSS”)4 and Texas Tech University Health\n\nSciences Center (“TTUHSC”) (collectively “defendants”) appeal\n\nrulings of the district courts, which held that, by accepting\n\nfederal funds offered on explicit conditions of waiver, defendants\n\nin fact waived their right to Eleventh Amendment5 immunity pursuant\n\n\n Separate district courts in the Eastern District of\n Louisiana dismissed all claims against the defendants based\n on state sovereign immunity except for those under § 504 of\n the Rehabilitation Act. ", "The defendants appeal, arguing that\n state sovereign immunity bars the appellees’ § 504 claims.", "\n\nB. Miller v. Texas Tech University Health Sciences Center,\n 330 F.3d 691, 691 (5th Cir. ", "2003).", "\n\n King-Miller began working as an administrator and\n professor at [Texas] Tech in 1997. ", "She notified Tech that\n she suffered from a degenerative eye condition in August\n 1998; she was diagnosed as legally blind in 1999. ", "In 2000,\n she sued Tech for allegedly failing to accommodate her\n disability in violation of § 504, which prohibits\n discrimination against the disabled by programs receiving\n federal funds.", "\n\n ...Tech moved to dismiss on the basis of state sovereign\n immunity. ", "The district court denied the motion, and Tech\n took this interlocutory appeal.", "\n\n 4\n The case before the panel in Johnson was a consolidated appeal by\nLADOE and the Department of Social Services for the State of Louisiana\n(“DSS”). ", "LADOE and DSS consolidated their arguments into one brief for\nthis rehearing en banc, and therefore all arguments accredited to LADOE\nare also made on behalf of DSS.", "\n 5\n The Eleventh Amendment to the United States Constitution states:\n\n The Judicial power of the United States shall not be\n construed to extend to any suit in law or equity, commenced\n or prosecuted against one of the United States by Citizens\n of another State, or by Citizens or Subjects of any Foreign\n State.", "\n\n 4\n\fto 46 U.S.C. § 2000d-7,6 and were therefore amenable to suit in\n\nfederal court for § 504 violations. ", " Later, a panel of this court\n\nin Pace v. Bogalusa City School Board7 (“Pace I”) held that,\n\ndespite the express provision in the grant that entitlement of the\n\ngrantee to accept the funds was conditioned on such a waiver, a\n\nState did not waive Eleventh Amendment immunity from suit under §\n\n504 by accepting federal funds at a time when, based on the then-\n\ncurrent state of the pertinent case law, the State had reason to\n\nbelieve that it had no such immunity to waive. ", " Two panels of this\n\ncourt, relying on Pace I, reversed the district courts’ denials of\n\nEleventh Amendment Immunity and dismissed the plaintiffs’ claims\n\nunder § 504.8\n\n We later reheard Pace en banc and held that, then as now, a\n\nState did waive Eleventh Amendment immunity from suit under § 504\n\nby accepting federal funds under such circumstances (“Pace II”).9\n\nPrior to rehearing Pace en banc, we had agreed to rehear the\n\ninstant cases en banc, but postponed rehearing them pending our\n\n 6\n Section 2000d-7 (a)(1) provides in pertinent part:\n\n A State shall not be immune under the Eleventh Amendment of\n the Constitution of the United States from suit in Federal\n court for a violation of section 504 of the Rehabilitation\n Act of 1973...or the provisions of any other Federal statute\n prohibiting discrimination by recipients of Federal financial\n assistance.", "\n 7\n 325 F.3d 609 (5th Cir. ", "2003).", "\n 8\n See Miller v. Tex. ", "Tech Univ. ", "Health Sci. ", "Ctr., ", "330 F.3d 691 (5th\nCir. ", "2003); Johnson v. La. Dept. ", "of Educ., ", "330 F.3d 362 (5th Cir. ", "2003).", "\n 9\n 403 F.3d 272.", "\n\n 5\n\fdecision in Pace II.", "\n\n After Pace II was announced, we asked the parties in these\n\ncases to submit supplemental briefs explaining which of their\n\narguments regarding Eleventh Amendment immunity from suits under §\n\n504 remained viable and which had been foreclosed. ", " In response,\n\nthe defendants conceded that Pace II forecloses all their arguments\n\nexcept three.", "\n\n First, both LADOE and TTUHSC contend that no valid waiver of\n\nEleventh Amendment immunity occurred because, even though they\n\nreceived federal funds, none of the state agencies was expressly\n\nauthorized by state law to waive its respective state’s immunity\n\nfrom suit under § 504. ", " Second, TTUHSC contends that Pace II did\n\nnot address the issue whether § 504 and § 2000d-7 place conditions\n\non federal funds that are not reasonably related to the purpose of\n\nthe expenditure, which is part of the test for valid Spending\n\nClause legislation set forth by the Supreme Court in South Dakota\n\nv. Dole.10 Third, LADOE asserts that it did not “knowingly waive”\n\nEleventh Amendment immunity under § 2000d-7 by accepting federal\n\nfunds, contending that this argument, although rejected in Pace II,\n\nshould be reexamined in light of the Supreme Court’s subsequent\n\ndecision in Jackson v. Birmingham Board of Education.11\n\n\n II. ", " STATE IMMUNITY UNDER THE ELEVENTH AMENDMENT\n\n\n 10\n 483 U.S. 203, 207 (1987).", "\n 11\n ___ U.S. ___, 125 S. Ct. ", "1497 (2005).", "\n\n 6\n\fA. Express Authority to Waive Immunity\n\n We consider first defendants’ argument that they did not waive\n\ntheir states’ Eleventh Amendment immunity from suit under § 504\n\nbecause they lacked express authorization to do so under state law.", "\n\nDefendants do not challenge that they were authorized under state\n\nlaw to accept federal funds or that each received federal funds.12\n\nDefendants insist, however, that as state agencies, their authority\n\nto accept federal funds is insufficient to waive Eleventh Amendment\n\nimmunity, which, they argue, cannot be validly waived without\n\nexpress statutory authority.", "\n\n Defendants’ argument fails to recognize that grant programs\n\n\n\n 12\n LADOE is authorized to accept federal funds pursuant to LA. ", "REV.", "\nSTAT. ", "ANN. § ", "17:24 (C), which provides in pertinent part:\n\n The board [LADOE] is hereby designated as the State Agency\n with respect to federal funds for those programs under the\n jurisdiction of the board. ", "The State Department of Education\n shall administer and distribute all federal funds received\n for the benefit of those phases of education under the\n jurisdiction of the board. (", "emphasis added).", "\n\n Similarly, LA. ", "REV. ", "STAT. ", "ANN. § ", "46:51(6) provides that the\nDepartment of Social Services of Louisiana [DSS] may “[a]ct as the\nagent of the state to cooperate with the federal government...and\nin the administration of federal funds granted in the state to aid\nin the furtherance of any functions of the department, and be\nempowered to meet such federal standards as may be established for\nthe administration of such federal funds.” (", "emphasis added).", "\n\n Likewise, TEX. ", "EDUC. ", "CODE. ", "ANN. § ", "110.08, which governs the funding of\nTTUHSC, provides in pertinent part, “The board [of TTUHSC], in its\ndiscretion, may accept and administer grants and gifts from the federal\ngovernment...for the use and benefit of the Health Sciences Center.”", "\n\n 7\n\fbased on the Spending Clause are to be interpreted under ordinary\n\ncontractual principles.13 In these cases, the defendants were\n\nauthorized by the State to accept the benefits of substantial sums\n\nof federal Spending Clause money burdened with the clearly stated\n\ncondition under § 2000d-7 that acceptance waives immunity from suit\n\nin federal court. ", "The statutory powers of attorney provided to\n\ndefendants by their respective state legislatures to accept,\n\nadminister, and expend such federal funds necessarily includes the\n\nauthorization to accept the conditions that come along with those\n\nfunds. ", "Clothed with this authority, the defendants held themselves\n\nout to have authority from their states to comply with the\n\nconditions imposed by Congress in the statute. ", " These conditions\n\nare inseparable from the offer of the funds: The States (or their\n\nauthorized agencies) may reject the condition of waiver of Eleventh\n\nAmendment immunity by rejecting the funds, or they may accept the\n\nfunds and the conditions; they cannot, however, accept the benefits\n\nof the funds and reject the inextricably intertwined condition of\n\nwaiver by claiming post hoc that the delegation of authority to\n\naccept the funds did not carry with it the authority to waive\n\nimmunity. ", " This is hornbook contract and agency law.", "\n\n Therefore, we reject defendants’ argument that they retain\n\n\n 13\n Barnes v. Gorman, 536 U.S. 181, 186 (2002).", "\n\n 8\n\fEleventh Amendment immunity because they lacked express statutory\n\nauthority to waive their states’ Eleventh Amendment immunity.14\n\nB. Relatedness\n\n We next address TTUHSC’s argument that § 504 and § 2000d-7 are\n\nunconstitutional Spending Clause legislation because they place\n\nconditions on federal grants that are not reasonably related to the\n\npurpose of the expenditure. ", " This is often referred to as the\n\n“relatedness” prong of the Dole test for valid Spending Clause\n\nlegislation.15 According to TTUHSC, they are not governed by § 504\n\nbecause none of the federal funds they received were earmarked for\n\n§ 504 goals of preventing disability discrimination or\n\naccommodating disability. ", " TTUHSC urges that, if we determine that\n\nthe immunity waiver condition imposed by § 504 is not limited to\n\nRehabilitation Act funding but that they accompany all federal\n\nfunding, we should hold that § 504 fails the “relatedness” prong of\n\nthe Dole test.", "\n\n TTUHSC failed to raise this argument in its briefs before\n\n\n 14\n This disposition makes it unnecessary for us to consider what\neffect the Supreme Court’s decision in Lapides v. Board of Regents of\nthe University System of Georgia, 535 U.S. 613 (2002), has on this\nissue.", "\n 15\n Under Dole, conditions attached to Spending Clause legislation are\nvalid only if they are (a) attached to expenditures that benefit the\ngeneral welfare; (b) unambiguous; (c) reasonably related to the purpose\nof the expenditure to which they are attached; and (d) not in violation\nof an independent constitutional provision. ", "483 U.S. at 207-08.", "\n\n 9\n\feither the district court or the original panel of this court.", "\n\nNeither did it argue the point in its original en banc brief. ", " In\n\nPace II, we concluded that the state defendant had waived this\n\n“relatedness” argument because it failed to argue the point before\n\nthe original panel and did not argue it in its en banc brief beyond\n\na bare assertion.16 The maxim is well established in this circuit\n\nthat a party who fails to make an argument before either the\n\ndistrict court or the original panel waives it for purposes of en\n\nbanc consideration.17\n\n If we are required to address this argument because it relates\n\nto Eleventh Amendment immunity, and as such may be a\n\n“jurisdictional” defense that cannot be waived,18 we reject it. ", " We\n\nagree with the four circuit courts that have addressed this issue\n\nand concluded that, if the involved state agency or department\n\naccepts federal financial assistance, it waives its Eleventh\n\n\n 16\n 403 F.3d at 281 n.32.", "\n 17\n See Communication Workers of America v. Ector County, 392 F.3d 733,\n748 (5th Cir. ", "2004) (failure to brief an issue constitutes waiver on\nappeal); Proctor & Gamble Co. v. Amway Corp., 376 F.3d 496, 499 (5th\nCir. ", "2004) (party waived argument not included in original brief to\npanel); Cooper Ind. v. Tarmac Roofing, Inc., 276 F.3d 704, 711 (5th Cir.", "\n2002) (argument not raised before original panel waived); and Lowry v.\nBankers Life and Cas. ", "Retirement Plan, 871 F.2d 522, 525 (5th Cir. ", "1989)\n(refusing to consider an argument raised for the first time in a\npetition for rehearing). ", "See also FED. ", "R. APP. ", "P. 28 (a)(9)(A) (stating\nthat an appellant’s brief must contain “appellant’s contentions and the\nreasons for them, with citations to the authorities and parts of the\nrecord on which the appellant relies.”).", "\n 18\n See Edelman v. Jordan, 415 U.S. 651, 677-78 (1974) (because defense\nof Eleventh Amendment immunity is a jurisdictional bar to the\nplaintiff’s suit, court of appeal did not err in considering defense\nwhen it was not argued before the district court).", "\n\n 10\n\fAmendment immunity even though the federal funds are not earmarked\n\nfor programs that further the anti-discrimination and\n\nrehabilitation goals of § 504.19 Chief Judge Scirica’s persuasive\n\nopinion for the Third Circuit in Koslow is particularly helpful in\n\nexplaining this point.", "\n\n In that case, the State of Pennsylvania received federal\n\nfinancial assistance for the State Criminal Alien Assistance\n\nProgram, established to alleviate costs states incur in imprisoning\n\nillegal aliens who commit state offenses.20 The state furnished\n\nthese funds to the Pennsylvania Department of Corrections.21 The\n\nplaintiff, Mr. Koslow, was employed by the Department of\n\nCorrections as a supervisor at the prison’s water treatment plant\n\nand brought a § 504 suit against his employer for failing to\n\naccommodate his disability following a work related injury.22\n\n The state defendants argued that the federal government’s\n\ninterest in the federally funded program was too attenuated from\n\nthe general waiver of immunity set forth in § 2000d-7 respecting\n\nclaims under § 504. ", " The Koslow court disagreed and concluded that\n\nreceipt of federal funding by an agency operated as a waiver of\n\n 19\n See Barbour v. Washington Metropolitan Area Transit Authority, 374\nF.3d 1161 (D.C. Cir. ", "2004); Lovell v. Chandler, 303 F.3d 1039 (9th Cir.", "\n2002); Koslow v. Commonwealth of Pennsylvania, 302 F.3d 161 (3d Cir.", "\n2002); Jim C. V. United States, Atkins School District, 235 F.3d 1079\n(8th Cir. ", "2000) (en banc).", "\n 20\n Koslow, 302 F.3d at 166-67.", "\n 21\n Id. at 167.", "\n 22\n Id. at 165.", "\n\n 11\n\fthat agency’s Eleventh Amendment immunity even though the funds are\n\nnot earmarked for § 504 purposes. ", " The court gave three reasons for\n\nits conclusion. ", " First, the panel found that:\n\n [t]hrough the Rehabilitation Act [§ 504], Congress has\n expressed a clear interest in eliminating disability-\n based discrimination in state departments or agencies.", "\n That interest, which is undeniably significant and\n clearly reflected in the legislative history, flows with\n every dollar spent by a department or agency receiving\n federal funds. ", "The waiver of the Commonwealth’s immunity\n from Rehabilitation Act claims by Department of\n Corrections employees furthers that interest directly.23\n\n\n Second, § 2000d-7 limits the waiver to the agency or\n\ndepartment that receives federal funds and does not require waiver\n\nby other agencies or the state as a whole.24 The court concluded\n\nthat “[t]his limitation helps ensure the waiver accords with the\n\n‘relatedness’ requirement articulated in Dole.", "”25\n\n Finally, the court observed that, as a practical matter, § 504\n\nfunds received by specific state departments or agencies are\n\nfrequently not tracked, making it virtually impossible to determine\n\nhow the agency spent the federal dollars and whether the federal\n\nfunds paid for the affected employee’s salary or benefits.26\n\n For the same reasons articulated in Koslow, we reject the\n\nTTUHSC’s argument that the substantial federal financial assistance\n\n\n 23\n Id. at 175-76 (internal citation omitted).", "\n 24\n Id. at 176.", "\n 25\n Id.\n 26\n Id.\n\n 12\n\ffor education it received is unrelated to the goals of § 504 and\n\ntherefore fails Dole’s “relatedness” requirement.", "\n\nC. Jackson v. Birmingham Board of Education\n\n Finally, LADOE argues that it did not “knowingly” waive\n\nEleventh Amendment immunity from suit in federal court under § 504\n\nin accordance with § 2000d-7 by accepting federal funds. ", " As LADOE\n\nacknowledges, this argument was considered and rejected by our en\n\nbanc majority in Pace II.27 LADOE nevertheless argues that the\n\nSupreme Court’s decision in Jackson v. Birmingham Board of\n\nEducation,28 requires us to re-examine the issue, repudiate the\n\nreasoning of Pace II, and adopt the analysis of Pace I. In Pace I,\n\nthe panel held that the state defendant did not “knowingly” waive\n\nits Eleventh Amendment immunity by accepting federal funds because,\n\nat the time it received those funds, the prevailing legal\n\nauthorities suggested that it had no Eleventh Amendment immunity\n\nfrom suits under § 504.29\n\n In rejecting the Pace I panel’s syllogism, the en banc court\n\nin Pace II held that, in accordance with Pennhurst State School &\n\nHospital v. Halderman,30 “the only ‘knowledge’ that the Court is\n\nconcerned about is a state’s knowledge that a Spending Clause\n\ncondition requires waiver of immunity, not a state’s knowledge that\n\n 27\n 403 F.3d at 282–85.", "\n 28\n ___ U.S. ___, 125 S. Ct. ", "1497 (2005).", "\n 29\n 325 F.3d at 617.", "\n 30\n 451 U.S. 1 (1981).", "\n\n 13\n\fit has immunity that it could assert.", "”31 We also stated in Pace II\n\nthat, “[a]t bottom...if Congress satisfies the clear statement\n\nrule, the knowledge prong of the Spending Clause waiver analysis is\n\nfulfilled.", "”32 Finding that § 504 and § 2000d-7 clearly and\n\nunambiguously conditioned the receipt of § 504 funds on waiver of\n\na State’s Eleventh Amendment immunity from suits grounded in § 504,\n\nwe held that the State had “knowingly waived” immunity from suits\n\nunder § 504.33\n\n LADOE does not argue that § 504 and § 2000d-7 fail the “clear\n\nstatement rule” of Pace II; rather LADOE contends that in Jackson\n\n(decided after Pace II), the Supreme Court repudiated this “clear\n\nstatement rule” and replaced it with a “notice” rule. ", " In Jackson,\n\nthe male coach of a high school’s girls basketball team asserted a\n\nretaliation claim against the local school board, grounding his\n\nclaim in Title IX. ", " The school board argued that, because\n\nretaliation claims are not expressly authorized by the language of\n\nTitle IX, it was not put on notice of the potential for retaliation\n\nclaims under the statute.34\n\n The Supreme Court agreed that, because Title IX was passed\n\npursuant to the Spending Clause, “private damage actions are\n\n\n 31\n 403 F.3d at 279 (emphasis in original); see also Dole, 483 U.S. at\n207 (quoting Pennhurst).", "\n 32\n 403 F.3d at 279.", "\n 33\n Id. at 282–85.", "\n 34\n 125 S. Ct. ", "at 1508–09.", "\n\n 14\n\favailable only where recipients of federal funding had adequate\n\nnotice that they could be liable for the conduct at issue.", "”35\n\nConsonant with its holding in Pennhurst, the Court reiterated its\n\nposition that a State must be aware of the conditions imposed on\n\nreceipt of federal funds for there to be “knowing acceptance” of\n\nthose conditions.36 Acknowledging that Title IX is silent on the\n\nquestion of the fund recipient’s amenability to retaliation suits,\n\nthe Court looked to its prior decisions dealing with the scope of\n\nremedies available under Title IX and concluded (in the absence of\n\na “clear statement”) that the school board nevertheless had\n\nsufficient “notice” because:\n\n [T]he Board should have been put on notice by the fact\n that our cases since Cannon [v. University of Chicago,\n 441 U.S. 677 (1979)], such as Gebser [v. Lago Vista\n Independent School Dist., ", "524 U.S. 274 (1998)] and Davis\n [v. Monroe County Bd. ", "of Ed., ", "526 U.S. 629 (1999)], have\n consistently interpreted Title IX’s private cause of\n action broadly to encompass diverse forms of intentional\n sex discrimination.37\n\n LADOE would have us read Jackson as the Court’s abandoning of\n\nCollege Savings Bank’s “clear statement rule” that we applied in\n\nPace II, and replacing it with a “notice” test of what the\n\nrecipients of the funds should have known at the time the funds\n\nwere accepted. ", " We cannot read such a sweeping change into the\n\ncourt’s opinion in Jackson. ", " Title IX, the statute at issue in\n\n\n 35\n Id. (internal citation omitted).", "\n 36\n Id. at 1509 (quoting Pennhurst, 451 U.S. at 17).", "\n 37\n Id.\n\n 15\n\fJackson, is silent (or at least ambiguous) regarding retaliation;\n\nin contrast, the Spending Clause statutes we addressed in Pace II\n\nwere clear and unambiguous regarding waiver: Section 2000d-7\n\nexpressly and unambiguously states that parties waive their\n\nEleventh Amendment immunity to actions under § 504 by accepting\n\nfederal funds. ", " Moreover, there is no language in Jackson that can\n\nbe pointed to in support of a conclusion that the Court desired to\n\nmodify, much less repudiate, the well-established rule with such a\n\nlong and distinguished history laid out in Pennhurst, Dole, and\n\nCollege Savings Bank that “if Congress intends to impose a\n\ncondition on the grant of federal moneys, it must do so\n\nunambiguously,” and “speak with a clear voice.", "”38 Stated\n\ndifferently, nothing in Jackson undermines Pace II’s holding that\n\na clear statement like the one found in § 2000d-7 is sufficient to\n\nsatisfy the “knowing” requirement for a waiver to be valid.” ", " Even\n\nif Jackson can be interpreted as standing for the proposition that\n\na clear and unambiguous statement from Congress is not the\n\nexclusive road to a “knowing waiver,” it cannot be read to call\n\ninto question the holding in Pace II that the presence of a clear\n\nstatement is sufficient to satisfy the need for a waiver to be\n\n“knowing.” ", " Accordingly, LADOE’s Jackson argument in this regard\n\nfails.", "\n\n III. ", " CONCLUSION\n\n\n 38\n Pennhurst, 451 U.S. at 17 (citations omitted); see also Dole, 483\nU.S. at 207.", "\n 16\n\f We hold that LADOE, DSS, and TTUHSC are not entitled to\n\nEleventh Amendment immunity in these consolidated cases. ", " We\n\ntherefore affirm the district courts’ denials of defendants’\n\nmotions to dismiss plaintiffs’ claims under § 504 on the basis of\n\nsuch immunity, and we remand the cases to the district courts from\n\nwhence they came for further proceedings.", "\n\nAFFIRMED AND REMANDED.", "\n\n\n\n\n 17\n\fEDITH H. JONES, Circuit Judge, joined by JOLLY, SMITH, GARZA,\n\nDeMOSS and CLEMENT, Circuit Judges, concurring in part and\n\ndissenting in part:\n\n\n\n The en banc decision in Pace v. Bogalusa City School\n\nBoard, 403 F.3d 272 (5th Cir. ", "2005), held that a state voluntarily\n\nand knowingly waived its Eleventh Amendment immunity, as a matter\n\nof federal law, from suits for damages in federal court by accept-\n\ning federal Rehabilitation Act funds made subject to 42 U.S.C.\n\n§ 2000d-7. ", " We adhere to the arguments in the dissent from that\n\ndecision. ", " We concur, however, in the court’s disposition of the\n\nstates’ fallback arguments in these cases.39\n\n\n\n\n 39\n Of course, the court’s conclusion here that state law properly\nauthorized the state officials to execute contracts in no way\nundercuts the arguments in dissent from Pace that the federal law\nduring the relevant time period (1996 through 1998) did not\ncommunicate to the states that they possessed Eleventh Amendment\nsovereign immunity to waive. ", "See Pace, 403 F.3d at 301 (Jones, J.,\ndissenting).", "\n 18\n\f" ]

