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In January, The Richmond Times-Dispatch reported that Gov. Ralph Northam’s proposed budget would give VCU the first right of refusal on the 20-acre ABC site. That item was approved. ABC expects to vacate the property in early 2021, when it intends to move into a new warehouse and headquarters site in Hanover County. The Flying Squirrels this offseason installed a $250,000 videoboard at The Diamond, which opened in 1985 and is outdated by modern ballpark standards. Lou DiBella, the franchise’s managing general partner, told The Times-Dispatch that the videoboard can be moved to a new stadium, and “we’ll be bringing that board with us in, hopefully, about three years. That’s my hope.” The Flying Squirrels, who open their 10th season at The Diamond on April 4, and the Eastern League have longed for a new stadium since Sept. 23, 2009, the day the franchise was relocated from Norwich, Conn., to Richmond. “I don’t think there’s any way in the world we anticipated 10 years ago that [The Diamond] would still be our home,” DiBella said. “We’ve done our best to make it as nice a place as it can be, which is really all we can do in that situation.
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Q: TypeScript generated JS files encoding I am using VS2015 and latest TypeScript (1.6.3). The generated JavaScript and map files are generated in Windows-1252 encoding. The source TypeScript files are UTF-8 with BOM. I do need the generated files to be UTF-8 with BOM as well in order to pass Windows Store certification. Once I manually fix encoding of the generated files it's fine. But then I must include the generated files in source control and fix any newly added files. There doesn't seem to be any settings to change the encoding. Is this a bug in the compiler? The project type is jsproj, which doesn't seem to support tsconfig.json according to https://github.com/Microsoft/TypeScript/issues/3124 A: Once I manually fix encoding of the generated files it's fine. But then I must include the generated files in source control and fix any newly added files. Use the emitBOM and charset options in tsconfig.json: { "compileOnSave": true, "compilerOptions": { //... other stuff "emitBOM": true, "charset": "utf8" }, // ... } See schema : http://json.schemastore.org/tsconfig A: Unfortunately TypeScript is not fully supported in VS2015 in its current state (will update this answer if it changes in future). In some project types you can use tsconfig.json and the compiler will then use the config. To do that you need to edit your project file and add element TypeScriptModuleKind with amd or commonjs specified to property group of the config file. If your project type is for example jsproj there is not way to use the config file at the moment. Then you must must Gulp/Grunt or just simply call tsc manually fro command line. Or you can run a Powershell script to fix the encoding: (Get-ChildItem ".\" -Recurse -Include ('*.js', '*.js.map')) | Foreach-Object { (Get-Content $_.FullName) | Set-Content -Encoding UTF8 $_.FullName }
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Q: Failed to create an ipc port; access is denied in MySQL Workbench I'm getting an error when I try to open MySQL Workbench: "failed to create an ipc port : access is denied" This is the dialog shown by the error A: What if you give a reboot to your machine, and then try opening up your workbench instance. According to this, the above issue is due to a locked resource.
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Letištní poplatky Předsedající Další bodem jednání je doporučení pro druhé čtení podané panem Ulrichem Stockmannem jménem Výboru pro dopravu a cestovní ruch o letištních poplatcích (08332/2/2008 - C6-0259/2008 -. Ulrich Stockmann zpravodaj. - (DE) Paní předsedající, pane komisaři, dámy a pánové, po tomto velmi dojemném tématu se nyní přesuneme k techničtějším záležitostem. Zítra na druhém čtení chceme odhlasovat směrnici o letištních poplatcích a po jednoznačném výsledku hlasování ve Výboru pro dopravu a cestovní ruch jsem si jist, že toho budeme také schopni. Čím se tato směrnice zabývá? Zavádí jednotné zásady a postupy vybírání letištních poplatků, platné pro celou Evropu. To znamená, že se jedná o transparentní východiska pro výpočet, nediskriminaci leteckých společností a určený postup konzultace, sloužící jako faktory použité spolu s některými dalšími ke stanovení spravedlivých letištních poplatků. Konflikty, které vznikly na základě těchto jasných pravidel, může řešit nezávislý dozorčí orgán. Dojde tak k posílení systémové partnerství mezi letišti a leteckými společnostmi a k vyloučení možnosti zneužití postavení na trhu. Jaké bylo východisko? Za posledních 15 let jsme podnikli dva pokusy o smíření konfliktních zájmů, které v této oblasti mají letiště a letecké společnosti. Jedním z důvodů, proč tyto pokusy ztroskotaly, byla skutečnost, že v členských státech máme naprosto odlišné postupy a struktury. Ve Spojeném království je například přísně fungující dozorčí orgán, který může určovat stropy, v pěti členských státech máme letištní síť a praxi křížové podpory, máme parlamenty, které rozhodují o letištních poplatcích, v Německu decentralizované pravomoci a k tomu ještě spoustu dalších věcí. Podařilo se nám nicméně vyjednat s Radou udržitelný kompromis. Co všechno tento kompromis obnáší? Zaměřili jsme se na letiště přepravující ročně více než pět milionů cestujících a k nim pak ještě na největší letiště v každém členském státě. V tuto chvíli to znamená, že se směrnice vztahuje na 69 letišť v Evropské unii. Zavedli jsme povinný postup pravidelné konzultace mezi letišti a leteckými společnosti a současně jsme stanovili strukturované rozhodčí řízení s danými lhůtami a zřídili jsme samozřejmě i onen dozorčí orgán, o kterém jsem již mluvil. Co míníme spravedlivými poplatky? Letištní poplatky musí mít v budoucnu silnější vazbu na výši nákladů, musí být odůvodněny transparentními výpočty a musí odpovídat uznané úrovni služeb. Současně platí přísný zákaz diskriminace. To v zásadě znamená tolik, že pro každou leteckou společnost platí na stejném letišti za stejné služby stejné poplatky, přičemž je možná diferenciace. Těší mě to, že jsme do toho započítali v první řadě hluk a znečištění. Některé země budou mít i nadále systémy společných poplatků, což se týká výše zmíněných letištních sítí a toho, co se nazývá letištními systémy ve městech a městských aglomeracích, ale i tyto systémy musí splňovat požadavky směrnice týkající se transparentnosti. Snažili jsme se reagovat na obavy našich kolegů z východoevropských členských států a zavedli opatření pro předběžného financování infrastruktury prostřednictvím poplatků. Bude to možné, i když na základě vnitrostátních kritérií obtížné, musí však být splněny normy Mezinárodní organizace pro civilní letectví (ICAO). Jaké očekáváme účinky? Větší hospodářská soutěž mezi evropskými letišti, větší hospodářská soutěž mezi různými leteckými společnostmi využívajících dané letiště a snad i postupný pokles cen letenek, pakliže je letecké společnosti sníží úměrně nižším poplatkům. K provedení směrnice je lhůta dvou let. Mé poděkování za úspěšná jednání patří všem stínovým zpravodajům a slovinskému úřadujícímu předsedovi Rady a Komisi. Antonio Tajani místopředseda Komise. - (IT) Paní předsedající, rád bych poblahopřál zpravodaji, panu Stockmannovi, k jeho vynikající práci. Velmi dobře přiblížil znění, návrh směrnice, kterou máme přijmout. Cílem tohoto návrhu je včlenit do práva Společenství určité zásady, s nimiž všechny členské státy již v rámci Mezinárodní organizace pro civilní letectví (ICAO) vyjádřily svůj souhlas: nediskriminace, transparentnost, konzultace. Směrnice stanoví rámec, který nám umožní strukturovat dialog mezi dopravci a letišti ohledně stanovení a vybírání poplatků. Směrnice bude například ukládat letištím povinnost konzultovat s leteckými společnostmi rozhodnutí týkající se letištních poplatků, dříve než tato rozhodnutí přijmou. Sám jsem postupoval podobným způsobem, předtím, než jsem předložil tento návrh, konzultoval jsem jej s leteckými společnostmi i letišti, a obě strany tento návrh schválily. Jak zmínil pan Stockmann, směrnice zavádí myšlenku vnitrostátních nezávislých dozorčích orgánů. Tyto orgánu budou hrát vlivnou úlohu, protože budou odpovědné za zajišťování toho, že budou dodržovány základní zásady, které jsem zde uvedl. To jsou zhruba řečeno cíle tohoto návrhu. Rád bych ještě jednou poděkoval panu zpravodaji za práci, kterou odvedl na druhém čtení při hledání shody s Radou. Výsledek nás stál sice spoustu práce, množství schůzek a velké úsilí, ale myslím, že se nám podařilo vytvořit dobrý dokument. Výsledky vyjednávání se projeví v určitém počtu pozměňovacích návrhů, jež si Komise vymínila, aby tomuto dokumentu mohl dát svůj plný souhlas. Velmi mne těší, že Výbor pro dopravu a cestovní ruch tuto dohodu rovněž jednomyslně podpořil. Jsem ovšem připraven pozorně sledovat rozpravu a vnímat všechny vaše poznámky. Zsolt László Becsey jménem skupiny PPE-DE. - (HU) Děkuji vám, paní předsedající. Pane komisaře, přestože venku prší, je dnes pěkný den. Rád bych poblahopřál jak panu zpravodaji, tak panu stínovému zpravodaji, protože se nám společnými silami spolu s Komisí, slovinským a pak francouzským předsednictvím podařilo po dlouhých diskusích dosáhnout dobrého kompromisu. I my činíme krok do neznáma, a tak bych ocenil, kdyby členské státy začaly s prováděním této směrnice co nejdříve a nikoli teprve po uplynutí sjednané dvouleté lhůty. To nám umožní skutečně posoudit, jakou má naše zákonodárná činnost hodnotu, a po čtyřech letech provést na základě přezkumu nezbytné úpravy. Věřím, že to členské státy pochopí a tam, kde je to potřeba, rychle dokončí nezbytné institucionální změny. Věřím také, že směrnice povede k zavedení transparentních poplatků a pouze mírnému zvyšování cen, a podaří se nám tak zabránit dravějším leteckým společnostem ve zneužívání svého silnějšího postavení k tomu, aby získávaly výhody nad svými konkurenty tím, že budou nabízet tytéž služby za nižší ceny, zatímco letiště si budou naříkat na nedostatek zákazníků. Zároveň bychom mohli také zajistit to, že letiště nebudou svévolně a netransparentním způsobem zvyšovat poplatky, k čemuž často dochází v náhlých skocích. V obou případech je cílem zajistit, aby evropští spotřebitelé platili pouze za to, co skutečně použili. To je další důvod, proč jsme nedovolili, aby se do těchto poplatků započítávaly i bezpečnostní výdaje nebo výdaje na pomoc zdravotně postiženým cestujícím. Za dobrý kompromis považuji i to, že jestli se budou, nebo nebudou brát v úvahu i příjmy z komerčních aktivit letiště, je ponecháno na rozhodnutí příslušného členského státu. Podobně bylo dosaženo dobrého výsledku na základě dohody ohledně letištních sítí; společný správní orgán je přijatelný, avšak co se týče stanovování výše poplatků, budou se účastníci řídit - jak přislíbila Komise - pravidly hospodářské soutěže, i když s ohledem na blízká letiště v sousedních zemích hrozí nebezpečí narušení trhu. Dobré je i kompromis týkající se oblastí působnosti. Sám bych dával přednost tomu, aby směrnice zahrnovala vedle letišť, která ročně přepraví více než 5 milionů cestujících, a letiště s největším pohybem cestujících v každém členském státě, také menší letiště v jejich blízkosti, která by případně také mohla konkurovat. V zájmu dosažení shody jsem však toto stanovisko opustil, i když při dalším přezkumu bych i tento bod znovu prošetřil. Přijímám, i když jen nerad, že jsme v bodech odůvodnění potvrdili možnost předběžného financování s odkazem na politiky Mezinárodní organizace pro civilní letectví (ICAO), ačkoli bych je byl raději viděl v hlavní části znění. Věřím, že pozvolné zvyšování cen poplatků namísto náhlých zvýšení cen budou cestující vnímat s větší benevolencí, ale i na to se budeme ještě muset při přezkumu podívat. Výsledkem je transparentnost financování ze strany státu či jiných veřejných orgánů. To je důležitý činitel v hospodářské soutěži mezi letišti a stejně důležité je i zohlednění hlediska ochrany životního prostředí. Za nejvýznamnější výsledek pokládám to, že každý jednotlivý členský stát bude muset vytvořit silný, nezávislý vnitrostátní orgán, který bude obdařen značnými pravomocemi. Jsem hrdý, že byla přijata a začleněna do zprávy zásada, díky níž by v případě neshod ohledně stanovování výše poplatků nemělo docházet k nekonečnému dohodovacímu postupu. Místo toho by mělo být přijato prozatímní rozhodnutí, které pak může zahájit dohodovací postup. Paní předsedající, velmi vám děkuji. Brian Simpson jménem skupiny PSE. - Paní předsedající, vítám zprávu svého kolegy, pana Ulricha Stockmanna, a děkuji mu za namáhavou práci, kterou na této dokumentaci odvedl. V průběhu celého procesu vznikání této zprávy se mé skupině jednalo o zajištění toho, že systém letištních poplatků v rámci celé EU bude spravedlivý a transparentní a že v případě neshody bude existovat propracované odvolací řízení. Lidé často uvažují o letectví jako o jednom jediném průmyslu, ale při bližším prozkoumání otázek, jako jsou letištní poplatky, začne být záhy zřejmé, že letištní a letecké odvětví mají odlišné názory a zájmy. Zpráva, kterou máme před sebou, nabízí vyvážené řešení, které nezvýhodňuje ani letecké společnosti ani letiště. I když bych osobně dával přednost hledisku založenému na procentu vnitrostátních cestujících a nikoli na arbitrárně stanoveném čísle, zpravodaj nás ve své zprávě ujistil, že toto číslo je na rozumné hranici pěti milionů cestujících - a nikoli směšného jednoho milionu, jak navrhovala Komise - a že zahrnuto musí být i hlavní letiště členského státu. Klíčovým prvkem všech těchto našich diskusí byla otázka, mají-li některá letiště dominantní postavení na trhu. Má skupina se domnívá, že kde tento případ nastává, by měly být letištní poplatky regulované. Mnoho letišť nicméně funguje v situaci hospodářské soutěže a letecké společnosti si mohou volně vybrat, kam budou létat. V mém regionu je manchesterské letiště, které ročně přepraví 22 milionů cestujících, ale v okruhu 150 km mu konkuruje dalších osm letišť. Za těchto okolností je samozřejmě dobrým regulátorem samotný trh. Vítám proto, že Spojené království bude mít možnost zachovat si svůj stávající systém monitorování letištních poplatků, protože se zde uplatňuje regulační rámec, který podporuje hospodářskou soutěž a poplatky reguluje prostřednictvím svého vlastního dozorčího orgánu pouze v případě letišť, které mají dominantní postavení. Připadalo by v úvahu, že by se tento regulační rámec, umožňující fungování spravedlivého a transparentního systému letištních poplatků, mohl začít uplatňovat i v jiných zemích. Věřím, že tuto směrnici budeme schopni ve druhém kole čtení odsouhlasit. Mělo by nám to pomoci k vydání směrnice, která bude znamenat konec tajným schůzkám, kde se domlouvají poplatky pro letiště mající monopolní nebo dominantní obchodní postavení. Mám dobrou naději, že letecké společnosti rovněž pochopí, že budeme mít nyní transparentní systém s propracovaným odvolacím řízením, s důkladnou konzultací, a že tak ustanou jejich neustálé stížnosti na letištní poplatky a budou společně s letišti pracovat na tom, aby pro všechny uživatele a cestující zajišťovaly nákladově efektivní služby za ceny odpovídající jejich hodnotě. Arūnas Degutis jménem skupiny ALDE. - (LT) Pane komisaři, dámy a pánové, myslím, že nikdo nepochybuje o tom, že evropský systém letištních poplatků a nákladů potřebuje transparentní a ospravedlnitelná pravidla, ne-li pro nic jiného, tedy proto, že některá letiště Společenství mají přirozený monopol. Evropský parlament nicméně od prvního okamžiku, kdy se o tomto dokumentu začalo diskutovat, velmi pečlivě zvažoval návrhy Komise a její přání kontrolovat více než 150 letišť Společenství. V rámci své účasti na přípravě různých dokumentů stáli poslanci Evropského parlamentu často před dilematem, kdy se museli rozhodnout, jaká je nezbytná míra kontroly a regulace a kdy se obojí stává cílem samo pro sebe a začíná ochromovat vlastní kontrolní činnost. To je obzvláště důležité v současné krizi, kdy je citlivost při zvažování otázek obchodního významu skutečnou nutností. Domnívám, že stanovením počtu letišť, která potřebují kontrolu, se Evropskému parlamentu stran dokumentu, o němž se má zítra hlasovat, podařilo nalézt a obhájit šťastnou střední cestu. Jsem potěšen, že také Rada byla podobného názoru a Komise že projevila pružnost nezbytnou k nalezení konstruktivního kompromisu. Další neméně důležitou věcí bylo nalezení rovnováhy mezi hlavními hráči působícími v tomto odvětví, tj. mezi zájmy letišť a leteckých společností. Mám za to, že i zde jsme vcelku projevili schopnost uspokojit očekávání obou stran. Je to věcí o to důležitější, že jakýkoliv jednostranný, nevyvážený návrh by měl tak či onak nepříznivý dopad na příležitosti evropských spotřebitelů používat tohoto nejbezpečnějšího způsobu dopravy. Toho všeho se podařilo dosáhnout díky profesionální práci pana zpravodaje. Pan Stockmann vždy vynikal jako nestranný politik, který je schopen naslouchat všem stranám. Na přípravě dokumentů týkajících se regulace letecké dopravy jsme spolu takto pracovali již po čtvrté. Ani tentokrát mne nezklamal, naopak mne obohatil o nové zkušenosti. Rád bych v tuto chvíli, kdy se diskuse o tomto dokumentu v Evropském parlamentu chýlí ke konci, poděkoval a poblahopřál panu Stockmannovi a ostatním svým kolegům. Rád bych také popřál úspěch Evropské komisi, protože ta nyní stojí před obtížným úkolem provedení této směrnice a monitorování její účinnosti, a hodně úspěchů bych chtěl popřát také všem zastupitelům. Roberts Zīle jménem skupiny UEN. - (LV) Děkuji vám, paní předsedající, pane Tajani, především bych rád blahopřál zpravodaji, panu Stockmannovi, a všem stínovým zpravodajům ke kompromisu, jehož s Radou dosáhli při druhém čtení. I podle mého názoru je třeba shodu ohledně rozsahu působnosti směrnice přivítat, protože její regulace bude mít dopad přinejmenším na ta nejdůležitější letiště všech členských států. Věřím, že za dva roky, kdy směrnice vstoupí v účinnost, už nebude možné, aby se v Evropské unii opakovala z právního hlediska tak nepochopitelná soudní rozhodnutí, jakým bylo rozhodnutí vydané nedávno jedním litevským regionálním soudem proti lotyšské letecké společnosti a jejímu hlavnímu letišti. Na základě tohoto rozhodnutí došlo k tomu, že soud jednoho členského státu zabavuje nejen majetek, který je ve vlastnictví letiště jiné země, ale i majetek, který je ve vlastnictví letecké společnosti jiné země v jiném členském státě. Rozhodnutí soudu se zakládalo na neobvykle rozdílném uplatňování letištních poplatků na hlavním lotyšském letišti. Velmi bych si přál, aby tato směrnice do budoucnosti vyloučila možnost těchto právně nejasných výkladů, protože na obchod v oblasti letecké dopravy mají zhoubné účinky. Děkuji vám. Gerard Batten jménem skupiny IND/DEM. - Paní předsedající, tato zpráva má zabránit tomu, aby jednotlivá letiště nezneužívala svého dominantního postavení na trhu, vytvořit přehledné hrací pole pro provozovatele a ochránit zájmy spotřebitelů. Kolikrát jsme již tento typ argumentace slyšeli? Dojde-li k jejímu provedení, bude mít tato harmonizace letištních poplatků s velkou pravděpodobností asi takový úspěch jako harmonizace, která nám přinesla společnou zemědělskou politiku, společnou rybářskou politiku a neustále narůstající břemeno evropských právních předpisů týkajících se obchodu, jež ročně stojí Spojené království přinejmenším 26 miliard britských liber. Tato směrnice přinese požadavek, aby se zcela zbytečně změnily britské právní předpisy upravující letištní poplatky a záležitosti související s dopravou. Vyžádá si zřízení údajně nezávislého dozorčího orgánu, čímž přibude další vrstva byrokracie, a nevyhnutelně i následné zvýšení nákladů. Ve Spojeném království samozřejmě existuje regulace a cenové stropy, koncipovaná tak, aby provozovatele letišť nutila k nákladové efektivitě. Cílem tohoto nepřetržitého proudu legislativy je harmonizovat v Evropské unii všechny aspekty života a podřídit jej nakonec moci Evropské unie. Všechny další úvahy jsou druhotné a nepodstatné. Čím si můžeme být naprosto jisti, to je zvýšení nákladů na úkor cestujících, k nimž tato opatření povedou. Georg Jarzembowski (DE) Paní předsedající, pane místopředsedo Komise, dámy a pánové, myslím, že můj předřečník jednoduše nepochopil dokumenty. Neděláme zde nic jiného, než že se snažíme určit pravidla pro transparentní ustanovení, jimiž se bude řídit vybírání letištních poplatků, přičemž smyslem celého tohoto podniku je zajistit, aby se výše letištních poplatků stanovovala objektivně a aby došlo k jejímu snížení ve prospěch uživatelů. To je náš úkol. Ve skutečnosti jsou zde dvě odlišné situace. Některá letiště jsou tak dominantní, že se letecké společnosti ocitají v zásadě v monopolní situaci, která může vést nakonec k tomu, že platí přemrštěně vysoké letištní poplatky. V případě jiných, vesměs menších letišť se letecká společnost může rozhodnout, bude-li tohoto letiště využívat či nebude na základě toho, jak nízké jsou zde letištní poplatky, a to je situace naprosto odlišná. Musím proto říci, že pan Stockmann se ve své zprávě dopracoval - a patří mu za to mé díky - k dobrému soupisu kritérií umožňujících stanovení správných a zdůvodnitelných letištní poplatků, které musí být hrazeny i ze strany cestujících, a jejich kontrolu vykonávanou vnitrostátním dozorčím orgánem. Pane místopředsedo, vy budete samozřejmě muset v průběhu následujících dvou let zajistit, aby vnitrostátní dozorčí orgány byly skutečně nezávislé. To znamená, že vnitrostátní dozorčí orgány nesmí být ve spojení s letišti či ve svazku s leteckými společnostmi. Velmi nám záleží na tom, aby dozorčí orgány udržovaly spravedlivou rovnováhu mezi leteckými společnostmi a letišti ve prospěch uživatelů. Zavedením těchto nových kritérií chceme za druhé také podpořit spravedlivější hospodářskou soutěž mezi letišti. V některých případech se letiště ve dvou různých členských státech nacházejí jen několik málo kilometrů od hranic. Chceme mít jistotu, aby zde nedocházelo k nekalé hospodářské soutěži. Jsem přesvědčen, že nová kritéria jsou správná. Dovolte, abych skončil otázkou, kterou chci adresovat vám, pane místopředsedo. Myslím, že od té doby, co Komise vydala pokyny pro regionální letiště, uplynuly už bezmála dva roky. Během několika posledních měsíců jste vyšetřoval, jestli některá letiště nedostávala nezákonné dotace, čímž míním státní dotace porušující hospodářskou soutěž ve prospěch některých konkrétních letišť. Všichni bychom rádi věděli, jaké jsou vaše závěry. Věřím, že nám dnes můžete slíbit, že výsledky vyšetřování nezákonné a zákonné regionální pomoci představíte v brzké době, protože oč jiného se zde v první řadě jedná než o to, že chceme spravedlivou hospodářskou soutěž mezi letišti ve prospěch cestujících. Silvia-Adriana Ţicău (RO) Ráda bych poblahopřála panu Stockmannovi za jeho úsilí o dosažení společného stanoviska s Radou, které by umožnilo přijetí směrnice stanovující společné zásady vybírání letištních poplatků na letištích Společenství. Uživatelům letišť navržený právní předpis nyní poskytuje rámec pro stanovování výše poplatků, který jim umožňuje podílet se na procesu rozhodování, je transparentní a připouští odvolání. Rada přijala návrh Parlamentu, který omezuje rozsah působnosti na letiště přepravující ročně více než 5 milionů cestujících a na největší letiště v každém členském státě. Rozdíly v letištních poplatcích se musí zakládat na transparentních, objektivních a jasných kritériích. V souladu se společným stanoviskem musí být letištní provoz nákladově efektivní a bude možné přidělovat pobídky na podporu nových tras do znevýhodněných a vzdálených regionů. Přidělování těchto pobídek však musí probíhat na základě transparentních kritérií. Podporujeme myšlenku, že členské státy podle informací od Komise v souladu s právními předpisy Společenství mohou zřídit letištní správní orgán, který bude uplatňovat společný transparentní systém poplatků na letištích, které slouží témuž městu nebo téže městské aglomeraci, s podmínkou, že každé letiště plně odpovídá požadavkům transparentnosti, stanoveným touto směrnicí. Upravování výše letištních poplatků se bude navíc řídit i environmentálními kritérii. Letištní správní orgán uveřejní rozhodnutí o změnách v systému poplatků nejméně dva měsíce před tím, než tyto změny vstoupí v platnost. Co se týče předběžného financování letištních investic, měly by se členské státy řídit politikami Mezinárodní organizace pro civilní letectví (ICAO) nebo vytvořit své vlastní zabezpečení. Parlament se domnívá, že je nutné, aby dozorčí orgány mohly pověřit uplatňováním ustanovení směrnice jiné nezávislé dozorčí orgány, které by za to nesly plnou odpovědnost a řídily by se týmiž normami. Paweł Bartłomiej Piskorski (PL) Paní předsedající, pane komisaři, rád by se také připojil ke gratulacím a poblahopřál panu Stockmannovi k výsledku jeho práce. Ve věci, o které diskutujeme, je regulace zapotřebí, s mým liberálním duchem není takováto regulace v rozporu, stejně jako s ním nejsou v rozporu regulační instituce. Nyní po finanční krizi vidíme, že volný trh by měl fungovat a že také funguje, musíme však vytvářet systémy, které v moderním hospodářství umožňují regulovat mechanismy, jež se občas zadrhnou nebo překročí rámec obvyklých mechanismů hospodářské soutěže, čisté hospodářské soutěže v rámci volného trhu. Naše nynější rozprava se týká konečného návrhu jistého dokumentu, práce, která, jak jsme si od samého začátku všichni uvědomovali, bude během na dlouhou trať, poněvadž regulovat přirozené monopoly - a letiště ze zřejmých důvodů obvykle fungují podle pravidel přirozených monopolů - je obtížné. Je to krok vpřed činěný v zájmu našich občanů, v zájmu občanů Evropské unie, kteří si po čase opět přejí, aby se od této sněmovny a Evropské komise dočkali něčeho hmatatelného, co se nějak projeví v jejich životě. Blahopřeji těm, kdo se na této práci podíleli, a věřím, že za dva roky, během nichž má být systém zaveden, dostojí členské státy svému úkolu. Luís Queiró - (PT) Mnoho z nás zde ve sněmovně používá internet k rezervaci a koupi letenek. Myslím však, že většina z nás neví, jak se stanovují letištní poplatky, které jsou součástí ceny letenek. Jelikož ale vím, že ne všechny poplatky uváděné na letenkách jsou letištní poplatky, požádal bych vás, abyste si se mnou dopřáli jednu malou slovní úlohu: letí-li cestující z Lisabonu do Bruselu například se společností Brussels Airlines, je na letence uvedený poplatek 48 EUR; cestuje-li s portugalskou leteckou společností TAP, je poplatek o 2 EUR nižší. Při zpátečním letu však už tento rozdíl není a cestujícímu je účtováno na poplatcích za jednu cestu o 15 EUR víc. Proč? Cestuje-li však náš imaginární cestující se společností Brussels Airlines do Londýna a letí z Bruselu na Gatwick Airport, činí poplatky za zpáteční letenku 124 EUR, když ale použije BMI a letí na Heathrow, zaplatí na poplatcích pouze 65 EUR. Poletí-li na Heathrow s BMI a vracet se bude s Lufthansou, zaplatí v takovém případě na poplatcích 70 EUR. Kde se tyto rozdíly berou? Jednou zaplatí jednu částku na cestě tam, jindy zase na cestě zpátky. Jednou si letecké společnosti účtují stejnou částku za stejné letiště, jindy nikoliv. V některých případech možná dokonce ani nevíte, kolik jste zaplatili. Existence různě vysokých letištních poplatků nicméně není špatná věc. Za rozdílné služby se musí platit rozdílné poplatky. Není však žádoucí, aby se stejné poplatky účtovaly za rozdílné služby a naopak aby služby jednoznačně stejné úrovně podléhaly různému zpoplatnění. Především však chceme, aby tyto poplatky byly stanovovány srozumitelným způsobem a podle jasných a transparentních kritérií. To je náš nejzazší cíl. Chceme zajistit spravedlivou a transparentní hospodářskou soutěž mezi hlavními evropskými letišti a tímto způsobem přispět ke zkvalitnění vnitřního trhu, zároveň však také ke snížení nákladů, které jsou účtovány cestujícím v ceně letenek, jež si kupují. Z tohoto důvodu jsme s dobrou nadějí v srdci tento návrh směrnice podpořili. Inés Ayala Sender (ES) Paní předsedající, musím nejprve poblahopřát svému kolegovi, panu Stockmannovi, za jeho vynikající zprávu a obzvláště pak za jeho trpělivost a vytrvalost, s jakou postupoval k výsledku. Je to text, který nám pomůže vytvořit společný vzdušný prostor a připravit se se zvláštním důrazem na transparentnost a nediskriminaci na to, co se stane velkým skokem do jednotného evropského nebe. Prostřednictvím tohoto společného systému vybírání uživatelských poplatků budeme schopni zajistit nezbytné podmínky spravedlivé a transparentní hospodářské soutěže. Budeme se tak rovněž připravovat na budoucnost, protože na modulaci poplatků budou mít vliv i environmentální kritéria a protože poplatky se nebudou vztahovat na pomoc poskytovanou zdravotně postiženým cestujícím. I v tomto směru se připravujeme na budoucnost. Musím rovněž zdůraznit zohlednění potřeby vyhnout se nadměrnému zatížení malých letišť, k čemuž vedlo stanovení minimální hranice pěti milionů cestujících ročně. Těší nás konečně, že byla uznána možnost vykonávání správy letištních sítí jediným orgánem, pakliže tento orgán prokáže své dobré fungování - jak je tomu v případě španělského letištního orgánu AENA - a že byly vzaty v úvahu i další způsoby kontroly a stanovování poplatků pod zákonným dohledem - což je také případ mé země - vedle dohledu nezávislých dozorčích orgánů. Těší mě proto, že tyto návrhy byly vzaty v úvahu. Panu zpravodajovi musí poblahopřát také k tomu, že stanovil pevné časové lhůty pro zveřejňování rozhodnutí. Předejde se tak právní nejistotě a uživatelům jsou dány záruky stran toho, kdy budou tato rozhodnutí uskutečněna. To je také pozitivní, protože ohledně těchto lhůt a rozhodnutí byl vzat v úvahu parlamentní dohled. Fiona Hall Paní předsedající, vítám zvýšenou transparentnost, kterou zavádějí tato nová pravidla týkající se letištních poplatků. Letiště až příliš často drží v tajnost dohody, které mají, a to i přesto, že jsou ve vlastnictví nebo částečném vlastnictví veřejných institucí. Veřejnost má právo vědět, jakým způsobem získávají a utrácejí své peníze. Jsme však zklamána tím, že práh pro podávání častějších zpráv byl stanoven na pět milionů bez ohledu na procentuální podíl na vnitrostátním trhu. Tento práh velmi tvrdě zasáhne regionální letiště jako například Newcastle. Newcastle, který ročně přepraví šest milionů cestujících, se ocitl nad prahem, ale je to zároveň malá ryba ve srovnání s obry, jako je Heathrow nebo Gatwick. Vzhledem k tomu, že regionální letiště konkurují hlavně svým nejbližším sousedům, bylo by bývalo spravedlivější mít systém, který by zacházel se všemi malými a středně velkými letišti stejným způsobem. Lituji proto, že se Komise nezabývala možností omezit rozsah působnosti směrnice na letiště přepravující ročně více než pět milionů lidí a současně pokryjí více než 15 % vnitrostátního pohybu cestujících. Takový práh by stále ještě zajišťoval, že velká evropská letiště nebudou diktovat letištní poplatky, které domluví za zavřenými dveřmi. Věřím, že až bude Komise směrnici přezkoumávat, pečlivě zhodnotí, nejsou-li regionální letiště jako Newcastle poškozována narušením trhu. Emanuel Jardim Fernandes (PT) Paní předsedající, pane komisaři, dámy a pánové, rád bych začal gratulací panu Stockmannovi k jeho otevřenosti a ochotě ke kompromisu, které projevil během přípravy této vynikající zprávy, která se bude přímo dotýkat letišť nad pět milionů cestujících a v konkrétním případě pak letiště ve Faru a Lisabonu v mé zemi. Tento návrh musí být v Parlamentu i v Radě přijat, protože zaručuje nediskriminaci při stanovování letištních poplatků s výjimkou případů, které jsou nezbytné a v souladu se Smlouvou. Měl by být zaveden povinný postup konzultace mezi orgány letištní správy a uživateli letišť. Všechny rozdíly v poplatcích budou transparentní a založené na jasných kritériích. Letiště budou za stejné služby účtovat stejné poplatky, uživatelům letišť mohou být nicméně v závislosti na kvalitě využívané služby poskytnuty slevy, pakliže této slevy mohou na základě veřejných, transparentních a objektivních podmínek využívat všichni uživatelé letišť. Slevy lze udělit uživatelům otevírajícím nové trasy v souladu s právními předpisy týkajícími se hospodářské soutěže. Měl by být zřízen vnitrostátní nezávislý dozorčí orgán, který zasáhne v případě neshody ohledně rozhodnutí o poplatcích. Mělo by být povoleno udělování pobídek pro otevírání nových tras, které budou zajišťovat spojení do méně oblíbených a vzdálených regionů. A konečně, členské státy by měly mít možnost pověřit správní orgán odpovědný za letištní síť k zavedení systému poplatků, který bude platit pro celou tuto síť. Paní předsedající, díky této nové směrnici zaručí budoucí letištní poplatky na našich letištích, a to dokonce i v tak odlehlých regionech, z jakého pocházím já, každému univerzální přístup k letecké dopravě. To je obzvláště důležité v regionu, jako je ten můj, kam a odkud se nelze dostat nijak jinak než pomocí letecké dopravy. Přeji si proto, že tento návrh bude zítra přijat a že je řádně přijme Komise i Rada. Robert Evans I já připojuji své díky panu Stockmannovi k díkům svých kolegů za to, co myslím charakterizoval jako použitelný kompromis v zájmu 69 evropských letišť. Jsou mi rovněž blízká slova pana Becseye a ovšem i mého kolegy Briana Simpsona stran spravedlivé a transparentní hospodářské soutěže. Těší mne, že tato zpráva ve své stávající prezentované podobě je dobrou službou nejen ve prospěch tří londýnských letišť, Heathrow, Stansted a Gatwick, ale i ve prospěch letišť ve zbytku Evropy, ať už je to Lotyšsko pana Zīleho, Rumunsko paní Ţicăuové či Portugalsko a ovšem i ve prospěch letišť v Itálii pana komisaře, a předpokládám, že i v Německu budou nějaká letiště, ačkoli tam mnoho lidí nelétá. Myslím si ale také, že je dobrou službou ve prospěch evropských cestujících, letiště samozřejmě nejsou ničím bez občanů, cestujících. Jsou naší prioritou, stejně jako je naší prioritou životní prostředí, které je v této zprávě myslím také zohledněno. Pan Batten, můj londýnský kolega, ve svém příspěvku, který by bylo možné nejvýstižněji charakterizovat slovy bodni a uteč (už totiž odešel), naznačuje, že mají být zřizovány nové orgány a ještě další poplašné zprávy. Tyto orgány - Úřad pro civilní letectví - ovšem už existují. Domnívám se proto, že na jeho straně došlo k nedorozumění - mám-li být zdvořilý. A poznámka k paní Fioně Hallové, nejsem si jistý, že by Newcastle přímo konkuroval Londýnu. Mezi oběma městy je celkem slušná vzdálenost a pokud se někdo rozhodne letět do Londýna místo, aby letěl do Newcastlu, má to odtamtud ještě pořádný kus cesty. Čili si myslím, že nesrovnáváte srovnatelné. Myslím, že je to dobrý, použitelný kompromis. Myslím, že jsme se dotkli všeho, co jsme chtěli původně řešit, a že balík ve svém celku vytváří vyvážené podmínky - v zájmu leteckých společností a v zájmu cestujících - o jejichž vytvoření nám šlo, a zároveň dává letištím dostatečnou svobodu, aby mohla fungovat v konkurenčním prostředí. Chovám naději, že se následkem toho snad jednou - člověk nikdy neví, kolegové, člověk nikdy neví - dočkáme na cestě do Štrasburku uspokojivých služeb. Je to jako střílet na dálku, člověk nikdy neví, ale má cenu se snažit. Bogusław Liberadzki (PL) Paní předsedající, rád bych nejprve vyslovil své díky panu Ulrichu Stockmannovi, našemu zpravodaji. Pan Stockmann odvedl velký kus práce, která začala u návrhu směrnice, k němuž přistoupil inovativním způsobem s tím, že chtěl náležitě připravit zprávu ve spolupráci s Komisí a Radou, což se mu také s úspěchem podařilo. Především bych chtěl zdůraznit jeho iniciativu stran zpřesnění definice letištních poplatků a za druhé letišť, kterých se směrnice bude týkat, a úrovně služeb poskytovaných na letištích a jejich souvislosti se závazky provozovatelů letišť. Stejně významná, obzvláště pro nové členské státy, je možnost financování nových infrastrukturních projektů. Vydáváme nový návrh směrnice, který z hlediska cestujících umožní těm z nás v Evropě, kdo využívají či provozují služby nebo za ně platí, abychom věděli, kolik máme platit, proč a kam tyto peníze jdou. To je významný krok směrem k vytvoření reálného evropského systému a evropské sítě aerolinií. Děkuji vám za to a jsem hluboce přesvědčen, že tento návrh směrnice prokáže dobrou službu civilnímu letectví. Zuzana Roithová (CS) Pro fungování vnitřního trhu Evropské unie je důležité, aby také dobře fungovaly letištní služby. Cestující i letecké společnosti kritizují netransparentní a někdy i nadhodnocené letištní taxy, které neodůvodněně prodražují cestovné. Tomu konečně odzvoníme přijetím této směrnice ve druhém čtení. Regulace přinutí letiště s více než pěti miliony cestujících zprůhlednit poplatky, zdůvodnit své náklady a zjednoduší to spory mezi uživateli a správou letišť. Jsem přesvědčena, že to povede ke snížení poplatků a že se zlepší konkurenční prostředí. Jsem ráda, že Rada také uznala otevření prostoru pro pobídky, které přispějí k otevření nových tras do znevýhodněných nejvzdálenějších destinací, a že se zdařilo dojít ke společné definici sítě letišť, která budou provozována stejným řídícím orgánem. Blahopřeji zpravodajům k těmto výsledkům. Mieczysław Edmund Janowski Paní předsedající, pane komisaři, pan Stockmann si zaslouží naši vděčnost. Jeho zpráva je opravdu dobrým kompromisem. Blahopřeji mu. Dokončujeme dnes práci na letištních poplatcích. Za krátkou dobu, už za dva roky, budeme mít konsolidovaný systém vybírání těchto poplatků, fungující v celé Evropské unii. Bude se týkat letišť přepravujících více než pět milionů cestujících ročně a největších letišť v každé zemi. Tato čísla mohou být sice stále diskutabilní, já si nicméně myslím, že jsou správná. Pokud vím, dotkne se to zhruba 80 letišť v Evropské unii. Zvláštní předností přijatých regulačních opatření je jejich transparentnost, která pomůže dozorčím orgánům. Letiště v méně oblíbených regionech budou moci uplatňovat příslušná zvýhodnění. V úvahu byly vzaty rovněž environmentální aspekty a situace zdravotně postižených lidí. Věřím, že směrnice vytvoří na letištích nejen podmínky pro spravedlivou hospodářskou soutěž, ale povede také ke zvýšení bezpečnosti cestujících a ochrání cestující před neúměrně vysokými poplatky za odlet a přistání. Antonio Tajani místopředseda Komise. - (IT) Paní předsedající, rozprava myslím ukázala, že Parlament a Komise odvedly dobrou práci, a chvála pana Stockmanna jen dokládá, že postupoval správným směrem. Rád bych mu zde veřejně ještě jednou poděkoval za jeho práci a spolupráci s Komisí při hledání úspěšného kompromisního řešení, které, jak jsem viděl, ocenili všichni, kdo zde dostali slovo. Jsem přesvědčen, že návrh směrnice, který se zde nyní zabýváme a který, jak doufám, bude touto sněmovnou přijat, jak řekla paní Ayala Senderová, není ničím jiným nežli krokem k dosažení jednotného nebe, což je cíl, za kterým je podle mého názoru, Komise, s podporou Parlamentu a s oporou v Radě třeba jít, abychom ještě před koncem tohoto parlamentního období vyslali jednoznačný signál. Podporuji všechna rozhodnutí a soudy ohledně zřízení nezávislého orgánu, který už v některých zemích Unie existuje. Myslím, že bychom o to měli usilovat; je to pozitivní rozhodnutí, které jsme společně učinili. Ještě než skončím, chtěl bych ještě jednou poděkovat všem poslancům, kteří přispěli k této rozpravě, a odpovědět na otázku pana Jarzembowského. Uvažuje se o sedmi regionálních letištích. Jednání, která trvají už 18 měsíců, byla zahájena v červenci 2007. Neočekávám proto, že výsledky budou před koncem tohoto roku nebo začátkem roku příštího. Výsledky budou samozřejmě zveřejněny, ale bylo to ode mě nespravedlivé a nepatřičné, aby se k této práci vyjadřoval ještě před jejím ukončením. Jakmile k tomu ale dojde a jakmile Komise učiní rozhodnutí, bude Parlament informován a kromě informace, kterou jsem byl nyní schopen podat, týkající se návrhů Komise pro sedm - a toto číslo, sedmičku, bych zde zdůraznil - případů, jimiž se nyní zabývá, dostane pan Jarzembowski úplnou odpověď. Ulrich Stockmann zpravodaj. - (DE) Paní předsedající, rád bych ještě jednou poděkoval svým kolegům poslancům za jejich skutečně konstruktivní spolupráci a za naše vzrušující diskuse. Spoléhám se zítra na vaši velkou podporu. Nyní je už pozdě a slov mezi námi padlo už dost. Zítra by měly přijít na řadu činy. Potěšilo by mně, kdyby se nám podařilo dokončit tento legislativní postup ve druhém čtení. (Potlesk) Předsedající Rozprava je ukončena. Hlasování se bude konat zítra, ve čtvrtek 23. října. Písemná prohlášení (článek 142) Corina Creţu písemně. - (RO) Evropský rámec pro regulaci letištních poplatků má zásadní význam pro snížení nákladů pro lidi cestující v rámci Evropské unie, a tudíž i pro zvýšení mobility pracovníků, zejména pracovníků s vysokou kvalifikací. Mobilita pracovníků je v souvislosti dané příslušnou kapitolou Lisabonské strategie, jejímž cílem je hospodářský růst a zvyšování počtu pracovních míst, skutečně klíčovým prvkem efektivního trhu práce. Zjednodušení pohybu pracovníků s vysokou kvalifikací dále povede ke zvýšení informačních toků a intenzivnější výměně užitečných znalostí ve výrobních odvětvích s vysokou přidanou hodnotou v souladu s cílem Lisabonské strategie, jímž je transformovat evropské hospodářství v nejdynamičtější, na znalostech založené hospodářství na světě. Christine De Veyrac Dámy a pánové, podařilo se dosáhnout kompromisu mezi Radou a naší institucí, a tuto záležitost tak bude možné ve druhém čtení uzavřít. Jsem touto shodou potěšena, obzvláště proto, že by měla zabránit zneužívání dominantního postavení a usnadnit vyvážený rozvoj evropského letištního odvětví. Tato směrnice o letištních poplatcích je skutečným krokem vpřed: vytvořením transparentnějších vztahů mezi letišti a leteckými společnostmi umožní zefektivnění a zlepšení často neprůhledných a konfliktních vztahů. Zavedení nezávislého orgánu navíc umožní objektivní řešení konfliktů mezi partnery. Příjemcem těchto nových pravidel by měli být vposled uživatelé letecké dopravy a to mě těší. Děkuji vám za pozornost.
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Q: blank file while copying a file in python I have a function takes a file as input and prints certain statistics and also copies the file into a file name provided by the user. Here is my current code: def copy_file(option): infile_name = input("Please enter the name of the file to copy: ") infile = open(infile_name, 'r') outfile_name = input("Please enter the name of the new copy: ") outfile = open(outfile_name, 'w') slist = infile.readlines() if option == 'statistics': for line in infile: outfile.write(line) infile.close() outfile.close() result = [] blank_count = slist.count('\n') for item in slist: result.append(len(item)) print('\n{0:<5d} lines in the list\n{1:>5d} empty lines\n{2:>7.1f} average character per line\n{3:>7.1f} average character per non-empty line'.format( len(slist), blank_count, sum(result)/len(slist), (sum(result)-blank_count)/(len(slist)-blank_count))) copy_file('statistics') It prints the statistics of the file correctly, however the copy it makes of the file is empty. If I remove the readline() part and the statistics part, the function seems to make a copy of the file correctly. How can I correct my code so that it does both. It's a minor problem but I can't seem to get it. A: The reason the file is blank is that slist = infile.readlines() is reading the entire contents of the file, so when it gets to for line in infile: there is nothing left to read and it just closes the newly truncated (mode w) file leaving you with a blank file. I think the answer here is to change your for line in infile: to for line in slist: def copy_file(option): infile_name= input("Please enter the name of the file to copy: ") infile = open(infile_name, 'r') outfile_name = input("Please enter the name of the new copy: ") outfile = open(outfile_name, 'w') slist = infile.readlines() if option == 'statistics': for line in slist: outfile.write(line) infile.close() outfile.close() result = [] blank_count = slist.count('\n') for item in slist: result.append(len(item)) print('\n{0:<5d} lines in the list\n{1:>5d} empty lines\n{2:>7.1f} average character per line\n{3:>7.1f} average character per non-empty line'.format( len(slist), blank_count, sum(result)/len(slist), (sum(result)-blank_count)/(len(slist)-blank_count))) copy_file('statistics') Having said all that, consider if it's worth using your own copy routine rather than shutil.copy - Always better to delegate the task to your OS as it will be quicker and probably safer (thanks to NightShadeQueen for the reminder)!
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Q: Start and end date of a current month I need the start date and the end date of the current month in Java. When the JSP page is loaded with the current month it should automatically calculate the start and end date of that month. It should be irrespective of the year and month. That is some month has 31 days or 30 days or 28 days. This should satisfy for a leap year too. Can you help me out with that? For example if I select month May in a list box I need starting date that is 1 and end date that is 31. A: There you go: public Pair<Date, Date> getDateRange() { Date begining, end; { Calendar calendar = getCalendarForNow(); calendar.set(Calendar.DAY_OF_MONTH, calendar.getActualMinimum(Calendar.DAY_OF_MONTH)); setTimeToBeginningOfDay(calendar); begining = calendar.getTime(); } { Calendar calendar = getCalendarForNow(); calendar.set(Calendar.DAY_OF_MONTH, calendar.getActualMaximum(Calendar.DAY_OF_MONTH)); setTimeToEndofDay(calendar); end = calendar.getTime(); } return Pair.of(begining, end); } private static Calendar getCalendarForNow() { Calendar calendar = GregorianCalendar.getInstance(); calendar.setTime(new Date()); return calendar; } private static void setTimeToBeginningOfDay(Calendar calendar) { calendar.set(Calendar.HOUR_OF_DAY, 0); calendar.set(Calendar.MINUTE, 0); calendar.set(Calendar.SECOND, 0); calendar.set(Calendar.MILLISECOND, 0); } private static void setTimeToEndofDay(Calendar calendar) { calendar.set(Calendar.HOUR_OF_DAY, 23); calendar.set(Calendar.MINUTE, 59); calendar.set(Calendar.SECOND, 59); calendar.set(Calendar.MILLISECOND, 999); } PS: Pair class is simply a pair of two values. A: If you have the option, you'd better avoid the horrid Java Date API, and use instead Jodatime. Here is an example: LocalDate monthBegin = new LocalDate().withDayOfMonth(1); LocalDate monthEnd = new LocalDate().plusMonths(1).withDayOfMonth(1).minusDays(1); A: Try LocalDate from Java 8: LocalDate today = LocalDate.now(); System.out.println("First day: " + today.withDayOfMonth(1)); System.out.println("Last day: " + today.withDayOfMonth(today.lengthOfMonth()));
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Predictors of sexual well-being after endometrial cancer: results of a national self-report survey. We examined whether sociodemographic, physical, reproductive, psychological and clinical factors at the time of diagnosis were related to women's sexual well-being 3-5 years following treatment for endometrial cancer. Of the 1,399 women in the Australian National Endometrial Cancer Study, 644 completed a follow-up questionnaire 3-5 years after diagnosis. Of these, 395 women completed the Sexual-Function Vaginal Changes Questionnaire, which was used to assess sexual well-being. Based on two questions assessing worry and satisfaction with their sexuality, women were classified into lower and higher sexual well-being. Multivariable-adjusted logistic regression models were used to examine sexual well-being 3-5 years following cancer treatment and the factors associated with this at diagnosis and at follow-up. Of the 395 women, 46 % (n = 181) were categorized into the "higher" sexual well-being group. Women who were older (odds ratio [OR] = 1.97; 95 % confidence limit [CI], 1.23-3.17), high school educated (OR = 1.75; 95 % CI, 1.12-2.73), who reported good mental health at the time of diagnosis (OR = 2.29; 95 % CI, 1.32-3.95) and whose cancer was treated with surgery alone (OR = 1.93; 95 % CI, 1.22-3.07) were most likely to report positive sexual well-being. At 3-5 years post-diagnosis, women with few symptoms of anxiety (OR = 2.28; 95 % CI, 1.21-4.29) were also most likely to report positive sexual well-being. Psychological, sociodemographic and treatment factors are important to positive sexual well-being post-cancer. Care that focuses on maintaining physical and psychosocial aspects of women's lives will be more effective in promoting positive sexual well-being than care that focuses solely on physical function.
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Genetics for the practicing dermatologist. In the era of robust genome sequencing, a working understanding of genetics has become important for the clinician. For the dermatologist, understanding the flow of genetic information from genotype to phenotype can aid in the delivery of effective patient care. In this article, we will review concepts in genetics and the human genome and how they contribute to clinical dermatology.
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Spider-Man 2211 Dr. Max Borne, the Spider-Man from 2211, is a genius who gave himself spider powers by building a highly advanced suit that increases his strength, agility, and resistance to damage. A member of an organization known as the Timespinners, he and those like him seek to prevent disruptions in the fabric of time itself.
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Almadex Minerals Almadex Minerals came out on top on last week’s TSXV list, with its shares rising 95.26 percent to $0.88. Year-to-date, the company’s shares have risen sharply by 467.74 percent. Almadex currently has exploration programs underway in Mexico, Canada and the US. The company announced on August 8 that it had completed its diamond drill hole EC-16-010 to a depth of 776.51 on the Norte Zone on its 100 percent owned El Cobre porphyry copper-gold project in Mexico. American Manganese American Manganese held the number two position on the TSXV for the second week in a row, with its shares rising 90 percent to reach $0.19. Year-to-date, however, American Manganese’s shares have risen sharply by 850 percent. According to the company’s website, American Manganese plans to produce electrolytic manganese for the steel and rechargeable battery markets. Of note, its Artillery Peak property is the largest known manganese deposit in the Southern United States. Last week, American Manganese announced a $1 million private placement, proceeds of which will be used to continue metallurgical testing of its proprietary hydrometallurgical process for large-scale recylcing of lithium-ion batteries. Cava Resources Cava Resources owns interest in properties in the White Gold District of Yukon, and aso has a 49 percent interest in the 33 claim Beschefer Property, and maintains a 70 percent interest in the Casa Berardi project. Last week, shares of Cava Resources rose 56 percent to $0.78, however its year-to-date increase is significantly more at 1,460 percent. Orla Mining Orla Mining’s shares rose 52.94 percent over a five-day period last week to $1.04. Like Cava Resources, Orla’s year-to-date gains are significantly more at 642.86 percent. The company holds a 50 percent interest in the Blue Quartz Gold Property in Ontario. MDN Rounding out last week’s top five TSX stocks is MDN Inc., who is actively developing the Crevier project, a niobium and tantalum resource in the Saint-Jean region in Quebec. The company also started an exploration program on its 100 percent owned Samaqua property in 2015. On August 4, MDN announced the closing of a non-brokered private placement of $1,795,000. Last week, the company’s shares rose 50 percent to $0.135 over a five day period, and has steadily increased 285.71 percent year-to-date. Data for 5 Top TSXV Stocks articles is retrieved each Friday after market close using The Globe and Mail’s market data filter. Only companies with a market capitalization greater than $10 million prior to the week’s gains are included. Companies within the mining and precious metals sectors are considered. Securities Disclosure: I, Jocelyn Aspa, hold no direct investment interest in any company mentioned in this article.
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This invention relates to inflatable air bladders, such as mattresses and the like, composed of three layers fused together to form plurality of air cells on opposite surfaces of the bladder. More particularly, the invention relates to an inflatable air bladder in which the middle layer is coated on opposite sides with barrier material which inhibits heat-sealing of one outer layer onto one side of the middle layer at the same sites that the middle layer is sealed to the other outer layer. Air mattresses consisting of individual air cells formed by sealing together two or three layers of heat-sealable polymeric material are known in the prior art. In this connection, for example, U.S. Pat. No. 2,691,179 to Kann discloses an air mattress comprising a pneumatic structure for a mattress formed by sealing together two sheets of heat-sealable material. To overcome sagging of the mattress, known as the "hammock" effect, the cells are superimposed in two layers, with the cells in one layer disposed transversely to the cells in the other layer. U.S. Pat. No. 2,731,652 to Bishop also discloses an air mattress formed by heat-sealing together two sheets of heat-sealable material. U.S. Pat. No. 4,483,030 to Flick, et al, discloses an air pad formed by heat-sealing two sheets of heat-sealable material to a middle layer in a selective rectangular pattern. During the fabrication of the air pad, a sealing barrier mechanism 54 is used having a plurality of parallel fingers 58 so that the middle layer will not be heat-sealed to both the outer sheets at corresponding points. U.S. Pat. No. 4,488,929 to Ostertag also discloses the use of a barrier apparatus for fabricating air mattresses composed of two outer sheets and center layer whereby the center layer will not be fused to both outer sheets at corresponding fusion points. In this patent, laterally-spaced, comb-like elements 5' and 6' are fitted between the opposite surface of the center layer and the two outer sheets whereby the center layer is alternately sealed to the outer sheets along laterally-spaced seal lines. It is the principal object of this invention to provide a multi-layer, inflatable air bladder construction in which the middle layer thereof is treated with a barrier material so that it will be adapted to be heat-sealed to both outer sheets of the bladder in a predetermined air cell pattern, but without corresponding points of the middle layer being sealed to both outer sheets. It is another object of this invention to provide an improved method of fabricating an inflatable air bladder which is simpler and more economical than methods heretofore available for the same purpose.
{ "pile_set_name": "USPTO Backgrounds" }
Q: Conditional agent in Jenkins I'm trying to set a conditional agent in Jenkins defined through the branch such as: cloud = myconditional() pipeline { agent { kubernetes { cloud cloud } } and, the function myconditional is defined in a library /vars/myconditional.groovy def call() { def cloud = "clusterB" echo "Branch ${env.GIT_BRANCH}" if ("${env.GIT_BRANCH}" != "master") { echo "use clusterA" cloud = "clusterA" }else{ echo "use clusterB" } return cloud ... But I get Branch null. Other way using scm def getGitBranchName() { return scm.branches[0].name } def call() { def cloud = "clusterB" def branch = getGitBranchName() echo "Branch ${branch}" if (branch != "master") { echo "use clusterA" cloud = "clusterA" }else{ echo "use clusterB" } return cloud But I get: org.jenkinsci.plugins.scriptsecurity.sandbox.RejectedAccessException: Scripts not permitted to use method hudson.plugins.git.BranchSpec getName and i don't have permissions to change the Jenkins configuration. I try to print the environment vars but I get this: def call() { sh 'env > env.txt' sh 'cat env.txt' .... I have got: org.jenkinsci.plugins.workflow.steps.MissingContextVariableException: Required context class hudson.FilePath is missing My question is, how can i get the actual branch out of the pipeline{}? Thanks a lot A: If you are using Jenkins Multibranch Pipeline, you can obtain the branch name by using the following variable. env.BRANCH_NAME You can use the following conditional: if ("${BRANCH_NAME}" != "master" ) { ... } else { ... }
{ "pile_set_name": "StackExchange" }
Wednesday, April 25, 2007 no complaints here! Today I was kicked out of the house.Last night I asked my husband what we were going to do on his day off and he said,"No,you tell me what you are going to do?""Huh?""I'm kicking you out, woman! That's right. You are not allowed to come back to the house until you have had a wonderful day all to yourself. I have plans for the girls and I and they include you being out to enjoy some time off."Oh, how I love this man. Have I mentioned lately how much I love Jeep. I love him so. If there were any doubts before...this is the clincher! lol I drove myself to the mall with thoughts of "What am I going to do?" and then as I rolled to a stop at the intersection, I cranked up the tunes, unrolled the windows and laughed, "What aren't I going to do? Yahooooo! A day off! I am highly favoured above woman! Yahooo!" Since I'm relying on God to change the habit of complaining in my life over these next 21 days I contemplated how I was going to work on this while I was in the mall...alone....did I mention ALONE! In case anyone missed it...ALONE!!!!! I was completely by myself...or was I?Nope, I wasn't. The presence of My King was tagging along and I had to say that I was quite grateful for it.I spent time walking, searching for deals, trying on clothes and enjoying the people and places around me. Bursting from my heart was an overwhelming sense of thankfulness I have towards God and His goodness. He is so good. He is just so good.And you know what else is good? New clothes! Oh yeah. And I spent 45 minutes in Ardene's picking out ten necklaces for $10 dollars. I tried everyone on ahead of time, I was fussy, I was picky, I made sure everything was to my liking. Do you know when the last time I've done that is? Hmmm...never!But, here I was, in the mall with nothing but time to spend on being frivilous.And that's when it hit me.I was being frivilious, and carefree and downright silly with my time.When I shop, especially when I am with my kids, I can be a bit of a supermarket-nazi. I have a printed list, I have a map planned in my head of the best way to go through aisles, I am efficient and I am purposed.Not today! Today I got to be free from care.And looking back over the days events I see now that God really designed for this day to happen. The bigger message He was sending me was, "Allie, rest in me. You don't have to have a written list or a prepared plan with how I am going to change your habits. Just enjoy the journey, crank up the music and have fun."
{ "pile_set_name": "Pile-CC" }
Startup Weekend Profile: Fixit Anhton Tran is an undergrad student at Notre Dame who is interested in giving people an outlet to express problems. After working with Participant Media around how to engage millennials civically and in a meaningful way, Anhton saw a lot of the problems, "our generation watches news but it's too big; we don't engage with it. We engage with social media so lets discuss societal issues there". That is where he came up with Fixit. The idea is allowing people to point out issues they see around them, things they see that they can affect, like pot holes or infrastructure changes, and allow people to vote those problems up or down. People will be able to see the problems around them and the city or college will be able to fix it, and they'll know which problems are most important to fix. "The scope has changed a lot, it's not about personal problems or huge issues like climate change - it's somewhere in between." Talking with Anhton you can see the passion behind this project, that you can truly change society if you put their problems in front of them in a way that they want to help. That is where Fixit will begin helping, to find out more check out https://twitter.com/fixitsb.