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[ "Ilmir Yakupov\n\nIlmir Fanilyevich Yakupov (; born 17 March 1994) is a Russian football player.", "\n\nHe made his professional debut in the Russian Football National League for FC Sibir Novosibirsk on 11 July 2015 in a game against FC Volgar Astrakhan.", "\n\nReferences\n\nExternal links\n Player page on the FNL website\n\nCategory:1994 births\nCategory:People from Ufimsky District\nCategory:Living people\nCategory:Russian footballers\nCategory:FC Sibir Novosibirsk players\nCategory:Association football forwards\nCategory:FC Ufa players\nCategory:FC Avangard Kursk players" ]

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

[ 0.0024625842925161123, 0.0015611909329891205, 0.0007408828823827207 ]

[ "Introduction {#s1}\n============\n\nEndovascular recanalization therapy (ERT) has been adopted as standard stroke care in patients with acute ischemic stroke ([@B1]--[@B6]). ", "Time to recanalization and degree of recanalization are the most important predictors of clinical outcomes after ERT ([@B7]). ", "Before recanalization, an effort to reduce the time from symptom onset to reperfusion is critical for penumbral salvage. ", "After recanalization, an effort to control BP is important for penumbral salvage and inhibition of hemorrhagic transformation.", "\n\nAdequate blood pressure management after recanalization is important for reducing reperfusion injury and improving outcomes in patients with acute ischemic stroke. ", "Both higher and lower baseline systolic blood pressures (SBPs) are associated with poor outcomes in patients with acute ischemic stroke after ERT ([@B8]). ", "Because of impaired cerebrovascular autoregulation after ischemic stroke, BP fluctuation directly affects the ischemic brain tissue, leading to the growth of the infarct core and poor functional outcomes ([@B9]).", "\n\nIncreased BPV is associated with sympathetic overactivity, hyperglycemia, immunosuppression, and coagulopathy ([@B10]). ", "Prior studies have indicated that high BPV is associated with poor neurological outcomes in acute ischemic stroke patients not indicated for ERT, non-recanalized patients after intravenous thrombolysis (IVT) for ICA occlusion, or patients with incomplete recanalization after ERT ([@B9], [@B11]--[@B13]). ", "The effect of BPV on the clinical outcomes in recanalized patients after ERT had not been evaluated before.", "\n\nA paucity of studies has investigated postreperfusion BPV and clinical outcomes after ERT. ", "In addition, data are lacking whether the effects of BPV on clinical outcomes are different in patients with different baseline collateral statuses. ", "In this study, we evaluated the effect of 24 h BPV on clinical outcomes in the acute ischemic stroke patients with successful recanalization after ERT.", "\n\nMethods {#s2}\n=======\n\nWe retrospectively selected patients from the database at a single hospital-based stroke registry. ", "The hospital institutional review board approved this retrospective study (B-1705-399-103). ", "This study included patients with anterior circulation occlusion who underwent ERT based on multiphase CT angiography (CTA) and achieved successful recanalization (thrombolysis in cerebral ischemia \\[TICI\\] ≥ 2b) at the institute between April 2015 and February 2017. ", "Baseline demographic and clinical information, including neurological outcomes and imaging data, were obtained from the registry. ", "Patients who underwent ERT because of posterior circulation occlusion or bilateral occlusion were excluded from the analysis.", "\n\nMultiphase CTA imaging was performed using a 256-slice multi-detector CT scanner (Brilliance iCT; Philips) equipped with a collimator of 128 × 0.625 mm, 120 kV, and 90 mAs. ", "The first phase of multiphase CTA was acquired from the aortic arch to the vertex during the peak arterial phase. ", "After a 4-s delay, patients were scanned from the skull base to the vertex for 3 s in the second phase (during the peak venous phase) and the third phase (during the late venous phase). ", "A total of 90 mL of contrast agent was injected at a rate of 5 mL/s.\n\nThe collateral status was evaluated by pial arterial filling in the symptomatic hemisphere compared with the unaffected hemisphere. ", "A 6-point scale was developed to assess collateral circulation in terms of the phase delay, vascular extent, and vascular prominence. ", "The scoring system was validated with good reliability in a previous study by Menon et al. ([", "@B14]). ", "The collateral score was established using a two-reader consensus. ", "Collateral degrees were dichotomized based on the pial arterial filling score. ", "A score of 0--3 indicates a poor collateral status, and a score of 4--5 indicates a good collateral status.", "\n\nBP was measured every 15 min for 2 h; then, every 30 min for 6 h; and subsequently, every hour for 24 h after IVT. ", "In the absence of any clinical event, BP was evaluated at least once every hour in the non-paretic arm of the patient in the stroke and intensive care units. ", "A non-invasive electronic monitoring device that automatically recorded the measurements in the electronic medical record was used. ", "Acute BP measurement and management followed the current guidelines proposed by the American Stroke Association and the Korean Stroke Society ([@B15]). ", "Before recanalization, blood pressure was not lowered unless exceeds 220 mmHg for SBP and 120 mmHg for diastolic blood pressure (DBP). ", "If indicated for IVT, blood pressure was controlled under 185 mmHg for SBP and 110 mmHg for DBP. ", "Once recanalized successfully after ERT, SBP was controlled over 100 mmHg and below 160 mmHg. ", "A method and a level of BP control was left to an attending clinician\\'s decision.", "\n\nWe calculated the following parameters of SBP, DBP, mean BP (MBP), and pulse rate (PR) 24 h after admission: mean, standard deviation (SD), coefficient of variation (CV, SD/mean), and variation independent of the mean (VIM). ", "SD and CV were frequently used and validated in previous studies to measure BPV ([@B11], [@B16], [@B17]). ", "Since SD and CV are positively correlated with mean BP, it is necessary to derive a supplemental variable uncorrelated with mean levels. ", "VIM is a transformation of SD and is devised to be independent of mean. ", "VIM is calculated as *k* × SD/(mean), where ß is derived from the regression coefficient of the plot of the natural SD logarithm (y-axis) on the natural mean logarithm (x-axis) ([@B18]). ", "We corrected VIM using the following equation:\n\nCorrected VIM\n\n=\n\n(\n\nVIM\n\n×\n\n mean of CV\n\n)\n\n/meanof VIM\n\nEarly neurological improvement (ENI) is defined as ≥50% or as an 8-point reduction from the baseline in National Institutes of Health Stroke Score (NIHSS). ", "A certified neurologist determined the neurological status of patients on days 1 and 7 using NIHSS. ", "For patients discharged prior to 7 days post-injury, the neurological assessment was performed at the day of discharge using NIHSS. ", "Functional outcomes were assessed using modified Rankin scale (mRS) by a neurologist at the outpatient clinic or by a trained nurse if a follow-up visit was not available after 3 months. ", "A favorable outcome was defined as modified Rankin scale score (mRS) ≤ 2.", "\n\nStatistical Analyses\n--------------------\n\nBaseline characteristics (age, sex, initial stroke severity, stroke risk factors, stroke mechanism, occlusion site, onset to recanalization time, and clinical outcome variables) were integratedly analyzed with the collateral circulation status and functional outcome. ", "Median or mean values of BPV parameters were compared according to occlusion site, stroke mechanism, baseline collateral status, and functional outcome. ", "Chi-squared or Fisher\\'s exact test was used to analyze categorical variables; independent *t*-test, or Mann--Whitney *U*-test was used to analyze continuous variables. ", "To estimate odds ratio (OR) and 95% confidence interval (CI) for the independent association of each BPV parameter with clinical outcomes, ordinal logistic regression analysis was performed. ", "Because there was a significant interaction between BPV parameters and the collateral status, the analysis was performed with stratification based on the collateral status. ", "Variables for adjustments were selected based on univariate analysis with a *p* ≤ 0.05. ", "Among the selected variables (age, sex, initial NIHSS, DM, current smoking, and occlusion site), variables that did not contribute to the model were excluded using a likelihood ratio test. ", "As a result, age, sex, initial NIHSS, and occlusion site were included in the final model. ", "Goodness-of-fit was evaluated using the Hosmer--Lemeshow test. ", "The predictive logistic model was internally validated by bootstrap simulations. ", "Analyses were performed using Stata version 13.0 (StataCorp, Austin, TX, USA). ", "All tests were 2-sided, and a *p* ≤ 0.05 was considered significant.", "\n\nResults {#s3}\n=======\n\nA total of 90 patients with acute ischemic stroke due to anterior circulation occlusion, who achieved successful recanalization (≥TICI 2b), were included in the analysis. ", "The median number of BP measurements was 31 (interquartile range, 26--37) and mean time from IAT to admission was 63.5 ± 46.6 min.", "\n\nThe mean age of the study subjects was 72.3 ± 11.8 years, and 60.0% of subjects were men. ", "The initial median systolic blood pressure was 149.0 (interquartile range, 134.0--166.0) mmHg. ", "The median baseline NIHSS score was 14.7 ± 5.5, and atrial fibrillation (51, 58.0%) was the most common risk factor in the patients. ", "The occlusion sites were presented in order of frequency as follows: M1 segment of middle cerebral artery (MCA) (49, 54.4%); internal carotid artery (ICA) (26, 28.9%); and M2 segment of MCA (15, 16.7%). ", "Anterior cerebral artery occlusion was noted in three patients, all of whom had tandem occlusion of the MCA. ", "Tandem occlusion of ICA and MCA was found in four patients. ", "The median time from symptom onset to recanalization was 216.0 min (interquartile range, 142.0--317.0). ", "The mean SBP during 24 h after admission was 128.8 ± 11.9. ", "Parenchymal hemorrhage ([@B19]) was observed in 16 patients (17.8%).", "\n\nIn addition, 40 patients (44.4%) had ENI on day 1, while 60 patients (66.7%) showed ENI on day 7 or discharge; 49 patients (54.4%) had poor collateral circulation. ", "Patients with poor collateral circulation had a significantly higher baseline NIHSS, were more likely to have coronary artery disease, and were less likely to have a smoking habit ([Table 1](#T1){ref-type=\"table\"}). ", "Moreover, patients with poor collateral circulation were less likely to have ENI at days 1 and 7 and favorable outcomes at month 3 ([Table 1](#T1){ref-type=\"table\"}).", "\n\n###### \n\nBaseline characteristics of the study subjects based on the collateral status and functional outcome.", "\n\n **Total** **Baseline collateral status** **Functional outcome at 3 month** \n ---------------------------------------------------------------- ---------------------- -------------------------------- ----------------------------------- -------- ---------------------- ---------------------- --------\n **DEMOGRAPHICS** \n Age, y, mean ± SD or median (IQR) 72.3 ± 11.8 74.8 ± 11.1 69.3 ± 12.1 0.03 78.0 (72.0--85.0) 68.0 (60.0--76.0) \\<0.01\n Male, *n*(%) 54 (60.0) 27 (55.1) 27 (65.9) 0.41 18 (43.9) 36 (73.5) 0.01\n Initial systolic blood pressure at ER, median (IQR) 149.0 (134.0--166.0) 145.0 (133.0--164.0) 152.0 (137.0--168.0) 0.55 154.0 (138.0--178.0) 147.0 (132.0--164.0) 0.18\n Initial NIHSS, mean ± SD 14.7 ± 5.5 17.1 ± 4.4 11.8 ± 5.3 \\<0.01 17.2 ± 4.7 12.6 ± 5.4 \\<0.01\n NIHSS at 24 h after admission, median (IQR) 8.0 (4.0--15.0) 11.0 (6.5--20.0) 4.0 (1.5--9.5) \\<0.01 \n **RISK FACTORS** \n Previous stroke 23 (25.8) 15 (30.6) 8 (20.0) 0.37 9 (22.0) 14 (29.2) 0.6\n DM, *n* (%) 25 (28.7) 17 (35.4) 8 (20.5) 0.2 17 (42.5) 8 (17.0) 0.02\n HT, *n* (%) 43 (49.4) 27 (57.4) 16 (40.0) 0.16 24 (61.5) 19 (39.6) 0.07\n Af, *n* (%) 51 (58.0) 32 (65.3) 19 (48.7) 0.18 25 (61.0) 26 (55.3) 0.75\n Smoking, *n* (%) 21 (24.1) 6 (12.8) 15 (37.5) 0.02 4 (10.3) 17 (35.4) 0.01\n Dyslipidemia, *n* (%) 17 (19.5) 8 (17.0) 9 (22.5) 0.71 7 (17.9) 10 (20.8) 0.95\n CAD, n (%) 10 (11.6) 9 (19.1) 1 (2.6) 0.04 8 (20.5) 2 (4.3) 0.05\n **TOAST** \n Cardioembolism, *n* (%) 54 (60.0) 34 (69.4) 20 (48.8) 0.08 25 (61.0) 29 (59.2) 1\n **OCCLUSION SITE, *n* (%)** \n M1 49 (54.4) 24 (49.0) 25 (61.0) 0.06 18 (43.9) 31 (63.3) \\<0.01\n M2 15 (16.7) 6 (12.2) 9 (22.0) 4 (9.8) 11 (22.4) \n ICA 26 (28.9) 19 (38.8) 7 (17.1) 19 (46.3) 7 (14.3) \n **PROCEDURE RELATED FACTORS, MIN, MEDIAN (IQR)** \n LNT to recanalization 216.0 (142.0--317.0) 214.0 (154.0--316.0) 218.0 (134.0--317.0) 0.69 203.0 (152.0--315.0) 219.0 (134.0--336.0) 0.91\n **MEAN BLOOD PRESSURE DURING 24 h AFTER ADMISSION, MEAN ± SD** \n SBP 128.8 ± 11.9 129.1 ± 10.3 128.5 ± 13.6 0.82 132.7 ± 10.1 125.5 ± 12.4 \\<0.01\n DBP 73.3 ± 9.6 73.4 ± 10.6 73.2 ± 8.3 0.90 73.5 ± 9.0 73.1 ± 10.1 0.84\n MBP 85.9 ± 8.9 86.0 ± 8.9 85.9 ± 9.0 0.97 87.1 ±7.4 84.9 ± 10.0 0.27\n Parenchymal hemorrhage, n(%) 16 (17.8) 10 (20.4) 6 (14.6) 0.66 9 (22.0) 7 (14.3) 0.50\n **EARLY NEUROLOGICAL IMPROVEMENT, *n* (%)** \n Day 1 40 (44.4) 16 (32.7) 24 (58.5) 0.03 7 (17.1) 33 (67.3) \\<0.01\n Day 7 or discharge 60 (66.7) 27 (55.1) 33 (80.5) 0.02 17 (41.5) 43 (87.8) \\<0.01\n **3 MONTH OUTCOME, *n* (%)** \n mRS ≤ 2 49 (54.4) 18 (36.7) 31 (75.6) \\<0.01 \n mRS ≤ 1 40 (44.4) 14 (28.6) 26 (63.4) \\<0.01 \n **COLLATERAL STATUS, *n* (%)** \n Poor collateral (0--3) 31 (75.6) 18 (36.7) \\<0.01\n\n*IQR, interquartile range; ER, emergency room; NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation; DM, diabetes mellitus; HT, hypertension; Af, atrial fibrillation; CAD, coronary artery disease; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; LNT, last --seen-- normal time; SBP, systolic blood pressure; DBP, diatolic blood pressure; MBP, mean blood pressure; mRS, modified Rankin Scale; ICA, internal carotid artery*.", "\n\nAntihypertensive medications during 24 h after admission were used in 39 patients (43.3%). ", "Calcium channel blocker was the most frequently used medication (*n* = 35, 89.7%), followed by beta blocker (*n* = 4, 10.3%), and angiotensin II receptor blocker (*n* = 2, 5.1%). ", "Four patients used 2 different kinds of antihypertensive medications. ", "A delivery method of continuous intravenous infusion was used in 17 (43.6%) patients.", "\n\nThe comparisons of BPV parameters according to the occlusion sites (ICA vs. MCA) and mechanisms of stroke \\[cardioembolic (CE) vs. non-CE\\] are presented in [Figure 1](#F1){ref-type=\"fig\"}. ", "Most BPV parameters \\[mean of SBP (SBP~mean~); SD, CV, and VIM of DBP (DBP~SD~, DBP~CV~, and DBP~VIM~) and MBP (MBP~SD~, MBP~CV~, and MBP~VIM~); and CV and VIM of PR (PR~CV~ and PR~VIM~)\\] were significantly higher in patients with ICA occlusion than in those with MCA occlusion ([Figure 1](#F1){ref-type=\"fig\"}, [Table 2](#T2){ref-type=\"table\"}). ", "DBP~SD~, DBP~CV~, and DBP~VIM~ were significantly higher in patients with CE stroke than in those with non-CE stroke ([Figure 2](#F2){ref-type=\"fig\"}, [Table 2](#T2){ref-type=\"table\"}).", "\n\n{#F1}\n\n###### \n\nComparison of BPV parameters according to the occlusion site, mechanism of stroke, and recanalization time.", "\n\n **Occlusion site** **Stroke mechanism** \n ----------- ---------------------- ---------------------- ---------------------- ------ ---------------------- ---------------------- ------\n SBP~mean~ 128.80 ± 11.87 126.98± 12.29 133.27 ± 9.58 0.02 128.36 ± 11.36 129.45 ± 12.74 0.67\n SBP~SD~ 14.36 (11.79--20.14) 13.90 (11.36--18.44) 16.91 (13.44--25.34) 0.06 14.44 (10.80--20.14) 14.36 (11.99--19.91) 0.68\n SBP~CV~ 0.11 (0.09--0.14) 0.11 (0.09--0.13) 0.13 (0.09--0.19) 0.15 0.11 (0.09--0.14) 0.12 (0.09--0.15) 0.75\n SBP~VIM~ 0.11 (0.07--0.17) 0.10 (0.07--0.16) 0.13 (0.07--0.26) 0.21 0.10 (0.07--0.17) 0.11 (0.07--0.17) 0.78\n DBP~mean~ 73.29 ± 9.58 73.26 ± 10.22 73.39 ± 7.95 0.95 74.18 ± 9.40 71.97 ± 9.82 0.29\n DBP~SD~ 10.83 (8.33--14.75) 10.16 (7.23--13.59) 14.07 (9.82--18.67) 0.01 12.24 (8.57--15.66) 9.59 (8.09--12.83) 0.04\n DBP~CV~ 0.16 (0.11--0.20) 0.14 (0.11--0.19) 0.18 (0.14--0.26) 0.01 0.17 (0.13--0.22) 0.14 (0.11--0.18) 0.06\n DBP~VIM~ 0.14 (0.07--0.25) 0.12 (0.06--0.21) 0.20 (0.12--0.42) 0.01 0.16 (0.11--0.29) 0.12 (0.07--0.18) 0.05\n MBP~mean~ 85.92 ± 8.89 85.53 ± 9.68 86.87 ± 6.68 0.46 86.72 ± 8.36 84.69 ± 9.65 0.30\n MBP~SD~ 10.24 (7.89--13.93) 9.54 (7.28--12.80) 12.22 (8.85--17.78) 0.03 10.65 (7.56--15.28) 9.56 (8.08--11.62) 0.43\n MBP~CV~ 0.12 (0.10--0.16) 0.12 (0.09--0.14) 0.14 (0.11--0.20) 0.03 0.12 (0.09--0.18) 0.12 (0.10--0.13) 0.48\n MBP~VIM~ 0.10 (0.07--0.19) 0.10 (0.06--0.16) 0.14 (0.08--0.31) 0.03 0.11 (0.07--0.21) 0.10 (0.08--0.13) 0.52\n PR~mean~ 76.19 ± 14.89 77.00 ± 15.11 74.19 ± 14.43 0.42 76.54 ± 15.37 75.66 ± 14.34 0.79\n PR~SD~ 8.19 (6.08--11.11) 7.88 (5.98--10.61) 8.76 (6.17--14.57) 0.09 8.61 (6.07--12.08) 7.88 (6.19--10.68) 0.52\n PR~CV~ 0.11 (0.09--0.15) 0.10 (0.09--0.14) 0.13 (0.10--0.21) 0.03 0.12 (0.90--0.14) 0.10 (0.09--0.15) 0.42\n PR~VIM~ 0.09 (0.06--0.17) 0.08 (0.06--0.15) 0.12 (0.07--0.35) 0.09 0.11 (0.06--0.16) 0.08 (0.06--0.17) 0.42\n\n*ICA, internal carotid artery; MCA, middle cerebral artery; CE, cardioembolism; non-CE, non-cardioembolism; SD, standard deviation; CV, coefficient of variation; VIM, variation independent of the mean; PR, pulse rate*.", "\n\n{#F2}\n\nMost of the BPV parameters (SBP~mean~, SBP~SD~, SBP~CV~, and SBP~VIM~; DBP~SD~, DBP~CV~, and DBP~VIM~; MBP~SD~, MBP~CV~, and MBP~VIM~; and PR~SD~, PR~CV~, and PR~VIM~) were significantly higher in patients with poor outcomes than in those with good outcomes among those with poor collateral circulation during the first 24 h after ERT. ", "However, no significant differences were observed in these BPV parameters in patients with good collateral circulation based on functional outcomes ([Table 3](#T3){ref-type=\"table\"}).", "\n\n###### \n\nAssociation of blood pressure variability parameters with clinical outcomes according to the collateral status.", "\n\n **Poor collateral** **Good collateral** \n ----------- ---------------------- ---------------------- ---------------------- -------- ---------------------- ---------------------- ---------------------- ------\n SBP~mean~ 129.06 ± 10.33 132.94 ± 9.29 122.38 ± 8.62 \\<0.01 128.48 ± 13.62 131.88 ± 12.86 127.38 ± 13.88 0.37\n SBP~SD~ 14.89 (11.84--20.95) 18.34 (14.44--23.72) 11.84 (10.72--12.95) \\<0.01 14.02 (11.79--19.10) 13.94 (11.62--20.14) 14.02 (11.83--18.74) 0.94\n SBP~CV~ 0.12 (0.09--0.16) 0.14 (0.11--0.17) 0.09 (0.09--0.10) \\<0.01 0.11 (0.09--0.14) 0.10 (0.09--0.15) 0.12 (0.09--0.14) 0.54\n SBP~VIM~ 0.11 (0.07--0.19) 0.15 (0.09--0.23) 0.07 (0.07--0.09) \\<0.01 0.11 (0.06--0.16) 0.08 (0.06--0.17) 0.11 (0.07--0.15) 0.48\n DBP~mean~ 73.41 ± 10.60 72.50 ± 9.89 74.97 ± 11.85 0.44 73.16 ± 8.32 76.69 ± 4.56 72.02 ± 8.98 0.04\n DBP~SD~ 10.28 (8.33--15.09) 14.23 (9.74--17.17) 7.58 (6.52--10.28) \\<0.01 11.14 (8.48--13.43) 9.12 (6.11--20.31) 11.14 (8.58--13.29) 0.57\n DBP~CV~ 0.16 (0.11--0.22) 0.20 (0.14--0.25) 0.11 (0.09--0.15) \\<0.01 0.15 (0.11--0.19) 0.11 (0.08--0.26) 0.16 (0.12--0.18) 0.39\n DBP~VIM~ 0.14 (0.08--0.29) 0.24 (0.12--0.37) 0.07 (0.05--0.14) \\<0.01 0.14 (0.07--0.19) 0.08 (0.04--0.42) 0.15 (0.09--0.19) 0.43\n MBP~mean~ 85.96 ± 8.91 86.14 ± 7.95 85.64 ± 10.60 0.85 85.87 ± 8.99 89.91 ± 4.60 84.53 ± 9.73 0.03\n MBP~SD~ 10.16 (7.94--13.93) 12.67 (9.46--16.96) 7.99 (5.73--9.54) \\<0.01 10.37 (7.29--13.83) 10.06 (7.13--17.78) 10.37 (7.96--13.27) 0.74\n MBP~CV~ 0.12 (0.10--0.16) 0.14 (0.12--0.20) 0.10 (0.08--0.11) \\<0.01 0.12 (0.09--0.15) 0.11 (0.08--0.20) 0.12 (0.10--0.14) 0.91\n MBP~VIM~ 0.12 (0.07--0.20) 0.17 (0.11--0.30) 0.07 (0.05--0.09) \\<0.01 0.10 (0.07--0.17) 0.09 (0.04--0.28) 0.10 (0.07--0.15) 0.7\n PR~mean~ 77.79 ± 16.72 77.99 ± 15.57 77.43 ± 18.99 0.91 74.28 ± 12.30 79.68 ± 9.76 72.54 ± 12.66 0.11\n PR~SD~ 8.68 (6.09--12.08) 10.49 (7.02--14.57) 7.09 (5.20--8.24) 0.01 7.85 (6.08--9.35) 8.21 (7.72--8.82) 7.66 (5.77--10.11) 0.46\n PR~CV~ 0.12 (0.09--0.16) 0.13 (0.10--0.18) 0.09 (0.08--0.12) \\<0.01 0.10 (0.09--0.14) 0.10 (0.09--0.13) 0.10 (0.08--0.14) 0.92\n PR~VIM~ 0.11 (0.06--0.20) 0.14 (0.08--0.327) 0.06 (0.04--0.11) \\<0.01 0.08 (0.06--0.14) 0.08 (0.06--0.13) 0.08 (0.05--0.15) 0.92\n\n*SD, standard deviation; CV, coefficient of variation; VIM, variation independent of the mean; PR, pulse rate*.", "\n\nAfter adjustment for age, sex, initial severity of stroke (i.e., NIHSS), and occlusion site, the SBP~SD~, SBP~CV~, SBP~VIM~, and PR~mean~ remained significant predictors of ENI on day 1 and mRS at month 3 in patients with poor collateral circulation. ", "MBP~SD~, MBP~CV~, and PR~SD~ were associated with mRS shift toward poor functional outcomes at month 3 ([Table 4](#T4){ref-type=\"table\"}). [", "Figure 3](#F3){ref-type=\"fig\"} indicates a positive association between the BPV parameters and mRS increment in the patients with poor collateral circulation.", "\n\n###### \n\nAssociation of blood pressure variability parameters with functional outcomes in poor collateral patients.", "\n\n **BPV parameters** **mRS at month 3 OR (95% CI)** **ENI on day 1 OR (95% CI)**\n -------------------- -------------------------------- ------------------------------\n SBP~SD~ 2.20 (1.20--4.04) 0.22 (0.06--0.77)\n SBP~CV~ 2.18 (1.22--3.91) 0.22 (0.06--0.83)\n SBP~VIM~ 2.12 (1.19--3.75) 0.10 (0.01--0.88)\n MBP~SD~ 1.88 (1.01--3.52) 0.35 (0.11--1.15)\n MBP~CV~ 2.03 (1.06--3.87) 0.41 (0.13--1.24)\n PR~mean~ 1.50 (1.05--2.08) 0.48 (0.26--0.89)\n PR~SD~ 1.75 (1.01--3.05) 0.51 (0.22--1.19)\n\n*Adjustment by age, sex, initial NIHSS, and occlusion site*.", "\n\n*Odds ratio per 10 mmHg increment of mean and per 1 SD increment of SD, CV, and VIM*.", "\n\n*Ordinal logistic regression for mRS at month 3; binary logistic regression for ENI on day 1*.", "\n\n*BPV, blood pressure variability; SBP, systolic blood pressure; MBP, mean blood pressure; PR, pulse rate; SD, standard deviation; CV, coefficient of variation; VIM, variation independent of the mean; ENI, early neurological improvement; OR, Odds ratio; CI, confidence interval*.", "\n\n{#F3}\n\nNo significant association between BPV and clinical outcomes were found after stratification based on the occlusion sites and stroke mechanisms.", "\n\nDiscussion {#s4}\n==========\n\nAs substantial reperfusion is achieved in 72--88% of cases currently ([@B20]), the importance of postreperfusion blood pressure management is increasing. ", "Our study was intended to investigate the effect of postreperfusion BPV on clinical outcomes in ischemic stroke patients with successful recanalization. ", "According to the result of recent study, increased BPV is associated with poor neurological outcome in patients with large ischemic core, large mismatch volume, proximal vessel occlusion, and good collaterals ([@B11]). ", "Contrary to the prior study, the detrimental effect of increased BPV after recanalization was evident in patients with poor collateral circulation.", "\n\nCollateral status is strongly correlated with initial stroke severity, baseline infarct volume, and the extent and speed of infarct growth ([@B21]). ", "Patients with poor collateral flow present with more severe neurological status and experience the least benefit from the recanalization therapy because of the quick progression of the infarct volume ([@B21]). ", "The ischemic core volume may be larger and peripheral vascular resistance may be greater in patients with poor collateral circulation than in those with good collateral circulation. ", "Therefore, increased BPV may induce hemorrhagic transformation more frequently in patients with poor collateral circulation. ", "Furthermore, BP fluctuation could induce a recurrent embolism from the proximal vasculature; the ability to wash out emboli may be reduced in patients with poor collateral circulation ([@B22]). ", "Therefore, stroke progression or recurrence may occur more frequently in these patients.", "\n\nThe differences of BPV in patients with different occlusion sites and stroke subtypes are noteworthy. ", "Although the absolute level of BP is not related to initial stroke severity and infarct volume ([@B23], [@B24]), higher BPV in patients with ICA occlusion suggests that these factors may have a correlation with BPV. ", "More severe stroke is associated with the increased sympathetic activity, and sympathetic overactivity induces high BPV ([@B16], [@B25], [@B26]). ", "Decreased function of arterial baroreceptor could also increase BPV ([@B16], [@B26]). ", "Higher BPV in patients with ICA occlusion may be due to sympathetic overactivity and decreased baroreflex sensitivity. ", "It is unclear why only DBP-related variables (DBP~SD~, DBP~CV~, and DBP~VIM~) are significantly higher in cardioembolic stroke than in other stroke types caused by different mechanisms including large artery atherosclerosis. ", "Further studies are needed to assess whether the results are due to changes in coronary perfusion pressure affected by diastolic BPV or merely chance findings without clinical meaning.", "\n\nThere are several limitations to consider when interpreting our findings. ", "First, the retrospective nature and small study population in this study warrant further investigation with a large, prospective, and multicenter cohort. ", "Second, the association of BPV with clinical outcomes in patients with poor collateral circulation does not constitute a causal relationship. ", "Because this study included a small number of hemorrhagic transformation or ischemic stroke recurrence, the mechanism of deleterious effects of BPV in patients with poor collateral status could not be determined. ", "Lastly, pretreatment or intraprocedural blood pressure could also have influence on clinical outcome and obtaining these data retrospectively was not available and beyond the scope of the current analysis.", "\n\nIn conclusion, BPV during the first 24 h after recanalization had a greater impact on functional outcomes in patients with poor collateral circulation (i.e., pial arterial filling score \\<4). ", "The results suggest that the close blood pressure management by decreasing BPV after recanalization might have effect on improving clinical outcomes in patients with acute large vessel occlusive stroke, particularly accompanied by poor collateral circulation. ", "To increase clinical benefits of ERT, postreperfusion BP management, as well as expedited and complete recanalization, may be important in cases of poor collateral circulation among patients achieving successful recanalization after ERT.", "\n\nEthics Statement {#s5}\n================\n\nSeoul National University Bundang Hospital Institutional Review Board approved the retrospective study. ", "Informed consent was waived for the retrospective chart review study.", "\n\nAuthor Contributions {#s6}\n====================\n\nJC and M-KH contributed to the study concept and design. ", "JC, CJ, and DG contributed to the acquisition of data. ", "JC and CJ contributed to the analysis and interpretation of data. ", "JC and M-KH drafted the manuscript. ", "S-BJ and M-KH performed critical revision of the manuscript for important intellectual content. ", "M-KH provided the final approval of the final version of this manuscript. ", "All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.", "\n\nConflict of Interest Statement\n------------------------------\n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "\n\n**Funding.** ", "This study received no specific grants from any funding agencies in the public, commercial, or not-for-profit sectors.", "\n\n[^1]: Edited by: Maxim Mokin, University of South Florida, United States\n\n[^2]: Reviewed by: Felix Schlachetzki, University of Regensburg, Germany; Viktor Szeder, UCLA David Geffen School of Medicine, United States\n\n[^3]: This article was submitted to Endovascular and Interventional Neurology, a section of the journal Frontiers in Neurology\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Nawaz Sharif is unhappy and he wants the country and the world to know it.", "\n\nBut Mr Sharif’s reaction to the end of the Faizabad protest is puzzling. ", "The ousted prime minister would like the country to believe that not only does he disapprove of his government’s handling of the protest, but that he was unaware of the decisions being made to try and bring the protest to an end.", "\n\nYet, on Saturday, when the police-led operation to try and end the Faizabad protest was under way and protests had begun to erupt in cities across the country, Mr Sharif was pictured in a meeting in his Raiwind residence with Prime Minister Shahid Khaqan Abbasi and Punjab Chief Minister Shahbaz Sharif.", "\n\nIn that meeting, Interior Minister Ahsan Iqbal reportedly briefed Mr Sharif about the police operation as did the Punjab chief minister on his government’s plans to deal with protests erupting in the province.", "\n\nBut after the spectacular failure of those plans and the shocking concessions made to the protesters, the three-term prime minister and president of the PML-N would like to pretend that his government’s decisions have nothing to do with him.", "\n\nThere are two other elements of Mr Sharif’s self-serving description of the events of the past few days that are disturbing. ", "First, the former prime minister is reportedly concerned that the outside world will once again see Pakistan as a defender of extremism and this may impact investments in the country, particularly Chinese investments under CPEC.", "\n\nConsider for a moment what that implies: Mr Sharif is more concerned about the image of Pakistan in foreign capitals than the security of the denizens of Pakistan’s cities, including the federal capital, which was under siege for nearly three weeks.", "\n\nWhile the country must be mindful of the image of Pakistan in an interconnected world, the obsession with foreign perceptions and desperation to please external benefactors is arguably part of the reason the country lurches from crisis to crisis.", "\n\nThe PML-N government’s fundamental duty is the people of Pakistan — ensuring their safety and security and protecting their rights. ", "If that duty is kept front and centre and informs all governmental decision-making, the country’s image will automatically improve and concerns in foreign capitals will dissipate.", "\n\nSecond, Mr Sharif’s lament that governance is suffering is to ignore that he is the reason his government is deeply distracted. ", "Ever since the Panama Papers issue erupted, and certainly since Mr Sharif’s ouster in July, the federal cabinet appears to exist largely to help Mr Sharif deal with his legal and political struggles.", "\n\nMoreover, the succession struggle in the PML-N between Mr Sharif’s side of the family and Shahbaz Sharif’s family appears to have severely damaged necessary coordination between Lahore and Islamabad. ", "Arguably, the Faizabad debacle began with Mr Sharif’s own selfishness in recent months.", "\n\nPublished in Dawn, November 30th, 2017" ]

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[ "Q:\n\nRedis on Spark:Task not serializable\n\nWe use Redis on Spark to cache our key-value pairs.", "This is the code:\nimport com.redis.", "RedisClient\nval r = new RedisClient(\"192.168.1.101\", 6379)\nval perhit = perhitFile.map(x => {\n val arr = x.split(\" \")\n val readId = arr(0).toInt\n val refId = arr(1).toInt\n val start = arr(2).toInt\n val end = arr(3).toInt\n val refStr = r.hmget(\"refStr\", refId).get(refId).split(\",\")(1)\n val readStr = r.hmget(\"readStr\", readId).get(readId)\n val realend = if(end > refStr.length - 1) refStr.length - 1 else end\n val refOneStr = refStr.substring(start, realend)\n (readStr, refOneStr, refId, start, realend, readId)\n })\n\nBut compiler gave me feedback like this:\nException in thread \"main\" org.apache.spark.", "SparkException: Task not serializable\n at org.apache.spark.util.", "ClosureCleaner$.ensureSerializable(ClosureCleaner.scala:166)\n at org.apache.spark.util.", "ClosureCleaner$.clean(ClosureCleaner.scala:158)\n at org.apache.spark.", "SparkContext.clean(SparkContext.scala:1242)\n at org.apache.spark.rdd.", "RDD.map(RDD.scala:270)\n at com.ynu.", "App$.main(App.scala:511)\n at com.ynu.", "App.main(App.scala)\n at sun.reflect.", "NativeMethodAccessorImpl.invoke0(Native Method)\n at sun.reflect.", "NativeMethodAccessorImpl.invoke(NativeMethodAccessorImpl.java:57)\n at sun.reflect.", "DelegatingMethodAccessorImpl.invoke(DelegatingMethodAccessorImpl.java:43)\n at java.lang.reflect.", "Method.invoke(Method.java:606)\n at org.apache.spark.deploy.", "SparkSubmit$.launch(SparkSubmit.scala:328)\n at org.apache.spark.deploy.", "SparkSubmit$.main(SparkSubmit.scala:75)\n at org.apache.spark.deploy.", "SparkSubmit.main(SparkSubmit.scala)\nCaused by: java.io.", "NotSerializableException: com.redis.", "RedisClient\n at java.io.", "ObjectOutputStream.writeObject0(ObjectOutputStream.java:1183)\n at java.io.", "ObjectOutputStream.defaultWriteFields(ObjectOutputStream.java:1547)\n at java.io.", "ObjectOutputStream.writeSerialData(ObjectOutputStream.java:1508)\n at java.io.", "ObjectOutputStream.writeOrdinaryObject(ObjectOutputStream.java:1431)\n at java.io.", "ObjectOutputStream.writeObject0(ObjectOutputStream.java:1177)\n at java.io.", "ObjectOutputStream.writeObject(ObjectOutputStream.java:347)\n at org.apache.spark.serializer.", "JavaSerializationStream.writeObject(JavaSerializer.scala:42)\n at org.apache.spark.serializer.", "JavaSerializerInstance.serialize(JavaSerializer.scala:73)\n at org.apache.spark.util.", "ClosureCleaner$.ensureSerializable(ClosureCleaner.scala:164)\n ... 12 more\n\nCould somebody tell me how to serialize the data get from Redis.", "Thanks a lot. ", " \n\nA:\n\nIn Spark, the functions on RDDs (like map here) are serialized and send to the executors for processing. ", "This implies that all elements contained within those operations should be serializable. ", "\nThe Redis connection here is not serializable as it opens TCP connections to the target DB that are bound to the machine where it's created.", "\nThe solution is to create those connections on the executors, in the local execution context. ", "There're few ways to do that. ", "Two that pop to mind are:\n\nrdd.mapPartitions: lets you process a whole partition at once, and therefore amortize the cost of creating connections)\nSingleton connection managers: Create the connection once per executor\n\nmapPartitions is easier as all it requires is a small change to the program structure:\nval perhit = perhitFile.mapPartitions{partition => \n val r = new RedisClient(\"192.168.1.101\", 6379) // create the connection in the context of the mapPartition operation\n val res = partition.map{ x =>\n ...\n val refStr = r.hmget(...) // use r to process the local data\n }\n r.close // take care of resources\n res\n}\n\nA singleton connection manager can be modeled with an object that holds a lazy reference to a connection (note: a mutable ref will also work). ", "\nobject RedisConnection extends Serializable {\n lazy val conn: RedisClient = new RedisClient(\"192.168.1.101\", 6379)\n}\n\nThis object can then be used to instantiate 1 connection per worker JVM and is used as a Serializable object in an operation closure. ", "\nval perhit = perhitFile.map{x => \n val param = f(x)\n val refStr = RedisConnection.conn.hmget(...) // use RedisConnection to get a connection to the local data\n }\n}\n\nThe advantage of using the singleton object is less overhead as connections are created only once by JVM (as opposed to 1 per RDD partition)\nThere're also some disadvantages:\n\ncleanup of connections is tricky (shutdown hook/timers)\none must ensure thread-safety of shared resources\n\n(*) code provided for illustration purposes. ", "Not compiled or tested.", "\n\n" ]

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[ "The streamer seems less interested in individual shows than creating the illusion that it has all the shows you need — and that may be a problem soon.", "\n\nNetflix is doing something weird this week — and yes, it does often partake in convention-defying bits of decisionmaking almost as a rule: On Friday it will premiere the second season of its acclaimed but hardly zeitgeisty drama Mindhunter after choosing not to send out screeners to critics and to only have a fan-based premiere of the first three episodes.", "\n\nWhich is, well, weird. ", "Not completely surprising but a lot surprising, even for Netflix. ", "And it certainly adds to the looming sense that, like it or not, the lead streamer might have to start doing business differently sooner than it thinks.", "\n\nBecause Netflix is the Death Star of the Streaming Wars, it's a little too easy for people to predict its imminent doom, whether from the very real threat of Disney+, by far the most dangerous among a slew of new competitors, declining subscribers and very bad days on Wall Street, perceived Emmy failures, international uproars or, well, just because detractors want it to be so.", "\n\nHistorically, wishful (hateful?) ", "thinking hasn't done much of any damage to Netflix.", "\n\nAll through the recent years chronicling the once-impending and now well-upon-us Streaming Wars, I've tried to be very dubious about all these predictions of doom. ", "And I firmly believe that's a very long way off. ", "But change is coming and something as seemingly insignificant as a second-season premiere indicates that Netflix, confident and comfortable, is showing zero interest in admitting that this change is something it will worry about right now.", "\n\nThat little promo decision can't be the tipping point, can it? ", "No, but it's indicative of an entrenched attitude. ", "And that attitude is likely to become a predicament — for a lot of reasons.", "\n\nOn Tuesday, in a back and forth discussion about summer TV with fellow THR critic Dan Fienberg, we both looked upon Stranger Things as something popular and fun (if repetitive), but hardly an Emmy threat, having won nothing of significance yet (losing last year to Game of Thrones). ", "As for the concluding — and excellent — series Orange Is the New Black, we agreed that it was probably the defining original series on Netflix, while acknowledging that such a thing is no longer really a business goal. ", "And by that, I mean that Netflix doesn't seem to care about \"defining\" itself with a series; its brand is volume.", "\n\nSo just for a few fleeting moments there, we were thinking of Past Netflix a little bit more than Present Netflix.", "\n\nBut moving forward, the streamer's \"volume\" strategy might not be tenable, especially when your volume isn't particularly noteworthy or desirable — and having identifiable hits might be the strategy that eventually wins the day in the Streaming Wars over something as nebulous as \"We have all the shows you need, even if you can only name five of them.\"", "\n\nAnd honestly, name five Netflix series right now, off the top of your head, and then see which of them were released in the past 18 months.", "\n\nTo be clear, Stranger Things is easily one of Netflix's most recognizable series and, argue all you want to about invisible ratings, probably one if its more massive offerings. ", "The difference between a legacy series like Orange Is the New Black and Stranger Things is that Netflix, new to the business, really promoted OITNB in 2013 and then worked to sustain it; the streamer didn't really know what it had when it \"launched\" Stranger Things in the summer of 2016. ", "But even then, the find-it-organically-like-a-surprise fit into what was an operationally successful plan. ", "By 2016 Netflix was all about volume and an out-of-nowhere hit like Stranger Things that seemed to surprise the people who bought it validated the concept. \"", "We have all the shows you need\" certainly seemed brilliantly accurate back then and, up until about a year or so ago, looked like a recipe that didn't need messing with.", "\n\nThe problem is this Streaming Wars thing is here, on the doorstep. ", "When Disney+ launches — the first real fully formed threat to Netflix and first of the new wave out of the gate — it not only has volume, it has brand identity, hyper-recognizable IP and is eye-poppingly less expensive. ", "Disney+ also comes with the promise — true or not — that subscribers will recognize future offerings. ", "Why? ", "Because colossally famous things are part of the Disney brand. ", "Put another way — Disney will have fewer series from Norway.", "\n\nThat's why not touting Mindhunter when it had the chance, the budget and the need to create something more identifiable than what the series was in 2017 seems like a missed opportunity. ", "I suspect that it doesn't seem like a missed opportunity to Netflix right now, but it might next year. ", "Is it possible that David Fincher said \"no hype, no nothing\" to season two? ", "Sure. ", "Maybe. ", "But the bigger point here is that dropping shows with no press and not much fanfare when you could be creating something sellable to new subscribers seems ... unwise.", "\n\nLook at it this way: Selling volume is great when you want market dominance over the early-days Hulu or the we-sell-TV-shows-in-addition-to-gadgets-era Amazon. ", "But now both of those streamers have their shit together and are making really good TV series. ", "That's already a problem. ", "Then here comes Disney+, with Apple+ and HBO Max right behind. ", "Then NBCUniversal soon after.", "\n\nVolume? ", "The whole streaming universe is going to be volume.", "\n\nSorry, but you can't sell excess to people who are about to be more overwhelmed with choice than they've ever been.", "\n\nBut you can sell recognizable, desirable, entertaining, quality TV series like Orange Is the New Black, Stranger Things, GLOW, Ozark, The Crown or Russian Doll (though I'd argue some of those later ones should have been marketed wider at release; Netflix would argue that viewers and Emmy voters found them anyway, validating its approach).", "\n\nSo it will be interesting going forward in the Streaming Wars (for everybody, really), but in particular Netflix, the one streaming service that sells ubiquity over specificity. ", "Will it focus on fine-tuning its series to win more Emmys (the streamer is obviously heavily invested in getting nominations, but ultimately wins will start to matter as the competition for subscribers heats up). ", "Will it start to change how it makes shows — a little more prestige mixed into the plentitude? ", "Will it change how it markets them? ", "How it promotes them to the press (Netflix is famous for oppressive review embargoes or just, you know, not making something available).", "\n\nAll of this, in various ways, matters. ", "It would be nice if Russian Doll broke out at the Emmys, but it's really a dark horse. ", "Ozark and Bodyguard got drama nominations and in any other year that might have mattered (it's probably going to be Game of Thrones, you know that). ", "When They See Us did great in the nominations but might be facing too much competition.", "\n\nWith Amazon and Hulu upping their respective creative games, and with HBO and FX as long-standing stalwarts, more competition from Disney+, Apple+, etc. ", "will just make it more essential that, if you want to use the Emmys as a marketing tool for subscriptions, curating and emphasizing individual series will be paramount.", "\n\nEmmys — nominations and wins — aren't everything, of course. ", "But notable content — as opposed to just content — certainly will be moving forward.", "\n\nWhat Netflix does in the face of this looming competition will be kind of fascinating, and you can bet others are watching. ", "At the moment it appears there's no evident strategy shift, which means Netflix probably has a new series premiering tonight, no matter what night you're reading this." ]