{ "pile_set_name": "Pile-CC" }
All relevant data are within the manuscript and its Supporting Information files. Introduction {#sec001} ============ Cytotoxic T Lymphocytes (CTLs) are key effectors in the adaptive immune response, therefore CTL function---or lack thereof---is relevant in many pathologies. A greater quantitative understanding of CTL effector function will aid in interpretation of prior experiments and should yield useful insights for the treatment of diseases in the future. However, the rate at which CTLs kill infected or malignant cells remains poorly characterised. Estimates of CTL killing based on *in vitro* and *in vivo* CTL killing assays vary, with some variation explained by e.g. different susceptibility of target cells to CTL killing or the type of antigen expressed by the targets \[[@pcbi.1007972.ref001],[@pcbi.1007972.ref002]\]. Moreover, especially *in vivo* the presence of stimulatory or suppressive factors and difficulty in controlling or estimating the ratio of CTLs to target cells at the site of killing might confound CTL killing estimates \[[@pcbi.1007972.ref001],[@pcbi.1007972.ref002]\]. As a frequently discussed example, consider the *in vivo* CTL killing assay of Barber *et*. *al*. \[[@pcbi.1007972.ref003]\], in which CTLs demonstrated rapid killing against Lymphocytic Choriomeningitic Virus (LCMV). Although Barber *et*. *al*. initially estimated that CTLs took 15 minutes to kill targets, subsequent modelling studies based on the same data have estimated much faster killing rates \[[@pcbi.1007972.ref004],[@pcbi.1007972.ref005],[@pcbi.1007972.ref006]\], with one study implying an expected target survival time of 16 seconds after contact from a CTL \[[@pcbi.1007972.ref004]\] (see also \[[@pcbi.1007972.ref001]\] for a detailed summary of these estimates). Given that killing in those experiments was perforin-dependent\[[@pcbi.1007972.ref003]\], these fast estimates seem to contradict recent *in-vivo* imaging showing that the perforin-dependent killing process requires a minimal contact time. For example, long-lasting (median: 80s) calcium fluxes linked with CTL killing of virally infected cells occurred, on average, 480s (median) after CTLs established contact with virally infected targets\[[@pcbi.1007972.ref007]\]. Such killing times of around 10 minutes are consistent with the duration of killing events that can be observed in various supplemental videos elsewhere \[[@pcbi.1007972.ref008],[@pcbi.1007972.ref009]\]. Given this lower bound it is difficult to see how solely granule-mediated killing could plausibly lead to killing rates in excess of \~6 hour^-1^, even in optimal situations where CTLs are not limited in their supply of targets and do not require time to search for new targets between killing events. A major limitation of many prior estimates of CTL killing is that analysis is performed on population level data in *in vivo* settings, with no direct measurements of the killing process. This approach has a number of drawbacks: First, it can be challenging to accurately assess the frequency of CTLs and target cells. Second, other immune cells may contribute to the killing process, confounding estimates of the true CTL killing rate. Third, the processes underlying CTL killing are complex and it may be insufficient to describe them with a single, time invariant rate constant. Indeed, recent observations have indicated that target cells may require multiple hits before death either *in vitro* \[[@pcbi.1007972.ref010]\], or *in vivo* \[[@pcbi.1007972.ref007]\]. We have previously shown that such multiple-hitting can lead to a time-increasing killing kinetic when CTLs are exposed to fresh targets \[[@pcbi.1007972.ref011],[@pcbi.1007972.ref012]\], further complicating the killing rate estimation procedure. Besides analysing CTL killing performance at the population level, a potentially useful approach is to analyse CTL killing at the single cell level. Such analysis can yield greater insights into the dynamics of the killing process. This was exemplified in studies undertaken in the 1970's in which the killing kinetics of CTLs conjugated with 1--4 EL4 tumour cell targets were examined under the microscope for a period of 3 hours \[[@pcbi.1007972.ref013],[@pcbi.1007972.ref014]\]. Subsequent mathematical analysis of these studies indicated that the CTL killing process was well described as a Poisson process \[[@pcbi.1007972.ref015]\], indicating that CTLs kill targets sequentially rather than simultaneously. This analysis allowed the authors to conclude that CTL killing was mediated by secretory lysosomes, several years before this was demonstrated conclusively \[[@pcbi.1007972.ref016]\]. The aforementioned studies also revealed that the rate of CTL killing was not diminished after target lysis, an observation which led the authors to deduce that CTLs were able to discriminate between viable and killed targets. More recently, *in vitro* studies of individual natural killer cells have shown that killing occurs via both granzyme and death receptor mediated pathways, each having different kinetics \[[@pcbi.1007972.ref017],[@pcbi.1007972.ref018]\]. Despite the utility of studying CTL killing at the single-cell level, there remains a shortage of *in vitro* CTL killing studies with statistical power sufficient to check the validity of the Poisson model first proposed in the 1980's by Perelson et. al. \[[@pcbi.1007972.ref015]\]. Recently one such a study was performed: Over a 12 hour period, image-based killing measurements were taken from human-derived CTL clones, each CTL being separately confined within small micro-wells that contained an excess of JY target cells \[[@pcbi.1007972.ref019]\]. During the studied time period, the killing rate of CTLs was dynamic, exhibiting a marked increase in the final hours of the experiment. The total number of targets killed per CTL was overdispersed compared to the Poisson distribution, implying greater heterogeneity between individual CTL killing performance than anticipated. Vasconcelos et. al. [(Vasconcelos et al. 2015)](https://paperpile.com/c/oMBHuP/ZTAi) found the data was well described by a Poisson mixture model, and they postulated the existence of a subset of "high rate killers" comprising 30% of the population that emerged 8--10 hours after first exposure to target cells. However, no mechanistic explanation could be found to explain this result, despite a search for membrane markers that might identify and/or explain the variability of CTL killing characteristics. We hypothesised that a requirement for "multiple hits" to kill targets before apoptosis induction might explain heterogeneous killing amongst clonal CTLs *in vitro*. Perelson et. al. \[[@pcbi.1007972.ref020]\] previously considered the possibility of multiple-hitting, noting however that such a model was excessively complex to describe the limited experimental data available at that time. Recent evidence has directly shown that multiple-hitting does occur at least in some settings \[[@pcbi.1007972.ref007],[@pcbi.1007972.ref010],[@pcbi.1007972.ref021]\], and our previous modelling work has demonstrated that multiple-hitting can indeed lead to population-level killing kinetics increasing over time when CTLs are exposed to fresh targets \[[@pcbi.1007972.ref011]\]. Therefore, we here used stochastic simulations to investigate the compatibility of the multiple-hitting hypothesis with the findings of Vasconcelos et. al. \[[@pcbi.1007972.ref019]\]. We found that multiple-hitting was indeed able to explain the late onset, high-rate bursting kinetic of individual CTLs, with physiologically plausible parameters. We also highlight that multiple-hitting is expected to lead to a complex dependence of realised killing rate upon the number of available targets and on the ability of individual CTLs to form and abort conjugates with target cells. We subsequently developed spatially explicit, agent based simulations of CTLs killing targets in micro-wells as a means of generating realistic yet noisy artificial data and assessing methods of recovering CTL hitting parameters from future microscopy data. Using these spatial simulations, we demonstrate how parameter estimation is substantially improved if contacts of individual targets with CTLs can be tracked throughout the duration of the experiments. Results {#sec002} ======= Multiple-hitting CTLs exhibit heterogeneous late onset killing {#sec003} -------------------------------------------------------------- We first sought to establish whether the multiple-hitting hypothesis was a feasible explanation for the heterogeneous, delayed onset, "burst" killing kinetics observed and defined by Vasconcelos *et*. *al*. \[[@pcbi.1007972.ref019]\]. In brief, these high rate killer CTLs were a subset among a clonal population whose killing suddenly accelerated after 8--10 hours of experimentation, with no explanation readily apparent (Methods). In the current study, we used Monte Carlo simulations of individual CTLs killing targets to identify conditions under which multiple-hitting might lead to heterogeneous, "burst" killing. In these Monte Carlo simulations, CTLs hit targets at a constant rate *λ*, then targets died after receiving *η* hits. We simulated single- and multiple-hitting scenarios on the basis that the expected (mean) time for one target in contact with a CTL to be killed was 1 hour, i.e., we set *λ*/*η* = 1 (valid for entire [Fig. 1](#pcbi.1007972.g001){ref-type="fig"}). ![Killing kinetics and heterogeneity of multiple-hitting CTLs.\ A) Gamma probability density functions describing expected time for a CTL to kill 1 target in monogamous contact (red lines). Each point represents the sample killing density of one series of simulations (N~S~ = 10), each series comprising N~w~ = 100 CTL:target pairs. Observations were binned at 15 minute intervals. B) Theoretical Gamma probability density function (PDF), survival function, and hazard function for different values of *η* as indicated. C) Estimation of parameters from simulations in panel A, by equating the first two moments (the mean and variance) with their estimators. D) Distribution of targets killed per CTL at 12 hours (red bars), with Poisson distributions for the initial number of targets (using the same initialising distribution for all *η*; blue bars). Each panel contains results from N~w~ = 5000 CTLs for different *η*, as indicated by facet labels on the right. Text inside panels indicates the mean and variance of the killed targets. E) Cumulative killing performance of N~w~ = 100 members (thin black lines) of the population shown in D; the red line is the mean calculated for the entire population (N~w~ = 5000). F) Distribution of target killing times over extended (24 hours) simulations with CTL parameters matching D, with the 12 hour censorship indicated by a red line (N~w~ = 5000, bars are kills per 30 min interval). G) Heatmap of the probability density for each simulation in C-D. Observations were binned according to unique combinations of the initial number of targets (individual columns), together with the number of killed targets at the indicated interval (individual rows). Thus, summing across columns will recover the initial Poisson distribution (blue bars in D), and summing across rows will produce the distribution of killed cells at the indicated time (e.g red bars in D at 12 hours).](pcbi.1007972.g001){#pcbi.1007972.g001} Firstly we simulated CTLs with *η* = 1,2, or 10, with each simulation containing one CTL interacting with a single target. For such a strictly 1:1 CTL:target ratio, the waiting times for target death were gamma distributed with rate parameter *λ* and shape parameter *η* ([Fig 1A](#pcbi.1007972.g001){ref-type="fig"}). The gamma distributions ([Fig 1B](#pcbi.1007972.g001){ref-type="fig"}, top panel), together with their accompanying survival probability functions ([Fig 1B](#pcbi.1007972.g001){ref-type="fig"}, middle panel), define the hazard function ([Fig 1B](#pcbi.1007972.g001){ref-type="fig"}, bottom panel), which is the momentary rate of death experienced by a target, given that the target has already survived an interaction for some time, *t*. When *η* = 1, the hazard experienced by contacted targets does not change with time. In contrast, when *η*\>1 the hazard experienced by contacted targets increases over time, as contacted targets become increasingly likely to have received (*η*−1) hits and thus be killed by the next hit. For the case where CTLs interact with targets in a strictly 1:1 ratio, the gamma(η, λ) distribution parameters could be estimated from the mean and variance of the samples of the waiting time (y~o~): $\overline{y_{o}} = \frac{\eta}{\lambda}$ and $\left. {Var\left( y \right.}_{o} \right) = \frac{\eta}{\lambda^{2}}$ ([Fig 1C](#pcbi.1007972.g001){ref-type="fig"}). We next extended our Monte Carlo simulations to allow CTL:target interactions in a 1:n ratio, for variable numbers of targets, *n*. CTLs were individually assigned their initial number of targets by drawing *n* from a Poisson distribution, with mean $\overline{n} = 16$ ([Fig 1D](#pcbi.1007972.g001){ref-type="fig"}, blue bars). The total number of targets killed by a CTL during one simulation, *x*, should also follow the Poisson distribution, if the killing rate of each simulated CTL would be the same. Moreover, the mean and variance should be approximately equal for any set of Poisson distributed samples. Therefore, observation of a ratio $\frac{var\left( x \right)}{\overline{x}} > 1$ for a set of killed targets would imply that the killing was more heterogeneous than expected under Poisson assumptions. For single-hit killing (*η* = 1), the variance of the 12 hour killing samples was in fact slightly below the mean ([Fig 1D](#pcbi.1007972.g001){ref-type="fig"}, upper row), resulting from some simulations where CTLs killed all their targets before the simulation had finished. However, for *η* = 2 ([Fig 1D](#pcbi.1007972.g001){ref-type="fig"}, central row), the variance approached the mean and for *η* = 10 far exceeded the mean ([Fig 1D](#pcbi.1007972.g001){ref-type="fig"}, bottom row). In the latter case, a bimodal distribution occurred, which could be interpreted as a subpopulation of high-rate killers, yet importantly such a population did not exist in our simulations. In our simulations, the additional variability in killing performance of multiple-hitting CTLs was due to the allocation of subsequent hits amongst several different targets. When a group of targets share hits evenly, the time for a specified target to be hit is proportional to the number of other targets sharing. This has no effect on the killing rate observed if *η* = 1, so the mean killing rate for our simulated single-hitting CTLs initially remained constant over time ([Fig 1E and 1F](#pcbi.1007972.g001){ref-type="fig"}, top row; time\<8h), gradually decreasing as some CTLs eliminated all their targets ([Fig 1E and 1F](#pcbi.1007972.g001){ref-type="fig"}, top row; time\>8h). In contrast, hit sharing in the case of multiple-hitting CTLs led to a delayed onset of killing ([Fig 1E and 1F](#pcbi.1007972.g001){ref-type="fig"}), with the length of the delay dependent on the number of targets sharing hits (compare [Fig 1A and 1B](#pcbi.1007972.g001){ref-type="fig"} with single targets to [Fig 1F](#pcbi.1007972.g001){ref-type="fig"} with multiple targets, for identical *η*). The interaction between *η* and the number of initial targets can also be understood from heatmaps of targets killed ([Fig 1G](#pcbi.1007972.g001){ref-type="fig"}). The expected cumulative number of kills increases over time for *η*,*λ* = 1, but this increase is independent of the initial number of targets except for the censorship implying a maximum target number that can be killed. For *η*,*λ* = 10, the dependency of the observed kills on the initial number of targets is very clear, with killing happening earlier in those wells with initially fewer targets. Moreover, these effects did not only depend on the initial number of targets. When we performed simulations with the hitting rate *λ* a random variable, this in turn increased the variability of killing amongst multiple-hitting CTLs to a greater extent than was the case for single-hitting CTLs ([S1 Fig](#pcbi.1007972.s003){ref-type="supplementary-material"}), implying that the killing of multiple-hitting CTLs is more sensitive to environmental variables than the single-hitting CTLs. Taken together, these results imply that multiple-hitting CTLs could explain both heterogeneous and delayed onset killing among clonal CTL populations. Multiple-hitting is not identifiable based on population killing statistics only {#sec004} -------------------------------------------------------------------------------- We asked if population-level killing statistics (as e.g. examined in \[[@pcbi.1007972.ref019]\])) could be used to identify the hitting parameters (*λ* and *η*) of CTLs. In our previous simulations ([Fig 1](#pcbi.1007972.g001){ref-type="fig"}) we studied a scenario of simultaneous risk for target cells, yet this may be an oversimplification. For example, due to physical constraints the number of targets CTLs can simultaneously contact and thus hit must be limited. Therefore, we extended our *1*:*n* Monte Carlo simulations to allow dynamic contacts between CTLs and targets, in order to check how the parameter estimates (*λ* and *η*) would be impacted. To achieve this, we included an additional state for target cells, now distinguishing between targets that are contacting the CTL, versus those not in-contact ([Fig 2A](#pcbi.1007972.g002){ref-type="fig"}; Methods). The killing kinetics realized by CTLs in these dynamic simulations indeed differed from those in our previous simulations ([Fig 1](#pcbi.1007972.g001){ref-type="fig"}), where all the targets shared risk and so the killing rate of each CTL was dictated by the total number of yet-living targets. In contrast, for our Monte Carlo simulations allowing dynamic conjugate formation, only the targets presently being contacted were relevant. Here, small bursting events occurred throughout the simulations, which was the result of accumulating hits followed by rapid sequential killing among a subset of contacted targets ([Fig 2B](#pcbi.1007972.g002){ref-type="fig"}). ![Burst killing and non-identifiability of dynamically interacting, multiple hitting CTLs.\ A) Schematic of the dynamic model (example with *η* = 3). Target cells are represented by circles containing fractions (numerator: hits received; denominator: *η*). The observable state \[*C U*\] consists of the total number of contacting, *C*, and non-contacting targets, *U*. The complete state of the system is represented by a matrix, with *η* rows indicating the number of hits received (subscript) and with columns indicating whether the target is contacting (*c*~*i*~) or non-contacting (*u*~*i*~). B) Measured killing events (red dots, filled white) during Monte Carlo simulations with *N*~*w*~ *= 10* CTLs and the number of targets drawn from a Poisson distribution with mean $\overline{n} = 16$ (top panels; *λ*,*η* = 10,*k*~*off*~ = 0,*k*~*on*~→∞), or a subset of targets at risk (bottom panels; *λ*,*η* = 10,*k*~*on*~ = 1*hr*^−1^,*k*~*off*~ = 0.3*hr*^−1^). Each horizontal strip is one single simulation, the right panel strips are colored according to the total number of alive targets and the left panel strips are colored according to the number of targets that are in contact with a CTL. C) Each line (coloured according to *η*) is the mean cumulative killing over time (CTL^-1^) from N~w~ = 10^4^ CTLs, simulated using parameters estimated by fitting the case with $\overline{n} = 16$ targets (central column). Straight lines show target values for fitting. All parameters except $\overline{n}$ are constant across columns. D-F) Measured statistics within simulations with $\overline{n}$ = 16 shown in the central column of C. Shown are the distribution of killed targets after 12 hours, with the mean and variance as indicated for each *η* (D), and the mean killing rate over time for CTLs grouped by *η* and shown either separately (E, rows), or together (F, colors), calculated as (*kills*⋅(6 *min*⋅*N*~*w*~)^−1^).](pcbi.1007972.g002){#pcbi.1007972.g002} Using our simulations including dynamic conjugate formation we searched for parameters consistent with the statistics reported previously \[[@pcbi.1007972.ref019]\]concerning high rate "burst killing" CTLs. For fitting we used the reported group mean (4) and variance (6.9) of the number of killed targets per CTL over 12 hours. Additionally, we aimed for a breakpoint in the mean killing rate such that half (2) of the observed kills occurred in the interval 0--9 hours and the other half in the interval 9--12 hours (see [Methods](#sec009){ref-type="sec"}). We performed this fit using different values for *η* (ranging from 1--5, or 10), and a Poisson variable with $\overline{n} = 16$ for the initial number of targets ([S2 Fig](#pcbi.1007972.s004){ref-type="supplementary-material"}). We obtained good fits for different values of *η*; in particular for all *η*\>2 the cumulative killing was very closely matched ([Fig 2C](#pcbi.1007972.g002){ref-type="fig"}, intersecting lines for $\overline{n} = 16$). Moreover, for values *η*\>3 the fits to the mean and variance for cumulative targets killed at 12 hours were all similarly close to their target values of 4 and 6.9, respectively ([Fig 2D](#pcbi.1007972.g002){ref-type="fig"}). Some differences for different *η* were apparent, for example as the number of hits increased towards *η* = 10 the breakpoint marking transition from low to high rate was more distinct ([Fig 2E](#pcbi.1007972.g002){ref-type="fig"}). However, overall differences between *η* were quite small ([Fig 2F](#pcbi.1007972.g002){ref-type="fig"}), and many simulated CTLs were required for these differences to emerge consistently (at least N~w~ = 10^3^ CTLs). Our results were also sensitive to the distribution for the initial number of targets per CTL: for simulations with $\overline{n} = 12$ or 20, substantial differences in the cumulative kills over time occurred ([Fig 2C](#pcbi.1007972.g002){ref-type="fig"}). Thus, we conclude that multiple-hitting is not only qualitatively, but also quantitatively consistent with the experimental results reported previously [(Vasconcelos et al. 2015)](https://paperpile.com/c/oMBHuP/ZTAi). However, our analysis shows that the mean and variance of the killing process measured for a group of CTLs are insufficient statistics to determine the number of hits CTLs require to kill targets, so CTL:target interactions should be explicitly accounted for if killing due to multiple-hitting is to be modelled accurately. An Agent Based Model of Multiple-hitting CTLs to test methods for estimation of killing parameters {#sec005} -------------------------------------------------------------------------------------------------- Since we found that in many situations the true hitting parameters for CTLs could not be determined based on group level killing mean and variance, we sought methods to compare the likelihood of different hitting models. We did not wish to consider a particular model for the process of CTLs finding targets, preferring a method that could be applied to determine the CTL hitting behaviour in general situations (i.e., in the absence of knowledge on contact dynamics). As a framework for testing we employed an agent based cellular Potts model (CPM) to generate 2D simulations of CTLs interacting with and killing targets ([Fig 3A](#pcbi.1007972.g003){ref-type="fig"}). The resulting datasets were visually similar to realistic microscopy data and could be used to investigate methods for recovering the hitting parameters (*η* and *λ*) of CTLs from experimental data under various conditions. For all CPM simulations we maintained the same underlying gamma model of CTL hit generation as was used for our Monte-Carlo simulations (Figs [1](#pcbi.1007972.g001){ref-type="fig"} and [2](#pcbi.1007972.g002){ref-type="fig"}), however we made several modifications that would lead to different (yet not [predictable]{.ul} *a priori*) distributions of hits amongst targets. Specifically, instead of allocating hits to all contacted targets with equal probability, target risk of receiving a hit was proportional to the length of the interface between CTL and target at the moment of hit generation ([Fig 3A](#pcbi.1007972.g003){ref-type="fig"}, target coloring on left images indicates interface length). We also considered the effect of a lower bound on the time required for a CTL to complete a hit, by introducing a delay condition that prohibited targets from being hit within an initial time window after contacting a CTL, which was reset every time the target broke contact with the CTL ([Fig 3A](#pcbi.1007972.g003){ref-type="fig"}, target coloring on right images). Note that the delay condition was applied per target and therefore does not preclude the possibility of CTLs hitting other contacted targets simultaneously. ![Characterisation of high- and low-motility *in silico* CTLs within CPM simulations.\ A) Still images of a high motility CTL with 15 minute minimal hitting time, interacting with targets. Left color scheme: CTLs are red, uncontacted targets are grey, and contacted targets have various shades of blue based on their share of total CTL:target interface, which determines their probability of receiving a hit. Targets are overlaid with the number of hits they have received. Right color scheme: Lattice sites inhabited by the CTL are colored according to actin activity \[[@pcbi.1007972.ref022]\]. Targets are black, turning yellow after 15 minutes of continuous contact with the CTL. Elapsed simulation time is displayed in the upper left corner of the stills, presented in minutes since the first frame shown. B-C) Track plots showing movement of 3 randomly sampled CTLs of high (B) and low (C) motility throughout a simulation, for simulated η as shown. D-E) Frequency at which CTLs form new conjugates (D) and mean number of simultaneously contacted targets per CTL (E) for low- and high-motility CTLs. Plots are based on 100 simulations per condition, with each dot representing one CTL, and circles and error bars indicating mean +/- SD.](pcbi.1007972.g003){#pcbi.1007972.g003} Finally we varied CTL migration to create two groups of CTLs which we termed "high-motility" ([Fig 3B](#pcbi.1007972.g003){ref-type="fig"}, [S1 Video](#pcbi.1007972.s009){ref-type="supplementary-material"}) or "low-motility" ([Fig 3C](#pcbi.1007972.g003){ref-type="fig"}, [S2 Video](#pcbi.1007972.s010){ref-type="supplementary-material"}) CTLs. For both motility conditions the migration of the CTLs was influenced by the presence of the targets, as CTLs became corralled by surrounding targets. The difference between these models was that high-motility CTLs exhibited an increased propensity to break free from confinement and roam the well. This roaming ensured that over the course of 12 hours the high-motility CTL made new contacts with far greater frequency than low-motility CTLs ([Fig 3D](#pcbi.1007972.g003){ref-type="fig"}), although the average number of simultaneously contacted targets at any time was similar ([Fig 3E](#pcbi.1007972.g003){ref-type="fig"}). Thus, the high-motility CTL is expected to approach the previously modeled 'all targets at risk' scenario more closely than the low-motility CTLs. We used the CPM model to simulate CTLs (with *η*,*λ* = 1,2, *or* 10), in either high- or low-motility scenarios. The total amount of targets killed by each CTL depended on the interaction between the parameters *λ* and *η*, the CTL motility, and the presence or absence of the delay condition. In particular, the combination of high motility plus 15 minute delay resulted in a substantial decrease in killing in comparison to the other simulation groups, for all values of *η* ([Fig 4A](#pcbi.1007972.g004){ref-type="fig"}). Together with the high rate of contact formation in that group ([Fig 3D](#pcbi.1007972.g003){ref-type="fig"}), this is consistent with targets spending significant time in transient contacts with the CTL, too short to result in successful hit delivery. The killing rate of the low-motility CTLs was initially greater than of high-motility CTLs, in particular for large *η* ([Fig 4B](#pcbi.1007972.g004){ref-type="fig"}), due to the more stable nature of the contacts leading to greater accumulation of hits among the contacted targets ([Fig 4C](#pcbi.1007972.g004){ref-type="fig"}). High-motility CTLs reduced this deficit over the course of the simulations due to an accumulation of latent hits among uncontacted targets ([Fig 4D](#pcbi.1007972.g004){ref-type="fig"}). These spatial simulations therefore illustrate how CTL:target contact dynamics can play a role in determining killing performance. Moreover, since in these models CTLs with the same killing parameters---but different motility parameters---generated different killing kinetics, they are useful to test how underlying killing parameters might be recovered from microscopy data that are similar to data emanating from our realistic simulations. ![Killing performance of multiple-hitting CTLs depends on motility.\ A) Mean cumulative killing over time (CTL^-1^) for CPM simulations of high- and low- motility CTLs (*η*,*λ* = 1,2, *or* 10) B) Mean killing rate (CTL^-1^) for each simulated condition in A. C-D) Mean number of hits received per target, sampled over targets currently contacting the CTL (C) or over targets not currently contacting the CTL (D).](pcbi.1007972.g004){#pcbi.1007972.g004} Estimating CTL hitting parameters through analysis of contact time and target survival {#sec006} -------------------------------------------------------------------------------------- Since we found that hitting parameters *η* and *λ* could not be recovered via analysis of population averages only, we employed a parametric survival analysis to study the hazard experienced by individual targets contacting CTLs. Our analysis considers the different hazard functions identified earlier ([Fig 1B](#pcbi.1007972.g001){ref-type="fig"}), which distinguish CTLs on the basis of their intrinsic hitting rate *λ* and the number of hits required for killing targets, *η*. Specifically, we analyse the cumulative duration of CTL:target contact events from the perspective of the target cells (example in [Fig 5A](#pcbi.1007972.g005){ref-type="fig"}). To take into account shared hazard amongst a set of co-contacting targets, we recorded for each sampled frame the statistic *θ* = (*c*)^−1^ (per-target), representing the probability that each separate target out of the subset of *c* targets co-contacting the CTL is presently being hit ([Fig 5B](#pcbi.1007972.g005){ref-type="fig"}). Note that targets not in contact with the CTL were assigned *θ* = 0. Subsequently, we integrated the *θ* values over time to arrive at a set of 'adjusted' contact times, *τ*, for each target ([Fig 5C](#pcbi.1007972.g005){ref-type="fig"}), which takes into account uncertainty with respect to hitting of multiple co-contacted targets ([Fig 5C](#pcbi.1007972.g005){ref-type="fig"}). This approach has the advantage that no explicit account needs to be taken of the CTL-target interaction dynamics. Moreover, estimation of cellular contact times occurs already frequently in time-lapse imaging data \[[@pcbi.1007972.ref007],[@pcbi.1007972.ref023]\], hence is feasible. ![Parameter retrieval for multiple-hitting CTLs based on adjusted contact time.\ A) Hypothetical example illustrating sharing of subsequent CTL hits by target cells. Interaction history during a period of 12 hours for each of three target cells contacted by a single CTL, sampled at 30 minute intervals. B) Estimated probability (expressed as fraction *θ*) that each target is being hit by the CTL, corresponding to the hypothetical interaction history shown in A. C) The quantity τ is defined as the cumulative sum over the course of the simulation of all sampled values of *θ* associated with each individual target. The samples resulting from interaction with this CTL include target 1, which was killed after a cumulative interaction period of \~1.7h, and targets 2 and 3, which remained alive after cumulative interaction periods of \~2.4h and \~7.9h, respectively. D) Heatmaps of the likelihood function around the maximum likelihood estimates for the killing parameters, in CPM simulations without hitting delay. Horizontal and vertical lines mark the values of the CPM parameters used to generate the data for each group. The boundary enclosing the 95% confidence region is also marked with a line. E) Results of fitting 30 randomly chosen subsets, each consisting of N~w~ = 10 simulations, of the CPM simulations without hitting delay.](pcbi.1007972.g005){#pcbi.1007972.g005} Applying the concept of adjusted contact times, *τ*, on all our CPM simulations, we established maximum likelihood estimates for the hitting parameters within the simulations ([S1 Text](#pcbi.1007972.s002){ref-type="supplementary-material"}; [S3 Fig](#pcbi.1007972.s005){ref-type="supplementary-material"}). This yielded excellent estimates for the parameters in simulations without delay ([Fig 5D](#pcbi.1007972.g005){ref-type="fig"}; *η*~*CPM*~,*λ*~*CPM*~ indicate input CPM parameter values, and $\hat{\lambda},\ \hat{\eta}$ indicate estimated values). We also tested our method of parameter recovery by fitting our model to small subsets taken from the CPM simulations each containing only N~w~ = 10 CTLs ([Fig 5E](#pcbi.1007972.g005){ref-type="fig"}), which led to good estimates. Additionally, we tested our model on sample data generated from a mixed dataset with two subpopulations of single-hitting CTLs, each with a different killing rate ([S1 Text](#pcbi.1007972.s002){ref-type="supplementary-material"}), in order to examine the high-rate-killer hypothesis put forth by Vasconcelos *et*. *al*. \[[@pcbi.1007972.ref019]\]. We found that the multiple-hitting model would not predict multiple-hitting unless multiple-hitting was indeed underlying the data, instead predicting a single-hitting population whose killing rate was the mean of the individual subpopulations ([S1 Text](#pcbi.1007972.s002){ref-type="supplementary-material"}; [S4 Fig](#pcbi.1007972.s006){ref-type="supplementary-material"}, [S5 Fig](#pcbi.1007972.s007){ref-type="supplementary-material"}). Thus, our maximum likelihood approach based on contact time monitoring can distinguish multiple-hitting from alternative hypotheses and is expected to work for a relatively small number of samples. Impact of a hitting threshold on killing parameter estimation {#sec007} ------------------------------------------------------------- Given the time needed for formation of a cytotoxic synapse that is required for hit delivery, brief interactions between CTLs and targets may not contribute to killing. Taking such brief interactions into account in our parameter estimation may thus interfere with correct estimation. Therefore, we tested our parameter recovery on those CPM simulations wherein a 15 minute minimal bound (+15m) was set for the time CTLs required to successfully execute each hit upon a target. In these CPM simulations, we generally obtained robust estimates for the number of hits needed to kill targets, $\hat{\eta}$ ([S6A Fig](#pcbi.1007972.s008){ref-type="supplementary-material"}). However, after rounding to the nearest integer value for *η*, the estimated hitting rate parameter, $\hat{\lambda}$, was underestimated compared to the generating value (*λ*~*CPM*~) in simulations with the 15m minimal hitting time. Since the realised killing was reduced in the 15m-delay simulations, particularly for high-motility CTLS ([Fig 4](#pcbi.1007972.g004){ref-type="fig"}), the estimated $\hat{\lambda}$ could be considered more appropriate than the generating value *λ*~*CPM*~. Nevertheless, to investigate further we performed additional simulations, using high motility CTLs, with variable hitting delays in the interval between 0--15 mins (Figs [6A](#pcbi.1007972.g006){ref-type="fig"} and [S6B](#pcbi.1007972.s008){ref-type="supplementary-material"}). We found that for the important boundary between single-hitting (*η* = 1) or multiple-hitting (*η* = 2), the estimated number of hits parameter $\hat{\eta}$ was accurately classified for limited delays of less than 15 minutes ([Fig 6A](#pcbi.1007972.g006){ref-type="fig"}, top row). ![Parameter retrieval for multiple-hitting CTLs with underlying hitting delay.\ A) Estimated parameters (points), compared to the underlying parameter values used (red lines) in CPM simulations, featuring high-motility CTLs, in which we varied the lower bound for the time (in minutes, as indicated) needed for hitting. B) Kaplan-Meier survival functions (black lines), or survival functions plotted with estimated parameters fitted to data from N~w~ = 100 CPM simulations generated by multiple-hitting (lower row, *η*~*CPM*~ = 2) or single-hitting CTLs (upper row, *η*~*CPM*~ = 1). C) Heatmaps from one CPM simulation containing high-motility, single-hitting CTLs who had a 15 minute lower bound set on the hitting time. Each row represents a single target. Target status is represented by colour: targets not-contacting the CTL are deep purple, and killed targets are grey. Contacted targets are coloured according to their momentary hazard according to two candidate parameter sets (top panel: $\hat{\eta} = 1,\hat{\lambda} = 0.65$; bottom panel: $\hat{\eta} = 2,\hat{\lambda} = 1.65$). D) Predicted killing rate according to two different candidate parameter sets ($\hat{\eta} = 1$, red lines; $\hat{\eta} = 2$, blue lines), candidates being themselves applied to CPM simulations with high-motility, +15m CTLs (*η*~*CPM*~ = 1, top panel; *η*~*CPM*~ = 2, bottom panel).](pcbi.1007972.g006){#pcbi.1007972.g006} A particular advantage of a parametric survivorship analysis such as that we employ here is that, having estimated the hitting parameters (*η*,*λ*), we can revisit the sample data and ask whether different subsets of targets were killed according to our expectation. We selected the high-motility +15m simulations with *η*~*CPM*~ = 1 for further study, since for this simulation group there was an ambiguous estimate of $\hat{\eta}$. For comparison, we also analysed the data from CPM simulations with multiple-hitting CTLs (*η*~*CPM*~ = 2). First, we inspected the Kaplan-Meier estimates of the survival functions ([Fig 6B](#pcbi.1007972.g006){ref-type="fig"}, black lines) marking close agreement when the correct parameter estimate ($\hat{\eta} = 2$) was applied to CPM data generated by multiple-hitting CTLs ([Fig 6B](#pcbi.1007972.g006){ref-type="fig"} bottom, blue line, *η*~*CPM*~ = 2), but not when the incorrect $\hat{\eta} = 1$ was applied ([Fig 6B](#pcbi.1007972.g006){ref-type="fig"} bottom, red line, *η*~*CPM*~ = 2). For data generated by single-hitting CTLs, the Kaplan-Meier estimate lay exactly between the estimates using $\hat{\eta} = 1$ or 2, yet the shape of the survival function over the entire length better matched that for the single-hitting estimate $\hat{\eta} = 1$ ([Fig 6B](#pcbi.1007972.g006){ref-type="fig"} top, red line, *η*~*CPM*~ = 1) than for the estimate $\hat{\eta} = 2$ ([Fig 6B](#pcbi.1007972.g006){ref-type="fig"} top, blue line, *η*~*CPM*~ = 1). Second, visual inspections of the hazard experienced by individual targets throughout the simulations ([Fig 6C](#pcbi.1007972.g006){ref-type="fig"}), revealed that in many CPM simulations with *η*~*CPM*~ = 1 and a +15m hitting delay there was substantial killing of targets that had not yet undergone long interactions with the CTL ([Fig 6C](#pcbi.1007972.g006){ref-type="fig"}, first two grey bars), as would not be expected for multiple-hitting. Thus, both results ([Fig 6B and 6C](#pcbi.1007972.g006){ref-type="fig"}) supported $\hat{\eta} = 1$ as the most likely candidate for the data derived from simulations with *η*~*CPM*~ = 1. However, the most conclusive result was obtained by evaluating the mean hazard experienced by contacted targets according to either of the two candidate estimates for the number of hits ($\hat{\eta}$ = 1 or 2). Integrating this value over the duration of the experiments ([Fig 6D](#pcbi.1007972.g006){ref-type="fig"}, black lines) led to predictions for the killing rate over time which closely followed the data whenever a correct estimate for $\hat{\eta}$ was applied ([Fig 6D](#pcbi.1007972.g006){ref-type="fig"}, comparing black and red lines in the upper panel, or black and blue lines below). In contrast, killing predictions from incorrect estimates of $\hat{\eta}$ were extremely poor, thus allowing for correct identification of the underlying *η*. Thus, our analysis shows that monitoring of cumulative interaction times between targets and single CTLs allows for proper estimates of the number of hits required for target cell death even when brief contacts between CTLs and targets cannot lead to hits, although the hitting rate may be underestimated in that case. Discussion {#sec008} ========== Here we have used stochastic simulations to show that 'multiple-hitting' is a plausible explanation for the heterogeneous and time-inhomogeneous killing activity recently observed for CTLs *in vitro* \[[@pcbi.1007972.ref019]\]. We showed that multiple-hitting leads to an increase in realised killing rate over time. Moreover, the extent of this late onset killing increases when more hits are required to kill targets, or when a greater number of antigen-presenting targets are simultaneously contacted. Furthermore, identical CTLs displayed varying killing performance depending on the number of targets available. Simulating CTLs with variable hitting rates, we also found that the killing performance of multiple-hitting CTLs is more heterogeneous than killing of single-hitting CTLs, given similar variation in underlying hitting rate. Overall, we conclude that multiple-hitting is sufficient to explain heterogeneous killing amongst clonal CTLs and there is no need to invoke an unobserved subpopulation of high-rate killers. Given the dependence of the killing performance of multiple-hitting CTLs on several parameters that we describe here, we developed spatially explicit CPM simulations to assess methods for investigating whether multiple hitting occurs *in vitro* or *in vivo*. Our specific goal was retrieval of the hitting rate and number of hits required for CTLs to kill targets. Our model of dynamic conjugate formation can be conceptualised using Kendall's notation as an M/E~r~/1 queue \[[@pcbi.1007972.ref024]\]. Within this framework there is 1 "server" (in our case the CTL), with markovian arrival times (M: in our case conjugate formation events), and Erlang distributed (E~r~) "service times" which represent the killing process. It is known that for such models, the mean and variance (or any similar measure of variability) are insufficient for estimating the true parameters, and can only be used to approximate the distribution \[[@pcbi.1007972.ref024]\]. Instead of using population-level killing statistics, we were able to accurately recover model parameters from the CPM data by analysing the 'adjusted' cumulative contact durations between CTLs and individual targets, i.e. the total length of the interaction until either the target was killed or the experiment ended. Importantly, we found that measurements for both killed and surviving cells are required for this approach to be successful. This is because the limited time window of observation renders data that are in part censored, yet elapsed contacts that have not yet resulted in killed targets also contain information on underlying killing parameters. In a similar fashion, we previously developed a method to estimate absolute (i.e., not cumulative) cellular interaction times based on time lapse imaging data \[[@pcbi.1007972.ref023]\]. Although CTL cooperativity and multiple-hitting have now been described in a number of settings \[[@pcbi.1007972.ref007],[@pcbi.1007972.ref010]--[@pcbi.1007972.ref012]\], a detailed quantitative description of the sequence of intracellular events which might underlie multiple-hitting does not yet exist. Several mechanisms can be envisaged which separately or collectively might result in target cells enduring sustained attacks from CTLs before death. A first factor which may explain the ability of target cells to endure sustained attacks is death occurring via the 'extrinsic apoptosis pathway', i.e., via tumour necrosis factor (TNF) or FAS-L. In the study of Vasconcelos et. al. \[[@pcbi.1007972.ref019]\], blockade of FAS-L did not diminish overall killing, suggesting that FAS-L was not involved in CTL killing. Moreover, separation of CTLs and targets in a transwell assay showed that contact was required before target cell apoptosis could occur. Although this result suggests that diffusible TNF did not contribute to target cell apoptosis, TNF is also expressed in transmembrane form \[[@pcbi.1007972.ref025]\] and may have contributed to contact-dependent killing, or could have synergised with other effector pathways. Furthermore, TNF or interferon-γ---another hallmark cytokine produced by activated CTLs---have been linked to an upregulation of FAS-L receptors in different cell types \[[@pcbi.1007972.ref026],[@pcbi.1007972.ref027]\], or might otherwise synergise with FAS-L to induce target cell apoptosis \[[@pcbi.1007972.ref028]\]. The possibility of synergistic activators of the extrinsic apoptosis pathway is intriguing since activation of such mechanisms might explain delayed onset of burst-killing. This was observed in recent studies in which natural killer cells initially controlled tumour cell targets with a fast-acting, perforin-dependent mechanism, before switching to a mechanism primarily depending on engagement of death receptors \[[@pcbi.1007972.ref017],[@pcbi.1007972.ref018]\]. It would be useful to investigate whether CTLs also utilise this mechanism. A second factor which may account for multiple-hitting is heterogeneity in delivery of perforin and granzymes. Perforin alone induces rapid pore formation in target cell membranes, with such membrane disruption expected to increase the metabolic burden on target cells. Even if insufficient to directly induce apoptosis, one would expect such depletion to divert resources from adaptive cellular stress responses, thereby sensitising cells to death from other mechanisms. Granzymes are a diverse set of cytotoxic proteases with a broad array of intracellular targets \[[@pcbi.1007972.ref029]\]. A recent review highlights that perforin-mediated pore formation may or may not be accompanied by delivery of granzyme molecules into the cytosol \[[@pcbi.1007972.ref030]\]; a requirement for granzyme delivery appears to be the establishment of a sufficiently large pore at the point of contact between CTL and target. Examination of recent 4D images of CTL--target engagement highlight potential for heterogeneous delivery of cytotoxic molecules \[[@pcbi.1007972.ref008]\]. That study showed the capability of a single CTL to rapidly organise lytic molecules around the centrosome upon initial target recognition and to subsequently polarise the centrosome towards the target. This sequence of events results in a strong and stable cytotoxic synapse with a high local density of perforin and granzymes. Anecdotal evidence from this same work indicates that there can also be an alternative outcome: In one observation a CTL attempted to form two immunological synapses with one target, with the result that effective centrosome polarisation towards either synapse did not occur and ultimately both synapses were aborted without target cell death (see S8 Video in reference \[[@pcbi.1007972.ref008]\]). Other observations of CTLs simultaneously polarising granules towards multiple targets \[[@pcbi.1007972.ref009]\] demonstrate that the formation of multiple immunological synapses does not necessarily preclude CTLs from killing. Taken together, these observations suggest that due to the diversity of possible damage pathways activated by CTLs as well as the potential for heterogeneity in delivery of granules, several mechanistic explanations for multiple-hit induced killing remain open. Given the breadth of cytotoxic weaponry available to a single CTL, it is apparent that experimental interference with one or more CTL effector functions is insufficient to conclude that one or another pathway is primarily involved in target cell death in a given experiment. We suggest high resolution, *in vitro* imaging as an effective means of achieving insight into the CTL killing process. Such high-resolution imaging would have several benefits: clear visualization of the polarisation of the lytic granules towards target cells would allow acquisition of statistics regarding the lethality of hits. Moreover, monitoring of individual target cells over time would provide statistics regarding the formation and abortion rates of immunological synapses and regarding the probability of target cell death after multiple hits. In addition, such approaches would allow investigation of the possibility of target cell recovery between successive hits, along with assessing the timescale over which such recovery might occur. Although such spatio-temporal resolution might be challenging to achieve experimentally, recent approaches using structured environments \[[@pcbi.1007972.ref031],[@pcbi.1007972.ref032]\] provide a possible means of achieving more refined control of CTL-target interactions. In conclusion, in addition to recent efforts to further characterise heterogeneity amongst CTLs, greater attention is needed to simultaneous monitoring of mechanisms activated in target cells after the target has been contacted by a CTL, assisted by statistical analyses and computational methods such as those presented here. Experimental research particularly involving use of e.g. caspase-8 reporters or reporters of granzyme activity to compare the relative importance of different killing mechanisms, as recently done in NK cells \[[@pcbi.1007972.ref017],[@pcbi.1007972.ref018]\] is crucial. Computational models can then be used to compare results between different experimental assays, thereby quantitatively assessing the contribution of identified CTL effector functions in different contexts. Methods {#sec009} ======= Monte Carlo simulations {#sec010} ----------------------- We devised stochastic simulations representing different "wells" in which individual CTLs killed targets. The setup of the simulations was based on published data by Vasconcelos *et al*. \[[@pcbi.1007972.ref019]\]. In brief, Vasconcelos *et al*. incubated pre-activated human-derived CTL clones with Epstein-Barr virus transformed B cell targets for 12 hours in microwells (*N*~*w*~ = 259). Each microwell contained a single CTL confined with an indeterminate (approximately 10--20, see Fig 4A in reference \[[@pcbi.1007972.ref019]\]) number of targets. Microwells were approximately cylindrical and had a cross-section diameter of approximately 100μm. A caspase reporter was used to determine the killing rate of individual CTLs over time. Similarly, our simulations featured *N*~*w*~ independent simulations, each containing *n* initially unhit targets and lasting for a simulated time period of 12 hours, or until all targets had been killed. The simulations proceed as follows: 1. A random variable *x*~*wait*~, representing the waiting time until the next CTL hit, is drawn from the exponential distribution with rate parameter equal to the CTL hitting rate *λ*. The current simulation time is increased by *x*~*wait*~. 2. A random target is selected and its number of hits is increased by one. 3. If a target has received sufficient hits for death (i.e., *η* hits), it is immediately removed from the simulation. In some simulations, we extended the rules in order to reflect typical *in vitro* assays more accurately: 1. ***Variable target numbers*.** Each simulation contained a single CTL and a variable number of targets *n*. For each well the number of targets was drawn from a Poisson distribution with mean $\overline{n}$. 2. ***Variable hitting rate*.** For each simulation the hitting rate *λ* of each CTL was a normally distributed random variable. The standard deviation of this distribution was used as a model parameter, with larger standard deviation reflecting CTL populations with greater intrinsic heterogeneity in killing performance between individuals. 3. ***Dynamic conjugate formation*.** We considered that hit delivery had to be preceded by conjugate formation and that at *t* = 0 *hrs* the CTL has not yet encountered any targets, and that CTLs form new conjugates with targets at constant rate *k*~*on*~ and abort conjugates with constant rate *k*~*off*~. Thus these simulations consider 4 distinct types of event: in addition to hitting and dying, we now have conjugate formation and conjugate abortation. The Gillespie algorithm was used to determine the type of event and waiting time between subsequent events \[[@pcbi.1007972.ref033]\], except for target cell death which occurs immediately after the lethal hit just as in our "all at risk" simulations. Parameter estimation for the dynamic conjugate formation model was based on four reported values from Vasconcelos *et*. *al*. \[[@pcbi.1007972.ref019]\]: the population killing averages for the high rate killers (6.4 targets killed per 12 hours) or low rate killers (2.8 targets killed per 12 hours), the fraction of the population reported to be high rate killers (⅓), and the breakpoint after which the high rate phenotype appeared (8--10 hours; we took 9 hours for this value). From these 4 reported values we derived three statistics for fitting our Monte Carlo simulations with dynamic conjugate formation: the mean (a~1~) and variance (a~2~) of the number of killed targets per CTL after 12 hours, and the expected number of killed targets per CTL at the breakpoint of 9 hours (a~3~). We estimated the killing at 9 hours by noting that the high rate group had not yet emerged at 9 hours, before which all cells killed at an approximately constant rate. Thus extrapolating from the low rate killing average at 12 hours (2.8 x 9/12) gives approximately 2 targets killed at the 9-hour breakpoint (note that this is also consistent with Fig 4B of Vasconcelos et. al \[[@pcbi.1007972.ref019]\]). Thus, the experimental estimates were: a~1~ = 4, a~2~ = 6.9 and a~3~ = 2. To fit to these estimates, we measured the same statistics (b~1,2,3~) from our simulations and then minimised the root mean squared error: $$RMSE = \sqrt{}\left( 1/3 \cdot {\sum_{i:1,2,3}\left( {a_{i} - b_{i}} \right)^{2}} \right),$$ for different values of the parameters *η*, *λ*, *k*~*on*~, and *k*~*off*~. For the stochastic optimisation we performed 10 repeats for all combinations of selected discrete values of *η*, *k*~*on*~, and *k*~*off*~ ([S2 Fig](#pcbi.1007972.s004){ref-type="supplementary-material"}), and then for each combination we estimated *λ* based on *N*~*w*~ = 1000 repeats and the optimise function in R. Dynamic conjugate simulations were written in C++ using the Rcpp package. Biological interpretation of parameters for the stochastic simulations are summarised in [Table 1](#pcbi.1007972.t001){ref-type="table"} and the parameter values used throughout the manuscript are provided in [S1 Table](#pcbi.1007972.s001){ref-type="supplementary-material"}. 10.1371/journal.pcbi.1007972.t001 ###### Stochastic simulation parameters. ![](pcbi.1007972.t001){#pcbi.1007972.t001g} parameter biological interpretation --------------------- ------------------------------------------ *η* number of hits required for target death $\overline{n}$ mean number of targets in a well *λ* (hr^-1^) hitting rate *k*~*on*~ (hr^-1^) conjugate formation rate *k*~*off*~ (hr^-1^) conjugate dissociation rate Spatial simulations {#sec011} ------------------- We developed spatial simulations of CTLs killing in microwells, with the aim of generating noisy and undersampled artificial data representative of data generated by microscopy, data which can be used to test methods for recovery of parameters governing CTL hitting. To this end we employed the cellular Potts model (CPM) framework \[[@pcbi.1007972.ref034]\], a formalism we used previously to simulate T cell-target cell interactions \[[@pcbi.1007972.ref011],[@pcbi.1007972.ref035],[@pcbi.1007972.ref036]\]. The CPM is a lattice based model, with entities such as cells represented by assigning individual lattice sites a 'spin' value, to identify them as belonging to a specific entity. The model evolves via minimisation of an energy function, the Hamiltonian: $$H = H_{sort} + H_{l} + H_{act}.$$ Here, *H*~*sort*~ represents interactions between cell surfaces and deviations from a target cell area; *H*~*sort*~ is defined as \[[@pcbi.1007972.ref034]\]: $$H_{sort} = {\sum_{{(a(\sigma) - A_{q(\sigma)})}^{2}}{J\left( {q\left( {\sigma\left( {i,j} \right)} \right),q\left( {\sigma\left( {i^{\prime},j^{\prime}} \right)} \right)} \right)\left( {1 - \delta_{\sigma({i,j}),\sigma({i^{\prime},j^{\prime}})}} \right) + \zeta_{a}{\sum_{spin\ types\ \sigma}\left( a(\sigma) - A_{q(\sigma)} \right)^{2}}},}$$ where *σ*(*i*,*j*) is the spin of an individual cell of type *q* at grid point with *x* coordinate *i* and *y* coordinate *j*; *J*(*q*,*q*′) is the surface energy between cells of type *q* and *q*′; *δ*~*σ*,*σ*′~ represents the Kronecker delta; *a*(*σ*) represents the actual area of a cell and *A*~*q*(*σ*)~ the target area for a cell of type *q* (we refer to this as area rather than volume because we employ 2D simulations); *ς*~*a*~ is a weighting term for the area constraint; Note that the sum of the surface energies are calculated over each third order neighbour of a 2D grid site. Our model also includes a term for surface area conservation of individual cells \[[@pcbi.1007972.ref037]\]: $$H_{l} = \zeta_{l}{\sum_{\sigma}\left( l(\sigma) - L_{q(\sigma)} \right)^{2},}$$ where *L*~*q*(*σ*)~ is the target perimeter for cells of type *q*, *l*(*σ*) is the current perimeter of a cell with type *σ* (determined as the total length of the boundary interfaces with grid sites of differing spin), and *ζ*~*l*~ is the weight of the perimeter constraint. We set $L_{q} = 2\pi\sqrt{A_{q}}$, i.e., the ratio of a circle's perimeter to its area, so that the term *H*~*l*~ is minimised when cells become perfectly circular. We set *ζ*~*l*~ lower for the CTLs than for the target cells, implying that the targets retained a spherical shape whereas CTLs were much more deformable in our simulations. Finally, the Hamiltonian includes a term *H*~*Act*~ to drive the motility of CTLs \[[@pcbi.1007972.ref022]\]: $$H_{Act} = \frac{\varsigma_{Act}}{{Max}_{Act}}\left( {GM}_{Act}\left( u \right) - {GM}_{Act}\left( v \right) \right).$$ This follows an actin-driven cell motility model with protrusions driving the migration of cells. In this model actin is modelled explicitly and when a cell occupies a new site on the lattice, the site is given an actin value *Max*~*Act*~. The actin activity *Act* in that site then decreases by one at every Monte carlo step until it reaches 0. The function: $${GM}_{Act}\left( u \right) = \left( {\prod_{y \in V(u)}{Act\left( y \right)}} \right)^{1/|{V(u)}|}$$ calculates the geometric mean actin activity around site *u*, where \|*V*(*u*)\| are the second order Moore neighbours of site *u* (see Fig 1 of reference \[[@pcbi.1007972.ref022]\]). The model favours updates from sites *u* with high actin activity into neighbouring sites *v* with low actin activity, resulting in local positive feedback. The CPM parameter *ς*~*Act*~ is a weighting term the strength of which we varied to control the motility of the CTLs. The *H*~*act*~ term was not applied to target cells, which are moved only passively via interactions with the CTL and other targets. In our spatial simulations we also implemented a contact-limited hitting behaviour for the CTL. We take CTL killing of targets to occur primarily via the perforin/granzyme pathway so we consider only contacted targets to be at risk, although our model should also apply to FAS-Ligand mediated killing, which is also contact-limited. When multiple targets are contacted by a CTL, it seems likely that the risk of getting hit is not equal for all targets, as polarisation of the lysosome towards specific targets should occur in order to permit delivery of lytic molecules to the target \[[@pcbi.1007972.ref008],[@pcbi.1007972.ref009]\]. Although we did not model the polarisation of the lysosome explicitly, we do take into account a tendency for CTLs to unequally distribute hits towards contacted targets. To achieve this, we implement the same baseline hitting probability as in the Gillespie simulations, and multiply this by *θ*~*i*~(*t*), the proportional fraction of CTL: target membrane interface occupied by the target at time point *t*: $$\theta_{i}\left( t \right) = \frac{l_{i}\left( t \right)}{L_{i}\left( t \right)},$$ where *l*~*i*~(*t*) is the length of the interaction interface between target *i* and the CTL inhabiting the same well, *L*~*i*~(*t*) the total interaction interface length of the CTL that contacts target *i*, including any other co-contacting targets. Because CTLs are considered to hit targets at a constant rate *λ*, for simulations without delayed hitting each target's risk of being hit during a brief time interval *Δt* equals *λθ*(*t*)⋅*Δt*. For some simulations we introduced a rule preventing CTLs from hitting targets for a specified delay period each time a CTL contacted or recontacted a target. This was implemented by means of a counting variable inside each target, such that hits would not register until the target had been in continuous contact with the CTL for the specified interval. Simulations had a spatial scale of 1 μm pixel^-1^ and were 100 μm^2^ in area. The simulation space consisted of a circular area representing a microwell within which one CTL and usually between 10--20 targets were constrained to move. Simulations had a temporal scale of 1 second per Monte Carlo step. Parameters employed in the CPM simulations are given in [Table 2](#pcbi.1007972.t002){ref-type="table"}. Simulation output was produced every 120 Monte Carlo steps (2 minute intervals), corresponding to a typical sampling frequency in time-lapse imaging data with multiple wells \[[@pcbi.1007972.ref019]\]. CPM simulations were developed within the morpheus framework \[[@pcbi.1007972.ref038]\]. 10.1371/journal.pcbi.1007972.t002 ###### Cellular Potts simulation parameters. ![](pcbi.1007972.t002){#pcbi.1007972.t002g} --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- parameter value Description --------------- ----------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------- *J*~*σ*,*σ*′~ *J~tar,tar~* = 0.7; *J*~*ctl*,*tar*~ = −3; *J*~*tar*,*well*~ = 0; *J*~*ctl*,*well*~ = 0 surface energies between cell types *A*~*q*~ *A*~*ctl*~ = 140 *μm*^2^\ the target area for a cell of type *q* *A*~*tar*~ = 340 *μm*^2^\ *L*~*q*~ $2\sqrt{\pi A_{q}}$ the target perimeter for a cell of type *q* *ς*~*l*~ *ς*~*l*,*ctl*~ = 0.1\ strength of cell perimeter constraint *ς*~*l*,*tar*~ = 0.25 *ς*~*a*~ *ς*~*a*,*ctl*~ = 1\ strength of cell area constraint *ς*~*a*,*tar*~ = 1 *ς*~*Act*~ *ς*~*Act*,*low*~ = 2\ strength of actin protrusion dynamics: *ς*~*Act*,*low*~ for low-motility and *ς*~*Act*,*high*~ for high motility CTLs *ς*~*Act*,*high*~ = 10 *Max*~*Act*~ 50 Actin activity value when CTLs occupy a new lattice site --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Supporting information {#sec012} ====================== ###### Summary of parameters used in stochastic simulations. Data and code used in this project are available (<http://doi.org/10.17605/OSF.IO/6GQYP>). (PDF) ###### Click here for additional data file. ###### Fitting procedure and hypothesis comparison for multiple-hitting model and subpopulation model. (PDF) ###### Click here for additional data file. ###### Multiple hitting increases inherent variability in killing performance between individual CTLs. A-B) Distribution of killed target numbers after 12 hours (A) when intrinsic hitting rates *λ* (B) are drawn from a normal distribution with mean $\overline{\lambda}$ and standard deviation $\sigma_{\lambda}\left( \lambda \sim Normal\left( \overline{\lambda},\sigma_{\lambda} \right) \right.$). C) Overdispersion for the variance in killed targets in A relative to the variance expected for a Poisson distribution, i.e., the ratio of the variance (*var*(*x*)) to the mean ($\overline{x}$) number of targets killed after 12 hours (vertical axis). The horizontal axis is the ratio of the standard deviation to the mean value of the intrinsic hitting rate. (TIFF) ###### Click here for additional data file. ###### Parameter estimation for Monte Carlo simulations with dynamic contacts. A\) Estimated hitting rates (*λ*, represented by colour) for various combinations of the number of hits (*η*, rows), contact formation rates (k~on~, vertical axes in sub-panels), or contact escape rates (k~off~, horizontal axes in sub-panels). Ten repeats (across columns) were performed for the optimisation step, using N~w~ = 10^3^ CTLs per tested value of *λ*. After fitting we validated our results by performing N~w~ = 10^4^ simulations with each best fitting parameter combination, which is shown here. B) Root mean square residual errors for the best fitting parameter estimates (panel arrangement is as described in S2A Fig legend). Results are from validation simulations, using N~w~ = 10^4^ simulations per parameter combination. (TIFF) ###### Click here for additional data file. ###### Monte Carlo simulated CTL:target interaction durations amongst surviving and killed targets. A\) Sample density of killed targets in Monte Carlo simulations lasting until all targets were killed, with different numbers of hits (*η*, on different rows). B) Sample density of killed targets in Monte Carlo simulations stopped after 12 hours. C) Sample density of surviving targets, corresponding to the 'absent' portion of the distribution for killed targets in B. The red line in A and B is the function f~k~, which describes how the relative probability until targets receive η hits arriving at a constant rate λ depends on the cumulative interaction time τ, for a gamma distributed waiting time. For all S3 Fig: N~w~ = 100, n = 12 targets per well, all targets equally at risk. Parameter combinations used were: (*η* = 1,*λ* = 0.34; *η* = 2,*λ* = 1.17; *η* = 3,λ = 2.12; *η* = 4,*λ* = 3.14; *η* = 5,*λ* = 4.22). (TIFF) ###### Click here for additional data file. ###### Maximum likelihood estimation for the killing rate of single-hitting CTLs. A\) Poisson distributions for the number of targets used to start simulations in S4 Fig, with mean $\overline{n} = 8\ or\ 16$ as shown. B) Number of killed targets after 12 hours for N~w~ = 2 x 3 x 1000 simulations, each group of N~w~ = 1000 started with one of the 2 distributions in A, and with one of the 3 indicated parameter settings. C) Density of killed targets after 12 hours from 'Mixed' distributions resulting from *η* = 1,*λ*~***LR***~ = **0**.2,*λ*~*HR*~ = 0.7 and either $\overline{n}$ = 8 *and m* = 0 (left panel), or $\overline{n}$ = 16 *and m* = 0.67 (right panel). Note that for $\overline{n}$ = 8 the killing of multiple-hitting CTLs became greater than the high rate subpopulation of single-hitting CTLs; $\overline{n}$ = 8 was only used for testing robustness of the estimators on heavily censored data. D) Relative likelihood of candidate hitting rate estimates, $\hat{\lambda}$, compared to the maximum likelihood estimate, ${\hat{\lambda}}_{ML}$, resulting from application of the Poisson estimator separately to each of the single-hitting (*η* = 1) datasets shown in B. Relative likelihood are shown either for the dataset in its entirety (dashed lines), or for a randomly selected sample of N~W~ = 10 (solid lines). E) Examples of testing datasets derived from the multiple-hitting population (B, $\overline{n}$ = 16, *η* = 10) or from a mixture of single-hitting CTLs (B, $\overline{n}$ = 16, *η* = 1, where the true density of killed targets in the mixture distribution is in C). F) Relative likelihood of candidate hitting rate estimates, $\hat{\lambda}$, compared to the maximum likelihood estimate, ${\hat{\lambda}}_{ML}$, for constrained fits constructed from either the subpopulation datasets, or from multiple-hitting datasets, for three samples with either N~w~ = 30,100, or 1000 (note the multiple-hitting-generated data (*η* = 10) is therefore fully represented by the N~w~ = 1000 case). (TIFF) ###### Click here for additional data file. ###### Testing for multiple-hitting CTLs versus subpopulations of single-hitting CTLs. A\) Maximum likelihood estimates for the hitting rate, ${\hat{\lambda}}_{ML}$, with either the gamma or Poisson estimators, both constrained to a uniform single-hitting population (i.e. by forcing *η* = 1 for the gamma estimator and by forcing *m* = 1 for the Poisson estimator). Each of the 2x4x10 = 80 points represents one of the 4x10 testing populations from [S4E Fig](#pcbi.1007972.s006){ref-type="supplementary-material"} (here indicated by facet labels), fit with both of our estimators (x-axis). B) Difference between the log likelihood function evaluated with the constrained versus unconstrained Gamma estimator $log\ L\left( {\hat{\lambda}}_{ML},{\hat{\eta}}_{ML} \right)$ (dark bars); or with the constrained versus unconstrained Poisson estimator $log\ L\left( {\hat{\lambda}}_{HR,ML},{\hat{\lambda}}_{LR,ML},{\hat{m}}_{ML} \right)$ (light bars). Each of the 40 testing populations occupies one horizontal bar, with the details of the testing populations as indicated in facet labels. For the x-axis scaling (negative values are not possible), the relative size of the dark v.s. light bars is proportional to the strength of the evidence for the multiple-hitting hypothesis (dark bars) versus the subpopulation hypothesis (light bars). C) The constrained estimates for the hitting rate parameters, ${\hat{\lambda}}_{ML}$, (circles; also shown in A) or their unconstrained counterparts (red asterisks) for each testing population (points on x-axis). For the Gamma estimator (top row) the estimated ${\hat{\eta}}_{ML}$ is shown only where ${\hat{\eta}}_{ML} > 1$. For the Poisson estimator (bottom row), the unconstrained estimates for ${\hat{\lambda}}_{HR,ML},{\hat{\lambda}}_{LR,ML}$ are above and below their counterpart constrained estimates, and the Gamma and Poisson estimators can be compared per population. D) Distribution of all cumulative interaction times, *τ* (killed and surviving targets shown separately in columns), for all N~w~ = 1000 members of each of the 3 generating populations (as shown in [S4B Fig](#pcbi.1007972.s006){ref-type="supplementary-material"}). Although the 2 single-hitting populations were combined (upper row), the separate contribution of the *λ*~*HR*~ (red) or *λ*~*LR*~ (blue) populations is indicated by color. Multiple-hitting CTLs (green) are shown separately (bottom row). (TIFF) ###### Click here for additional data file. ###### Maximum likelihood estimation for CPM simulations with a hitting threshold time. A-B) Heatmaps of the likelihood function around the maximum likelihood estimates for the killing parameters *η* and *λ*, in CPM simulations under various conditions. In A, results are shown for various *η* values (rows) and for both high-motility (left colum) and low-motility (right column) conditions for simulations with 15 minute hitting delay. In B, results are shown for high motility CTLs at all tested values of the delay (in range 0--15 minutes, across columns). The horizontal and vertical lines in A-B mark the values of the CPM parameters used to generate the data for each group and the boundary enclosing the 95% confidence region is marked with a thin blue line. (TIFF) ###### Click here for additional data file. ###### Simulation of high-motility CTL, requiring 5 hits to kill targets. (AVI) ###### Click here for additional data file. ###### Simulation of low-motility CTL, requiring 5 hits to kill targets. In all videos, CTLs are shown in red whilst uncontacted targets are in grey. Contacted targets are shaded blue based on their share of total CTL:target interface, i.e. the probability that they will receive the next hit generated by the CTL. Targets are overlaid with the number of hits they have received. Elapsed simulation time (hours:minutes) is displayed in the upper right corner of the videos. (AVI) ###### Click here for additional data file. We would like to thank Delphine Guipouy and Loïc Dupré for useful discussions on the set-up of previously published microwell experiments. 10.1371/journal.pcbi.1007972.r001 Decision Letter 0 De Boer Rob J. Deputy Editor Yates Andrew J. Associate Editor © 2020 De Boer, Yates 2020 De Boer, Yates This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 12 Feb 2020 Dear Dr. Beltman, Thank you very much for submitting your manuscript \"Heterogeneous, Delayed-Onset Killing by Multiple-Hitting T Cells: Stochastic Simulations to Assess Methods for Analysis of Imaging data\" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers\' comments. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers\' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: \[1\] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. \[2\] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don\'t hesitate to contact us if you have any questions or comments. Sincerely, Andrew J. Yates Associate Editor PLOS Computational Biology Rob De Boer Deputy Editor PLOS Computational Biology \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* Reviewer\'s Responses to Questions **Comments to the Authors:** **Please note here if the review is uploaded as an attachment.** Reviewer \#1: Comments: Beck et al simulate CTL-mediated immune responses in different settings to better understand how CTL-mediated killing of target cells is regulated in vitro. They use different simulation approaches to address the very important open question of how CTL-mediated killing of target cells can be better understood. This remains a very important question, given the high clinical importance of CTL-mediated immune responses against infectious diseases and cancer in the current age of immune-cell based therapeutic approaches. Reviewer comments regarding the text: Regarding the Monte Carlo Simulations in Figure 1, it remains a little unclear how a small increase in simulated target cell numbers (plus 1) would change the outcome of the simulation in the way presented in Figure 1B (for the 100 hit case). Obviously, the "100 hit case" is a very extreme situation -- but maybe this outcome of the simulation could be discussed and explained in more detail. Maybe a plotting of the effector-to-target cell ratio of these simulations would help to better understand this result? Regarding the "over-dispersion" -- maybe a short explanation of how such a conclusion was reached might be helpful (how was dispersion measured, and how can the cut-off that determines over-dispersion be justified). Regarding the spatial model, it remains unclear how the "two CTL motility patterns" are used in the simulations: how are the two states set for individual cells? Does target cell contact decrease motility? Based on what experimental data are these motility features defined? Finally, to better understand how "cumulative contact time" in the simulations can be interpreted a short description of how the simulated CTL deliver the "lethal hits" in relation to contact duration would be helpful. How is "hit delivery" defined in the spatial model? Could one contact event lead to multiple "hits"? Reviewer comments on Material and Methods section: 1.) Monte Carlo simulations: How were these simulations performed? How was the data from Vasconcelos et al used exactly and where can the used data be found? How many simulations were performed? 2.) Spatial simulations How was target cell motility defined? Why are the targets motile -- how much does that affect the different conclusions (Maybe check results with non-motile and motile targets). Reviewer comments on Figures: Figure 1: Fig 1B: what does the Y-axis label really mean ("frequency")? Maybe this can be described in the figure legend. Fig 1D: The Y axis is cut at 10 -- is this really necessary? Fig 1E: what does the Y-axis label mean -- is it different to Fig 1B? Figure 2: Usually, target cell binding is expected to alter CTL migration -- so how does target binding affect the CTL motility here? How are the high vs low motility states "regulated" in these simulations? Reviewer \#2: In this study, the authors use stochastic simulations to examine if heterogeneity in CTL killing dynamics can be explained by the requirement of target cells to receive multiple lytic hits. Using explicit spatial simulations based on the CPM-framework, they further investigate how this hitting rate and the number of required hits per target cell can be inferred from imaging data. Based on their analyses they show that measuring the cumulative duration of CTL-target contacts would improve the accuracy of estimating CTL killing kinetics. The topic is timely and relevant as understanding CTL efficacy is an important aspect for designing optimal therapeutic vaccination and treatment strategies, as e.g. against cancer. The study is well written and thoroughly structured. With this theoretical analysis the authors provide a reasonable explanation for previous observations from experimental studies and propose required measurements for further experiments. However, the study remains a bit limited by focusing on only one explanation for CTL killing dynamics. \# Major points: (1.) The authors state that with the multiple-hitting-scenario, there is no need to invoke an unobserved subpopulation of high-rate killers (p. 22) as suggested by other studies. While this is true and nicely shown, I think the study would substantially benefit if the authors also show how the proposed information from imaging studies should differ in case of the latter scenario or others. It could be quite interesting to know on what type of measurements one has to focus in order to differ between different hypotheses, such as having cell populations that are heterogeneous (either in their killing efficacy (CTL) or susceptibility to killing (target cell)), having serial or multiple-killing, or assuming single- or multiple hit killing. (2.) The ability to infer the hitting parameters in case of multiple-hitting CTL from CTL-target (cumulative) contact times in case of multiple-hitting is quite robust and interesting. However, measuring the cumulative contact times might be not sufficient in case that active conjugate formation would require the stopping of CTLs to allow them to deliver their lethal hits (Wiedemann et al., PNAS 2006), i.e., requiring a minimal contact time. This seems not to be directly implemented within the CPM as the hitting probability only considers the contact length for distributing the hit across multiple target cells. (3.) Another question concerns the parameterizations of the CPM. Do "high-" and "low-motility" CTL correspond in some way to the dynamics observed within the experiments or were they arbitrarily chosen? (4.) Why is the average number of target cells killed after 12 hours for a density of 15 target cells higher when several hits are required compared to only one? This seems to be counterintuitive unless the hitting rates differ between the scenarios, maybe due to the adjustment done before and mentioned in the text? However, Figure 1E actually shows that for a given target cell concentration, the distribution gets shifted to the left the more hits are required. The values of the rates used for simulation should be mentioned within the text or the figure legends. The corresponding Table (Table 1) seems to be empty. \# Minor points: \- Figure 4A and Figure 5F are very difficult to read. Maybe there are better ways of representation, e.g. using different colors for each given (correct) parameter combination and similar colors with point sizes corresponding to frequencies for the estimates? \- Figure 1B: Does the red dotted line always refer to the 16 targets case for each row separately, i.e. for each number of hits (1,10,100)? \*\*\*\*\*\*\*\*\*\* **Have all data underlying the figures and results presented in the manuscript been provided?** Large-scale datasets should be made available via a public repository as described in the *PLOS Computational Biology* [data availability policy](http://journals.plos.org/ploscompbiol/s/data-availability), and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information. Reviewer \#1: None Reviewer \#2: No: The parameters used for simulating the results shown in Figure 1 seem to be missing. \*\*\*\*\*\*\*\*\*\* PLOS authors have the option to publish the peer review history of their article ([what does this mean?](https://journals.plos.org/ploscompbiol/s/editorial-and-peer-review-process#loc-peer-review-history)). If published, this will include your full peer review and any attached files. If you choose "no", your identity will remain anonymous but your review may still be made public. **Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our [Privacy Policy](https://www.plos.org/privacy-policy). Reviewer \#1: No Reviewer \#2: No [Figure Files:]{.ul} While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, [[https://pacev2.apexcovantage.com](https://pacev2.apexcovantage.com/)]{.ul}. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at [<figures@plos.org>]{.ul}. [Data Requirements:]{.ul} Please note that, as a condition of publication, PLOS\' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: <http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5>. [Reproducibility:]{.ul} To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions, please see [[http://journals.plos.org/compbiol/s/submission-guidelines\#loc-materials-and-methods](http://journals.plos.org/plospathogens/s/submission-guidelines)]{.ul} 10.1371/journal.pcbi.1007972.r002 Author response to Decision Letter 0 13 May 2020 ###### Submitted filename: review response.pdf ###### Click here for additional data file. 10.1371/journal.pcbi.1007972.r003 Decision Letter 1 De Boer Rob J. Deputy Editor Yates Andrew J. Associate Editor © 2020 De Boer, Yates 2020 De Boer, Yates This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 21 May 2020 Dear Dr. Beltman, We are pleased to inform you that your manuscript \'Heterogeneous, Delayed-Onset Killing by Multiple-Hitting T Cells: Stochastic Simulations to Assess Methods for Analysis of Imaging data\' has been provisionally accepted for publication in PLOS Computational Biology. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution\'s press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology.  Best regards, Andrew J. Yates Associate Editor PLOS Computational Biology Rob De Boer Deputy Editor PLOS Computational Biology \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* 10.1371/journal.pcbi.1007972.r004 Acceptance letter De Boer Rob J. Deputy Editor Yates Andrew J. Associate Editor © 2020 De Boer, Yates 2020 De Boer, Yates This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 22 Jun 2020 PCOMPBIOL-D-19-02233R1 Heterogeneous, Delayed-Onset Killing by Multiple-Hitting T Cells: Stochastic Simulations to Assess Methods for Analysis of Imaging data Dear Dr Beltman, I am pleased to inform you that your manuscript has been formally accepted for publication in PLOS Computational Biology. Your manuscript is now with our production department and you will be notified of the publication date in due course. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Soon after your final files are uploaded, unless you have opted out, the early version of your manuscript will be published online. The date of the early version will be your article\'s publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting PLOS Computational Biology and open-access publishing. We are looking forward to publishing your work! With kind regards, Laura Mallard PLOS Computational Biology \| Carlyle House, Carlyle Road, Cambridge CB4 3DN \| United Kingdom <ploscompbiol@plos.org> \| Phone +44 (0) 1223-442824 \| [ploscompbiol.org](http://ploscompbiol.org) \| \@PLOSCompBiol [^1]: The authors have declared that no competing interests exist.
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Centering, grounding. Aligns energies, "stone of harmony." Stimulates circulation and blood flow. This stone is an infection fighter and helps to strengthen the lungs. It is a cubic lead structure that adds balance to the emotions and the etheric body Warning: Galena is the principle ore of lead, and forms glistening silver cubes with almost unnaturally perfect shapes. Although lead is normally extremely flexible, the sulfur content of galena makes it extraordinarily brittle and reactive to chemical treatment. Galena is capable of taking an equally heavy toll on workers and amateur researchers who are exposed to it. Contact with specimens may lead to lead dust exposure, while workers in mines face a high risk of poisoning from contact with the mineral and the deadly dusts released through production. Once extracted, the lead content from this mineral poses environmental and health threats during treatment and extraction. Galena has a cubic fracture, and if hit with a hammer, the crystal will shatter into multiple smaller replicas of its original shape. Let us make your custom made Galena pendant, purchase a stone from above or send us one you have, then choose your findings $35.00 Choose Wire Or Cap These gem essences, and essential oils are properly prepared by an expert and the healing properties are sent into the essences without ever actually touching the water and oils. This particular product, works well as an INDIRECT ELIXIR, which means it does not actually touch the water, but rather is prepared by a process that allows the stone's energies to be absorbed into the liquid, and does not bring its poisonous attributes to the product.
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Molecular phylogenetic analyses of reverse-transcribed bacterial rRNA obtained from deep-sea cold seep sediments. A depth profile of naturally occurring bacterial community structures associated with the deep-sea cold seep push-core sediment in the Japan Trench at a depth of 5343 m were evaluated using molecular phylogenetic analyses of RNA reverse transcription-PCR (RT-PCR) amplified 16S crDNA fragments. A total of 137 clones of bacterial crDNA (complimentary rDNA) phylotypes (phylogenetic types) obtained at three different depths (2-4, 8-10 and 14-16 cm) were identified in partial crDNA sequencings. crDNA phylotypes from the cold seep sediment were dominantly composed of delta- and epsilon-Proteobacteria (36% and 42% respectively). Phylotype analysis of crDNA clone libraries and terminal restriction fragment length polymorphism (T-RFLP) analysis revealed that the majority of bacterial components shifted from delta- Proteobacteria to epsilon-Proteobacteria with increasing depth. Among the delta-proteobacterial crDNA clones, the sequences related to the genus Desulfosarcina were dominant. Almost all sequences of crDNA belonging to epsilon-Proteobacteria were affiliated with the same cluster (epsilon-CSG: epsilon-proteobacterial cold seep group), and were closely related with rDNA sequences from deep-sea hydrothermal vent environments.
{ "pile_set_name": "PubMed Abstracts" }
Improved ECG pre-processing for beat-to-beat QT interval variability measurement. The aim of this study was to enhance the ECG pre-processing modalities for beat-to-beat QT interval variability measurement based on template matching. The R-peak detection algorithm has been substituted and an efficient baseline removal algorithm has been implemented in existing computer software. To test performance we used simulated ECG data with fixed QT intervals featuring Gaussian noise, baseline wander and amplitude modulation and two alternative algorithms. We computed the standard deviation of beat-to-beat QT intervals as a marker of QT interval variability (QTV). Significantly a lower beat-to-beat QTV was found in the updated approach compared the original algorithm. In addition, the updated template matching computer software outperformed the previous version in discarding fewer beats. In conclusion, the updated ECG preprocessing algorithm is recommended for more accurate quantification of beat-to-beat QT interval variability.
{ "pile_set_name": "PubMed Abstracts" }
Submit a definitive, introspective paper describing your spiritual and ministerial journey (from the time of your call, through your career and life seasons, until the present). Request transcript(s) from all previous baccalaureate and any graduate-level work be sent directly to Hood Theological Seminary Office of Admissions & Recruitment. Contact the governing board of your ministry setting and ask the board to send us a letter indicating (a) your present involvement in ministry, (b) a reasonable assurance of your continuity in that setting of ministry for the duration of this program, and (c) their willingness to support you financially and programmatically during your participation in the program. Official transcript indicating a bachelor's degree or its equivalent, from a college or university accredited by an agency recognized by the Council for Higher Education Accreditation or holding membership in the Association of Universities and College in Canada, or the educational equivalent. All students who want to transfer credits earned at Hood to another institution must verify prior to registering that the course will be accepted as transfer credit by the other institution.
{ "pile_set_name": "Pile-CC" }
(Dallas, Texas) – This week Students for Concealed Carry (SCC) announced that Antonia Okafor, a graduate student at The University of Texas at Dallas, will be the Southwest Regional Director and Texas State Director effective immediately. Antonia has already hit the ground running, debuting her first news appearance on Al Jeezera America, debating Colin Goddard of Everytown for Gun Safety, in favor of the campus concealed carry law recently passed in Texas. Antonia graduated from The University of Texas at Dallas with a Bachelors of Arts degree in international political economy and currently studies public policy as a graduate student. Her passion to protect student’s gun rights was exemplified during the recent Texas legislative session where she had the opportunity to advocate for campus concealed carry in the general assembly. Antonia is actively involved on campus as a Leadership Institute Campus Reform Correspondent, founder and President of the Network of enlightened Women chapter and a former Resident Assistant. She is also extensively involved in her hometown and state level politics, having served in and volunteered for several key political races and positions. “Madison [Welch, outgoing Texas and Southwest Regional Director] did a fantastic job this legislative session helping to right a wrong and move the ball downfield,” said Michael Newbern, SCC board member at large. “Antonia’s experience and network will help her carry on Students SCC’s efforts in Texas. We’re already making plans to further the great work Madison did and are confident Antonia is the best person for the job.”
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President Yoweri Museveni has called on the Organization of Islamic Cooperation (OIC) to increase investments in member state countries especially in the areas of infrastructure development saying this would boost economic development especially in the East African region. President Yoweri Museveni has congratulated Mityana Diocese for contributing not only to the development of the Diocese but also of the nation by constructing two multi-billion student hostels at the Church of Uganda founded Ndejje University whose proceeds will also be partly used to cater for the clergy.
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using System; using LanguageExt; using LanguageExt.Common; using static LanguageExt.Prelude; using LanguageExt.ClassInstances; using LanguageExt.TypeClasses; using System.Diagnostics.Contracts; using System.Collections.Generic; /// <summary> /// Extension methods for RWS /// </summary> public static class RWSExtensions { /// <summary> /// Monadic join /// </summary> [Pure] public static RWS<MonoidW, R, W, S, A> Flatten<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, RWS<MonoidW, R, W, S, A>> ma) where MonoidW : struct, Monoid<W> => ma.Bind(identity); /// <summary> /// Runs the RWS monad and memoizes the result in a TryOption monad. Use /// Match, IfSucc, IfNone, etc to extract. /// </summary> public static RWSResult<MonoidW, R, W, S, A> Run<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, R env, S state) where MonoidW : struct, Monoid<W> { if (self == null) throw new ArgumentNullException(nameof(self)); if (state == null) throw new ArgumentNullException(nameof(state)); try { return self(env, state); } catch (Exception e) { return RWSResult<MonoidW, R, W, S, A>.New(state, Error.New(e)); } } [Pure] public static RWS<MonoidW, R, W, S, int> Sum<MonoidW, R, W, S>(this RWS<MonoidW, R, W, S, int> self) where MonoidW : struct, Monoid<W> => self; [Pure] public static RWS<MonoidW, R, W, S, Seq<A>> ToSeq<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self) where MonoidW : struct, Monoid<W> => self.Map(x => x.Cons()); [Pure] public static RWS<MonoidW, R, W, S, Seq<A>> AsEnumerable<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self) where MonoidW : struct, Monoid<W> => ToSeq(self); [Pure] public static Seq<A> ToSeq<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, R env, S state) where MonoidW : struct, Monoid<W> { IEnumerable<A> Yield() { var res = self(env, state); if (!res.IsFaulted) { yield return res.Value; } } return Seq(Yield()); } [Pure] public static Seq<A> AsEnumerable<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, R env, S state) where MonoidW : struct, Monoid<W> => ToSeq(self, env, state); [Pure] public static RWS<MonoidW, R, W, S, int> Count<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, int>.New(res.Output, state, res.Error) : RWSResult<MonoidW, R, W, S, int>.New(res.Output, res.State, 1); }; [Pure] public static RWS<MonoidW, R, W, S, bool> Exists<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Func<A, bool> pred) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, bool>.New(res.Output, state, false) : RWSResult<MonoidW, R, W, S, bool>.New(res.Output, res.State, pred(res.Value)); }; [Pure] public static RWS<MonoidW, R, W, S, bool> ForAll<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Func<A, bool> pred) where MonoidW : struct, Monoid<W> => Exists(self, pred); [Pure] public static RWS<MonoidW, R, W, S, B> Fold<MonoidW, R, W, S, A, B>(this RWS<MonoidW, R, W, S, A> self, B initialValue, Func<B, A, B> f) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, B>.New(res.Output, state, res.Error) : RWSResult<MonoidW, R, W, S, B>.New(res.Output, res.State, f(initialValue, res.Value)); }; [Pure] public static RWS<MonoidW, R, W, S, R> Fold<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Func<R, A, R> f) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, R>.New(res.Output, state, res.Error) : RWSResult<MonoidW, R, W, S, R>.New(res.Output, res.State, f(env, res.Value)); }; /// <summary> /// Force evaluation of the monad (once only) /// </summary> [Pure] public static RWS<MonoidW, R, W, S, A> Strict<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> ma) where MonoidW : struct, Monoid<W> { Option<RWSResult<MonoidW, R, W, S, A>> cache = default; object sync = new object(); return (env, state) => { if (cache.IsSome) return cache.Value; lock (sync) { if (cache.IsSome) return cache.Value; cache = ma(env, state); return cache.Value; } }; } /// <summary> /// Impure iteration of the bound value in the structure /// </summary> /// <returns> /// Returns the original unmodified structure /// </returns> public static RWS<MonoidW, R, W, S, A> Do<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> ma, Action<A> f) where MonoidW : struct, Monoid<W> => (env, state) => { var r = ma(env, state); if (!r.IsFaulted) { f(r.Value); } return r; }; /// <summary> /// Monadic state transformer. /// Maps an old state to a new state inside a RWS monad. The old state is thrown away. /// </summary> [Pure] public static RWS<MonoidW, R, W, S, Unit> Modify<MonoidW, R, W, S, A>(RWS<MonoidW, R, W, S, A> self, Func<S, S> f) where MonoidW : struct, Monoid<W> => (env, state) => RWSResult<MonoidW, R, W, S, Unit>.New(default(MonoidW).Empty(), f(state), unit); [Pure] public static RWS<MonoidW, R, W, S, B> Map<MonoidW, R, W, S, A, B>(this RWS<MonoidW, R, W, S, A> self, Func<A, B> project) where MonoidW: struct, Monoid<W> => self.Select(project); /// <summary> /// Pass is an action that executes the monad, which /// returns a value and a function, and returns the value, applying /// the function to the output. /// </summary> [Pure] public static RWS<MonoidW, R, W, S, A> Pass<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, (A, Func<W, W>)> self) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, A>.New(res.Output, state, res.Error) : RWSResult<MonoidW, R, W, S, A>.New(res.Value.Item2(res.Output), res.State, res.Value.Item1); }; /// <summary> /// Listen is an action that executes the monad and adds /// its output to the value of the computation. /// </summary> [Pure] public static RWS<MonoidW, R, W, S, (A, B)> Listen<MonoidW, R, W, S, A, B>(this RWS<MonoidW, R, W, S, A> ma, Func<W, B> f) where MonoidW : struct, Monoid<W> => (env, state) => { var res = ma(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, (A, B)>.New(res.State, res.Error) : RWSResult<MonoidW, R, W, S, (A, B)>.New(res.Output, res.State, (res.Value, f(res.Output))); }; /// <summary> /// Censor is an action that executes the monad and applies the function f /// to its output, leaving the return value unchanged. /// </summary> [Pure] public static RWS<MonoidW, R, W, S, A> Censor<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> ma, Func<W, W> f) where MonoidW : struct, Monoid<W> => Pass(ma.Bind(a => RWS<MonoidW, R, W, S, (A, Func<W, W>)>((a, f)))); [Pure] public static RWS<MonoidW, R, W, S, B> Bind<MonoidW, R, W, S, A, B>(this RWS<MonoidW, R, W, S, A> ma, Func<A, RWS<MonoidW, R, W, S, B>> f) where MonoidW : struct, Monoid<W> => (env, state) => { var ra = ma(env, state); if (ra.IsFaulted) return RWSResult<MonoidW, R, W, S, B>.New(ra.Output, ra.State, ra.Error); var rb = f(ra.Value)(env, ra.State); var noutput = default(MonoidW).Append(ra.Output, rb.Output); return rb.IsFaulted ? RWSResult<MonoidW, R, W, S, B>.New(noutput, state, rb.Error) : RWSResult<MonoidW, R, W, S, B>.New(noutput, rb.State, rb.Value); }; [Pure] public static RWS<MonoidW, R, W, S, B> Select<MonoidW, R, W, S, A, B>(this RWS<MonoidW, R, W, S, A> ma, Func<A, B> f) where MonoidW : struct, Monoid<W> => (env, state) => { var ra = ma(env, state); return ra.IsFaulted ? RWSResult<MonoidW, R, W, S, B>.New(ra.Output, state, ra.Error) : RWSResult<MonoidW, R, W, S, B>.New(ra.Output, ra.State, f(ra.Value)); }; [Pure] public static RWS<MonoidW, R, W, S, C> SelectMany<MonoidW, R, W, S, A, B, C>( this RWS<MonoidW, R, W, S, A> ma, Func<A, RWS<MonoidW, R, W, S, B>> bind, Func<A, B, C> project) where MonoidW : struct, Monoid<W> => (env, state) => { var ra = ma(env, state); if (ra.IsFaulted) return RWSResult<MonoidW, R, W, S, C>.New(ra.Output, ra.State, ra.Error); var rb = bind(ra.Value)(env, ra.State); var noutput = default(MonoidW).Append(ra.Output, rb.Output); return rb.IsFaulted ? RWSResult<MonoidW, R, W, S, C>.New(noutput, state, rb.Error) : RWSResult<MonoidW, R, W, S, C>.New(noutput, rb.State, project(ra.Value, rb.Value)); }; [Pure] public static RWS<MonoidW, R, W, S, A> Filter<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Func<A, bool> pred) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); if (res.IsFaulted) return res; return pred(res.Value) ? res : RWSResult<MonoidW, R, W, S, A>.New(res.Output, state, Error.Bottom); }; [Pure] public static RWS<MonoidW, R, W, S, A> Where<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Func<A, bool> pred) where MonoidW : struct, Monoid<W> => Filter(self, pred); public static RWS<MonoidW, R, W, S, Unit> Iter<MonoidW, R, W, S, A>(this RWS<MonoidW, R, W, S, A> self, Action<A> action) where MonoidW : struct, Monoid<W> => (env, state) => { var res = self(env, state); return res.IsFaulted ? RWSResult<MonoidW, R, W, S, Unit>.New(res.Output, state, res.Error) : RWSResult<MonoidW, R, W, S, Unit>.New(res.Output, res.State, fun(action)(res.Value)); }; }
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Program["{{module}}"] = function ( module, exports ) { {{source}} };
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MENU September 30, 2012 It is no surprise that soft hues and simple silhouettes make a great outfit! And immediately we think about a very lady like style when looking at this fabulous trends! here are 5 tips on how to look like a lady super easy! September 28, 2012 I am in loooove of these pants! actually I am in love with everything I post on my blog (I¡m sorry is kind of my guilty pleasure hahaha). But talking serious this trend is so feminine and so classic and elegant! September 25, 2012 Final! Yes my latest post of how to pack smart ! Comfortableness vs that not-so-great piece I wanted to bring! I know everyone has an experience with these kind of pieces but now you won't have it anymore! September 21, 2012 Oh yes! I am seeing myself catching a plain in a couple of weeks now! I am so excited to be going to Argentine with my friends for a Latin american Fashion event!!! But with this all the over packing stress gets on me again !!! September 20, 2012 The sun finally decided to go out so I am in the mood for a pretty summer entry! Well... in 2 days or maybe tomorrow (I am not very good at astronomic) I know that spring will start and let me tell you HOW excited I am! I am tired with the cold and I am so ready for the super high temperatures to come! September 15, 2012 One of my favorite long time designers is Diano Von Frustenberg, I love how she mixes simple and classic pictures but adding that color pop that make the clothes for every single personality in this world! September 9, 2012 I know it is a little bit late, but better later than never right? As you all know the VMA's were on Thursday 6 Spt. (wow, really late actually) But I could not resist not posting my best dressed list and some gossip about this crazy award show! September 8, 2012 I am seeing my self in the rushing of wanting to buy a new camera! First to start, I do have a great camera, sometimes better than a SLR one but I have to say I can accomplish that very focused on you very blur background effect. September 5, 2012 I'm crazy about baroque print, it is inspired by the versace print and it combines the gold, navy blue and black all together. This trend is really on its high up and yes I did fell over this by buying a super cool sheer baroque blouse from Primark in London ! September 4, 2012 Another trend across the whole Europe, but I have to say I think it stand out more in Spain, The Statement Necklace. I love how simple outfits can be change with these crazy jewelry pieces! And the best, they are not expensive at all! (unless you choose a gold one or real jewelry!) September 2, 2012 It is a new month and that means 30 days of pure The Style Stash super cool entries! As you may already know I was travelling in Europe for a whole month and let me tell you It was the BEST experience EVER! I cannot believe my dream came true and got to see some incredible things in incredible parts of the world! My trip included London, Paris, Prague, Morocco and Spain.
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482 So.2d 428 (1985) Ford S. HAUSMAN, Etc., et al., Appellants, v. VTSI, INC., Etc., et al., Appellees. Nos. 84-650, 84-1339. District Court of Appeal of Florida, Fifth District. December 26, 1985. Rehearing Denied January 30, 1986. *429 Steven R. Bechtel, of Mateer, Harbert, Frey, Bechtel & Phalin, P.A., Orlando, and Gaylord A. Wood, Jr., Fort Lauderdale, for appellants Hausman and Earl Wood. Jim Smith, Atty. Gen., and Jospeh Mellichamp, III, Asst. Atty. Gen., Tallahassee, for appellant Dept. of Revenue. James M. Spoonhour, of Lowndes, Drosdick, Doster & Kantor, Orlando, and Elliott Messer and Robert S. Goldman, of Messer, Rhodes & Vickers, Tallahassee, for appellees Vistana, Inc., Vistana Resort Management, Inc., and Vistana Condominium Ass'n, Inc. UPCHURCH, Judge. Ford Hausman, the Orange County property appraiser, appeals from a final judgment which held that he improperly assessed time share developments on a per time share basis and that the assessed values exceeded the property's fair market value. Hausman also appeals from a separate order awarding VTSI $13,450.60 in costs. These appeals have been consolidated for our review. We affirm. The question submitted to the lower court concerned the correct method of formulating tax assessments of time share units created in certain condominium units by appellee VTSI, Inc., and managed by appellee Vistana Resort Management, Inc. In 1980, VTSI purchased ninety-eight rental units and associated recreational facilities. In July of 1980, VTSI commenced operating the property as a hotel under a hotel license. Sixty of these units were turned into condominiums and eventually became the time share properties at issue in this case. Each time share unit was divided into fifty-one unit weeks with one week set aside for annual maintenance. At the time the appraisals were done, the unit weeks which had not been conveyed as time share estates were still rented out as hotel rooms. Also, if the owners agreed, their time share units could be rented during the time they were unoccupied. The time share estates at issue here were created by individual deeds, each of which was recorded in the public records for the particular time unit conveyed. Since VTSI was conveying each time share estate by warranty deed, Hausman determined that the assessment for tax year 1982 would be based on the value of each of the three thousand sixty "unit weeks", instead of the actual condominiums. The assigned value appearing on the assessment notice for each condominium unit was derived by adding together actual or assumed sales prices for all the unit weeks which had been or could be conveyed in the condominium and then deducting thirty percent off of the total amount.[1] Of that thirty percent, five percent was a deduction for personalty included in the sales price. The other twenty-five percent deduction was not specifically supported by evidence at trial but was explained by the assistant property appraiser as an attempt to be fair. After examining Florida statutes applicable to tax year 1982, the court below determined that the time share estate or unit week was a fractional or partial interest in real estate. The trial court concluded that since there was no authority under existing law for the appraisal of unit weeks as partial interests and because Hausman did not appraise the actual condominium parcels, the assessments were void. The court also concluded that Hausman failed to adequately consider the criteria for determining just valuation set forth in section 193.011, Florida Statutes (1983). *430 First, we agree with the trial court that at the time Hausman assessed the time share developments he lacked the authority to separately appraise each unit week. Florida's constitution provides that "no tax shall be levied except in pursuance of law." Art. VII, § 1(a), Fla. Const. From this it follows that property taxes are "of a purely statutory nature which can be levied, assessed and collected only as provided by statute." State ex. rel. Seaboard Airline Railway Co. v. Gay, 160 Fla. 445, 35 So.2d 403 (1948). An assessment not authorized by statute is void. Lewis State Bank v. Bridges, 115 Fla. 784, 156 So. 144 (1934). At the time Hausman conducted these assessments, the Florida time share statutes provided: Notwithstanding other provisions of this chapter, either expressed or implied, to the contrary, it is the legislative intent that nothing herein be deemed to alter the existing procedure for the assessment and collection of ad valorem taxes on accommodations or facilities subject to a time-sharing plan. § 721.03(3), Fla. Stat. (1981). Since VTSI's time shares were created in condominium facilities, they should have been assessed accordingly. The Florida Condominium Act provides in part that "[e]ach condominium parcel shall be separately assessed for ad valorem taxes and special assessments as a single parcel." § 718.120(1), Fla. Stat. (1981). The existing statutes did not authorize Hausman to appraise the partial time share interests created in VTSI's condominium units. Due to this lack of authority, the trial court correctly concluded that Hausman's appraisal based on the value of the unit weeks was unlawful. Since Hausman did not proceed lawfully, his assessment is not protected by a presumption of correctness. Blake v. Xerox Corp., 447 So.2d 1348 (Fla. 1984). We note that even though this issue is one of first impression in Florida, it will have limited precedential value. Effective in 1983, the legislature provided for appraisal of time share developments as follows: Fee time-share real property shall be listed on the assessment rolls as a single entry for each time-share development. The assessed value of each time-share development shall be the value of the combined individual time-share periods or time-share estates contained therein. § 192.037(2), Fla. Stat. (1983). Tax statutes, however, operate only prospectively unless legislative intent to the contrary clearly appears. State v. Green, 101 So.2d 805 (Fla. 1958). We find no legislative intent to have section 192.037(2) operate retroactively and thus Hausman cannot rely on this statute to validate his assessment. Second, we conclude that the court below was also correct in finding the assessment unlawful since it exceeded the just value of the real property. The legislature has provided property assessors with statutory criteria to be considered when determining the just valuation or fair market value of real property § 193.011, Fla. Stat. (1981). The parties agreed that five percent of the gross sales price of an individual week was attributable to household furnishings and other items of personal property which should not be included in the assessment of real property. In addition, the trial court found that at least forty-five percent of the gross sales price consisted of the usual and reasonable sales costs and merchandising costs. The court also recognized that atypical and unconventional financing added another seven percent to the cost of the time share units. The court determined that, as a matter of law, the method used by Hausman failed to consider these costs which resulted in an assessment substantially in excess of just value. This conclusion is supported by section 193.011(8), Florida Statutes (1983), which states in relevant part: In arriving at just valuation as required under s. 4, Art. VII of the State Constitution, the property appraiser shall take into consideration the following factors: * * * * * * *431 (8) The net proceeds of the sale of property, as received by the seller, after deduction of all of the usual and reasonable fees and costs of the sale, including the costs and expenses of financing, and allowance for unconventional or atypical terms of financing arrangements... . An assessor's discretionary judgment as to the weight given to the criteria under section 193.011 will not be disturbed by a reviewing court provided each factor is first carefully considered. Atlantic Int'l. Investment Corp. v. Turner, 383 So.2d 919 (Fla. 5th DCA 1980); Lanier v. Walt Disney World, 316 So.2d 59 (Fla. 4th DCA 1975), cert. denied, 330 So.2d 19 (1976); Clearly, Hausman did not consider the statutory criteria. The conclusory twenty-five percent reduction by Hausman used to approximate fair market value is not a valid exercise of discretion. We suspect that if he had examined these extraneous costs, which add nothing to just value, the appraised value would approximate, if not equal, the value of the same condominium unit if owned by a single fee owner. Third, we find no error in the trial court's award of costs to VTSI. The other points raised by Hausman on appeal are without merit. Since we find no error, the judgment and the award of costs are AFFIRMED. COBB, C.J., and LEE, R.E., Associate Judge, concur. NOTES [1] The sixty condominium parcels involved in this litigation include thirty villas and thirty townhouses. The villas were assigned assessed values by Hausman from $151,059 to $151,063; the townhouses from $182,700 to $189,917. At trial. VTSI contended that the market value of a villa was $61,000 and a townhouse was $65,000.
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Insights Into Glucan Polysaccharide Recognition Using Glucooligosaccharide Microarrays With Oxime-Linked Neoglycolipid Probes. Glucans are polysaccharides of increasing biomedical interest because of their involvement in mechanisms of pathogen recognition, modulation of the immune system and anticancer, and health-promoting activities. Most of these biological activities occur through specific interactions with glucan-recognizing proteins. However, detailed molecular studies of glucan recognition remain a challenge mainly due to the inherent sequence heterogeneity and polydispersity of glucan polysaccharides, and associated difficulties in their purification and sequence characterization. It is thus ideal to have a series of sequence-defined glucooligosaccharides to represent the sequence diversity of glucan polysaccharides and to apply these to gain insight into glucan recognition processes. In this chapter, we describe the the methods for developing of oligosaccharide microarrays derived from a collection of glucans with different linkages based on the neoglycolipid (NGL) microarray system. The microscale oxime-ligation method has provided access in microarrays to over 150 sequence-defined glucooligosaccharides with different chain lengths, linkages, and branching patterns. We focus on the essential steps in the preparation of NGL-based glucooligosaccharide microarrays, which include (1) the depolymerization and purification methods to obtain oligosaccharide fractions of defined chain lengths; (2) a mass spectrometry-based method for linkage and sequence analysis of glucooligosaccharides; (3) improved procedures for preparation of oxime-linked NGLs from glucooligosaccharides for construction of microarrays; and (4) analyses of the recognition of these oligosaccharide sequences by various glucan-recognizing proteins: monoclonal antibodies, other proteins of the immune system such as Dectin-1 and DC-SIGN, and carbohydrate-binding modules of bacterial glycoside hydrolases.
{ "pile_set_name": "PubMed Abstracts" }
UPDATE: Following yesterday's Ant-Man casting buzz, Simon Pegg returned to Twitter with an update on the photo of him at Marvel. As it turns out -- perhaps not surprisingly -- he wasn't hinting at anything at all (via Coming Soon ): "FFS the Internet," Pegg tweeted , "all I did was point at the central character in my dear friend's next movie, because I'm excited for him."The original story follows below... Without jumping to any conclusions, Simon Pegg tweeted an image of himself earlier today possibly hinting that he's in Edgar Wright's Ant-Man movie.Why do we think this? Well, check out the photo below and see for yourself (and note Pegg's sly index finger pointing at the Ant-Man figure on the wall): Of course, an image like this doesn't prove much of anything. Indeed, this could just be Pegg having a bit of fun with his followers. On the other hand, Pegg's involvement wouldn't be totally unbelievable. After all, he's starred in three of Wright's four feature films. As for whether he'd play Ant-Man himself or another character, well, that's up for discussion. Nevertheless, this could be our first whiff of casting news on the film (if Pegg's coy smirk is anything to go on).Would you like to see Pegg as Edgar Wright's Ant-Man? Let us know in the comments! Loading Max Nicholson is a writer for IGN, and he desperately seeks your approval. Show him some love by following @Max_Nicholson on Twitter, or MaxNicholson on IGN.
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111 F.3d 127 Paul Rizzov.Paul Revere Insurance Group NO. 96-5408 United States Court of Appeals,Third Circuit. Mar 17, 1997 1 Appeal From: D.N.J. ,No.95cv01791 , 925 F.Supp. 302 2 Affirmed.
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--- abstract: 'We study the effects of an electron-electron effective interaction on the formation of entangled states in a two-qubit system, driven by the coupling of electronic states with vibrational modes. The system is composed by four quantum dots separated in pairs, each pair with one excess electron, which is able to tunnel between the dots. Also, the dots from each pair are coupled with different vibrational modes. The combined action of both, this effective interaction and the electronic tunneling explains not only features on the spectrum and the eigenstates of the Hamiltonian, but also the formation of electronic Bell states by exploiting the quantum dynamics of the system.' author: - 'F. M. Souza' - 'P. A. Oliveira' - 'L. Sanz' title: 'Quantum entanglement driven by electron-nanomechanical coupling' --- Introduction {#sec:intro} ============ For many years, the single-molecule electronics has being an outstanding issue due to its potentiality for future implementations of a cheaper and faster single-electron transistor [@xiang2016; @Ratner05]. There are already many successful examples of single-molecule devices that operate in the Coulomb-blockade regime, presenting transistor-like behavior [@park2002]. To increase further the functionality of a single-electron transistor, it is possible to couple nanomechanical and electronic degrees of freedom [@park2000; @steele20092; @lassagne2009]. It is well known that this kind of interaction plays a signifcant role, bringing a wealth of interesting effects, such as quantum-shuttles in quantum dots (QDs) systems [@gorelik1998; @armour2002; @donarini2005], local cooling [@kepesidis2016], phonon-assisted transport in molecular quantum dot junctions [@walter2013; @Sowa17], and Franck-Condon blockade [@leturcq2009]. Concerning this single electron systems, there is an emerging interest in the interplay between the electronic degrees of freedom, confined inside nanoparticles, and discrete vibrational modes. In particular, this problem has being analyzed considering two different contexts: carbon nanotubes quantum dots and vibrational modes of a cavity coupled with quantum dots. Carbon nanotubes (CNT) become one of the most successful new materials in front of their wide set of direct applications [@dresselhaus2001]. These include the implementation of ultrahigh tunable frequency resonators [@sazonova2004; @deng2016], nanoradios[@jensen2007], and ultrasensitive mass sensors [@chiu2008; @jensen2008]. Moreover, when operated as mechanical ressonators, nanotubes show high quality factors [@lassagne2009; @laird2012; @moser2016] being possible, for instance, to excite, detect and control specifical vibrational modes of a CNT with a current being injected from a scanning tunneling microscopy (STM) tip into a CNT [@leroy2004]. Additionally, it have been reported strong coupling regimes between single-electron tunneling and nanomechanical motion on a suspended nanotube, tuned via electrical gates [@benyamini2014]. Regarding applications in micro and nanoelectronics, carbon nanotubes presented balistic conduction [@laird2015] and Coulomb blockade effect in single and double nanotube based quantum dot devices [@steele2009]. Particularly, it was proposed a mechanically induced “two-qubit" quantum gate and the generation of entanglement between electronic spin states in CNT [@wang2015]. Also, phonons on CNTs showed its potentiality as “flying” qubits for electron spin communications over long distances [@deng2016]. Alternatively, regarding the second experimental context, the coupling between electronic degrees of freedom and vibrational modes can also be accomplished in piezoelectric phononic cavities, based on Bragg mirrors that confine a vibrational mode [@Chen15]. This coupling was experimentally demonstrated in transport measurements as a phonon assisted tunneling in a double quantum dot structure embedded in the cavity. The electron-vibrational mode coupling factor in this quantum dots system is ten times bigger if compared with couplings found on cavity quantum electrodynamics (CQED) and can be enhanced, on demand, by a factor of 20-500 of its regular value [@Chen15]. In front of the advantages cited above, both systems have a great potentiality as a solid state based quantum information processing. In the present work, we explore the properties of a Hamiltonian which describes two electrons on four quantum dots, considering a general model of coupling between electrons and vibrational modes, which applies to both experimental setups. Our proposal is based on charge-qubits, instead of spin, where the states of two qubits are defined depending of the occupation of the quantum dots. We are interested on the interplay between the electron-vibrational mode coupling and the tunneling of electrons between adjacent quantum dots. In Sec. \[sec:model\], by using the unitary transformation of Lang-Firsov, we demonstrate that both couplings are responsible for the apparition of an effective electron-electron interaction. Section \[sec:eigenproblem\] is devoted to the exploration of the signatures of this effective interaction and correlated phenomena on the spectrum and eigenstates of the model. Finally, in Sec. \[sec:dynamics\] , using our previous experience on quantum dynamics on coupled quantum dots [@Oliveira15; @souza2017], we study the formation of Bell states under specific conditions. Section \[sec:summary\] contains our final remarks. Model {#sec:model} ===== Consider a multipartite system with two main parts: the electronic subspace $\mathcal{D}$, consisting on four quantum dots, and the bosonic subspace $\mathcal{V}$, with two devices containing vibrational modes. Vibrational mode $1$ couples with electronic levels of the dots $1$ and $3$, while vibrational mode $2$ couples with dots $2$ and $4$. Tunneling is allowed between dots $1$ ($3$) and $2$ ($4$) so the pair $1-2$ ($3-4$) can be described as a qubit. A possible experimental setup is illustrated in Fig. \[fig:system\], where the bosonic devices are carbon nanotubes. Electronic levels on the quantum dots can be populated by using sources and drains, with additional gates to control the process of tunneling between the dots [@Shinkai07]. The electron-vibrational interaction does not change the electronic population, although creates or destroys vibrational excitations in both devices. Although electrons in different qubits could interact, for instance, by Coulomb interaction [@Hayashi03], we assume this interaction is weak enough to be ignored. ![A possible experimental setup of the system of interest: quantum dots $1$ and $3$ ($2$ and $4$) are coupled with the vibrational (bosonic) mode $1$ ($2$) on carbon nanotubes. Also, the dots 1 (3) and 2 (4) are coupled to each other by tunneling, encoding a qubit.[]{data-label="fig:system"}](figure1){width="0.5\linewidth"} The Hamiltonian that describes the two charged qubits and vibrational modes is given by $$\label{eq:Hgeneral} H=H_{\mathcal{D}} \otimes I_{\mathcal{V}}+I_{\mathcal{D}} \otimes H_{\mathcal{V}}+V_{\mathcal{DV}}.$$ Here $H_{\mathcal{D}}$ and $H_{\mathcal{V}}$ are the free Hamiltonians of the quantum dots and vibrational modes subspaces, respectively, $V_{\mathcal{DV}}$ is the dots-vibrational modes coupling and $I_{\mathcal{D(V)}}$ is the identity matrix for quantum dots ($\mathcal{D}$) or the vibrational modes ($\mathcal{V}$) subspaces. While each pair of dots is a $2$-dimensional subspace, the vibrational mode spans on an infinite dimension subspace $N_v$, where $N_{v}\rightarrow \infty$ for $v$-th subspace ($v=1,2$). The elements of the computational basis have the general form ${\mathinner{|{n_1 n_2 n_3 n_4}\rangle}}_{\mathcal{D}}\otimes{\mathinner{|{N_1 N_2}\rangle}}_{\mathcal{V}}={\mathinner{|{n_1 n_2 n_3 n_4; N_1 N_2}\rangle}}$ with the first four indexes indicating the occupation of the specific dot ($0$-empty and $1$-occupied) and the last two being the population of the vibrational modes. One example is the state ${\mathinner{|{1010,00}\rangle}}$ which represents the situation where dots 1 and 3 contains a single electron each and there is no excitations in the vibrational modes. We proceed to write each term of the Hamiltonian (\[eq:Hgeneral\]). The free Hamiltonian for the four quantum dots subsystem is written as ($\hbar=1$): $$\begin{aligned} \label{eq:Hmol} H_{\mathcal{D}}&=&\left[\sum_{i=1,2}\varepsilon_i N^{\mathcal{D}}_i+\Delta_{12}\left(S_1^\dagger S_2+S_2^\dagger S_1\right)\right]\otimes I^{\otimes 2}\\ &&+ I^{\otimes 2}\otimes\left[\sum_{j=3,4}\varepsilon_j N^{\mathcal{D}}_j+\Delta_{34}\left(S_3^\dagger S_4+S_4^\dagger S_3\right)\right],\nonumber\end{aligned}$$ where $S_{i(j)}^\dagger$ $\left[S_{i(j)}\right]$ are the creation (annihilation) operators for the $i(j)$-th quantum dot and $N^{\mathcal{D}}_{i(j)}=S_{i(j)}^\dagger S_{i(j)}$ ($i=1,2$ while $j=3,4$). The parameters $\varepsilon_{i(j)}$ are the electronic levels for each dot while $\Delta_{12(34)}$ describes the tunneling coupling. If we consider a single vibrational mode per bosonic subsystem, the free Hamiltonian $ H_{\mathcal{V}}$ becomes $$H_{\mathcal{V}} = \omega_1 B_1^\dagger B_1 \otimes I^{\otimes N_2} + I^{\otimes N_1} \otimes \omega_{2} B^\dagger_2 B_2,$$ where $\omega_{1(2)}$ is the energy of the corresponding vibrational mode. Here $B^{\dagger}_{v}$ ($B_v$) creates (annihilates) an excitation in a $v$-th vibrational mode subspace. Now we focus on the term $V_{\mathcal{DV}}$, which provides the electron-vibrational mode coupling. This coupling happens when a single electron on dot $i$ interacts with the vibrational subsystem thus creating or annihilating one excitation in the corresponding vibrational mode. We consider that the electron-vibrational mode coupling is the same for both bosonic modes, with a strength given by $g_v$. The term $V_{\mathcal{DP}}$ is written as $$\begin{aligned} \label{eq:Vmp} &&V_{\mathcal{DV}}=g_1\left(N^{\mathcal{D}}_1\otimes I^{\otimes 2}+I^{\otimes 2}\otimes N^{\mathcal{D}}_3\right) \otimes \left({B}_{1}^\dagger+{B}_{1}\right)\otimes I^{\otimes N_2}\nonumber\\ &&\;\;+g_2\left(N^{\mathcal{D}}_2\otimes I^{\otimes 2}+I^{\otimes 2}\otimes N^{\mathcal{D}}_4\right) \otimes I^{\otimes N_1}\otimes \left({B}_{2}^\dagger+{B}_{2}\right).\end{aligned}$$ As pointed out by Sowa *et. al* [@Sowa17], there can be a phase difference in the coupling parameters $g_v$ given by where $\phi_v=\mathbf{k}_v \cdot \mathbf{d}_v$, with $\mathbf{k}_v$ being the wavevector of the $v$ vibrational mode and $\mathbf{d}_v$ the distance between dots coupled with this specific mode. Here, we assume that the distance between dots inside a molecule is smaller than the vibrational wavelength so the phase difference can be ignored and $g_1=g_2=g$. In order to analyze the action of electron-vibrational mode and tunneling couplings, we apply the Lang-Firsov [@Mahanbook] unitary transformation over the Hamiltonian in Eq.(\[eq:Hgeneral\]) calculating $\bar{H} = e^{S} H e^{-S}$, where $$\begin{aligned} &&S=\alpha_1 \left(N^{\mathcal{D}}_1\otimes I^{\otimes 2}+I^{\otimes 2}\otimes N^{\mathcal{D}}_3\right) \otimes \left(B_1^\dagger - B_1\right)\otimes I^{\otimes N_2} \nonumber \\ &&+\alpha_2 \left(N^{\mathcal{D}}_2\otimes I^{\otimes 2}+I^{\otimes 2}\otimes N^{\mathcal{D}}_4\right) \otimes I^{\otimes N_1}\otimes \left(B_2^\dagger - B_2\right),\end{aligned}$$ with $\alpha_v=\frac{g}{\omega_v}$. This calculation results on a new form for the Hamiltonian written as $$\label{eq:Htrans} \bar{H}=\left(\bar{H}_{\mathcal{D}}+V^{C}_{\mathrm{eff}}\right)\otimes I_{\mathcal{V}}+I_{\mathcal{D}}\otimes H_{\mathcal{V}}+\Delta^T_{\mathcal{DV}},$$ where $$\label{eq:Hmtrans} \bar{H}_{\mathcal{D}}=\sum_{i=1,2}\widetilde{\varepsilon}_i N^{\mathcal{D}}_i\otimes I^{\otimes 2}+I^{\otimes 2}\otimes \sum_{j=3,4}\widetilde{\varepsilon}_j N^{\mathcal{D}}_j,$$ is the transformed Hamiltonian for the dots with $\widetilde{\varepsilon}_{i(j)}$ being an energy level shifted due to the action of the electron-vibrational mode coupling. Specifically, $\widetilde{\varepsilon}_{1(3)}=\varepsilon_{1(3)}-\alpha_1^2\omega_1$ while $\widetilde{\varepsilon}_{2(4)}=\varepsilon_{2(4)}-\alpha_2^2\omega_2$. Apart from this dressed uncoupled electronic Hamiltonian, we want to highlight two new terms on Eq.(\[eq:Htrans\]). The first one can be seen as an effective electron-electron interaction $$\label{eq:Heeeff} V^{C}_{\mathrm{eff}}=-2\alpha_1^2\omega_1N^{\mathcal{D}}_1\otimes N^{\mathcal{D}}_3-2\alpha_2^2\omega_2N^{\mathcal{D}}_2\otimes N^{\mathcal{D}}_4,$$ which cooperates with tunneling in order to generate maximally entangled states. The last term $$\begin{aligned} \label{eq:Hvmvmeff} &&\Delta^T_{\mathcal{DV}}=\left[\left(\Delta_{12} S_1^\dagger S_2\right)\otimes I^{\otimes 2} + I^{\otimes 2}\otimes\left(\Delta_{34}S_3^\dagger S_4\right)\right]\otimes X_{12}\nonumber\\ &&\;\;+\left[\left(\Delta_{12} S_1 S_2^\dagger\right)\otimes I^{\otimes 2} + I^{\otimes 2}\otimes \left(\Delta_{43} S_3 S_4^\dagger\right)\right]\otimes X^{\dagger}_{12},\end{aligned}$$ describes an effective interaction between the two vibrational modes considered on our problem. Here $X_{12}=e^{-\alpha_1\left(B_1 - B^\dagger_1\right)}\otimes e^{-\alpha_2\left(B^\dagger_2- B_2\right)}=D_1(\alpha_1)\otimes D_2(\alpha_2)$, being a tensorial product of displacement operators for the quantum harmonic oscillator [@Scullybook]. The new transformed Hamiltonian, Eq. (\[eq:Htrans\]) and its terms Eqs. (\[eq:Hmtrans\])-(\[eq:Hvmvmeff\]), highlights important effects of the couplings considered on this particular physical system. The first is a shift on the value of the electronic levels which depends on both, the coupling parameter $g$ and $\omega_v$. The second is the effective electron-electron interaction which couples the electrons from different qubits, which is mediated by the electron-vibrational mode coupling. As we discuss below, the effective electron-electron interaction, together with electronic tunneling, is behind the apparition of entangled eigenstates of the full Hamiltonian and the subsequent possibility of generation, by quantum dynamics, of Bell states. Spectral analysis {#sec:eigenproblem} ================= We proceed to explore the characteristics of energy spectrum and eigenstates of the Hamiltonian in Eq. (\[eq:Hgeneral\]). Along with the study of energy spectrum, we are interested on the entanglement properties of the eigenstates. It is well known that Coulomb interaction is behind the formation of entangled states in coupled quantum dots molecule [@Fujisawa11; @Oliveira15], once this interaction couples two single electrons, making viable the encoding of two qubits. In the present problem, we expected the apparition of signatures of the effective electron-electron interaction on the entanglement degree of the eigenstates. To perform our numerical analysis, both basis associated with the vibrational modes are truncated at $N_1=N_2=13$, although both basis for vibrational modes have infinite dimension. This number of computational states is enough to guarantee the accuracy of the calculation of lower energies and eigenstates. To analyze the formation of entangled states, we first build up a density matrix for each eigenstate in the complete basis $\hat{\rho}_l={\mathinner{|{\psi_l}\rangle}}{\mathinner{\langle{\psi_l}|}}$, where ${\mathinner{|{\psi_l}\rangle}}$ is the $l$th eigenstate of Hamiltonian (\[eq:Hgeneral\]). The second step is the calculation of the reduced $4\times 4$ density matrix for the two qubits, by tracing out the degrees of freedom of the vibrational modes so $\hat{\rho}_{\mathcal{D},l}=\mathrm{Tr}_{\mathcal{V}}[\hat{\rho}_l]$. Then, the concurrence, defined by Wootters [@Wootters98], is used as a measurement of entanglement. ![The first $24$ eigenvalues of Hamiltonian (\[eq:Hgeneral\]) varying the detuning $\delta=\varepsilon_1-\varepsilon_2$ considering $\varepsilon_3=\varepsilon_4=0$ and $g=0.5\omega$ and $\Delta_{12}=\Delta_{34}=5\times 10^{-2}\omega$. The energy increases from panel (c) to panel (a) showing the first four states (black solid lines and squares), the next eight states (red dashed lines and circles), and the following twelve states (blue dotted lines and triangles).[]{data-label="fig:eigenproblem"}](figure2){width="0.7\linewidth"} An auxiliary Hermitian operator [@Hill97] $R_l$ is defined as $R_l=\sqrt{\sqrt{\hat{\rho}_{\mathcal{D},l}}\;\widetilde{\hat{\rho}_{\mathcal{D},l}}\sqrt{\hat{\rho}_{\mathcal{D},l}}}$, where $\widetilde{\hat{\rho}_{\mathcal{D},l}}=(\sigma_y \otimes \sigma_y)\hat{\rho}^\star_{\mathcal{D},l}(\sigma_y \otimes \sigma_y)$, is the spin-flipped matrix with $\hat{\rho}^\star_{\mathcal{D},l}$ being the complex conjugate of $\hat{\rho}_{\mathcal{D},l}$. The concurrence is obtained once $C=\mathrm{max}(0,\lambda_1-\lambda_2-\lambda_3-\lambda_4)$ where $\lambda_k$ ($k=1...4$) are the eigenvalues of the operator $R_l$ in decreasing order. Figures \[fig:eigenproblem\](a) to (c) show the behavior of the first $24$ eigenvalues of the Hamiltonian as a function of detuning $\delta=\varepsilon_1-\varepsilon_2$, considering $\varepsilon_3=\varepsilon_4=0$, a resonance condition for the dots 3 and 4. We consider that both vibrational modes have the same frequency value so $\omega_1=\omega_2=\omega$. The coupling parameters are defined in terms of the frequency $\omega$ being $g=\omega/2$ the electron-vibrational mode coupling and $\Delta_{12}=\Delta_{34}=\Delta/2=\omega/20$ the tunneling rates. The energy spectrum shows the emergence of branches, spanned on an energy interval $\Delta E=\omega$, each with an increasing number of inner states as energy increases: while the first branch (solid black lines) has the four states shown in Fig. \[fig:eigenproblem\] (c) including the ground level, the second branch (dashed red lines) has eight states, as seen in Fig. \[fig:eigenproblem\] (b). The subsequent branch (dotted blue lines) contains twelve eigenstates, shown in Fig. \[fig:eigenproblem\] (a). The branches share some common features. The first is the appearance of anticrossings at $\delta=\pm 0.5$, due to first order transitions that switch only one electron per time, e.g., ${\mathinner{|{1001}\rangle}}_{\mathcal{D}}$ $\leftrightarrow$ ${\mathinner{|{1010}\rangle}}_{\mathcal{D}}$. The second is a little anticrossing arising at $\delta=0$, related to higher order transition processes. For instance, two electrons can start at dots 1 and 4 (state ${\mathinner{|{1001}\rangle}}_{\mathcal{D}}$) ending at dots 2 and 3 (state ${\mathinner{|{0110}\rangle}}_{\mathcal{D}}$)[^1]. For each branch, the inner states have interesting properties concerning entanglement as can be seen from Fig. \[fig:eigenconcurrence\] (a) to (c), where we show the behavior of concurrence as a function of detuning $\delta$. Comparing our findings with results on a previous work [@Oliveira15], some similarities let us to conclude that the effective electron-electron coupling is behind the apparition of dressed Bell states as eigenstates. A signature of this fact is the increasing value of maximally entangled states at $\delta=0$, as shown by the scattered plots: there is one on the black branch \[filled squares on Fig. \[fig:eigenconcurrence\] (a) and Fig. \[fig:eigenproblem\] (c)\], two inside the red branch \[filled and open circles on Fig. \[fig:eigenconcurrence\] (b) and Fig. \[fig:eigenproblem\] (b)\] and three on the blue branch \[filled and open triangles point up and down on Fig. \[fig:eigenconcurrence\] (c) and Fig. \[fig:eigenproblem\] (a)\]. Additionally, some satellite peaks at $\delta=\pm 0.5$ are observed, having a lower value of concurrence. While those secondary peaks are related to first order processes, the sharp peak at zero energy arises from second and higher order transitions. Those features of the eigenstates can be explored theoretically through a straightforward calculation (see Appendix \[ap:dressedbell\] for details) which consists on perform a basis transformation going from the electronic computational four-dimensional basis given by $\left\{{\mathinner{|{1010}\rangle}},{\mathinner{|{0101}\rangle}},{\mathinner{|{1001}\rangle}},{\mathinner{|{0110}\rangle}}\right\}_{\mathcal{D}}$ to an electronic Bell basis ordered as $\{{\mathinner{|{\Psi_{-}}\rangle}},{\mathinner{|{\Phi_{-}}\rangle}},{\mathinner{|{\Psi_{+}}\rangle}},{\mathinner{|{\Phi_{+}}\rangle}}\}_{\mathcal{D}}$, where ${\mathinner{|{\Psi_{\pm}}\rangle}}_{\mathcal{D}}=\frac{1}{\sqrt{2}}\left({\mathinner{|{1001}\rangle}}\pm{\mathinner{|{0110}\rangle}}\right)$ and ${\mathinner{|{\Phi_{\pm}}\rangle}}_{\mathcal{D}}=\frac{1}{\sqrt{2}}\left({\mathinner{|{1010}\rangle}}\pm{\mathinner{|{0101}\rangle}}\right)$. For the specific case of equal tunneling rates and $\delta=0$, the calculation shows that the terms of the Hamiltonian regarding ${\mathinner{|{\Psi_{-}}\rangle}}_{\mathcal{D}}$ can be written as a tensorial product given by $$\begin{aligned} \label{eq:HtermsPsi-} H_{\mathrm{with }{\mathinner{|{\Psi_-}\rangle}}}&=&({\mathinner{|{\Psi_-}\rangle}}{\mathinner{\langle{\Psi_-}|}})_{\mathcal{D}}\otimes\big\{\big[\mathbf{{\mathinner{|{00}\rangle}}_{\mathcal{V}}}\big(E_{00}{\mathinner{\langle{00}|}}_{\mathcal{V}}+g{\mathinner{\langle{10}|}}_{\mathcal{V}} +g{\mathinner{\langle{01}|}}_{\mathcal{V}}\big)\big] +\big[\mathbf{{\mathinner{|{01}\rangle}}_{\mathcal{V}}}\big(E_{01}{\mathinner{\langle{01}|}}_{\mathcal{V}}+g{\mathinner{\langle{11}|}}_{\mathcal{V}}+\sqrt{2}g{\mathinner{\langle{02}|}}_{\mathcal{V}}\big)\nonumber\\ &&+\mathbf{{\mathinner{|{10}\rangle}}_{\mathcal{V}}}\big(E_{10}{\mathinner{\langle{10}|}}_{\mathcal{V}}+g{\mathinner{\langle{11}|}}_{\mathcal{V}}+\sqrt{2}g{\mathinner{\langle{20}|}}_{\mathcal{V}}\big)\big] +\big[\mathbf{{\mathinner{|{11}\rangle}}_{\mathcal{V}}}\big(E_{11}{\mathinner{\langle{11}|}}_{\mathcal{V}}+\sqrt{2}g{\mathinner{\langle{21}|}}_{\mathcal{V}}+\sqrt{2}g{\mathinner{\langle{12}|}}_{\mathcal{V}}\big)\nonumber\\ &&+\mathbf{{\mathinner{|{02}\rangle}}_{\mathcal{V}}}\big(E_{02}{\mathinner{\langle{02}|}}_{\mathcal{V}}+...\big)+\mathbf{{\mathinner{|{20}\rangle}}_{\mathcal{V}}}\big(E_{20}{\mathinner{\langle{20}|}}_{\mathcal{V}}+...\big)\big]+...+\mathrm{h.c.}\big\}.\end{aligned}$$ Other terms on Hamiltonian cannot be written as a tensorial product of the form ${\mathinner{|{\psi}\rangle}}{\mathinner{\langle{\psi}|}}_{\mathcal{D}}\otimes\sum \alpha{\mathinner{|{N'_1N'_2}\rangle}}_{\mathcal{V}}{\mathinner{\langle{N_1N_2}|}}$: terms with ${\mathinner{|{\Psi_+}\rangle}}$ are coupled with ${\mathinner{|{\Phi_+}\rangle}}$ by electron-vibrational mode interaction, while elements ${\mathinner{|{\Phi_{+}}\rangle}}$ and ${\mathinner{|{\Phi_{-}}\rangle}}$ are also coupled to each other by tunneling (see Appendix \[ap:dressedbell\]). In the Eq. \[eq:HtermsPsi-\], we use bold type and the square brackets, $[\;]$, to emphasize the new dressed basis $\left\{{\mathinner{|{\psi_{\mathrm{Bell}},N_1N_2}\rangle}}\right\}$. The number of eigenstates per branch and the number of maximally entangled molecular states at $\delta=0$ are linked with the dimension of original subspaces with the same value of the sum $N_1+N_2$, as can be seen from Eq.(\[eq:HmatrixBell\]). Although these subspaces are coupled with each other, each branch can be seen as dressed Bell states, with an energy increasing as $N=N_1+N_2$ grows. ![Behavior of the concurrence, $C$, for the electronic part of the first $24$ eigenstates. We use the same physical parameters and the same color, lines and symbol conventions that in Fig. \[fig:eigenproblem\]. Note that the condition $\delta=0$ is related with the apparition of electronic maximally entangled states, with $C=1$.[]{data-label="fig:eigenconcurrence"}](figure3){width="0.8\linewidth"} Dynamical generation of electronic Bell states {#sec:dynamics} ============================================== After studying the properties of the eigenstates of the model, it is worthwhile to explore the preparation of electronic entangled states by quantum dynamics. We again use a numerical approach, considering the general Hamiltonian (\[eq:Hgeneral\]), to simulate the quantum dynamics through the evolution of the density matrix $\rho(t)={\mathinner{|{\psi(t)}\rangle}}{\mathinner{\langle{\psi(t)}|}}$. Tracing out the vibrational degrees of freedom, it results on the electronic reduced density matrix $$\rho_{\mathcal{D}}(t)=\mathrm{Tr}_{\mathcal{V}}[\rho(t)],$$ used to explore the behavior of the electronic part of the system through the calculation of physical properties as populations, fidelity, and concurrence. Initially, we perform a test to check the precision of our calculation together with our findings about the special character of the electronic Bell state ${\mathinner{|{\Psi_-}\rangle}}_{\mathcal{D}}$ as discussed on Sec. \[sec:eigenproblem\]. We consider $\Delta_{12}=\Delta_{34}$ (equal tunneling couplings), detuning $\delta=0$ and the initial state given by $$\rho(0)= \left({\mathinner{|{\Psi_-}\rangle}}{\mathinner{\langle{\Psi_-}|}}\right)_{\mathcal{D}}\otimes{\mathinner{|{00}\rangle}}_{\mathcal{V}}{\mathinner{\langle{00}|}}.$$ After the calculation of $\rho(t)$ and the $ \rho_{\mathcal{D}}(t)$, we obtain the fidelity of the evolved electronic state with this initial state being $\mathcal{F}(t)=\mathrm{Tr}_{\mathcal{D}}[\rho_{\mathcal{D}}(t)\rho_{\mathcal{D}}(0)]$. Our results shown that the fidelity remains constant with value $\mathcal{F}(t)=1$, showing that, from the electronic point of view, any initial state with $\left({\mathinner{|{\Psi_-}\rangle}}{\mathinner{\langle{\Psi_-}|}}\right)_{\mathcal{D}}$ as the electronic part, acts as a stationary state. In order to explore the generation of electronic entangled states, we now assume the system is being prepared as $$\rho_0={\mathinner{|{1001}\rangle}}_{\mathcal{D}}{\mathinner{\langle{1001}|}}\otimes{\mathinner{|{00}\rangle}}_{\mathcal{V}}{\mathinner{\langle{00}|}},$$ which is an experimentally feasible initial state, once experimental setups include a set of sources and drains attached to the quantum dots, that can inject electrons. We consider the condition of $\delta=0$ and the same choices of physical parameters used in Figs. \[fig:eigenproblem\]-\[fig:eigenconcurrence\]. In Fig. \[fig:popconcfid\] (a), we show the evolution of the populations of electronic states $\left\{{\mathinner{|{1001}\rangle}},{\mathinner{|{0110}\rangle}},{\mathinner{|{0101}\rangle}},{\mathinner{|{1010}\rangle}}\right\}$. At initial times, the values is given by $P_{1001}=1$ (black line), $P_{0110}=0$ (red line), and $P_{0101}=P_{1010}=0$ (green line) in agreement with the initial condition. As time evolves, $P_{1001}$ and $P_{0110}$ oscillates out of phase between zero (non-occupied) and $1$ (occupied), while $P_{1010}$ and $P_{0101}$ remain oscillating close to zero. This is a promising sign toward the formation of a state similar with ${\mathinner{|{\Psi_{\pm}}\rangle}}$ states on Bell basis, once the population of states ${\mathinner{|{1001}\rangle}}$ and ${\mathinner{|{0110}\rangle}}$ is $0.5$ at $\omega t = 300$. We also plot the concurrence, solid blue line in Fig. \[fig:popconcfid\] (a), which reaches the value $C\approx 1$ when $P_{1001}=P_{0110}$, indicating the actual formation of a maximally entangled electronic state. A similar effect was originally reported in Ref.  in the context of two-qubits coupled via Coulomb interaction. In the present case, this evolution shows that the effective electron-electron interaction mediated by the vibrational modes turns out to be responsible for the coupling between the qubits. In order to give a closer look at the entangled states created by quantum dynamics, we compute the fidelity compared with a pre-defined target Bell state, $\mathcal{F}(t)=\mathrm{Tr}_{\mathcal{D}}[\rho_{\mathcal{D}}(t)\rho_{\mathcal{D}}^{\mathrm{tar}}]$. For this calculation, we use as target state the electronic density matrix $\rho_{\mathcal{D}}^{\mathrm{tar}}={\mathinner{|{\Psi(\varphi)}\rangle}}_{\mathcal{D}}{\mathinner{\langle{\Psi(\varphi)}|}}$, where $${\mathinner{|{\Psi(\varphi)}\rangle}}_{\mathcal{D}} = \frac{1}{\sqrt{2}} [|1001\rangle_{\mathcal{D}}+e^{i\varphi} |0110\rangle_{\mathcal{D}}], \label{eq:psi_fase}$$ where $\varphi$ is a relative phase between the state. Note that if $\varphi=0$ ($\varphi=\pi$) then ${\mathinner{|{\Psi(0)}\rangle}}\equiv{\mathinner{|{\Psi_+}\rangle}}$ (${\mathinner{|{\Psi(\pi)}\rangle}}\equiv{\mathinner{|{\Psi_-}\rangle}}$). In Fig. \[fig:popconcfid\] (b) we show how $\mathcal{F}$ evolves with time for different values of $\varphi$. For $\varphi=0$ the fidelity remains stationary, with a value of $0.5$, while for $\varphi=\pi$, the fidelity shows small oscillations around those value. By setting the $\varphi=\pm \pi/2$, we fulfill our goal of find the correct relative phase of the dynamically created entangled state, once the fidelity for both cases oscillates out of phase between $0$ and $1$. The concurrence maximum values being $1$ let us to conclude that the electronic entangled state alternates between ${\mathinner{|{\Psi(\pi/2)}\rangle}}_{\mathcal{D}}$, at $\omega t=300$ and ${\mathinner{|{\Psi(-\pi/2)}\rangle}}_{\mathcal{D}}$, at $\omega t=600$. This means that the dynamics shows not only the ability of create Bell states related with ${\mathinner{|{\Psi_{\pm}}\rangle}}_{\mathcal{D}}$ but also an additional ingredient, which is the imprint of a relative phase $\varphi$. Finally in Fig. \[fig:concvsg\] we explore the effect of the electron-vibrational mode coupling parameter, $g$, on the formation of the electronic entangled states, going into a weak coupling regime. We first notice that, by decreasing the value of $g$, we still obtain values of $C\approx 1$ at some evolved time. Second feature is that it becomes clear that the period of oscillations of the formation of the electronic Bell states is governed by this coupling parameter. This shows that the formation of electronic maximally entangled states is a quite robust effect, which can become accessible in a wide range of experimental devices, even for weak values of electron-vibrational mode coupling. ![Dynamics of populations, concurrence, and fidelity of electrons in quantum dots considering $\delta=\varepsilon_1-\varepsilon_2=0$, $\varepsilon_3=\varepsilon_4=0$, $g=0.5\omega$ and $\Delta_{12}=\Delta_{34}=5\times 10^{-2}\omega$. (a) Populations $P_{1001}$ (black line), $P_{0110}$ (red line) and $P_{1010}=P_{0101}$ (green line), and concurrence (blue line) as functions of $\omega t$. (b) Dynamics of the fidelity between the evolved state and the target state given by Eq. (\[eq:psi\_fase\]), for different values of relative phase $\varphi$: $\varphi=-\pi/2$ (blue line), $\varphi=0$ (green line), $\varphi=+\pi/2$ (black line), and $\varphi=\pi$ (red line).[]{data-label="fig:popconcfid"}](figure4){width="1\linewidth"} ![Concurrence as a function of $\omega t$ for the same values of $\delta$, $\varepsilon_3$, $\varepsilon_4$, $\Delta_{12}$ $\Delta_{34}$ used in Fig. \[fig:popconcfid\], considering several values of electron-vibrational mode coupling $g$: $g=0.5\omega$ (black line), $g=0.1\omega$ (red line), and $g=0.05\omega$ (blue line).[]{data-label="fig:concvsg"}](figure5){width="1\linewidth"} Conclusion {#sec:summary} ========== In this work, we analyze a general model which describes a system where two electrons inside a set of four quantum dots interact with vibrational modes, shown in Fig. \[fig:system\]. The goal is to explore the interplay between tunneling, detuning of the electronic levels inside the quantum dots, and the electron-vibrational mode coupling. The model can describe several experimental scenarios, including electrons inside carbon nanotubes quantum dots or the coupling between electrons and an acoustic cavity. Our findings include the study of the characteristics of the spectrum, the eigenstates, and the quantum dynamics of the system, focusing on the search of electronic maximally entangled states. We find that the electron-vibrational mode coupling is responsible for the apparition of dressed electronic Bell states. Concerning the dynamics, the generation of those entangled states is possible for a wide range of physical parameters. Acknowledgments =============== This work was supported by CNPq (grant 307464/2015-6), and the Brazilian National Institute of Science and Technology of Quantum Information (INCT-IQ). The matrix representation of hamiltonian on the dressed Bell basis {#ap:dressedbell} ================================================================== The entanglement behavior of the system of interest can be explored by writing down its Hamiltonian in terms of the electronic Bell states. Let us calculate the representation of the original Hamiltonian (\[eq:Hgeneral\]) as a matrix written in the dressed basis ${\mathinner{|{\psi_{\mathrm{Bell}},N_1N_2}\rangle}}$, where the electronic part is ordered following $${\mathinner{|{\psi_{\mathrm{Bell}}}\rangle}}_{\mathcal{D}}=\{{\mathinner{|{\Psi_{-}}\rangle}},{\mathinner{|{\Phi_{-}}\rangle}},{\mathinner{|{\Psi_{+}}\rangle}},{\mathinner{|{\Phi_{+}}\rangle}}\}_{\mathcal{D}},$$ where ${\mathinner{|{\Psi_{\pm}}\rangle}}_{\mathcal{D}}=\frac{1}{\sqrt{2}}\left({\mathinner{|{1001}\rangle}}\pm{\mathinner{|{0110}\rangle}}\right)$ and ${\mathinner{|{\Phi_{\pm}}\rangle}}_{\mathcal{D}}=\frac{1}{\sqrt{2}}\left({\mathinner{|{1010}\rangle}}\pm{\mathinner{|{0101}\rangle}}\right)$. We choose to keep together the states with the same number of total excitations $N=N_1+N_2$. This choice remarks the fact that the basis for the whole system has an internal structure of coupled subspaces. For each value of $N$, there is an associated family of subspaces $\mathcal{S}_{\mathrm{B},(N_1N_2)}$: $N=0$ has only the subspace $\mathcal{S}_{\mathrm{B},(00)}$ with four inner states, $N=1$ has two subspaces being $\mathcal{S}_{\mathrm{B},(10)}$ and $\mathcal{S}_{\mathrm{B},(01)}$ (eight inner states), $N=3$ has twelve inner states associated with $\mathcal{S}_{\mathrm{B},(11)}$, $\mathcal{S}_{\mathrm{B},(20)}$, and $\mathcal{S}_{\mathrm{B},(02)}$, and so on. Let us write the matrix representation of the Hamiltonian for this first six $4$D subspaces $\mathcal{S}_{\mathrm{B},(N_1N_2)}$, ordered as $\{\mathcal{S}_{B,(00)},\mathcal{S}_{B,(01)},\mathcal{S}_{B,(10)},\mathcal{S}_{B,(11)},\mathcal{S}_{B,(02)},\mathcal{S}_{B,(20)}\}$: $$\label{eq:HmatrixBell} H=\left( \begin{array}{c|cc|ccc} B_{00} & G_{2} & G_{1} & 0 & 0 & 0 \\ \hline G_{2} & B_{01} & 0 & G_{1} & \sqrt{2}G_{2} & 0 \\ G_{1} & 0 & B_{10} & G_{2} & 0 & \sqrt{2}G_{1} \\ \hline 0 & G_{1} & G_{2} & B_{11} & 0 & 0 \\ 0 & \sqrt{2}G_{2} & 0 & 0 & B_{02} & 0 \\ 0 & 0 & \sqrt{2}G_{1} & 0 & 0 & B_{02} \\ \end{array} \right).$$ using the order ${\mathinner{|{\Psi_{-},N_1N_2}\rangle}}$, ${\mathinner{|{\Phi_{-},N_1N_2}\rangle}}$, ${\mathinner{|{\Psi_{+},N_1N_2}\rangle}}$, and ${\mathinner{|{\Phi_{+},N_1N_2}\rangle}}$, the $4$D matrices $B_{N_1N_2}$ and $ G_{v}$ are defined as $$\begin{aligned} \label{eq:4DBellmatrix} B_{N_1N_2}&=&\left( \begin{array}{cccc} E_{N_1N_2} & \Delta_- & \delta_-/2 & 0 \\ \Delta_- & E_{N_1N_2} & 0 & \delta_+/2 \\ \delta_-/2 & 0 & E_{N_1N_2} & \Delta_+ \\ 0 & \delta_+/2 & \Delta_+ & E_{N_1N_2} \\ \end{array} \right),\end{aligned}$$ and $$\label{eq:4DGmatrix} G_{v}=\left( \begin{array}{cccc} g_{v} & 0 & 0 & 0 \\ 0 & g_{v}/2 & 0 & (-1)^{(v-1)}g_{v}/2 \\ 0 & 0 & g_{v} & 0 \\ 0 & (-1)^{(v-1)}g_{v}/2 & 0 & g_{v}/2 \\ \end{array} \right),$$ where $E_{N_1N_2}=\sum_{i=1,2}\sum_{j=3,4}\sum_{v=1,2}\left(\varepsilon_i+\varepsilon_j+\omega_v\right)$ are the energy of the state ${\mathinner{|{\psi_{\mathrm{Bell}},N_1N_2}\rangle}}$, the tunneling couplings are defined as $\Delta_{\pm}=\Delta_{34}\pm\Delta_{12}$ and $\delta_{\pm}=\delta_{12}\pm\delta_{34}$, with $\delta_{lm}=\varepsilon_l-\varepsilon_m$ ($l=1,3$ and $m=2,4$). The first matrix resembles the rotated matrix on Bell basis, whose properties discussed in details on Ref. , and the matrices $G_v$ depends on $g_v$ and carry on the effect of electron-vibrational mode coupling, where the factor $\sqrt{N_v}$ appears on the specific elements of the matrix (\[eq:HmatrixBell\]) which depends on the values of $N_v$ of the coupled subspaces. If we consider a full resonance condition between electronic levels $\delta_{\pm}=0$, the matrix $B_{N_1N_2}$ becomes $$\begin{aligned} \label{eq:4DBellmatrixv1} B_{N_1N_2}&=&\left( \begin{array}{cccc} E_{N_1N_2} & 0 & 0 & 0 \\ 0 & E_{N_1N_2} & 0 & 0 \\ 0 & 0 & E_{N_1N_2} & \Delta_+ \\ 0 & 0 & \Delta_+ & E_{N_1N_2} \\ \end{array} \right).\end{aligned}$$ At first sight, it seems that the states with electronic part being ${\mathinner{|{\Psi{-}}\rangle}}_\mathcal{D}$ and ${\mathinner{|{\Phi{-}}\rangle}}_\mathcal{D}$ are decoupled, at the same time that ${\mathinner{|{\Psi{+}}\rangle}}_\mathcal{D}$ and ${\mathinner{|{\Phi{+}}\rangle}}_\mathcal{D}$ are not, in the same way that in Ref. . Nevertheless, if elements for the first two lines on matrix (\[eq:HmatrixBell\]), associated with ${\mathinner{|{\Psi_-,00}\rangle}}$ and ${\mathinner{|{\Psi_-,00}\rangle}}$ respectively, are written using the notation ${\mathinner{|{\;}\rangle}}{\mathinner{\langle{\;}|}}$ we obtain: $$\begin{aligned} \label{eq:HtermsPsi-Phi-} H&=&{\mathinner{|{\Psi_-,00}\rangle}}\big(E_{00}{\mathinner{\langle{\Psi_-,00}|}}+g_2{\mathinner{\langle{\Psi_-,01}|}}+g_1{\mathinner{\langle{\Psi_-10}|}}\big)\nonumber\\ &+&{\mathinner{|{\Phi_-,00}\rangle}}\left(E_{00}{\mathinner{\langle{\Phi_-,00}|}} +\frac{g_2}{2}{\mathinner{\langle{\Phi_-,01}|}}-\frac{g_2}{2}{\mathinner{\langle{\Phi_+,01}|}}\right.\nonumber\\ &&\left.+\frac{g_1}{2}{\mathinner{\langle{\Phi_-,10}|}}+\frac{g_1}{2}{\mathinner{\langle{\Phi_+,10}|}}\right)+...\end{aligned}$$ The term with ${\mathinner{|{\Psi_-}\rangle}}_{\mathcal{D}}$ can be written as $\big({\mathinner{|{\Psi_-}\rangle}}{\mathinner{\langle{\Psi_-}|}}\big)_{\mathcal{D}}\otimes\big(E_{00}{\mathinner{|{00}\rangle}}{\mathinner{\langle{00}|}}+g_2{\mathinner{|{00}\rangle}}{\mathinner{\langle{01}|}}+g_1{\mathinner{|{00}\rangle}}{\mathinner{\langle{10}|}}\big)$, while the others do not permit the same. Continuing with the calculation, we realize that only the terms on Hamiltonian associated with ${\mathinner{|{\Psi_-}\rangle}}_{\mathcal{D}}$ are decoupled, at least from the electronic point of view, from the rest of the Bell basis. In this way, there is a Bell state, dressed by vibrational modes, becoming an eigenstate of the Hamiltonian (\[eq:Hgeneral\]) for the specific condition of equal tunneling couplings, $\Delta_{34}=\Delta_{12}$ and full resonance between the electronic levels. [37]{}ifxundefined \[1\][ ifx[\#1]{} ]{}ifnum \[1\][ \#1firstoftwo secondoftwo ]{}ifx \[1\][ \#1firstoftwo secondoftwo ]{}““\#1””@noop \[0\][secondoftwo]{}sanitize@url \[0\][‘\ 12‘\$12 ‘&12‘\#12‘12‘\_12‘%12]{}@startlink\[1\]@endlink\[0\]@bib@innerbibempty @noop [****,  ()]{} [****,  ()](\doibase 10.1002/qua.20484) @noop [****,  ()]{} @noop [****, ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [**]{} (, , ) @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} [****, ()](\doibase 10.1038/nnano.2009.71) @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [****,  ()]{} @noop [**]{},  ed. (, , ) @noop [**]{} (, ) @noop [****,  ()]{} @noop [****,  ()]{} [****,  ()](\doibase 10.1103/PhysRevLett.78.5022) [^1]: Although not shown here, the second-order time-dependent perturbation theory can be used to show this transition
{ "pile_set_name": "ArXiv" }