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[ "Q:\n\nCheck similarity of table/csv of Product Names\n\nWe've got a list of approximately 18,000 product names (they're from 80-90 sources, so quite a few that are similar but not duplicates - these were picked as DISTINCT from a table) unfortunately there are different ways of expressing these names. ", "We have to try and normalize the dataset so we present our users with more meaningful names.", "\nFor example, a list like this:\nCanon EOS 5D Mark III\nCanon EOS 5D mk III\nCanon EOS 5DMK3\nCanon EF 70-200mm f/2.8L IS II USM Lens\nCanon EF 70-200mm f/2.8L IS II USM Telephoto Zoom Lens\nCanon EF 70-200mm f/2.8L IS USM Lens\nCanon EF 70-200mm f/4L USM Lens\n\nI'd like to be able to assess those strings and collapse them into something like this:\nCanon EOS 5D Mark III\nCanon EF 70-200mm f/2.8L IS II USM \nCanon EF 70-200mm f/2.8L IS USM Lens\nCanon EF 70-200mm f/4L USM Lens\n\nBut I'd like to know how similar two strings are to be able to determine this. ", "I do realise that the F2.8 IS II and IS USM may be a bit hard, but thought I'd throw it in.", "\nThe real product names are far less exciting (they're parts for the farm equipment we stock).", "\nWe also store these names in a Postgres (9.5) database table. ", "Examples i've seen compare two lists, but we don't have a master product list to do that unfortunately.", "\n\nA:\n\nYour problem is known as detection of near-duplicate documents, i.e. you have strings that are similar but not exact duplicate. ", "The most common approaches are using cosine similarity and Jaccard similarity. ", "You could check this page for more information \nFirst you have to convert your strings to a vector of features, this features could be tf-idf vectors of all the tokens (words) that appear in the database, could also be a vector of n-grams. ", "For a discussion of semantic and syntactic features you can look here.", "\nFinally you would have to check the similarity of every pair of documents, in your case 18000. ", "The brute force approach is O(n^2), so this could be unfeasible. ", "A common technique to deal with this issue is to use fingerprinting (hashing) together with Locality Sensitive Hashing (LSH). ", "\nYou can find an introduction and a general discussion of the whole topic in Chapter 3 of Mining Massive Datasets\n\n" ]

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[ "Q:\n\nBurninate the \"physics\" tag\n\nWhat's the purpose of the physics tag? ", "Every question is supposed to be about physics.", "\nI've tried removing some myself but new users keep using it.", "\n\nA:\n\nThere is indeed some room for debate on whether all questions on this site must absolutely be about physics, or whether some non-physics astronomy questions are a good fit here. ", "But this debate is irrelevant: questions on this site do not have to specify that they're about physics. ", "The tag conveys no information.", "\nFurther, it leaves the option for new users to use only that tag, e.g. this question. ", "Chances are, if no other tag applies, that the question is off-topic here. ", "The existence of the physics tag makes that less evident.", "\nPlease burninate and blacklist it.", "\n\nA:\n\nphysics is now an intrinsic tag. ", "\n\n" ]

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[ "Over 1.5 billion people live in countries whose economies are dependent on the revenue from natural resource exports. ", "With growing demand from China and other emerging markets, the demand for minerals and oil will continue to increase. ", "And prices will increase even further in response to the accelerated depletion of these non-renewable resources. ", "What effect will mushrooming reliance on oil and minerals have on commodity exporters’ politics, legal institutions, and economics?", "\n\nConventional wisdom says that, over the long run, the results will be devastating. ", "Increased natural resource reliance will promote authoritarianism, corruption and the weakening of the rule of law, economic stagnation and even war. ", "This definitely seems like more than what these countries bargained for when they were ostensibly blessed by the gods of oil and precious metals.", "\n\nThe idea of a resource curse can be found in academic writings ranging from country case studies of oil and mineral reliant states, such as Iran and Nigeria, and large-n statistical analyses. ", "It has also spread beyond academia. ", "Several country case studies, policy papers produced by multilateral aid organizations, popular books on world politics and economics, and articles in the mass media, have been seduced by the idea that there is a resource curse. ", "While well-respected magazines such as The Economist continue to run frequent special reports on this phenomenon, perhaps the most well-known popularization is New York Times columnist Thomas Friedman’s so-called first law of petropolitics: the claim that recent turns toward authoritarianism in Russia, Venezuela, and Iran have been induced by big increases in the price of oil. ", "Moreover, the scope of the policy prescriptions espoused by resource curse advocates has been ambitious, matching the sweeping claim that oil and mineral wealth is universally bad for countries’ political and economic development. ", "Some scholars have gone as far as to recommend that countries that discover oil and precious metals are better off leaving their resources in the ground—a policy that, unsurprisingly, resource rich countries have eschewed so far. ", "Many have a good reason to do so: they are poor, and can ill-afford to simply leave the “big bills” associated with minerals and oil “on the sidewalk.”", "\n\nDespite overwhelming consensus, there is reason to be skeptical of the resource curse theory. ", "Over the past few years, Stephen Haber and I have researched this issue extensively. ", "Unlike other research on this topic, we have looked at the historical trajectory of resource-reliant countries and conducted before-and-after comparisons, in order to see if the discovery and increased production of oil and minerals had any effect on countries’ political institutions; we have also compared these countries to non-resource reliant countries that were similar to them on the eve of resource discovery, save for reliance on oil and minerals. ", "We were surprised to learn that, upon closer inspection, there really is no there there!", "\n\nIndeed, take a look at the time-series graphs for Australia, Canada, and the United States below: they have historically enjoyed some of the highest levels of income from natural resources per capita (well-above the historical global mean).", "\n\nSource: Haber and Menaldo (2010). ", "Total Natural Resources Income is: Total Fuel Income plus Total Metals Income in Real 2007 dollars.", "\n\nWe know that these countries have been consistently liberal democracies, even in the face of increased income from natural resources. ", "On the economic front, Gavin Wright (and coauthors) has written extensively about the fact that the United States’ industrial revolution was bankrolled by its absurdly generous endowments of copper, iron ore, antimony, magnesite, mercury, nickel, silver and zinc, and, of course, petroleum. ", "He further argues that these endowments did not fall from the sky like manna from heaven; US resource wealth was instead engendered by a conspiracy of political and legal factors: a favorable legal environment, engineering prowess, and a favorable business climate that rewarded otherwise risky investments in knowledge and technology.", "\n\nAlso, consider Chile, the world’s largest copper producer. ", "A consolidated democracy, it is the wealthiest country in Latin America (it’s fast approaching $15,000 Real Per Capita GDP). ", "These attributes undoubtedly contributed to its ability to rescue the 33 miners that were trapped inside one of its modern and productive copper mines.", "\n\nPercent of the Global Copper Market, 2006\n\nSource: Haber and Menaldo (2010).", "\n\nCONCLUSION\n\nWhen it comes to the claim that there is a Resource Curse, does the Emperor have no clothes?", "\n\n10 comments\n\nLaw of petropolitics is an unnecessary complication of a simple phenomenon. ", "When resource wealth increases, more and more people in those countries have a stake in the political and economic stability of the country. ", "To ensure that stability, they choose authoritarian rule over an unstable democracy. ", "Over time, once their people are more educated and seek political changes in their countries, authoritarian one-man rule will give way to democracy.", "\n\nExtremely short-sighted argument, Stephen and Victor. ", "US, Canada and Australia had established their liberal governance structures and supporting institutions before they became heavily dependent on the extraction of natural resources. ", "Establishing these norms, cultures of open expression and rule of law that ensures these has been critical to the dispersion of wealth resulting from natural resource extraction. ", "The Natural Resource-curse arguments have always said that the flaw, for countries such as Nigeria, Venezuela, Saudi Arabia, Iran, etc is that the democracy/debate institutions have not had the opportunity to develop, act and flourish independently of the governing parties that have opened their countries to resource extraction.", "\n\n[...] The Resource Curse: Does the Emperor Have No Clothes? – ", "Plawtoic – Over 1.5 billion people live in countries whose economies are dependent on the revenue from natural resource exports. ", "With growing demand from China and other emerging markets, the demand for minerals and oil will continue to increase. ", "And prices will increase even further in response to the accelerated depletion of these non-renewable resources. ", "What effect will mushrooming reliance on oil and minerals have on commodity exporters’ politics, legal institutions, and economics? [...]", "\n\nIf a country discovers large reserves of oil (for eg), then doesn’t that country’s currency tend to appreciate (assuming currency is allowed to float) and doesn’t that then make their non-oil exports far less competitive? ", "I.e., while some “resource curse” advocates are looking at correlation rather than causality, is it not fair to say that there are indeed negative externalities as a result of resource discoveries?", "\n\nthx for the insight and great blog entry. ", "looking forward to your thoughts on this.", "\n\nSo your argument is a couple of resource abundant countries have done well, hence, no resource curse? ", "You have only succedeed in showing that not all countries with natural resources succumb to the curse, a position that no-one would argue for. ", "This is why we have statistics. ", "A couple of anecdotes do not prove a general point.", "\nI haven’t looked at the actual papers, where you presumably actually argue for your thesis. ", "But this post could hardly be less convincing.", "\n\nHaber and Menaldo consistently fail to appreciate the role of institutions for controlling extractive wealth. ", "The natural resource curse, better described as a “rentier effect”, is robust on the large-n level for nations with a significant proportion (1/3 or more) of GDP deriving from extractive wealth. ", "Nations with more diversified economies, like Chile, Australia, and the US, do not experience a rentier effect because government revenue is not dependent on a single extracted commodity. ", "Haber and Menaldo’s papers are no more convincing than this post.", "\n\n[...] economic growth success, yet why were their two bad decades so very, very bad?Victor Menaldo on THE RESOURCE CURSE: Does the Emperor Have No Clothes?Alex Evans on THE RESOURCE CURSE: Does the Emperor Have No [...]\n\n[...] The Resource Curse: Does the Emperor Have No Clothes? – ", "Plawtoic – Over 1.5 billion people live in countries whose economies are dependent on the revenue from natural resource exports. ", "With growing demand from China and other emerging markets, the demand for minerals and oil will continue to increase. ", "And prices will increase even further in response to the accelerated depletion of these non-renewable resources. ", "What effect will mushrooming reliance on oil and minerals have on commodity exporters’ politics, legal institutions, and economics? [...]" ]

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[ "<!", "DOCTYPE html>\n<html>\n<head>\n <meta charset=\"UTF-8\">\n <title>Initialize Value for ComboGrid - jQuery EasyUI Demo</title>\n <link rel=\"stylesheet\" type=\"text/css\" href=\"../../themes/default/easyui.css\">\n <link rel=\"stylesheet\" type=\"text/css\" href=\"../../themes/icon.css\">\n <link rel=\"stylesheet\" type=\"text/css\" href=\"../demo.css\">\n <script type=\"text/javascript\" src=\"../../jquery.min.js\"></script>\n <script type=\"text/javascript\" src=\"../../jquery.easyui.min.js\"></script>\n</head>\n<body>\n<h2>Initialize Value for ComboGrid</h2>\n<div class=\"demo-info\">\n <div class=\"demo-tip icon-tip\"></div>\n <div>Initialize value when ComboGrid is created.</div>\n</div>\n<div style=\"margin:10px 0\"></div>\n<input class=\"easyui-combogrid\" style=\"width:250px\" value=\"EST-12\" data-options=\"\n\t\t\tpanelWidth: 500,\n\t\t\tidField: 'itemid',\n\t\t\ttextField: 'productname',\n\t\t\turl: '../combogrid/datagrid_data1.json',\n\t\t\tcolumns: [[\n\t\t\t\t{field:'itemid',title:'Item ID',width:80},\n\t\t\t\t{field:'productname',title:'Product',width:120},\n\t\t\t\t{field:'listprice',title:'List Price',width:80,align:'right'},\n\t\t\t\t{field:'unitcost',title:'Unit Cost',width:80,align:'right'},\n\t\t\t\t{field:'attr1',title:'Attribute',width:200},\n\t\t\t\t{field:'status',title:'Status',width:60,align:'center'}\n\t\t\t]],\n\t\t\tfitColumns: true\n\t\t\">\n</body>\n</html>" ]

{ "pile_set_name": "Github" }

[ 0.006595523562282324, 0.000750729173887521 ]

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", "Benzodiazepines such as alprazolam are controversial due to a possible link to cleft lip/palate.", "\n8 , olanzapine arrow 5 mg\n9 Desipramine and fluoxetine were chosen as relatively specific blockers of the reuptake of norepinephrine and serotonin, respectively. ", "A 2009 study found that physical inactivity contributes to erectile dysfunction – essentially a no-brainer. [", "35 ] Aos dezessete anos, em 23 de agosto de 2003, Germanotta ganhou uma admissão antecipada para a Tisch School of Arts e morou em um dormitório da universidade na Rua 11. ", "Through the initiative of the City of Ayia Napa all the beaches in Cyprus are under the management of the local authorities(cities and villages).", "\n\nOlanzapine tablets 10mg\n\nI hope you’ll consider taking a moment to sign up for the monthly newsletter on the home page. 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{ "pile_set_name": "Pile-CC" }

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[ "Americans spend much of their day at work, and more than half of Americans rated their overall work environment poorly last year. ", "Although the number of workers who gave their workplace a positive overall review is up to 48% from an all-time low of 47.2% in 2011, it has yet to recover to past levels of over 51%.", "\n\nOf course, workers in different cities can have markedly different feelings about their jobs. ", "According to the recent Gallup-Healthways Well-Being Index, San Luis Obispo, Calif., was the metropolitan area with the best work environment. ", "The area with the worst work environment was Fayetteville, N.C.\n\nTo determine the best and worst work environments, Gallup surveyed hundreds of thousands of Americans in 189 metropolitan areas in the U.S. in 2012 and 2013. ", "The Work Environment Index included four metrics: job satisfaction; whether employees felt they used their strengths at work; how employees were treated by their supervisors; and whether supervisors created an open and trusting work environment.", "\n\nHow workers were treated by their supervisors was perhaps the most meaningful indicator of a healthy workplace. ", "According to Dan Witters, research director of the Gallup-Healthways Well-Being Index, workers were far more likely to give positive evaluations to other elements of their jobs if they felt treated like a partner at work. ", "As a result, the cities with the best work environments were largely those where workers most often felt treated like a partner.", "\n\nIn fact, seven of the 10 best cities for work also had among the 10-highest percentages of workers who felt treated like a partner at work. ", "Workplace environments were also tied to other well-being measures such as emotional and physical health. \"", "Emotional health gets better where work environment well-being is higher,\" Witters said.", "\n\nBut, he added, the relationship between emotional health and work environment is reciprocal. ", "Emotionally healthy workers make more valuable employees and are more likely to be hired in the first place. ", "In the cities where people most enjoyed work, residents were more likely to say they learned something new every day, a key measure of emotional health in the Well-Being Index. ", "In the San Luis Obispo metro area, more than 73% of residents said they had learned something new or interesting in the past day, a higher rate than in all but three other metro areas nationwide.", "\n\nThe opposite was frequently true in poorly ranked cities, where workers were far less likely to feel they had daily learning opportunities. ", "Witters also highlighted that a good work environment is often connected to better exercise and eating habits.", "\n\n\"Workplaces that advocate and promote high well-being lifestyles can have a very significant influence [on employees],\" Witters explained. ", "Simultaneously, \"people who exhibit those healthier behaviors are more attractive for a workplace to hire.\"", "\n\nFor instance, all but two of the 10 best cities for work had smoking rates below the national rate, and just 11.1% of San Jose residents smoked, the second lowest rate in the nation. ", "At the other end, residents in the nation's worst cities for work were more likely to smoke and practice other unhealthy behaviors.", "\n\nIn Charleston, W. Va., more than 34% of residents smoked, the highest percentage in the nation. ", "Since answers to questions from Gallup's work environment index were provided by people who had jobs, the health of the areas' job market may not always have a huge impact on workplace environment well-being.", "\n\nWhile six of the 10 highest rated cities had unemployment rates below the national rate as of December, four did not. ", "In the Visalia, California metro area, the unemployment rate was 13.1%, nearly double the national rate of 6.7% that month. ", "Similarly, among the worst rated cities, Charleston's unemployment rate was 5.4% — much lower than the national rate. ", "While not a direct relationship, the health of the job market can affect workplaces.", "\n\nFor instance, the recession and constant daily layoffs has created stressful work environments overall and therefore also impacted workers with a job. ", "In some cases, when it is harder find a job, \"you'll see [some] supervisor-worker relationships erode, and suffer, as a result of that shifted power arrangement.\" ", "Median income and educational attainment rates might be expected to have substantial effects on workplace evaluations, but that was not always the case. ", "In several instances, respondents from relatively poor areas overwhelmingly approved of their jobs, while residents of wealthier areas were often likely to give poor assessments.", "\n\nFor example, in the Fort Smith metro area, located in Arkansas and Oklahoma, median household income was just $36,061 in 2012, but residents rated their workplaces fifth-best. ", "Median household income in the Poughkeepsie, New York metro area, on the other hand, was $66,612 that year, but residents their rated their workplaces among the worst. ", "According to Witters, this is due primarily to the weight a supervisor carries in determining the quality of a work environment.", "\n\nIf you have a bad supervisor, your work experience will be poor regardless of the level of your education and financial situation. ", "Witters said, as your education improves, however, the kinds of jobs available to you are going to be different. ", "For example, in \"the low education, low income jobs, you're going to be more likely to be in a hierarchical arrangement — you're less likely to be in a role that requires you to be imaginative and creative and collaborative.\" ", "Rather, \"you're more likely to be in a role where you just need to take your orders and do what you're told to.\" ", "To identify the best and worst cities for work, 24/7 Wall St.reviewed the metropolitan areas with the best and worst scores on the Work Environment Index, part of the Gallup-Healthways Well-Being Index.", "\n\nThe Gallup-Healthways Well-Being Index assessed 189 metropolitan statistical areas. ", "The Work Environment Index is one of five subindices included in the groups' overall score. ", "The index measures workplace happiness for the U.S., states, metropolitan areas and occupations, based on answers to four questions.", "In addition to these figures, we also considered income, poverty and educational attainment data from the U.S. Census Bureau, all from 2012. ", "Local, seasonally adjusted unemployment rates, current as of December 2013, are from the Bureau of Labor Statistics. ", "These are the cities with the most content and miserable workers.", "\n\nUnlike some of the cities where workers are most satisfied, Kingsport area residents had low educational attainment rates, with slightly more than 19.2% of adults 25 and older having graduated college, considerably lower than the national rate. ", "A typical household in the area also made just $37,769 in 2012, considerably lower than most other metro areas. ", "Despite the low education levels and incomes, area workers had among the most pleasant work environments. ", "Employees in the Kingsport metro area had among the best supervisors in the nation last year. ", "Nearly 65% of survey-respondents felt their supervisors treated them like a partner, and 84.6% felt their supervisors created a trusting work environment, more than all but a handful of other areas reviewed.", "\n\nA typical household in the San Jose metro area earned more than $90,000 in 2012, more than in any other metro area in the nation. ", "High incomes are likely the result of the strong presence of traditionally high-paying sectors. ", "For instance, the professional, scientific, and management sector accounted for 18.4% of the area jobs, much higher than the sector's proportion of less than 11% of workers nationwide. ", "Large companies such as Google and Apple are based in the area and provide lucrative job opportunities to area residents. ", "Like a number of high-paying tech companies, both companies were listed on Glassdoor's Best Places to Work this year. ", "Additionally, residents of the San Jose metro area, along with those of Washington, D.C., had the highest economic confidence in the nation, according to a recent Gallup survey. ", "ALSO READ: States With the Highest (and Lowest) Taxes\n\nNearly nine in 10 respondents from the Kennewick region said they used their strengths at work last year, more than in all but four other metro areas. ", "Supervisors in the region were also well-regarded, with 66.7% of respondents reporting their supervisor treated them like a partner last year, second-highest among all areas reviewed. ", "Residents earned more than most Americans, with a median household income of $57,189 in 2012, compared to $51,371 nationwide. ", "While the relationship to workplace satisfaction is unclear, a relatively large percentage — 8.4% of the workforce — was employed in the agricultural industry, more than four times the rate across the nation.", "\n\nUnlike other metro areas with highly rated workplaces, supervisors in Roanoke were not as likely to create a trusting work environment. ", "Less than 80% of respondents thought their supervisor did so in 2013, in-line with the average across all metro areas. ", "However, this did not prevent residents from liking their jobs, with 90.5% of survey respondents reporting job satisfaction, among the best job evaluations among all metro areas surveyed. ", "The job climate in Roanoke is also relatively good, with just a 5.4% unemployment rate in December last year, below the national rate of 6.7% that month.", "\n\nThe unemployment rate in the Visalia metro area was an abysmal 13.1% last December, considerably higher than the national rate of 6.7% that month. ", "Meanwhile educational attainment rates were well below the national rate, with fewer than 15% of residents over 25 holding a college degree. ", "Despite all this, survey respondents felt much better about their workplace than most metro areas surveyed. ", "Respondents rated supervisors, in particular, very well, with 65.6% of residents saying their superiors treated them like a partner. ", "Like several other regions with positively-reviewed work environments, the agriculture sector made up a large proportion of employment in the Visalia area, accounting for nearly 19% of the workforce, compared with just 2.0% nationwide.", "\n\nResidents of the Fort Smith metro area were more likely to say their supervisors provided a trusting environment than Americans anywhere else, with 88.2% saying so in the last year. ", "Nearly 92% were also satisfied with their jobs, more than the vast majority of metro areas reviewed by Gallup. ", "Job satisfaction, however, does not seem to be connected with high incomes in Fort Smith, where a typical household earned just $36,061 in 2012, among the lowest nationwide. ", "Additionally, it did not seem to have much bearing on how people rated other elements of their lives. ", "Fort Smith residents rated their present lives and their future expectations lower than residents anywhere else in the U.S. More than 17% of the workforce in Fort Smith were employed in the manufacturing sector, compared with slightly more than 10% of workers nationwide.", "\n\nNaples residents reported feeling less stressed than those in any other metro area reviewed by Gallup, with more than 70% reporting no stress during the majority of the previous day last year. ", "Low stress levels in the area may be due to a healthy work environment and a relatively good job market. ", "Nearly 64% of respondents thought their supervisors treated them like an equal, compared with just 56.6% nationwide. ", "The area unemployment rate was less than 6.0% in December of that year, much lower than the national unemployment rate of 6.7%.", "\n\nLike many of the cities where workers are satisfied, residents of the Fort Collins metro area are well educated, with nearly 45% of adults 25 years and older having at least a bachelor's degree as of 2012. ", "Much of the work in the area demands high skills and education. ", "This may translate, for many residents, into intellectually stimulating work. ", "Nearly 72% of residents said they learned something new daily, more than all but six metro areas. ", "The area is home to a large number of high-tech manufacturers, as well as Colorado State University, a major research institution. ", "Overall, more than 90% of Fort Collins respondents were satisfied with their jobs, among the highest rates in the U.S.\n\nMore than 91% of Lincoln inhabitants said they were satisfied with their jobs last year, the 12th-highest percentage in the nation. ", "Additionally, nearly 64% of respondents felt treated like a partner at work, higher than in all but a handful of other metro areas. ", "Like many of the cities where workers are satisfied, the area is home to a major research university. ", "Lincoln is home to the University of Nebraska-Lincoln, which spent a quarter-billion dollars on research and development in fiscal 2012 and had more than 8,000 employees as of 2013. ", "The area's job market was excellent as of December last year, with an unemployment rate of just 3.3%.", "\n\nSan Luis Obispo residents evaluated their work experiences better than residents in any other metro area. ", "Nearly nine in 10 area residents were satisfied with their jobs last year. ", "This may be due in part to the fact that respondents believed their lives were filled with interesting experiences and intellectual growth. ", "More than 73% of respondents said they learned something new or interesting the previous day, more than in all but three other metro areas. ", "Additionally contributing to residents' high ratings of their workplace, more than 88% said they utilized their strengths at work and more than 67% felt treated like a partner, both among the highest rates in the country. ", "Workers were also relatively well-paid, with a median household income of $60,264 in 2012, well above the national median of $51,371 that year.", "\n\n24/7 Wall St. is a USA TODAY content partner offering financial news and commentary. ", "Its content is produced independently of USA TODAY." ]

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[ "e the prime factors of 3192010678?", "\n2, 17, 19, 4941193\nWhat are the prime factors of 3583543798?", "\n2, 17, 137, 173, 4447\nWhat are the prime factors of 139991796?", "\n2, 3, 7, 555523\nList the prime factors of 222393605.", "\n5, 7, 29, 113, 277\nList the prime factors of 28391947.", "\n19, 1494313\nList the prime factors of 452479444.", "\n2, 41, 53, 52057\nList the prime factors of 3205870288.", "\n2, 4397, 45569\nList the prime factors of 2819007699.", "\n3, 457, 907, 2267\nList the prime factors of 33226135.", "\n5, 6645227\nList the prime factors of 2504021225.", "\n5, 100160849\nList the prime factors of 816075598.", "\n2, 13, 4003, 7841\nList the prime factors of 571073882.", "\n2, 199, 1039, 1381\nWhat are the prime factors of 2505536877?", "\n3, 1619, 515861\nList the prime factors of 28554693.", "\n3, 1061, 8971\nList the prime factors of 35497400.", "\n2, 5, 177487\nList the prime factors of 646786085.", "\n5, 11, 37, 317831\nList the prime factors of 9044467.", 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2135699\nList the prime factors of 34860037.", "\n34860037\nWhat are the prime factors of 124731287?", "\n67, 1861661\nWhat are the prime factors of 5178605?", "\n5, 761, 1361\nWhat are the prime factors of 35329455?", "\n3, 5, 7, 19, 5903\nList the prime factors of 2553273652.", "\n2, 37, 89, 193841\nWhat are the prime factors of 16915905?", "\n3, 5, 125303\nWhat are the prime factors of 4369561253?", "\n4369561253\nList the prime factors of 49870725.", "\n3, 5, 19, 79, 443\nList the prime factors of 56616784.", "\n2, 7, 61, 8287\nWhat are the prime factors of 104171798?", "\n2, 37, 1407727\nWhat are the prime factors of 49208074?", "\n2, 24604037\nList the prime factors of 403094159.", "\n13, 23, 691, 1951\nWhat are the prime factors of 172648796?", "\n2, 31, 73, 19073\nWhat are the prime factors of 111024997?", "\n111024997\nWhat are the prime factors of 344134056?", "\n2, 3, 7, 292631\nWhat are the prime factors of 152336314?", "\n2, 13, 23, 269, 947\nWhat are the prime factors of 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37, 161333\nList the prime factors of 90464947.", "\n19, 4761313\nList the prime factors of 7620978.", "\n2, 3, 31, 40973\nList the prime factors of 52743343.", "\n41, 389, 3307\nWhat are the prime factors of 53161260?", "\n2, 3, 5, 886021\nList the prime factors of 37103849.", "\n37103849\nList the prime factors of 29957240.", "\n2, 5, 43, 17417\nWhat are the prime factors of 6938085392?", "\n2, 7, 61947191\nWhat are the prime factors of 4475201045?", "\n5, 7, 41, 3118607\nList the prime factors of 871628495.", "\n5, 29, 173, 34747\nList the prime factors of 2269368621.", "\n3, 13, 19396313\nList the prime factors of 21506496.", "\n2, 3, 11, 17, 599\nWhat are the prime factors of 4306772715?", "\n3, 5, 7, 43, 953881\nWhat are the prime factors of 17385263?", "\n7, 23, 83, 1301\nList the prime factors of 2799747794.", "\n2, 47, 491, 60661\nWhat are the prime factors of 47624211?", "\n3, 2099, 2521\nWhat are the prime factors of 2841887416?", "\n2, 17, 37, 659, 857\nList the prime factors of 206689869.", "\n3, 2917, 7873\nWhat are the prime factors of 766616545?", "\n5, 569, 269461\nList the prime factors of 45482862.", "\n2, 3, 659, 11503\nList the prime factors of 1757082611.", "\n739, 1193, 1993\nList the prime factors of 412858610.", "\n2, 5, 71, 581491\nList the prime factors of 464154989.", "\n464154989\nWhat are the prime factors of 2357593737?", "\n3, 785864579\nWhat are the prime factors of 5534184917?", "\n89, 62181853\nWhat are the prime factors of 124967026?", "\n2, 631, 99023\nList the prime factors of 75676654.", "\n2, 2609, 14503\nList the prime factors of 2318583382.", "\n2, 5087, 227893\nWhat are the prime factors of 586087361?", "\n29, 20209909\nList the prime factors of 655581933.", "\n3, 293, 248609\nWhat are the prime factors of 3918380122?", "\n2, 22147, 88463\nList the prime factors of 727971790.", "\n2, 5, 7, 13, 17, 47057\nWhat are the prime factors of 663049634?", "\n2, 13, 25501909\nList the prime factors of 172057036.", "\n2, 47, 915197\nWhat are the prime factors of 68243640?", "\n2, 3, 5, 557, 1021\nWhat are the prime factors of 1292927?", "\n1292927\nList the prime factors of 4103302920.", "\n2, 3, 5, 17, 179, 661\nList the prime factors of 37970559.", "\n3, 11, 173, 739\nWhat are the prime factors of 5054272449?", "\n3, 23857, 70619\nList the prime factors of 4735642377.", "\n3, 29, 727, 74873\nList the prime factors of 656238112.", "\n2, 19, 1079339\nWhat are the prime factors of 118084968?", "\n2, 3, 103, 15923\nWhat are the prime factors of 15480765?", "\n3, 5, 344017\nList the prime factors of 2278365715.", "\n5, 19, 29, 28517\nWhat are the prime factors of 3408626188?", "\n2, 11, 317, 244381\nList the prime factors of 146787965.", "\n5, 137, 421, 509\nList the prime factors of 7331462327.", "\n7, 61, 17169701\nList the prime factors of 15723203.", "\n19, 827537\nList the prime factors of 85885705.", "\n5, 53, 324097\nList the prime factors of 63500624.", "\n2, 11, 191, 1889\nWhat are the prime factors of 283636946?", "\n2, 61, 38113\nList the prime factors of 2110005262.", "\n2, 5323, 198197\nList the prime factors of 1416023189.", "\n7, 37, 5467271\nWhat are the prime factors of 2905160830?", "\n2, 5, 11, 13, 359, 5659\nWhat are the prime factors of 65106273?", "\n3, 37, 586543\nWhat are the prime factors of 412709295?", "\n3, 5, 29, 97, 9781\nList the prime factors of 1220275411.", "\n1220275411\nList the prime factors of 88231367.", "\n7, 271, 46511\nWhat are the prime factors of 615228200?", "\n2, 5, 3076141\nList the prime factors of 1688730213.", "\n3, 179, 3144749\nWhat are the prime factors of 3890611?", "\n19, 23, 29, 307\nWhat are the prime factors of 97539833?", "\n97539833\nWhat are the prime factors of 582929492?", "\n2, 127, 1147499\nList the prime factors of 353426190.", "\n2, 3, 5, 13, 29, 31249\nList the prime factors of 123151397.", "\n131, 940087\nList the prime factors of 39256549.", "\n43, 547, 1669\nWhat are the prime factors of 2900280226?", "\n2, 1433, 1011961\nWhat are the prime factors of 3501148230?", "\n2, 3, 5, 38901647\nWhat are the prime factors of 876740898?", "\n2, 3, 11, 1" ]