// Copyright 2016 The Chromium Authors. All rights reserved. // Use of this source code is governed by a BSD-style license that can be // found in the LICENSE file. #include "DiagnosticsReporter.h" #include "llvm/Support/ErrorHandling.h" using namespace clang; namespace { const char kClassMustLeftMostlyDeriveGC[] = "[blink-gc] Class %0 must derive from GarbageCollected in the left-most position."; const char kClassRequiresTraceMethod[] = "[blink-gc] Class %0 requires a trace method."; const char kBaseRequiresTracing[] = "[blink-gc] Base class %0 of derived class %1 requires tracing."; const char kBaseRequiresTracingNote[] = "[blink-gc] Untraced base class %0 declared here:"; const char kFieldsRequireTracing[] = "[blink-gc] Class %0 has untraced fields that require tracing."; const char kFieldsImproperlyTraced[] = "[blink-gc] Class %0 has untraced or not traceable fields."; const char kFieldRequiresTracingNote[] = "[blink-gc] Untraced field %0 declared here:"; const char kFieldShouldNotBeTracedNote[] = "[blink-gc] Untraceable field %0 declared here:"; const char kClassContainsInvalidFields[] = "[blink-gc] Class %0 contains invalid fields."; const char kClassContainsGCRoot[] = "[blink-gc] Class %0 contains GC root in field %1."; const char kFinalizerAccessesFinalizedField[] = "[blink-gc] Finalizer %0 accesses potentially finalized field %1."; const char kRawPtrToGCManagedClassNote[] = "[blink-gc] Raw pointer field %0 to a GC managed class declared here:"; const char kRefPtrToGCManagedClassNote[] = "[blink-gc] scoped_refptr field %0 to a GC managed class declared here:"; const char kWeakPtrToGCManagedClassNote[] = "[blink-gc] WeakPtr field %0 to a GC managed class declared here:"; const char kReferencePtrToGCManagedClassNote[] = "[blink-gc] Reference pointer field %0 to a GC managed class" " declared here:"; const char kUniquePtrToGCManagedClassNote[] = "[blink-gc] std::unique_ptr field %0 to a GC managed class declared here:"; const char kMemberToGCUnmanagedClassNote[] = "[blink-gc] Member field %0 to non-GC managed class declared here:"; const char kStackAllocatedFieldNote[] = "[blink-gc] Stack-allocated field %0 declared here:"; const char kMemberInUnmanagedClassNote[] = "[blink-gc] Member field %0 in unmanaged class declared here:"; const char kPartObjectToGCDerivedClassNote[] = "[blink-gc] Part-object field %0 to a GC derived class declared here:"; const char kPartObjectContainsGCRootNote[] = "[blink-gc] Field %0 with embedded GC root in %1 declared here:"; const char kFieldContainsGCRootNote[] = "[blink-gc] Field %0 defining a GC root declared here:"; const char kOverriddenNonVirtualTrace[] = "[blink-gc] Class %0 overrides non-virtual trace of base class %1."; const char kOverriddenNonVirtualTraceNote[] = "[blink-gc] Non-virtual trace method declared here:"; const char kMissingTraceDispatchMethod[] = "[blink-gc] Class %0 is missing manual trace dispatch."; const char kVirtualAndManualDispatch[] = "[blink-gc] Class %0 contains or inherits virtual methods" " but implements manual dispatching."; const char kMissingTraceDispatch[] = "[blink-gc] Missing dispatch to class %0 in manual trace dispatch."; const char kMissingFinalizeDispatch[] = "[blink-gc] Missing dispatch to class %0 in manual finalize dispatch."; const char kFinalizedFieldNote[] = "[blink-gc] Potentially finalized field %0 declared here:"; const char kManualDispatchMethodNote[] = "[blink-gc] Manual dispatch %0 declared here:"; const char kStackAllocatedDerivesGarbageCollected[] = "[blink-gc] Stack-allocated class %0 derives class %1" " which is garbage collected."; const char kClassOverridesNew[] = "[blink-gc] Garbage collected class %0" " is not permitted to override its new operator."; const char kClassDeclaresPureVirtualTrace[] = "[blink-gc] Garbage collected class %0" " is not permitted to declare a pure-virtual trace method."; const char kLeftMostBaseMustBePolymorphic[] = "[blink-gc] Left-most base class %0 of derived class %1" " must be polymorphic."; const char kBaseClassMustDeclareVirtualTrace[] = "[blink-gc] Left-most base class %0 of derived class %1" " must define a virtual trace method."; const char kClassMustCRTPItself[] = "[blink-gc] GC base class %0 must be specialized with the derived class " "%1."; const char kIteratorToGCManagedCollectionNote[] = "[blink-gc] Iterator field %0 to a GC managed collection declared here:"; const char kTraceMethodOfStackAllocatedParentNote[] = "[blink-gc] The stack allocated class %0 provides an unnecessary " "trace method:"; const char kMemberInStackAllocated[] = "[blink-gc] Member field %0 in stack allocated class declared here (use " "raw pointer or reference instead):"; const char kUniquePtrUsedWithGC[] = "[blink-gc] Disallowed use of %0 found; %1 is a garbage-collected type. " "std::unique_ptr cannot hold garbage-collected objects."; const char kOptionalUsedWithGC[] = "[blink-gc] Disallowed construction of %0 found; %1 is a garbage-collected " "type. optional cannot hold garbage-collected objects."; } // namespace DiagnosticBuilder DiagnosticsReporter::ReportDiagnostic( SourceLocation location, unsigned diag_id) { SourceManager& manager = instance_.getSourceManager(); FullSourceLoc full_loc(location, manager); return diagnostic_.Report(full_loc, diag_id); } DiagnosticsReporter::DiagnosticsReporter( clang::CompilerInstance& instance) : instance_(instance), diagnostic_(instance.getDiagnostics()) { // Register warning/error messages. diag_class_must_left_mostly_derive_gc_ = diagnostic_.getCustomDiagID( getErrorLevel(), kClassMustLeftMostlyDeriveGC); diag_class_requires_trace_method_ = diagnostic_.getCustomDiagID(getErrorLevel(), kClassRequiresTraceMethod); diag_base_requires_tracing_ = diagnostic_.getCustomDiagID(getErrorLevel(), kBaseRequiresTracing); diag_fields_require_tracing_ = diagnostic_.getCustomDiagID(getErrorLevel(), kFieldsRequireTracing); diag_fields_improperly_traced_ = diagnostic_.getCustomDiagID(getErrorLevel(), kFieldsImproperlyTraced); diag_class_contains_invalid_fields_ = diagnostic_.getCustomDiagID( getErrorLevel(), kClassContainsInvalidFields); diag_class_contains_gc_root_ = diagnostic_.getCustomDiagID(getErrorLevel(), kClassContainsGCRoot); diag_finalizer_accesses_finalized_field_ = diagnostic_.getCustomDiagID( getErrorLevel(), kFinalizerAccessesFinalizedField); diag_overridden_non_virtual_trace_ = diagnostic_.getCustomDiagID( getErrorLevel(), kOverriddenNonVirtualTrace); diag_missing_trace_dispatch_method_ = diagnostic_.getCustomDiagID( getErrorLevel(), kMissingTraceDispatchMethod); diag_virtual_and_manual_dispatch_ = diagnostic_.getCustomDiagID(getErrorLevel(), kVirtualAndManualDispatch); diag_missing_trace_dispatch_ = diagnostic_.getCustomDiagID(getErrorLevel(), kMissingTraceDispatch); diag_missing_finalize_dispatch_ = diagnostic_.getCustomDiagID(getErrorLevel(), kMissingFinalizeDispatch); diag_stack_allocated_derives_gc_ = diagnostic_.getCustomDiagID( getErrorLevel(), kStackAllocatedDerivesGarbageCollected); diag_class_overrides_new_ = diagnostic_.getCustomDiagID(getErrorLevel(), kClassOverridesNew); diag_class_declares_pure_virtual_trace_ = diagnostic_.getCustomDiagID( getErrorLevel(), kClassDeclaresPureVirtualTrace); diag_left_most_base_must_be_polymorphic_ = diagnostic_.getCustomDiagID( getErrorLevel(), kLeftMostBaseMustBePolymorphic); diag_base_class_must_declare_virtual_trace_ = diagnostic_.getCustomDiagID( getErrorLevel(), kBaseClassMustDeclareVirtualTrace); diag_class_must_crtp_itself_ = diagnostic_.getCustomDiagID(getErrorLevel(), kClassMustCRTPItself); diag_iterator_to_gc_managed_collection_note_ = diagnostic_.getCustomDiagID( getErrorLevel(), kIteratorToGCManagedCollectionNote); diag_trace_method_of_stack_allocated_parent_ = diagnostic_.getCustomDiagID( getErrorLevel(), kTraceMethodOfStackAllocatedParentNote); diag_member_in_stack_allocated_class_ = diagnostic_.getCustomDiagID(getErrorLevel(), kMemberInStackAllocated); // Register note messages. diag_base_requires_tracing_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kBaseRequiresTracingNote); diag_field_requires_tracing_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kFieldRequiresTracingNote); diag_field_should_not_be_traced_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kFieldShouldNotBeTracedNote); diag_raw_ptr_to_gc_managed_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kRawPtrToGCManagedClassNote); diag_ref_ptr_to_gc_managed_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kRefPtrToGCManagedClassNote); diag_weak_ptr_to_gc_managed_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kWeakPtrToGCManagedClassNote); diag_reference_ptr_to_gc_managed_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kReferencePtrToGCManagedClassNote); diag_unique_ptr_to_gc_managed_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kUniquePtrToGCManagedClassNote); diag_member_to_gc_unmanaged_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kMemberToGCUnmanagedClassNote); diag_stack_allocated_field_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kStackAllocatedFieldNote); diag_member_in_unmanaged_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kMemberInUnmanagedClassNote); diag_part_object_to_gc_derived_class_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kPartObjectToGCDerivedClassNote); diag_part_object_contains_gc_root_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kPartObjectContainsGCRootNote); diag_field_contains_gc_root_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kFieldContainsGCRootNote); diag_finalized_field_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kFinalizedFieldNote); diag_overridden_non_virtual_trace_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kOverriddenNonVirtualTraceNote); diag_manual_dispatch_method_note_ = diagnostic_.getCustomDiagID( DiagnosticsEngine::Note, kManualDispatchMethodNote); diag_unique_ptr_used_with_gc_ = diagnostic_.getCustomDiagID(getErrorLevel(), kUniquePtrUsedWithGC); diag_optional_used_with_gc_ = diagnostic_.getCustomDiagID(getErrorLevel(), kOptionalUsedWithGC); } bool DiagnosticsReporter::hasErrorOccurred() const { return diagnostic_.hasErrorOccurred(); } DiagnosticsEngine::Level DiagnosticsReporter::getErrorLevel() const { return diagnostic_.getWarningsAsErrors() ? DiagnosticsEngine::Error : DiagnosticsEngine::Warning; } void DiagnosticsReporter::ClassMustLeftMostlyDeriveGC( RecordInfo* info) { ReportDiagnostic(info->record()->getInnerLocStart(), diag_class_must_left_mostly_derive_gc_) << info->record(); } void DiagnosticsReporter::ClassRequiresTraceMethod(RecordInfo* info) { ReportDiagnostic(info->record()->getInnerLocStart(), diag_class_requires_trace_method_) << info->record(); for (auto& base : info->GetBases()) if (base.second.NeedsTracing().IsNeeded()) NoteBaseRequiresTracing(&base.second); for (auto& field : info->GetFields()) if (!field.second.IsProperlyTraced()) NoteFieldRequiresTracing(info, field.first); } void DiagnosticsReporter::BaseRequiresTracing( RecordInfo* derived, CXXMethodDecl* trace, CXXRecordDecl* base) { ReportDiagnostic(trace->getBeginLoc(), diag_base_requires_tracing_) << base << derived->record(); } void DiagnosticsReporter::FieldsImproperlyTraced( RecordInfo* info, CXXMethodDecl* trace) { // Only mention untraceable in header diagnostic if they appear. unsigned diag = diag_fields_require_tracing_; for (auto& field : info->GetFields()) { if (field.second.IsInproperlyTraced()) { diag = diag_fields_improperly_traced_; break; } } ReportDiagnostic(trace->getBeginLoc(), diag) << info->record(); for (auto& field : info->GetFields()) { if (!field.second.IsProperlyTraced()) NoteFieldRequiresTracing(info, field.first); if (field.second.IsInproperlyTraced()) NoteFieldShouldNotBeTraced(info, field.first); } } void DiagnosticsReporter::ClassContainsInvalidFields( RecordInfo* info, const CheckFieldsVisitor::Errors& errors) { ReportDiagnostic(info->record()->getBeginLoc(), diag_class_contains_invalid_fields_) << info->record(); for (auto& error : errors) { unsigned note; if (error.second == CheckFieldsVisitor::kRawPtrToGCManaged) { note = diag_raw_ptr_to_gc_managed_class_note_; } else if (error.second == CheckFieldsVisitor::kRefPtrToGCManaged) { note = diag_ref_ptr_to_gc_managed_class_note_; } else if (error.second == CheckFieldsVisitor::kWeakPtrToGCManaged) { note = diag_weak_ptr_to_gc_managed_class_note_; } else if (error.second == CheckFieldsVisitor::kReferencePtrToGCManaged) { note = diag_reference_ptr_to_gc_managed_class_note_; } else if (error.second == CheckFieldsVisitor::kUniquePtrToGCManaged) { note = diag_unique_ptr_to_gc_managed_class_note_; } else if (error.second == CheckFieldsVisitor::kMemberToGCUnmanaged) { note = diag_member_to_gc_unmanaged_class_note_; } else if (error.second == CheckFieldsVisitor::kMemberInUnmanaged) { note = diag_member_in_unmanaged_class_note_; } else if (error.second == CheckFieldsVisitor::kPtrFromHeapToStack) { note = diag_stack_allocated_field_note_; } else if (error.second == CheckFieldsVisitor::kGCDerivedPartObject) { note = diag_part_object_to_gc_derived_class_note_; } else if (error.second == CheckFieldsVisitor::kIteratorToGCManaged) { note = diag_iterator_to_gc_managed_collection_note_; } else if (error.second == CheckFieldsVisitor::kMemberInStackAllocated) { note = diag_member_in_stack_allocated_class_; } else { llvm_unreachable("Unknown field error."); } NoteField(error.first, note); } } void DiagnosticsReporter::ClassContainsGCRoots( RecordInfo* info, const CheckGCRootsVisitor::Errors& errors) { for (auto& error : errors) { FieldPoint* point = nullptr; for (FieldPoint* path : error) { if (!point) { point = path; ReportDiagnostic(info->record()->getBeginLoc(), diag_class_contains_gc_root_) << info->record() << point->field(); continue; } NotePartObjectContainsGCRoot(point); point = path; } NoteFieldContainsGCRoot(point); } } void DiagnosticsReporter::FinalizerAccessesFinalizedFields( CXXMethodDecl* dtor, const CheckFinalizerVisitor::Errors& errors) { for (auto& error : errors) { ReportDiagnostic(error.member->getBeginLoc(), diag_finalizer_accesses_finalized_field_) << dtor << error.field->field(); NoteField(error.field, diag_finalized_field_note_); } } void DiagnosticsReporter::OverriddenNonVirtualTrace( RecordInfo* info, CXXMethodDecl* trace, CXXMethodDecl* overridden) { ReportDiagnostic(trace->getBeginLoc(), diag_overridden_non_virtual_trace_) << info->record() << overridden->getParent(); NoteOverriddenNonVirtualTrace(overridden); } void DiagnosticsReporter::MissingTraceDispatchMethod(RecordInfo* info) { ReportMissingDispatchMethod(info, diag_missing_trace_dispatch_method_); } void DiagnosticsReporter::ReportMissingDispatchMethod( RecordInfo* info, unsigned error) { ReportDiagnostic(info->record()->getInnerLocStart(), error) << info->record(); } void DiagnosticsReporter::VirtualAndManualDispatch( RecordInfo* info, CXXMethodDecl* dispatch) { ReportDiagnostic(info->record()->getInnerLocStart(), diag_virtual_and_manual_dispatch_) << info->record(); NoteManualDispatchMethod(dispatch); } void DiagnosticsReporter::MissingTraceDispatch( const FunctionDecl* dispatch, RecordInfo* receiver) { ReportMissingDispatch(dispatch, receiver, diag_missing_trace_dispatch_); } void DiagnosticsReporter::MissingFinalizeDispatch( const FunctionDecl* dispatch, RecordInfo* receiver) { ReportMissingDispatch(dispatch, receiver, diag_missing_finalize_dispatch_); } void DiagnosticsReporter::ReportMissingDispatch( const FunctionDecl* dispatch, RecordInfo* receiver, unsigned error) { ReportDiagnostic(dispatch->getBeginLoc(), error) << receiver->record(); } void DiagnosticsReporter::StackAllocatedDerivesGarbageCollected( RecordInfo* info, BasePoint* base) { ReportDiagnostic(base->spec().getBeginLoc(), diag_stack_allocated_derives_gc_) << info->record() << base->info()->record(); } void DiagnosticsReporter::ClassOverridesNew( RecordInfo* info, CXXMethodDecl* newop) { ReportDiagnostic(newop->getBeginLoc(), diag_class_overrides_new_) << info->record(); } void DiagnosticsReporter::ClassDeclaresPureVirtualTrace( RecordInfo* info, CXXMethodDecl* trace) { ReportDiagnostic(trace->getBeginLoc(), diag_class_declares_pure_virtual_trace_) << info->record(); } void DiagnosticsReporter::LeftMostBaseMustBePolymorphic( RecordInfo* derived, CXXRecordDecl* base) { ReportDiagnostic(base->getBeginLoc(), diag_left_most_base_must_be_polymorphic_) << base << derived->record(); } void DiagnosticsReporter::BaseClassMustDeclareVirtualTrace( RecordInfo* derived, CXXRecordDecl* base) { ReportDiagnostic(base->getBeginLoc(), diag_base_class_must_declare_virtual_trace_) << base << derived->record(); } void DiagnosticsReporter::ClassMustCRTPItself( const RecordInfo* derived, const CXXRecordDecl* base, const CXXBaseSpecifier* base_spec) { ReportDiagnostic(base_spec->getBeginLoc(), diag_class_must_crtp_itself_) << base << derived->record(); } void DiagnosticsReporter::TraceMethodForStackAllocatedClass( RecordInfo* info, CXXMethodDecl* trace) { ReportDiagnostic(trace->getBeginLoc(), diag_trace_method_of_stack_allocated_parent_) << info->record(); } void DiagnosticsReporter::NoteManualDispatchMethod(CXXMethodDecl* dispatch) { ReportDiagnostic(dispatch->getBeginLoc(), diag_manual_dispatch_method_note_) << dispatch; } void DiagnosticsReporter::NoteBaseRequiresTracing(BasePoint* base) { ReportDiagnostic(base->spec().getBeginLoc(), diag_base_requires_tracing_note_) << base->info()->record(); } void DiagnosticsReporter::NoteFieldRequiresTracing( RecordInfo* holder, FieldDecl* field) { NoteField(field, diag_field_requires_tracing_note_); } void DiagnosticsReporter::NoteFieldShouldNotBeTraced( RecordInfo* holder, FieldDecl* field) { NoteField(field, diag_field_should_not_be_traced_note_); } void DiagnosticsReporter::NotePartObjectContainsGCRoot(FieldPoint* point) { FieldDecl* field = point->field(); ReportDiagnostic(field->getBeginLoc(), diag_part_object_contains_gc_root_note_) << field << field->getParent(); } void DiagnosticsReporter::NoteFieldContainsGCRoot(FieldPoint* point) { NoteField(point, diag_field_contains_gc_root_note_); } void DiagnosticsReporter::NoteField(FieldPoint* point, unsigned note) { NoteField(point->field(), note); } void DiagnosticsReporter::NoteField(FieldDecl* field, unsigned note) { ReportDiagnostic(field->getBeginLoc(), note) << field; } void DiagnosticsReporter::NoteOverriddenNonVirtualTrace( CXXMethodDecl* overridden) { ReportDiagnostic(overridden->getBeginLoc(), diag_overridden_non_virtual_trace_note_) << overridden; } void DiagnosticsReporter::UniquePtrUsedWithGC( const clang::Expr* expr, const clang::FunctionDecl* bad_function, const clang::CXXRecordDecl* gc_type) { ReportDiagnostic(expr->getBeginLoc(), diag_unique_ptr_used_with_gc_) << bad_function << gc_type << expr->getSourceRange(); } void DiagnosticsReporter::OptionalUsedWithGC( const clang::Expr* expr, const clang::CXXRecordDecl* optional, const clang::CXXRecordDecl* gc_type) { ReportDiagnostic(expr->getBeginLoc(), diag_optional_used_with_gc_) << optional << gc_type << expr->getSourceRange(); }
{ "pile_set_name": "Github" }
Energy dampening devices have been known for many years. A most common usage for such energy dampening devices is in the vehicle bumpers so that the force of impact will be dissipated by such energy dampening apparatus, thereby minimizing the actual damage to the motor vehicle. For example, U.S. Pat. Nos. 3,960,397 to Janci, 3,961,818 to Roth, 4,366,876 to Granig and 4,257,581 to Keeler are representative of such devices for absorbing shock and preventing damage to a motor vehicle by connecting such energy dampening devices to the bumper thereof.
{ "pile_set_name": "USPTO Backgrounds" }
AUSTIN (KXAN) — The family of Isaac Villafranca raised money and awareness Saturday about the immune system disease that took the high-schooler’s life this week. “No one should have to go through what Isaac went through,” his stepmom, Celeste Villafranca, told KXAN during an event to sell plates of food to pay for his funeral expenses and research into the disease. Isaac was 17, a senior at Akins High School in south Austin, when a cancer diagnosis turned his world upside down. He complained of shoulder pain, and doctors found a germ cell malignant tumor in his chest. He underwent surgery for 10 hours on Sept. 26, and everything looked good, Villafranca said. A few days later, though, he developed a fever that wouldn’t go away. It took a few days for doctors to diagnose him with HLH Syndrome, short for hemophagocytic lymphohistiocytosis. “They did everything they could, but Isaac was so sick,” Villafranca said. “The doctors told us this is rare on top of rare.” HLH turns the body’s immune system against the body itself, destroying organs and bone marrow. The rare condition was triggered by the cancer, one of two ways it can manifest. Isaac’s HLH diagnosis came on Oct. 5. and five days later, he died from the immune system disorder. “It happened so fast,” his aunt, Freedom Garcia, said. Garcia remembers her nephew as “a great, wonderful kid who inspired so many.” Now she’s helping to inspire more research into HLH. She joined Villafranca, plus Isaac’s biological parents and stepdad, in cooking up burgers to sell to raise money. In addition to funeral expenses, the family wants it to go to better diagnosis and treatments. There are two GoFundMe pages set up to accept donations: one that his sister initiated during his cancer treatment to help pay the bills and one Villafranca set up after his death. “We just want to… prevent this from happening to another precious life,” Garcia said.
{ "pile_set_name": "OpenWebText2" }
Snail represses the expression of human phospholipid scramblase 4 gene. Human phospholipid scramblases (hPLSCRs) are a group of transmembrane ATP independent lipid transporters mediating bi-directional transport of phospholipids. There are four homologues hPLSCR1-hPLSCR4 and hPLSCR1 is the extensively studied homologue among them. hPLSCR4 shares 48% homology with hPLSCR1 and mediates scrambling of PLs similar to hPLSCR1 in Ca(2+) dependent manner. Transcriptional regulation helps in better understanding of the function and the expression of a protein. Till date there are no reports suggesting the transcriptional regulation of hPLSCR4. In this study, we identified Snail to be a potent regulator of hPLSCR4. ConSite tool predicted the presence of a putative Snail binding site with a consensus sequence of (-1521)CAGGTG(-1516) on hPLSCR4 promoter. Luciferase assays depicted a dose dependent decrease in hPLSCR4 promoter activity with an increase in amount of Snail. Deletion analysis revealed that the region from -1380 to -2100 to be the regulatory region of hPLSCR4. Knock down studies further confirmed Snail mediated downregulation of hPLSCR4, as the mRNA and the protein levels of hPLSCR4 considerably increased under knock down conditions. The in vivo interaction of Snail with hPLSCR4 promoter was further confirmed by ChIP assay. This is the first report on the transcriptional regulation of hPLSCR4, where Snail was shown to downregulate the expression of hPLSCR4.
{ "pile_set_name": "PubMed Abstracts" }
Q: Search a file in sub folders When i try to search the zip file in sub-folders of "Input_Files", the command is not running after "\172.24.191.117\data1\NEW-ENDORSEMENTS\Backlog_checked\%J%\CLIENT-SUPPLIED\Backlog". I think the space is problem to get the path. Kindly check and clear. @echo off echo. set /p J=Enter Journal ID : set /p A=Enter Article ID : set "BaseDir=\\172.24.191.117\data1\NEW-ENDORSEMENTS\Backlog_checked\%J%\CLIENT-SUPPLIED\Backlog Transfer\Non EV articles\%J%%A%" For /f "delims=" %%A in (' Dir /B/S/A-D "%BaseDir%\*.zip" ^| Findstr /I "\\Input_Files\\[^\\]*\.zip$" ') Do start %%A pause A: Replace start %%A by start "" "%%A". DIR outputs the found file matching the pattern with full qualified file name (file path + file name + file extension) never enclosed in double quotes. So it is necessary to reference the file with embedding it in double quotes as done here with "%%A". The first double quoted string is interpreted by command START as optional title. For that reason a title must be explicitly specified to avoid interpreting the full qualified file name in " as title string. As the started application for opening the *.zip file is most likely a GUI application, an empty title string can be used with "" because no command process with a console window is opened in this case.
{ "pile_set_name": "StackExchange" }
A systematic review of medical mistrust measures. Medical mistrust is seen as a barrier to health promotion and addressing health disparities among marginalized populations. This study seeks to examine how medical mistrust has been measured as a step towards informing related health promotion efforts. A systematic review of medical mistrust scales was conducted using four major databases: PubMed, PsycINFO, ERIC, and Communication & Mass Media Complete. Databases were searched using the terms "medical mistrust scale" "medical mistrust" and "medical distrust." The search returned 1595 non-duplicate citations; after inclusion and exclusion criteria were applied, 185 articles were retained and coded. Almost a quarter of studies used a single-item or a few items. Among validated scales, the Group-Based Medical Mistrust Scale, Medical Mistrust Index, and Health Care System Distrust Scale were most frequently used. There were important differences among these scales such as the object of mistrust (e.g., system, individual physician) and referent specificity (e.g., group). The measurement of medical mistrust varied by health topic and sample population. These differences in scales and measurement should be considered in the context of intervention goals. Researchers should be aware of differences in measures and choose appropriate measures for a given research question or intervention.
{ "pile_set_name": "PubMed Abstracts" }
Rising from the unhallowed wastes of Western Sydney, Australia, extreme metal outfit THY ART IS MURDER have carved a trail of bloody mayhem since their inception in 2006. With an acclaimed EP and debut album in Infinite Death and The Adversary to their name and an insane online following, the band have traversed the highways and autobahns of Australia, the UK and Europe on a relentless crusade to destroy every venue and audience they can with like minded peers in a who’s who of heavy metal. April 5, 2013 brings a new ritual offering of darkness from the five piece. Simply titled Hate, the band’s second full length is the pointed result of THY ART IS MURDER’s growing dissatisfaction with all aspects of modern life – political, religious, social and environmental – everyone is to blame. Fusing the blasting technicality of metal luminaries The Black Dahlia Murder with thunderous breakdowns and the intensity born of their nascent hometown scene; the blackened grandeur of Behemoth and the pit churning groove of Tampa originators Morbid Angel and Cannibal Corpse, the furious musical arrangements provide a bloody canvas for vocalist CJ McMahon’s outpourings of bile. No strangers to stoking controversy and criticism, the band have not toned down their art for the sake of palatability and have introduced a morose melodicism into their maelstrom – the rumination before pulling the trigger. With their best work to date ready to be unleashed on an unsuspecting world, THY ART IS MURDER will once again take to the road to unleash the Hate with one simple message – get in the pit or get out of the way.
{ "pile_set_name": "Pile-CC" }
# Czech translation for gnome-pomodoro # Copyright (c) 2012 gnome-pomodoro contributors # This file is distributed under the same license as the gnome-pomodoro package. # Jakub Veverka, 2012. # msgid "" msgstr "" "Project-Id-Version: gnome-pomodoro\n" "Report-Msgid-Bugs-To: https://github.com/codito/gnome-pomodoro/issues\n" "POT-Creation-Date: 2016-10-02 19:50+0200\n" "PO-Revision-Date: 2016-10-04 06:18+0200\n" "Last-Translator: Petr Hložek <petr@petrhlozek.cz>\n" "Language-Team: <>\n" "Language: cs\n" "MIME-Version: 1.0\n" "Content-Type: text/plain; charset=UTF-8\n" "Content-Transfer-Encoding: 8bit\n" "Plural-Forms: nplurals=3; plural=(n==1) ? 0 : (n>=2 && n<=4) ? 1 : 2;\n" "X-Generator: Poedit 1.8.7.1\n" #: data/org.gnome.Pomodoro.appdata.xml.in:7 #: data/org.gnome.Pomodoro.desktop.in:3 lib/resources/ui/menus.ui:51 #: lib/resources/ui/window.ui:275 lib/about-dialog.vala:31 #: lib/notifications-capability.vala:106 src/main.vala:30 msgid "Pomodoro" msgstr "Pomodoro" #: data/org.gnome.Pomodoro.appdata.xml.in:8 msgid "A time management utility for GNOME" msgstr "Jednoduchý nástroj pro time management" #: data/org.gnome.Pomodoro.appdata.xml.in:10 msgid "" "A GNOME utility that helps managing time according to Pomodoro Technique. It " "intends to improve productivity and focus by taking short breaks after every " "25 minutes of work." msgstr "" "Nástroj pro Gnome, který vám pomůže se správou času pomocí techniky " "Pomodoro. Záměrem je zlepšit vaši produktivitu a koncentraci pomocí krátkých " "přestávek po každých 25 minutách práce." #: data/org.gnome.Pomodoro.appdata.xml.in:19 msgid "Main window" msgstr "Hlavní okno" #: data/org.gnome.Pomodoro.appdata.xml.in:23 lib/preferences-dialog.vala:721 msgid "Preferences" msgstr "Předvolby" #: data/org.gnome.Pomodoro.appdata.xml.in:27 msgid "Indicator for GNOME Shell" msgstr "Indikátor pro GNOME Shell" #: data/org.gnome.Pomodoro.appdata.xml.in:32 msgid "Kamil Prusko" msgstr "Kamil Prusko" #: data/org.gnome.Pomodoro.desktop.in:4 lib/about-dialog.vala:32 msgid "A simple time management utility" msgstr "Jednoduchý nástroj pro time management " #: data/org.gnome.Pomodoro.desktop.in:5 msgid "timer;" msgstr "Časovač;" #: data/org.gnome.Pomodoro.desktop.in:7 msgid "gnome-pomodoro" msgstr "Pomodoro" #: lib/resources/ui/menus.ui:6 lib/resources/ui/menus.ui:68 msgid "_Timer" msgstr "Časovač" #: lib/resources/ui/menus.ui:10 lib/resources/ui/menus.ui:72 msgid "_Preferences" msgstr "Předvolby" #: lib/resources/ui/menus.ui:16 msgid "_About" msgstr "_O aplikaci" #: lib/resources/ui/menus.ui:20 lib/resources/ui/menus.ui:76 msgid "_Quit" msgstr "_Konec" #: lib/resources/ui/menus.ui:29 lib/application.vala:69 msgid "Start" msgstr "Start" #: lib/resources/ui/menus.ui:34 lib/resources/ui/window.ui:173 #: lib/application.vala:78 lib/window.vala:161 msgid "Pause" msgstr "Pozastavit" #: lib/resources/ui/menus.ui:39 lib/application.vala:81 lib/window.vala:147 msgid "Resume" msgstr "Pokračovat" #: lib/resources/ui/menus.ui:44 lib/resources/ui/window.ui:200 #: lib/application.vala:72 msgid "Stop" msgstr "Stop" #: lib/resources/ui/menus.ui:56 lib/resources/ui/window.ui:290 msgid "Short Break" msgstr "Krátká přestávka" #: lib/resources/ui/menus.ui:61 lib/resources/ui/window.ui:305 msgid "Long Break" msgstr "Dlouhá přestávka" #: lib/resources/ui/preferences.ui:8 lib/preferences-dialog.vala:725 msgid "Plugins" msgstr "Rošíření" #: lib/resources/ui/preferences.ui:47 msgid "Back" msgstr "Zpět" #: lib/resources/ui/preferences-keyboard-shortcut-page.ui:29 msgid "Keyboard shortcut to toggle the timer. Enter new shortcut to change." msgstr "Klávesová zkratka pro spuštění časovače. Nastavte novou." #: lib/resources/ui/preferences-keyboard-shortcut-page.ui:83 msgid "Disable" msgstr "Vypnuto" #: lib/resources/ui/preferences-main-page.ui:45 msgid "Timer" msgstr "Časovač" #: lib/resources/ui/preferences-main-page.ui:112 msgid "Pomodoro duration" msgstr "Délka pomodora" #: lib/resources/ui/preferences-main-page.ui:164 msgid "Break duration" msgstr "Délka přestávky" #: lib/resources/ui/preferences-main-page.ui:217 msgid "Long break duration" msgstr "Délka dlouhé přestávky" #: lib/resources/ui/preferences-main-page.ui:249 msgid "Pomodoros before a long break" msgstr "Počet pomodor před dlouhou přestávkou" #: lib/resources/ui/preferences-main-page.ui:298 msgid "Keyboard shortcut" msgstr "Klávesové zkratky" #: lib/resources/ui/preferences-main-page.ui:363 msgid "Notifications" msgstr "Notifikace" #: lib/resources/ui/preferences-main-page.ui:410 msgid "Screen notifications" msgstr "Oznámení na obrazovce" #: lib/resources/ui/preferences-main-page.ui:452 msgid "Remind to take a break" msgstr "Připomenout vzít si přestávku" #: lib/resources/ui/preferences-main-page.ui:514 msgid "Extras" msgstr "Další" #: lib/resources/ui/preferences-main-page.ui:561 msgid "Wait for activity after a break" msgstr "Po ukončení přestávky počkat na akci " #: lib/resources/ui/preferences-main-page.ui:603 msgid "Hide other notifications" msgstr "Skrýt ostatní notifikace" #: lib/resources/ui/preferences-main-page.ui:639 msgid "Plugins…" msgstr "Rozšíření" #: lib/resources/ui/preferences-sound-page.ui:33 msgid "Volume:" msgstr "Hlasitost:" #: lib/resources/ui/preferences-sound-page.ui:168 msgid "Add Sound" msgstr "Přidat zvuk" #: lib/resources/ui/preferences-sound-page.ui:180 msgid "Remove Sound" msgstr "Odstranit zvuk" #: lib/resources/ui/screen-notification.ui:31 #: lib/resources/ui/screen-notification.ui:65 lib/resources/ui/window.ui:98 #: lib/resources/ui/window.ui:132 msgid "00" msgstr "00" #: lib/resources/ui/screen-notification.ui:49 lib/resources/ui/window.ui:116 msgid ":" msgstr ":" #: lib/resources/ui/screen-notification.ui:89 msgid "It's time to take a break" msgstr "Je čas udělat si přestávku..." #: lib/resources/ui/window.ui:31 msgid "Start Pomodoro" msgstr "Začni pomodoro" #: lib/about-dialog.vala:30 msgid "About Pomodoro" msgstr "O Pomodoro" #: lib/about-dialog.vala:41 msgid "translator-credits" msgstr "Petr Hložek" #: lib/application.vala:66 msgid "Start/Stop" msgstr "Start/Stop" #: lib/application.vala:75 msgid "Pause/Resume" msgstr "Pozastavit/Pokračovat" #: lib/application.vala:84 msgid "Run as background service" msgstr "Spustit na pozadí" #: lib/application.vala:87 msgid "Show preferences" msgstr "Předvolby" #: lib/application.vala:90 msgid "Quit application" msgstr "Ukončit program" #: lib/application.vala:93 msgid "Print version information and exit" msgstr "Zobrazí informaci o verzi a ukončí se" #: lib/notifications-capability.vala:107 msgid "Focus on your task." msgstr "Soustřeď se na svůj úkol" #: lib/notifications-capability.vala:118 lib/notifications-capability.vala:139 msgid "Take a break" msgstr "Dej si pauzu!" #: lib/notifications-capability.vala:133 #, c-format msgid "You have %d minute" msgid_plural "You have %d minutes" msgstr[0] "Zbývá %d minuta" msgstr[1] "Zbývá %d minuty" msgstr[2] "Zbývá %d minut" #: lib/notifications-capability.vala:135 #, c-format msgid "You have %d second" msgid_plural "You have %d seconds" msgstr[0] "Zbývá %d vteřina" msgstr[1] "Zbývá %d vteřiny" msgstr[2] "Zbývá %d vteřin" #: lib/notifications-capability.vala:140 msgid "Take a longer break" msgstr "Dej si delší pauzu!" #: lib/notifications-capability.vala:156 msgid "Lengthen it" msgstr "Prodlužte si ji" #: lib/notifications-capability.vala:161 msgid "Shorten it" msgstr "Zkraťte si ji" #: lib/notifications-capability.vala:166 msgid "Start pomodoro" msgstr "Začni pomodoro" #: lib/preferences-dialog.vala:158 #, c-format msgid "" "Using \"%s\" as shortcut will interfere with typing. Try adding another key, " "such as Control, Alt or Shift." msgstr "" "Klávesovou zkratku \"%s\" nelze použít protože by nešlo psát.\n" "Zkuste ji stisknout zároveň s CTRL, ALT nebo Shiftem." #: lib/preferences-dialog.vala:579 plugins/sounds/sounds-plugin.vala:595 msgid "Off" msgstr "Vypnuto" #: lib/preferences-dialog.vala:729 msgid "Keyboard Shortcut" msgstr "Klávesové zkratky" #: lib/presence.vala:78 msgid "Available" msgstr "Dostupný" #: lib/presence.vala:81 msgid "Busy" msgstr "Zaneprázdněný" #: lib/presence.vala:84 msgid "Idle" msgstr "Nečinný" #: lib/presence.vala:87 msgid "Invisible" msgstr "Neviditelný" #: lib/utils.vala:64 #, c-format msgid "%d hour" msgid_plural "%d hours" msgstr[0] "%d hodina" msgstr[1] "%d hodiny" msgstr[2] "%d hodin" #: lib/utils.vala:73 #, c-format msgid "%d minute" msgid_plural "%d minutes" msgstr[0] "%d minuta" msgstr[1] "%d minuty" msgstr[2] "%d minut" #: plugins/gnome/gnome-shell-extension.vala:340 #: plugins/gnome/gnome-shell-extension.vala:359 #: plugins/gnome/gnome-shell-extension.vala:392 msgid "Failed to enable extension" msgstr "Nepodařilo se zapnout rozšíření" #: plugins/gnome/gnome-shell-extension.vala:341 msgid "It seems to be uninstalled" msgstr "Zdá se být odinstalováno" #: plugins/gnome/gnome-shell-extension.vala:360 msgid "Extension is out of date" msgstr "Rozšíření je zastaralé" #: plugins/gnome/gnome-shell-extension.vala:361 msgid "Upgrade" msgstr "Upgrade" #: plugins/gnome/gnome-shell-extension.vala:394 msgid "Report issue" msgstr "Nahlásit problém" #: plugins/sounds/sounds-plugin.vala:35 plugins/sounds/sounds-plugin.vala:402 msgid "Clock Ticking" msgstr "Tikání" #: plugins/sounds/sounds-plugin.vala:36 plugins/sounds/sounds-plugin.vala:403 msgid "Timer Ticking" msgstr "Tikání časovače" #: plugins/sounds/sounds-plugin.vala:37 plugins/sounds/sounds-plugin.vala:404 msgid "Woodland Birds" msgstr "Lesní ptáci" #: plugins/sounds/sounds-plugin.vala:38 plugins/sounds/sounds-plugin.vala:462 #: plugins/sounds/sounds-plugin.vala:502 msgid "Bell" msgstr "Zvonek" #: plugins/sounds/sounds-plugin.vala:39 plugins/sounds/sounds-plugin.vala:463 #: plugins/sounds/sounds-plugin.vala:503 msgid "Loud Bell" msgstr "Hlasitý zvonek" #: plugins/sounds/sounds-plugin.vala:328 msgid "Select Custom Sound" msgstr "Vyberte vlastní zvuk" #: plugins/sounds/sounds-plugin.vala:561 msgid "Ticking Sound" msgstr "Tikání" #: plugins/sounds/sounds-plugin.vala:565 msgid "End of Break Sound" msgstr "Zvuk na konci přestávky" #: plugins/sounds/sounds-plugin.vala:569 msgid "Start of Break Sound" msgstr "Zvuk na začátku přestávky" #: plugins/sounds/sounds-plugin.vala:728 msgid "Ticking sound" msgstr "Tikání" #: plugins/sounds/sounds-plugin.vala:733 msgid "Start of break sound" msgstr "Zvuk na začátku přestávky" #: plugins/sounds/sounds-plugin.vala:738 msgid "End of break sound" msgstr "Zvuk na konci přestávky" #~ msgid "Pomodoro Timer" #~ msgstr "Časovač Pomodoro" #~ msgid "A new pomodoro is starting" #~ msgstr "Nové pomodoro začíná" #~ msgid "Hey, you're missing out on a break" #~ msgstr "Hej, zapomínáš na přestávku" #~ msgid "Could not run pomodoro" #~ msgstr "Pomodoro nelze spustit" #~ msgid "Something went badly wrong..." #~ msgstr "Stalo se něco moc špatného..." #~ msgid "Looks like gnome-pomodoro is not installed" #~ msgstr "Vypadá to, že jste nenainstalovali gnome-pomodoro" #~ msgid "Install" #~ msgstr "Instalovat" #~ msgid "Short break duration" #~ msgstr "Délka krátké přestávky" #~ msgid "Shortcut to toggle the timer" #~ msgstr "Klávesová zkratka k přepnutí časovače" #~ msgid "Select sound for start of break" #~ msgstr "Vyberte zvukový soubor, který se přehraje na začátku přestávky" #~ msgid "Select sound for pomodoro start" #~ msgstr "Vyberte zvukový soubor, který se přehraje na začátku pomodora" #~ msgid "Pomodoro start sound" #~ msgstr "Zvuk na začátku pomodora" #~ msgid "Presence" #~ msgstr "Dostupnost" #~ msgid "Postpone pomodoro when idle" #~ msgstr "Odložit pomodoro v době nečinnosti" #~ msgid "Status during pomodoro" #~ msgstr "Stav během pomodora" #~ msgid "Status during break" #~ msgstr "Stav během přestávky" #~ msgid "" #~ "System notifications including chat messages won't show up during " #~ "pomodoro." #~ msgstr "" #~ "Systémová oznámení a zprávy z chatu se nebudou zobrazovat dokud je " #~ "pomodoro aktivní." #~ msgid "" #~ "System notifications including chat messages won't show up during break." #~ msgstr "" #~ "Systémová oznámení a zprávy z chatu se nebudou během přestávky zobrazovat." #~ msgid "System notifications including chat messages won't show up." #~ msgstr "Systémová oznámení a zprávy z chatu se nebudou zobrazovat vůbec." #~ msgid "OK" #~ msgstr "OK" #~ msgid "" #~ "The shortcut \"%s\" cannot be used because it will become impossible to " #~ "type using this key.\n" #~ "Please try with a key such as Control, Alt or Shift at the same time." #~ msgstr "" #~ "Klávesovou zkratku \"%s\" nelze použít protože by nešlo psát.\n" #~ "Zkuste ji stisknout zároveň s CTRL, ALE nebo Shiftem." #~ msgid "_No sound" #~ msgstr "_Bez zvuku" #~ msgid "_Cancel" #~ msgstr "_Zrušit" #~ msgid "_Open" #~ msgstr "_Otevřít" #~ msgid "Select a file" #~ msgstr "Zvolte soubor" #~ msgid "All files" #~ msgstr "Všechny soubory" #~ msgid "Other…" #~ msgstr "Další..." #~ msgid "None" #~ msgstr "Žádný" #~ msgid "Supported audio files" #~ msgstr "Podporované zvukové soubory" #~ msgid "Manage your time and tasks" #~ msgstr "Správa času a úkolů" #~ msgid "time;timer;tasks;manage;organize;" #~ msgstr "čas;časovač;úkoly;řídit;organizovat;" #~ msgid "Options" #~ msgstr "Možnosti" #~ msgid "Reset Counts and Timer" #~ msgstr "Vynulovat cykly a časovač" #~ msgid "Away From Desk" #~ msgstr "Nepřítomen" #~ msgid "Control Presence Status" #~ msgstr "Zkontroluj stav dostupnosti" #~ msgid "No Completed Sessions" #~ msgstr "Žádný kompletní cyklus" #~ msgid "%d Completed Session" #~ msgid_plural "%d Completed Sessions" #~ msgstr[0] "%d kompletní cyklus" #~ msgstr[1] "%d kompletních cyklů" #~ msgid "Pause finished." #~ msgstr "Konec pauzy." #~ msgid "Time in seconds you are supposed to be working." #~ msgstr "Délka pracovní doby ve vteřinách." #~ msgid "Short pause duration" #~ msgstr "Trvání krátké pauzy" #~ msgid "Time in seconds you are supposed to have a short break." #~ msgstr "Délka krátké pauzy ve vteřinách." #~ msgid "Long pause duration" #~ msgstr "Trvání dlouhé pauzy" #~ msgid "Time in seconds you are supposed to have a longer break." #~ msgstr "Délka dlouhé pauzy ve vteřinách." #~ msgid "Whether to show a notification dialog when pause starts." #~ msgstr "Jestli ukazovat notifikační dialog když začíná pauza." #~ msgid "Disable flexible breaks" #~ msgstr "Zakaž upravitelné pauzy" #~ msgid "Whether you are not using a computer to work." #~ msgstr "Jestli nepoužíváš k práci počítač." #~ msgid "Change user presence status to busy" #~ msgstr "Změň status uživatele na zaneprázdněn" #~ msgid "Whether to change user and IM presence to busy." #~ msgstr "Zdali změnit status uživatele a IM na zaneprázdněn." #~ msgid "Whether to play a sound to notify of events." #~ msgstr "Zdali přehrát zvuk při notifikaci události." #~ msgid "Notification sound file" #~ msgstr "Zvukový soubor pro notifikaci" #~ msgid "Restore timer state" #~ msgstr "Obnovit stav časovače" #~ msgid "Whether to restore state on startup." #~ msgstr "Jestli obnovit stav při startu." #~ msgid "Number of completed sessions" #~ msgstr "Počet kompletních cyklů" #~ msgid "Number of completed sessions since long break" #~ msgstr "Počet kompletních cyklů od dlouhé pauzy" #~ msgid "Saved timer state" #~ msgstr "Uložený stav časovače" #~ msgid "Time of saved state" #~ msgstr "Ćas uloženého stavu" #~ msgid "Click to reset session counts to zero" #~ msgstr "Klikni pro vynulování cyklů" #~ msgid "Set optimal settings for doing paperwork" #~ msgstr "Nastav optimální čas pro papírování" #~ msgid "Show a dialog message at the end of pomodoro session" #~ msgstr "Ukaž dialogové zprávy na konci pomodora" #~ msgid "Play a sound at start of pomodoro session" #~ msgstr "Přehraj zvuk na začátku pomodora" #~ msgid "Pomodoro Finished!" #~ msgstr "Konec pomodora" #~ msgid "Hide" #~ msgstr "Skryj" #~ msgid "Show dialog" #~ msgstr "Ukaž dialog" #~ msgid "Timer toggle key" #~ msgstr "Přepínací tlačítko časovače"
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Abstract This article examines the relationships between governance structures and regulatory approaches. It develops a typology to explain and fine-tune supranational regulatory models for the governance of markets. The article suggests, firstly, a range of regulatory options which are defined according to two dimensions: (a) the degree of centralization of regulation, which includes networks, meta-organizations, and single central authorities; and (b) the degree of invasiveness of regulation, which ranges from sunshine regulation to command and control approaches. The aim is to relate structural alternatives (considered in terms of centralization) to regulatory approaches (considered in terms of invasiveness). The typology here constructed is applied to analyse the governance structure of EU competition law. Secondly, the article focuses on the recent structural changes reshaping the governance of European financial markets. The reform is discussed through the lens of the typology. It appears that, differently from what was observed in the EU competition law model, the newly established European Supervisory Agencies (ESAs) are part of a complex structural development, in which the separation between a highly invasive regulatory approach and a decentralised supervisory structure adds further complexity. The article concludes by noting a set of possible normative implications, suggested by the typology, to ensure a consistent governance model for financial markets regulation and supervision in the EU.
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Globala fonden för energieffektivitet och förnybar energi (debatt) Talmannen Nästa punkt är ett betänkande av Claude Turmes, för utskottet för industrifrågor, forskning och energi, om den globala fonden för energieffektivitet och förnybar energi. Claude Turmes föredragande. - (DE) Herr talman! Martin Luther King hade en dröm. Han drömde om ett samhälle där hudfärg inte ledde till diskriminering. Det var en dröm som revolutionerade Amerika och världen. I dag har Europa en dröm, eller snarare en vision: att utveckla framtidens energi, inte bara i Europa utan också utanför våra gränser, och att förnybara energikällor ska spela en huvudroll i mitten av detta århundrade och bidra till att förhindra konflikter om de återstående olje- och gastillgångarna, lindra klimatförändringen och ge miljarder människor världen över tillgång till energi som är utom räckhåll för dem i dag. Jag menar att kommissionen, i dag företrädd av sitt miljösamvete Stavros Dimas, har all anledning att vara stolt över denna globala fond för energieffektivitet och förnybar energi (Geeref). Vi utgår från att det inom fyra eller fem år kommer att finnas 500 miljoner euro i fonden, vilket gör den till världens största fond för investeringar i förnybar energi och energieffektivitet. Dessa 500 miljoner euro kommer delvis att komma från offentliga medel, med mellan 80 och 150 miljoner euro från EU-budgeten, men även från de nationella regeringarnas budgetar. Vi har i dagsläget konkreta åtaganden från Tyskland och även från Norge. Vad kommer då fonden att uppnå? De finansanalytiker som tittar närmare på investeringsflöden till enskilda projekt avseende förnybar energi och energieffektivitet har konstaterat att det är svårt att uppbåda riskkapital för investeringar under 10 miljoner euro. Fonden kommer främst att inriktas på sådana medelstora projekt på upp till 10 miljoner euro. Den kommer därför att vara en fondandelsfond, vilket betyder att den inte kommer att investera direkt i vindkraftparker i Marocko eller solenergisystem i Kina utan kommer att förvärva andelar i investeringsfonder i södra Afrika, Centralafrika, Kina, Ryssland eller Sydamerika. Den offentliga kassan kommer på politisk väg att avgöra vart finansieringen ska gå. Fonden kommer att vara attraktiv för privata investerare eftersom den offentliga kassan i praktiken kommer att täcka hela investeringsrisken, så att den eventuella avkastningen på investeringarna först går till de privata investerarna och först i ett andra skede tillbaka till den offentliga kassan. Det innebär naturligtvis en stor säkerhet för privata investerare. Vi som parlamentsledamöter har tagit upp fyra eller fem frågor i anslutning till denna fond. Den första är också en konkret fråga till kommissionsledamot Stavros Dimas. Vid en tidpunkt då biobränslen är en oerhört kontroversiell fråga har vi som parlamentsledamöter ansett att vi måste tillämpa mycket strikta kriterier för alla investeringar från fondens sida i projekt avseende biomassa eller biobränsle. Det är inte bara den miljömässiga balansen som kan vara problematisk, utan det skulle också innebära ett imageproblem för fonden om dess rykte skulle fläckas av sådana investeringar. Kan ni alltså återigen, herr kommissionsledamot, garantera att kommissionen kommer att göra sitt bästa för att tillämpa de strikta kriterier som krävs? Den andra fråga som är viktig för oss som parlamentsledamöter, och särskilt de av oss som är intresserade av utveckling, är att vi vill att fonden i betydande utsträckning ska bidra till att lindra energifattigdomen. Vi måste därför utnyttja den kunskap som finns hos mikrofinansieringsinstitut som Grameen Bank och andra som redan genomför projekt för de allra fattigaste, t.ex. solfångare och fotoelektriska system. Vi måste engagera dessa mikrofinansieringsinstitut. Min andra fråga till er är denna: Är kommissionen, som den största offentliga givaren, villig att se till att 20-25 procent av finansieringen verkligen används för denna typ av mikroprojekt genom mikrofinansieringsarrangemang? För det tredje är vi rädda att all finansiering från Geeref kommer att gå till Kina, om det håller på att bli så lätt att investera där. Vi vill dock ha en god geografisk spridning av investeringarna, och därför behöver vi ett politiskt åtagande från kommissionen om att medel även kommer att beviljas för investeringar i länder i Afrika, Västindien och Sydamerika. Som parlament kräver vi sträng övervakning och utvärdering med regelbundna rapporter till parlamentet och dess budgetutskott och budgetkontrollutskott, för vi vill att denna fond om möjligt ska växa under de närmaste åren. Det kräver givetvis att parlamentet har förtroende för hur fonden fungerar. Detta är mina inledande kommentarer, och jag ser fram emot debatten med mina kolleger i parlamentet. (Applåder) Stavros Dimas ledamot av kommissionen. - (EL) Herr talman, mina damer och herrar! Mer än ett år har gått sedan offentliggörandet av kommissionens meddelande ”Mobilisering av offentlig och privat finansiering för global tillgång till klimatvänlig, ekonomiskt överkomlig och trygg energiförsörjning genom den globala fonden för energieffektivitet och förnybar energi” (Geeref). Sedan dess har mycket hänt - vi fick exempelvis Baliöverenskommelsen i december förra året. Initiativet framstår därför nu som ännu viktigare och lägligare. Detta är därmed en lämplig tidpunkt att debattera betänkandet, och jag konstaterar med tillfredsställelse att Europaparlamentet är mycket positivt till detta nya och innovativa sätt att stödja projekt som avser energieffektivitet och förnybar energi. Låt mig först förklara varför kommissionen har föreslagit att den globala fonden för riskkapital för näringsverksamhet ska få offentliga bidrag, även om Claude Turmes redan har angett de främsta skälen till att vi fattade detta beslut och dessutom har ställt en del frågor. Trots de kontinuerliga framstegen när det gäller användning av förnybara energikällor utgör de fortfarande en liten del av de totala energikällorna världen över. Det är också väl känt att en förbättrad energieffektivitet kan ge större vinster än skapandet av en ny energiinfrastruktur. Med de investeringar i energieffektivitet som görs världen över utnyttjas ändå inte de befintliga möjligheterna till förbättringar till fullo. De avsevärda svårigheterna med att finna privat finansiering för projekt som gäller energieffektivitet och förnybar energi är alltså ett stort problem. Orsakerna är komplexa och hänger främst samman med bristen på riskkapital till näringsverksamhet. Riskkapital är nödvändigt i utvecklingsländer, och i övergångsekonomier uppskattas behovet till mer än 9 miljarder euro per år. Det är mycket mer än vad som finns tillgängligt i dag. De offentliga bidragen har visserligen ökat på senare år, men det totala tillgängliga beloppet är otillräckligt. Ytterligare kapital krävs i energisektorn fram till 2030. Sökandet efter finansiering från den privata sektorn är alltså av avgörande betydelse. De många år som krävs innan investeringar i ren teknik lönar sig hindrar dock investerarna, särskilt i geografiska områden som bedöms vara förknippade med hög risk. De privata investeringarna i Afrika söder om Sahara är exempelvis mycket små, och just därför är ett av syftena med Geeref att främja investeringar i dessa områden. Det belopp som Claude Turmes nämnde är ungefärligt, och det är ett minimum för investeringarna i dessa områden. Ett annat problem som Claude Turmes tog upp är projektens omfattning. Kostnaderna för administration och genomförande kan vara högre för småskaliga projekt i avlägsna länder. Internationella finansieringsorgan är därför ovilliga att finansiera sådana projekt, särskilt om de understiger 10 miljoner euro, som ni sa. Syftet med Geeref är just att övervinna sådana hinder för småskaliga investeringar. Vi kommer att koncentrera våra insatser till projekt av det slaget. Fonden kommer att dra till sig privata investerare genom att använda offentliga medel för att skydda dem mot de risker jag nyss nämnde. För att Geerefs verksamhet ska kunna komma i gång kommer kommissionen att anslå omkring 80 miljoner euro från och med i år och fram till 2010. Som ni sa tidigare har vi, med de ytterligare åtagandena från regeringarna i Tyskland och Norge, nått över 100 miljoner euro. Vi förväntar oss att ytterligare riskkapital kommer att hämtas från den privata sektorn - minst 300-500 miljoner euro och kanske så mycket som 1 miljard euro på lite längre sikt. Det gläder mig att Europaparlamentet i detta betänkande stöder inrättandet av den globala fonden för energieffektivitet och förnybar energi. Jag vill tacka föredraganden Claude Turmes för hans insatser och även Anders Wijkman och Eija-Riitta Korhola från utskottet för utveckling respektive utskottet för miljö, folkhälsa och livsmedelssäkerhet för deras bidrag. Jag anser att detta är ett viktigt och lägligt initiativ som visar att EU vidtar åtgärder och är fast beslutet att hjälpa utvecklingsländerna att få möjligheter till energieffektivitet och tillgång till förnybara energikällor. Det grundläggande villkoret för finansiering av projekt - inte bara sådana som avser biomassa eller biobränsle - kommer utan tvekan att vara respekt för hållbarhetskriterier, som inte kommer att vara mindre stränga än de som fastställts i EU:s lagstiftning på olika områden. Detta kommer att stärka det förtroendeförhållande vi måste upprätta med de här länderna, särskilt med avseende på det globala klimatförändringsavtalet, som bör ingås före utgången av 2009. (Applåder) Eija-Riitta Korhola föredragande för yttrandet från utskottet för miljö, folkhälsa och livsmedelssäkerhet. - (FI) Herr talman! Klimat- och energifrågorna har snabbt fått en avgörande betydelse inom nästan alla EU:s politikområden. Kravet på ökad användning av förnybar energi är aktuellt just nu, inte minst mot bakgrund av de kvalitativa mål som nu beslutats för förnybar energi. Denna fond är ett lysande och hoppingivande exempel. Detta är dock inte alltid en självklar fråga. Något som ligger i tiden politiskt sett kan bli ett avgörande prov på politisk korrekthet, och det hela kan resultera i en tävling om vem som snabbast tar ställning för allt som är bra. Så verkar det ha varit den senaste tiden när det gäller det mål för förnybar energi som tillkännagetts. Förslaget framstår också till viss del som överambitiöst, och den tidtabell som fastställts har uppenbara risker. När den verkliga tekniska potentialen fortfarande saknas finns det en risk för att ett bindande mål kommer att förverkligas på ett sätt som innebär att naturliga värden oåterkalleligen går förlorade. Alla biobränslen är inte bra för miljön, och alla förnybara energiformer bidrar inte till minskade utsläpp, som Claude Turmes helt riktigt påpekade alldeles nyss. Det finns ett behov av förnybar energi, men frågan bör hanteras på ett förnuftigt sätt. Den globala fond för energieffektivitet och förnybar energi som vi nu diskuterar är ett utmärkt exempel på hur någonting bra kan främjas på ett sätt som medför en lång rad fördelar. Det finns ett gammalt ordspråk om att man inte bara ska ge de fattiga fisk utan också lära dem att fiska. Detta kan tillämpas på finansiering av lokala projekt, så att kunskap och färdigheter förbättras och bibehålls i tredjeländer. På så sätt kan projekt göras hållbara och varaktiga. Romana Jordan Cizelj för PPE-DE-gruppen. - (SL) Åtgärder mot klimatförändringen och energifrågor är två viktiga inslag i EU:s utvecklingspolitik. Så bör det också vara. Jag ställer mig bakom alla initiativ som kan bidra till en säker och hållbar energiförsörjning, inte bara i EU utan även i tredjeländer. Jag vill dock lyfta fram några frågetecken som måste rätas ut innan fonden inrättas. För det första ökar ständigt antalet initiativ inom energi- och utvecklingspolitiken. Tyvärr är det relativt sällan som de uppsatta målen faktiskt nås. Initiativen i form av olika fonder är inte harmoniserade sinsemellan, och framför allt används de sällan för direktfinansiering av enskilda projekt. Detta gäller även den fond vi diskuterar, som bör fungera genom att regionala delfonder inrättas och finansieras i utvecklingsländer. Vi bör överväga hur det kommer att påverka insynen i utnyttjandet av medlen och i vilken utsträckning de institutionella förutsättningarna i utvecklingsländerna kommer att underlätta det planerade utnyttjandet. För det andra är det endast åtgärder som ligger rätt i tiden som kan vara effektiva. När det gäller den föreslagna globala fonden framgår det inte tydligt att tidpunkten är lämplig. Förslaget lades fram 2006 och vi debatterar det först i år. För det tredje vill jag framhålla det som sägs i själva dokumentet: de medel som anslagits för fonden är inte tillräckliga. Inte ens det minimibelopp som krävs för att fonden ska fungera på ett framgångsrikt sätt har säkrats. Detta kommer knappast att bidra till att stimulera investeringar av den privata sektorn. För det fjärde har jag svårt att föreställa mig att fonden kan fungera effektivt enbart genom samarbete mellan EU och internationella finansinstitut. Vårt förslag saknar en tydlig ambition och en plan för samarbete med andra industriländer i världen och för internationalisering av den globala fonden. Som tidigare sagts är tanken god, men mervärdet och det faktiska genomförandet kräver en del övervägande. Matthias Groote för PSE-gruppen. - (DE) Herr talman, herr kommissionsledamot, mina damer och herrar! Först och främst vill jag gratulera föredraganden Claude Turmes till hans goda arbete och hans engagemang. Den globala fonden för energieffektivitet och förnybar energi är ett aktivt bidrag från EU till kampen mot klimatförändringen. Som skuggföredragande från utskottet för miljö, folkhälsa och livsmedelssäkerhet vill jag ta upp två frågor. För det första är det viktigt att se till att hållbarhet har absolut prioritet i samband med projekt som ska stödjas av fonden. Utsläppen av växthusgaser måste analyseras över hela livscykeln, och ingen finansiering bör ges till projekt med ett otillfredsställande resultat i fråga om koldioxidutsläpp. Denna analys är särskilt viktig för projekt som avser biomassa. För det andra är jag optimist och utgår därför från att FN:s klimatförändringskonferens i Köpenhamn nästa år blir framgångsrik och att vi kommer att kunna ta nästa steg mot ett avtal som utgör Kyotoprotokollets efterföljare. Användning av förnybar energi kommer då att spela en viktig roll för utvecklingsländerna. Kommissionen måste i dag anpassa fonden med hänsyn till detta. Fiona Hall för ALDE-gruppen. - (EN) Herr talman! Kommissionens förslag om en global fond för energieffektivitet och förnybar energi (Geeref) är naturligtvis välkommet. Det är av avgörande betydelse att energieffektivitet och förnybar energi spelar en större roll i utvecklingsländer och framväxande ekonomier, och det av ett antal olika skäl: för att minska koldioxidutsläppen, begränsa beroendet av energiförsörjning, åtgärda energifattigdomen och skapa sysselsättnings- och utvecklingsmöjligheter - i själva verket av samma skäl som gör att energieffektivitet och förnybar energi måste spela en större roll här i EU. Jag har dock ett antal farhågor när det gäller kommissionens förslag. För det första är den föreslagna finansieringen oerhört blygsam i förhållande till projektets omfattning. Femton miljoner euro per år i offentlig finansiering är en struntsumma - även som såddkapital för att dra till sig och säkra privata investeringar. Beloppet kan lätt slukas av bara ett par projekt i de större framväxande ekonomierna som Kina eller Indien. I kommissionens meddelande nämns visserligen möjligheten till samfinansiering från nionde Europeiska utvecklingsfonden, men det är inte alls klart hur besluten kommer att fattas om budgetens fördelning mellan AVS-länderna och de mer utvecklade och avancerade östeuropeiska länder utanför EU som får stöd genom samfinansiering från Europeiska banken för återuppbyggnad och utveckling (EBRD). Det är därför inte alls klart hur fonden kommer att bidra till fattigdomsbekämpningen. Det verkar vara en makrofond snarare än en mikrofond, utformad för att uppbåda privat finansiering till stöd för projekt som, även om de är relativt små med europeiska mått mätt, skulle vara stora i många afrikanska länder. Det framgår inte hur finansieringen från Geeref ska tränga ned till projekt på EU-nivå, t.ex. PV-paneler för vårdcentraler och skolor eller solkök och solvärmda varmvattenberedare. I allmänhet är det utveckling på gräsrotsnivå som innebär störst förbättringar av de fattigaste människornas liv. Slutligen bekymrar det mig att förhållandet mellan fonden och mekanismen för en ren utveckling (CDM) inte tydligt har förklarats. Det vore bra om kommissionen kunde tala om hur fonden kommer att bidra till att förbättra utvecklingsländernas tillgång till CDM. Esko Seppänen för GUE/NGL-gruppen. - (FI) Herr talman! Claude Turmes betänkande gäller ett mycket ambitiöst mål för utvecklingsländerna i fråga om ett effektivt utnyttjande av energitillgångarna. Dessa länder är ofta belägna i geografiska områden där det är möjligt att exploatera billiga naturliga förnybara energitillgångar. Utvecklingen kan också gå framåt utan enorma investeringar i den senaste tekniken. Produktion av träkol med användning av de knappa skogsresurserna i de områden i Afrika söder om Sahara som håller på att omvandlas till öken är ett mer kostnadseffektivt sätt att använda skogsresurserna än att bara bränna upp dem. De måste få veta hur trä bränns till kol innan det eldas. Det behövs inte särskilt mycket pengar för att lära ut sådana och andra färdigheter. Jag tolkar principerna för hur Geeref fungerar som att det inte kommer att vara möjligt att få pengar från fonden bara för att sprida färdigheter och kunskap, men andra former av utvecklingsbistånd kan givetvis användas i detta syfte. Finansiering av projekt genom riskkapitalinvesteringar är ett intressant alternativ. Det som är bra med detta sett ur mottagarnas och användarnas perspektiv är att det inte ökar skuldsättningen för redan skuldsatta länder. Frågan uppstår dock hur dyrt det kommer att bli att förvalta dessa investeringar och kontrollera småföretagens förmåga att betala tillbaka pengarna. Denna fond skulle i bästa fall kunna göra utvecklingsländerna redo att öka sin användning av fossila bränslen i långsammare takt. Vår grupp stöder enhälligt Claude Turmes betänkande. Paul Rübig (DE) Herr talman! Tack så mycket, Claude. Du har hållit väldigt många möten om det här ämnet. Det är en mycket komplex fråga, och jag vill tacka dig särskilt för din konsekventa öppenhet under alla dessa förhandlingar och för att du gett oss möjlighet att se projektet ur ett holistiskt perspektiv. Dagens globala utmaning är att sträva efter effektivitet, i samband med energiförbrukning men även i samband med produktion. Detta kan dock inte bara gälla på makronivån. Vi måste alltid låta oss vägledas av grundsatsen ”tänk litet först” - titta på mikronivån först, och om det fungerar där kommer det också att fungera på makronivån. Vi måste inrikta oss på att se till att vi tillämpar den bästa teknik som finns att tillgå globalt sett. Det kan handla om enkel, tydligt strukturerad teknik - det behöver inte vara elektronik och nanoteknik. Vi måste i möjligaste mån försöka göra denna teknik ekonomiskt tillgänglig, så att alla har råd att använda den. Å andra sidan måste vi givetvis också straffa dem som förslösar vår jords tillgångar. Detta är också en stor utmaning för vår kommissionsledamot - att titta på de globala strukturerna och straffa dem som slösar med energi och belöna dem som använder den bästa och mest effektiva tekniken. Detta är en central princip även inom klimatpolitiken. Undersökningar i EU visar att kostnaderna för klimatförändringen kommer att uppgå till många miljarder euro. Det är därför nödvändigt att inte bara göra något för länderna utanför Europa - rådet bör också överväga att tillhandahålla nya medel för forskning och utveckling på energieffektivitetsområdet, särskilt vid det nya Europeiska tekniska institutet. Jorgo Chatzimarkakis (DE) Herr talman, herr kommissionsledamot! Tack för ert bidrag. Europaparlamentet välkomnar denna fond. Kommissionsledamot Dimas, ni har tagit rätt slags initiativ vid rätt tidpunkt. Om vi som européer är beslutna att begränsa koldioxidutsläppen spelar det ingen roll var koldioxiden släpps ut. Koldioxidutsläppen måste minska världen över, och vi måste därför tillämpa den nya tekniken överallt. Jag ser emellertid inte denna fond enbart som ett utvecklingsinstrument utan även som ett strategiskt instrument. Det handlar inte bara om att ge utvecklingsbistånd. Vi européer måste i själva verket inte bara vara banbrytande i klimatförändringsfrågan, utan vi måste också uppmuntra andra att följa med oss på resan. De måste kunna följa samma väg som vi. Där tror jag att denna fond kan bidra på ett avgörande sätt. Om vi sätter upp alltför ambitiösa mål och det slutar med att vi blir isolerade och ensamma kommer det att innebära slutet även för vår industriella bas. Därför finns det ett behov av globalt styre här. Bali var en god ansats och Köpenhamn blir ännu en. I ett system med globalt styre handlar det emellertid inte bara om maktspel. Vi måste skapa stimulanssystem och jag anser att rätt slags incitament skapas med hjälp av denna fond. Claude Turmes talade i inledningen av sitt anförande om Martin Luther Kings dröm. Som européer kan vi bara förverkliga vår dröm om att rädda klimatet om vi konsekvent fortsätter längs denna väg. Claude Turmes, ni kommer att säkra en mycket stor majoritet för detta betänkande i morgon, och jag vill här och nu gratulera er till det resultatet. Jag är mycket glad för er skull. Silvia-Adriana Ţicău (RO) EU:s fond för energieffektivitet och förnybar energi är en innovativ lösning för att maximera effektiviteten hos de offentliga medel som används för energieffektivitet och förnybara energikällor genom att mobilisera privata investeringar. Fonden utgör ett offentlig-privat partnerskap avsett för finansiering av konkreta projekt som föreslås av små och medelstora företag och vars värde inte överstiger 10 miljoner euro. Startkostnaderna för projekt avseende förnybar energi är 37 gånger högre än för konventionella energikällor, och vi beklagar därför att fondens planerade värde i dagsläget bara är 100 miljoner euro. År 2005 importerade EU 50 procent av sin energi, och bland medlemsstaterna är det bara Danmark som är nettoexportör. Under perioden 1995-2005 ökade utnyttjandet av förnybara energikällor med 40 procent i EU. Energikällor som inte ger upphov till föroreningar stod därmed för 42 procent av EU:s produktion av primärenergi under 2005. Om denna fond utnyttjas effektivt skulle mellan 1 och 3 miljoner medborgare kunna förses med energi, samtidigt som koldioxidutsläppen skulle minska med 1-2 miljoner ton per år. Jag vill gratulera föredraganden. Teresa Riera Madurell (ES) Herr talman, herr kommissionsledamot! Jag vill till att börja med gratulera Claude Turmes till hans betänkande och kommissionen till dess initiativ. Många av oss menar att EU måste överväga stöd för förnybara energikällor och energieffektivitet inte bara som en integrerad del av sin energi- och klimatstrategi, utan även som en integrerad del av sin utvecklingspolitik. Förslaget om att inrätta en global fond för energieffektivitet och förnybar energi för att mobilisera privata investeringar för utvecklingsländer och övergångsekonomier är därför mycket intressant. För att på bästa sätt uppbåda blygsam finansiering krävs att prioriteringar fastställs och synergieffekter åstadkoms med befintliga program och med Världsbanken och regionala utvecklingsbanker, som i allt större utsträckning investerar i förnybara energikällor och i energieffektivitet. Efter de första årens genomförande av det nya instrumentet måste dock resultaten utvärderas och insatser göras för att främja avsevärt ökade bidrag från de berörda aktörerna. Jag håller med om att allt för närvarande tyder på att stödet främst bör gå till Afrika och Latinamerika. Jerzy Buzek (PL) Herr talman! Jag vill tacka kommissionsledamoten och vår föredragande för ett lysande förslag, som jag stöder till fullo. Det sänder en mycket bra signal från EU:s sida. Jag talar om viljan att stödja utvecklingsländerna och att bekämpa klimatförändringen. Jag vill dock ställa följande fråga till kommissionsledamoten: Hur tänker kommissionen förhindra avskogning, som ofta hänger samman med produktion av biomassa och biobränslen i utvecklingsländer? Håller kommissionen dessutom ett lämpligt avstånd till produktionen av första generationens biomassa och biobränslen, eftersom det är väl känt att den inte är särskilt säker? Jag vill uttrycka mitt starka stöd för Jorgo Chatzimarkakis uttalande. EU måste sända en signal av detta slag. Vi ansvarar för de klimatförändringskonferenser som snart ska hållas i Poznań och Köpenhamn, och för att förhandlingarna om Kyotoprotokollets efterföljare blir framgångsrika. Vi har också ansvaret för att sända rätt signaler till övriga världen. Detta program är just en sådan signal. Zbigniew Krzysztof Kuźmiuk (PL) Herr talman! Jag vill uppmärksamma tre frågor. Det är helt riktigt av betänkandets föredragande att påpeka att klimatförändringen får allvarligast konsekvenser i de fattigaste länderna. Detta beror på att de har mycket begränsade resurser, särskilt ekonomiska, för att bemöta klimatförändringen. För det andra är det rätt att mot denna bakgrund stödja kommissionens förslag om att inrätta en fond, även om de 80 miljoner euro som föreslås är ett ynkligt belopp. Men eftersom avsikten med fonden är att bidra till ökade investeringar av den privata sektorn för att finansiera lokala projekt kan den ändå komma att visa sig mycket effektiv. För det tredje vill jag passa på att påpeka att den börda som kampen mot klimatförändringen utgör inte alls delas lika inom EU självt. De olika länderna tilldelades gränsvärden för koldioxidutsläppen utan tillräcklig hänsyn till hur långt efter de låg i sin utveckling. Länder som Polen gavs därför mycket låga gränsvärden, och det ledde nästan omedelbart till att elkostnaden steg med mellan 10 och 20 procent. Czesław Adam Siekierski (PL) Herr talman! Det främsta syftet med denna fond är att främja privata investeringar och stöd från regionala fonder till världens fattigaste och minst utvecklade länder. Fonden är avsedd att stödja energieffektivitet, energibesparingar, utveckling av förnybar energi och minskade utsläpp av växthusgaser. Den är också avsedd att bidra till en bättre tillgång till grundläggande energitjänster. EU:s insatser på detta område bör hjälpa fattigare regioner att motverka klimatförändringen och att diversifiera energikällorna. Vi måste komma ihåg att det är de fattigaste invånarna på vår planet som först känner av klimatförändringens effekter. Det vore fel av oss att begränsa åtgärderna för att bekämpa klimatförändringen och minska energiförbrukningen enbart till vårt eget område. Om fattigare länder ges tillgång till stöd för sådana åtgärder kan de göra lämpliga insatser på sitt eget territorium. Stödet kommer att få stor effekt och kommer att leda till en ökad medvetenhet om betydelsen av dessa problem. Detta är rätt initiativ vid rätt tidpunkt. Ewa Tomaszewska (PL) Herr talman! Jag vill bara påpeka att vi när det gäller förnybara energikällor inte har ägnat särskilt stor uppmärksamhet åt geotermala tillgångar, dvs. ren energi. Om man använder befintliga borrhål som gjorts för geologiska forskningsändamål skulle kostnaden kunna begränsas. Stavros Dimas ledamot av kommissionen. - (EN) Herr talman! Naturligtvis ingår geotermisk energi. Vi är mycket intresserade av både geotermisk energi och andra förnybara energikällor. När det gäller Polen och tilldelningen av utsläppsrätter vill jag påpeka att de för den första handelsperioden fick mycket mer än vad som var nödvändigt för energibehovet och industrins behov, och det var denna övertilldelning som orsakade problemet med priset på utsläppsrätter. Inför den andra handelsperioden ansåg vi att de utsläppsrätter som Polen tilldelats återigen gott och väl räcker för att tillgodose den polska industrins behov. För den tredje handelsperioden finns det ett nytt system som kommer att grundas på vad industrin eller kraftverken behöver för att täcka sina behov, med auktioner i en omfattning som vi kommer att enas om. När det gäller avskogning är det givetvis en mycket viktig fråga med anknytning till både biologisk mångfald och klimatförändring - båda har lika stor betydelse. Att motverka avskogning bidrar både till att stoppa förlusten av biologisk mångfald och till att bekämpa klimatförändringen, så detta är av mycket stor betydelse. Avskogningsprojekt har dock en egenhet: de är mycket svåra. Ändå är det en av de främsta prioriteringar vi måste ta itu med, inte bara med hjälp av denna fond, utan även genom ett antal andra åtgärder. Framför allt måste vi enas om vilka incitament som bör kopplas till de olika metoderna för att bekämpa avskogning, t.ex. att minska avskogningstakten och bevara skogarna eller andra metoder som främjas i olika länder. Vi arbetar med detta, särskilt tillsammans med Världsbanken, och pilotprojekt kommer att inledas. Det finns alltså olika finansieringskällor för olika ändamål. Jag vill först och främst uttrycka min uppskattning för de utmärkta och positiva bidragen, och jag kan försäkra er att vi kommer att ta hänsyn till era förslag och synpunkter i vårt arbete. De är mycket värdefulla och gäller olika viktiga frågor. Jag tänker inte i dag ge något svar om t.ex. betydelsen av CDM-projekt i Afrika söder om Sahara. Jag vill bara påminna er om att vi 2006 i Nairobi fick initiativet av FN:s dåvarande generalsekreterare Kofi Annan för att främja CDM-projekt i Afrika söder om Sahara. Vi har i likhet med FN för avsikt att genomföra fler projekt där och inte bara koncentrera oss på projekt i Kina och Indien. Er kommentar är alltså mycket viktig, men förhållandet mellan denna fond och CDM-projekt kan givetvis urskiljas och kan vara av betydelse. Jag har ytterligare tre kommentarer. För det första efterlyser ni en särskild betoning av behoven i länder söder om Sahara och AVS-länder. Vi är självfallet rädda för att projekt i stora länder som Kina och Ryssland kommer att sluka alla eller en alltför stor del av de tillgängliga resurserna. Detta har förresten hänt i fallet med CDM, och därför är er iakttagelse riktig. Geeref kommer att användas för befintliga investeringsmöjligheter, men vi håller med om att en särskild betoning på AVS-ländernas behov är nödvändig. Vi kommer också att se till att eventuella delfonder som bara omfattar ett land inte får sluka alla eller större delen av de tillgängliga resurserna. Geeref måste spridas till olika delar av världen, även för att sprida investeringsrisken, och Claude Turmes förslag om den procentuella andelen är helt riktigt. Låt mig för det andra återvända till fattigdomsaspekten, som givetvis är grundläggande. Som ni nämnt i dag finns det fortfarande omkring 1,6 miljarder människor i världens fattigare länder som inte har regelbunden tillgång till tillförlitliga energitjänster. Jag anser att vi med Geeref kan bidra till att ge människor tillgång till ren och billig energi - en nödvändig förutsättning för att minska den globala fattigdomen och främja hållbar utveckling. För det tredje och sista - ni välkomnar fondens inriktning mot att öka de privata investeringarna, även om ni har påpekat att medlen inte är tillräckliga. Jag tror inte att medlen någonsin är tillräckliga. Ni uppmanar också fler medlemsstater att erbjuda ytterligare finansiellt stöd. Jag stöder er naturligtvis till fullo och ställer mig bakom ert förslag. Kommissionen arbetar med att få fler investerare att ansluta sig, och det arbetet kommer att fortsätta. I detta avseende vill jag också be om ert stöd när det gäller att marknadsföra Geeref hos alla relevanta aktörer. Ju mer stöd vi har desto fler konkreta insatser kommer vi att kunna göra på fältet. Claude Turmes föredragande. - (EN) Herr talman! Detta blir en fond på potentiellt 500 miljoner euro, eftersom den har en hävstångsfaktor på mellan 3 och 5 för det privata kapitalet. De offentliga medlen på 100, 120 eller 150 miljoner euro hoppas vi kommer att kunna öka med ytterligare 300 eller 400 miljoner euro så att vi når 500 miljoner euro. Och det finns fortfarande regeringar som kan ansluta sig. Om vi har god övervakning kommer parlamentet att ge kommissionen tillåtelse att höja. Jordan Cizelj tog upp en mycket viktig fråga: Hur förberedda är vissa regioner i världen för investeringar? Vi i parlamentet har röstat för att ytterligare 5 miljoner euro från en annan budgetpost för institutionell kapacitetsuppbyggnad ska användas för uppbyggnaden av detta program. Vi behöver alltså bygga upp små och medelstora företag i afrikanska länder och i Indien, som sedan utvecklar affärsmodeller. Vi måste lära av tidigare utvecklingspolitiska misstag där vi bara tillhandahöll teknik utan att tänka på att vi också måste informera människor om denna teknik. Detta säger jag inför kommissionsledamoten med ansvar för utveckling, och vi vet att GD Bistånd hjälper dessa länder med att öka sin institutionella kapacitet. Vad vi alltså behöver göra nu - och ni har rätt, herr kommissionsledamot - är att försöka nå ut till investerarna. På fredag kommer det att hållas ett bankmöte i Luxemburg, som är världens näst största investeringscentrum. Vi kommer att presentera ett Luxemburgbaserat SICAV-bolag för dem. Jag hoppas att kommissionen kommer att utarbeta en bra kommunikationsstrategi. Åk till City of London, åk till Frankfurt, till Paris, till Zürich, för bankerna måste få information om detta bolag. Varför är det viktigt just nu? Vi upplever fortfarande en press till följd av Liechtensteinskandalen och subprime-krisen. Under flera månader har vi förstört hundratals miljarder i kapital. Att få in ett miljötänkande i finansvärlden kanske är en ännu viktigare uppgift för vår planet och beslutsfattarna än att göra motsvarande i industrin. Med denna typ av bolag ser vi till att kapitalet går till rätt investeringar. Avkastningen kanske inte är lika hög som för vissa spekulativa investeringar, men det är en investering på medellång och lång sikt, och det är antagligen precis vad vissa pensionsfonder och andra fonder är ute efter. Denna fond har alltså också enorma möjligheter att dra till sig institutionella investerare, och det är det vi bör sträva efter. Tack så mycket för ert stöd för vad jag kallar supportergemenskapen för en förnybar och bättre värld. Talmannen Herr Turmes! Tillåt mig att gratulera er till er utmärkta engelska och till ert engagemang i detta ämne. Debatten är härmed avslutad. Omröstningen kommer att äga rum på torsdag den 14 mars. Skriftliga förklaringar (artikel 142) John Attard-Montalto skriftlig. - (EN) Skälen till att inrätta denna fond förtjänar vårt beröm. Men resurserna som tillförs fonden är ett skämt. Huvudsyftena med fonden bör vara att främja energieffektivitet, energibesparingar, förnybara energikällor, minskade utsläpp av växthusgaser och förbättrad tillgång till energitjänster i de fattigaste länderna, för att inte nämna ett breddat utbud av energikällor i utvecklingsvärlden. Statistiken (som redan är föråldrad) tyder på att 1,6 miljarder människor inte har tillgång till grundläggande energitjänster och 2,4 miljarder människor litar till traditionell biomassa för matlagning och uppvärmning. Internationella energiorganet uppskattar att det till 2010 kommer att behöva investeras 241 miljarder US-dollar i alstring av förnybar energi. För utvecklingsländerna uppskattas att det krävs minst 10 miljarder US-dollar, eller 9 miljarder euro. Den föreslagna budgeten för denna fond, som nu diskuteras, ligger på 80 miljoner euro mellan 2007 och 2010, med 15 miljoner euro för 2008 för att sätta fart på initiativet. Siffrorna talar för sig själva. Dessa resurser är en droppe i havet av vad som behövs. Avsikterna är goda, men avsikter med påvra medel är inte ett seriöst initiativ. Gyula Hegyi skriftlig. - (HU) Europeiska unionens stöd till fjärrvärme! Jag välkomnar kommissionens initiativ till den nya globala fonden för energieffektivitet och förnybar energi (Geeref). Att trygga vår energiförsörjning - och att göra detta på ett sätt som inte riskerar våra miljövärderingar, vår strategiska säkerhet eller konkurrenskraft - är en av 2000-talets största utmaningar. Den billigaste energin är självklart den energi vi inte använder, med andra ord den energi vi sparar. I dessa energifattiga tider ligger energibevarande i allas största intresse, oavsett om det handlar om konsumenter eller större samhällen. Från ett vänsterperspektiv måste det framhållas att energibevarande och effektivt energiutnyttjande också är en samhällsfråga, eftersom det oftast är de fattigaste, framför allt, som förbrukar mest energi. Detta gäller särskilt de nya medlemsstaterna, till exempel hushåll i ungerska bostadsområden, som använder dubbelt så mycket energi per kvadratmeter som i västra Europa. Därför är det viktigt att tillhandahålla EU-medel för modernisering av östra Europas fjärrvärmesystem. I teorin är fjärrvärme ett energisparande system och har fördelen att den är enkel att anpassa till förnybara energikällor. När det gäller individuell uppvärmning skulle detta behöva göras i varje enskilt hus. Att göra EU:s resurser tillgängliga för fjärrvärme är därför centralt. Man skulle också kunna överväga att införa enhetliga skattelättnader i hela EU för att underlätta investeringar i energibevarande och skapa resurser för detta ändamål. Bogusław Rogalski skriftlig. - (PL) Förnybar energi och energieffektivitet bidrar till att bromsa höjningen av snittemperaturen i världen. Som forskning och rapporter visar är det just de fattigare samhällena och deras fattigaste invånare som drabbas hårdast av klimatförändringarnas negativa konsekvenser. Det är därför vår skyldighet att skydda dessa samhällsgrupper, på grund av att de är mer ekonomiskt sårbara. Användningen av förnybara energikällor bidrar bland annat till att höja miljöstandarderna, till exempel genom att minska koldioxidutsläppen och andra växthusgaser. De bidrar också till att öka sysselsättningen och sänka kostnaderna. Ett annat viktigt argument för förnybara energikällor är att de minskar beroendet av specifika energikällor när alltfler människor saknar tillgång till grundläggande energitjänster. Detta är särskilt viktigt när det handlar om att forma utvecklingsländernas ekonomier. De flesta av dessa länder upplever ekonomisk tillväxt, och efterfrågan på energi är därför stor i dessa områden. Att utveckla förnybara energikällor i utvecklingsländer är högst relevant för arbetet med att begränsa utsläppen av växthusgaser och trygga en säker försörjning i länder som bara delvis kan uppfylla sina egna energibehov. Unionen bör därför stödja förnybara energikällor och energieffektivitet, särskilt i utvecklingsländer, eftersom de är mycket viktiga led i strategin för energi och klimatförändringar, och även inom utvecklingspolitiken.
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Im excited because Im still holding out hope that we are either going to draft Geno, or trade back and get our 2nd back + more picks. If we end up take Fisher or Joker 1st overall I'll probably go kick a puppy. And to think I wasted a lot of emotions pulling for losses after it became apparent we were going nowhere last fall. I think we would be better off if we were drafting a few slots back ... better possibility for a trade to recover the 2nd. round pick. If they could some how trade back and recover a 2nd. round pick, I'd be more interested. There is suppose to be really good prospects in the 2nd. round & I do believe Dorsey/Reid are better talent evaluators than the last so called "expert." So, I'll check to see just who the 1.1 choice will be and go about more important things. May not be the proper thread to express this ... but, if they pass on a QB in this draft, a couple things better happen: #1. Alex better win at least one S.B.; #2. or Geno, Barkley, etc. all better be busts. If one of them turns out to be even a franchise QB, I'm going to be really upset. #3. Just thought ... in the next couple of years, I guess they could hit on finding an elite QB (i.e. Kap., Russel Wilson, Brees, Farve, etc.) in the mid rounds and that would erase the sting of not getting one this year. I would have been okay with a drafted QB leading us to the same ole 40+ years of frustrations ... at least they would have tried at drafting and developing a QB. I'll not be satisfied with another "Montana" experiment ... win a lot of games but not quite to the promise land. So, you can see that I'm really hopeful for the Chiefs future!!! Another reason I'm not excited about this draft. I think there is less than a 5% chance of Reid/Alex winning a SB. Retread guys seldom win it all. I think the only good thing that will come from this draft is that maybe guys will stop mocking the chiefs to take LTs in the first round next year. Other than that, I'm pretty pessimistic about it. Whoever we pick will never live up to the expectations of a first overall pick. If you had told me we would have 1.1 this year and that I would not be excited, I wouldn't have believed you. Yet, here we are. If we have a realistic shot at taking Geno, yes otherwise totally meh on a lineman. __________________ "Not every one that saith unto me, Lord, Lord, shall enter into the kingdom of heaven; but he that doeth the will of my Father ... And then will I profess unto them, I never knew you: depart from me, ye that work iniquity." "If the people let government decide what foods they eat and what medicines they take, their bodies will soon be in as sorry a state as are the souls of those who live under tyranny." - Thomas Jefferson Why should I be excited? Im suppose to be excited about my favorite team chasing its tail? Am i suppose to be excited about a team using the first overall draft pick to replace a player who doesn't need to be replaced? Maybe my excitement will grow once rumors start breaking that we are NOT drafting a LT.
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Image copyright BBC/Getty Images Image caption Chukky (left) is a dancehall choreographer - it's a genre which Sean Paul (right) has helped popularise "I used to be in the back of my yard in Jamaica dancing barefoot for hours in the sun, waiting for days like this," says dancehall choreographer Chukky. He's just been part of the choreography team for a big Christmas advert. In the ad, for M&S, people's jumpers make them dance - and a lot of the moves come from the Jamaican genre of dancehall. But there was a bit of backlash as some people felt the advert was co-opting a genre to sell jumpers, without giving credit to its Jamaican origins. BBC Radio 1Xtra DJ Seani B - who plays a lot of Caribbean music on his show - posted on Instagram: "People in the mainstream need to know where this... comes from." He put up a video of the ad which had replaced the original track (House of Pain's Jump Around) with dancehall song Flair is in the Air by Ding Dong. But once he realised that Chukky and other Jamaican dancehall choreographers were involved, he posted another video giving them props: "I'm smiling, I'm happy... but we gotta gatekeep the culture," he said In another Insta post, Seani B said "respect" needs to be shown to Ding Dong and his team Ravers Clavers - who he says originally came up with dance moves you see in the M&S advert. "This year Carnival and every festival where dancehall was played it was all about Gas. "Now for Xmas it looks like everyone is gonna be flinging their shoulders "I remember in 2017 I told label execs see your superstar here. They listened but never heard me." Chukky - real name Keyama Cammock - is happy to share the style of dance with whoever wants to be involved. He teaches classes in London, where he says "everyone is welcome." And he says he borrows from other genres such as Afrobeat when he's creating steps. The signature move of the M&S advert is a shoulder roll - not a dancehall move - but Chukky says he was happy to incorporate it into the choreography. Image copyright M&S Image caption M&S's festive clothing ad features people in Christmas jumpers dancing to the song Jump Around by House of Pain Chukky's been dancing professionally for over 10 years - but since he moved to the UK two years ago, he's seen the genre grow in popularity. "When I first came in, there was no real scene for dancers like that." Now, he says: "Everyone comes because it's knowledge. It's fun. It's a vibe. And people crave for these things." Along with dancehall moves being more popular, the music has also made its way into mainstream pop. Rihanna's Work, Drake's Controlla and Ed Sheeran and Justin Bieber's I Don't Care are some examples of this. Image copyright Getty Images Image caption Drake, Justin Bieber and Ed Sheeran have used dancehall influences in their music A few acts - such as Sean Paul - successfully move between dancehall and pop music. But he's called out Drake in the past for not "giving more accolades" towards the Jamaican influence on songs such as One Dance. He told Newsbeat earlier this year that a "language barrier" might put people off the more hardcore dancehall music, but over time he thinks the genre will be better recognised. "One day we are going to get people logging on back to what we do," he said. "We just feel proud of that fact and we humbly wait for our turn to make the city burn again." Image caption Chukky with the Bulletproof 876 crew Chukky thinks the dancers do get credit from the outside - and he feels dancehall is having its moment now. "I've been preparing myself for this for many years," he says. "Big up to every dancer in Jamaica that creates their steps." He adds: "We all aim to be choreographers... that would be shown on big international TV someday and we've managed to do that." Chukky and his dance crew Bulletproof 876 have also worked on a Levi's advert and the music video for Nafe Smallz and Tory Lanez's track Good Love. Image copyright Getty Images Image caption Chukky worked with Nafe Smallz and Tory Lanez in their music video Rather than trying to block others from being influenced by dancehall, Chukky wants to see more unity within the community. For him, it starts with more mutual respect between dancers and musicians. "Remember, dancers [in dancehall] have bigger fan bases than a lot artists. So if we dance to your song, and it goes viral, and then everyone starts listening, it's only right for you to give that credit." He says it's something the Afrobeats community is good at doing. He adds: "There's no specific way - even sometimes just through posting on your Instagram as an artist can mean a lot to a dancer." Follow Newsbeat on Instagram, Facebook, Twitter and YouTube. Listen to Newsbeat live at 12:45 and 17:45 weekdays - or listen back here.
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Aquarion Logos is an anime series produced by Satelight, and the third in the Aquarion franchise, after Genesis of Aquarion and Aquarion Evol, celebrating its 10th anniversary. The series is directed by Eiichi Sato, with character designs by Takeshi Mamezuka. The series' opening theme was composed by Yoko Kanno and performed by May'n. The series began airing in July 2015. In North America, Funimation simulcasted the anime as it aired in Japan. The series was added to the Crunchyroll catalog on June 15, 2017. This series follows an entirely new storyline, unrelated to the previous entries in the franchise. Plot Twelve thousand years ago, human voices had defined the true nature of all things, yet the invention of text changed the status quo which created a "Logos World" between the realities of voice and the truth. Up until the modern day, advancements of civilizations have made the Logos World too big to control texts down to their very concept. Seeking to upset this fragile balance is a mogul and sorcerer named Sōgon Kenzaki, who creates monsters called the MJBK (Menace of Japanese with Biological Kinetic energy) who threaten the modern society. To counter the MJBK, a group of young people blessed with the power of "Verbalism" is assembled by the organization DEAVA (Division of EArth Verbalism Ability) to pilot the vector machines, which are used to form the mechas dubbed "Aquarions", and among them, a boy and self-proclaimed savior named Akira Kaibuki living in Asagaya. Characters Verbalism Club The main protagonist, Akira is a stoic and level-headed youngster who behaves according to his belief that he is bent into become a "savior", although not even he remembers why or when he started doing so. He is the grandson of a famous calligrapher and pilots the all-around, red-colored Vector-01, which he nicknames as "Savior-go". After his vector is destroyed, he obtains another ancient vector known as Vector-ga, far increasing his powers. Trained since childhood to be Subete's partner, she grew up blindly following Sōgon's teachings until her first sortie when she is forced to combine with Akira and defeat the M.J.B.K. she was supposed to protect. After being held prisoner by DEAVA, she obtains a chance to return to NESTA, but Sōgon instead instructs her to pretend that she switched sides in order to investigate Akira further. However, she eventually learns to think by herself and joins forces with Akira and the others against Sōgon to defeat him instead. She pilots the purple-colored Vector-02, focused on air superiority. She is a human created from Verbalism Power with the purpose of awakening the Aquarion Logos and destroy the world. She met Akira once when they were children and he promised her to become the savior who would save the world so Maia was allowed to live on. A shy girl who can barely talk, Kokone lost her ability to talk with confidence after a tragic event from her childhood. She aims to become an actress and joined the Verbalism Club in order to improve her speech and eventually falls in love with Akira, but views Maia as a rival, believing that she is also infatuated on him as well while she was just following him around by Sōgon's orders. She pilots the white-colored Vector-03, specialized in enemy disruption and rear support. A cool-headed young man who aims to become a politician like his late father, and just like Tsutomu, joined the Verbalism Club seeking to improve his speech for his own sake, and his will to develop detailed strategies before acting usually puts him at odds with Akira, who usually acts without much thinking. He pilots the blue-colored Vector-05, focused on mobility and high speed. A young aspiring comedian whose older brother is a famous comedian himself, and despite knowing that he is not near as talented as him, he seeks his own form of comedy, performing unusual sketches that so far earned him only one avid fan. He joined the Verbalism Club seeking to make use of the training against the M.J.B.K. to improve his comedy skills, and pilots the attack-oriented, yellow-colored Vector-04, specialized in hit and run tactics. The youngest member of the team, Karan is a little girl who was aiming to become an idol and joined the Verbalism Club seeking support for her career, until Akira realizes that she wanted to be an idol just to please her mother's selfish desires and when he helped them reconcile, she started pursuing her true dream, which is to become a voice actor. She pilots the pink-colored Vector-06, specialized in reconnaissance and ambush. DEAVA Sakurako was Sōgon's secretary until realizing the true nature of his plans, thus she betrays him and defects to the Japanese Government taking the Vectors and several other equipment from NESTA which she uses to establish DEAVA. Since then she is DEAVA's chief of operations, monitoring and instructing the members of the Verbalism Club during battles. She also manages the Shirobaco Maid Café which serves as a front for DEAVA's headquarters and as a place for Akira and the others to run several activities to train their Verbalism skills. Sakurako's aid who works at DEAVA. She was scouted at first to be part of the Verbalism Club, but later it was revealed that she has no Verbaism power at all, which is a strange fact itself as it is said that every individual has some kind of Verbalism on itself, albeit weak. Later it is revealed that said trait was a Verbalism power in itself, which was used to break free those under control of Subete's Verbalism skills. She also becomes Tsutomu's girlfriend and then assumes command of Vector-04 after his death. Sakurako's right hand man who also works as Shirobaco's cook. NESTA The heir of NESTA Communications and Sōgon Kenzaki's son, he always tried to please his father to no avail. Upon giving up trying to find emotional support on him, he started trying to bond with Maia, the partner he was assigned to defend the MJBK's with. However, when Maia was forced to join DEAVA's side, he started desperately looking for a way to bring her back to his side by all means possible, including developing a dangerous method of increasing his powers by fusing his black-colored Vector-00 with the MJBK's themselves, risking his own body in the process. In the final battle against Sōgon, Subete is ultimately rejected by Maia, who disapproves his behavior. He later reappears, having learned the powers of the Book of Verbalism from his father to increase his power, and determined to destroy the world as Akira's self-proclaimed nemesis. The CEO of NESTA Communications. He was the major antagonist for the first half of the series, creating MJBK's to destroy the written culture, and by consequence, the world in order to have it start over again. He claims that with the advent of Internet, the use of words was banalized to the point of doing more harm than good to society, thus it would lead to its eventual downfall. He is eventually stopped and defeated by the Verbalism Club in a final battle inside the Logos World and crushed to his death by a falling boulder. NESTA's chief researcher who developed the Vectors and remained loyal to Sōgon after Sakurako's betrayal. After Sōgon's death, he remains working at NESTA, now supporting Subete. MJBK The minions of Sōgon, the MJBK are monsters formed from the Logos World upon a text receiving his mystical syringes spawned from his book of magic. Upon formation the text they form in the real world will dissipate following their birth before using their meaning to cause physical destruction. Upon reaching full power the MJBK will erase the concept of their meaning in the collective minds of humanity, irreparably damaging their ability to communicate and think. Maki: Appears in episode 1. Powers include matter twisting matter, tentacles, and tornado summoning. Byou: Appears in episode 2. Powers include illness spreading, tentacles, and body fog. Yume: Appears in episode 3. Powers include passion increasing related to dreams and twin laser beams. Koi: Appears in episode 4. Powers include love amplifying, suction mouth waves, extendable arms, a detachable head, and a forehead laser. Natsu: Appears in episode 5. Powers include low body temperature, ice blast, and icicle spawning. Dan: Appears in episodes 6 and 7. Powers include severing, probe spawning, and wall forming. En: Appears in episode 7. Powers include fire ball spawning and restraining bars. Mushi: Appears in episode 8. Powers include will power increasing based on desires and asexual reproduction. Kage: Appears in episode 9. Powers include dark mist, despair increasing, and stealth. Oto: Appears in episode 10. Powers include wave nullification, mouth sonic waves, and a thick shell. Uzu: Appears in episode 11. Powers include consuming messages via magnetic field, burrowing, coiling body Hanare: Appears in episode 12. Powers include body levitation, part separation, teleportation, a circular energy barrier, psychological deterioration kanji blasts, energy halo that can divide into two razors, and spatial loops. Mu: Appears in episode 13. concept erasing rocks, black hole body, and an energy beam. Hito: Appears in episode 14. It has no known powers. Teki: Appears in episode 17. Powers include hostility increase, a wormhole, and levitation. Uso: Appears in episode 18. Powers include emitting fog and stretching. Emi: Appears in episode 21. Mind control, levitation, laser spew, and teeth tentacles. Den: Appears in episodes 22 and 23. Powers include electric shocks, disabling electronics, and a magnetic net around the body. Subete: Appears in episodes 24 and 25. Powers include existential erasing and an eye energy beam. Others Episode list References External links Official website Aquarion Logos at FUNimation Category:2015 anime television series Category:Action anime and manga Category:Anime with original screenplays Category:Aquarion Category:C2C (studio) Category:Funimation Category:Mecha anime and manga Category:Science fiction anime and manga Category:Satelight
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The present invention relates to a mullion assembly and, more particularly, to a mullion assembly for a double door mounted in a double doorway. It is usual to mount a mullion assembly in a double doorway for engaging with two latches of two doors (or known as a double door) pivotably mounted on opposite sides of a door frame. Easy removal of the mullion assembly is required when a full door opening is desired for unobstructed pass purposes. Furthermore, to prevent the doors from being opened when exposed to a fire, it is desirable for the mullion assembly to have enhanced structural strength and fire resistant functions. In a proposed design, the mullion assembly includes a top fitting mounted to the top of a door frame, a bottom fitting assembly mounted to the bottom of the door frame, a mullion head detachably engaged with the top fitting, and a mullion tube mounted between the mullion head and the bottom fitting assembly. A fusible spacer is disposed between the top fitting and the mullion head for accommodating thermal expansion of the mullion assembly in case of fire to resist warping of the mullion assembly. The top fitting includes a vertical slot into which a locking bolt extends. The locking bolt moves upwardly in the vertical slot due to thermal expansion of the mullion assembly to maintain the locked condition without buckling the mullion assembly when the fusible spacer melts due to the heat of the fire. However, a high pressure gas could be generated due to high temperature of combustion or explosion in the fire to destroy the mullion assembly. This is because the engaging force between the mullion tube and the top fitting depends only on the locking bolt and is, thus, insufficient to withstand the high pressure gas, resulting in undesired opening of the doors and flowing of smoke and fire from the outside into the inside. Thus, a need exists for a mullion assembly with a removable post that allows easy assembly while having improved structural strength to withstand fire.
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The free Ca2 ion concentration (Ca2 ion) of the cytosol, an important parameter in the regulation of carbohydrate metabolism, is itself regulated through the combined actions of the Ca2 ion transport systems of cellular membranes. Since these systems have been studied under unphysiological conditions, little is known of the details of cytosolic (Ca2 ion) regulation in an intracellular environment. This laboratory's approach has therefore been to measure directly the functional result of subcellular Ca2 ion transport under simulated in vivo conditions. An ion-selective electrode continuously monitors ambient (Ca2 ion) in a cytosol-like medium containing either isolated fractions of mitochondria and endoplasmic reticulum (microsomes) from rat liver or isolated rat liver cells pre-treated to make only their plasma membranes permeable to solutes. Having already documented joint steady-state regulation of ambient (Ca2 ion) by mitochondria plus microsomes at values approximating those of liver cell cytosol, this project will investigate 1) inter-organellar effects on Ca2 ion homeostasis through reciprocal alteration of internal Ca2 ion content and 2) modulatory effects on Ca2 ion homeostasis of a) phosphate, adenosine triphosphate and oxidized/reduced pyridine nucleotide, which reflect the status of carbohydrate metabolism, and b) glucagon, epinephrine and norepinephrine, which alter the rate of carbohydrate metabolism.
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/* --COPYRIGHT--,BSD * Copyright (c) 2016, Texas Instruments Incorporated * All rights reserved. * * Redistribution and use in source and binary forms, with or without * modification, are permitted provided that the following conditions * are met: * * * Redistributions of source code must retain the above copyright * notice, this list of conditions and the following disclaimer. * * * Redistributions in binary form must reproduce the above copyright * notice, this list of conditions and the following disclaimer in the * documentation and/or other materials provided with the distribution. * * * Neither the name of Texas Instruments Incorporated nor the names of * its contributors may be used to endorse or promote products derived * from this software without specific prior written permission. * * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS" * AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, * THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR * PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT OWNER OR * CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, * EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, * PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; * OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, * WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR * OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, * EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE. * --/COPYRIGHT--*/ #ifndef IMAGEBUTTON_H_ #define IMAGEBUTTON_H_ //***************************************************************************** // //! This structure defines the characteristics of a ImageButton // //***************************************************************************** typedef struct Graphics_ImageButton { uint16_t xPosition; /*!< x coordinate for upper left corner of button */ uint16_t yPosition; /*!< y coordinate for upper left corner of button */ uint8_t borderWidth; /*!< border width in pixels */ bool selected; /*!< draws button with selected colors enabled */ uint16_t imageHeight; /*!< image height in pixels */ uint16_t imageWidth; /*!< image width in pixels */ uint32_t borderColor; /*!< Border color, border is drawn if borderWidth >0 */ uint32_t selectedColor; /*!< Background button color when selected */ Graphics_Image *image; /*!< Pointer to the image */ } Graphics_ImageButton; //***************************************************************************** //globals //***************************************************************************** extern Graphics_Context g_sContext; //***************************************************************************** // the function prototypes //***************************************************************************** extern void Graphics_drawImageButton(const Graphics_Context *context, const Graphics_ImageButton *imageButton); extern bool Graphics_isImageButtonSelected( const Graphics_ImageButton *imageButton, uint16_t x, uint16_t y); extern void Graphics_drawSelectedImageButton(const Graphics_Context *context, const Graphics_ImageButton * imageButton); extern void Graphics_drawReleasedImageButton(const Graphics_Context *context, const Graphics_ImageButton * imageButton); #endif /* IMAGEBUTTON_H_ */
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NAME SYNOPSIS DESCRIPTION Test::Data provides utility functions to check properties and values of data and variables. Functions Plug-in modules define functions for each data type. See the appropriate module. How it works The Test::Data module simply emports functions from Test::Data::* modules. Each module defines a self-contained function, and puts that function name into @EXPORT. Test::Data defines its own import function, but that does not matter to the plug-in modules. If you want to write a plug-in module, follow the example of one that already exists. Name the module Test::Data::Foo, where you replace Foo with the right name. Test::Data should automatically find it. BUGS I'm not a very good Windows Perler, so some things don't work as they should on Windows. I recently got a Windows box so I can test things, but if you run into problems, I can use all the patches or advice you care to send.
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51 F.3d 1052 Frank Wilson, Jr.v.Memorial Medical Center Incorporated, Larry Hill NO. 93-9483 United States Court of Appeals,Eleventh Circuit. Mar 31, 1995 S.D.Ga., 43 F.3d 679 1 DENIALS OF REHEARING EN BANC.
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Cost-effectiveness of case-based training for primary care physicians in evidence-based medicine of patients with coronary heart disease. We have shown that a case-based training programme for general practitioners, aimed to implement evidence-based care of patients at very high risk of coronary death, was associated with decreased mortality. In the present study we assessed long-term cost-effectiveness of this programme. Registry-based long-term cost-effectiveness analysis on a clinical trial. Costs of the programme, health care, drugs and added years of life were included. Costs were adjusted to 2012 level and discounted by 3%. Life-years gained were estimated as the difference between the survival curves of the trial. The effectiveness measure, quality adjusted life-years (QALYs), was constructed by multiplying each life-year with a quality of life weight corresponding to the health status of that year. QALYs were also discounted by 3%. Incremental cost-effectiveness ratio (ICER) was estimated as the incremental cost per QALY gained. The number of undiscounted life-years gained was 365 days in the intervention group as compared to control (p = 0.02). The number of discounted QALYs gained was 0.66. The net increase in total costs was estimated as 17,862 € when costs of added years of life were included and 4621 € exclusive of these costs. This implied an ICER of 27,063 € per gained QALY. This ICER is well below commonly used threshold values of the societal willingness to pay for a QALY. The results show that a case-based training programme of general practitioners is a cost-effective way to save years of life in patients with very high risk of coronary death.
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Your homework took you 2 hours to finish? It should have taken 4, next time I'll give you more problems to do 174 shares
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DELAWARE COUNTY ESTATE PLANNING COUNCIL Welcome to the Delaware County Estate Planning Council site. Our council, formed in 1971 as an association, was created with the goal of advancing the field of Estate Planning by providing educational resources to our members and the public. These resources will hopefully assist our members and the public in making more informed decisions regarding estate assets presently and into the future. Delaware County Estate Planning Council is affiliated with the National Association of Estate Planners & Councils and joining can fulfill the requirement of belonging to an affiliated local estate planning council to become an Accredited Estate Planner® (AEP®) designee. Please contact the national office at 866-226-2224 to learn more about the Accredited Estate Planner® designation.
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You are here Sway Bar Tuning Submitted by protomor on Thu, 01/03/2013 - 12:36 Tuning sway bars seems to be a black art. Some say to run no rear sway bar and some say to run the thickest sway bars possible. The definitive answer is "it depends". Thanks to modern aftermarket sway bars, they are easily adjustable at the track. They are usually much simpler to adjust as opposed to swapping out springs. Generally suspension tuning idealism is to adjust spring rates to remove sway then tune the rest with sway bars. It is preferred to soften sway bars first instead of stiffening. The softest sway bar possible is the preferred setup. As a result of stiff sway bars, a car may lift the inside tire mid corner. This is an apparent sign to soften the sway bar. This is inefficient simply because the inside tire can no longer perform as intended (either turn the car or drive the car forward). The outside tire, as a result, will tend to become overloaded. Therefore, both tires will not adhere to their fullest extent. Soft sway bars give a similar problem. The entire car will lean over and cause the outside tires to overload. As with anything, there is always a point where either side is simply too much. General Sway Bar Tuning Guidelines Stiffer Sway Bar Cons Can lift inside tire/unloads inside tire Faster weight transfer (snap back) Potential for tires skipping or skipping over uneven/rough surfaces Softer Sway Bar Cons Potential to overload the outside tire More body roll If your car exhibits one of the major "cons", you may want to go stiffer/softer accordingly. On top of this, if you are understeering/oversteering during a track day, here is a simple way to remember:
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A lot of threads with various roster discussions going on. I'll try this to consolidate some of it... and kick it off with this: Quote: @adamgfisher 2h2 hours agoMore Adam Fisher Retweeted Michael MayerIf you look at his history, nagging injuries seem to be a pretty big culprit with regard to his poor performances. So the question moving forward is can he stay healthy? The aging curve will make that more of a challenge.Adam Fisher added, Quote: @mikemayerMMOJay Bruce in 16 games since returning from the DL:.275/.362/.569 with 3 doubles, 4 homers, 10 RBI and 7 BB/10K Just when you decide to be down on Jay Bruce, he will surprise you. I think he's a very proud guy who will want to make up for this lost year with a big 2019 and I wouldn't count him out. Has to stay healthy. And I think whoever is running the team can maximize his output by limiting his exposure to LHers. I think he's in RF most of the way next yr (facing RHers). Don't believe the hype about holding back Alonso. They're going to desperately need his bat in the lineup. Good idea. I'll copy and paste my proposal here, which assumes we are not investing a ton or tearing it all down: Focus resources (what little they'd likely invest) on the bullpen, maybe a bench piece. I like what I'm seeing from Plaw, and TdA is back next year, but maybe a backup C type. - See if Mark Reynolds or Marwin Gonzalez will take a 1 or 2 year deal. - See which catcher will take a one year deal: Maldonado, Suzuki, Rivera, AJ Ellis, Hundley.- Sign two or three from this group, at least one lefty: Robertson, Familia, Ottavino, Herrera, Andrew Miller, Justin Wilson, Blevins, Ollie (.64 WHIP this year in 28 innings!). - Cespedes mid-season boosts that lineup, plus any trades if they are in it. Bruce, Nimmo, Conforto in the outfield? that a good outfield.Grab a stud 3B and slide Frazier over to 1B to go with "Real Deal" McNeil and Rosario.Or a 1B who crushes LHP and leave Frazier at 3B Grandall in here to platoon with PlawExtend WheelerSpend some money in the penExtend deGrom Bruce, Nimmo, Conforto in the outfield? that a good outfield.Grab a stud 3B and slide Frazier over to 1B to go with "Real Deal" McNeil and Rosario.Or a 1B who crushes LHP and leave Frazier at 3B Grandall in here to platoon with PlawExtend WheelerSpend some money in the penExtend deGrom Who is online You cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot post attachments in this forum
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The Departed Box Office Take is Over 77 Million and Counting... I was in Boston the only time anyone ever called me a nigger to my face. A bunch of us college interns were pumping gas, and a cherry-red pick up containing a couple of white boys sped by and screamed the word.Our group stopped and stared. Things moved in slow motion. We were stunned into silence.The Departed is Bloody HellThis memory emerged this weekend, when my husband took me to see The Departed, Martin Scorsese's ultra-violent pseudo remake of Wai Keung Lau and Siu Fai Mak’s 2002 Hong Kong action film, Infernal Affairs. Set in the gritty side of Boston, away from the cobble-stoned niceness of Newbury Street, The Departed opens with Jack Nicholson using the slur. I sat there in the packed theater and tried to play it off like most blacks do in that sort of situation, pretending it didn’t really matter, and went ahead and absorbed myself into the crime drama, experiencing it as sort of a black fly on a rough white underworld wall of the Irish Mob. Besides, Scorsese has a predilection for the N-word, I remembered, as he displayed so honestly in that Taxi Driver scene where he watched his wife's silhouette in the window of a black man from the vantage point of the back of Deniro's cab. "You know who lives there?" a young Scorsese asked nutso Deniro. "A nigger lives there." It was so no-holds-bar that I can write the lines from memory.
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1. Introduction {#sec1-sensors-15-27142} =============== Accurate exhaust gas recirculation (EGR) rate control and air-fuel ratio (AFR) control are important technologies to satisfy the increasingly stringent emission regulations, which are dependent on the precise calculation of the EGR rate and AFR \[[@B1-sensors-15-27142],[@B2-sensors-15-27142]\]. The accuracy of the EGR rate and AFR can be improved by a mass air flow (MAF) sensor, in which a sensor element is heated to a fixed temperature, and the difference in temperature attributed to heat transfer from the heating element to the air flow is a measure of the air mass flow \[[@B3-sensors-15-27142],[@B4-sensors-15-27142],[@B5-sensors-15-27142]\]. However, there are many different local flow fields within the inlet piping due to the three-dimensional turbulence flow, leading to measurement biases in the MAF sensor installed between the air filter and the intake manifold. In addition, the MAF sensor is also subjected to aging phenomena owing to the accumulation of dust on the sensing element, which causes the deterioration of the measurement accuracy \[[@B6-sensors-15-27142],[@B7-sensors-15-27142]\]. These errors will bring about an inaccurate EGR rate and AFR and have adverse impacts on the emission performance of diesel engine. It is difficult to accurately establish an analytical model for the MAF sensor error. In view of the relatively low computational load, maps (or lookup tables) have been widely used to characterize systems where the functional relationship is unavailable or too complex to represent analytically \[[@B8-sensors-15-27142]\]. Therefore, the relative error of the MAF sensor is described as a one-dimensional (1D) map taking compressor mass air flow as input \[[@B2-sensors-15-27142]\]. In order to track MAF sensor aging, the extended Kalman filter (EKF) for updating maps is presented in \[[@B9-sensors-15-27142],[@B10-sensors-15-27142],[@B11-sensors-15-27142]\], in which the 1D map is represented as a piecewise linear interpolation model and the map parameters are considered as parameter states. Due to the piecewise linear interpolation model having the characteristic of partition calculation and due to the the map input being able to enter only one input interval of the 1D map at any time, then only two parameter states participating in linear interpolation are observable and the other not. Therefore, the error covariance matrix elements of EKF corresponding to the locally unobservable parameter states will increase linearly. Although the solution is to limit this growth in \[[@B9-sensors-15-27142],[@B10-sensors-15-27142],[@B11-sensors-15-27142]\], the convergence of EKF with a confined covariance matrix cannot be guaranteed. In addition, the measurement error of the MAF sensor depends on the engine operating point, which is usually defined as fuel mass injection quantity and engine speed. The 1D map representing MAF sensor error ignores the engine speed, reducing the accuracy when the diesel engine is run over a wide speed range. The adaptive observer with the advantage of simple convergence conditions is an alternative method for updating maps. Recursive algorithms designed for joint estimation of states and parameters in state space systems are usually known as adaptive observers, and some early works with adaptive observers to jointly estimate states and parameters in multi-input-multi-output linear time varying systems can be found in \[[@B12-sensors-15-27142],[@B13-sensors-15-27142]\]. In order to estimate sensor faults, adaptive observers for linear time varying systems with unknown parameters in output equations have been studied \[[@B14-sensors-15-27142],[@B15-sensors-15-27142]\]. However, the existing adaptive observers cannot directly update maps. In this paper, an adaptive observer is developed to update the map, in which the MAF sensor error is described as a two-dimensional (2D) map taking the operating point as the input to improve the model accuracy comparing the 1D map. Then, two problems are studied. First, in order to expediently analyze and design the parameter estimation method, the input-output relationship of the MAF sensor error 2D map is expressed as a dot product between the regression vector and the unknown parameter vector. Second, based on the linear parameter varying (LPV) system of the diesel engine with EGR and variable geometry turbocharger (VGT), a 2D map estimation method with a simple structure and low computational load is designed to facilitate the algorithm implementation. This paper is organized as follows. In [Section 2](#sec2-sensors-15-27142){ref-type="sec"}, the 2D map is expressed as the dot product between the regression vector and the unknown parameter vector, and the estimation problem for a class of LPV systems with an unknown parameter vector is given. In [Section 3](#sec3-sensors-15-27142){ref-type="sec"}, the LPV adaptive observer is proposed, as well as the convergence analysis. Simulation results from enDYNA are presented in [Section 4](#sec4-sensors-15-27142){ref-type="sec"}, and the conclusions are summarized in [Section 5](#sec5-sensors-15-27142){ref-type="sec"}. 2. Problem Formulation {#sec2-sensors-15-27142} ====================== 2.1. A Diesel Engine Air Path LPV Model {#sec2dot1-sensors-15-27142} --------------------------------------- [Figure 1](#sensors-15-27142-f001){ref-type="fig"} shows the model structure of a diesel engine with EGR and VGT, and the model can be expressed as \[[@B16-sensors-15-27142]\]: $$\begin{array}{ll} {\overset{˙}{p}}_{im} & {= \frac{R_{a}T_{im}}{V_{im}}\left( {W_{c} + W_{egr} - W_{ei}} \right)} \\ {\overset{˙}{p}}_{em} & {= \frac{R_{e}T_{em}}{V_{em}}\left( {W_{f} + W_{ei} - W_{t} - W_{egr}} \right)} \\ {\overset{˙}{\omega}}_{t} & {= \frac{P_{t}\eta_{m} - P_{c}}{J_{t}\omega_{t}}} \\ \end{array}$$ where $W_{c}$ is the compressor mass air flow, $W_{egr}$ is the EGR mass flow, $W_{ei}$ is the cylinder mass flow, $W_{f}$ is the fuel rate injected to cylinder, $W_{t}$ is the turbine mass flow, $P_{t}$ is the turbine power, $P_{c}$ is the compressor power, $\eta_{m}$ is the turbocharger mechanical efficiency, $p_{im}$ is the intake manifold pressure, $p_{em}$ is the exhaust manifold pressure and $\omega_{t}$ is the turbine speed. ![Schematic of the diesel engine model with exhaust gas recirculation (EGR) and variable geometry turbocharger (VGT).](sensors-15-27142-g001){#sensors-15-27142-f001} Meanwhile, $W_{c}$, $W_{egr}$, $W_{ei}$, $W_{t}$, $W_{f}$, $P_{c}$ and $P_{t}\eta_{m}$ in Equation ([1](#FD1-sensors-15-27142){ref-type="disp-formula"}) can be obtained as follows: $$\begin{array}{l} {W_{c} = \frac{p_{amb}\pi R_{c}^{3} \cdot \Phi_{c}\left( {p_{im},\omega_{t}} \right)}{R_{a}T_{amb}}\omega_{t},W_{egr} = \frac{A_{egr}\left( u_{egr} \right) \cdot \Psi_{egr}\left( {p_{im},p_{em}} \right)}{\sqrt{T_{em}R_{e}}}p_{em}} \\ {W_{ei} = \frac{\eta_{vol}\left( {p_{im},n_{e}} \right) \cdot n_{e}V_{d}}{120R_{a}T_{im}}p_{im},W_{t} = \frac{A_{vgt\max} \cdot f_{\Pi_{t}}\left( p_{em} \right) \cdot f_{vgt}\left( u_{vgt} \right)}{\sqrt{T_{em}R_{e}}}p_{em}} \\ {W_{f} = \frac{10^{- 6}}{120}n_{cyl}n_{e}u_{\delta},P_{c} = \frac{W_{c}\left( {p_{im},\omega_{t}} \right) \cdot c_{pa}T_{amb} \cdot \left( {\Pi_{c}^{1 - {1{{/\phantom{1\gamma_{a}}}}\gamma_{a}}} - 1} \right)}{\eta_{c}\left( {p_{im},\omega_{t}} \right)}} \\ {P_{t}\eta_{m} = \eta_{tm}\left( {p_{em},\omega_{t}} \right) \cdot W_{t}\left( {p_{em},u_{vgt}} \right) \cdot c_{pe}T_{em} \cdot \left( {1 - \Pi_{t}^{1 - {1{{/\phantom{1\gamma_{e}}}}\gamma_{e}}}} \right)} \\ \end{array}$$ However, it is difficult to estimate the measurement error of the MAF sensor based on the complicated nonlinear model Equation ([1](#FD1-sensors-15-27142){ref-type="disp-formula"}). In order to simply present the state space equation and the error estimation, define variables:$$\begin{array}{l} {\rho_{1} = \frac{p_{amb}\pi R_{c}^{3} \cdot \Phi_{c}\left( {p_{im},\omega_{t}} \right)}{R_{a}T_{amb}},\rho_{2} = \frac{A_{egr}\left( u_{egr} \right) \cdot \Psi_{egr}\left( {p_{im},p_{em}} \right)}{\sqrt{T_{em}R_{e}}}} \\ {\rho_{3} = \frac{\eta_{vol}\left( {p_{im},n_{e}} \right) \cdot n_{e}V_{d}}{120R_{a}T_{im}},\rho_{4} = \frac{A_{vgt\max} \cdot f_{\Pi_{t}}\left( p_{em} \right) \cdot f_{vgt}\left( u_{vgt} \right)}{\sqrt{T_{em}R_{e}}}} \\ {\rho_{5} = \frac{c_{pa}p_{amb}\pi R_{c}^{3} \cdot \Phi_{c}\left( {p_{im},\omega_{t}} \right) \cdot \left( {\Pi_{c}^{1 - {1{{/\phantom{1\gamma_{a}}}}\gamma_{a}}} - 1} \right)}{J_{t}\omega_{t}R_{a} \cdot \eta_{c}\left( {p_{im},\omega_{t}} \right)}} \\ \end{array}$$ According to Equation ([3](#FD3-sensors-15-27142){ref-type="disp-formula"}), the variables $\rho_{i}\mspace{600mu}\left( i = 1,2,3,4,5 \right)$ are available in real-time since $p_{im}$, $p_{em}$, $\omega_{t}$, $u_{egr}$, $u_{vgt}$, $u_{\delta}$ and $n_{e}$ can be measured or estimated online. Therefore, the nonlinear model Equation ([1](#FD1-sensors-15-27142){ref-type="disp-formula"}) can be cast into an LPV system:$$\begin{array}{r} {\overset{˙}{x} = A\left( \rho \right)x + E} \\ \end{array}$$ where:$$\begin{array}{l} {\rho = \begin{pmatrix} \rho_{1} & \rho_{2} & \rho_{3} & \rho_{4} & \rho_{5} \\ \end{pmatrix}} \\ {x = \begin{pmatrix} p_{im} \\ p_{em} \\ \omega_{t} \\ \end{pmatrix},A\left( \rho \right) = \begin{pmatrix} {- a_{1}\rho_{3}} & {a_{1}\rho_{2}} & {a_{1}\rho_{1}} \\ {a_{2}\rho_{3}} & {- a_{2}\rho_{2} - a_{2}\rho_{4}} & 0 \\ 0 & 0 & {- \rho_{5}} \\ \end{pmatrix}} \\ {E = \begin{pmatrix} 0 \\ {a_{2}W_{f}} \\ {{P_{t}\eta_{m}}{{/\phantom{{P_{t}\eta_{m}}{J_{t}\omega_{t}}}}}{J_{t}\omega_{t}}} \\ \end{pmatrix},a_{1} = \frac{R_{a}T_{im}}{V_{im}},a_{2} = \frac{R_{e}T_{em}}{V_{em}}} \\ \end{array}$$ In order to determine the bounds on the parameter vector *ρ*, a simulation study is performed using a 1.9 L four-cylinder common rail turbo diesel engine of enDYNA provided by Tesis \[[@B17-sensors-15-27142],[@B18-sensors-15-27142]\]. The bounds of the parameter vector *ρ* are found using the simulation data from enDYNA over the European Transient Cycle (ETC), Federal Test Procedure 75 (FTP75) and New European Drive Cycle (NEDC) \[[@B19-sensors-15-27142],[@B20-sensors-15-27142],[@B21-sensors-15-27142]\]. Then, the results are listed in [Table 1](#sensors-15-27142-t001){ref-type="table"}. It follows that each parameter $\rho_{i}$ from parameter vector *ρ* is bounded by a minimum and maximum value ${\underline{\rho}}_{i}$ and ${\overline{\rho}}_{i}$. sensors-15-27142-t001_Table 1 ###### Bounds on the parameter vector *ρ* under three conditions. ETC, European Transient Cycle; FTP75, Federal Test Procedure 75; NEDC, New European Drive Cycle. Parameter ETC FTP75 NEDC ------------ ----------------------------------------------------------- ------------------------------------------------------------ ------------------------------------------------------------ $\rho_{1}$ $\left\lbrack {19,150} \right\rbrack \times 10^{- 7}$ $\left\lbrack {146,110} \right\rbrack \times 10^{- 7}$ $\left\lbrack {49,130} \right\rbrack \times 10^{- 7}$ $\rho_{2}$ $\left\lbrack {- 1.65,1.6} \right\rbrack \times 10^{- 7}$ $\left\lbrack {- 0.56,1.15} \right\rbrack \times 10^{- 7}$ $\left\lbrack {- 0.003,1.0} \right\rbrack \times 10^{- 7}$ $\rho_{3}$ $\left\lbrack {1.09,6.4} \right\rbrack \times 10^{- 7}$ $\left\lbrack {1.18,6} \right\rbrack \times 10^{- 7}$ $\left\lbrack {1.1,5.4} \right\rbrack \times 10^{- 7}$ $\rho_{4}$ $\left\lbrack {0.61,6.01} \right\rbrack \times 10^{- 7}$ $\left\lbrack {0.75,5.4} \right\rbrack \times 10^{- 7}$ $\left\lbrack {0.62,4.7} \right\rbrack \times 10^{- 7}$ $\rho_{5}$ $\left\lbrack {0,3.15} \right\rbrack$ $\left\lbrack {0,2.78} \right\rbrack$ $\left\lbrack {0,2.67} \right\rbrack$ 2.2. 2D Map Description for the MAF Sensor Error {#sec2dot2-sensors-15-27142} ------------------------------------------------ The intake manifold pressure $p_{im}$, turbine speed $\omega_{t}$ and compressor mass air flow $W_{c}$ are the outputs of interest to analyze the MAF sensor error, which is:$$\begin{array}{r} {y = \begin{pmatrix} y_{1} \\ y_{2} \\ \end{pmatrix} = \begin{pmatrix} p_{im} \\ \omega_{t} \\ W_{c} \\ \end{pmatrix}} \\ \end{array}$$ where $y_{1} = \begin{pmatrix} p_{im} & \omega_{t} \\ \end{pmatrix}^{T},y_{2} = W_{c}$. Due to the existence of MAF sensor error, the output Equation ([6](#FD6-sensors-15-27142){ref-type="disp-formula"}) becomes: $$\begin{array}{r} {y_{m} = \begin{pmatrix} y_{1m} \\ y_{2m} \\ \end{pmatrix} = \begin{pmatrix} y_{1} \\ {y_{2} + \Delta W_{c}} \\ \end{pmatrix}} \\ \end{array}$$ where $y_{m}$ is the measured value from sensors. ${\Delta W}_{c}$ is the measurement error of the MAF sensor, which depends on the engine operating point (fuel mass injection quantity $u_{\delta}$ and engine speed $n_{e}$), *i.e.*, $\Delta W_{c}\left( {u_{\delta}.n_{e}} \right)$. Since it is difficult to accurately build an analytical model for $\Delta W_{c}\left( {u_{\delta}.n_{e}} \right)$, a 2D map is adopted in this paper to describe $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$. Therefore, define the partition of the 2D map input $\upsilon = \left( {u_{\delta},n_{e}} \right)$ as: $$\begin{matrix} {a = u_{\delta}^{1} < u_{\delta}^{2} < \ldots < u_{\delta}^{p_{1}} = b} \\ {c = n_{e}^{1} < n_{e}^{2} < \ldots < n_{e}^{p_{2}} = d} \\ \end{matrix}$$ where $a,b \in \mathbb{R}$ are the minimum and maximum values of $u_{\delta}$ and $p_{1}$ is the number of the grid points in $\left\lbrack {a,b} \right\rbrack$. $c,d \in \mathbb{R}$ are the minimum and maximum values of $n_{e}$, and $p_{2}$ is the number of the grid points in $\left\lbrack {c,d} \right\rbrack$. Assume that the measurement error of the input grid points $\left( {u_{\delta}^{i},n_{e}^{j}} \right)$ is $\theta^{i,j}$, *i.e.*, $$\begin{matrix} {\theta^{i,j} = \Delta W_{c}\left( {u_{\delta}^{i},n_{e}^{j}} \right)} \\ {i = 1,2,\cdots p_{1};j = 1,2,\cdots p_{2}} \\ \end{matrix}$$ Then, for $\forall\upsilon \in \left\lbrack {u_{\delta}^{i},u_{\delta}^{i + 1}} \right\rbrack \times \left\lbrack {n_{e}^{j},n_{e}^{j + 1}} \right\rbrack$, $\forall i \in \left\lbrack {1,2,\cdots,p_{1} - 1} \right\rbrack$ and $\forall j \in \left\lbrack {1,2,\cdots,p_{2} - 1} \right\rbrack$, we can hold the $n_{e}$ value fixed and apply one dimensional (1D) linear interpolation in the $u_{\delta}$ direction. Using the Lagrange form, the result is: $$\begin{matrix} {q_{u_{\delta}}^{j}\left( \theta^{i,j} \right) = \frac{u_{\delta}^{i + 1} - u_{\delta}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i,j} + \frac{u_{\delta} - u_{\delta}^{i}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i + 1,j}} \\ {u_{\delta} \in \left\lbrack {u_{\delta}^{i},u_{\delta}^{i + 1}} \right\rbrack,i = 1,2,\cdots p_{1} - 1} \\ \end{matrix}$$ Equation ([10](#FD10-sensors-15-27142){ref-type="disp-formula"}) can then be used to linearly interpolate along the $n_{e}$ dimension to yield the piecewise bilinear interpolation model of the measurement error $\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right)$ as:$$\begin{matrix} {\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right) = \frac{n_{e}^{j + 1} - n_{e}}{n_{e}^{j + 1} - n_{e}^{j}}q_{u_{\delta}}^{j}\left( \theta^{i,j} \right) + \frac{n_{e} - n_{e}^{j}}{n_{e}^{j + 1} - n_{e}^{j}}q_{u_{\delta}}^{j + 1}\left( \theta^{i,j} \right)} \\ {\upsilon \in \left\lbrack {u_{\delta}^{i},u_{\delta}^{i + 1}} \right\rbrack \times \left\lbrack {n_{e}^{j},n_{e}^{j + 1}} \right\rbrack,i = 1,\cdots p_{1} - 1;j = 1,\cdots p_{2} - 1} \\ \end{matrix}$$ For the undefined region $\upsilon \in \left( {\mathbb{R} \times \mathbb{R}} \right)\backslash\left( {\left\lbrack {a,b} \right\rbrack \times \left\lbrack {c,d} \right\rbrack} \right)$, we extend Equation ([11](#FD11-sensors-15-27142){ref-type="disp-formula"}) to the final result: $$\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right) = \left\{ \begin{matrix} {q_{u_{\delta}}^{1}\left( \theta^{i,j} \right)} & {,u \in \mathbb{R} \times \mathbb{R}_{n_{e}}^{0}} \\ {\frac{n_{e}^{j{ +}1} - n_{e}}{n_{e}^{j{ +}1} - n_{e}^{j}}q_{u_{\delta}}^{j}\left( \theta^{i,j} \right) + \frac{n_{e} - n_{e}^{j}}{n_{e}^{j{ +}1} - n_{e}^{j}}q_{u_{\delta}}^{j{ +}1}\left( \theta^{i,j} \right)} & {,u \in \mathbb{R} \times \mathbb{R}_{n_{e}}^{j}} \\ {q_{u_{\delta}}^{p_{2}}\left( \theta^{i,j} \right)} & {,u \in \mathbb{R} \times \mathbb{R}_{n_{e}}^{p_{2}}} \\ \end{matrix} \right.$$ where: $$\begin{matrix} {q_{u_{\delta}}^{j}\left( \theta^{i,j} \right) = \left\{ \begin{matrix} \theta^{1,j} & {,u_{\delta} \in \mathbb{R}_{u_{\delta}}^{0}} \\ {\frac{u_{\delta}^{i + 1} - u_{\delta}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i,j} + \frac{u_{\delta} - u_{\delta}^{i}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i + 1,j}} & {,u_{\delta} \in \mathbb{R}_{u_{\delta}}^{i}} \\ \theta^{p_{1},j} & {,u_{\delta} \in \mathbb{R}_{u_{\delta}}^{p_{1}}} \\ \end{matrix} \right.} \\ {i = 1,2,\cdots p_{1} - 1;j = 1,2,\cdots p_{2} - 1} \\ \end{matrix}$$ and: $$\mathbb{R}_{u_{\delta}}^{k} = \begin{cases} {\left( {- \infty,u_{\delta}^{1}} \right\rbrack,} & {k{ = 0}} \\ {\left( {u_{\delta}^{k},u_{\delta}^{k + 1}} \right\rbrack,} & {k{ =}1,\ldots,p_{1} - 1} \\ {\left( {u_{\delta}^{p_{1}}, + \infty} \right),} & {k{ =}p_{1}} \\ \end{cases}$$ $$\mathbb{R}_{n_{e}}^{l} = \begin{cases} {\left( {- \infty,n_{e}^{1}} \right\rbrack,} & {l{ = 0}} \\ {\left( {n_{e}^{l},n_{e}^{l + 1}} \right\rbrack,} & {l{ =}1,\ldots,p_{2} - 1} \\ {\left( {n_{e}^{p_{2}}, + \infty} \right),} & {l{ =}p_{2}} \\ \end{cases}$$ For the purposes of estimating unknown parameter $\theta^{i,j}$ in $\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right)$ expediently, Equation ([12](#FD12-sensors-15-27142){ref-type="disp-formula"}) in vector-vector form is needed. According to the input interval Equations ([14](#FD14-sensors-15-27142){ref-type="disp-formula"}) and ([15](#FD15-sensors-15-27142){ref-type="disp-formula"}), we define membership function as: $$\begin{matrix} {\delta_{u_{\delta}}^{k} = \left\{ \begin{matrix} {1,} & {u_{\delta} \in \mathbb{R}_{u_{\delta}}^{k}} \\ {0,} & {other} \\ \end{matrix} \right.} \\ {k = 0,1,\cdots,p_{1}} \\ \end{matrix}$$ and: $$\begin{matrix} {\delta_{n_{e}}^{l} = \left\{ \begin{matrix} {1,} & {n_{e} \in \mathbb{R}_{n_{e}}^{l}} \\ {0,} & {other} \\ \end{matrix} \right.} \\ {l{ = 0,}1,\ldots,p_{2}} \\ \end{matrix}$$ Using membership function Equations ([16](#FD16-sensors-15-27142){ref-type="disp-formula"}) and ([17](#FD17-sensors-15-27142){ref-type="disp-formula"}), Equation ([12](#FD12-sensors-15-27142){ref-type="disp-formula"}) becomes: $$\begin{array}{cl} {\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right)} & {= \delta_{n_{e}}^{0}q_{u_{\delta}}^{1}\left( \theta^{i,j} \right) + \sum\limits_{j = 1}^{p_{2} - 1}{\delta_{n_{e}}^{j}\left( {\frac{n_{e}^{j + 1} - n_{e}}{n_{e}^{j + 1} - n_{e}^{j}}q_{u_{\delta}}^{j}\left( \theta^{i,j} \right) + \frac{n_{e} - n_{e}^{j}}{n_{e}^{j + 1} - n_{e}^{j}}q_{u_{\delta}}^{j + 1}\left( \theta^{i,j} \right)} \right)} + \delta_{n_{e}}^{p_{2}}q_{u_{\delta}}^{p_{2}}\left( \theta^{i,j} \right)} \\ & {= \Psi_{n_{e}} \cdot q_{u_{\delta}}\left( \theta^{i,j} \right)} \\ \end{array}$$ where: $$\begin{array}{r} {\Psi_{n_{e}} = \begin{pmatrix} {\delta_{n_{e}}^{0} + \delta_{n_{e}}^{1}\frac{n_{e}^{2} - n_{e}}{n_{e}^{2} - n_{e}^{1}}} \\ {\delta_{n_{e}}^{1}\frac{n_{e} - n_{e}^{1}}{n_{e}^{2} - n_{e}^{1}} + \delta_{n_{e}}^{2}\frac{n_{e}^{3} - n_{e}}{n_{e}^{3} - n_{e}^{2}}} \\ \vdots \\ {\delta_{n_{e}}^{p_{1} - 2}\frac{n_{e} - n_{e}^{p_{2} - 2}}{n_{e}^{p_{2} - 1} - n_{e}^{p_{2} - 2}} + \delta_{n_{e}}^{p_{1} - 1}\frac{n_{e}^{p_{2}} - n_{e}}{n_{e}^{p_{2}} - n_{e}^{p_{2} - 1}}} \\ {\delta_{n_{e}}^{p_{1} - 1}\frac{n_{e} - n_{e}^{p_{2} - 1}}{n_{e}^{p_{2}} - n_{e}^{p_{2} - 1}} + \delta_{n_{e}}^{p_{1}}} \\ \end{pmatrix}^{T},q_{u_{\delta}}\left( \theta^{i,j} \right) = \begin{pmatrix} {q_{u_{\delta}}^{1}\left( \theta^{i,j} \right)} \\ {q_{u_{\delta}}^{2}\left( \theta^{i,j} \right)} \\ \vdots \\ {q_{u_{\delta}}^{p_{2} - 1}\left( \theta^{i,j} \right)} \\ {q_{u_{\delta}}^{p_{2}}\left( \theta^{i,j} \right)} \\ \end{pmatrix}} \\ \end{array}$$ and: $$\begin{array}{cl} {q_{u_{\delta}}^{j}\left( \theta^{i,j} \right)} & {= \delta_{u_{\delta}}^{0}\theta^{1,j} + \sum\limits_{i = 1}^{p_{1} - 1}{\delta_{u_{\delta}}^{i}\left( {\frac{u_{\delta}^{i + 1} - u_{\delta}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i,j} + \frac{u_{\delta} - u_{\delta}^{i}}{u_{\delta}^{i + 1} - u_{\delta}^{i}}\theta^{i + 1,j}} \right)} + \delta_{u_{\delta}}^{p_{1}}\theta^{p_{1},j}} \\ & {= \Psi_{u_{\delta}} \cdot \theta_{u_{\delta}}^{j}} \\ \end{array}$$ where: $$\begin{array}{r} {\Psi_{u_{\delta}} = \begin{pmatrix} {\delta_{u_{\delta}}^{0} + \delta_{u_{\delta}}^{1}\frac{u_{\delta}^{2} - u_{\delta}}{u_{\delta}^{2} - u_{\delta}^{1}}} \\ {\delta_{u_{\delta}}^{1}\frac{u_{\delta} - u_{\delta}^{1}}{u_{\delta}^{2} - u_{\delta}^{1}} + \delta_{u_{\delta}}^{2}\frac{u_{\delta}^{3} - u_{\delta}}{u_{\delta}^{3} - u_{\delta}^{2}}} \\ \vdots \\ {\delta_{u_{\delta}}^{p_{1} - 2}\frac{u_{\delta} - u_{\delta}^{p_{1} - 2}}{u_{\delta}^{p_{1} - 1} - u_{\delta}^{p_{1} - 2}} + \delta_{u_{\delta}}^{p_{1} - 1}\frac{u_{\delta}^{p_{1}} - u_{\delta}}{u_{\delta}^{p_{1}} - u_{\delta}^{p_{1} - 1}}} \\ {\delta_{u_{\delta}}^{p_{1} - 1}\frac{u_{\delta} - u_{{}_{\delta}}^{p_{1} - 1}}{u_{\delta}^{p_{1}} - u_{\delta}^{p_{1} - 1}} + \delta_{u_{\delta}}^{p_{1}}} \\ \end{pmatrix}^{T},\theta_{u_{{}_{\delta}}}^{j} = \begin{pmatrix} \theta^{1,j} \\ \theta^{2,j} \\ \vdots \\ \theta^{p_{1} - 1,j} \\ \theta^{p_{1},j} \\ \end{pmatrix}} \\ \end{array}$$ and $\Psi_{n_{e}} \in \mathbb{R}^{1 \times p_{1}},\Psi_{n_{e}} \in \mathbb{R}^{1 \times p_{2}},\theta_{u_{{}_{\delta}}}^{j} \in \mathbb{R}^{p_{1} \times 1},q_{u_{\delta}}\left( \theta^{i,j} \right) \in \mathbb{R}^{p_{2} \times 1}$. Now, following Equations ([18](#FD18-sensors-15-27142){ref-type="disp-formula"})--([21](#FD21-sensors-15-27142){ref-type="disp-formula"}), $\Delta W_{c,T}\left( {\theta^{i,j},\upsilon} \right)$ can be written as a dot product between regression vector $\Psi\left( \upsilon \right)$ and unknown parameter vector *θ* as follows: $$\begin{array}{r} {\Delta W_{c,T}\left( {\theta,\upsilon} \right) = \Psi\left( \upsilon \right) \cdot \theta,\forall\upsilon \in \mathbb{R} \times \mathbb{R}} \\ \end{array}$$ where: $$\begin{array}{r} {\Psi\left( \upsilon \right) = \Psi_{n_{e}} \cdot \begin{pmatrix} \Psi_{u_{\delta}} & 0 & \cdots & 0 \\ 0 & \Psi_{u_{\delta}} & \cdots & 0 \\ \vdots & \vdots & \ddots & \vdots \\ 0 & 0 & \cdots & \Psi_{u_{\delta}} \\ \end{pmatrix},\theta = \begin{pmatrix} \theta_{u_{\delta}}^{1} \\ \theta_{u_{\delta}}^{2} \\ \vdots \\ \theta_{u_{\delta}}^{p_{2}} \\ \end{pmatrix}} \\ \end{array}$$ and $\Psi\left( \upsilon \right) \in \mathbb{R}^{1 \times p},\theta \in \mathbb{R}^{p \times 1},p = p_{1} \cdot p_{2}$. With the combination of Equations ([4](#FD4-sensors-15-27142){ref-type="disp-formula"}), ([7](#FD7-sensors-15-27142){ref-type="disp-formula"}) and ([22](#FD22-sensors-15-27142){ref-type="disp-formula"}), the diesel engine air path LPV model can be described by the following state space equation: $$\begin{aligned} \overset{˙}{x} & {= A\left( \rho \right)x + E} \\ y_{m} & {= C\left( \rho \right)x + G\Psi\left( \upsilon \right)\theta} \\ \end{aligned}$$ where: $$\begin{array}{r} {C\left( \rho \right) = \begin{pmatrix} 1 & 0 & 0 \\ 0 & 0 & 1 \\ 0 & 0 & \rho_{1} \\ \end{pmatrix},G = \begin{pmatrix} 0 \\ 0 \\ 1 \\ \end{pmatrix}} \\ \end{array}$$ Equation ([24](#FD24-sensors-15-27142){ref-type="disp-formula"}) indicates that the estimation of the MAF sensor error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ becomes joint estimation of state *x* and parameter *θ* for LPV system Equation ([24](#FD24-sensors-15-27142){ref-type="disp-formula"}). 