{ "pile_set_name": "DM Mathematics" }

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[ "Turning to the Past to Envision a Different Future: Family Accountability in Eliaichi Kimaro’s “A Lot Like You”\n\nby Wendy Elisheva SomersonSeptember 8, 2011\n\nSo I think there is a responsibility, in a sense, to adapt. ", "Not to adapt in a self-sacrificing way or in a foolish way of ignoring completely that you have an identity. ", "But recognizing that even within yourself, the children that you have, the grandchildren that you have … they have a different expectation, they have a different value system, and so think not only in terms of I’m going to do a thing the way my grandfather did it, or going to sing the way my grandfather sang. ", "But maybe also sing knowing that there is this person I have to sing to.", "\n\n—Sadikiel Kimaro\n\nWhen I saw Eliaichi Kimaro’s documentary A Lot Like Youpremierat the Seattle International Film Festival this year, one of my first responses to this moving and complex film was to recognize it as a model for a personal and family accountability process. ", "Having just finished reviewing The Revolution Starts at Home: Confronting Intimate Violence Within Activist Communities for Bitchmagazine, I was interested in seeing more concrete examples of community accountability, which Ching-In Chen, Jai Dulani, and Leah Lakshmi Piepzna-Samarasinha define as “any strategy to address violence, abuse or harm that creates safety, justice, reparations, and healing without relying on police, prisons, childhood protective services, or any other state systems.” ", "A Lot Like You brings to life the complicated, messy, beautiful, and liberatory process of addressing harm and seeking healing within a family context.", "\n\nTo discuss the process of creating her film, I sought out Kimaro, a Seattle filmmaker and activist, and was excited to learn that she too sees her film as capturing the beginning of a family accountability process. ", "The film was originally titled Worlds Apart, and its change to A Lot Like You reflects the journey that Kimaro embarked upon while creating this documentary about her relationship to her father’s side of the family—the Chagga tribe in Tanzania who live on the slopes of Mt. Kilimanjaro. ", "The first cut of the film emphasized the cultural differences of her family that “spans many different bridges, continents, and worlds,” but the final version emphasizes Kimaro’s discovery of her connection with her Chagga relatives.", "\n\nAfter growing up in Tanzania, her father Sadikiel Kimaro earned a scholarship to pursue his Ph.D. in economics in the United States where he met his wife, Young, a student from Korea. ", "He spent the next forty years or so working for the IMF, while his wife worked at the World Bank, and they raised Eliaichi and her brother in a suburb of Washington, DC. ", "After her parents retired to Tanzania, Eliaichi and her partner Tom decided to join them with the intention of filming for nine months, partly because the filmmaker feels only a “hazy connection” to her Tanzanian family in spite of having spent every other summer there as a kid.", "\n\nSetting out to portray “culture” in Tanzania, they interview members of Kimaro’s family and film different aspects of Chagga life, but often bump into cultural disconnect and miscommunication. ", "In the film’s voiceover narration, Kimaro describes how “everyone around us performed their version of Chagga culture, one they thought I, as a tourist, wanted to see.” ", "The first cut of the film was focused on the filmmaker’s father’s story, but included interviews with her two aunts who describe, in brutal detail, how their marriage rituals involved violence. ", "Her aunts did not know that Kimaro herself was also a survivor of sexual abuse.", "\n\nWhen Kimaro and her partner screened Worlds Apart to a Seattle test audience in September 2009, they thought they were just about done with the film they’d been working on for the past seven years. ", "They focused on perfecting details such as the film’s soundtrack and subtitles, yet Kimaro describes “feeling nothing” when she watched the screening. ", "A local filmmaker took her aside and told her that she had made a “nice” film, but if she didn’t step toward her aunts’ stories, then she was doing them a disservice and being complicit in the silence that had kept them quiet about their experiences for most of their lives. ", "He suggested that she ask her parents if they knew how her aunts got married.", "\n\nEliaichi Kimaro with her parents, Sadikiel and Young. ", "Credit: Seattle International Film Festival.", "\n\nThe next day, Eliaichi sat down to interview her parents before they flew back to Tanzania. ", "Afterward, she realized that her story could no longer center on her father: “I am Chagga because of him, but my understanding of what it means to be Chagga can get only so far by following his path, and then there’s a fork where his path goes one way, and mine goes the other.” ", "Facing up to male dominance in Chagga culture, Kimaro described “getting real” with what it meant to have Chagga women’s history as part of her history. ", "Although she added only one scene to the film (the conversation with her parents), she rewrote the entire narration to center her own experience. ", "Once she became the center for the film, the narrative revealed her surprising connection to Chagga women, and the changed title, A Lot Like You, reflects the new emphasis.", "\n\nWhat begins Kimaro’s journey through her family’s cultural history is her desire to pass on a Chagga cultural inheritance to her daughter. ", "But what deepens the story is her realization that she actually wants to shift the next generation’s stance toward family trauma by bringing it to light. ", "Faced with the daunting task of representing her extended Chagga family, her parents, her own sexual abuse, and her aunt’s sexual abuse, Kimaro still manages not to reduce all of Chagga culture to this connecting thread in the film. ", "In fact, one reason this film works as a model for doing accountability work is that Kimaro situates her personal family story within a social, historical, and political context of African decolonization, transnational relations, race, class, and gender politics. ", "The result is a complex and beautiful film that brings the audience along with Kimaro to bear witness to some difficult truths.", "\n\nClass Matters Among Family\n\nOne powerful way Kimaro turns toward the truth is by refusing to simplify the differences between her immediate and extended family. ", "We first get the sense that there are tensions within her father’s family when Kimaro gathers the six siblings together at her father’s house. ", "All the siblings except her father seem uncomfortable, and Kimaro discovers that they rarely get together on their own in spite of living within walking distance of one another. ", "With some bitterness, her Aunt Awonyisa describes how she did just as well in school as Sadikiel, but was not allowed to pursue an education because she was a girl. ", "Directing her comments at the filmmaker’s father, Awonyisa explains, “If God had helped me, I would have been the one to go overseas. ", "And I would travel all over the place. ", "And then you would come, and I would be the one to receive you.”", "\n\nSadikiel’s siblings, in their seventies and eighties, have lived in the same place their entire lives, and like all families, have complicated relationships with each other. ", "They also have huge class and culture differences from Sadikiel. ", "In the film Kimaro describes how her aunts, uncles, and neighbors would find her alone in the summer when she was a kid and ask her for money, while insisting that she not tell her parents. ", "Sharing her memory of being on a ski lift with her father as a kid, Kimaro narrates how her father told her that the money they spent that day on skiing was more than his brothers would make in an entire year. ", "As an economist, her father must have always been making that conversion between his life in the United States and his family’s life in Tanzania. ", "While we see images of her parents enjoying their beautiful house and swimming pool they retired to in Tanzania, Kimaro asks, “I wonder if there is a cost to us from my parents’ hard-won success?”", "\n\nWhat I appreciate about this question is that it captures both her nuclear family’s class privilege and something that is harder to pinpoint—the loss of culture and disconnection that can accompany class mobility. ", "As Kimaro described to me:\n\nGrowing up with that degree of class difference in my family, I didn’t know where to go as a child to make sense of that. ", "My cousins were living in mud huts assembled with cow dung and sticks and no running water or electricity. ", "How do you explain that to folks at school who came back from very different family vacations?", "\n\nShe chose to talk to her peers about going on safari because it was something they could understand. ", "Having that degree of poverty in her family has been shameful for Kimaro at the same time that having privilege has also been shameful. ", "But she points out that the one directive she had with the film was “to sit with the messiness of all of it … to just sit with the messiness of race and class, of the migrant experience and my dad being the lucky one to leave, and what it means to be the beneficiary of that.”", "\n\nI see this radical honesty and refusal to simplify things as a wonderful model for moving toward a complex understanding of class and family relationships. ", "When we try to explain our family histories, we often find that words and concepts fall short. ", "The activist language of anti-oppression work is helpful in naming privilege and oppression, but it doesn’t always describe some of the spaces in between, including what it means to “pass” from one identity to another with a simultaneous material gain and cultural loss. ", "This sense of loss and the accompanying longing to feel connected to a culture is what propelled Kimaro to make this film.", "\n\nBearing Witness to Women’s Stories\n\nIn the film’s narration, Kimaro describes how hearing her aunt’s story of not being allowed to pursue an education at the family gathering made her recognize the need to interview the women on their own. ", "While her aunts always seemed closed off to her, she found that when she approached them with curiosity, “they opened up and shared with me more than I was prepared to hear.” ", "She juxtaposes her aunts’ stories of violent marriage rituals with images from her own wedding, where she incorporated a Chagga ritual of sharing beer between the two families. ", "When she asked her Uncle Mkunde who attended her wedding if this ritual reminded him of his own wedding, he didn’t answer. ", "In fact, as she narrates, all of the men remained “tight lipped and unclear about how they got married, but when I spoke with the women on their own … they remembered everything.”", "\n\nHer aunts describe how men could do as they pleased with them once they were considered ready for marriage. “", "The situation was bad, my dear,” Aunt Awonyisa says. ", "Her aunts and a family friend describe how if they struggled against the violence, the men would just gather a larger group to physically overpower them. ", "Aunt Awonyisa describes how her brother colluded in helping a friend of his to rape her. ", "Though she tried to run away after being raped, her brother and father returned her to her new husband. ", "Both aunts describe having to be subservient and obedient to their husbands: “I would work for him; he would abuse me,” Aunt Ndereriosa describes, “and I’d be forced to return to him … and he would continue to abuse me.” ", "The story that unfolds until this point holds only gentle surprises, but her aunt’s stories, whose trauma they embody with physical gestures, come as a shock.", "\n\nKimaro believes that her special relation to Chagga culture allowed her aunts to open up to her: “I was insider enough to have access to my aunts, but I was outsider enough not to know any better than to ask questions about how they got married.” ", "Because her Swahili and Kichagga were not good enough for Kimaro to verbally support her aunts, she simply gave them the space to share their stories without interruption. ", "They had no idea that she had been working as a domestic violence counselor over the past ten years. “", "I’d seen how bearing witness to someone’s suffering can transform their life just as it had for me,” Kimaro narrates in the film. “", "When I was seven,” she describes matter-of-factly, “I was raped repeatedly by someone who worked in our home. ", "I kept this abuse to myself for many years, and the secret almost destroyed me.” ", "Being able to tell her story allowed her to come to terms with her own feelings of rage, shame, and fear.", "\n\nJust as we are asked to bear witness to her aunt’s stories along with Kimaro, we are also asked to bear witness to Kimaro’s story of child sexual abuse. ", "At the festival screening, it was incredibly powerful to hear these stories in a packed movie theater because sexual abuse is rarely discussed in public without being sensationalized. ", "When I shared this with her, Kimaro told me that she wished it had been her intention from the start to make this film. ", "I find it amazing that she had the courage to follow the film down this incredibly personal path. ", "She models a process of seeking out, highlighting, and listening to marginalized voices in a family accountability process, as well as a radical willingness to shift her understanding of her family narrative based on those voices.", "\n\nBoth aunts express their gratitude to Kimaro for asking them to share their stories. ", "Aunt Ndereriosa says, “After speaking like this, I feel a burden has been lifted off my heart … I did not know how to unload it and start living.” ", "She claims that God told her the day would come when she could share her story, and Aunt Awonyisa concurs that God was with them that day. ", "While Kimaro doesn’t subscribe to the same notion of a Christian God, she also feels like a larger force was present that day. ", "Her aunts looked like different people after telling their stories because “they gave voice to trauma they had been carrying for their entire lives.”", "\n\nThe Hardest Conversation: Family Accountability\n\nWhen Kimaro asks her parents whether they knew about how her aunts got married, she finds out that her mom had no idea (until she saw the film), but her dad knew and says, “it was accepted.” ", "He explains that these women’s stories do not indicate that they were assaulted or that they wished to involve the police or courts. ", "It would be missing the point, he insists, to dramatize this aspect of the culture “because this is how the practice of marriage took place there. ", "It wasn’t criminal activity. ", "It wasn’t violence. ", "But it’s a way of getting married.” ", "Kimaro’s mom, on the other hand, argues that women in the Chagga culture were being doubly punished: first by being raped and then by their own families who refuse to let them return home after being raped. ", "Her father responds that “it is fundamentally an ethnic thing, a cultural thing that should be understood in the cultural context.”", "\n\nKimaro describes this conversation as “possibly one of the hardest conversations I’ve ever had with my parents.” ", "Having convinced herself that her dad didn’t know about this practice, Kimaro was completely taken aback by his explanation. ", "Watching the film, I was also shocked and disturbed by her father’s words. ", "Having just seen the aunts describe their experiences in visceral detail, I didn’t understand how this seemingly sensitive man could possibly say her aunts’ assaults weren’t violent.", "\n\nGrateful that her mom could be her voice, Kimaro didn’t know how to express her extreme emotions because she had never told her dad about her own abuse. ", "Her mom, on the other hand, was able to disagree with her father in a way that was loving and respectful of her dad’s dignity, while calling out the limits of his purview. ", "Her mom’s support made the conversation tolerable for Kimaro, but it was still incredibly painful. ", "She was surprised that after having lived in the United States with his family for so many years, her father would still “have a hard time reaching for the fact that what happened to the women in his family was actually a legitimate harm that was violent and traumatic.”", "\n\nWhen I told Kimaro that it was striking to me that her dad uses the police as a measure of harm, Kimaro explained how his comments made little sense because nobody on the mountain even has a phone, let alone a sense of whom to contact for help in a culture where this practice was normalized. ", "Her dad displays his double perspective by saying it was an “ethnic thing” and then referring to the American criminal justice system to judge this practice. ", "His defensiveness about Chagga culture may also result from having to carry the weight of representing his culture in the face of Western assumptions about how women are treated in Africa. ", "He thought that his daughter was making a film to celebrate Chagga culture, and he couldn’t understand why she would focus on this one aspect. ", "While Kimaro believes that the film captures the “beauty and brutality of Chagga culture,” she also recognizes that that it takes a turn after her aunts’ stories and points out that “you have to be in love with mom and dad, to be rooting for them, for the second half of the film to work.”", "\n\nKimaro has reached a place of “spaciousness and compassion” for her dad by recognizing it was most likely the first time he was asked to explain Chagga marriage practices to the last person with whom he wanted to have this conversation. ", "During that conversation, Kimaro kept thinking that her father just didn’t look like himself. ", "After talking with a friend who is an expert in trauma, she realized that she may have been seeing her dad regress to the age when he first learned about this practice as a child. ", "She wonders, “If you know that is true about your sisters and how they got married and how your mother possibly got married, where do you have to go as a human to survive that?” ", "How could her dad live with this knowledge, she wonders, and thrive in his life without losing himself in something to numb the pain?", "\n\nHearing Kimaro try to understand her father, I felt my own compassion kick in because it forced me to think about how trauma has affected him as well. ", "While the main targets of this practice were women, the violence affected everyone in the family. ", "Offering a model for doing accountability work, Kimaro puts the survivors’ stories at the center, while considering the effects of the trauma on everyone. ", "Near the end of the film, Kimaro narrates “given the different roads we’ve traveled, we may never see eye to eye on his sister’s stories, but I love [my father].” ", "Watching the film, when I heard the softness and complexity in her tone when she says “love,” I recognized the power of her stretching to hold on to this connection amid emotional disconnection.", "\n\nKimaro describes what her aunts demanded of her: they asked, “Now that we’ve shared our stories with you, what are you going to do about it?” ", "Her response was to make this film and decide to tell her father about her own sexual abuse. ", "While she did tell him about her abuse before he saw a copy of the film, they still haven’t had the full conversation because he is back in Tanzania, and she wants to have that conversation in person. ", "She believes the film is forcing her family to have conversations that will only strengthen their bonds. ", "While as viewers, we want to know how it turns out (after one screening, an audience member demanded of Kimaro “tell me how to feel about your father”), that conversation is still in progress, and the film does not offer any tidy resolution. ", "What it does offer is a moment in time where Kimaro is confronting family trauma, while respecting the complexity and humanity of everyone in her family.", "\n\nIntergenerational Trauma and the Future\n\nIn the film Kimaro says:\n\nIt’s horrifying to think that abuse this rampant, this brutal, could have been a part of my family’s history without me knowing it. ", "But then maybe I did know because all the seemingly random life choices I made from the time I was seven were paving the way for me to sit down with my aunts in front of the camera twenty-five years later.", "\n\nIn person, she described how she always had a feeling of inevitability about her abuse, which made her realize that she needed to face this history in order not to pass it on to her own children.", "\n\nThe film ends with an image of her aunt holding the filmmaker’s daughter Lucy. ", "According to Kimaro, this image had a lighter emotional weight in the first cut of the film: before they reframed and contextualized her aunts’ stories, it felt “sentimental and cloying.” ", "This film’s evolution demonstrates that moving toward the painful and silenced parts of our histories allows us to envision a different future. ", "Ending with that image, the film asks us to reflect on what is being passed on to the next generation. ", "By making this film, Kimaro is giving her daughter the tools to develop a different relationship to her cultural inheritance.", "\n\nThe tagline for the film, “the truth has no borders” refers to the ripple effect that started after her aunts summoned Kimaro to rise to the occasion. ", "She feared that if she focused on her experience as a queer-identified, mixed-race, first-generation Seattleite, the film would not speak to most people. ", "But she discovered that the opposite was true. ", "Once her personal narrative emerged, everyone involved in making the film, from the composer to the editor, delved into their own family histories and came to a deeper understanding of their identities. ", "This ripple effect continues as the film moves out into the world and our collective consciousness; everyone who sees it has their own response to this truth telling. ", "There’s something about the film that is bigger than any one of us.", "\n\n“It is calling out the truth in all of us,” Kimaro says. “", "The story demands of us what my aunts had demanded of me. ", "It compels us all forward.”", "\n\nWendy Elisheva Somerson—one of the founders of the Seattle chapter of Jewish Voice for Peace—believes that art, activism, and ritual help us envision and create the world to come. ", "She is a somatic practitioner in Seattle.", "\n\nCOMMENT POLICY Please read our comments policy. ", "We invite constructive disagreement but do not accept personal attacks and hateful comments. ", "We reserve the right to block hecklers who repost comments that have been deleted. ", "We do have automated spam filters that sometimes miscategorize legitimate comments as spam. ", "If you don't see your comment within ten minutes, please click here to contact us. ", "Due to our small staff it may take up to 48 hours to get your comment posted.", "\n\n4 Responses to Turning to the Past to Envision a Different Future: Family Accountability in Eliaichi Kimaro’s “A Lot Like You”\n\nI saw this remarkable film last night and recommend you go see it when showing near you! ", "I am grateful to return to this article again to help sort out a myriad of feelings invoke by the film.", "\n\nThis film was Eliaichi’s personal story, her journey to answer ‘Who am I in this world?’. ", "Her journey is vulnerable, thought provoking, honest, and simply brave. ", "The film also holds many family stories within her story, where each person took the risk to be vulnerable, open, and centering in their personal truth. ", "Powerful and real. ", "Personal story unfolding and holding inter-sectional complexities of race, gender, class, violence.", "\n\nOn my own path of healing from past family abuse, using my voice to share my story and truth has been vital. ", "It has been difficult but a transformative process breaking my silence, the silence within my family, silence within my larger community, within the silencing culture here in the US which encourages such things to be hidden, not brought to light, and certainly not discussed. ", "Using our voice is often the beginning of transformation. ", "I share that feeling of a weight being lifted each time I listen to a survivor’s story where they are bringing their truth to the surface.", "\n\nI left this film feeling cracked open and inspired with a renewed sense of how important it is to gently hold and honor the struggle and complexity of my own experiences. ", "Only you can share your story, only I can share mine, but when we do so in a vulnerable and truthful way, an opportunity emerges to uncover points of important connection, understandings, and the important realization we are not alone in our struggles and healing.", "\n\nThis film will certainly inspire you to look inside yourself and hopefully ignite many conversations.", "\n\nOwning read this I assumed it had been incredibly insightful. ", "I value you using some time and energy to put this article jointly. ", "I when again identify myself shelling out way for you to a lot time both equally studying and commenting. ", "But so what, it absolutely was nevertheless worthwhile!" ]

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[ "Q:\n\nWhat is the difference between ‘interest in' & ‘interest for' ?", "\n\nWhen I should use 'for' after the noun 'interest' & when 'in' should be used after that?", "\nFor example, is it correct to say \"I have no interest for drug\"?", "\nIf you can give an elucidation with example, it will be better for me to understand. ", "\n\nA:\n\nIn most of the cases, you are generally interested in.... something. ", "The word here serves as an adjective. ", "\nAs Jason says, \n\nI am not interested in drugs OR I am very interested in history\n\nHowever, 'interest for...' is not incorrect! ", "But it's used differently. ", "It then becomes a noun. ", "\n\nThis museum holds particular interest for geologists.", "\n\nA:\n\nWith interest as a noun meaning something that draws or holds one's attention, in is generally used to specify the object of the interest:\n\nAlmost fifty years after the end of the Second World War, scholarly interest in its history appears to be as vigorous as ever. ", "Soviet Military Deception in the Second World War\n\nin can also be used to specify a time period:\nAs it can be seen, only seven elements (As, Br, Cr, Hg, I, Se and V) were of interest in the last few years. ", "Handbook of mineral elements in food\nand also to specify a location:\n\nExclusion from school has excited a great deal of research interest in England during the 1990s. ", "Combating social exclusion through education\n\nfor is much less widely used, and generally specifies who is interested in something:\n\n...the 2011 Commission Decision is of great interest for social services... Financing Services of General Economic Interest\n\nIt could also be used to specify a time period\n\nThe equation of state (EOS) of dense hydrogen has been a subject of great interest for years because of its astrophysical importance and its theoretical novelty. ", "The Link Foundation Energy Fellowship Program\n\nYou cannot use for to identify the object of interest\n\nI have no interest for drugs - wrong\n\nbut you could turn it round to specify who is interested\n\nDrugs have no interest for me\n\n" ]

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[ "Intermediate-temperature solid oxide fuel cells (IT-SOFCs) have garnered much attention in recent years due to their potential to meet cost and reliability targets required of commercial products. ", "Two areas of interest in IT-SOFCs are reducing electrolyte thickness and/or discovering new electrolyte materials with improved ionic conductivity. ", "In searching for new electrolyte materials, proton conducting ceramics emerge as strong electrolyte candidates for IT-SOFCs. ", "Among these proton conductors, yttrium-doped barium zirconate (BZY) has appeal due to its high bulk proton conductivity, excellent chemical stability in CO2 and good mechanical strength. ", "However, this material is refractory and requires a very high temperature (from about 1700° C. to about 2100° C.) and a long sintering time (often greater than 24 hours), even with nanosize starting powders, to achieve a dense microstructure. ", "Higher temperature or longer time often results in a deficiency in barium and other impurity phases, causing high grain-boundary resistance. ", "Although the sintering temperature of BZY can be effectively reduced by adding sintering aids, e.g. NiO, ZnO, MgO, CuO, and Sc2O3, such sintering aids can lead to a lowered ionic conductivity and increased electronic conductivity, especially in reducing atmospheres.", "\nA Li2CO3—K2CO3 eutectic mixture supported by a porous LiAlO2matrix is a standard electrolyte package for molten carbonate fuel cells (MCFCs). ", "The pore size and porosity in the LiAlO2 matrix used by the MCFC industry are carefully tailored so that the molten carbonate phase is retained within the porous LiAlO2 matrix by capillary forces. ", "The pores in LiAlO2 are, therefore, filled with the molten carbonate phase, making the solid/liquid electrolyte membrane gastight.", "\nAs such, a need exists for a dense proton conductor membrane that can benefit from such a strategy. ", "Methods of manufacturing such a membrane would also be desirable." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "// Copyright 2014 The Chromium Authors. ", "All rights reserved.", "\n// Use of this source code is governed by a BSD-style license that can be\n// found in the LICENSE file.", "\n\n#ifndef CONTENT_BROWSER_DEVTOOLS_PROTOCOL_PAGE_HANDLER_H_\n#define CONTENT_BROWSER_DEVTOOLS_PROTOCOL_PAGE_HANDLER_H_\n\n#include <stddef.h>\n\n#include \"base/compiler_specific.h\"\n#include \"base/macros.h\"\n#include \"base/memory/weak_ptr.h\"\n#include \"base/time/time.h\"\n#include \"cc/output/compositor_frame_metadata.h\"\n#include \"content/browser/devtools/protocol/devtools_protocol_dispatcher.h\"\n#include \"content/public/browser/notification_observer.h\"\n#include \"content/public/browser/notification_registrar.h\"\n#include \"content/public/browser/readback_types.h\"\n\nclass SkBitmap;\n\nnamespace content {\n\nclass NavigationHandle;\nclass RenderFrameHostImpl;\nclass WebContentsImpl;\n\nnamespace devtools {\nclass PageNavigationThrottle;\n\nnamespace page {\n\nclass ColorPicker;\n\nclass PageHandler : public NotificationObserver {\n public:\n typedef DevToolsProtocolClient::Response Response;\n\n PageHandler();\n ~PageHandler() override;\n\n void SetRenderFrameHost(RenderFrameHostImpl* host);\n void SetClient(std::unique_ptr<Client> client);\n void Detached();\n void OnSwapCompositorFrame(cc::CompositorFrameMetadata frame_metadata);\n void OnSynchronousSwapCompositorFrame(\n cc::CompositorFrameMetadata frame_metadata);\n void DidAttachInterstitialPage();\n void DidDetachInterstitialPage();\n bool screencast_enabled() const { return enabled_ && screencast_enabled_; }\n\n Response Enable();\n Response Disable();\n\n Response Reload(const bool* bypassCache,\n const std::string* script_to_evaluate_on_load,\n const std::string* script_preprocessor = NULL);\n\n Response Navigate(const std::string& url, FrameId* frame_id);\n\n Response StopLoading();\n\n using NavigationEntries = std::vector<scoped_refptr<NavigationEntry>>;\n Response GetNavigationHistory(int* current_index,\n NavigationEntries* entries);\n\n Response NavigateToHistoryEntry(int entry_id);\n\n Response CaptureScreenshot(DevToolsCommandId command_id);\n\n Response StartScreencast(const std::string* format,\n const int* quality,\n const int* max_width,\n const int* max_height,\n const int* every_nth_frame);\n Response StopScreencast();\n Response ScreencastFrameAck(int session_id);\n\n Response HandleJavaScriptDialog(bool accept, const std::string* prompt_text);\n\n Response QueryUsageAndQuota(DevToolsCommandId command_id,\n const std::string& security_origin);\n\n Response SetColorPickerEnabled(bool enabled);\n Response RequestAppBanner();\n\n Response SetControlNavigations(bool enabled);\n Response ProcessNavigation(const std::string& response, int navigation_id);\n\n Response AddScriptToEvaluateOnLoad(const std::string& source,\n std::string* identifier);\n Response RemoveScriptToEvaluateOnLoad(const std::string& identifier);\n Response SetAutoAttachToCreatedPages(bool auto_attach);\n Response GetResourceTree(scoped_refptr<FrameResourceTree>* tree);\n Response GetResourceContent(DevToolsCommandId command_id,\n const std::string& frame_id,\n const std::string& url);\n Response SearchInResource(DevToolsCommandId command_id,\n const std::string& frame_id,\n const std::string& url,\n const std::string& query,\n bool* case_sensitive,\n bool* is_regex);\n Response SetDocumentContent(const std::string& frame_id,\n const std::string& html);\n Response ConfigureOverlay(const bool* is_suspended,\n const std::string* message);\n Response GetAppManifest(\n std::string* url,\n std::vector<scoped_refptr<AppManifestError>>* errors,\n std::string* data);\n Response GetLayoutMetrics(\n scoped_refptr<LayoutViewport>* layout_viewport,\n scoped_refptr<VisualViewport>* visual_viewport);\n\n std::unique_ptr<PageNavigationThrottle> CreateThrottleForNavigation(\n NavigationHandle* navigation_handle);\n\n void OnPageNavigationThrottleDisposed(int navigation_id);\n void NavigationRequested(const PageNavigationThrottle* throttle);\n\n private:\n WebContentsImpl* GetWebContents();\n void NotifyScreencastVisibility(bool visible);\n void InnerSwapCompositorFrame();\n void ScreencastFrameCaptured(cc::CompositorFrameMetadata metadata,\n const SkBitmap& bitmap,\n ReadbackResponse response);\n void ScreencastFrameEncoded(cc::CompositorFrameMetadata metadata,\n const base::Time& timestamp,\n const std::string& data);\n\n void ScreenshotCaptured(\n DevToolsCommandId command_id,\n const unsigned char* png_data,\n size_t png_size);\n\n void OnColorPicked(int r, int g, int b, int a);\n\n // NotificationObserver overrides.", "\n void Observe(int type,\n const NotificationSource& source,\n const NotificationDetails& details) override;\n\n bool enabled_;\n\n bool screencast_enabled_;\n std::string screencast_format_;\n int screencast_quality_;\n int screencast_max_width_;\n int screencast_max_height_;\n int capture_every_nth_frame_;\n int capture_retry_count_;\n bool has_compositor_frame_metadata_;\n cc::CompositorFrameMetadata next_compositor_frame_metadata_;\n cc::CompositorFrameMetadata last_compositor_frame_metadata_;\n int session_id_;\n int frame_counter_;\n int frames_in_flight_;\n\n std::unique_ptr<ColorPicker> color_picker_;\n\n bool navigation_throttle_enabled_;\n int next_navigation_id_;\n std::map<int, PageNavigationThrottle*> navigation_throttles_;\n\n RenderFrameHostImpl* host_;\n std::unique_ptr<Client> client_;\n NotificationRegistrar registrar_;\n base::WeakPtrFactory<PageHandler> weak_factory_;\n\n DISALLOW_COPY_AND_ASSIGN(PageHandler);\n};\n\n} // namespace page\n} // namespace devtools\n} // namespace content\n\n#endif // CONTENT_BROWSER_DEVTOOLS_PROTOCOL_PAGE_HANDLER_H_\n" ]

{ "pile_set_name": "Github" }

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[ "group \"Battery_Config\" struct {\n value \"poll_interval\" int: 512;\n value \"alert\" int: 30;\n value \"alert_p\" int: 10;\n value \"alert_timeout\" int: 0;\n}\n" ]

{ "pile_set_name": "Github" }

[ 0.0007834880379959941 ]