3. Adaptive Observer Design {#sec3-sensors-15-27142} =========================== The observer to estimate state *x* and parameter *θ* jointly for the LPV system Equation ([24](#FD24-sensors-15-27142){ref-type="disp-formula"}) is given: $$\begin{array}{ll} \overset{˙}{\hat{x}} & {= A\left( \rho \right)\hat{x} + E + L\left( {y_{m} - C\left( \rho \right)\hat{x} - G\Psi\left( \upsilon \right)\hat{\theta}} \right)} \\ \overset{˙}{\hat{\theta}} & {= \Gamma\Psi\left( \upsilon \right)^{T}\left( {y_{m2} - C_{2}\left( \rho \right)\hat{x} - \Psi\left( \upsilon \right)\hat{\theta}} \right)} \\ \end{array}$$ where $C_{2}\left( \rho \right) = \begin{pmatrix} 0 & 0 & \rho_{1} \\ \end{pmatrix}$, $\hat{x} \in \mathbb{R}^{3 \times 1}$ is the state estimate, $\hat{\theta} \in \mathbb{R}^{p \times 1}$ is the parameter estimate, gain $\Gamma \in \mathbb{R}^{p \times p}$ is the positive definite diagonal matrix and $L \in \mathbb{R}^{3 \times 3}$ is the feedback gain matrix. The asymptotical stability of the proposed algorithm Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) is analyzed in the following theorem. *If the following Conditions (1) and (2) hold, then LPV adaptive observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) is asymptotically stable, i.e., for any initial conditions* $x\left( 0 \right),\hat{x}\left( 0 \right),\hat{\theta}\left( 0 \right)$ *and parameter vector θ, the errors $\hat{x} - x$ and $\hat{\theta} - \theta$ tend to zero asymptotically when $\left. t\rightarrow\infty \right.$*. *(1) There exist matrices L, $P = P^{T} > 0$, $Q = Q^{T} > 0$ and constant $\varepsilon_{1},\varepsilon_{2} > 0$, such that the following set of linear matrix inequalities (LMIs) is feasible for $\forall\rho_{i} \in \left\lbrack {{\underline{\rho}}_{i},{\overline{\rho}}_{i}} \right\rbrack$, $i = 1,2,3,4,5$:* $$M\left( \rho \right) = \begin{bmatrix} {A_{cl}\left( \rho \right)^{T}P + PA_{cl}\left( \rho \right) + Q} & {PLG} & {C_{2}^{T}\left( \rho \right)} \\ {G^{T}L^{T}P^{T}} & {- \varepsilon_{1}I} & 0 \\ {C_{2}\left( \rho \right)} & 0 & {- \varepsilon_{2}I} \\ \end{bmatrix} < 0$$ $$\begin{array}{r} {2 - \varepsilon_{1} - \varepsilon_{2} > 0} \\ \end{array}$$ *where $A_{cl}\left( \rho \right) = A\left( \rho \right) - LC\left( \rho \right)$* . *(2) There exists map input υ, such that the regression vector $\Psi\left( \upsilon \right)$ is persistently exciting, i.e., $\exists\delta_{1},\delta_{2} > 0;\exists T > 0;\forall t \geq 0$:* $$\begin{array}{r} {\delta_{1}I_{p} \leq \int_{t}^{t + T}{\Psi\left( {\upsilon\left( \tau \right)} \right)^{T}\Psi\left( {\upsilon\left( \tau \right)} \right)d\tau} \leq \delta_{2}I_{p}} \\ \end{array}$$ Set the estimation error $\widetilde{x} = \hat{x} - x,\widetilde{\theta} = \hat{\theta} - \theta$. Notice that $\overset{˙}{\theta} = 0$; the error dynamic system between Equations ([24](#FD24-sensors-15-27142){ref-type="disp-formula"}) and ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) is: $$\begin{aligned} \overset{˙}{\widetilde{x}} & {= \left( {A\left( \rho \right) - LC\left( \rho \right)} \right)\widetilde{x} - LG\Psi\left( \upsilon \right)\widetilde{\theta}} \\ \overset{˙}{\widetilde{\theta}} & {= - \Gamma\Psi\left( \upsilon \right)^{T}\left( {C_{2}\left( \rho \right)\widetilde{x} + \Psi\left( \upsilon \right)\widetilde{\theta}} \right)} \\ \end{aligned}$$ A valid Lyapunov function candidate is considered as $V = \eta^{T}P\eta + {\widetilde{\theta}}^{T}\Gamma^{- 1}\widetilde{\theta}$. For $\forall\widetilde{x} \neq 0$, the derivative of *V* along with the error dynamic system Equation ([30](#FD30-sensors-15-27142){ref-type="disp-formula"}) is: $$\begin{array}{cl} \overset{˙}{V} & {= 2{\widetilde{x}}^{T}P\overset{˙}{\widetilde{x}} + 2{\widetilde{\theta}}^{T}\Gamma^{- 1}\overset{˙}{\widetilde{\theta}}} \\ & {= 2{\widetilde{x}}^{T}PA_{cl}\left( \rho \right)\widetilde{x} - 2{\widetilde{\theta}}^{T}\Psi\left( \upsilon \right)^{T}\Psi\left( \upsilon \right)\widetilde{\theta} - 2{\widetilde{x}}^{T}PLG\Psi\left( \upsilon \right)\widetilde{\theta} - 2{\widetilde{\theta}}^{T}\Psi\left( \upsilon \right)^{T}C_{2}\left( \rho \right)\widetilde{x}} \\ \end{array}$$ There exist $\varepsilon_{1},\varepsilon_{2} > 0$, such that the following inequalities hold: $$\begin{matrix} {- 2{\widetilde{x}}^{T}PLG\Psi\left( \upsilon \right)\widetilde{\theta} \leqslant {\parallel {\frac{1}{\sqrt{\varepsilon_{1}}}{\widetilde{x}}^{T}PLG} \parallel}^{2} + {\parallel {\sqrt{\varepsilon_{1}}\Psi\left( \upsilon \right)\widetilde{\theta}} \parallel}^{2}} \\ {- 2{\widetilde{\theta}}^{T}\Psi\left( \upsilon \right)^{T}C_{2}\left( \rho \right)\widetilde{x} \leqslant {\parallel {\frac{1}{\sqrt{\varepsilon_{2}}}C_{2}\left( \rho \right)\widetilde{x}} \parallel}^{2} + {\parallel {\sqrt{\varepsilon_{2}}{\widetilde{\theta}}^{T}\Psi\left( \upsilon \right)^{T}} \parallel}^{2}} \\ \end{matrix}$$ According to Condition (1) and Equation ([31](#FD31-sensors-15-27142){ref-type="disp-formula"}), the following inequality holds: $$\begin{array}{cl} \overset{˙}{V} & {\leq {\widetilde{x}}^{T}\left( {A_{cl}\left( \rho \right)^{T}P + PA_{cl}\left( \rho \right) + \frac{1}{\varepsilon_{1}}PLGG^{T}L^{T}P + \frac{1}{\varepsilon_{2}}C_{2}^{T}\left( \rho \right)C_{2}\left( \rho \right)} \right)\widetilde{x}} \\ & {- \left( {2 - \varepsilon_{1} - \varepsilon_{2}} \right){\widetilde{\theta}}^{T}\Psi\left( \upsilon \right)^{T}\Psi\left( \upsilon \right)\widetilde{\theta}} \\ & {< - {\widetilde{x}}^{T}Q\widetilde{x} < 0} \\ \end{array}$$ That is $\overset{˙}{V} < - \omega\left( t \right) < 0$, for $\forall\rho_{i} \in \left\lbrack {{\underline{\rho}}_{i},{\overline{\rho}}_{i}} \right\rbrack,i = 1,2,3,4,5$, where $\omega\left( t \right) = {\widetilde{x}}^{T}Q\widetilde{x}$. Based on the Lyapunov stability theory, we know that the equilibrium $\widetilde{x} = 0$ and $\widetilde{\theta} = 0$ are stable. Now, integrating $\overset{˙}{V} < - \omega\left( t \right)$ from zero to *t* yields: $$\begin{array}{r} {V\left( t \right) + \int_{0}^{t}{\omega\left( \tau \right)d\tau} < V\left( 0 \right)} \\ \end{array}$$ and this means that $\int_{0}^{t}{\omega\left( \tau \right)d\tau} < V\left( 0 \right)$ since $V > 0$. Therefore, we have $\lim\limits_{t\rightarrow\infty}\int_{0}^{t}{\omega\left( \tau \right)d\tau} \leq V\left( 0 \right)$, and this implies that $\lim\limits_{t\rightarrow\infty}\int_{0}^{t}{\omega\left( \tau \right)d\tau}$ exists and is finite. By Barbalat's Lemma \[[@B22-sensors-15-27142]\], we know that $\lim\limits_{t\rightarrow\infty}\omega\left( t \right) = 0$, and this leads to $\lim\limits_{t\rightarrow\infty}\widetilde{x}\left( t \right) = 0$. Under Condition (2), the vector $\Psi\left( \upsilon \right)$ is persistently exciting, that is we have $\lim\limits_{t\rightarrow\infty}\widetilde{\theta}\left( t \right) = 0$ \[[@B22-sensors-15-27142]\]. ☐ *With the concept of multi-convexity \[[@B23-sensors-15-27142]\], the solution of the infinite LMI Equation ([27](#FD27-sensors-15-27142){ref-type="disp-formula"}) can be reduced to be a solution of the finite LMIs for the vertex set, that is:* $$\begin{matrix} {{M\left( w \right) < 0},{\forall w \in \mathcal{V} = \left\{ {\left. \left( {w_{1},\cdots,w_{5}} \right) \right|w_{i} \in \left\{ {{\underline{\rho}}_{i},{\overline{\rho}}_{i}} \right\},i = 1,2,3,4,5} \right\}}} \\ \end{matrix}$$ *Therefore, feedback gain L can be obtained by the solution of inequality Equations ([28](#FD28-sensors-15-27142){ref-type="disp-formula"}) and ([33](#FD35-sensors-15-27142){ref-type="disp-formula"})*. *With the membership function $\delta_{u_{\delta}}^{k},\delta_{n_{e}}^{l}$ in Equations ([16](#FD16-sensors-15-27142){ref-type="disp-formula"}) and ([17](#FD17-sensors-15-27142){ref-type="disp-formula"}), we know that $\delta_{u_{\delta}}^{k}$ = $\delta_{n_{e}}^{l}$ = 1 when $\upsilon \in \mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$ and $\delta_{u_{\delta}}^{k}{ =}\delta_{n_{e}}^{l}{ = 0}$ when $\upsilon \notin \mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$. Therefore, the regression vector $\Psi\left( \upsilon \right)$ is a sparse vector*. According to the partition of the map input $\upsilon = \left( {u_{\delta},n_{e}} \right)$ defined in Equation ([8](#FD8-sensors-15-27142){ref-type="disp-formula"}) and the piecewise bilinear interpolation model Equation ([12](#FD12-sensors-15-27142){ref-type="disp-formula"}), the input *υ* (engine operating point) moves in only one region $\mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$ at any time, and only the parameters ${\hat{\theta}}^{i,j}$ corresponding to the region $\mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$ can participate in the interpolation. That is, for $\forall\upsilon \in \mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$: Case 1: $\left( {k,l} \right) \in \left\{ {0,p_{1}} \right\} \times \left\{ {0,p_{2}} \right\}$. Only one parameter ${\hat{\theta}}^{i,j},\left( {i,j} \right) \in \left\{ {1,p_{1}} \right\} \times \left\{ {1,p_{2}} \right\}$ takes part in the interpolation, *i.e.*, $\Delta W_{c,T}\left( {{\hat{\theta}}^{i,j},\upsilon} \right) = {\hat{\theta}}^{i,j}$. Case 2: $\left( {k,l} \right) \in \left\{ {1,2,\cdots p_{1} - 1} \right\} \times \left\{ {0,p_{2}} \right\}$. Two parameters ${\hat{\theta}}^{i,j},{\hat{\theta}}^{i + 1,j},\left( {i,j} \right) \in \left\{ {1,2,\cdots p_{1} - 1} \right\} \times \left\{ {1,p_{2}} \right\}$ take part in the interpolation, *i.e.*, Δ W c , T θ \^ i , j , υ = u δ i \+ 1 − u δ u δ i \+ 1 − u δ i θ \^ i , j \+ u δ − u δ i u δ i \+ 1 − u δ i θ \^ i \+ 1 , j Case 3: $\left( {k,l} \right) \in \left\{ {0,p_{1}} \right\} \times \left\{ {1,2,\cdots p_{2} - 1} \right\}$. Two parameters ${\hat{\theta}}^{i,j},{\hat{\theta}}^{i,j + 1},\left( {i,j} \right) \in \left\{ {1,p_{1}} \right\} \times \left\{ {1,2,\cdots p_{2} - 1} \right\}$ take part in the interpolation, *i.e.*, Δ W c , T θ i , j , υ = n e j \+ 1 − n e n e j \+ 1 − n e j θ \^ i , j \+ n e − n e j n e j \+ 1 − n e j θ \^ i , j \+ 1 Case 4: $\left( {k,l} \right) \in \left\{ {1,2,\cdots p_{1} - 1} \right\} \times \left\{ {1,2,\cdots p_{2} - 1} \right\}$. Four parameters ${\hat{\theta}}^{i,j}$, ${\hat{\theta}}^{i + 1,j}$, ${\hat{\theta}}^{i,j + 1}$, ${\hat{\theta}}^{i + 1,j + 1}$, $\left( {i,j} \right) \in \left\{ {1,2,\cdots p_{1} - 1} \right\} \times \left\{ {1,2,\cdots p_{2} - 1} \right\}$ take part in the interpolation, *i.e.*, Δ W c , T θ \^ i , j , υ = n e j \+ 1 − n e n e j \+ 1 − n e j u δ i \+ 1 − u δ u δ i \+ 1 − u δ i θ \^ i , j \+ n e j \+ 1 − n e n e j \+ 1 − n e j u δ − u δ i u δ i \+ 1 − u δ i θ \^ i \+ 1 , j \+ n e − n e j n e j \+ 1 − n e j u δ i \+ 1 − u δ u δ i \+ 1 − u δ i θ \^ i , j \+ 1 \+ n e − n e j n e j \+ 1 − n e j u δ − u δ i u δ i \+ 1 − u δ i θ \^ i \+ 1 , j \+ 1 In order to expediently discuss the convergence of the parameter estimate ${\hat{\theta}}^{i,j}$ corresponding to different regions $\mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$, a local regression vector $\Psi_{l}\left( \upsilon \right)$ is defined based on the above four classifications of the region partition as follow: $$\Psi_{l}\left( \upsilon \right) = \begin{cases} 1 & {{if}~{\upsilon \in \left( {\mathbb{R}_{u_{\delta}}^{0} \cup \mathbb{R}_{u_{\delta}}^{p_{1}}} \right) \times \left( {\mathbb{R}_{n_{e}}^{0} \cup \mathbb{R}_{n_{e}}^{p_{2}}} \right)}} \\ \begin{pmatrix} {1 - \eta_{1}} & \eta_{1} \\ \end{pmatrix} & {{if}~{\upsilon \in \mathbb{R}_{u_{\delta}}^{i} \times \left( {\mathbb{R}_{n_{e}}^{0} \cup \mathbb{R}_{n_{e}}^{p_{2}}} \right)}} \\ \begin{pmatrix} {1 - \eta_{2}} & \eta_{2} \\ \end{pmatrix} & {{if}~{\upsilon \in \left( {\mathbb{R}_{u_{\delta}}^{0} \cup \mathbb{R}_{u_{\delta}}^{p_{1}}} \right) \times \mathbb{R}_{n_{e}}^{j}}} \\ \begin{pmatrix} {\left( {1 - \eta_{1}} \right)\left( {1 - \eta_{2}} \right)} \\ {\eta_{1}\left( {1 - \eta_{2}} \right)} \\ {\left( {1 - \eta_{1}} \right)\eta_{2}} \\ {\eta_{1}\eta_{2}} \\ \end{pmatrix}^{T} & {{if}~{\upsilon \in \mathbb{R}_{u_{\delta}}^{i} \times \mathbb{R}_{n_{e}}^{j}}} \\ \end{cases}$$ where: $$\begin{matrix} {\eta_{1} = \frac{u_{\delta} - u_{\delta}^{i}}{u_{\delta}^{i + 1} - u_{\delta}^{i}},\eta_{2} = \frac{n_{e} - n_{e}^{j}}{n_{e}^{j + 1} - n_{e}^{j}}} \\ {i = 1,2,\cdots p_{1} - 1;j = 1,2,\cdots p_{2} - 1} \\ \end{matrix}$$ When $\upsilon \in \mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$, regression vector $\Psi\left( \upsilon \right)$ in Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) can be replaced by local regression vector $\Psi_{l}\left( \upsilon \right)$; then, observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) can be replaced by: $$\begin{aligned} \overset{˙}{\hat{x}} & {= A\left( \rho \right)\hat{x} + E + L\left( {y_{m} - C\left( \rho \right)\hat{x} - G\Psi_{l}\left( \upsilon \right){\hat{\theta}}_{l}^{i,j}} \right)} \\ {\overset{˙}{\hat{\theta}}}_{l}^{i,j} & {= \Gamma_{l}\Psi_{l}\left( \upsilon \right)^{T}\left( {y_{m2} - C_{2}\left( \rho \right)\hat{x} - \Psi_{l}\left( \upsilon \right){\hat{\theta}}_{l}^{i,j}} \right)} \\ \end{aligned}$$ where ${\hat{\theta}}_{l}^{i,j}$ is the local parameter estimate of appropriate size and $\Gamma_{l}$ is a local positive definite diagonal matrix of appropriate size. According to Theorem 1, the local parameter estimate ${\hat{\theta}}_{l}^{i,j}$ is convergent if local regression vector $\Psi_{l}\left( \upsilon \right)$ is persistently exciting. Meanwhile, the parameter estimate $\hat{\theta}$ is also convergent if the trajectory of the map input *υ* passes through all of the interpolation regions $\mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{u_{2}}^{l}$. There are heavy matrices calculated in real time for the covariance matrix equation of EKF in \[[@B9-sensors-15-27142],[@B10-sensors-15-27142],[@B11-sensors-15-27142]\], preventing it from being implemented in commercial electronic control units (ECUs) for map adaptation. Nevertheless, the computational burden of the proposed observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) without the additional matrix equation is lower. Moreover, the number of parameter estimates $\hat{\theta}$ updated in Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) is no more than four at any time; then, the computational load can be further reduced by stopping estimating ${\hat{\theta}}^{i,j}$ corresponding to $\upsilon \notin \mathbb{R}_{u_{\delta}}^{k} \times \mathbb{R}_{n_{e}}^{l}$. *For the area S where the trajectory of the map input υ does not move, the parameters ${\hat{\theta}}^{i,j}$ corresponding to the interpolation region belonging to S cannot be estimated by observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}). In order to get the map parameters corresponding to S, an extrapolation model can be taken as follows:* $$\begin{array}{r} {\Delta W_{c,e}\left( {u_{\delta},n_{e}} \right) = a_{2}u_{\delta}^{2}{ +}a_{1}u_{\delta} + b_{2}n_{e}^{2} + b_{1}n_{e} + c_{2}u_{\delta}n_{e} + c_{1}} \\ \end{array}$$ *where $a_{2},a_{1},b_{2},b_{1},c_{2},c_{1}$ are polynomial parameters. Based on the data from the estimated map parameters, extrapolation model Equation ([37](#FD39-sensors-15-27142){ref-type="disp-formula"}) can be fitted by polynomial fitting approach, and then map parameters corresponding to S can be obtained*. 4. Simulation Results {#sec4-sensors-15-27142} ===================== In this section, the simulation study of 2D map estimation is presented in the environment of a 1.9 L four-cylinder common rail turbo diesel engine of enDYNA, in which the ETC and FTP75 are used as test conditions, respectively. The observer architecture is illustrated in [Figure 2](#sensors-15-27142-f002){ref-type="fig"}, where $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ is the additive reference error as the true measurement error from enDYNA. ![Schematic diagram of the adaptive observer.](sensors-15-27142-g002){#sensors-15-27142-f002} Bounds on the parameter vector *ρ* are presented in [Table 1](#sensors-15-27142-t001){ref-type="table"}. When the inequality Equations ([28](#FD28-sensors-15-27142){ref-type="disp-formula"}) and ([33](#FD35-sensors-15-27142){ref-type="disp-formula"}) are solved with $\varepsilon_{1} = 0.25$ and $\varepsilon_{2} = 0.11$, the gain matrix *L* can be given by: $$\begin{array}{r} {L = \begin{pmatrix} \text{1635.83} & {- \text{124.95}} & {\text{6.52} \times \text{10}^{- 7}} \\ {- \text{16,063.4}} & \text{3135.43} & {\text{1.67} \times \text{10}^{- 7}} \\ \text{4.2} & \text{29.7} & {\text{4.55} \times \text{10}^{- 20}} \\ \end{pmatrix}} \\ \end{array}$$ The initial values of observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) used in the simulation are $\hat{x}\left( 0 \right) = \begin{bmatrix} {9.8 \times 10^{5}} & {9.8 \times 10^{5}} & 0 \\ \end{bmatrix}^{T},\hat{\theta}\left( 0 \right) = 0$, and the parameter gain is $\Gamma = 200I$. Here, the reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ assumed as MAF sensor measurement error is depicted in [Figure 3](#sensors-15-27142-f003){ref-type="fig"}, which is superimposed on the signal $W_{c}$ in enDYNA as the measured value $y_{m2}$ in the simulation. ![Reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ used as the mass air flow (MAF) sensor error in enDYNA.](sensors-15-27142-g003){#sensors-15-27142-f003} 4.1. 2D Map Estimation under ETC {#sec4dot1-sensors-15-27142} -------------------------------- There are three parts of the ETC representing three different driving conditions, including urban, rural and motorway driving. Due to the engine speed range from ETC Part 1 covering the other two parts, ETC Part 1 is employed as the test condition in this section. Accordingly, the fuel mass injection quantity $u_{\delta}$ and engine speed $n_{e}$ from ETC Part 1 are plotted in [Figure 4](#sensors-15-27142-f004){ref-type="fig"}a, and the trajectory of the operating point $\upsilon = \left( {u_{\delta},n_{e}} \right)$ is depicted in [Figure 4](#sensors-15-27142-f004){ref-type="fig"}b, in which the trajectory does not move in area $S = \left\lbrack {\left( {0,56} \right) \times \left( {0,800} \right)} \right\rbrack \cup \left\lbrack {\left( {40,56} \right) \times \left( {0,2000} \right)} \right\rbrack$. According to the range $u_{\delta} \in \left\lbrack {0,56} \right\rbrack$ and $n_{e} \in \left\lbrack {0,3100} \right\rbrack$ from [Figure 4](#sensors-15-27142-f004){ref-type="fig"}a, an average partition can be respectively given as \[0:4:56\] and \[0:250:3000\]. ![Evolution of operating point $\upsilon = \left( {u_{\delta},n_{e}} \right)$ during ETC part one. (**a**) Evolution of $u_{\delta}$ and $n_{e}$. (**b**) Trajectory of operating point $\upsilon = \left( {u_{\delta},n_{e}} \right)$.](sensors-15-27142-g004){#sensors-15-27142-f004} The estimation results of the MAF sensor error using observer Equation ([26](#FD26-sensors-15-27142){ref-type="disp-formula"}) under ETC Part 1 are shown in [Figure 5](#sensors-15-27142-f005){ref-type="fig"}a, in which the map parameters have been estimated, except area *S*. According to Remark 3, the map parameters corresponding to area *S* can be obtained from the extrapolation model Equation ([37](#FD39-sensors-15-27142){ref-type="disp-formula"}). Based on the estimated map parameters from [Figure 5](#sensors-15-27142-f005){ref-type="fig"}a, the polynomial parameters in Equation ([37](#FD39-sensors-15-27142){ref-type="disp-formula"}) can be fitted as follows: $$\begin{array}{l} {a_{2} = 9.12 \times 1\text{0}^{- 6},a_{1} = - 4.39 \times 1\text{0}^{- 4},b_{2} = 1.30 \times 1\text{0}^{- 9}} \\ {b_{1} = - 5.74 \times 1\text{0}^{- 6},c_{2} = - 5.37 \times 1\text{0}^{- 8},c_{1} = 0.0012887} \\ \end{array}$$ The parameters corresponding to area *S* obtained from Equation ([37](#FD39-sensors-15-27142){ref-type="disp-formula"}) are presented in [Figure 5](#sensors-15-27142-f005){ref-type="fig"}b, which can roughly reflect the trend of the map. In order to evaluate the accuracy of the estimated 2D map shown in [Figure 5](#sensors-15-27142-f005){ref-type="fig"}a, the comparison between the reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and the estimated 2D map during the ETC segment is presented in [Figure 6](#sensors-15-27142-f006){ref-type="fig"}a. Accordingly, the true mass air flow $y_{2}$, measured mass air flow $y_{m2}$ and map compensation are shown in [Figure 6](#sensors-15-27142-f006){ref-type="fig"}b. The mean relative error between reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and estimated 2D map is $10.41\%$, which demonstrates that the measured output $y_{m2}$ of the MAF sensor after map correction can approximate the true value of $W_{c}$ acceptably. ![The estimated 2D map for the MAF sensor error. (**a**) Estimation results of the 2D map under ETC Part 1; (**b**) Extrapolation results based on the estimated 2D map.](sensors-15-27142-g005){#sensors-15-27142-f005} ![2D map compensation during the ETC segment. (**a**) Simulation results between reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and the estimated 2D map; (**b**) Simulation results of true mass air flow $y_{2}$, measured mass air flow $y_{m2}$ and the map compensation.](sensors-15-27142-g006){#sensors-15-27142-f006} 4.2. 2D Map Estimation under FTP75 {#sec4dot2-sensors-15-27142} ---------------------------------- In order to verify the effectiveness of the proposed method under different conditions, the cold start transient phase of the FTP75 is used in this section. Accordingly, $u_{\delta}$ and $n_{e}$ are plotted in [Figure 7](#sensors-15-27142-f007){ref-type="fig"}a, and the trajectory of *υ* is depicted in [Figure 7](#sensors-15-27142-f007){ref-type="fig"}b, in which the trajectory does not move in area $S = \left\lbrack {\left( {0,56} \right) \times \left( {0,650} \right)} \right\rbrack \cup \left\lbrack {\left( {25,37} \right) \times \left( {0,2000} \right)} \right\rbrack \cup \left\lbrack {\left( {37,56} \right) \times \left( {0,3500} \right)} \right\rbrack$. ![Evolution of operating point $\upsilon = \left( {u_{\delta},n_{e}} \right)$ FTP75 cold start transient phase. (**a**) Evolution of $u_{\delta}$ and $n_{e}$; (**b**) Trajectory of operating point $\upsilon = \left( {u_{\delta},n_{e}} \right)$.](sensors-15-27142-g007){#sensors-15-27142-f007} ![The estimated 2D map for the MAF sensor error. (**a**) Estimation results of the 2D map under FTP75 cold start transient phase; (**b**) Extrapolation results based on the estimated 2D map.](sensors-15-27142-g008){#sensors-15-27142-f008} The estimation results of the MAF sensor error under the cold start transient phase of the FTP75 are shown in [Figure 8](#sensors-15-27142-f008){ref-type="fig"}a, and the polynomial parameters in Equation ([37](#FD39-sensors-15-27142){ref-type="disp-formula"}) are fitted as follows: $$\begin{array}{l} {a_{2} = 2.10 \times 1\text{0}^{- 5},a_{1} = - 8.62 \times 1\text{0}^{- 4},b_{2} = 1.46 \times 1\text{0}^{- 9}} \\ {b_{1} = - 6.40 \times 1\text{0}^{- 6},c_{2} = - 1.84 \times 1\text{0}^{- 8},c_{1} = 0.0032316} \\ \end{array}$$ The map added the parameters corresponding to area *S* are shown in [Figure 8](#sensors-15-27142-f008){ref-type="fig"}b, which can also roughly reflect the trend of the map. Under the FTP75 segment, the comparison between the reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and the estimated 2D map from [Figure 8](#sensors-15-27142-f008){ref-type="fig"}a is shown in [Figure 9](#sensors-15-27142-f009){ref-type="fig"}a. Accordingly, the MAF sensor measured value $y_{m2}$ using map compensation is presented in [Figure 9](#sensors-15-27142-f009){ref-type="fig"}b. The mean relative error between reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and the estimated 2D map is $5.28\%$, demonstrating that the measured output $y_{m2}$ after map correction can approximate the true value of $W_{c}$ acceptably. ![2D map compensation during the FTP75 segment. (**a**) Simulation results between reference error $\Delta W_{c}\left( {u_{\delta},n_{e}} \right)$ and the estimated 2D map; (**b**) Simulation results of true mass air flow $y_{2}$, measured mass air flow $y_{m2}$ and the map compensation.](sensors-15-27142-g009){#sensors-15-27142-f009} 5. Conclusions {#sec5-sensors-15-27142} ============== A method for updating and storing sensor bias from different operating points is developed and investigated. This method achieves simultaneous estimation of model states and map parameters and applies to updating the MAF sensor error 2D map in the engine. The map in the form of a vector-vector dot product is given to conveniently analyze and design the parameter estimation method. An LPV adaptive observer to estimate map parameters is designed, which has the advantage of a simple structure and low computational load. Under ETC Part 1 and the cold start transient phase of the FTP75, the effectiveness of the presented algorithm is verified and validated in the engine software enDYNA. The results demonstrate that the proposed method can estimate the MAF sensor error acceptably. The authors would like to acknowledge the support of the National Nature Science Foundations of China (No. 61034001). Changhui Wang contributed to the theoretical analysis, algorithm design, simulation verification, and the writing. Zhiyuan Liu supervised the research, and participated in writing the paper. The authors declare no conflict of interest. p a m b ambient pressure (Pa) p i m intake manifold pressure (Pa) p e m exhaust manifold pressure (Pa) ω t turbine speed (rad/s) n e engine speed (rpm) W c compressor mass air flow (kg/s) W e g r EGR mass flow (kg/s) W e i cylinder mass flow (kg/s) W f fuel rate injected to cylinder (kg/s) W t turbine mass flow (kg/s) P c compressor power (W) P t turbine power (W) Φ c volumetric flow coefficient Ψ e g r energy transfer coefficient η v o l volumetric efficiency η t m turbine efficiency η m turbocharger mechanical efficiency η c compressor efficiency T a m b ambient temperature (K) T i m intake manifold temperature (K) T e m exhaust manifold temperature (K) V i m intake manifold volume (m 3 ) V e m exhaust manifold volume (m 3 ) V d displaced volume (m 3 ) R a air gas constant (J/(kg·K)) R e exhaust gas constant (J/(kg·K)) R c compressor blade radius (m) γ a air specific heat capacity ratio γ e exhaust specific heat capacity ratio Π c compressor pressure quotient Π t turbine pressure quotient J t turbine inertia (kg·m 2 ) n c y l number of cylinders A e g r EGR valve effective area (m 2 ) A v g t m a x VGT nozzle maximum effective area (m 2 ) f Π t choking function f v g t effective area ratio function u e g r EGR valve opening percentage (%) u v g t VGT vane opening percentage (%) u δ injected amount of fuel (mg/cycle) c p a air specific heat capacity at constant pressure (J/(kg·K)) c p e exhaust specific heat capacity at constant pressure (J/(kg·K))
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Want more great deals? Sign up for our Daily Digest emails! Leave some for the rest of us! Hey, you can only buy 1 of these. Long Flight Specially designed for on-the-go web browsing and communicating. Just not with your fellow passengers. "Let's see. 10 … 12 … here we are. 14B. Yep, that's me. I've got the window. You know, they claim they've added more leg room, but I'd have liked to know where exactly, am I right?" Yeah. It's a little cramped. "Oh, and don't worry. I know what you're thinking, but I'm not one of those super chatty guys. I brought my Asus Tablet and Keyboard Dock to keep me busy." It's fine. Really. "Well, it's a long flight and I can see that you're trying to sleep. So just wanted to let you know I won't be disturbing you. Great. Thanks. "What's it, like, 9 hours? Yeesh. But it's cool because I've got like 15 hours of extended battery life, so I'll totally be out of your hair." Cool. "I can't say the same for all those babies, though. I think I counted like four on my way back. Too bad you don't have one of these set-ups. The tablet has an incredible audio experience with ASUS Sonicmaster Technology and the keyboard features unique Android Fn keys so you can easily play video and music to drown out the screams." Yeah. Too bad. "Just let me know if this light bothers you. It's just the back-illuminated CMOS sensor on the crystal clear 8MP auto-focus camera. Not that I'll be taking a lot of photos of you while you're sleeping or anything. That would be weird." That would be weird. "Oh, and hey. If you get tired of sleeping and want to watch a movie, I don't mind if you look over my shoulder." That's very nice, thanks. "You should be able to see pretty well, actually. The IPS panel has viewable angles up to 178 degrees at a 1280 x 800 resolution. So what would you rather watch? I've got Tyler Perry's Diary of a Mad Black Woman and Ghost ... Good idea. Let's ask the Flight Attendant." Back to top
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Forking Good (Hardcover) An Unofficial Cookbook for Fans of The Good Place By Valya Dudycz Lupescu, Stephen H. Segal, Dingding Hu (Illustrator) Quirk Books, 9781683691556, 160pp. Publication Date: October 22, 2019 List Price: 19.99* * Individual store prices may vary. Description For fans of NBC's The Good Place, a pun-filled and fully illustrated cookbook of 30 original recipes inspired by the philosophy and food humor of the hit show. With its high concept, exceptional writing, eye-popping set design, stellar cast, meaningful explorations of what it means to be a good person, and clam chowder fountains, The Good Place has captured the hearts and minds of critics and viewers alike. For the first time ever, fans can indulge their cravings for The Good Place with delicious, comforting, original recipes like “Macaroni and Socra-cheese,” “I Think Therefore I Clam (Chowder),” “I Kant Believe It’s Not Buttermilk Pancakes,” and more. Each recipe title references a philosopher or philosophical concept from the show and uses food analogies to explain those concepts to readers who, like Eleanor, can’t always follow Chidi’s lectures. A refreshing and entertaining twist on cookbooks, Forking Good will help you plan your next viewing party as you re-binge your favorite show. About the Author Valya Dudycz Lupescu is the author of The Silence of Trees and the coauthor of Geek Parenting. Her story “Honey,” about dinnertime hospitality at moments of life-or-death, appeared in the Publishers Weekly starred anthology A World of Horror. Her food writing has most recently appeared in the cheese magazine Culture. Stephen H. Segal is the coauthor of Geek Wisdom and Geek Parenting and the Hugo Award– winning former editorial director of Weird Tales. He’s edited award-winning food writers at Philadelphia Weekly, WQED Pittsburgh, and InPittsburgh Weekly. He currently writes about death-related topics as senior editor at Legacy.com, the world’s largest online hub of obituaries. Dingding Hu is a New York based illustrator, best known for her delightful illustration work featuring adorable food and hilarious characters. She has worked on projects for Google, the Museum of Chinese in America, and MIT Media Lab. Her work has appeared in Time Out, the New York Times, and Lucky Peach. She is the recipient of a silver medal in the digital media category at the Comic and Cartoon Annual by the Society of Illustrators. For more information, visit dingdinghu.com and her Etsy shop, Hu is Hungry. Praise For Forking Good: An Unofficial Cookbook for Fans of The Good Place… A 2019 Goodreads Choice Awards Semifinalist Featured in Good Housekeeping’s “28 Funny Gag Gifts to Get Your Friends, Family, and Coworkers Laughing” List “Unlike any cookbook you've encountered previously...It's educational and thoughtful...And the resulting recipes? Well, they're absolutely delicious...Fans of The Good Place will absolutely love this cookbook.”—Hypable “[The recipes] include a fun, easy to understand philosophy lesson that might not keep the cook out of the Bad Place, but would make a fun dinner party.”—The Palm Beach Post “An extended inside joke that show fans will delight in adding to their shelves, Forking Good is a comfort-food laden, lightly philosophical cookbook worth indulging in.”—Foreword Reviews
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// // FBAppDelegate.h // AnnotationClustering // // Created by Filip Bec on 06/04/14. // Copyright (c) 2014 Infinum Ltd. All rights reserved. // #import <UIKit/UIKit.h> @interface FBAppDelegate : UIResponder <UIApplicationDelegate> @property (strong, nonatomic) UIWindow *window; @end
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U małp nie ma oznak, by możliwe było ponowne zakażenie się koronawirusem SARS-CoV-2 po przejściu choroby COVID-19 - informują naukowcy z kilku instytutów w Pekinie. Na platformie preprintów bioRxiv.org opublikowali właśnie wyniki badań na czterech makakach w związku z pojawieniem się doniesień o tym, że u niektórych wyzdrowiałych pacjentów koronawirus pojawił się ponownie. Nie było jasne, czy to oznacza, że u ludzi mogło dojść do nawrotu choroby, czy ponownej infekcji. Eksperymenty na zwierzętach, które są jednym z modeli wykorzystywanych w badaniach COVID-19 sugerują, że po przejściu choroby nabywa się odporność. To bardzo istotne z punktu widzenia szans opanowania epidemii i ważne w pracach nad szczepionką. Makak / Pixabay Zwierzęta zakażono w laboratorium i obserwowano przez cały czas objawy typowe dla COVID-19, w tym utratę wagi, replikację wirusa w nosie, gardle płucach i układzie pokarmowym, a także zapalenie płuc. Jedno ze zwierząt uśpiono w 7. dniu, by zbadać postępy choroby. Po wyzdrowieniu i ustaniu objawów u pozostałych trzech makaków, a także pojawieniu się we krwi specyficznych przeciwciał, dwa z badanych zwierząt próbowano zakazić ponownie, ale objawy choroby ani oznaki ponownej replikacji wirusa w ciągu 5 dni się się nie pojawiły. Nie było wirusa ani w wymazach, ani próbkach tkanek. Porównano wyniki badań wirusologicznych, radiologicznych i patologicznych zwierząt, którym ponownie podano wirusa i tego, które COVID-19 przechodziło raz. Wyniki były praktycznie takie same. Zdaniem autorów pracy wyniki sugerują, że przebycie infekcji wirusem SARS-CoV-2 powinno dać odporność przy ponownym kontakcie. Trzy makaki zostały uznane za wyzdrowiałe według stosowanych obecnie procedur, kiedy po 28 dniach od zakażenia nie wykazywały objawów, w ich organizmie w dwóch testach nie stwierdzono obecności wirusa, a wyniki prześwietlenia rentgenowskiego wróciły do normy. U dwóch zwierząt poddanych próbie ponownego zakażenia zauważono co najwyżej przejściowe podwyższenie temperatury. Zarówno badania laboratoryjne, jak i sekcja wykonana po uśpieniu jednego z nich, nie wykazały objawów choroby. Autorzy pracy zwracają uwagę, że ponowne zakażenie nie było możliwe po tym, jak na wczesnym etapie pierwszej infekcji w organizmie zwierząt pojawiły się neutralizujące koronawirusy przeciwciała. Można oczekiwać, że w przypadku ludzi, pacjenci po pojawieniu się tych przeciwciał nie powinni już zarażać. Badania tkanek makaków pokazały, że przy próbie ponownej infekcji wirus nie był w stanie nigdzie się replikować, a więc nie może się nigdzie przez dłuższy czas ukrywać. Jak więc wytłumaczyć opisane przypadki ponownego pojawienia się wirusa u tych już wcześniej wyleczonych? Zdaniem Chińczyków to prawdopodobnie skutek fałszywie negatywnych wyników testów. Być może pacjentów wypuszczono też ze szpitala przedwcześnie, mimo że spełniali przyjęte wtedy warunki wypisu. Te procedury z pewnością trzeba dopracować. Kluczowa informacja jest taka, że po przejściu choroby COVID-19 powinniśmy być na koronawirusa odporni. Kolejne badania powinny to jednak potwierdzić.
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Metasynthesis findings: potential versus reality. Early on, qualitative researchers predicted that metasynthesis research had the potential to significantly push knowledge development forward. More recently, scholars have questioned whether this is actually occurring. To examine this concern, a randomly selected sample of metasynthesis articles was systematically reviewed to identify the types of findings that have been produced. Based on this systematic examination, it appears that findings from metasynthesis investigations might not be reaching their full potential. Metasynthesis investigations frequently result in isolated findings rather than findings in relationship, and opportunities to generate research hypotheses and theoretical models are not always fully realized. With this in mind, methods for moving metasynthesis findings into relationship are discussed.
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--- layout: post title: "「译」iOS 9,为前端世界都带来了些什么?" subtitle: "iOS 9, Safari and the Web: 3D Touch, new Responsive Web Design, Native integration and HTML5 APIs" date: 2015-12-15 author: "Hux" header-img: "img/post-bg-ios9-web.jpg" catalog: true tags: - Web - 译 --- 2015 年 9 月,Apple 重磅发布了全新的 iPhone 6s/6s Plus、iPad Pro 与全新的操作系统 watchOS 2 与 tvOS 9(是的,这货居然是第 9 版),加上已经发布的 iOS 9,它们都为前端世界带来了哪些变化呢?作为一个 web 开发者,是时候站在我们的角度来说一说了! > **注!** 该译文存在大量英文术语,笔者将默认读者知晓 ES6、viewport、native app、webview 等常用前端术语,并不对这些已知术语进行汉语翻译 > 对于新发布或较新的产品名称与技术术语,诸如 Apple Pen、Split View 等专有名词,笔者将在文中使用其英文名,但会尝试对部分名词进行汉语标注 > 另外,出于对 wiki 式阅读的偏爱,笔者为您添加了很多额外的链接,方便您查阅文档或出处 ## 简而言之 如果你不想阅读整篇文章,这里为你准备了一个总结: #### 新的设备特性 * iPhone 6s 与 6s Plus 拥有 **“[3D Touch](http://www.apple.com/iphone-6s/3d-touch/)”**,这是一个全新的硬件特性,它可以侦测压力,是一个可以让你拿到手指压力数据的 API * iPad Pro 的 viewport 为 1024px,与以往的 iPad 全都不同 * 想在 iPad Pro 上支持新的 Apple Pen?不好意思,目前似乎并没有适用于网站的 API #### 新的操作系统特性(与 web 相关的) * iPad 上的 Safari 现在可以通过 [Split View](https://developer.apple.com/library/prerelease/ios/documentation/WindowsViews/Conceptual/AdoptingMultitaskingOniPad/QuickStartForSlideOverAndSplitView.html#//apple_ref/doc/uid/TP40015145-CH13-SW1)(分屏视图)与其他应用一起使用,这意味着新的 viewport 尺寸将会越来越常见 * 新的 Safari View Controller([`SFSafariViewController`](https://developer.apple.com/library/prerelease/ios/documentation/SafariServices/Reference/SFSafariViewController_Ref/index.html#//apple_ref/occ/cl/SFSafariViewController))可以让你在 native app 内提供与 Safari 界面、行为连贯一致的应用内网页浏览体验 * 注意啦!Safari 新加入了 Content Blocker(内容拦截器)。以后,并不是所有的访问都一定会出现在你的 Google Analytics 了 * [Universal Links](https://developer.apple.com/library/prerelease/ios/documentation/General/Conceptual/AppSearch/UniversalLinks.html#//apple_ref/doc/uid/TP40016308-CH12) 可以让应用的拥有者在 iOS 内部“占有”自己的域名。因此,访问 yourdomain.com 将会打开你的应用(类似 Android 的 Intents 机制) * [App Search(应用搜索)](https://developer.apple.com/library/prerelease/ios/documentation/General/Conceptual/AppSearch/index.html#//apple_ref/doc/uid/TP40016308):现在,Apple 将会抓取你的网页内容(与 native app 内容)用于 Spotlight 与 Siri 的搜索结果,[想知道你的标签都兼容吗?](https://developer.apple.com/library/prerelease/ios/documentation/General/Conceptual/AppSearch/WebContent.html#//apple_ref/doc/uid/TP40016308-CH8) * 你的网站现在可以通过 JavaScript API 访问 iCloud 的用户数据 #### 新的 API 支持 * [Performance Timing API](https://developer.mozilla.org/en-US/docs/Web/API/Performance/timing) 在 iOS 9 得到回归 * 关于 HTML5 Video,你现在可以在支持 [Picture in Picture(画中画)](https://developer.apple.com/library/prerelease/ios/documentation/WindowsViews/Conceptual/AdoptingMultitaskingOniPad/QuickStartForPictureInPicture.html#//apple_ref/doc/uid/TP40015145-CH14)的 iPad 设备上提供这项新功能;你的视频甚至可以在 Safari 关闭后继续播放 * 更好的 ES6 支持:classes(类), computed properties(可计算属性), template literals(模版字符串)等 * Backdrop CSS filters(背景滤镜) * CSS @supports 与 CSS Supports JavaScript API * CSS Level4 伪选择器 * 用于支持分页内容的 CSS Scroll Snapping * WKWebView 现在可以访问本地文件了 * 我们仍然需要等待 Push Notification,camera access,Service Workers 这些现代 web API 的到来 #### 新的操作系统 * 新一代 Apple TV 的 **tvOS**: 没有浏览器,也没有 webview。但是 JavaScript、XHR 和 DOM 可以通过一个叫做 TVML 的标记语言来使用 * Apple Watch 的 **watchOS**:完全没有任何浏览器和 webview > **再注!** 由于原文写于 Apple 发布会之前,为了不让读者感到奇怪,笔者将会对文章进行适当改写与补充,以保证本文的连贯性 ## 新的 iOS 设备特性 ### iPhones 6s 与 3D Touch 从 web 设计与开发的角度来说,新的 iPhone 6s 与 6s Plus 与之前的版本并没有太多差别。不过,有一个特性注定会吸引我们的目光:**3D Touch** 我们无法确定 Apple 是不是只是重命名了一下 “Force Touch”(用于 Apple Watch、TrackPad 2 与最新的 MacBook 上)或者 3D Touch 的确是一个为 iPhone 定制的似曾相识却不同的东西。3D Touch 允许操作系统和应用侦测每一个手指与屏幕接触时的压力。从用户体验的角度来说,最大的变化莫过于当你用点力去触碰或者拖拽屏幕时,操作系统将会触发诸如 peek,pop 这些新机制。那么问题来了:**我们是否能够在网站中使用这个新玩意呢?让我们一点点来看:** iOS 9 搭载的 Safari 包含了一些用于 “Force Touch” 的新 API,但它们其实并不是那个用于 iPhone 6s 3D Touch 的 API。你可以理解为这些 API 就是 MacBook 版 Safari 里为 Force Touch 准备的那些 API ,因为共享一套 codebase,所以它理所当然得存在了 iOS 版里而已。 Force Touch API 为我们添加了两个新东西: 1. 你的 click 事件处理函数将会从 MouseEvent 中收到一个新的属性:`webkitForce` 2. DOM 也新增了四个事件:`(webkit)mouseforcewillbegin`,`mouseforcedown`,`mouseforceup` 与 `mouseforcechange`。下边的示意图将告诉你这些事件是在何时被触发的: ![Force Events](http://www.mobilexweb.com/wp-content/uploads/2015/09/foceevents.png) 相信你已经从它们的名字中意识到了,这些事件都是基于鼠标而非触摸的,毕竟它们是为 MacBook 设计的。并且,TouchEvent 也并没有包含 `webkitForce` 这个属性,它仅仅存在于 MouseEvent 里。在 iOS Safari 里,你确实可以找到 `onwebkitmouseforce` 这一系列事件处理器,但是很可惜它们并不会被触发,click 返回的 MouseEvent 也永远只能得到一个 `webkitForce: 0` 可喜可贺的是,故事还没有结束。[Touch Events v2 draft spec(触摸事件第二版草案)](https://w3c.github.io/touch-events/) 中正式添加了 `force` 属性。3D Touch 也得以在 iPhone 6s 与 6s+ 中通过 TouchEvent 访问到。不过,笔者也要在这里提醒大家,由于没有 `webkitmouseforcechange` 这样给力的事件,在手机上我们只能通过 **轮询 TouchEvent 的做法** 来不断检测压力值的改变……非常坑爹 [@Marcel Freinbichler](https://twitter.com/fr3ino) 第一个在 Twitter 上晒出了自己的 [Demo](http://freinbichler.me/apps/3dtouch)。在 6s 或 new Macbook 的 Safari(目前仅 Safari 支持)上访问就可以看到圆圈会随着压力放大。墙内的小伙伴可以直接试试下面这个圆圈,体验下 3D/Force Touch 带来的的奇妙体验。 <iframe src="//huangxuan.me/forcify/" style=" width:100%; height:500px; border: 0; "></iframe> 如果你不巧在用不支持 3D/Force Touch 的设备,发现尼玛用力按下去之后居然圆圈也有反映!? 放心,这真的不是你的设备突然习得了“感应压力”这项技能,而是因为 [Forcify](http://huangxuan.me/forcify) 是一个用于在所有设备上 polyfill 3D/Force Touch API 的 JS 库……它不但封装了 OSX/iOS 两个平台之间 API 的差异,还使用"长按"来模拟了 `force` 值的变化…… ### iPad Pro 全新的 iPad Pro(12.9 寸)打破了以往 iPad 渲染网站的方式。在此之前,市面上所有的 iPad(从初代 iPad,到 iPad Air 4,到 iPad Mini)都是以 768px 的宽度提供 viewport。 而屏幕更大的 iPad Pro 选择了宽 1024px 的 viewport,这使得它天生就能容纳更多的内容。不少人说iPad Pro 就是抄 Microsft Surface Pro 的嘛……嗯哼,IE/Edge 在 Surface Pro 上就是以 1024px 作为视口宽度的…… 从交互的角度上来说,iPad Pro 虽然不支持 3D Touch,但是可以搭配 Smart Keyboard 与/或 Apple Pen(带有压力侦测)使用。对于键盘其实并没有什么好说的,如果一个网站在搭配键盘的桌面电脑上好用,它在 iPad Pro 上应该也不赖。而对于 Apple Pen,很可惜,目前似乎并没有 API 能让你在网站上获得这根笔的压力与角度。 ## 新的 iOS 操作系统特性 ### iPad 上的多任务处理 自 iOS 9 起,iPad 允许两个应用在同一时刻并肩执行,有三种方式:**Slide Over**,**Split View** 与 **Picture-in-Picture**。不过,每一种方式都有其硬件需求,比如说 Slide Over 需要 iPad Air, iPad Mini 2 以上的设备,而 Split View 由于对内存的要求目前只支持 iPad Air 2 与 iPad Pro。 #### Slide Over(滑过来!) Slide Over 支持的 App 并不多,不过 Safari 名列其中,这意味着我们的网站将可能在这个模式下被渲染。当网站处于 Slide Over 模式下时,它将在屏幕的右 1/4 位置渲染,并且置于其他 native app 之上。 这个模式也为 Responsive Web Design(响应式网站设计)提出了新的挑战:**一个只为 iPad 优化的网站,也需要能在该设备上以无需手动刷新的形式支持小屏幕的渲染。**因此,如果你正在使用服务器端探测(RESS),那么你的 iPad 版本需要以某种方式包含手机版本的网站,或者在进入该模式后重新加载一次。(如果你不了解 RESS,你可以观看我的[另一篇博文](/2014/11/20/responsive-web-design/)) ![Slide Over](http://www.mobilexweb.com/wp-content/uploads/2015/09/slideover.png) 在这个模式下,无论横屏还是竖屏,所有的 iPad(包括 Pro)都会把你的网站以 320px 的 viewport 宽度进行渲染,就好像在一个大 iPhone 5 上一样。你可以在 CSS 中通过 media query(媒体查询)探测到这个模式: ```css /* iPad Air or iPad Mini */ (device-width: 768px) and (width: 320px) /* iPad Pro */ (device-width: 1024px) and (width: 320px) ``` #### Split View(分屏视图) 在较新版本的 iPad 上,你可以将 Slide Over 的 Side View(侧视图)升级为 Split View。此时,两个应用将以相同比例在你的屏幕上同时工作。 在这个模式下,我们的网站将可能…… * **以屏幕 1/3 比例渲染时**,viewport 在 iPad Air/mini 犹如 iPhone 5,宽 320px。而在 iPad Pro 上则像是 iPhone 6:宽 375px * **以屏幕 1/2 比例渲染时**,viewport 在 iPad Air/mini 上呈现为 507px 宽,而在 iPad Pro(横屏)下呈现为 678px 宽 * **以屏幕 2/3 比例渲染时**,viewport 在 iPad Air/mini 上呈现为 694px 宽,而在 iPad Pro(横屏)下呈现为 981px 宽 ![Split View](http://www.mobilexweb.com/wp-content/uploads/2015/09/splitview.png) #### Picture in Picture(画中画) 在一些较新版本的 iPad 上,使用 HTML5 video 标签的网站可以将其暴露到 Picture in Picture 机制中。通过 API(本文稍后会讲)或用户的触发,视频可以独立于网站在其他应用的上方继续播放。 ![Picture in Picture](http://www.mobilexweb.com/wp-content/uploads/2015/09/pip.png) ### iOS 9 下的响应式网页设计 下图向你展示了 iOS 9 所有可能的 viewport 尺寸,检查检查你的响应式断点都包含它们了吗? ![iOS 9 RWD](http://www.mobilexweb.com/wp-content/uploads/2015/09/ios9rwd.png) ### Safari View Controller 如果你用过 Twitter 或者 Facebook(或者微信,微博……),那么你一定知道很多 native app 在打开一个网页链接时并不会默认使用 Safari。它们试图让你留在它们的应用里,所以通过提供 webview 让你在应用内进行网页浏览。可是问题在于,这类 webview 并不会与浏览器共享 cookies,sessions,autofill(自动填充)与 bookmark(书签),为了解决这些问题,就有了 Safari View Controller。 现在,native app 可以使用 Safari View Controller 来打开网站,它提供与 Safari 完全一致的隐私政策、local storage,cookies、sessions 同时让用户留在你的 app 中,它通过一个 “Done”(完成)按钮使用户可以回到 native app 的上一个 controller。这个全新的 controller 还可以让我们在 Share(分享)按钮上添加自定义的操作,这些操作在用户使用 Safari 应用时并不会出现。同时,native app 对这个自定义 Safari 实例具有完全的内容控制,你可以屏蔽不想被渲染的内容。 当你需要基于 web 的鉴权,比如 OAuth 时,使用 Safari View Controller 同样是一个好主意,这样就不再需要打开浏览器再重定向回你的应用。不过注意了,Safari View Controller 只适用于在线、公开的 web 内容。如果你的 web 内容假设在本地或者私服,那么 WKWebView 仍然是最推荐的选择。 > 笔者八卦一下,Safari View Controller 实际上也算是半个社区推进的产物。早在 2014 年 12 月,Tumblr 的 iOS 工程师 Bryan 就发表了一篇著名的 [We need a “Safari view controller”](http://bryan.io/post/104845880796/we-need-a-safari-view-controller) 叙述现有 webview 在第三方登录鉴权时的窘境。 > 2015 年 6 月,Apple Safari 工程师 Ricky Mondello 的 Twitter 宣告了这个设想的落地:You all asked for it. Come see me introduce it. Introducing Safari View Controller 1:30 PM, Tuesday. Nob Hill. ### Safari Content Blockers 现在,iOS 9 上的 Safari 支持一种全新的 App Extensions(应用拓展):**Content Blocker**(内容拦截器)。这类拓展以 native app 的形式存在,你可以在 App Store 上下载到,它们可以拦截 Safari 内的任何内容,包括:跟踪器、广告、自定义字体、大图片、JavaScript 文件等等。 作为 web 开发者,尽管我们不能禁用 Content Blocker,我们仍然应该注意到它们的存在。诸如 Crystal 的一些拦截器宣称他们[可以提高网页的打开速度](http://murphyapps.co/blog/2015/8/22/crystal-benchmarks)。Crystal 声称可以加快网页的加载速度 3.9 倍并且少用 53% 的带宽。不过问题是:到底哪些东西被拦截器拦截了?[这篇文章](http://thenextweb.com/apple/2015/08/27/content-blocking-in-ios-9-is-going-to-screw-up-way-more-than-just-ads/)提到了一些我们未来可能会遇到的问题。 ![crystal](http://www.mobilexweb.com/wp-content/uploads/2015/09/crystal.png) 在 iOS 9 发布后,Peace,一个 Content Blocker,曾在 App Store 排名跻身前十。从用户的角度来说,如果一个网站由于被 Content Blocker 拦截了某些重要资源而不能正常工作,你可以长按重新加载按钮并且以不启用 Content Blocker 的方式重新加载这个网站(见下图,来自 MacWorld.com) ![disable content blocker](http://www.mobilexweb.com/wp-content/uploads/2015/09/macworld.png) Content Blocker 能隐藏元素,也有能力通过 CSS 选择器、域名、类型、或者 URL 来过滤并拦截某个文件的加载,[Purify Blocker](https://itunes.apple.com/us/app/purify-blocker-fast-clutter/id1030156203?ls=1&mt=8) 给用户提供了拦截某一种内容类型的进阶选项,比如 Web Fonts。 ![purify](http://www.mobilexweb.com/wp-content/uploads/2015/09/purify.png) ### WKWebView 的增强 UIWebView 已经被官方弃用,虽然它还在在那,不过它再也不会得到什么升级。与此相反,WKWebView 正在取代它的位置。一个最受期待的特性现在终于推出:加载本地文件到 WKWebView。因此,现在 Apache Cordova 应用与其他 web 内容都可以直接从 iOS 包中使用本地文件了,不再需要各种诡异的 hack 了。 此外,还有一些新特性也一并推出。比如说,通过 WKWebsiteDataStore,Objective-C 或 Swift 有能力查询与管理 webview 的本地存储(比如 localStorage 或 IndexedDB)。这就允许我们将原有的数据存储替换成新的某些东西,比如说替换成一个不永久的(Chrome for iOS 的隐身模式就需要这种东西) ### Universal Links(通用链接) 如果你既有一个网站,又有一个 native app,你现在可以通过 Universal Links 来增强用户体验。它允许你在操作系统内“占有”自己的域名,这样,一切指向你网站的链接都会被重定向到你的 app。 目前,所有的 app 都是通过自定义 URI 来达到这个效果的,比如 `comgooglemaps://` 就可以用来从网站或者其他原生 iOS 应用中打开 Google Maps。 想要提供这个特性的话,你首先需要在 native app 中实现 Deep Linking(深度链接),让应用中的内容与 Safari 的 URL 吻合。然后,你需要在 Apple 的网站上关联你的域名,取得这个域名的 SSL 认证并且把签名后的 JSON 部署到该域名上。这是为了防止第三方的应用“占据”了属于你而不属于他们的域名,比如说 twitter.com 被非 Twitter 的其他应用占据掉。 目前唯一的缺点是用户好像并不能决定到底以哪种方式来打开内容(使用 web 还是 app),不过我们可以观望一段时间看看它会如何发展。在不远的这段时间里,你可能会发现在网站或 Google 搜索里点击一个链接时会没有任何预警的就跳进了 native app 里。 ### App Search(应用搜索) Apple 带着自己的 web 蜘蛛杀进了搜索的市场,而我们需要支持它得以在 Siri 与 Spotlight 中提升自己的曝光率。这在我们同时拥有网站与 app 时尤为重要,因为现在 Apple 会索引你网站的内容,但打开时却可能将用户带到了 app 里去。 尽管这会开启 SEO 的新篇章,不过却相当容易。你需要使用一些标签标准,诸如 [Web Schema](http://schema.org/)、[AppLinks](http://applinks.org)、[OpenGraph](http://ogp.me) 或者 [Twitter Cards](https://dev.twitter.com/cards/mobile),配合上 App Banner 与 `app-argument`,如果你有你自己的 native app 的话。 > 关于“让你的网页支持 Apple 搜索”的更多详情,请查阅 Apple 官方文档 [Mark Up Web Content](https://developer.apple.com/library/prerelease/ios/documentation/General/Conceptual/AppSearch/WebContent.html#//apple_ref/doc/uid/TP40016308-CH8-SW5) Apple 刚刚发布了一个 [App Search Validation Tool(应用搜索验证工具)](https://search.developer.apple.com/appsearch-validation-tool/)来帮助你搞清楚,需要向你的网站添加什么才能支持 App Search ![App Search](http://www.mobilexweb.com/wp-content/uploads/2015/09/appsearch-1024x467.png) ### CloudKit JS 如果你拥有一个 native app,你很可能会将用户数据保存在 iCloud 上。在过去,只有 iOS 与 Mac 应用被允许使用它。现在,通过 CloudKit JS,你的网站也可以连接上 iCloud 数据了。 ### Back Button 现在,当你链接到一个 native app 时(通过自定义 URI 或者 Universal Link),Safari 会询问用户是否想要使用 native app 打开这个链接(见下图)。如果用户同意了,这个应用将被打开,并且在左上角会有一个返回按钮可以返回 Safari ,返回到你的网站。 <img src="http://www.mobilexweb.com/wp-content/uploads/2015/09/back.png" alt="backbutton" width="320" /> ## 新的 API 支持 ### Navigation Timing API Navigation Timing API 在 iOS 9 迎来了回归。让我们回忆一下,这货添加于 8.0 却在一周后的 8.1 中去掉了。这对于 Web 性能是个好消息。通过这个 API,我们可以更精确的测量时间,还可以获得一系列有关加载过程的时间戳,它们对于追踪与在真实场景中做决策来改进用户体验都非常有用。 ### Picture in Picture PiP API(被称为 Presentation Mode API)目前只支持 iOS,它允许我们手动让一个 `<video>` 元素进入或离开 PiP 模式如果 `video.webkitSupportsPresentationMode` 是支持的。 举个例子,我们可以在内嵌模式与 PiP 模式中切换: ```js video.webkitSetPresentationMode( video.webkitPresentationMode === "picture-in-picture" ? "inline" : "picture-in-picture" ); ``` 我们还可以通过新的 `onwebkitpresentationmodechanged` 事件来检测 Presentation Mode(展示模式)的变化。 ### Backdrop CSS iOS 7 与最近的 Mac OS 使用 Backdrop filter(背景滤镜)来模糊背景(指 native 开发),而在网站上实现这个却并不容易。 iOS 9 上的 Safari 现在支持了来自 Filter Effect v2 spec(滤镜特效第二版规范)的 **backdrop-filter**。比如说,我们可以使用一个半透明的背景并且对其背后的背景使用滤镜: ```css header { background-color: rgba(255, 255, 255, 0.4); -webkit-backdrop-filter: blur(5px); backdrop-filter: blur(5px); } ``` ![backdrop](http://www.mobilexweb.com/wp-content/uploads/2015/09/backdrop.png) ### CSS Scroll Snapping 在 web 上实现分页内容(比如相册跑马灯)总是非常麻烦,无论是使用 JavaScript 框架、touch 事件还是 hacking 滚动条等等。Apple 新添加了一个很赞的 CSS 特性叫做 CSS Scroll Snapping。这个特性新增了一系列的 CSS 属性让你定义规则或者不规则的 snap zone(停留区域),这样滚动的位置就会“啪”地一下停在这个区域,而非像以前一样可以停在任何地方。 来看个例子: ```css #photo-gallery{ width: 100%; overflow-x: scroll; -webkit-scroll-snap-points-x: repeat(100%); -webkit-scroll-snap-type: mandatory; } ``` > 想要看个跑起来后的例子?笔者为大家准备了 webkit 的官方 [demo](http://www.webkit.org/demos/scroll-snap/),不过这个属性目前只支持 iOS 9 Safari 哦,并不支持 webview ### CSS Supports CSS Supports,包括 CSS `@supports` 与来自 CSS Conditional Rules Module Level 3 spec 的 JavaScript CSS Supports API 都在 iOS 上迎来降临。现在,我们可以针对某个 CSS 属性的特定值的支持情况来编写代码: ```css @supports(-webkit-scroll-snap-type: mandatory) { /* we use it */ } ``` 同样,使用 JavaScript: ```js if (CSS.supports("-webkit-scroll-snap-type", "mandatory")) {} ``` ### 一些细微的改进 * ECMAScript 6 的更完善支持:classed、computed properties、template literial 与 week sets * 新的 CSS Level4 伪类/元素选择器:`:not`、`:matches`、`:any-link`、`:placeholder-shown`、`:read-write`、`:read-only` * Native app 现在可以通过 extension 来向 Safari 的 Shared Links(分享链接)窗口上注入信息 * 大量无前缀 CSS 属性的支持(终于),比如 transition、animation、@keyframes、flex 与 columns * Mac OS El Capitán 上的 Safari 9 提供了一个全新设计的 Web Inspector(Web 检查器)。幸运的是,iOS 9 的远程调试完全兼容 Mac OS 上的 Safari 8,所以你倒是不用急着升级你的 Mac OS * iOS 9 通过 `-apple-font` 加入了一些 Dynamic Fonts(动态字体),并且它们现在应用的是 Apple 的新字体:San Francisco,笔者的博客就已经用上它啦 * scrollingElement 现在可用了 * `<input type=file>` 现在允许你从 iCloud Drive 与已安装的第三方应用,比如 Google Drive 中选择文件 <img src="http://www.mobilexweb.com/wp-content/uploads/2015/09/IMG_2017.png" alt="input file" width="320" /> * 当你加载一个 HTTPS 协议的页面时,你不能混用 HTTP 与 HTTPS 的资源 ## Bugs Bug 通常都要在几周之后才会显露出来,我也会持续跟进并更新这篇文章。目前为止,我的发现如下: * 对于 Home Screen webapps(添加至主屏的 web 应用),`apple-mobile-web-app-status-bar-style` 这个 meta 标签不起作用了!所以你现在不能再像过去一样使用 `black-translucent` 让你的 webapp 渲染在状态栏的后面了。(iOS 9.2 fixed 了这个 bug) * Speech Synthesis API (语音综合 API)不再工作了 ## 仍在等待…… 当 Mac 上的 Safari、桌面电脑与 Android 上的 Chrome 都已经为网站支持 Push Notification (通知推送)时,iOS 上的 Safari 仍然不支持这个特性。就 API 而言,我们仍然没有:WebRTC、getUserMedia、Service Worker、FileSystem API、Network Information API、Battery Status API、Vibration API 等等……你又在 iOS 上等待哪些特性呢? ## watchOS 与 tvOS 新发布的 watchOS 2.0 与 tvOS 9.0 都是基于 iOS 的操作系统,它们针对特定的设备发行(Apple Watch 与新的 Apple TV)。从用户的角度来说,那里并没有浏览器了。从开发者的角度,那里也没有 Webview 了。 尽管有不少人抱怨(大部分都是针对 webview 的缺失),我并不能确定这是不是个坏主意。我猜测 Apple 会尝试通过 Siri 来将 “web” 带给 TV、手表、甚至 CarPlay 的用户。所以,如果你遵循了上述的 “App Search” 的步骤,你的内容将可能通过 Siri 在这些设备上以 widget(小部件)或者快捷回复的形式变得可以访问。 对于 Apple TV ,它支持使用 JavaScript、DOM API 与 XMLHttpRequest 来让我们构建某种类似 Client-Server webapp 的东西。没有 HTML 和 CSS,这是什么把戏?其实它支持的叫 TVML,是一种基于 XML、为那些可以被渲染在 TV 屏幕上的特定内容而优化后的标签。这些标签只可以在来自应用商店的 native app 中渲染,但是这些 TVML 是由服务器端来生成的。 ## 著作权声明 本文译自 [iOS 9, Safari and the Web: 3D Touch, new Responsive Web Design, Native integration and HTML5 APIs --- Breaking the Mobile Web](http://www.mobilexweb.com/blog/ios9-safari-for-web-developers) 译者 [黄玄](http://weibo.com/huxpro),首次发布于 [Hux Blog](http://huangxuan.me),转载请保留以上链接
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Main Text {#sec1} ========= (Structure *20*, 101--112, January 11, 2012) The original article unfortunately has an author error in the units for *k*~*cat*~ and *k*~*cat*~*/K*~*m*~ on page 108. In Table 2, row 2, all *k*~*cat*~ and *k*~*cat*~*/K*~*m*~ units should be "min^−1^" and "min^−1^μM^−1^," respectively, rather than be "s^−1^" and "s^−1^μM^−1^." The scientific interpretations remain the same, only the units change. Our conclusions about the active site structure based on the kinetic analysis of the mutants do not change. [^1]: These authors contributed equally to this work
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The present disclosure relates generally to wheeled vehicles. More particularly, the present disclosure is related to embodiments of an apparatus providing wheeled vehicles such as bicycles capable of assuming a reduced size for transport. Currently, most vehicles are not capable of quickly folding into a small footprint.
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Among the four women flanking Donald Trump at his Facebook-Lived news conference before the second presidential debate, Paula Jones stood out. The women had been assembled by Trump to counter criticism following the leak of a 2005 video in which the GOP candidate bragged about using his star power to sexually assault women. And so he turned to Juanita Broaddrick, Kathleen Willey, Kathleen Shelton, and Jones, who all shared a mutual opposition to the Clintons—three, including Jones, had accused Bill Clinton of sexual assault or harassment in the past. The fourth, Kathleen Shelton, was raped when she was 12 years old. Hillary Clinton was her accused rapist’s defense lawyer. When a reporter asked Trump whether he’d actually groped women as he claimed in the leaked Access Hollywood video, Jones—a plucky 49-year old Arkansan wearing head-to-toe Victoria’s Secret loungewear and a bedazzled hat—snapped back in her trademarked drawl, “Why don’t you go ask Bill Clinton that? Why don’t you ask Hillary as well?” Two days before, Jones had railed against Trump having to apologize for his boorish comments, in effect saying, “Where is my apology?” Trump supporters praised Jones’s moxie online as reporters whipped up “Who is Paula Jones?” explainers for millennials, and far-right media outlets clamored for interviews. Jones’s dive back into the national spotlight via Trump’s campaign feels at once an unexpected and somehow wholly appropriate end to an election that’s laid bare the political truth that truly nothing matters. Trump, who once publicly ridiculed Jones as “a loser” for claiming Bill Clinton had sexually harassed her, was parading her onstage to distract voters from his own growing list sexual-assault accusations. Democratic nominee Hillary Clinton—who as first lady dismissed Jones as a pawn of her husband’s political enemies and called her accusations fiction—quietly changed the language in her sexual-assault platform, erasing the notion that professed victims should “be believed.” Meanwhile, the conservatives who, back in the ’90s, peddled in faux outrage to manipulate and profit from Jones and her claims—then deserted her when she no longer advanced their political agenda—are the same ones who are compromising their professed Christian values in order to embrace their undeniably vulgar, possibly criminal, Republican nominee. What’s most surprising, is that 16 years after acknowledging she’d been used by the far-right movement in a crusade to take down the Clintons, Jones is enthusiastically taking her place back on their team. Paula Jones’s story was, and is, catnip for conservatives: She has consistently claimed that in 1991, when she was a 24-year-old state employee making $6.35 an hour, Bill Clinton, then Arkansas’s governor, made several unwanted sexual advances and exposed himself to her in a Little Rock hotel room. When Jones expressed shock and disgust, she says Clinton stopped, and told her, “Well, I don’t want to make you do anything you don’t want to do.” After the alleged encounter, Jones claimed she was threatened, intimidated, and reassigned—all, she claimed, as retribution for refusing Clinton. The sexual-harassment lawsuit her allegations spawned dragged on five long years—thanks to a group of anti-Clinton conservatives who saw Jones as a means to take down the president—and ended with Clinton handing over an $850,000 out-of-court settlement but never an apology or acknowledgment of any wrongdoing. The president also survived the impeachment fight her case triggered. Clinton has steadfastly denied Jones’s allegations and maintained he doesn’t remember meeting her. “I’m glad it’s over with, that’s for sure,” Jones told Joe Conason in a 2000 Penthouse interview—the third, and only voluntary time, Jones appeared in the magazine. “And I wish it could have been over with a lot sooner. I’m not looking for fame or fortune or anything like that.” Jones had reason to be relieved; the ’90s had been hell. She had taken a beating from the Clinton camp and the national media, been ostracized or ignored by feminist groups, and used then discarded many times over—by the press and pornographers, as well as politically or financially motivated conservative groups that feigned to help her, while working against her best interests. Jones first appeared on the public eye in the pages of the American Spectator, the ultra-conservative magazine funded by billionaire Richard Mellon Scaife that acted as the central cog in what Hillary Clinton would famously described as “a vast right-wing conspiracy” out to ruin her husband. In a December 1993 article, “His Cheatin’ Heart,” by David Brock (a self-described reformed conservative who now supports Hillary Clinton), a former Arkansas state trooper described escorting a “Paula” to Bill Clinton’s hotel room in 1991. When she emerged an hour later, according to the trooper, “Paula told him she was available to be Clinton’s regular girlfriend if he so desired.” (Brock did not respond to requests for comment from The Daily Beast for this article.) The story only used her first name—an inclusion the Spectator editor in chief would later admit was an “editorial mistake”—but Little Rock was a small place and everyone, Jones thought, knew who the trooper was talking about. She’d never had sex with Clinton, as the article implied; in fact, she told family and friends, when the governor allegedly dropped his pants and asked her to “kiss it,” that she had rejected him. So at a friend’s suggestion, Jones sought legal counsel “to clear her good name.” Bill Clinton had been president for a year, and amassed plenty of enemies on his way to the White House. And Jones soon found that a horde of Clinton’s adversaries were happy to champion her cause. Jones and her lawyer held a press conference at the Conservative Political Action Conference. Jones then went on Pat Robertson’s 700 Club, telling the televangelist, “I felt raped. Whether he touched me or not, it was disgusting what he did.” Anti-abortion group Operation Rescue’s leader Patrick Mahoney created a legal defense fund for Jones, because he said, “sexual harassment is wrong.” (Mahoney has not formally endorsed a candidate in 2016, but on Twitter, called Trump’s behavior toward women during the campaign, “troubling and shameful.” Roberston defended Trump on his program last week, dismissing the leaked video as “macho talk.”) She also appeared on National Empowerment Television, a precursor to InfoWars that peddled in Clinton conspiracy theories alleging the Clintons to be murderers. Accuracy in Media, a conservative media watchdog, spent thousands on newspaper ads criticizing the hypocrisy of the liberal media for covering Anita Hill’s complaints while ignoring those from Jones. And Southern Baptist Old Time Gospel Hour televangelist Jerry Falwell, founder of Moral Majority, a political organization for religious conservatives, paid for, distributed, and tirelessly promoted The Clinton Chronicles, a truth-lite “documentary” which accused the president of being a drug-running, murderous womanizer, and prominently featured Jones and her husband, Steve. The tape sold for a donation of $40 plus $3 shipping and handling. The reaction from the left to Jones’ $700,000 civil suit against President Clinton—filed just days before the statute of limitations would run out—was equal and opposite from the support she received by the far-right. Clinton’s camp was cruel. Longtime loyalist James Carville famously said of Jones, “If you drag a hundred-dollar bill through a trailer park, you never know what you’ll find.” And women’s-rights groups were noticeably silent. Susan Estrich, a lawyer and feminist pioneer, wrote in Slate, “This is just one more political assault on the president, politically motivated and politically pursued. You can’t tell me this woman didn’t know whom she was hiring as a lawyer, whom she was allying herself with, whom she was using, and who being used by.” This year Estrich colorfully referred to Trump as “the most vulgar, rude, offensive, racist, bombastic, insensitive, unqualified, disrespectful boor ever to be nominated by a major party in our lifetimes”—then baffled feminists when she signed on to defend Roger Ailes against a sexual-harassment lawsuit brought by anchor Gretchen Carlson that led to the Fox News founder’s ouster. While not offering their exact support, eventually the National Organization for Women, which stood by Clinton, told the president’s supporters they had gone too far in their bashing of Jones. NOW President Patricia Ireland told the New York Daily News in 1997, “I would urge President Clinton to rein in his lawyers on this,” calling their threats to dig up further dirt on Jones in response to a defamation suit she brought, an “inappropriate and disappointing strategy using the so-called ‘nuts and sluts’ defense.” But none of it compared to Jones’s Penthouse treatment. Less than a year after coming forward, Jones’s lawyers were fighting to keep 12 nude photos of their client from being published. Penthouse argued the photos were protected by free-speech laws because of their newsworthiness—ostensibly that they betrayed Jones’s true character and undermined her “I’m not that kind of girl” defense. Jones’s lawyers contended publishing the photos, taken when Jones was 19 years old by her 31-year-old boyfriend, was a violation of New York privacy laws. A judge disagreed. “Publication of these photos was the functional equivalent of a rape—a public raping of Paula Jones—where the rapist instead of being punished gets paid for his behavior,” Jones’s attorney Joseph Cammarata said in response to the ruling. (Cammarata is currently representing seven women who say they were sexually assaulted by Bill Cosby.) While Jones was trying to repair her reputation, the 1995 article that accompanied the photos sought to destroy it. Through dozens of anecdotes—provided by Jones’s brother-in-law, former boyfriends, neighbors, even a manager at the shoe store where she once worked—writer Rudy Maxa crafted a profile of Jones as a “small-town vamp.” For rural Arkansas, Jones’s makeup and short skirts, her devil-may-care attitude, and popularity with boys all added up to something. “Jones’s accusations, detailed in a lawsuit filed against Clinton last spring, did nothing to to help raise the public’s perception of the president’s character,” Maxa wrote. “But what about Paula Jones’s character?… What about Paula Jones’s reputation?” To add insult to injury, Penthouse reprinted the photos in April 1998, the month a federal district judge dismissed Jones’s case. (She would appeal.) For this, Maxa went back to Arkansas for more local dirt on Jones’s alleged promiscuity and again rehashed back-fence gossip about her tight dresses and loose morals. Even the headline, “The Devil in Paula Jones,” was the same. Maxa wondered once more: Why had Paula Jones waited so long to come forward? And why had she not been more upset when telling family what Bill Clinton had allegedly asked of her in that hotel room? But he included new details, too: She’d supposedly had sex in a car once; Jones’s landlord said the Joneses never had money; her handyman allegedly said Jones flirted with him. According to the unnamed handyman, Jones responded to his rejection of her advances with, “You men… I can get back at you, you’ll see.” (If this seems like an unlikely quote, a look at Maxa’s own record raises further questions concerning the Penthouse writer’s dedication to facts and accuracy. Two months after the Jones story, Penthouse retracted an equally explosive article from Maxa on New York Episcopal priests who, he reported, had engaged in homosexual orgies with Brazilian men. Most of the allegations were found to be untrue. In 1991, he left or was booted from his gig at Washingtonian magazine shortly after the publication printed an apology and settled a libel suit with Washington Redskins owner Jack Kent Cooke over a profile that painted him as racist who knew about the fixing of football games.) After the Penthouse shaming, some of Jones’s staunchest conservative supporters turned their backs on her; among them, Operation Rescue’s Rick Mahoney, who set up Paula’s first legal defense fund. “All the sudden these pictures surface and and then they dumped me like a hot potato,” Jones would later explain to Joe Conason. “I guess because I was dirty and this and that…” Meanwhile, Jones’s harassment suit was being commandeered for a greater cause—the takedown of a president. The search for evidence in Jones’s case uncovered the affair between the president and Monica Lewinsky, and the discovery that Clinton had lied under oath about his relationship with the White House intern, which in turn led to independent counsel Kenneth Starr’s report and Clinton’s impeachment. Things were moving fast for Jones, and it wasn’t always clear just who was in control of her case. In 1997, Jones was being represented by Gilbert Davis and Joseph Cammarata—two moderate Republicans who suggested that Jones accept a settlement offer of $700,000. For her part, Jones later said, “Oh, I instructed them many times to try and get the case settled…” But there were other lawyers steering the ship from behind the scenes, a group of young conservatives who referred to themselves as Elves (as in the muscle and magic that runs Santa’s workshop). These elves included George Conway—husband to Kellyanne Conway, Trump’s third and current campaign manager who has defended Trump’s trotting out of Jones and the other women, telling Anderson Cooper, “I believe that voters should know who Hillary Clinton is.” George Conway wrote the Supreme Court brief that allowed Jones’s case to continue and leaked to Matt Drudge details of a sealed affidavit that would later be used to discredit Jones—one in which she described a “distinguishing characteristic” of the president’s penis, specifically a bend, a condition that doctors who examined Clinton disputed. Another “Elf,” now-famous conservative firebrand Ann Coulter, was little-known outside far-right DC circles at the time, but made no secret of her distaste for the quick settlement that Jones said she always wanted. In Michael Isikoff’s Uncovering Clinton, Coulter called news of a settlement “a fucking disaster!” “We were terrified that Jones would settle,” Coulter reportedly said. “It was contrary to our purpose of bringing down the president.” While other accounts downplay Coulter’s actual contributions, Bob Guccione Jr., the eldest son to Penthouse magazine’s publisher, and one-time boyfriend to Coulter in the ’90s, said the blonde political commentator was clear about her role then, and what she thought of Jones. “[Coulter] boasted about surreptitiously writing Jones’s legal complaint with a couple of her conservative lawyer friends in DC,” Guccione Jr. told The Daily Beast. “She bemoaned that Jones made a fool of herself in the media, because not only had she not been involved in writing her own complaint, she hadn’t bothered to read it when it was done.” Coulter did not respond to a request for comment. When Susan Carpenter McMillan, an antiabortion activist who had befriended Jones, got wind of a settlement in the spring of 1997, she officially signed on as her official spokesperson, telling Jones’s lawyers: “I’m on board. You don’t have to like it, you don’t have to approve of it. I’m here. I’m going to defend her.” Jones’s advisers and husband convinced her not to take the 1997 settlement, leading her attorneys, Davis and Cammarata, to quit. McMillan held a press conference in front of her home to announce the split. No case was more publicized at the time, and Jones’s case was quickly taken over by Dallas lawyers provided by conservative a Christian legal organization, the Rutherford Institute, whose first order of business involved sending out direct-mail requests for donations. When the money didn’t come rolling in—they only collected $300,000—Rutherford President John Whitehead could only guess why. “There’s a sexual angle to the case that bothers some people,” Whitehead told the Associated Press. “I thought I would have people patting me on the back… but I haven’t heard a thing from anybody.” When a settlement was finally reached in 1998, Jones had incurred hundreds of thousands of dollars of unnecessary debt. Her reputation was ruined: She was mocked mercilessly on late-night television, and in a 1998 national poll, only a quarter of Americans said they believed Jones was telling the truth. After legal fees, her $850,000 settlement turned into $151,000, and because of mismanagement of one of her legal defense funds, Jones owed thousands in taxes and penalties to the IRS. A year after the settlement, Jones was an unemployed, broke, divorced mother of two boys, and all her conservative friends had disappeared. So she agreed to pose for a tasteful spread in the very magazine that she had sued to stay out of, the same one that had disparaged her twice before. The money, she said, would be used for her sons’ college funds. Upon hearing Jones was posing for Penthouse, conservatives who had abandoned her in droves, began to actively attack her. Ann Coulter made her disdain public, writing, “[Jones] used to be a hero in a David and Goliath conflict. She used to have dignity and nobility and tremendous courage. Now she’s just the trailer-park trash they said she was.” In 2000, Jones sat down for an accompanying Penthouse interview with Joe Conason, coauthor of that same year’s The Hunting of the President: The Ten-Year Campaign to Destroy Bill and Hillary Clinton. Jones still thought she had been “done wrong” by the Clintons and their attack machine, but she seemed to have also grown wary of the right, concluding, “I was used by a lot of people to get to him.” “I feel like I came out with the wrong end of the stick, you know?” she said. But that was then. These days, though many of the players are the same, Jones seems like a woman on her own mission. Jones came out against Hillary Clinton’s presidential bid in a 2015 interview with the Daily Mail and told Inside Edition in September, “I am a big Trump supporter, I think he would be our next best president since Ronald Reagan.” After joining Trump’s impromptu press conference last week, Jones appeared with the same women on non-journalist Sean Hannity’s Fox News show. There, Jones alluded to the conspiracy theories first pushed in the Clinton Chronicles in which she appeared decades ago: “There’s been so many things to happen to so many people that are connected to the Clintons.” When Hannity asked if Jones fears for her own life, she answered, “Absolutely I feel that way if she becomes the president. She’s going the rule the world.” Jones declined an interview with The Daily Beast. Her husband, with whom she lives in Arkansas, Steven McFadden, told me that Jones is cautious these days when it comes to the media, but in a brief telephone call, praised his wife for weathering more than most could imagine. “Paula’s definitely a strong lady. She’s not one that you want to back into a corner,” McFadden said. Jones hasn’t commented on the spate of women who came forward last week with stories alleging Donald Trump had sexually assaulted them, or his denials, which routinely invoke the unattractiveness of his accusers—a tactic with which Jones, ridiculed mercilessly for her appearance and social class, should feel all too familiar. She’s also stayed quiet regarding the recently rediscovered tapes of Trump disparaging her in the press. In 1998 on Fox News, Trump said that Bill Clinton himself had been a victim of a “truly an unattractive cast of characters,” naming Jones among them. He was more direct on MSNBC, telling Chris Matthews in 1998, “Paula Jones is a loser.” Still, if Jones harbors any animosity toward the Republican nominee or his alt-right backers who, not so long ago, used her for their own political agendas, she hasn’t made it known. For Jones, whatever happened in that Little Rock hotel room—and the price she ultimately paid for it—seems to trump all. Tatyana Bellamy-Walker contributed research.
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1. Field of the Invention The present invention relates to a glass setting plate for a glass polishing system, and more particularly to a glass setting plate that supports a lower surface of a glass in a glass polishing system for polishing a glass used for liquid crystal displays. 2. Description of the Related Art Generally, it is very important that a glass (or, a glass pane) applied to a liquid crystal display keeps its flatness to a certain level so as to accurately realize images of the liquid crystal display. Thus, fine waviness or unevenness existing on a surface of a float glass formed in a float manner should be removed. Such a glass polishing process may be classified into so-called ‘Oscar’ type polishing in which glasses are individually polished one by one, and so-called ‘inline’ type polishing in which a series of glasses are successively polished. Also, the glass polishing process may be classified into ‘single side polishing’ in which only one surface of a glass is polished, and ‘double side polishing’ in which both surfaces of a glass are polished. In a conventional glass polishing device, while a polishing plate (or, an upper plate) having a polishing pad installed thereto is moved in a horizontal direction and a polishing stage (or, a lower plate or a glass setting plate) having a glass located thereon is rotated, the glass is polished using a polishing slurry freely falling down onto the polishing plate. However, as a glass to be polished becomes bigger to cope with the tendency that liquid crystal devices are larger, the upper plate serving as a polishing plate and the glass setting plate serving as a polishing stage naturally become bigger. Here, the glass setting plate should have sufficient flatness in order to ensure flatness of a glass pane completely polished. Also, it is important that the glass setting plate has a sufficient rigidity against deformation so as not to cause permanent deformation. In order to meet such requirements, it is urgently demanded to develop a glass setting plate using light and rigid materials. A conventional glass setting plate for polishing so-called 8th generation glass panes still has a burden on weight (for example, about 10 tons) though it can ensure good rigidity against deformation, because the conventional glass setting plate is generally made of carbon steel.
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NV2500 High Roof V6 NV3500 Standard Roof V8 NV2500 High Roof V8 NV2500 High Roof V8 S $43,193 NV2500 High Roof V8 SV $45,043 NV3500 High Roof V8 NV3500 High Roof V8 S $44,543 NV3500 High Roof V8 SV $46,393 Disclaimer: Prices do not include sales taxes, licensing, other options, installation, administration and other dealer program fees. Prices include freight and P.D.E. In Ontario, prices include all fees except for sales taxes. Models and pictures shown for illustration purposes only. Options and accessories may vary by trim. Data and prices are provided by a third-party and we cannot guarantee their accuracy.
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Azi (scribe) Azi (fl. c. 2500 BC) is the name of a scribe from the kingdom of Ebla. His name has been found on a number of clay tablets, making possible an extrapolation of his career path. Career He began as a student and passed examinations to become a scribe. He was a highly competent teacher, known from his title, dub-zu-zu, or "one who knows the tablets." Finally, he became a top administrator in the kingdom. Sources References Category:Ebla Category:Ancient Near Eastern scribes Category:Writing teachers Category:Syrian educators Category:25th-century BC people Category:Year of birth unknown Category:Year of death unknown
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Acacia vittata Acacia vittata is a shrub of the genus Acacia and the subgenus Plurinerves. It is native to an area in the Wheatbelt and Mid West regions of Western Australia. The dense rounded shrub typically grows to a height of . It blooms in August and produces yellow flowers. See also List of Acacia species References vittata Category:Rosids of Western Australia
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Automated system recovery Automated system recovery (ASR) is a feature of the Windows XP operating system that can be used to simplify recovery of a computer's system or boot volumes. ASR consists of two parts: an automated backup, and an automated restore. The backup portion can be accessed in the Backup utility under System Tools. ASR does not back up user files or other data, only data necessary for restoring the system configuration state. Other backup systems should be put in place to ensure user's actual data files are also backed up. In the event of a failure, an ASR restore is performed first, which allows user files to then be recovered. ASR should be used only as a last resort because in preparation for a restore ASR will format the system and boot volumes, making other, less-drastic recovery methods impossible. References External links Recover with Windows Automated System Recovery Category:Backup software Category:Windows administration Category:Windows XP
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Story highlights Stephanie Coontz: Indiana, Arkansas governors caught off guard by outrage, boycotts over anti-LGBT law She says religious conservatives who discriminate no longer hold sway in a culture comfortable with diversity, including same-sex marriage Stephanie Coontz teaches at The Evergreen State College in Olympia, Washington, and is director of research and public education at the Council on Contemporary Families. She is the author of "Marriage, a History: How Love Conquered Marriage." The opinions expressed in this commentary are solely those of the author. (CNN) The public outrage over the "religious freedom" bills recently passed in Arkansas and Indiana caught the governors of those states completely off-guard, judging by their confused and contradictory responses. As poll watchers, they surely knew that most Americans now oppose the discriminatory laws and practices they accepted as normal only a dozen years ago . But the politicians underestimated the pushback organized by local and national businesses, including companies with no previous record of public support for social equality. Stephanie Coontz They had better adjust to a new reality. For the past three decades, socially conservative evangelicals and pro-business interests have been powerfully allied against government regulations, environmental initiatives and social welfare programs, while supporting lower taxes for the wealthy and pushing back against the growing diversity in America's population. For many, this alliance been puzzling: Other, equally devout Christians who place more emphasis on Jesus Christ's message of unconditional love and on his denunciations of excessive wealth and neglect of the poor, have been uncomfortable with it, as have many business leaders. Their priorities, after all, are based on the bottom line. And companies that sell goods and services to the public are learning that support for discrimination -- or even passive acceptance of it -- threatens that bottom line.
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PRINT-N-PLAY (PnP) Your dollar gets you all of our updates, input on stretch goals, and a PnP version of Control. Retailers: Choose this reward and contact us for bulk options. Less
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Home > Blog > Choosing the Right Way to Implement a Clip, Zip and Ship Solution Choosing the Right Way to Implement a Clip, Zip and Ship Solution March 2, 2018 Public and private organizations manage an increasing amount of data for sharing. Whether it’s for the general public or a controlled and restricted audience, the number of data access requests continues to grow. Self-service applications, such as Clip, Zip and Ship, can help funnel these requests. There are two ways to implement a Clip, Zip and Ship solution: As part of a part of an open data sharing project As part of a controlled-access data sharing project To lay the foundations for the right solution, you must first pinpoint the needs of your organization with the help of a few key questions: Is this solution part of an open data sharing project, or is it intended for a restricted public? Who will be using the Clip, Zip and Ship application? Is this solution replacing a process that requires manual intervention for each request? Is this solution improving another solution from a pre-existing self-service platform, or is it a new solution being implemented for the first time? Open data project This type of implementation is mainly used for distributing data to the general public, as is the case for Open Government. Access to the site is not controlled by a user name or password. Open data comes from various sources, and sensitive data is generally filtered there before distribution. Clip, Zip and Ship can act as an open data sharing portal on its own, but it can also enhance a solution from a pre-existing platform like CKAN, Socrata, ArcGIS Open Data, FTP or AWS. In this case, implementing in conjunction with Clip, Zip and Ship provides the added value of enabling targeted requests like selecting one or more datasets, output coordinate systems and formats, or even an area of interest. In either case, the solution usually requires the creation of an application with a graphic interface that includes at least the following elements: Access-controlled data This type of implementation meets the needs of one or more specific groups. Access to the site is password-controlled because the data distributed there is more sensitive. An example of this type of implementation could be the extraction of infrastructure data for property developers. For this type of project, Clip, Zip and Ship often replaces a process that requires manual intervention. It used to be that custom and ad hoc data access requests needed a technician to process them. With this type of solution, these requests can now be sent directly and without delay to a Clip, Zip and Ship-type portal. Although these two approaches put emphasis on processing spatially referenced data requests, a Clip, Zip and Ship project can also process requests for non-spatial data (PDF, CSV, Excel, etc.) just as efficiently. The main advantage of this solution is the way it enables users to include different kinds of data within a single request. Our seasoned team can develop a portal to let you efficiently and securely share your data.
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A 5-Year-Old Girl Gave a TED Talk Cassandra Creighton — with the help of her father, a video-game developer — created the words, art, and story behind Sissy's Magical Ponycorn Adventure, a video-game phenomenon that is blossoming worldwide, and they spoke about it in Toronto. And what did you do this year? We understand the reasons for blocking, but Vulture depends on ads to pay our writers and editors. We're working hard to improve the ad experience on our site, but in the mean time, we'd really appreciate it if you added us to the approved list in your ad blocker. Thanks for the support!
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include 'meta_dataset/learn/gin/setups/mini_imagenet.gin' EpisodeDescriptionConfig.num_support = 5 include 'meta_dataset/learn/gin/models/baselinefinetune_cosine_config.gin' LearnerConfig.learning_rate = 1e-4 LearnerConfig.decay_learning_rate = True
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List of flag bearers for Congo at the Olympics List of flag bearers for Congo at the Olympics may refer to: List of flag bearers for the Republic of the Congo at the Olympics List of flag bearers for the Democratic Republic of the Congo at the Olympics
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Минюст задействовал все инструменты для возвращения украденного прошлой властью и расследования соответствующих уголовных дел, заявил Павел Петренко Закон о гражданской конфискации, разработанный Министерством юстиции, позволит вернуть в государственный бюджет $1,5 млрд средств, украденных экс-президентом Виктором Януковичем и лицами из его окружения. Об этом на брифинге сообщил глава ведомства Павел Петренко, передает корреспондент ЛІГА.net. "Хочу обратиться к депутатам парламента с предложением, чтобы на следующей сессионной неделе был рассмотрен закон о гражданской конфискации, который разрабатывался последние несколько месяцев Минюстом, народными депутатами и экспертами, который даст возможность в рамках гражданского производства вернуть те деньги, которые сейчас заблокированы в украинских банках. Речь идет о 50 млрд гривнях (1,5 млрд долларов), украденных из украинского бюджета", - сказал он. По словам Петренко, Минюст задействовал "все возможные" законодательные инструменты для возвращения активов Януковича и расследования соответствующих уголовных производств. "Украина с точки зрения законодательства является одной из наиболее продвинутых стран, а наши правоохранительные органы имеют огромный арсенал для расследований, конфискаций и возвращения коррупционных средств", - пояснил он. Читайте также: В Минюсте придумали, как вернуть украденные деньги Петренко добавил, что когда дела об украденных Януковичем и Семьей средствах попадут в украинские суды, у Минюста появится легальный инструмент международного сотрудничества со странами, где находятся заблокированные активы подозреваемых лиц из окружения беглого экс-президента. Подписывайтесь на аккаунт ЛІГА.net в Twitter и Facebook: в одной ленте - все, что стоит знать о политике, экономике, бизнесе и финансах. Если Вы заметили орфографическую ошибку, выделите её мышью и нажмите Ctrl+Enter.
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Background {#Sec1} ========== We present the complete genome sequence and analysis of a novel *Serratia* species that, in conjunction with the nematode *Caenorhabditis briggsae*, forms a putative entomopathogenic association lethal to *Galleria mellonella* larvae \[[@CR2]\]. This *Serratia* species was isolated from *C. briggsae* nematodes recovered from three separate *Galleria* traps baited in soil in the Kawa Zulu Natal province in South Africa and resembles the other entomopathogenic nematode (EPN) associations. EPNs are mutualistic associations between a bacterium and a nematode that enables them to kill insects and benefit both partners with nutrients and breeding sites \[[@CR16], [@CR41]\]. Although all three players in the EPN life cycle - pathogenic bacteria, nematode and host insect larvae -- are ancient and abundant taxa in nature, only two independently evolved entomopathogenic partnerships are well studied. One is the association between bacteria in the genus *Photorhabdus* and Heterorhabditid nematodes \[[@CR29], [@CR100]\] and the other is the association between bacteria in the genus *Xenorhabdus* with Steinernematid nematodes \[[@CR46]\]. EPN associations involve complex interactions between the pathogens and the nematode worms. In typical EPN associations the nematode is responsible for locating suitable host, penetrating the host insect and releasing the bacteria into the hemocoel while the bacteria are responsible for killing the host, bioconversion of complex compounds and protection of the insect cadaver from scavenging competitors thus ensuring nutrition for itself and its nematode partner \[[@CR29], [@CR100]\]. Significant bacterial adaptations to the EPN lifestyle include the regulation of the switch between mutualism and pathogenicity, accelerated insect killing, cadaver bioconversion, and re-association with infective juveniles \[[@CR23], [@CR48]\]. Recent studies have revealed that in both canonical EPN bacterial species L-proline in the insect hemolymph is the main trigger that initiates a metabolic shift from a quasi-dormant state in the nematode gut to a dramatic increase in secondary metabolite production in the insect hemocoel \[[@CR33]\]. Following this L-proline-induced metabolic shift, major regulatory events take place. In the *Photorhabdus*/*Heterorhabdus* association, two global regulators, HexA \[[@CR58]\] and Ner \[[@CR69]\], control the switch between mutualism and pathogenesis, while the *phoP*/*phoQ* and the *astS*/*astR* two-component systems \[[@CR38], [@CR39]\] and the *pgbPE* operon \[[@CR12]\] regulate pathogenicity and mutualism genes. Furthermore, Heterorhabditid nematodes fail to grow and reproduce normally when grown with *Photorhabdus* mutants defective in *ngrA*, suggesting that its phosphopantetheinyl (Ppant) transferase product is required for nematode growth and reproduction \[[@CR27]\]. Finally, the reassociation of infective juveniles and their cognate bacteria as well as the retention of the bacteria in the nematode gut seems to be mediated by the expression of adhesion fimbriae encoded in one of the many genomic islands rich in phage remnants \[[@CR46], [@CR68], [@CR86]\]. By comparison, in the *Xenorhabdus*/*Steinernema* association, a similar, but non-homologous, mechanism operates in which the global regulator Lrp and the two component system *cpxRA* and the *lysR* regulator *lrhA* \[[@CR32]\] orchestrate all three major stages of the life cycle: infection, reproduction and transmission. Whereas many compounds are implicated in insect killing and sanitization of the insect cadaver \[[@CR84], [@CR85]\] transmission in *X. nematophila* seems to require the *nilABC* operon which encodes three surface-localized colonization factors whose mutations invariantly lead to defective recolonization of Steinernematid worms by *X. nematophila* bacteria \[[@CR77], [@CR78]\]. The absence of the *nilABC* genes in *X. bovienii* and in *Photorhabdus* species suggest that bacteria-nematode recolonization is realized by different mechanisms in these two well-studied EPN systems. To summarize, the genetic mechanisms by which *Photorhabdus* and *Xenorhabdus* achieve entomopathogenicity are quite distinct and evidence of independent evolution of a similar phenotype. The bacterium we describe here, *Serratia* sp. SCBI, belongs to the genus *Serratia* that consists of several species with diverse lifestyles that include free soil dwellers \[[@CR49]\], plant associates in the rhizosphere \[[@CR11], [@CR34], [@CR88], [@CR98]\], opportunistic pathogens \[[@CR66], [@CR96], [@CR97]\] and obligate intracellular endosymbionts \[[@CR22]\]. Most *Serratia* spp. secrete an array of active extracellular enzymes such as nucleases, proteases \[[@CR17], [@CR25]\], lipases \[[@CR64]\] and hemolysin and have swarming and swimming mobility \[[@CR4], [@CR65], [@CR70]\]. These features may enable them to colonize a wide variety of niches and contribute to their success as opportunistic pathogens. Of the sequenced *Serratia* spp., the closest species to our isolate, *S. marcescens* DB11, is a confirmed pathogen of invertebrates \[[@CR49], [@CR63]\], a function that is likely required for evolution of an EPN complex. Although *Serratia* sp. SCBI was initially isolated as an associate of *Caenorhabditis briggsae*, this bacterium will also associate with strains of the well-studied model eukaryote *Caenorhabditis elegans* and allow these bacteriovorus nematodes to kill insects \[[@CR2]\]. Both *C. briggsae* and C. *elegans* are well known associates of invertebrates \[[@CR79], [@CR83]\], a likely pre-adaptation to an EPN life cycle. Recent discoveries of *Serratia* spp. in EPN associations \[[@CR89], [@CR105]\] suggest the possibility that *Serratia* sp. SCBI may belong to a unique lineage within the genus *Serratia* that has evolved the capacity to confer an EPN lifestyle to diverse insect-associated nematodes. The *Serratia* sp. SCBI and Caenorhabditid EPN complex represents a unique opportunity to explore the evolution of symbiosis in a third EPN lineage. Here we present the complete genome sequence of *Serratia* sp. SCBI and explore how it is unique with respect to other closely related *Serratia* and how the predicted functional proteome compares to features found in the well-studied EPN-associated bacteria, *Xenorhabdus* and *Photorhabdus*. Results and discussion {#Sec2} ====================== Overview of the *Serratia* sp. SCBI Genome Structure and Annotation {#Sec3} ------------------------------------------------------------------- The genome of *Serratia* sp. SCBI is comprised of a single circular 5.04 Mb chromosome with an overall GC content of 59.7 %, 4599 predicted protein coding genes, 84 tRNA genes and seven sets of rRNA genes (Table [1](#Tab1){ref-type="table"}, Fig. [1](#Fig1){ref-type="fig"}). In addition, *Serratia* sp. SCBI contains a single 64.8 Kb conjugative plasmid with 74 putative protein coding genes, 28 of which lack similarity to known proteins. (Additional file [1](#MOESM1){ref-type="media"}: Table S1: Plasmid ORFs). Blast analysis (data not shown) has shown that the *Serratia* sp. SCBI plasmid shows no obvious homology to the other known *Serratia* plasmid found in *S. proteamaculans* 568. The annotated genome is available at NCBI under accession numbers CP003424 and CP003425.Table 1Comparison of physical parameters of Serratia sp. SCBI with three of the sequenced Serratia genomesGenome featureOrganismS_SCBIS_DB11†S_AS12S_568‡Genome size (MB)5.045.125.445.45GC content (%)59.359.155.955Predicted ORFs4599473649524891Protein coding DNA (KB)4.44.494.734.75Protein coding DNA GC content (%)61.160.9357.356.35Genes with assigned functions3736380439944111Genes without assigned functions863932958780rRNA sets7777tRNA genes84888785Plasmid Size(KB)64.8N/AN/A46.8Plasmid GC content (%)54.92N/AN/A49Plasmid encoded ORFs74N/AN/A51\*SMAR gene prediction: 4736 ORF by FgeneSB, 4763 SANGER prediction† EBI, Sanger; ‡DOE, JGI*S_SCBI Serratia* sp. SCBI; *S_DB11 S. marcescens* DB11; *S_AS12 Serratia* sp. AS12; *S_568 S. proteamaculans* 568Fig. 1Circular representation of the *Serratia* sp. SCBI genome. Circular representation of Genomic features in *Serratia* sp. SCBI. From outer to innermost: First and fourth circles, genes in the plus and minus strands, respectively, by COG category (COG category color Scheme A, side panel); second circle, genes shared with other *Serratia* and EPN species (see color scheme B); third circle, genomic Islands (GIs) (Color Scheme C); fifth circle, GC content, sixth, innermost, circle, GC skew (Color Scheme A Side panel) Among complete *Serratia* genomes, the SCBI genome was the smallest in size and encoded fewer genes (Table [1](#Tab1){ref-type="table"}). All the compared *Serratia* genomes shared a highly conserved genomic architecture as inferred from synteny of protein coding orthologs, tRNA genes, rRNA modules and their origins of replication. These genomes shared 3094 genes by MAUVE progressive alignment \[[@CR35], [@CR36]\] at 70 % coverage and 30 % identity. An additional 809 protein coding genes were shared by *S. marcescens* DB11 and *Serratia* sp. SCBI (Fig. [2](#Fig2){ref-type="fig"}). The *Serratia* sp. SCBI, *S. marcescens* DB11, *Serratia* sp. AS12 and *S. proteamaculans* 568 genomes had 519, 587, 1015 and 1011 unique genes, respectively (Fig. [2](#Fig2){ref-type="fig"}). An additional 1267 genes were shared between two or three species. The patterns of shared and unique genes are consistent with the evolutionary history of the species defined by 16S rDNA phylogeny (Fig. [3](#Fig3){ref-type="fig"}).Fig. 2Venn diagram of shared and unique genes found in four *Serratia* genomes. The unique and shared genome among the compared genomes was determined by a dual cutoff of 30 % or greater amino acid identity and sequence length coverage of at least 70 %. Analysis was done using the MAUVE genome alignment tool \[[@CR42]\]. SCBI: *Serratia* sp. SCBI; SMAR: *S. marcescens*DB11; SPRO: *S. proteamaculans*568, SAS12, *Serratia* sp. AS12Fig. 3Evolutionary relationships of *Serratia* and representative bacteria from the entomopathogenic genera *Photorhabdus* and *Xenorhabdus.* Evolutionary relationships of *Serratia* and representative bacteria from the entomopathogenic genera *Photorhabdus* and *Xenorhabdus.* **a** Phylogenetic relationships inferred from the alignment of 1500 bp of 16S rDNA using the Maximum Likelihood \[[@CR90]\]; **b** Phylogenetic relationships inferred from the alignment of 2623 bp of concatenated DNA from four housekeeping genes: *atpD* (634 bp), *gyrB* (742 bp), *ifnB* (613 bp) and *rpoB* (634 bp) using the Maximum Likelihood \[[@CR90]\]. Numbers on internal branches are the results of Bootstrap analysis where the test was done with 1000 replicates \[[@CR43]\]. Where applicable the trees are drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. Evolutionary analyses were conducted in MEGA6 \[[@CR91], [@CR92]\] Phylogenetic placement of SCBI {#Sec4} ------------------------------ To place *Serratia* sp. SCBI in an evolutionary framework we compared the near complete 16S rRNA genes from diverse *Serratia* species and other relevant entomopathogenic bacteria (Fig. [3](#Fig3){ref-type="fig"}) as well as concatenated sequences from four housekeeping genes: *atpD, gyrB, ifnB* and *rpoB*. The phylogenetic tree from the concatenated housekeeping genes suggest that *Serratia* sp. SCBI is found in a clade of five *Serratia* which are all known insect associates and SCBI was closest to *S. ureilytica*. Among the well-studied and completely sequenced species included in the 16S phylogeny, *Serratia* sp. SCBI was most closely related to *S. marcescens* DB11, which is an insect pathogen \[[@CR49], [@CR50], [@CR63]\] and antagonist of *C. elegans* \[[@CR61], [@CR76], [@CR82]\]. This close relationship provides an ideal opportunity to identify candidate genes critical to the evolution of the EPN lifestyle. Another closely related species is *S. nematodiphila*, which was described as part of an EPN association with a Rhabditid nematode \[[@CR104], [@CR105]\]. Other close relatives include *S. entomophila* \[[@CR50]\], which is pathogenic to New Zealand grass grubs, and *S. ureilytica* which is a nickel resistant *Serratia* isolated from the River Torsa in West Bengal, India \[[@CR13]\]. This phylogeny suggests that *Serratia* sp. SCBI may represent a novel, independently evolving EPN association from within a lineage of *Serratia* commonly associated with insects. Genomic alignment and comparative genomic analysis {#Sec5} -------------------------------------------------- Whole genome alignment of SCBI with three of the sequenced *Serratia* genomes show extensive synteny (Fig. [4](#Fig4){ref-type="fig"}) where large colinear blocks of genes are interrupted by insertions that resulted in genomic islands, deletions relative to SCBI and a small number of rearrangements involving relatively small genomic regions. In the context of this study, a genomic island (GI) was broadly defined as any stretch of five or more consecutive protein coding genes that: 1) are not present in the other members of the genus, and 2) show a divergent %GC content compared to the core genome. Our analysis predicts at least 29 GIs in *Serratia* sp. SCBI. Based on these criteria 326 of 519 (62.8 %) of unique genes are located in the genomic islands of SCBI and as discussed below most of these GIs encode functions of potential biological relevance to the EPN lifestyle (Table [2](#Tab2){ref-type="table"}). To ascertain the significance of the *Serratia* sp. SCBI-*C. briggsae* association in relation to other *Serratia* and the established EPN bacteria, we conducted comparative analysis of the predicted proteome against the respective groups using the MAUVE \[[@CR35]\] genome alignment tool. The cutoff values of 60 % identity and 70 % coverage, i.e. similarity of 60 % of the compared residues covering 70 % of the total length of the shorter sequence in the comparison, were used to include only hits with high confidence levels and exclude spurious hits (Table [3](#Tab3){ref-type="table"}).Fig. 4Genomic alignment of the four compared *Serratia* spp. Alignment statistics were generated and rendered by MAUVE progressive alignment software \[[@CR35], [@CR36]\]. SMAR: *S. marcescens* DB11, SCBI: *Serratia* sp. SCBI, and SPRO: *S. proteamaculans*586, SAS12: *Serratia* sp. AS12. Color schemes represent blocks of contiguous genes interrupted by colorless patches where the genomes differ from each other significantly and identified as GIs are locatedTable 2Serratia sp. SCBI Genomic Islands and their putative/predicted phenotypesGI\#Locus tagsGenomic locationPutative/Predicted roleGI-1SCBI_0047-005246958..52205UnknownGI-2SCBI_0298-0302358841..362952AdhesionGI-3SCBI_0465-0482533080..558686UnknownGI-4SCBI_0809-00817928240..935735Symbiosis/MetabolicGI-5SCBI_0963-09811080968..1096217VirulenceGI-6SCBI_1013-10191130653..1141194Virulence, DefenseGI-7SCBI_1042-10611164353..1197133Virulence, SymbiosisGI-8SCBI_1205-12091349465..1355183DefenseGI-9SCBI_1258-12631405041..1410636SymbiosisGI-10SCBI_1467-14781614753..1632962MetabolicGI-11SCBI_1483-14981639797..1656736MetabolicGI-12SCBI_1540-15471701960..1709609UnknownGI-13SCBI_1814-18191993067..1996355UnknownGI-14SCBI_1883-18882062882..2068451DefenseGI-15SCBI_1970-19752150551..2156393SymbiosisGI-16SCBI_2176-21802367813..2374480UnknownGI-17SCBI_2225-22322418731..2436006SymbiosisGI-18SCBI_2295-23002513930..2520831MetabolicGI-19SCBI_2738-27942980185..3019378Defense, virulence, AdhesionGI-20SCBI_2953-30113191699..3264229Defense, virulence, AdhesionGI-21SCBI_3036-30413289235..3297687MetabolicGI-22SCBI_3184-32033460520..3479027Adhesion, DefenseGI-23SCBI_3369-33733652152..3658481SymbiosisGI-24SCBI_3376-33803662181..3666951UnknownGI-25SCBI_3539-35393835598..3842153DefenseGI-26SCBI_3778-37944112710..4132272Defense, SymbiosisGI-27SCBI_3962-39664314901..4319983MetabolicGI-28SCBI_4358-43664751221..4757933MetabolicGI-29SCBI_4408-44124806030..4811621Unknown(see Additional file [2](#MOESM2){ref-type="media"}: Table S2 for the full/expanded version)Table 3The distribution of Virulence/defense/symbiosis factors in Serratia and the EPN bacteriaSCBISMARSODOSPROPASYPLUMXBOVXNEMToxicity/VirulenceGroEL1111111Hemolysin66666855LopT12Mcf1211MtpB1311MtpD1211MtpE1211NRPS-PKS1716131242373346PirA1111121PirB-JHE121RtxA3411TC11119712Symbiosis/RecolonizationCipA22CipB11ExbD22222222HexA1111LrhA1111NgrA11211111NilA1NilB1NilC1NilR1122PbgPE66667767PhoP22221111PhoQ11111111Immune_evasion/BioconversionBacillolysin11111112Cif11CpxA11111111CpxR22221111FlhC11111111FlhD11111111FliA11111111LPS21121111Lrp22222211MalP22221111MalQ11111111MalT11111111SctC11Serralysin44221111XlpA1111*SCBI Serratia* sp. SCBI; *SMAR S. marcescens* DB11; S_AS12, *Serratia* sp. AS12; *SPRO S. proteamaculans* 568; *PASY P. asymbiotica*; *Plum P. luminescens*; *Xbov X. bovienii*; Xnem, *X. nematophila* COG analysis among *Serratia* {#Sec6} ----------------------------- Analysis of the functional categories and genome wide distribution of all unique genes with assigned Clusters of Orthologous Groups (COG) functions among the sequenced *Serratia* genomes revealed that the unique genes in *Serratia* sp. SCBI were biased towards categories that have direct bearing on the symbiosis and/or pathogenesis life style (Fig. [5](#Fig5){ref-type="fig"}). Specifically, the gains were in COG categories: \[M\]- Cell wall/membrane/envelope biogenesis; \[N\]- Cell motility; \[Q\]- Secondary metabolites biosynthesis, transport and catabolism; \[U\] - Intracellular trafficking and secretion and \[V\]- Defense mechanisms.Fig. 5Relative COG category abundance in the core proteome in comparison with unique proteins in *Serratia*. The relative abundance of COG categories between the core and unique gene pools was calculated as follows: the number of proteins in each COG category was determined and the unique pools normalized to their respective total predicted protein numbers. Then the percentage of each COG category in the core proteome was subtracted from the corresponding COG percentage in the unique category and the difference plotted. COG functional categories descriptions are: \[A\] RNA processing and modification; \[B\] Chromatin structure and dynamics; \[C\] Energy production and conversion; \[D\] Cell cycle control and mitosis; \[E\] Amino acid metabolism and transport; \[F\] Nucleotide metabolism and transport; \[G\] Carbohydrate metabolism and transport; \[H\] Coenzyme metabolism; \[I\] Lipid metabolism; \[J\] Translation; \[K\] Transcription; \[L\] Replication and repair; \[M\] Cell wall/membrane/envelope biogenesis; \[N\] Cell motility; \[O\] Post-translational modification\] protein turnover\] chaperone functions; \[P\] Inorganic ion transport and metabolism; \[Q\] Secondary metabolites biosynthesis, transport and catabolism; \[T\] Signal transduction; \[U\] Intracellular trafficking and secretion; \[R\] General functional prediction only ; \[S\] Function unknown; \[V\] Defense mechanisms. \[X\] No cog category Functional properties of *Serratia* sp. SCBI shared with other entomopathogens {#Sec7} ------------------------------------------------------------------------------ To evaluate the *Serratia* sp. SCBI in the context of its role in an EPN complex, we searched the SCBI genome for homologs or functional analogs of all genes previously shown or implicated to be involved in host immune defense, host killing and cadaver protection, pathogenesis and symbiosis and reassociation in the canonical EPN species *Xenorhabdus* and *Photorhabdus* (Table [3](#Tab3){ref-type="table"}). Although most of these genes appear in GIs in *Serratia* SCBI, we focused the comparison on three functions with well documented roles in EPN lifestyle but not confined to putative Genomic Islands: evading host defense, toxicity to host and competitors and recolonization. Functional studies on the *Serratia* sp. SCBI-*C. elegans* complex has shown that hemolysin, NRPS proteins (Petersen, LaCourse et al. submitted) and extracellular proteases are crucial to cytotoxicity and virulence in this putative EPN symbiosis \[[@CR72]\]. The dynamics of mRNA expression of the alkaline metalloproteases (prtA1-prtA4) compared to the serine metalloproteases which peak before and after the death of the host, respectively, suggest a complex regulatory mechanism in killing the host and bioconversion of the cadaver \[[@CR72]\]. Furthermore, inactivation of the hemolysin gene in *Serratia* sp. SCBI, which resulted in loss of hemolysis, failed to attenuate insecticidal activity but significantly increased motility and antimicrobial activity (Petersen et. al., submitted). Furthermore comparative study on the physiology of three sequenced strains, *Serratia* sp. SCBI, *S. marcescens* DB11 and *S. proteamaculans* 568, revealed that DB11 and SCBI were similar in insect virulence and cytotoxicity consistent with their phylogenetic proximity, but motility and lipase and hemolytic activities differed significantly between them \[[@CR71]\]. The implication of these functional studies is that the *Serratia* sp. SCBI-*C. briggsae* association is a promising model to study the dynamics of gene expression during the transition from starved, inactive stay in nematode gut to active state during pathogenesis --killing and bioconversion-- of insect hosts. Breaching host defense {#Sec8} ---------------------- Breaching the insect host's defense --both the humoral and cellular components- is crucial for the establishment of infection. EPNs neutralize humoral response elements like lysozyme and cecropins with serralysin-like proteases such as the PrtA \[[@CR42], [@CR67]\] and by haemolysins (XhlA) and lipases (XlpA) and the FhlDC regulator operon \[[@CR47], [@CR67]\]. Cellular response evasion is directed mainly at suppressing the phenoloxidase pathway to prevent hemocyte aggregation and melanization. Several mechanisms are employed to suppress the insects' cellular immune response. These include: inhibition of phospholipase A2 (PLA2) using stilbene and MalPQT operon products in *Photorhabdus* and expression of LPS in *Xenorhabdus,* the suppression of phagocytosis by Type III secretion system-mediated deposition of LopT and SctC directly into hemocytes \[[@CR19], [@CR20]\] and the production of cytotoxins such as Cif and MrxA that lead to apoptotic cell death. With the exception of the *xlpA* gene which is absent from *Serratia* spp. and the *cif* and *stc* genes that are absent not only from *Serratia* spp. but also from *Xenorhabdus* spp., all other genes identifies as instrumental in the toxicity of EPNS are present in *Serratia* spp. as well including SCBI. The presence of more serralysins in *Serratia spp.,* by comparison to the EPN genomes, suggests that the SCBI *C. briggsae* association may heavily rely on the expression of multiple serralysin genes and extracellular lipases and hemolysin production to breach the host immune system. Toxicity {#Sec9} -------- Toxicity --both for killing the insect host and warding off bacterial and fungal competitors- is mediated by a plethora of insecticidal and bactericidal gene products \[[@CR44]\]. These include the *Photorhabdus* Toxin Complex (TC) operons *tcaABCD* and their counterparts in *Xenorhabdus xptABCD*, as well as other toxicity genes like the *pirAB, xaxB*, *sepA*, *groEL*, *lopT*, *mcf*, *mcf2*, *rtxA*, *mptBDE*. Various drug efflux systems and numerous nonribosomal peptide synthase (NRPS) and polyketide synthase (PKS) genes \[[@CR15], [@CR37], [@CR45], [@CR53], [@CR55]\] are also part of the overall toxicity caused by EPN systems. The redundancy evident in the toxin gene repertoire of *Photorhabdus* and *Xenorhabdus* is astounding -- at the time of its sequencing in 2003, *P. luminescens* was described as having more genes encoding toxins than any other genome sequenced to date \[[@CR40]\], however, *Serratia sp.* SCBI also has over 200 genes encoding toxins, NRPS genes, multiple drug efflux systems and assorted virulence factors. Nematode recolonization {#Sec10} ----------------------- Nematode recolonization involves two key elements: acquisition of partner bacteria by horizontal transmission via endotokia matricida \[[@CR28]\], in which eggs hatch within the sacrificial mother to gain access to bacteria before emerging from the maternal corpse and the retention of bacteria in the gut of the infective juvenile. The latter seems to be mediated by *ngrA* \[[@CR27], [@CR59]\], the Type I fimbriae *mrxA* \[[@CR24]\] and at least in *X. nematophila*, by the products of the *nilABC* and *nilR* genes \[[@CR30], [@CR31], [@CR52]\]. Both of these requirements seem to be met in SCBI since *Caenorhabditids*, when grown on SCBI, almost exclusively reproduce by endotokia matricida \[[@CR1]\] and SCBI possess homologs of both genes implicated in recolonization. Furthermore, the absence of *the nilABC* genes of *X. nematophila* in *Xenorhabdus boveinii* as well as *Photorhabdus* spp. show that colonization, like other aspects of EPN biology, can be produced by different mechanisms in EPNs. From this comparison three patterns emerge: 1) *Serratia* lack homologs of the toxicity genes *lopT, rtxA, prtA, pirB, cif, mcf*, and *mcf*2 and the *TC* operons but have substantial number of secreted proteases and lipases, and hemolysins and 2) the majority of the *Photorhabdus/Xenorhabdus* virulence, symbiosis and regulatory genes are equally represented in *Serratia* (Table [3](#Tab3){ref-type="table"}), and 3) the presence of key genes is not uniform among the different species --*nilABC* absent in *Photorhabdus* spp. and c*if, stc, cipAB* and *lopT* missing from *Xenorhabdus* spp.-suggesting that there is no single possible path to pathogenicity, cadaver bioconversion, repelling of competitors and bacterial re-association. Unique genes and Genomic Islands (GI) of SCBI {#Sec11} --------------------------------------------- Apart from those summarized in Table [3](#Tab3){ref-type="table"}, many other genes with well-documented pathogenicity/symbiosis functions in other microbial systems are found in the genome of SCBI more than half of which are located on genomic islands. Of the 29 genomic islands identified in *Serratia* sp. SCBI genome comparison (Fig. [1](#Fig1){ref-type="fig"}, third circle, Additional file [2](#MOESM2){ref-type="media"}: Table S2), many were enriched in defense and virulence genes and in - phage remnants which, in many bacteria including those in EPN associations, have been diverted into novel toxin/virulence factor delivery vehicles \[[@CR8], [@CR21], [@CR56], [@CR62]\]. Perhaps the most notable feature among the genomic islands is the urea pathway genes located on GI-4. The *hoxN/hupN/nixA* family nickel/cobalt transporter and the urea metabolism pathway proteins found in GI-4, are absent from other members of the genus *Serratia* but interestingly present in all the EPN bacteria. The *hoxN* transporter is necessary for urea hydrolysis \[[@CR60], [@CR103]\] making it an integral part of the pathway. While there is no evidence so far of a direct role for urea metabolism in the EPN lifestyle, a potential role for these pathways can be exemplified by current research on diatoms where the urea pathway is a key to facilitating rapid recovery from prolonged nitrogen limitation followed by rapid growth under nutrient rich conditions \[[@CR6]\]. The EPN life cycle has a similar pattern in that the symbionts that survive in nutrient-limited conditions while in transit to the next cycle of infection face a sudden abundance of organic compounds upon entering the insect hemocoel, thus requiring rapid transitioning from starved state to exponential growth of the bacteria. Furthermore, the regulation of the urea pathway in the diatoms has been linked to proline \[[@CR5]\] which has also been identified as the cue for the transition from starved to metabolically active state in *Photorhabdus* and *Xenorhabdus*. Among the unique genes of SCBI that are relevant to its association with *C. briggsae* as a putative EPN are the O-antigen biosynthesis protein(SCBI_1044), NRPS proteins(SCBI_1017, SCBI_1055-1059, SCBI_2978), colicins (SCBI_1883-1887), Type IV secretion systems (SCBI_2992, SCBI_2984, SCBI_2994), and iron acquisition proteins(SCBI_1973-1975). These genes have been shown to be required for both symbiotic and pathogenic properties \[[@CR12], [@CR101], [@CR102]\] and may play a similar role in the *Serratia*-*Caenorhabditis* EPN association. The list of genes unique to SCBI also include efflux system proteins (SCBI_1013, SCBI_1208) that are specific for macrolide- a class of antibiotics that inhibit the growth of bacteria- and the resistance-nodulation- division (RND) efflux proteins (SCBI_3788-3791) that are known to actively scavenge antimicrobial compounds released by competitors or the host immune system \[[@CR3], [@CR14], [@CR73], [@CR74], [@CR87], [@CR93], [@CR94]\], a predicted HtpX protease, a heat shock/stress inducible membrane bound zinc metalloprotease \[[@CR81]\], the DinI family protein also known as MsgA (macrophage survival protein) (SCBI_3186) and prophage lysozyme proteins (SCBI_2756-2758) an endolysin/autolysin system known to degrade the peptidoglycan structures in bacterial cell walls \[[@CR18], [@CR51], [@CR99]\]; Microcin H47(SCBI_2968, SCBI_3536), a bactericidal peptide antibiotic related to the Colicin V family secretion protein \[[@CR10]\] and associated secretion ATPase required for its export \[[@CR95]\]; several fimbrial proteins with functional annotations ranging from pilus assembly to anchoring which, in light of recent findings that implicate *Photorhabdus* and *Xenorhabdus* adherence to the gut walls of their respective worm associates via fimbrial proteins, \[[@CR46], [@CR68], [@CR86]\] and two homologs of the HigB toxin protein/HigA protein (antitoxin to HigB)( SCBI_0907-0908), which in *Vibrio*, have been shown to inhibit cell growth in *Escherichia coli* upon ectopic expression \[[@CR26]\]. Conclusions {#Sec12} =========== EPN associations are complex tripartite interactions between bacterial pathogens, symbiotic entomophagous nematodes and susceptible insect/insect larval hosts. Thus far our understanding of the mechanisms of EPN associations is limited to two superficially similar and convergent systems. Here we report the complete genome sequence of the bacterium involved in a novel independently evolving putative EPN association between a species of *Serratia* and nematodes in the genus *Caenorhabditis*. This *Serratia* is most closely related to another recently discovered EPN association, *Serratia nematodiphila,* and the well-studied insect pathogen *Serratia marcescens* DB11. Based on a comparison to the two well studies EPN systems, the genome of *Serratia* sp. SCBI contains a large number of genes that are potential candidates for EPN adaptations. Among the most notable shared functions with other EPN associates are the O-antigen, the *syrP* protein, several non-ribosomal peptide synthetases, bacteriocins, many fimbrial biogenesis and ushering proteins, secondary metabolite and toxin secretion systems and multiple drug resistance/efflux systems. However, the SCBI genome carries neither the TC complexes nor the *mcf* genes, which implies its use of different mechanisms of insect killing. The presence of several ORFs encoding putative virulence factors in horizontally acquired genomic islands suggest that EPN associations can be established by dissimilar sets of mechanisms for killing, bioconversion, sanitization and colonization. The presence of these sets of genes in many bacteria further suggests that the major hurdle in EPN complex formation may be the initial development of co-tolerance between potential partners. This complete genome sequence of one of the partners in a nascent EPN association should enable future analysis of the *Serratia/Caenorhabditis* EPN complex. Methods {#Sec13} ======= Bacterial isolation and identification {#Sec14} -------------------------------------- The bacterium was isolated from a *Galleria mellonela* trap laid in soil in the Kawa Zulu Natal province of South Africa. The detailed procedure has been previously described elsewhere \[[@CR2]\]. Following isolation bacterial identity was determined by 16S rDNA PCR which shows 99 % identity with *Serratia marcescens* rDNA sequences at NCBI (CP003959.1). Genomic DNA isolation {#Sec15} --------------------- Genomic DNA (gDNA) was isolated from overnight cultures grown in LB medium \[10 g Bacto-tryptone, 5 g Bacto-yeast, 5 g NaCL, H2 O to 1 liter, pH 7.5\] (BD, Sparks, MD) using the Qiagen Genomic DNA isolation kit (Qiagen, Germantown, MD) and following the procedure outlined for bacterial gDNA isolation. Precipitated DNA was collected by spooling the DNA using flame-sterilized and cooled glass rod. The spooled gDNA was immediately transferred to a microcentrifuge tube containing 1.5 ml sterile, nuclease free water. The DNA was dissolved on a shaker at 55 °C for 2 h. The yield, purity, and length of the DNA was determined for 1-5 μl samples by electrophoresis on 0.8 % agarose gel and by spectrophotometry on a NanoDrop 1000 (Thermo Scientific, USA). Fosmid Library construction {#Sec16} --------------------------- The fosmid library was constructed from the genomic DNA (gDNA) using the CopyControl pCC1FOS™ Vector that contains both the *E. coli* F-factor single-copy origin of replication and the inducible high-copy *oriV* according to the manufacturer's protocol (Epicentre, Madison, U.S.A.). Briefly, gDNA was mechanically sheared by passing through a narrow gage sterile syringe then it was separated by pulse field gel electrophoresis (PFGE) overnight. A gel slice was excised from the 36-40 KB size window and the DNA extracted by gel extraction. The gel extracted gDNA was subsequently ligated into the fosmid vector exactly as described in the Epicenter protocol. The ligated mixture was then packaged into lambda phages using MaxPlax Lambda Packaging Extracts (Epicentre, Madison, U.S.A.). The packaged library was then transduced into *E. coli* EPI300™ Plating Strain, and transformants were selected on LB agar supplemented with 34 mg/ml Chloramphenicol. The library clones were picked by the Genetix Q-bot colony picking robot (Genetix Ltd, UK) and inoculated into 384 well plates and allowed to grow for 24 h at 37oC in humidified chamber. Colonies were stored in -80oC freezers until they were retrieved for downstream processing. To isolate fosmid DNA, randomly selected individual clones were grown overnight in Chloramphenicol supplemented LB broth and plasmid copy number were amplified by adding 5ul induction solution and incubating further for 4 hours. Fosmids were isolated by alkaline lysis method using Qiagen plasmid isolation buffers. The presence of recombinant DNA in the isolated fosmids and the polymorphism of the insert DNA were evaluated by agarose gel electrophoresis of BamHI (NEB, USA) digestion of the purified plasmid DNA. PCR primer design and amplicon sequencing {#Sec17} ----------------------------------------- The genome sequencing gaps were closed using PCR based amplicon sequencing. To this end batches of PCR primer were designed by the Primer3 software driven by an in-house Perl script. Primers were synthesized by IDG (IDG Inc., MA, USA) and they were used to both amplify and sequence the amplicons after cleaning the PCR product from any unused primers. PCR fragments were purified using magnetic beads and SPRI solution. The primers were designed to have a melting point of 60 °C or above for increased specificity and simultaneous amplification at a single annealing temperature. Cycling conditions were as follows: Initial denaturation of plasmid, 5 min at 95 °C; 30 cycles or denaturation, annealing and primer extension at 95 °C 30 s, 60 °C 30 s and 2 min at 72 °C, respectively; a final synthesis hold at 72 °C for 10 min and a 4 °C hold until reactions were removed from the iCycler PCR machine (Biorad Inc. CA, USA). Long PCR for amplification of 3-8 KB fragments were performed the same way except that the 10X buffer was supplemented with additional MgCl~2~ to bring the final concentration to 25 mM and the extension time was increased to 6 min. All PCR amplifications were done using Finnzymes PCR kit (NEB, MA, USA) and the 15 mM 10X buffer was used for fragments between 100 to 2000 bases long. Fosmid end sequencing and quality monitoring {#Sec18} -------------------------------------------- DNA isolated from 209 plasmids was end sequenced using the pCC1FOS™ forward and reverse primers designed by Epicenter. Half of the clones were sent to a commercial sequencing facility (Genewiz Inc, NJ, USA) the other half were sequenced in house by the ABI 3130 genetic analyzer. Efficiency of Fosmid library construction and the quality of the library were monitored by selecting at random 209 clones and subjecting them to different analyses. A subset of these (46 clones) were tested by Bam HI digestion and, except for a failed plasmid isolation in one clone, all 45 (100 %) of them gave distinct digestion patterns and one common band at 8 KB, representing the plasmid backbone. BLAST results showed that except for 4 clones that failed to sequence, probably due to sample cross over contamination, all fosmid end sequences hit the assembled genome at 34 to 45 KB apart in the right orientation giving an overall high efficiency of library construction and quality. Genome sequencing by 454 technology and assembly of contigs {#Sec19} ----------------------------------------------------------- An aliquot of the *Serratia* sp. SCBI gDNA was sent to the genome sequencing center at the University of Indiana for genome sequencing by 454 pyrosequencing technology. Two plates of genomic sequencing and one plate of 2 KB paired end sequencing were done to generate the complete genomic sequence of one circular chromosome and one large, circular plasmid of 68 KB size. The 454 sequencing resulted in ten contigs ranging in size from 2 KB to 3.5 MB and harbored 236 gaps of ranging from 4 nucleotides to 2 kb in length which were closed by PCR amplicon sequencing as detailed in the PCR primer design and amplicon sequencing section. The genome sequencing output from the 2 plates of 454 genomic reads and one plate of 2 KB paired end sequencing yielded 40 and 21 MB data, giving an overall 12X coverage of the genome. The main chromosome was resolved in seven genomic regions separated by seven sets of rDNA assemblies of 5 KB length as outlined below. Sequence gap filling, genome assembly and bioinformatics analysis {#Sec20} ----------------------------------------------------------------- The 10 scaffolds assembled by the Newbler Assembler sequence initially included 236 gaps ranging from 4 to 2050 bases long. PCR based amplicon end sequencing resolved all the gaps bringing the sequence assembly to a satisfactory level of completion. PCR primers were designed on regions flanking gaps by the Primer3 program \[[@CR80]\] after orientation and order of scaffolds were determined by a combination of bioinformatics and laboratory based methods. Briefly, truncated scaffold sequences consisting of 500 bp from the start and end of each scaffold were generated by a Perl script. These truncated sequences were then blasted against the *S. marcescens* DB11 genome which identified their counterparts unambiguously showing a great deal of synteny between the two genomes. This finding was then confirmed by long PCR performed using primers pointing outward from the pairs of gap ends predicted by the bioinformatics analysis. All of the predicted combinations resulted in the amplification of the expected 6 KB fragment confirming both the order and orientation of the clones as well as their size. The remaining two fragments were resolved into a circular plasmid by blast hit with two fosmid clones which hit the two scaffolds unambiguously. This was also confirmed by PCR that amplified predicted size of amplicons from primers designed at the ends of the two scaffolds and individual fosmids used as template. Long PCR and amplicon sequencing were performed as described above and the resultant amplicon sequences were then added to the 454 reads and reassembled by the Newbler to generate the complete genome sequence. Comparative genomic analysis of *Serratia* sp. SCBI genome with the two other completed genomic sequences in the genus, *S. marcescens*DB11 and *S. proteamaculans*568 was done to determine the genes shared between the three genomes and the three way paired genomes (*Serratia* sp. SCBI-DB11, *Serratia* sp. SCBI-SPRO, DB11-SPRO) and the genes unique to each of them using MAUVE \[[@CR35], [@CR36]\], MURASAKI \[[@CR75]\] and Blast \[[@CR7], [@CR57]\] bioinformatics tools, the RAST Annotation Server \[[@CR9]\] and in house developed Perl scripts. A comparison was also done with *P. luminescens* and *X. nematophilia* to shed light on the entomopathogenic aspects of the *Serratia* sp. SCBI-*Caenorhabditis* relationship and to determine whether it resembles the *Photorhabdus*/*Heterorhabdus* or the *Xenorhabdus*/*Steinernema* type association or it constitutes a novel class of EPN association with a different entomopathogenic signature driven by a novel set of genes and pathways. Accession numbers {#Sec21} ----------------- The genome sequence and its annotations are available at NCBI under the accession numbers CP003424 and CP003425. Additional files {#Sec22} ================ Additional file 1: Table S1.*Serratia* sp. SCBI predicted plasmid encoded genes.Additional file 2: Table S2.*Serratia* sp. SCBI Genomic Island genes with putative/Predicted functions relevant to EPN life style. **Competing interests** The authors declare that they have no competing interests. **Authors' contribution** FAA, WKT, VSC, LST and EA conceived of and provided project oversight. FAA conducted the molecular biology and comparative genomics analysis and manuscript draft. PJH provided key scripts for the analysis. All authors edited, read and approved manuscript. This work was supported in part by Hatch grant NH496, and by the College of Life Sciences and Agriculture, The University of New Hampshire, Durham, NH. Partial funding was provided by the New Hampshire Agricultural Experiment Station. This is Scientific Contribution Number 2571. We thank Heidi-Goodrich-Blair and Jonathan Ewbank for access to the *Xenorhabdus* and *Serratia* genome databases, respectively. We thank Jobriah Anderson for technical help.