[ "Decreased prevalence of asthma among farm-reared children compared with those who are rural but not farm-reared.", "\nFarm exposure has been associated with decreased asthma prevalence. ", "We compared asthma prevalence among rural farm-reared and non-farm-reared children and examined farm demographic and environmental factors. ", "We performed a cross-sectional, population-based survey among 36,500 rural kindergarten through 12th grade school children. ", "Surveys were distributed through schools and returned by mail. ", "Of the 4152 participants, 18% had lived or were currently living on a farm. ", "Compared to other rural children, farm children had more siblings (3.0 vs 2.5; P < .015), were more likely to be breast-fed (64% vs 58%; P < .002), to have pets (88% vs 79%; P < .001), and were less likely to have attended daycare (39% vs 50%; P < .001). ", "Farm-reared children were less likely to have had a history of wheezing (28% vs 34%; P < .003) or a diagnosis of asthma (22% vs 26%; P < .002). ", "This effect was greater among children younger than 10 years of age than among older children. ", "There was no difference in the frequency of either asthma or non-asthma allergy symptoms during the previous 12 months. ", "When analyzed by age and sex, decreased asthma prevalence was associated with farm rearing among younger children more than among adolescents. ", "Farm residence beginning during the first 5 years, but not later, was associated with decreased rates of ever asthma (23.7% vs 33.7%; P < .005). ", "Asthma, but not other manifestations of allergy, is less commonly reported among farm-reared children. ", "Early exposures may be more important than those occurring later. ", "Without ongoing exposures, their effects on disease expression may diminish over time." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Sensitivity mapping of the human foot: thresholds at 30 skin locations.", "\nMechanoreceptors in the skin provide sensory input for the central nervous system about foot placement and loading. ", "This information is used by the brain to actively control or regain balance and is important to establish memory traces for subsequent movement. ", "A sensitivity map of the human foot could help to understand the mechanisms of the foot as a sensory organ for movement adjustment and balance control. ", "Touch and vibration perception threshold values from 30 plantar and dorsal foot locations were determined in more than 40 women and men between 20 and 35 years. ", "Semmes Weinstein monofilaments and a vibrotactile neurothesiometer were used for skin sensitivity threshold detection. ", "Large sensitivity differences were present between the 30 different foot sites. ", "Gender effects were not present for touch but women had better sensitivities for vibration (p < 0.01), especially on the dorsal aspect of the foot. ", "Age, in our cohort of 20- to 35-year-olds, did not have an influence on vibration or touch sensitivity. ", "The heel had the highest detection thresholds for touch but was very sensitive for vibration stimuli. ", "Compared to the dorsum, the plantar foot was substantially more sensitive, especially for vibration detection. ", "The results suggest that primarily the fast adapting plantar mechanoreceptors are important in assisting balance control during human locomotion. ", "The sensitivity map of the foot will help in understanding the function of the foot as a sensory organ and could be useful in creating footwear for better balance control and for the design of comfortable shoes." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Article content continued\n\nOther groups of similar magnitude have always been able to find ways to push on when important members\n\nAll of this — even Neil Peart’s remorseless flintiness — reflects the distinctive, endearing characteristics of Rush: the band has now ceased to exist for some of the same reasons it attracted adoring generations of listeners. ", "As a commercial proposition, Rush remains a potential superpower. ", "Other groups of similar magnitude have always been able to find ways to push on when important members, or even every member that anyone might recognize, came to the end of the road. (", "In a rock group there is usually at least one person who could really use the cash from a tour.)", "\n\nCould Geddy Lee and Alex Lifeson find some young drummer with healthy wrists and ankles, take “Rush” to the casino circuit, and sell mountains of $75 tickets? ", "They probably could, and they would probably put on a wonderful show. ", "But it is unthinkable (he wrote, knocking on the wood of his desk) for them to do such a thing under the Rush name.", "\n\nPhoto by SunMedia\n\nThey could probably even devise a low-stress acoustic-heavy setlist, with slowed-down versions of the hits, that they could take to small venues with Peart in tow. ", "Tempting as such schemes must be — Lee was publicly in denial about Peart’s second retirement for ages, and Lifeson says he would go on if it were entirely up to him — they do not suit the nature of Rush.", "\n\nThe group is a three-piece in which every piece counts more or less equally. ", "And part of what their fans pay to see is physical effort of the highest intricacy. ", "I hope it will not offend my fellow Rush fans if I compare it to juggling or acrobatics, or at least suggest that it has such an aspect. ", "Rush songs are full of unpredictable, shifting time signatures and difficult cues. ", "The band’s numerical paucity leaves nowhere to hide dropped chords or melodic clangers. ", "Unlike most three- and four-piece groups, Rush has almost always refused to ever bring a hired sideman onto the live stage, even though this requires Lee to operate sequencers with foot pedals while playing what are often ludicrously difficult bass lines — AND singing like, well, like Geddy Lee." ]

{ "pile_set_name": "OpenWebText2" }

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[ "Surgical treatment of fixed cervical kyphosis with myelopathy.", "\nA retrospective clinical study. ", "To investigate clinical and radiographic outcomes following the surgical treatment of fixed cervical kyphosis with myelopathy. ", "To our knowledge, a study specifically addressing the surgical treatment of fixed cervical sagittal deformity has never before been published. ", "Sixteen patients treated surgically for fixed cervical kyphosis and myelopathy were followed for a mean of 4.5 years (range, 25-112 months). ", "The study group consisted of 9 males and 7 females, with an average age of 52 years (range, 31-78 years). ", "The principal etiologies of cervical deformity were prior laminectomy (63%), advanced spondylosis (19%), infection (6%), neuromuscular disease (6%), and metabolic disease (renal osteodystrophy) (6%). ", "All patients were clinically evaluated by the Nurick classification and Odom criteria both before surgery and at the time of most recent follow-up. ", "Radiographic analysis was performed using thin-cut CT scans, dynamic radiographs, and 14 x 36-inch scoliosis films. ", "The mean preoperative cervical Cobb angle as measured from the C2-C7 was +38 degrees and improved to -10 degrees at final follow-up, yielding an average correction of 48 degrees . ", "The mean number of anterior and posterior segments fused was 4.8 (range, 2-6) and 7.2 (range, 3-14), respectively. ", "The mean Nurick score improved from 2.4 before surgery to 1.5 at the time of follow-up. ", "According to Odom criteria, outcomes were as follows: excellent (38%), good (50%), fair (6%), and poor (6%). ", "At the time of most recent follow-up, solid bony arthrodesis and maintenance of correction occurred in all patients; however, revision was required in one patient. ", "The treatment of fixed cervical kyphosis with myelopathy using circumferential spinal osteotomies and instrumented reconstruction is technically demanding; however, restoration and maintenance of a neutral or lordotic cervical profile and excellent clinical outcomes are achievable." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nGet list of recent projects when opening Visual Studio in Windows 8 and 2012\n\nOn Windows 7 I open Visual Studio by hitting Start, choosing VS, and then choosing the solution I want from a list of recent solutions.", "\nOn the variants of Windows with no start button I cannot do it this way. ", " I hit start, type \"Vis...\" and get VS showing up on the search bar. ", " But I do not see any way to get a list of recent projects.", "\nThis is annoying because it means this is a two step process rather than one click. ", " Does anyone know how to open Visual Studio and a recent project with one click?", "\nWindows 7 shows a list of recent solutions:\n\nWindows 8 with no list of recent files:\n\nA:\n\nif you pin visual studio to your taskbar, and do a right click on it, you will find your recent projects list.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Diagnostic performance of CT findings in differentiation of perforated from nonperforated appendicitis.", "\nTo assess performance of CT finding in differentiation of perforated from non-perforated appendicitis in Siriraj hospital, Bangkok, Thailand and evaluate accuracy of each finding by using multidetector row computer tomography (MDCT). ", "Between June 2006 and May 2009, all adult patients (age more than 15 years) who had a diagnosis of acute appendicitis in Siriraj Hospital that was confirmed by pathology or surgical records and received a CT scan whole abdomen or lower abdomen with contrast administration before surgical or medical treatment were included in this study. ", "The 48 consecutive CTs of whole or lower abdomen examinations were retrospectively reviewed by two radiologists. ", "Sensitivity specificity, and accuracy of CT compared with pathologic or surgical findings. ", "In 48 patients, 21 patients of non-perforated appendicitis and 27 patients of perforated appendicitis were enrolled. ", "The CT findings of abscess, extraluminal appendicolith, and extraluminal air had the highest specificities for perforated appendicitis, 95.24%, 100%, 95.24%, respectively. ", "The best accurate finding was defect in enhancing appendiceal wall. ", "The CT findings of enlarged mesenteric lymph nodes at right lower quadrant region and defect in enhancing appendiceal wall had the highest sensitivities, 88.88% and 88.46%, respectively. ", "Group 3 of combined specific findings had the best sensitivity (92.59%) and accuracy (83.3%). ", "Multi-detector CT can help to differentiate perforated from non-perforated appendicitis." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. ", "We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. ", "A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. ", "PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). ", "These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. ", "We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.", "\n\nWe report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. ", "We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). ", "A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. ", "PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. ", "Early failures were particularly frequent in the SP group (15.2%). ", "Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. ", "This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. ", "Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. ", "For Bundi Bugyo, we recommend a combination of artesunate and AQ. ", "Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. ", "Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.", "\n\nThe current first-line and second-line drugs for Plasmodium falciparum malaria in South Sudan, chloroquine and sulfadoxine-pyrimethamine (SP), were evaluated and compared with amodiaquine, in an MSF-Holland-run clinic in eastern Upper Nile, South Sudan from June to December 2001. ", "Patients with uncomplicated malaria and fever were stratified by age group and randomly allocated to one of 3 treatment regimes. ", "A total of 342 patients was admitted and followed for 14 d after treatment. ", "The dropout rate was 10.2%. ", "Of those who completed the study, 104 were treated with chloroquine (25 mg/kg, 3 d), 102 with SP (25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine, single dose) and 101 with amodiaquine (25 mg/kg, 3 d). ", "Adequate clinical response was observed in 88.5% of patients treated with chloroquine, 100% of patients treated with SP and 94.1% of patients treated with amodiaquine. ", "In children aged < 5 years, the success rate was lower: 83.3% for chloroquine and 93.0% for amodiaquine. ", "In adults no treatment failures were found, but children aged 5-15 years showed intermediate levels. ", "In addition, we determined the initial genotypes of dhfr and dhps of 44 isolates from the SP-treated group and > 80% were found to be wild type for dhfr and 100% for dhps. ", "Two percent of isolates had a single mutation and 16% had double mutations of dhfr. ", "These data are in full agreement with the clinical effectiveness of SP. ", "A change in malaria treatment protocols for South Sudan is recommended.", "\n\nMulti-drug resistant falciparum malaria is widespread in Asia. ", "In Thailand, Cambodia and Vietnam the national protocols have changed largely to artesunate combined treatment regimens but elsewhere in East and South Asia chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are still widely recommended by national malaria control programmes. ", "In Kachin State, northern Myanmar, an area of low seasonal malaria transmission, the efficacy of CQ (25 mg base/kg) and SP (1.25/25 mg/kg), the nationally recommended treatments at the time, were compared with mefloquine alone (M; 15 mg base/kg) and mefloquine combined with artesunate (MA; 15:4 mg/kg). ", "An open randomized controlled trial enrolled 316 patients with uncomplicated Plasmodium falciparum malaria, stratified prospectively into three age-groups. ", "Early treatment failures (ETF) occurred in 41% (32/78) of CQ treated patients and in 24% of patients treated with SP (18/75). ", "In young children the ETF rates were 87% after CQ and 35% after SP. ", "Four children (two CQ, two SP) developed symptoms of cerebral malaria within 3 days after treatment. ", "By day 42, failure rates (uncorrected for reinfections) had increased to 79% for CQ and 81% for SP. ", "ETF rates were 2.5% after treatment with M and 3.9% after treatment with MA (P > 0.2). ", "Overall uncorrected treatment failure rates at day 42 following M and MA were 23% and 21%, respectively. ", "Chloroquine and SP are completely ineffective for the treatment of falciparum malaria in northern Myanmar. ", "Mefloquine treatment is much more effective, but three day combination regimens with artesunate will be needed for optimum efficacy and protection against resistance.", "\n\nOBJECTIVE: To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. ", "METHODS: A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. ", "Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). ", "RESULTS: Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. ", "Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). ", "PCR analysis showed that some of these cases were novel infections. ", "The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). ", "The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. ", "Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. ", "The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. ", "CONCLUSIONS: The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. ", "However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. ", "The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh.", "\n\nFalciparum Malaria is hyperendemic in southern Nigeria and chloroquine resistance is an increasing problem. ", "Therefore, the parasitological and haematological response to treatment with amodiaquine was studied in children under 5 years during a 14-day follow-up. ", "Of 105 children who accomplished the study (out of 114 who were enrolled), 95.3% were parasite-negative on thick blood film on day 7, which decreased to 89.5% on day 14. ", "The haemoglobin levels increased on average by 1.3% on day 14 (+/-1.9) and more pronounced in children with anaemia<10 g/dl on enrollment. ", "The number of patients with adverse events (mainly pruritus and nausea) was few. ", "This study shows that amodiaquine is effective, safe and affordable in an area with high resistance to chloroquine.", "\n\nBangladesh faces growing levels of Plasmodium falciparum resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP). ", "Alternative antimalarial therapies, particularly combination regimens, need to be considered. ", "Therefore, the efficacy of three antimalarial combination therapies was assessed in Chittagong Hill Tracts. ", "A total of 364 P. falciparum patients were recruited and randomly assigned to either CQ + SP, mefloquine + artesunate (MQ + AS) or lumefantrine + artemether (Coartem). ", "Results showed that CQ + SP therapy was less effective than the two artemisinin-based combination therapies. ", "The day 42 PCR-corrected efficacy rate was 62.4% for CQ + SP, 100% for MQ + AS and 97.1% for Coartem. ", "Failures occurred at a shorter interval after CQ + SP treatment than after Coartem. ", "The artemisinin-based therapies effectively prevented development of gametocytes, whereas CQ + SP did not. ", "All three therapies were well tolerated, although reports of mild complaints during treatment appeared higher with MQ + AS. ", "We conclude that CQ + SP is not a viable option for replacing CQ monotherapy as first-line P. falciparum treatment in this area of Bangladesh. ", "A change to artemisinin-based combination therapy is recommended. ", "Both Coartem and MQ + AS appear to be good options, effective in curing P. falciparum malaria and in preventing recrudescences following treatment.", "\n\nWe report the results of an in vivo antimalarial efficacy study with chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) conducted between 2003 and 2004 in Koumantou, southern Mali. ", "A total of 244 children were included in the study; 210 children were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescence from re-infection. ", "Global failure proportions at Day 14, without taking into account re-infections, were 44.2% (95% CI 34.9-53.5%) in the CQ group and 2.0% (95% CI 0.0-4.8%) in the SP group. ", "PCR-adjusted failure proportions at Day 28 were even higher in the CQ group (90.5% (95/105), 95% CI 84.8-96.2%) and relatively low in the SP group (7.0% (7/100), 95% CI 1.9-12.1%). ", "These results show that CQ is no longer efficacious in Koumantou. ", "The use of SP in monotherapy is likely to compromise its efficacy. ", "We recommend the use of artemisinin-based combination therapy as first-line treatment for uncomplicated Plasmodium falciparum malaria in Koumantou.", "\n\nWe report two 28-day in-vivo antimalarial efficacy studies carried out in the urban centres of Bongor and Koumra, southern Chad. ", "We assess chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) to treat Plasmodium falciparum uncomplicated malaria. ", "Methods and outcome classification complied with latest WHO guidelines. ", "Out of the 301 and 318 children aged 6-59 months included in Bongor and Koumra, respectively, 246 (81.7%) and 257 (80.8%) were eligible for analysis. ", "In Bongor and Koumra, the 28-day PCR-adjusted failure rates for CQ were 23.7% (95% CI 14.7-34.8%) and 32.9% (95% CI 22.1-45.1%), respectively, and those for SP were 16.3% (95% CI 9.4-25.5%) and 4.3% (95% CI 1.2-10.5%). ", "AQ failure rates were 6.4% (95% CI 2.1-14.3%) and 2.2% (95% CI 0.3-7.6%). ", "The current use of CQ in Bongor and Koumra is questionable, and a more efficacious treatment is needed. ", "Considering the reduced efficacy of SP in Bongor, AQ seems to be the best option for the time being. ", "Following WHO recommendations that prioritize the use of artemisinin-based combinations, artesunate plus amodiaquine could be a potential first-line treatment. ", "Nevertheless, the efficacy of this combination should be evaluated and the change carefully prepared, implemented and monitored.", "\n\nTo provide advice on the rational use of antimalarial drugs, Médecins Sans Frontières conducted a randomized, an open label efficacy study in Kajo Keji, an area of high transmission of malaria in southern Sudan. ", "The efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) were measured in a 28-day in vivo study, with results corrected by PCR genotyping. ", "Of 2010 children screened, 115 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were randomized into each group to receive a supervised course of treatment. ", "Of these, 114, 103 and 111 were analysed in the CQ, SP and AQ groups, respectively. ", "The overall parasitological failure rates at day 28 were 93.9% [95% confidence interval (CI) 87.3-97.3] for CQ, 69.9% (95% CI 60.0-78.3) for SP, and 25.2% (95% CI 17.7-34.5) for AQ. ", "These results provide important missing data on antimalarial drug efficacy in southern Sudan. ", "They indicate that none of the drugs could be used in monotherapy and suggest that even in combination with artemisinin, cure rates might not be efficacious enough. ", "We recommend a combination of artemether and lumefantrine as first-line treatment for uncomplicated P. falciparum malaria cases in Kajo Keji county.", "\n\nBACKGROUND: Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs), the new first-line treatments of malaria. ", "There is no ideal method to quantify drug requirements for malaria. ", "Morbidity data give uncertain estimations. ", "This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. ", "METHODS: The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe). ", "From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. ", "RESULTS: Identifying and obtaining data from the private sector was difficult. ", "The quality of information on drug supply and distribution in countries must be improved. ", "The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. ", "Current adult treatment prices for ACTs range US$ 1-1.8. ", "Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. ", "In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum). ", "There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania). ", "CONCLUSION: Additional studies are required to build a more robust methodology, and to assess current consumptions more accurately in order to better quantify volumes and finances for production and procurement of ACTs.", "\n\nOBJECTIVES: To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country. ", "METHODS: Between October 2002 and May 2003, standard WHO methodology for in vivo efficacy assessment was used in five sites to study the therapeutic response of 6-59 months old uncomplicated Plasmodium falciparum malaria cases treated with CQ (n = 247), SP (n = 353) or AQ (n = 434). ", "Follow-up was of 28 days, with polymerase chain reaction genotyping to distinguish late recrudescences from re-infections. ", "RESULTS: Overall 85.3% of patients reached an analysable endpoint. ", "CQ failure proportions were very high, ranging from 39.5% (95% CI: 25.0-55.6) in Kabala to 78.8% (65.3-88.9) in Kailahun. ", "Early failures under CQ were frequent. ", "SP efficacy was also disappointing, with failure from 23.2% (13.9-34.9) in Kabala to 46.1% (35.4-57.0) in Kailahun. ", "AQ resistance was more moderate, ranging from 5.4% (1.8-12.1) in Makeni to 29.8% (20.3-40.8) in Kailahun, with almost no early failures. ", "AQ also provided more rapid fever and parasite clearance. ", "CONCLUSION: In a consensus meeting organized by the Ministry of Health and Sanitation, and based on these findings, artesunate (AS) + AQ and artemether-lumefantrine (Coartemtrade mark) were identified as the only options to rapidly replace CQ. ", "The choice fell on AS + AQ because of expected high efficacy, lower cost in a blister presentation, and the absence of safety data on artemether-lumefantrine in pregnancy. ", "Donor support is required to support this policy change. ", "Throughout Africa, as SP resistance increases, these two regimens are probably the only options available while newer combinations are developed. ", "Efficacy studies should focus on testing AQ and AS + AQ.", "\n\nBoth northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). ", "In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). ", "We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). ", "Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. ", "The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. ", "Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). ", "CQ use should be rapidly discontinued in this region. ", "SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.", "\n\nThe objectives of these analyses were to assess the feasibility of the latest WHO recommendations (28-day follow-up with PCR genotyping) for the assessment of antimalarial drug efficacy in vivo and to examine how different statistical approaches affect results. ", "We used individual-patient data from 13 studies of uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). ", "We assessed the use effectiveness and test performance of PCR genotyping in distinguishing recurrent infections. ", "In analyzing data, we compared (i) the risk of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or excluding (method 2) new infections, (iii) and day 14 versus day 28 results. ", "Of the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. ", "Of the 695 recurrences occurring post-day 14, 650 could be processed and 584 were resolved (PCR use effectiveness, 84%; test performance, 90%). ", "The risks of failure on day 28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close (except in smaller studies) because the numbers of dropouts were minimal, but attrition rates on day 28 were higher with the latter method. ", "Method 2 yielded higher risks of failure than method 1. ", "Extending observation to 28 days produced higher estimated risks of failure for SP and AQ but not for CQ (high failure rates by day 14). ", "Results support the implementation of the current WHO protocol and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows for dropouts) and retaining new infections (which minimizes losses).", "\n\nBACKGROUND: Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. ", "To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. ", "METHODS AND FINDINGS: We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. ", "The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. ", "Resistance lineages were common to all sites within these regions. ", "The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. ", "CONCLUSIONS: Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. ", "Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. ", "We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.", "\n\nIn Rakhine State, on the western border of Myanmar, the efficacy of chloroquine (CQ) and pyrimethamine/ sulfadoxine (PS), the current treatments for uncomplicated Plasmodium falciparum malaria in this area, was evaluated in an open comparative study of 289 patients, stratified prospectively into 3 age groups. ", "Chloroquine treatment was associated with more rapid clinical recovery (P = 0.03), but the overall cure rates were worse than for PS treatment; failure to clear parasitaemia or recrudescence within 14 d occurred in 72% (102/141) of cases treated with CQ compared to 47% (69/148) of those who received PS (P < 0.0001, adjusted for age). ", "Failure rates at day 28 increased to 82% (116/141) in the CQ group and 67% (99/148) in the PS group (P = 0.003). ", "The risk of treatment failure was significantly higher in children under 15 years old than in adults for both CQ (relative risk [RR] = 2.6; 95% confidence interval [95% CI] 1.3-5.2) and PS (RR = 2.2; 95% CI 1.4-3.3). ", "Mefloquine (15 mg base/kg) proved to be highly effective as a treatment for CQ and PS resistant P. falciparum; only 2 of 75 patients (3%) had early treatment failures (< or = day 7), and the overall failure rate by day 42 was 7%. ", "There is a very high level of chloroquine and PS resistance in P.falciparum on the western border of Myanmar, but mefloquine was effective in the area.", "\n\nOBJECTIVE: To assess the efficacy of chloroquine in the treatment of Plasmodium vivax malaria in in Dawei District, southern Myanmar. ", "METHODS: Enrolled patients at Sonsinphya clinic >6 months of age were assessed clinically and parasitologically every week for 28 days. ", "To differentiate new infections from recrudescence, we genotyped pre- and post-treatment parasitaemia. ", "Blood chloroquine was measured to confirm resistant strains. ", "RESULTS: Between December 2002 and April 2003, 2661 patients were screened, of whom 252 were included and 235 analysed. ", "Thirty-four per cent (95% CI: 28.1-40.6) of patients had recurrent parasitaemia and were considered treatment failures. ", "59.4% of these recurrences were with a different parasite strain. ", "Two (0.8%) patients with recurrences on day 14 had chloroquine concentrations above the threshold of 100 ng/ml and were considered infected with chloroquine resistant parasites. ", "21% of failures occurred during the first 3 weeks of follow-up: early recurrence and median levels of blood chloroquine comparable to those of controls suggested P. vivax resistance. ", "CONCLUSIONS: Plasmodium vivax resistance to chloroquine seems to be emerging in Dawei, near the Thai-Burmese border. ", "While chloroquine remains the first-line drug for P. vivax infections in this area of Myanmar, regular monitoring is needed to detect further development of parasite resistance.", "\n\nA four-arm drug sensitivity study compared chloroquine, sulfadoxine-pyrimethamine (SP), mefloquine and mefloquine-artesunate in Sonitpur and Karbi Anglong districts in Assam state, India. ", "Two criteria were used to ascertain outcome: success of clinical treatment and parasitologic cure. ", "In Sonitpur, at 14 days, there were 36/56 early and late treatment failures plus late parasitologic failures to chloroquine and 16/56 for SP. ", "In Karbi Anglong, combined treatment failure at 14 days was 16/56 to chloroquine and 8/60 to SP. ", "Mefloquine and mefloquine-artesunate demonstrated 93.9% and 93.6% sustained responses respectively at 42 days. ", "High failure rates to both chloroquine and SP preclude the use of these drugs as first-line treatment for uncomplicated falciparum malaria in this region. ", "A mefloquine-artesunate combination presents an effective alternative utilizing the currently recommended higher dose of mefloquine.", "\n\nExport search results\n\nThe export option will allow you to export the current search results of the entered query to a file. ", "Different\nformats are available for download. ", "To export the items, click on the button corresponding with the preferred download format.", "\n\nBy default, clicking on the export buttons will result in a download of the allowed maximum amount of items.", "\n\nTo select a subset of the search results, click \"Selective Export\" button and make a selection of the items you want to export.", "\nThe amount of items that can be exported at once is similarly restricted as the full export.", "\n\nAfter making a selection, click one of the export format buttons. ", "The amount of items that will be exported is indicated in the bubble next to export format." ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\njava - list question - Why did it print out -4 on the 3rd printout when i ran it?", "\n\npackage javaapplication8;\n\npublic class Main {\n\n public static void main(String[] args) {\n int[] list1 = {1, 2, 3,4};\n int[] list2 = {5, 6, 7,8};\n\n for (int i = 0; i < list2.length; i++){\n System.out.print(list2[i] + \" \");\n }\n System.out.println(\"\");\n\n list2 = list1;\n\n for (int i = 0; i < list2.length; i++){\n System.out.print(list2[i] + \" \");\n }\n System.out.println(\"\");\n\n //Change list1\n list1[0] = -1;\n\n //Change list2\n list2[3] = -4;\n\n //List1 output\n for (int i = 0; i < list1.length; i++){\n System.out.print(list1[i] + \" \");\n }\n System.out.println(\"\");\n\n //List2 output\n for (int i = 0; i < list2.length; i++){\n System.out.print(list2[i] + \" \");\n }\n System.out.println(\"\");\n\n //Set list1\n list1 = new int[2];\n list1[0] = 100;\n list1[1] = 99;\n\n //List1 output\n for (int i = 0; i < list1.length; i++){\n System.out.print(list1[i] + \" \");\n }\n System.out.println(\"\");\n\n //List2 output\n for (int i = 0; i < list2.length; i++){\n System.out.print(list2[i] + \" \");\n }\n System.out.println(\"\");\n\n }\n}\n\nrun:\n5 6 7 8 \n1 2 3 4 \n-1 2 3 -4 \n-1 2 3 -4 \n100 99\n-1 2 3 -4 \n\nA:\n\nList 1 and List 2 are pointing to same array object after you do List2 = list1;\nso doing List2[3] = -4; actually does it for array object that earlier was pointed by List1.", "\nand remember the array object that was earlier related to List2 now stands for garbage collection.", "\nSo earlier when u did List1 = x and List2 = y there were two array objects in the memory pointed out by list1 and list2 variables. ", "However after doing list2 = list1 u made both variables point to x array and the other array is free now and java will need to recollect this memory sometime and hence whatever changes ur doing is done to object x rather than y\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Sequence of functions, uniform convergence\n\n1. ", "The problem statement, all variables and given/known data\n{f_n} is a sequence of continuous functions on E=[a,b] that converges uniformly on E. for each x in E, set g(x)=sup{f_n(x)}. ", "Prove that g is continuous on E\n\n2. ", "Relevant equations\n\n3. ", "The attempt at a solution\nI've got an idea to prove it:\nLet e>0 be given, there is a N such that\n|f_n(x)-f(x)|<e\nfor all n>N and all x in E.\nLet K_n={x|f_n(x)>=e+f(x)}, n=1,2,3....,N.\neach K_n is closed since f_n is continuous.", "\nLet [tex]A=\\cup^{N}_{1} K_{i}[/tex] then A is closed.", "\ng(x) is continuous on A (since there are only N functions to deal with. ", "And I find it tedious to prove?)", "\nLet B=E-A.\nThen f(x)<=g(x)<f(x)+e, for any x in B.\nlet p be an interior point in B.\nif g(p)=f_k(p), for some k>N.\nsince f_k(p) is continuous, there is a neighborhood of p such that if q is in it and also in B.\n|f_k(p)-f_k(q)|<e\nthen,\n|g(p)-g(q)|<=|f_k(p)-f_k(q)|+|f_k(q)-g(q)|<=e+|f_k(q)-f(q)|+|f(q)-g(q)|<=e+e+e=3e.", "\nhence g(x) is continuous at p.\nif g(p)=f(p).", "\n|g(p)-g(q)|<=|f(p)-f(q)|+|f(q)-g(q)|=2e, which implies\ng(x) is continuous at p.\nIt is analogous to say that g(x) is continuous if p is the boundary point of B.\n\nIt seems okay. ", "But I'm not satisfied with it, it looks so lenthy and not well organized and I believe there is some other proof much better than this one. ", "Any hint?", "\n\nImagine if your functions were just fk(x) = 1-1/k on the whole interval. ", "Then fk converges to 1 uniformly, and clearly A is empty as fn < f everywhere for all n. Then B is the whole interval, yet g(x) =/= fk(x) for any x,k combination. ", "I think this is fixed by a better definition of Kn (probably what you wrote isn't what you really intended)" ]

{ "pile_set_name": "Pile-CC" }

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[ "Lower plasma triglycerides are associated with increased need for insulin requirement in poorly controlled Type 2 diabetic patients.", "\nTo identify factors associated with insulin requirement in Type 2 diabetic patients, and to examine the significance of a normal plasma triglyceride level. ", "One hundred and three poorly controlled (HbA1c = 9.4 +/- 1.9%) Type 2 diabetic patients initially not treated with insulin were followed up for 5 years. ", "Insulin was administered if HbA1c > 8% despite maximal oral anti-diabetic treatment and bodyweight control. ", "Variables were compared between insulin requiring and non-insulin-treated patients using unpaired t-tests. ", "The outcomes of initially normotriglyceridaemic (< 1.7 mmol/l) and hypertriglyceridaemic patients were compared using unpaired t-tests, and a survival analysis (Cox proportional hazards model). ", "Sixty-three patients were transferred to insulin. ", "They were 5 years older (P = 0.004), with a 3-year longer duration of their diabetes (P = 0.03), a 1.2% higher HbA1c (P = 0.002), and 50% lower triglyceride levels (P = 0.02) than the others. ", "The survival analysis showed that a long duration of diabetes, a high HbA1c, and a normal triglyceride level were associated with the need for insulin; the effect of normotriglyceridaemia was significant in the most poorly controlled (HbA1c > 9.5%) patients (relative risk: 2.35, 95% confidence interval: 1.16-5.52, P = 0.016). ", "The 46 normotriglyceridaemic patients were leaner (P = 0.0004) and had lower C-peptide levels (P = 0.0008) than the others. ", "Despite similar diabetes duration and HBA1c, more were transferred to insulin (normotriglyceridaemic: 71%, hypertriglyceridaemic: 52%, P = 0.03). ", "A normal triglyceride level is associated with a need for insulin in poorly controlled Type 2 diabetes." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "The effect of walking intervention on blood pressure control: a systematic review.", "\nHypertension is a major public health problem and a key risk factor of cardiovascular diseases. ", "Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. ", "However the optimal characteristics for a physical activity programme remain open to debate. ", "Walking is recommended by healthcare professionals as a form of exercise for controlling hypertension and nurses find it difficult to provide advice about this form of physical activity. ", "Studies testing the effect of walking on blood pressure have produced inconsistent findings. ", "To systematically review the evidence for the effectiveness of walking intervention on blood pressure. ", "A systematic search of the literature was conducted using a range of electronic and evidence-based databases to identify studies. ", "Criteria for study inclusion were a randomised controlled trial design with a non-intervention control group; study samples were aged 16 years and over; the intervention was predominantly focused on walking and blood pressure was an outcome. ", "Data extraction and quality appraisal were carried out independently by two reviewers; a third reviewer was consulted when needed. ", "A total of 27 randomised controlled trials were included and nine of the 27 trials found an effect of walking intervention on blood pressure control. ", "Walking intervention tends to be effective from studies with larger sample size. ", "A beneficial effect of walking on blood pressure tended to employ moderate to high-intensity walking and a longer intervention period than those trials not showing the effect. ", "The results of this review provide evidence of the beneficial effects of walking on lowering blood pressure. ", "Recommendations on lowering blood pressure with a walking activity should address the issue of walking intensity to achieve a beneficial effect on lowering blood pressure. ", "Future research investigating the effect of walking intensity on blood pressure levels and rigorous design of walking interventions to achieve better adherence and methodological quality is required." ]

{ "pile_set_name": "PubMed Abstracts" }

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{ "pile_set_name": "DM Mathematics" }

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[ "Derby Castle terminus\n\nDerby Castle is the southern terminus of the Manx Electric Railway. ", "It is located on the north side of Douglas, Isle of Man; Douglas Station on the Isle of Man Railway is located on the south side of town, with the MER station being termed \"Derby Castle\" to differentiate between the two.", "\n\nBeginnings\nThe site that now forms the station at Derby Castle is so called because the area to the north at that time housed the vast entertainment complex of the same name. ", " The enterprising railway company owned the entire site, including the row of houses at Strathallan Crescent and the horse tram sheds and offices above. ", " Behind this building lay the Calvary Glen which too was the property of the company until 1934. ", " The houses of the crescent were sold off in 1978 when the entire railway network became government owned, and the railway's offices took up residence in the building above the horse tram sheds at this time also. ", " This office is now in the ownership of the local authority and renamed the \"Strathallan Suite\". ", " This area has been the terminus of the line since it opened in 1893. ", " At the northerly end of the site was the main entrance to the ballroom complex, and later the car park for the now-demolished Aquadrome Swimming Pool & Sauna which was part of the Summerland complex.", "\n\nBooking Office\nThe station still retains the original station booking office dating from 1897, built in a distinctive \"rustic\" style with half-log cladding, and steep alpine roofing. ", "The facilities are basic and the office measures only 12' 6\" by 8' (3.8 m by 2.4 m) and has room for station master and crew only; the station has never had its own toilets for instance, sharing facilities with the nearby Strathallan Hotel (latterly renamed \"Terminus Tavern\" as it is next to the electric and horse tram termini). ", "Aside from the tarmacadam surfacing and modern shelter, the site remains unchanged since opening.", "\n\nTrack\nThere is a loop of track to allow the motor car to be shunted around the trailer car.", "\n\nStrathallan Hotel\nThe pub next to the station, now called the \"Terminus Tavern\", was built in 1890 as the Strathallan Lodge, later becoming a hostelry and remained so until 1982 when it was given its current name. ", "It was railway-owned until nationalisation in 1957, having been taken over by the local brewery at that time. ", " It still forms an integral part of the station, the walls being lined with numerous photographs of the line and other handbills, posters, etc., ", "and it still plays host to off-duty railway workers today.", "\n\nCanopy\nUntil 1979 there was a large open roof known as the \"Great Canopy\". ", "The stanchions for this canopy are now used as flagpoles and/or lampposts, and it can clearly be seen where the canopy was. ", "The canopy, although erected by the railway, provided cover for the tramcars of the Douglas Bay Horse Tramway which also terminates here; the canopy originally featured detailed and intricate metalwork culminating in a central clock tower, distinctive on many early views, but latterly this was removed and a plain roof replaced it.", "\n\nOther structures\nIn 1999 a long shelter was added, with a sign to say it was for use in connection with both the electric railway and bus services. ", "Previously a defunct tramcar purchased from Lisbon, Portugal was housed on the siding to the side of the station, and this functioned as a waiting area until it was removed for off-site storage some time later, and now the station offers no cover for waiting passengers other than the incongruous modern shelter. ", "For a short time in the 1980s, a horse car from the horse tramway was used as a shelter.", "\n\nFeatures\nThe station is well known for its many and varied advertising signages, with many any varied styles in evidence denoting \"The Highspot Of Your Holiday\" in connection with a trip on the Snaefell Mountain Railway and \"Shining By The Sea\" for Royal Ramsey among the posters. ", " The station is always covered with informative signage. ", " A framed manually operated clock face attached to a traction pole shows the time of the next departure. ", " For the line's centenary in 1993 large planters were added to the site.", "\n\nSources\n\nCategory:Railway stations in the Isle of Man\nCategory:Manx Electric Railway\nCategory:Railway stations opened in 1893" ]

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[ "Q:\n\nHow to upload a pdf file using faraday with header\n\nI'm having issues attempting to upload a file to a web service using Faraday.", "\nconn = Faraday.new('http://myapi') do |f|\n f.request :multipart\n f.adapter Faraday.default_adapter\nend\n\npayload = Faraday::UploadIO.new(file_io, 'application/pdf') \n\nconn.post '/upload', payload\n\nThe java api accepts POST to a 'Content-Type' => 'multipart/form-data'. ", "The request is supposed to send file with required boundaries. ", "It is not. ", "\nWhen the request is intercepted it shows the header set to be x-url encoded. ", "If the header is preset to have Content-Type, the boundary is not added by faraday.", "\nthe API throws,\n\n2016-05-09 11:36:03,068 [1] [e02b7381] [jetty-139] INFO \n com.fm.rest.services.interceptor.", "RequestLoggingInInterceptor -\n Request info :\n POST http://localhost:8080/api/projects/1/files/f719137f-702a-4801-9654-95f5a58d78f2 ISO-8859-1 multipart/form-data Headers:\n {Accept=[/],\n accept-encoding=[gzip;q=1.0,deflate;q=0.6,identity;q=0.3],\n connection=[close], Content-Length=[217115],\n content-type=[multipart/form-data], Host=[localhost:8080],\n User-Agent=[Ruby], X-Newrelic-Id=[12YHU123wsC123wE=],\n X-Newrelic-Transaction=[P9TDFcABCAEEVQ8JFTs=]}\n 2016-05-09 11:36:03,072 [1] [e02b7381] [jetty-139] WARN \n org.apache.cxf.phase.", "PhaseInterceptorChain - Interceptor for\n {http://services.rest.fm.api.com/}DirectoryRestService has thrown\n exception, unwinding now org.apache.cxf.interceptor.", "Fault: Couldn't\n determine the boundary from the message! ", " at\n org.apache.cxf.interceptor.", "AttachmentInInterceptor.handleMessage(AttachmentInInterceptor.java:66)\n\nI am unable to set the header in the post request\n\nA:\n\nThe problem was not wrapping the faraday uploader io in a hash \npayload = { :file => Faraday::UploadIO.new(file, 'application/pdf') }\n\nThis solved the problem of faraday not setting proper header. ", "The last argument of Faraday::Connection post is the header as seen from the docs\nheader = {'Authorization': 'Basic =A123CD'}\nconn.post url, payload, header\n\n" ]

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[ "{\n \"name\": \"lodash._shimkeys\",\n \"version\": \"2.4.1\",\n \"description\": \"The internal Lo-Dash function `shimKeys` as a Node.js module generated by lodash-cli.\",", "\n \"homepage\": \"http://lodash.com/custom-builds\",\n \"license\": \"MIT\",\n \"author\": {\n \"name\": \"John-David Dalton\",\n \"email\": \"john.david.dalton@gmail.com\",\n \"url\": \"http://allyoucanleet.com/\"\n },\n \"contributors\": [\n {\n \"name\": \"John-David Dalton\",\n \"email\": \"john.david.dalton@gmail.com\",\n \"url\": \"http://allyoucanleet.com/\"\n },\n {\n \"name\": \"Blaine Bublitz\",\n \"email\": \"blaine@iceddev.com\",\n \"url\": \"http://www.iceddev.com/\"\n },\n {\n \"name\": \"Kit Cambridge\",\n \"email\": \"github@kitcambridge.be\",\n \"url\": \"http://kitcambridge.be/\"\n },\n {\n \"name\": \"Mathias Bynens\",\n \"email\": \"mathias@qiwi.be\",\n \"url\": \"http://mathiasbynens.be/\"\n }\n ],\n \"bugs\": {\n \"url\": \"https://github.com/lodash/lodash-cli/issues\"\n },\n \"repository\": {\n \"type\": \"git\",\n \"url\": \"https://github.com/lodash/lodash-cli.git\"\n },\n \"dependencies\": {\n \"lodash._objecttypes\": \"~2.4.1\"\n },\n \"readme\": \"# lodash._shimkeys v2.4.1\\n\\nThe internal [Lo-Dash](http://lodash.com/) function `shimKeys` as a [Node.js](http://nodejs.org/) module generated by [lodash-cli](https://npmjs.org/package/lodash-cli).\\n\\n## Author\\n\\n| [](https://twitter.com/jdalton \\\"Follow @jdalton on Twitter\\\") |\\n|---|\\n| [John-David Dalton](http://allyoucanleet.com/) |\\n\\n## Contributors\\n\\n| [](https://twitter.com/blainebublitz \\\"Follow @BlaineBublitz on Twitter\\\") | [](https://twitter.com/kitcambridge \\\"Follow @kitcambridge on Twitter\\\") | [](https://twitter.com/mathias \\\"Follow @mathias on Twitter\\\") |\\n|---|---|---|\\n| [Blaine Bublitz](http://www.iceddev.com/) | [Kit Cambridge](http://kitcambridge.be/) | [Mathias Bynens](http://mathiasbynens.be/) |\\n\",\n \"readmeFilename\": \"README.md\",\n \"_id\": \"lodash._shimkeys@2.4.1\",\n \"_from\": \"lodash._shimkeys@~2.4.1\"\n}\n" ]

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[ "Q:\n\nMYSQL: Like Method, Similar Words - But Don't Show the Searched Word\n\nactually i use this method to show similar words for a search request..\n$query = \"SELECT * FROM searches WHERE Query LIKE '%$search%' ORDER BY Query\"; \n\nif someone searches for \"nelly\" it looks up in the database for similar words \n\"nelly furtado, nelly ft. ", "kelly\"... \nbut i dont want to show up the searched word..\nexample: you've searched for nelly - try this too: nelly, nelly furtado, nelly ft., ", "\nthe bold word should not showed up again, because it's the searched word.. is there maybe a method with MATCH AGAINST? ", "thank you!", "\n\nA:\n\nCouldn't you just do something like ...WHERE Query LIKE \"%$search%' AND Query <> '$search'...?", "\nCase-insensitive: Query LIKE \"%$search%' AND STRCMP(Query, '$search') == 0\n\n" ]

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[ "Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart.", "\nSkeletal myoblast transplantation is a promising alternative to treat heart failure. ", "A single fiber, the minimal functional unit of skeletal muscle, retains skeletal myoblasts beneath the basal lamina. ", "When surrounding muscle is injured, myoblasts migrate from the fiber into the damaged area to regenerate muscle. ", "We hypothesized that such isolated fibers could be used as an efficient vehicle to deliver myoblasts into damaged myocardium, resulting in improved cardiac function. ", "Living single fibers of rat skeletal muscle were isolated, and their behavior was characterized in vitro. ", "Single fibers were injected into the myocardium (at 4 sites, each receiving a single fiber) of rats in 2 models of heart failure induced either by means of doxorubicin administration or left coronary artery occlusion. ", "Skeletal myoblasts dissociated from an isolated single fiber, proliferated, and differentiated into multinucleated myotubes in vitro. ", "Within 3 days after grafting in vivo, original fibers provided putative myoblasts and disappeared. ", "At 4 weeks, discrete loci consisting of several multinucleated myotubes were observed. ", "Furthermore, single-fiber transplantation significantly improved cardiac function compared with the control treatment in either doxorubicin-treated hearts (maximum dP/dt, 4013.9 +/- 96.1 vs 3603.1 +/- 102.3 mm Hg/s; minimum dP/dt, -2313.7 +/- 75.1 vs. -2057.1 +/- 52.4 mm Hg/s) or ischemic hearts (maximum dP/dt, 3905.6 +/- 103.0 vs 3572.6 +/- 109.7 mm Hg/s; minimum dP/dt, -2336.1 +/- 69.7 vs -2106.4 +/- 74.2 mm Hg/s). ", "Single-fiber transplantation acts as a vehicle for delivering putative skeletal myoblasts that appear to differentiate into myotubes within the myocardium. ", "This was associated with improved function of failing hearts, suggesting its efficacy as a novel graft for cellular cardiomyoplasty." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "KDE4 Netherlands language pack\n" ]

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[ "Sudan frees 57 victims of human trafficking\n\nSudanese security has captured 4 human traffickers as they were preparing to take 57 foreign nationals towards the Libyan border.", "\n\nSudan Media Center (SMC) Sunday said the victims were hidden at a house in East Nile locality, east of Khartoum, pointing that the police is still searching for 3 other traffickers.", "\n\nIt added the initial legal action was taken against the human traffickers.", "\n\nSudan is considered a country of origin and transit for illegal migration and human trafficking. ", "Thousands of people from Eritrea and Ethiopia are monthly crossing the border into the Sudanese territories on their way to Europe through Libya or Egypt.", "\n\nLast July, the Higher Committee to Combat Human Trafficking said it would develop a national anti-trafficking strategy as well as activating existing laws to counter the phenomenon in accordance with the established international standards.", "\n\nIn January 2014, the Sudanese parliament approved an anti-human trafficking law which punishes those involved with human trafficking with up to 20 years imprisonment.", "\n\nAlso, in 2014, Khartoum hosted a conference on human trafficking in the Horn of Africa, organised by the African Union (AU), the UN High Commissioner for Refugees (UNHCR), the International Organization for Migration (IOM) and the Sudanese government.", "\n\nThe East African nation has also forged a strategic partnership with several European countries and the EU to combat illegal migration and human trafficking." ]

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