{ "pile_set_name": "PubMed Central" }
New approaches to antiplatelet therapy. The importance of platelets in the pathophysiology of cardiovascular and cerebrovascular disorders has been demonstrated by numerous clinical and pathological studies. Conventional antiplatelet agents are effective in both the primary and secondary prevention of vascular disorders, but suffer for the combined shortcomings of lack of selectivity and relative potency. Many new antiplatelet agents have been developed to overcome these differences, including serotonin receptor antagonists, prostanoid derivatives and antagonists, fibrinogen receptor antagonists, and selective thrombin inhibitors. In this review we consider the mechanisms by which these novel antiplatelet agents impair platelet function and their potential clinical utility.
{ "pile_set_name": "PubMed Abstracts" }
http://clones.soonlabel.com/public/improvfriday/20120811_one_way_ticket_to_mars_blues_ND.mp3 One Way Ticket to Mars Blues is an internet collaborative effort by bassist Glenn Smith and myself. The purpose of my post though is to illustrate a technique I developed many years ago to play my guitar in relative quiet while sounding like I have intensely loud amplification. The basic idea is to clamp a speaker to your guitar. Thus, this is temporary and doesn’t ruin anything if you are careful with what you are doing. Since I record direct in I use a Y connection to split the guitar signal between the amplifier driving the clamped speaker and my audio recoding device. Nearly any amplifier will do – right now I mostly use a honeytone practice amp that has a 1/8″ speaker by-pass socket I installed. What you see clamped is a Dayton Audio Sound Exciter DAEX25 – this works the best of everything I’ve tried so far. Like this: Like Loading...
{ "pile_set_name": "OpenWebText2" }
Like this: Wikipedia Poem, No. 888 “One must desire the ultimate essence even if it is ‘contaminated.’” Cy Twombly, 1957 No echt government drives badly would abet its economy through a bouquet of contemporary tariffs which only serve within a hobnail millennia? Nishore Jailubani, a Washington academic… Read More Like this: computer christopher christopher on view at emerson college in boston ash used giroux straus and marrow of gesture the house the sonnets for beaches everywhere used giroux as ash started used giroux started used giroux straus and marrow of gesture of light of marrowbone of… Read More Like this: Wikipedia Poem, No. 870 saskatchewan, i have—by a mile—the heat of whirlwindthis whirlwind of what i know… after-time gotta study and get on with all the whirlwind heatthis whirlwind of preparing for the heat of the best poems published in saskatchewan o well and study… Read More Like this: Wikipedia Poem, No. 832 “This book I bought in Venice for one Ducat in the year 1507.” Albrecht Dürer and bought a mousemat.d bought a mousemat.ht a mousemat.a mousemat.wo hours there and bought a mousemat.bought a mousemat.re and bought a mousemat.nt two hours there and bought… Read More Like this: Wikipedia Poem, No. 709 i drink nothing-gas operation form the breech) the other room gold scream and sweet firearms operate for a headache fired gas operation) that killed the potted sky) nothing departs logical at the sky from the other room gold cream and sweet… Read More Like this: A great poetry website, Poets Reading The News, has published another one of my poems, Agraphia, along with one my recent photos, Car 5 (above). I’m extraordinarily fond, and proud, of this poem. It’s about the way that war and violence affect one’s humanity. It begins… Read More
{ "pile_set_name": "Pile-CC" }
It should be obvious that a car is not a smartphone. Apple Inc. is acting as if they’re the same. It’s no secret that Apple is working on self-driving vehicle technology; it is among dozens of companies that have California permits to test autonomous cars on public roads. Chief Executive Officer Tim Cook, in his way, acknowledged the driverless transportation project in a 2017 Bloomberg Television interview, and the company last week confirmed earlier reports that it had acquired autonomous vehicle startup Drive.ai. And yet Apple remains far more closed than its peers. Alphabet Inc.’s Waymo, Uber Technologies Inc., Tesla Inc., General Motors Co.’s Cruise and other companies working on this technology talk fairly openly about their broad ambitions for autonomous transportation, milestones in progress and issues for the industry. Apple does none of this. It’s always Apple’s tendency to keep mum about a product in development until it’s perfect and ready for a world debut. But driverless cars are not smartphones or augmented reality glasses. Emerging technologies, particularly those that have the potential to save human life and also to take lives, need an open debate and deserve a relatively transparent process — warts and all. Driverless cars have the potential to transform the nature of cities, upend a country’s workforce, impact the environment and necessitate revisions to laws and ethics. The public is not well served by Apple’s inclination against engaging on a subject of such importance. Apple may not be well served by its approach, either. The driverless car industry as a whole has not been an open book. Advocates, and some regulators, have pushed companies to disclose far more than they do about safety metrics and to collaborate with rivals to ensure better and safer progress on autonomous technology. But Apple is taking the industry’s discretion to the absurd. Cook reiterated to stock analysts that Apple is interested in autonomous technology and has “a large project going and are making a big investment in this.” And that’s about it. “I don’t want to go any further with that,” Cook said. He’s been similarly vague since then. By comparison, Waymo executives regularly talk about the implications of driverless car technology and its potential drawbacks. In Alphabet’s most recent earnings call, executives talked about opening a Michigan facility with dedicated autonomous vehicle production, explained Waymo’s focus on Uber-like ride services and mentioned making its in-house vehicle sensors available to outside companies. Last week, an Alphabet executive answered a shareholder’s question about how autonomous vehicles might affect tax revenue. For Apple investors, driverless technology is a “free optionality” for long-term stock owners, CFRA Research said this week. The costs are already being absorbed. Apple’s operating margin is at its lowest level in a decade as a share of revenue. Largely that’s because spending on research and development — which presumably includes Apple’s driverless car project — amounted to 6 percent of Apple’s revenue in the last 12 months. It was 3 percent just five years ago. It’s possible Apple is keeping mum about driverless technology because openness is not in the company’s DNA. Or maybe Apple’s laggard status in the technology explains its silence. California regulatory reports show that Apple’s autonomous test cars require more intervention by human backup drivers than many other companies’ prototypes. (There is debate about whether this data is the best measure of progress, but it’s one of the few available publicly.) Apple has the power to shape public perception in a way that maybe no other company can. It uses that power to sell smartphones, of course, but also to win people over to the company’s views of U.S. immigration policy, the importance of teaching software coding to children and the pernicious effects of social media. Driverless cars won’t be ubiquitous on public roads for many years, but policies and public perception are being set now. People in the U.S. are skeptical about driverless cars, and if nothing else, a little more engagement from Apple might help change opinion.
{ "pile_set_name": "OpenWebText2" }
"""SCons.Tool.swig Tool-specific initialization for swig. There normally shouldn't be any need to import this module directly. It will usually be imported through the generic SCons.Tool.Tool() selection method. """ from __future__ import print_function # # Copyright (c) 2001 - 2017 The SCons Foundation # # Permission is hereby granted, free of charge, to any person obtaining # a copy of this software and associated documentation files (the # "Software"), to deal in the Software without restriction, including # without limitation the rights to use, copy, modify, merge, publish, # distribute, sublicense, and/or sell copies of the Software, and to # permit persons to whom the Software is furnished to do so, subject to # the following conditions: # # The above copyright notice and this permission notice shall be included # in all copies or substantial portions of the Software. # # THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY # KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE # WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND # NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE # LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION # OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION # WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. # __revision__ = "src/engine/SCons/Tool/swig.py 74b2c53bc42290e911b334a6b44f187da698a668 2017/11/14 13:16:53 bdbaddog" import os.path import re import subprocess import SCons.Action import SCons.Defaults import SCons.Tool import SCons.Util import SCons.Node verbose = False swigs = [ 'swig', 'swig3.0', 'swig2.0' ] SwigAction = SCons.Action.Action('$SWIGCOM', '$SWIGCOMSTR') def swigSuffixEmitter(env, source): if '-c++' in SCons.Util.CLVar(env.subst("$SWIGFLAGS", source=source)): return '$SWIGCXXFILESUFFIX' else: return '$SWIGCFILESUFFIX' # Match '%module test', as well as '%module(directors="1") test' # Also allow for test to be quoted (SWIG permits double quotes, but not single) # Also allow for the line to have spaces after test if not quoted _reModule = re.compile(r'%module(\s*\(.*\))?\s+("?)(\S+)\2') def _find_modules(src): """Find all modules referenced by %module lines in `src`, a SWIG .i file. Returns a list of all modules, and a flag set if SWIG directors have been requested (SWIG will generate an additional header file in this case.)""" directors = 0 mnames = [] try: matches = _reModule.findall(open(src).read()) except IOError: # If the file's not yet generated, guess the module name from the file stem matches = [] mnames.append(os.path.splitext(os.path.basename(src))[0]) for m in matches: mnames.append(m[2]) directors = directors or m[0].find('directors') >= 0 return mnames, directors def _add_director_header_targets(target, env): # Directors only work with C++ code, not C suffix = env.subst(env['SWIGCXXFILESUFFIX']) # For each file ending in SWIGCXXFILESUFFIX, add a new target director # header by replacing the ending with SWIGDIRECTORSUFFIX. for x in target[:]: n = x.name d = x.dir if n[-len(suffix):] == suffix: target.append(d.File(n[:-len(suffix)] + env['SWIGDIRECTORSUFFIX'])) def _swigEmitter(target, source, env): swigflags = env.subst("$SWIGFLAGS", target=target, source=source) flags = SCons.Util.CLVar(swigflags) for src in source: src = str(src.rfile()) mnames = None if "-python" in flags and "-noproxy" not in flags: if mnames is None: mnames, directors = _find_modules(src) if directors: _add_director_header_targets(target, env) python_files = [m + ".py" for m in mnames] outdir = env.subst('$SWIGOUTDIR', target=target, source=source) # .py files should be generated in SWIGOUTDIR if specified, # otherwise in the same directory as the target if outdir: python_files = [env.fs.File(os.path.join(outdir, j)) for j in python_files] else: python_files = [target[0].dir.File(m) for m in python_files] target.extend(python_files) if "-java" in flags: if mnames is None: mnames, directors = _find_modules(src) if directors: _add_director_header_targets(target, env) java_files = [[m + ".java", m + "JNI.java"] for m in mnames] java_files = SCons.Util.flatten(java_files) outdir = env.subst('$SWIGOUTDIR', target=target, source=source) if outdir: java_files = [os.path.join(outdir, j) for j in java_files] java_files = list(map(env.fs.File, java_files)) def t_from_s(t, p, s, x): return t.dir tsm = SCons.Node._target_from_source_map tkey = len(tsm) tsm[tkey] = t_from_s for jf in java_files: jf._func_target_from_source = tkey target.extend(java_files) return (target, source) def _get_swig_version(env, swig): """Run the SWIG command line tool to get and return the version number""" swig = env.subst(swig) pipe = SCons.Action._subproc(env, SCons.Util.CLVar(swig) + ['-version'], stdin = 'devnull', stderr = 'devnull', stdout = subprocess.PIPE) if pipe.wait() != 0: return # MAYBE: out = SCons.Util.to_str (pipe.stdout.read()) out = SCons.Util.to_str(pipe.stdout.read()) match = re.search('SWIG Version\s+(\S+).*', out, re.MULTILINE) if match: if verbose: print("Version is:%s"%match.group(1)) return match.group(1) else: if verbose: print("Unable to detect version: [%s]"%out) def generate(env): """Add Builders and construction variables for swig to an Environment.""" c_file, cxx_file = SCons.Tool.createCFileBuilders(env) c_file.suffix['.i'] = swigSuffixEmitter cxx_file.suffix['.i'] = swigSuffixEmitter c_file.add_action('.i', SwigAction) c_file.add_emitter('.i', _swigEmitter) cxx_file.add_action('.i', SwigAction) cxx_file.add_emitter('.i', _swigEmitter) java_file = SCons.Tool.CreateJavaFileBuilder(env) java_file.suffix['.i'] = swigSuffixEmitter java_file.add_action('.i', SwigAction) java_file.add_emitter('.i', _swigEmitter) if 'SWIG' not in env: env['SWIG'] = env.Detect(swigs) or swigs[0] env['SWIGVERSION'] = _get_swig_version(env, env['SWIG']) env['SWIGFLAGS'] = SCons.Util.CLVar('') env['SWIGDIRECTORSUFFIX'] = '_wrap.h' env['SWIGCFILESUFFIX'] = '_wrap$CFILESUFFIX' env['SWIGCXXFILESUFFIX'] = '_wrap$CXXFILESUFFIX' env['_SWIGOUTDIR'] = r'${"-outdir \"%s\"" % SWIGOUTDIR}' env['SWIGPATH'] = [] env['SWIGINCPREFIX'] = '-I' env['SWIGINCSUFFIX'] = '' env['_SWIGINCFLAGS'] = '$( ${_concat(SWIGINCPREFIX, SWIGPATH, SWIGINCSUFFIX, __env__, RDirs, TARGET, SOURCE)} $)' env['SWIGCOM'] = '$SWIG -o $TARGET ${_SWIGOUTDIR} ${_SWIGINCFLAGS} $SWIGFLAGS $SOURCES' def exists(env): swig = env.get('SWIG') or env.Detect(['swig']) return swig # Local Variables: # tab-width:4 # indent-tabs-mode:nil # End: # vim: set expandtab tabstop=4 shiftwidth=4:
{ "pile_set_name": "Github" }
I. Field of the Invention The invention relates in general to apparatus for lifting objects into a structure and, more particularly, to a folding, lightweight apparatus that easily can assist in lifting panels or the like into preformed openings of a building under construction. II. Description of the Prior Art Modern tall office buildings are generally constructed as a shell with openings for panels and windows or the like. Buildings of this type can reach heights of 70 stories. The shell of the building is constructed with openings. Precast or prefabricated panels are then placed within these openings. These construction panels are of various sizes, shapes and thicknesses. Precast panels are made of reinforced concrete and may have heights as tall as 10 feet and lengths to 20 feet. These thicknesses may vary from 3 to 12 inches. Reinforced concrete panels with dimensions of this order are extremely heavy. Maneuvering of such heavy reinforced concrete panels is therefore difficult. The openings for receiving such a concrete panel may be at or above the 10th story making it necessary to lift panels to the 10th story or higher, and place them within the openings. Ordinarily, cranes are used to lift the panel up to the openings. The cranes may be situated on the ground or as the number of stories of the building increases, it is necessary to position the crane on the top floor of the building as it is being constructed or use a tower crane. A further complication arises in the construction of modern concrete steel buildings in that spandral beams are required. These spandral beams are so constructed that the openings for precast concrete panel may be as much as 3 feet inside the face of the spandral beam. The spandral beam therefore functions as a hindrance to the insertion of the precast concrete panel into the opening of the building. Without going into unnecessary detail, it is well known that the spandrals are required. The spandrals are required to be in place before the precast concrete panels are fit into the opening. Normally, the method of installing a panel of this type in the recessed opening in the building would be to attach lifting rings to the top of the panel. The rings would be attached with suitable bolts and a crane would be hooked to the lifting ring to lift the precast panel to the desired height in the building. Once the panel is lifted in close proximity to the opening it is to be fit into, construction workers will begin attempting to grab the panel and pull the panel into the opening. It is to be appreciated that the panel is large and heavy and the workers must manually pull the panel into the opening. After the panel has been pulled into the opening, it must be secured in place within the opening. The panel may be secured in place by bolting the panel to the structure in the building, welding the panel to the building, or by other suitable means. This procedure has obvious shortcomings. These shortcomings include the amount of time that workers take to fit one panel in place, and also due to the awkwardness of grabbing and fitting the panel in the opening, the possibility of an accident involving the workers. U.S. Pat. No. 4,671,721 issued to applicants on Jun. 9, 1987, addressed the problems previously outlined above. In this embodiment, an apparatus and method for positioning an object in a building was disclosed. This invention showed that precast panels can be delivered to openings in office buildings in a controlled manner which facilitated placing the panels in the building. The invention had many advantages over the prior art. On the other hand, the invention had a shortcoming in that the apparatus used to lift the panels was of itself extremely bulky and heavy. Although this shortcoming did not necessarily affect the performance of what can be described as "the flying forklift," it did affect its use in construction sites as transportation of the apparatus to and from various sites became a major drawback. Put simply, it would be desirable to have an apparatus that can be transported by a pickup truck as opposed to other more costly methods, and still make installation of precast panels or the like in openings in a building easier and safer than had been in the prior art. Applicants have therefore come up with a new apparatus which fulfills all the desired requirements, as shown in U.S. Pat. No. 4,671,721 and has further advantages in its use and transportation as will become clear from the specification herein.
{ "pile_set_name": "USPTO Backgrounds" }
An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Myogenic tone is an important determinant of vascular tone and blood flow in small resistance arteries of certain vascular beds. The role of the endothelium in myogenic responses is unclear. We hypothesized that endothelium-derived NO release modulates myogenic constriction in small resistance arteries and that mesenteric small arteries from mice with targeted disruption of the gene for endothelial NO synthase (eNOS) (knockout mice) demonstrate greater myogenic tone than do wild-type mice. Third-order mesenteric arteries (approximately 200 micrometer) were isolated and mounted in a pressure myograph. Internal diameter was recorded over a pressure range of 10 to 80 mm Hg. Removal of the endothelium significantly (P<0.05) enhanced the magnitude of myogenic constriction in wild-type mice. Similarly, pretreatment of arteries with N(G)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/L) produced a comparable significant (P<0.05) increase in myogenic tone, whereas indomethacin (5 micromol/L) had no effect. eNOS knockout arteries also exhibited myogenic constriction. Neither L-NAME nor indomethacin had any effect on myogenic tone in the arteries of eNOS knockout mice. However, blockade of potential endothelium-derived hyperpolarizing factor-like mechanisms via inhibition of K(+) flux using either apamin (100 nmol/L) with charybdotoxin (100 nmol/L), Ba(2+) (30 micromol/L) with ouabain (1 mmol/L), or 18alpha-glycyrrhetinic acid (100 micromol/L) significantly (P<0.01) enhanced myogenic constriction. This study demonstrates that basal endothelium-derived NO modulates myogenic tone in mesenteric small arteries of wild-type mice. However, eNOS knockout arteries display normal myogenic responsiveness despite the absence of basal NO activity. The data suggest that this compensatory effect is due to the activity of an endothelium-derived hyperpolarizing factor to normalize vascular tone.
{ "pile_set_name": "PubMed Abstracts" }
The regularity of operation of an escapement mechanism is conditional upon the proper control of maintenance of oscillations and particularly of the impulse, whose intensity may be irregular in a watch whose barrel torque varies. The search for optimum operating security is a constant preoccupation of designers of timepiece movements. FR Patent Application No 2928015A1 in the name of LENOBLE discloses a tangential impulse escapement device with a pallet lever for a watch, including a toothed escape wheel, a pallet lever and at least one sprung balance. The pallet lever is in two parts each pivoting on a distinct axis, the two parts are hinged to each other via two transmission arms terminating at their adjacent ends in a common hinge, so that the two parts of the pallet lever rotate at the same speed but in opposite directions. Each part of the pallet lever includes a locking pallet-stone and an impulse pallet-stone, the latter receiving impulses from the escape wheel teeth in a tangential manner. This escapement device includes two sprung balances with distinct axes of oscillatory rotation, and each part of the pallet lever comprises a fork engage able in driving mesh on an impulse pin of the corresponding sprung balance. Patent Application No WO 2011/064682 A1 in the name of FERRARA concerns a pallet lever in two parts hinged to each other, the hinge including an eccentric cam integral with the part of the pallet lever carrying the horns and guard pin, and cooperating with a fork integral with the part of the pallet lever carrying the pallet-stones. Patent Application No EP2444 860A1 in the name of AUDEMARS PIGUET RENAUD ET PAPI discloses a pallet lever which includes two parts, each pivoting about an axis, and hinged to each other, the pivoting of one of the parts causing the other to pivot with higher amplitude. Patent No EP2105806 in the name of GIRARD PERREGAUX discloses an escapement mechanism arranged to transmits impulses from a drive source to an oscillating regulator such as a sprung balance, via a strip spring which works by buckling about an inflection point. This strip spring is capable of accumulating energy from the drive source between two impulses and transmitting it to the oscillating regulator on each impulse via first and second levers. To optimise adjustment of the tension of the strip spring, the spring is mounted on a frame which is deformable symmetrically relative to a first axis passing through the axes of rotation of the regulator, of the first and second levers, and through the inflection point, and relative to a second axis perpendicular to the first axis and passing through the ends of the strip spring.
{ "pile_set_name": "USPTO Backgrounds" }
--- abstract: 'Work in time-domain astronomy necessitates robust, automated data processing pipelines that operate in real time. We present the BANZAI pipeline which processes the thousands of science images produced across the Las Cumbres Observatory Global Telescope (LCOGT) network of robotic telescopes each night. BANZAI is designed to perform near real-time preview and end-of-night final processing for four types of optical CCD imagers on the three LCOGT telescope classes. It performs instrumental signature removal (bad pixel masking, bias and dark removal, flat-field correction), astrometric fitting and source catalog extraction. We discuss the design considerations for BANZAI, including testing, performance, and extensibility. BANZAI is integrated into the observatory infrastructure and fulfills two critical functions: (1) real-time data processing that delivers data to users quickly and (2) derive metrics from those data products to monitor the health of the telescope network. In the era of time-domain astronomy, to get from these observations to scientific results, we must be able to automatically reduce data with minimal human interaction, but still have insight into the data stream for quality control.' author: - Curtis McCully - 'Nikolaus H. Volgenau' - 'Daniel-Rolf Harbeck' - 'Tim A. Lister' - 'Eric S. Saunders' - 'Monica L. Turner' - 'Robert J. Siverd' - Mark Bowman bibliography: - 'main.bib' title: 'Real-time processing of the imaging data from the network of Las Cumbres Observatory Telescopes using BANZAI' --- Introduction {#sect:intro} ============ In the era of time-domain astronomy, we need to rethink the way that we handle observational data. The traditional procedure of taking data manually, visually inspecting every image, and spending significant a amount of time and effort to produce final reduced products does not scale to upcoming surveys such as the Zwicky Transient Facility[@ZTF] (ZTF) and the Large Synoptic Survey Telescope[@LSST] (LSST), which will produce hundreds of thousands to millions of alerts per night. The volume of data is not the only consideration. We are starting to find new classes of astrophysical sources that vary on a vast range of time scales: from seconds for fast radio bursts [@Katz2016], to minutes for gamma-ray burst afterglows, to hours for kilonovae [@LIGO2017], to days for supernovae. Thus, work in time-domain astronomy requires fast-turnaround data reduction without human intervention. Las Cumbres Observatory Global Telescope[@Brown2013] (LCOGT) is pioneering the future of time domain follow-up. We currently operate a network of 21 small-aperture telescopes around the world which produce nearly 50,000 images ($\sim 1.5$ TB uncompressed raw data) per month. Rather than acting individually, our telescopes operate in unison. Specifically, users submit requests to a single access point, which are then dynamically scheduled across the network resources[@Saunders2014]. From a user’s perspective, LCOGT is a single facility, so it is necessary to produce homogeneous data for heterogeneous instruments by removing the instrumental signatures across the whole network of telescopes. To meet these challenges we have produced the “Beautiful Algorithms to Normalize Zillions of Astronomical Images” (BANZAI) pipeline[@banzai]. BANZAI reduces all of the images taken with LCOGT in real time. Below, we present the design choices we made for the BANZAI pipeline and how the pipeline is integrated into the overall dataflow of the observatory. Finally, we discuss the lessons LCOGT has learned which illustrate the challenges of running a high volume data processing service. Data flow from telescope to user ================================ LCOGT provides three tiers of data to users: raw, preview, and processed. The “raw” files contain unprocessed, 16-bit image data exactly as it was downloaded from the CCD. The “preview” and “processed” files have been calibrated to remove the instrument signature and also include source catalogs as additional extensions. Although both preview and processed files follow the same procedure, they may differ in which calibration files were used. “Preview” files are produced on-the-fly using recent calibration data, often from the previous day. “Processed” files are produced at the end of each night, using master calibration files from the same day as the observations (if available). All of our files are provided in Rice-compressed, “fpacked”[@fpack1; @fpack2] format. The interaction between users and the LCOGT telescopes is significantly different than with traditional facilities. For classical observing, an astronomer would travel to the telescope, observe through the night, and take their data home on an external hard drive (or even DAT tapes) to reduce. Processing data from a single observational run often required significant time and effort. Queue observing solves the issue of needing to travel to the telescope which makes rapid follow-up possible. However, many queue scheduled observatories still require manual data reduction. Both rapid response and automatic, robust data reduction are necessary to follow up alerts from upcoming surveys like ZTF and LSST. ![ \[fig:dataflow\] Schematic of the flow of data from the end of exposure to being available to users. Once the shutter closes, the FITS file is placed on the queue to be shipped back to the LCOGT headquarters. After it arrives, BANZAI pulls it off the FITS Exchange and processes the data. After the data is processed it gets ingested into the archive (hosted in the cloud) where it can be downloaded by users.](LCO-Dataflow.pdf){width="\textwidth"} Instead, LCOGT dynamically responds to changes in the system. When a user submits a request, a dynamic scheduler then optimizes when the observation should be attempted and at which site[@Saunders2014]. Figure \[fig:dataflow\] illustrates the dataflow after an observation is taken. Once the shutter closes, the telescope writes a FITS file that is “fpacked”[@fpack1; @fpack2] to on-site storage. The name and location of this file are added to a transfer queue (we use RabbitMQ[@rabbitmq], but we are not limited to this choice of implementation). The “Shipper” then transfers the file back to the LCOGT headquarters, and puts it on another queue, the “FITS Exchange” (again implemented using RabbitMQ[@rabbitmq]). The raw frames are then pushed to the science archive, which is hosted in the cloud using Amazon Web Services[@aws], where they can be downloaded by users. BANZAI also listens to the FITS Exchange, reducing images as they are added running in a “preview” mode. These processed images are then placed back on the FITS Exchange to be ingested into the science archive. BANZAI does standard image processing on every image taken with LCOGT: we mask bad pixels, subtract the overscan, subtract a master bias frame and a master dark, divide out a master flat, extract photometry for the sources in the field, and solve for the astrometry. We use SEP[@sep] to do source extraction and Astrometry.net[@Lang10] to solve for the astrometry. Raw files compared to a stack of reduced images from BANZAI are shown in Figure \[fig:example\_reduction\]. The median time from shutter close to the “preview“ data being available for download by users is 10 minutes (the full distribution is shown in Figure \[fig:archive\_lag\]). The tail to longer delays is often due to network issues. The median time for BANZAI to process an image is 2 minutes; Figure \[fig:processing\_lag\] shows the distribution of processing times for images. The long tail of processing times is due to dense fields, e.g. microlensing fields near the galactic center, that take longer to extract photometry and solve the astrometry than sparse fields. At the end of the local night for each site, we reprocess the images using master calibration images produced from calibrations taken during evening and morning twilight of that night. These constitute the science-quality reductions for users. By having both a preview and an end-of-night mode we satisfy users that need data quickly for rapidly evolving transients, but also use the best calibration data for the final reduction. ![ \[fig:example\_reduction\] An example of reduced frames from BANZAI. The left shows some example raw frames and the right panel shows a stack of BANZAI processed images.](banzai_example_reduction.pdf){width="\textwidth"} ![ \[fig:archive\_lag\] Distribution of time between the end of the observation and availability on the archive. The median time between shutter close and being available to users is 10 minutes. Network issues and minor isolated pipeline failures drive the tail of the distribution to longer delays.](archive_lag.pdf){width="\textwidth"} ![ \[fig:processing\_lag\] Distribution of time it takes BANZAI to process an image. The median reduction time is 35 s. Dense fields like those taken near the galactic center for microlensing take longer to extract photometry and solve for the astrometry, driving the tail of the distribution to longer processing times.](processing_lag.pdf){width="\textwidth"} BANZAI architecture =================== There are several architectural decisions that we made when developing BANZAI to minimize the barrier to entry for the code, to encourage transparency, and to allow for outside contributions from the broader astronomical community. The first choice is that we implemented BANZAI primarily in Python. Python has become one of the standard languages for astronomy, making it possible for a broad set of people to contribute to the development of the code base. The sections of the code that require high performance are written in Cython, with a few sorting algorithms implemented in C. Code Availability ----------------- LCOGT is committed to being an open-source organization so the BANZAI pipeline is publicly available on GitHub. Being open-source encourages best practices like transparency, code readability, and maintainability. The open source community has also built a variety of useful tools like Coveralls to measure test coverage and ReadTheDocs[@readthedocs] that enables clear and easily accessible documentation. Because BANZAI is an open-source project, people outside of LCOGT can improve the quality of data that it produces because the code is not a proprietary black box. This improves the reproducibility of scientific results and allows for customizations for specific projects. By hosting BANZAI on GitHub, every commit is recorded, making every individual person’s contributions apparent. Object model ------------ BANZAI is built as individual stages which are chained together to process images. The stage object is implemented as an abstract class which is used as the template for the Template Method pattern[@design_patterns]; the superclass contains all of the logic to pass images to the stage and for the top-level script to run the stage. The only piece that an individual stage needs to implement is a single method that takes a list of images and returns a list of processed images. The Template Method pattern employed here keeps the infrastructure for the pipeline simple and self-contained; the individual stages do not need to reimplement wrapper code, a common problem with pipelines. All of the images are kept in memory rather than being written to disk for each stage which keeps the file size small and the performance high. Master calibrations ------------------- Each night, every telescope in the LCOGT network takes calibration frames, e.g. biases, darks, and sky flats. BANZAI includes two utility template stage classes for these observations: a calibration stacker and a stage to correct science frames using a calibration stack. All of the file structure and retrieval logic for the most recent master calibration frames are built into the template classes. The specific stages, e.g., subtracting a dark frame, only have to implement the specialized logic to subtract the scaled dark from an image. Again the generic infrastructure is in a single location, making extension simple and limiting bugs from propagating via copy and paste. The master calibration metadata, such as the file path, are stored in a database. We use MySQL for our production instance but BANZAI itself is agnostic to the choice of database technology. We accomplish this by writing all of the queries in BANZAI using the Object Relational Model in SQLAlchemy[@sqlalchemy]. SQLAlchemy provides a unified frontend for most common database backends. This enables faster deployment and simpler testing; e.g. we use SQLite for testing and MySQL for production. Tests on the master calibration frames have been crucial for high-quality results. If a bad calibration frame slips into the reductions (e.g. a camera warms unexpectedly), images from multiple nights can be affected. To safeguard against this, we do two sets of comparisons on every calibration frame. The first is to compare the new calibration frames to previous “good” master calibration frames. A new “good” frame is created using the frames that pass this check. This allows the master calibration frames to evolve slowly over time, but rejects outliers. Prompt notification (early enough to allow intervention when needed) is an added benefit of real-time alerting. The second set of comparisons are done between all of the frames taken in the evening and morning twilight of an observing night. We employ a pixel-by-pixel comparison and reject any frames that fall outside the expected distribution (which is estimated using the median absolute deviation). Deployment ---------- The BANZAI code is deployed inside a Docker[@docker] container which allows rapid deployment on any machine as all of the dependencies are encapsulated in the container. If a user wants or needs to install the code locally instead of using Docker, the *Dockerfile* acts as a recipe to install the necessary dependencies. Using Docker also allows us to run multiple instances of the pipeline in parallel, e.g. a preview mode that produces fast-turnaround reductions and an end-of-night mode that applies master calibration frames taken in the morning after a given observation. The lifecycles of the Docker containers are managed by Rancher[@rancher], a container orchestration platform. Rancher schedules CPU resources, creates and destroys containers, and maps network ports between containers. The frontend streamlines deploying upgrades: simply changing a version in a web form and clicking “upgrade” is all that is required to deploy a new version of the pipeline. Rancher also provides access to a terminal inside containers which can be used to debug issues. ![\[fig:dq\_report\] An example summary report on the state of data processing for the LCOGT network. Each column corresponds to an individual instrument. The top rows show the total number of images taken and processed from last night. The middle section shows the results from a variety of data quality tests. The bottom colored section shows the ages of flat-fields for common filters. Green denotes that the flat-fields are recent, less than a week old. Red shows filters for which a flat has not been taken for more than two weeks and require human intervention.](banzai_dq.pdf){width="\textwidth"} Testing ------- Unit tests for BANZAI are automatically run using continuous integration (CI) services: we use a public Travis-CI site[@travis] and an internal Jenkins[@jenkins] server. The Travis-CI page allows outside users to see the results of the unit tests, while the internal Jenkins server allows us to test deployment and to do integration and end-to-end tests that require large test datasets. Failure Detection and Performance Metrics ========================================= One of the key challenges to run a data reduction service at this scale is detecting failures automatically. LCOGT produces thousands of images per night, more than is reasonable for any human being to check manually. Instead we have to rely on automated checks to detect and, if necessary, reject failed frames. The results of these checks and performance metrics are stored in ElasticSearch[@elasticsearch], a NoSQL database. The NoSQL format for ElasticSearch makes it simple to add metrics or change the format of stored results. ElasticSearch also provides a web API to query the results of our tests. Using the APIs, we have developed several monitoring tools. One is a summary report that is emailed to several members of the LCOGT operations team. An example table is shown in Figure \[fig:dq\_report\]. This report is designed to quickly visualize the age of the master calibration frames (less than a week old is shown in green) and to summarize the occurrence of known failure modes across the LCOGT network. We also use the metrics to generate real-time alerts. These alerts can be sent via email or to the operations team in Slack[@slack], a real-time communication platform. As these alerts are generated less than 10 minutes after shutter close, issues can be addressed before the whole observing night is affected and errors are more quickly detected rather than needing to wait for errors to be reported by users. ![\[fig:grafana\] An example dashboard that can be used to monitor the data quality being produced by the LCOGT network. The top panel shows the FWHM for each of our telescopes. Individual sites or cameras (shown with different colored points) can be selected using the dropdown menus at the top. The middle panel shows the offset between the requested center of the frame and the actual pointing. The bottom panel shows the number of frames per telescope that were not able to solve for the astrometry. The astrometry failure rate for BANZAI is 12.4% for the last six months. About half of those failures are due to focus issues on the 0.4-m telescopes. The rest are typically due to the sky transparency being too low.](grafana.png){width="\textwidth"} We also use metrics calculated by BANZAI to preform long-term monitoring of the network (e.g. the optical performance of LCOGT[@Harbeck2018]). As with the summary reports, we can use the ElasticSearch APIs to visualize data-quality metrics. We use Grafana[@grafana] to plot time series of metrics based on image quality, telescope pointing, etc. Figure \[fig:grafana\] shows an example dashboard with the Full Width Half Maximum (FWHM), the pointing quality, and the number of astrometric solution failures from the last week. A few example data-quality tests are described below. There are two main failure modes of the cameras at LCOGT. The first is when the camera produces an image that is only electric noise around the value of 1000 (this value is an artifact of the firmware). Frames are automatically rejected if a significant fraction of the image exactly equals 1000. When this happens, an alert is posted to Slack so that the operations team can restart the camera. The second failure mode comes from electrical interference. To detect this, we employ a 2D Fast Fourier Transform (FFT) and check for excess power due to pattern artifacts in the frame. This is recorded in ElasticSearch but does not currently generate an alert. Tuning the threshold to detect this pattern noise is still a work in progress to avoid false positives. This was producing an overwhelming number of alerts, making them counterproductive. *Limiting alert fatigue is essential for monitoring a dataflow of this size.* Detecting and recovering from failures is an area of active development. Conclusion ========== Data reduction at the scale of the LCOGT network is not without challenges: reducing thousands of images per night requires a high-performance pipeline, which was the motivation for BANZAI. Our median time to process an image is 35 seconds (see Figure \[fig:processing\_lag\]), and the median time between the shutter closing and the processed image being available to the user on the science archive is less than 10 minutes as shown in Figure \[fig:archive\_lag\]. As LCOGT is producing data 24 hours a day, 7 days a week, robust deployment is essential: BANZAI is deployed in a Docker container that is managed by Rancher, making it easy to upgrade and redeploy the pipeline as necessary. As new instruments come online, BANZAI needs to be able to adapt, so the code is designed with the idea of extensibility in mind. Monitoring a dataflow of this size without human intervention is another significant challenge. To solve this, we have tightly integrated the BANZAI pipeline into telescope operations via queues and APIs. We also send status and metrics to an ElasticSearch database that we use to produce summary plots and metrics to monitor the health of the telescope network. As future surveys like ZTF and LSST begin, going from follow-up observations to scientific results will require that facilities be able to reduce data with minimal human interaction, but still have insight into the datastream. The lessons we have learned at LCOGT will help to make that possible. We thank Martin Norbury, Todd Boroson, and Stefano Valenti for discussion about the design of BANZAI. CM was supported by supported by NSF grant AST-1313484.
{ "pile_set_name": "ArXiv" }
Failure of anticytokeratin 18 antibody to improve flow cytometric detection of bladder cancer. Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods. The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis. Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis. However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity.
{ "pile_set_name": "PubMed Abstracts" }
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{ "pile_set_name": "Pile-CC" }
A phase I safety and pharmacokinetic study of OGT 719 in patients with liver cancer. OGT 719 (Oxford GlycoSciences, Abingdon, UK) is a novel nucleoside analogue with a galactose molecule attached to a fluorinated pyrimidine. OGT 719 has the capacity selectively to bind to asialoglycoprotein receptors that are found exclusively on hepatocytes and hepatocellular carcinoma (HCC) cells. The aim of this study was to establish the safety and to examine the pharmacokinetics of this novel compound in patients with liver cancer. Fourteen patients received a total of 37 cycles of OGT 719 at four dose levels ([500 mg/m2 first cycle, 1 000 mg/m2 subsequent cycles], 1000 mg/m2, 3 300 mg/m2 and 7500 mg/m2). OGT 719 was administered as a 3-h intravenous infusion in a 250 ml saline solution, daily for 5 days every 4 weeks. Pharmacokinetic parameters were studied during the first cycle of dose levels 1 and 2 (500 mg/m2. and 1 000 mg/m2, respectively). The maximum plasma concentration was attained within 5 min of completing the infusion and almost doubled, dose dependently, with a doubling of the infused dose. The plasma level declined rapidly in a monophasic manner with an elimination half-life of 2.1 and 2.5 h for dose level 1 and 2, respectively The mean area under the curve (AUC(o - infinity) area under the curve to 24 h; AUC(o - infinity), area under the curve to infinity) doubled at the higher dose level. None of the patients had a significant tumor response. Elimination half-life of OGT 719 by 3-h intravenous infusion is short and monophasic. Toxicity was minimal at the highest dose level.
{ "pile_set_name": "PubMed Abstracts" }
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{ "pile_set_name": "Pile-CC" }
Regio- and Enantioselective Rhodium-Catalyzed Addition of 1,3-Diketones to Allenes: Construction of Asymmetric Tertiary and Quaternary All Carbon Centers. An unprecedented highly regio- and enantioselective rhodium-catalyzed addition of 1,3-diketones to terminal and 1,1-disubstituted allenes furnishing asymmetric tertiary and quaternary all-carbon centers is reported. By applying a RhI /phosphoramidite/TFA catalytic system under mild conditions, the desired chiral branched α-allylated 1,3-diketones could be obtained in good to excellent yields, with perfect regioselectivity and in high enantioselectivity. The reaction shows a broad functional-group tolerance on both reaction partners highlighting its synthetic potential.
{ "pile_set_name": "PubMed Abstracts" }
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{ "pile_set_name": "Pile-CC" }
This invention relates to a paint system including a flexible conduit or hose arrangement to supply a liquid coating composition from a paint supply system to a spray gun. More particularly, this invention relates to an improved spray gun for the paint system. As those familiar with the prior art will appreciate, in previous paint supply systems, a base coat of paint is applied at a first station and then the article, such as an automobile body, is conveyed to a new station where a clear coat paint is applied, the clear coat paint adding the feeling of depth to the paint. The ability to apply a clear coat and a base coat at the same time would provide a dramatic reduction in the cost of painting the car in the sense that half of the spray booths could be eliminated or deactivated and therefore half of the equipment and half of the manpower could be eliminated from the painting operation. Additionally, the modern factory is typically spread out and paint booths are not localized in one area or arranged so as to be parallel to one another. As a result, the use of a series connection between paint booths requires extensive tubing, particularly when the paint must be supplied to opposite sides of each booth. Accordingly, it would be desirable to minimize the number of lines needed to supply paint in a paint system and the cost associated with these lines. A continuing problem associated with the spray application of liquid paints is the presence of foreign particulate matter in the liquid paint supply which causes imperfections on the surfaces of the article being spray painted, frequently necessitating a refinishing or repainting thereof. Such foreign particulate matter, sometimes referred to as "seeds," or "strings," or "snotters" are formed in many instances as a result of an agglomeration of the paint constituents during standing or recirculation of the liquid paint necessitating removal prior to discharge through the spray nozzle. The foregoing problem is particularly pronounced in recirculating type liquid paint systems, although they are present in direct Line systems as well. Recirculating paint supply systems conventionally comprise a mixing tank equipped with suitable agitation for maintaining the liquid coating composition uniformly mixed and a pump for transferring the liquid coating composition under a desired pressure to a manually manipulable supply conduit connected to the spray nozzle. A suitable return hose is provided for returning the excess quantity of paint back to the mixing tank for recirculation and to keep the paint in suspension. Typical of such a system is the recirculating paint supply system shown in U.S. Pat. No. 5,060,861, the specification of which is incorporated herein by reference. In this paint supply system, the supply and return hoses are interconnected by suitable fluid fittings so as to form a single conduit having coaxial passages for supplying and returning the liquid composition. This and like paint systems typically will utilize many different fittings, connectors and coupling arrangements to complete the necessary fluid interconnections. Such fittings are often generally made of metal which can result in the conduit being relatively heavy. However, the paint supply hoses or unitized fluid conduit, and the associated fluid fittings, should be as light as possible to reduce operator fatigue and enable the operator to manipulate the position of the spray gun. Moreover, conventional spray guns are also generally made of metal which results in the spray gun, including the fittings to be relatively heavy. This weight may cause operator fatigue or ailments based upon the continuous and repetitive use of the heavy spray gun, which typically weighs about 22 ounces. Still further, as the work day draws on, this fatigue increases which may cause an appreciable decrease in finish quality of the object being coated. This decreased quality generally occurs because the operator may angle the spray delivered from the spray gun as opposed to maintaining the spray substantially perpendicular to the object which is desired. Seals and filters are also included in the paint supply line to seal the interconnections as well as to remove particulate matter from the paint being provided to the spray gun. In spite of the seals and filters, foreign matter can still be present. For example, the quick connectors used for the spray gun tend to create spit at the quick disconnect upon disconnecting which is generally not noticeable but, when dry, will cause leakage and contamination to occur. Further, to prevent leakage, it is known to cover the threaded sections of fluid fittings with pipe dope and then assemble the fittings. While this arrangement works well in many fluid sealing applications, it has several disadvantages. First, a pipe fitter must be called to assemble or disassemble the unit, which can be an inconvenience. Further, exposed threads create voids in the joint between the components which causes paint to accumulate and generates paint particles (dirt, etc.) that will be sent downstream and end up on the car, resulting in the need to rebuff and/or repaint the car. Various flow control devices or paint restrictors are also used with paint supply systems. In many cases such prior art constructions have been handicapped by their tendency to become plugged over periods of use, necessitating frequent replacement and/or downtime to permit cleaning to restore them to proper operating conditions. The build up of deposits in such flow regulators cause a progressive decrease in the pressure of the liquid coating composition supplied to the spray nozzle, thereby resulting in variations in the quality and thickness of the coating, thus detracting from their use. Moreover, a flow control device must include an element that moves relative to its valve body in order to change the flow rate. For example, a conventional ball valve has a rotatable ball member through which fluid can flow and seal portions positioned at the opposing upstream and downstream faces of the ball to inhibit flow therearound. Extended use of the valve member in one flow position can result in paint coagulating in voids formed around the seal portions. When the ball member is rotated, paint portions can break loose, thus detracting its use. Paint flakes, particles and dirt can result from the mating of fluid connector members, notwithstanding a seal being positioned to prevent flow around mated portions. Accordingly, it would be desirable to Limit or replace the use of threaded fittings with compression fittings, or those that use only pressure, thereby eliminating voids which tend to cause the paint to accumulate. Moreover, it would also be desirable to reduce the weight of the conventional spray gun and fittings, thereby reducing operator fatigue and increasing finish quality.
{ "pile_set_name": "USPTO Backgrounds" }
--- abstract: 'Dans ce papier, on résout d’abord le $\partial\bar\partial$ pour les courants prolongeables définis dans $\C^n$ privé d’une boule $B$ de $\C^n$, ensuite dans une variété analytique complexe $X$, on le résout pour un domaine $D=X\setminus\bar{\Omega}$, où $\Omega$ est un domaine borné de $X$ défini par $\{z\in X\,\ /\,\ \varphi(z)<0\}$, (avec $\varphi$ une fonction d’exhaustion strictement plurisousharmonique). [A]{}[BSTRACT.]{} In this present paper, we first solve the $\partial\bar\partial$ for extendable currents defined in $\C^n\setminus B$, where $B$ is a ball of $\C^n$, then in a analytic complex manifold $X$, and in a domain $D=X\setminus\bar{\Omega}$ where $\Omega$ is a bounded domain of $X$ defined by $\{z\in X\,\ /\,\ \varphi(z)<0\}$, ($\varphi$ is an exhaustion strictly plurisubharmonic function). 1.3mm *Classification mathématique 2010 :* 32F32.' address: | Département de Mathématiques\ UFR des Sciences et Thechnologies\ Université Assane Seck de Ziguinchor, BP: 523 (Sénégal) author: - | Eramane Bodian & Ibrahima Hamidine\ & Salomon Sambou title: 'Résolution du $\partial\bar\partial$ pour les courants prolongeables définis dans un anneau' --- ¶ \[section\] \[section\] \[section\] \[section\] \[section\] \[section\] \[section\] Introduction {#introduction .unnumbered} ============ Soit $B\subset\C^n$ la boule unité, on se pose la question suivante : si $T$ est un courant prolongeable $d$-ferm[é]{} sur $\C^n\setminus \bar B$, existe-t-il un courant prolongeable sur $\C^n\setminus \bar B$ tel que $\partial \bar{\partial} u = T$? Tenant compte de consid[é]{}rations classiques, nous devons pour r[é]{}pondre [à]{} cette question, avoir [à]{} r[é]{}soudre l’[é]{}quation $$\label{Equa1} d u =T,$$ o[ù]{} $T$ est un courant prolongeable, la solution obtenue se d[é]{}compose sans perte de généralités en une partie $\partial$-ferm[é]{}e et l’autre $\bar{\partial}$- ferm[é]{}e. $\C^n\setminus \bar B$ a les conditions géométriques nécessaires à la résolution du $\partial$ et $\bar \partial$ pour les courants prolongeables (voir [@Samb]). Partant de r[é]{}sultats connus de cohomologie de de Rham et de l’analogue convexe (voir [@SBD]), alors l’[é]{}quation admet une solution. La r[é]{}solution du $\partial \bar{\partial}$ devient alors une cons[é]{}quence des r[é]{}sultats de r[é]{}solution du $\bar{\partial}$ pour les courants prolongeables obtenus dans [@Samb]. Dans le cas d’une variété, on introduit la notion d’extension contractile et on résout le $\partial\bar{\partial}$ dans ce cadre. Pr[é]{}liminaires et notations ============================== Soit $B$ la boule de $\C^n$. $~~ $\ Un courant $T$ défini sur $\C^n\setminus \bar B$ est dit prolongeable s’il existe un courant $\check{T}$ défini sur $\C^n$ tel que $\check{T}_{|(\C^n\setminus \bar B)}=T$. D’après Martineau [@Mart], puisque $\stackrel{\circ}{(\overline{\C^n\setminus \bar B})}=\C^n\setminus \bar B$, les courants prolongeables de degré $p$ sur $\C^n\setminus \bar B$ sont égaux au dual topologique des $(2n - p)$-formes diff[é]{}rentielles de classe $\CC^{\infty}$ sur $\C^n$ à support compact sur $\C^n\setminus B$. On note $\check{\mathcal{D}}'^p(\C^n\setminus \bar B)$ l’espace des $p$-courants définis sur $\C^n\setminus \bar B$ et prolongeables à $\C^n$, $\A_c^p (\C^n\setminus \bar B)$ les $p$-formes diff[é]{}rentielles de classe $\CC^{\infty}$ sur $\C^n$ à support compact dans $\C^n\setminus \bar{B}$. Sur $\C^n$, on note $\check{\mathcal{D}}'^{p, q} (\C^n\setminus \bar{B})$ l’espace des $(p, q)$-courants prolongeables d[é]{}finis sur $\C^n\setminus \bar{B}$ et $\A_c^{p, q} (\C^n\setminus \bar{B})$ l’espace des $(p, q)$-formes diff[é]{}rentielles [à]{} support compact dans $\C^n\setminus \bar{B}$. On note $\check{{\rm H}}^p(\C^n\setminus \bar{B})$ le $p^{{\rm ieme}}$ groupe de cohomologie de de Rham des courants prolongeables d[é]{}finis sur $\C^n\setminus \bar{B}$, $\check{{\rm H}}^{p, q} (\C^n\setminus \bar{B})$ le $(p,q)^{{\rm ieme}}$ groupe de cohomologie de Dolbeault des courants prolongeables d[é]{}finis sur $\C^n\setminus \bar{B}$. Si $F \subset \C^n$, alors ${\rm H}_{\infty}^p (F)$ d[é]{}signe le $p^{{\rm ieme}}$ groupe de cohomologie de de Rham des $p$-formes diff[é]{}rentielles de classe $\CC^{\infty}$ d[é]{}finis sur $\C^n$, ${\rm H}_{\infty, c}^p (\C^n)$ est le groupe de cohomologie de de Rham des $p$-formes diff[é]{}rentiables de classe $\CC^{\infty}$ sur $\C^n$ [à]{} support compact et enfin $\A^p (F)$ l’espace des $p$-formes diff[é]{}rentielles de classe $\CC^{\infty}$ sur $F$. On note aussi, pour tout domaine $D$ de $\C^n$, $\flat D$ le bord de $D$. Résolution de l’équation $du=T$ =============================== Tout le long de cette section, nous considérons $$S=\{z\in\C^n\, ; |z|=1\}$$ et $$B=\{ z\in \C^n\, ; |z|<1\},$$ la sphère et la boule unité respectivement dans $\C^n$. Considérons la suite courte suivante, pour $0\leq p\leq 2n$ $$0\to \A^p(\C^n)\to \A^p(\C^n\setminus \bar B)\oplus\A^p(\bar B)\to \A^p(S)\to 0.$$ Sur le plan de cohomologie de de Rham, on a la suite longue de cohomologie suivante : $$\label{suitelong1} \begin{split} & 0 \to {\rm H}^0(\C^n)\to {\rm H}^0(\C^n\setminus \bar B)\oplus {\rm H}^0(\bar B)\to{\rm H}^0(S)\to\\ & {\rm H}^1(\C^n)\to {\rm H}^1(\C^n\setminus \bar B)\oplus {\rm H}^1(\bar B)\to{\rm H}^1(S)\to \ldots\to \\ & {\rm H}^{2n-1}(\C^n)\to {\rm H}^{2n-1}(\C^n\setminus \bar B)\oplus {\rm H}^{2n-1}(\bar B)\to {\rm H}^{2n-1}(S)\\ &\to {\rm H}^{2n}(\C^n)\to {\rm H}^{2n}(\C^n\setminus \bar B)\oplus {\rm H}^{2n}(\bar B)\to 0 \end{split}$$ On sait que $${\rm H}^p(\C^n\setminus \bar B)={\rm H}^p(\C^n\setminus B).$$ \[remark1\] $$\left\{ \begin{array}{ll} {\rm H}^p(S)=0, & \hbox{ si }\, 1< p < 2n-1\\ {\rm H}^0(S)={\rm H}^{2n-1}(S)=\R, \\ {\rm H}^p(\R^{2n})=0, & \hbox{ si }\, p\geq 1\\ {\rm H}^0(\R^{2n})=\R, \\ {\rm H}^p(B)=0, & \hbox{ si }\, p\geq 1\\ {\rm H}^0(B)=\R. \end{array} \right.$$ \[thm1\]$~~ $\ $$\check{{\rm H}}^j(\C^n\setminus\bar B)=0 \mbox{ pour } 2\leq j\leq 2n-2.$$ Pour démontrer le théorème \[thm1\], on a besoin du lemme suivant : \[lem1\]$~~ $\ $\A_c^p(\C^n\setminus B)\cap \ker d=d(\A_c^{p-1}(\C^n\setminus B)\big)$ pour $2\leq p\leq 2n-1$. $~~ $\ On utilse les résultats suivants: $${\rm H}_c^p(\C^n)=0, \mbox{ si } p \leq 2n-1$$ $${\rm H}_c^{2n}(\C^n)=\R, \mbox{ pour } p=2n.$$ Si $f\in\A_c^p(\C^n\setminus B)\cap \ker d$, alors $f\in\A_c^p(\C^n)\cap \ker d$ si $1\leq p\leq 2n-1$. ${\rm H}_c^{p}(\C^n)=0$, alors il existe $u\in \A_c^{p-1}(\C^n)$ telle que $du=f$. Si $p=1$, $u$ est une $0$-forme différentielle à support compact. Alors $du_{|_B}=0$. Ainsi $u=cst$ sur $B$. Par suite $du_{|_{\C^n\setminus\bar{B}}}\not\in \A_c^p(\C^n\setminus B)$ sauf pour $u$ identiquement nulle. Si $p\geq 2$, $du_{|_B}=0$. Puisque $${\rm H}^{p-1}(B)={\rm H}^{p-1}(\bar{B})=0, \mbox{ pour } 1\leq p-1;$$ i.e; $p\geq 2$, il existe $v\in \A^{p-2}(\bar{B})$ tel que $dv=u$ sur $B$. Posons $\tilde{v}$ une extension à support compact dans $\C^n$ de $v$, on a $$\tilde{u}=u-d\tilde{v}$$ qui est un élément de $\A_c^{p-1}(\C^n\setminus B)$ tel que $d\tilde{u}=f$. $~~ $\ *Étape 1:* Soit $T\in \check{\mathcal{D}'}^p(\C^n\setminus \bar{B})\cap\ker d$, $2\leq p\leq 2n-2.$ L’espace $d\A_c^{2n-p}(\C^n\setminus \bar{B})$ est fermé dans $\A_c^{2n-p+1}(\C^n\setminus B)$ pour $2\leq 2n-p+1\leq 2n-1$, (voir par exemple [@Samb], remarque 2). Pour $K$ un compact de $\C^n\setminus B$, notons $\A_{c,K}^{2n-p+1}(\C^n\setminus B)$ le sous-espace des formes différentielles appartenant à $\A_c^{2n-p+1}(\C^n\setminus B)]$ et qui ont leur support dans $K$. L’espace $\A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\A_c^{2n-p}(\C^n\setminus B)$ est fermé dans $\A_{c,K}^{2n-p+1}(\C^n\setminus B)$ qui est un espace de Fréchet, par conséquent, c’est un espace de Fréchet. $$\A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\A_c^{2n-p}(\C^n\setminus B)=\bigcup_{\nu\in\N}\big(\A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\A_{K_\nu}^{2n-p}(\C^n\setminus B)\big);$$ avec $K_\nu=\{z\in\C^n \; |z|\leq R_\nu,\,\ R_\nu\in\R_+^*\}\setminus B $ et $R_\nu > 1$ une suite exhaustive de compacts dans $\C^n\setminus B$. Il existe $\nu_0$ tel que $\A_c^{2n-p+1}(\C^n\setminus B)\cap d\A_{K_{\nu_0}}^{2n-p}(\C^n\setminus B)$ soit de deuxième catégorie de Baire. L’opérateur $d$ est alors un opérateur fermé de domaine de définition $$\{ \varphi\in\A_{K_{\nu_0}}^{2n-p}(\C^n\setminus B)| d\varphi\in \A_c^{2n-p+1}(\C^n\setminus B)\}$$ entre les espaces de Fréchet $\A_{K_{\nu_0}}^{2n-p}(\C^n\setminus B)$ et $\A_c^{2n-p+1}(\C^n\setminus B)\cap d\A_c^{2n-p} (\C^n\setminus B)$ dont l’image est de seconde catégorie de Baire. Le théorème de l’application ouverte implique que cet opérateur est surjectif et ouvert (voir par exemple [@Samb], Lemme 3.1). Donc $$d\A_{c,K_{\nu_0}}^{2n-p}(\C^n\setminus B)\cap \A_{c,K}^{2n-p+1}(\C^n\setminus B)=\A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\A_{c}^{2n-p}(\C^n\setminus B).$$ Posons $\tilde{K}=K_{\nu_0}$. L’application $$\begin{split} {\rm L}_T^K~: \A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)&\to \C \\ d\varphi & \mapsto \langle{\rm T},\varphi\rangle \end{split}$$ est bien définie. En effet, si $d\varphi=d\varphi'$, on a $d(\varphi-\varphi')=0$, $\varphi-\varphi'$ est une $(2n-p)$-forme différentielle, $d$-fermée à support dans $\tilde{K}$, en particulier dans $\C^n\setminus \bar B$. Par conséquent, il existe $\theta\in\A_{c}^{2n-p-1}(\C^n\setminus B)$ tel que $\varphi-\varphi'=d\theta$. Par densité de $\A_{c}^{2n-p-1}(\C^n\setminus\bar B)$ dans $\A_{c}^{2n-p-1}(\C^n\setminus B)$, il existe une suite $(\theta_j)_{j\in\N}$ d’éléments de $\A_{c}^{2n-p-1}(\C^n\setminus \bar B)$ qui converge uniforment vers $\theta$ dans $\A_{c}^{2n-p-1}(\C^n\setminus B)$ et par conséquent $$\langle T,\varphi\rangle=\langle T,\varphi'\rangle+\langle T,d\theta\rangle=\langle T,\varphi'\rangle$$ car $T$ étant $d$-fermé, $$\langle T,d\theta\rangle=\lim_{j\to+\infty}\langle T,d\theta_j\rangle=0.$$ Donc $${\rm L}_T^K(d\varphi)={\rm L}_T^K(d\varphi').$$ L’application ${\rm L}_T^K$ est linéaire et aussi continue comme composée de deux applications continues (et de la dualité entre $\check{\mathcal{D}}_D^p(\C^n)$ et $\A_c^{2n-p}(\C^n\setminus B)$) : $$T~: \A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)\to \C$$ et $$\delta~: \A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\big[\A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)\big]\to \A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)$$ qui vérifie $d\circ \delta={\rm Id}$ et qui est obtenue par application du théorème de l’application ouverte appliqué à $$\begin{split} d~: \{ \varphi\in \A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)/\,\ d\varphi\in \A_{c,K}^{2n-p+1}(\C^n\setminus B)\}\subset \A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)\\ \qquad \qquad \to \A_{c,K}^{2n-p+1}(\C^n\setminus B)\cap d\big[\A_{c,\tilde{K}}^{2n-p}(\C^n\setminus B)\big]. \end{split}$$ D’après le théorème de Hahn-Banach, on peut [é]{}tendre ${\rm L}_T^K$ en un op[é]{}rateur lin[é]{}aire et continu : $$\tilde{\rm L}_T^K~: \A_c^{2n-p+1} (\C^n\setminus B) \to\C$$ qui est linéaire et continu. Donc $\tilde{{\rm L}}_T^K$ est un courant prolongeable défini dans $\C^n\setminus \bar B$ et $d \tilde{\rm L}_T^K = (- 1)^{2n-p} T$ sur $\stackrel{\circ}{K}$ car ${\rm supp}\varphi\subset K$, $$d\varphi \in\A_{c,K}^{2n-p+1}(\C^n\setminus B)$$ et $$\langle\tilde{{\rm L}}_T^K,d\varphi\rangle=(-1)^{2n-p}\langle T,\varphi\rangle.$$ On pose $S^{(K)}=(-1)^{2n-p}\tilde{{\rm L}}_T^K.$ D’o[ù]{} $S^{(K)} = (- 1)^{2n-p} \tilde{{\rm L}}_T^K $ est un courant prolongeable solution de $d u = T$ sur $K$. *Étape 2:* Soit maintenant $K_1$, $K_2$ et $K_3$ trois compacts d’intérieur non vide de $\C^n\setminus B$ tels que $\stackrel{\circ}{K_1}\subset\subset\stackrel{\circ}{K_2}\subset\subset\stackrel{\circ}{K_3}$ et $\stackrel{\circ}{K_i}\cup \bar B=\{z\in\C^n\,\; \mid z \mid<\eta_i\}$, $i=1,2,3$. Soit $T$ un courant prolongeable sur $\C^n\setminus\bar{B}$ tel qu’il existe $S_2$ et $S_3$ deux $p-1$ courants définis sur $\stackrel{\circ}{K_2}$ et $\stackrel{\circ}{K_3}$ et prolongeables à $\C^n$ tels que, pour tout indice $i=2,3$, $d S_i=T$ sur $\stackrel{\circ}{K_i}$ et soit $\epsilon > 0$, alors il existe un courant prolongeable $\tilde{S_3}$ défini sur $\stackrel{\circ}{K_3}$ tel que : $d\tilde{S_3}=T$ sur $\stackrel{\circ}{K_3}$ et $\tilde{S_3}_{|\stackrel{\circ}{K_1}}=(S_2)_{|\stackrel{\circ}{K_1}}$ si $2\leq p\leq 2n-1.$ En effet, comme $dS_2=T$ sur $\stackrel{\circ}{K_2}$ et $dS_3=T$ sur $\stackrel{\circ}{K_3}$, $d(S_2-S_3)=0$ sur $\stackrel{\circ}{K_2}$. Puisque sur $\stackrel{\circ}{K_2}$, on peut résoudre le $d$ pour les formes différentielles à support compact dans $\stackrel{\circ}{K_2}\cup\flat B$ de degré $p$ avec $2\leq 2n-p+1\leq 2n-1$ et $d\big[\A_c^{2n-p-1}(\stackrel{\circ}{K_2}\cup\flat B)\big]$ est fermé dans $\A_c^{2n-p-1}(\stackrel{\circ}{K_2}\cup\flat B)$, on a d’après l’étape 1 et pour $K$ un compact tel que $\stackrel{\circ}{K_1}\subset\subset K\subset\subset \stackrel{\circ}{K_2}$ un courant $S^{(K)}$ sur $\stackrel{\circ}{K}$ prolongeable à $\stackrel{\circ}{K_2}\cup\bar B$ tel que $S_2-S_3=dS^{(K)}$ sur $\stackrel{\circ}{K}$. Soient $\chi$ une fonction dans $\CC^\infty(\C^n)$ à support compact dans $\stackrel{\circ}{K}\cup \bar{B}$ qui vaut $\bf 1$ dans $K_1$ et $\tilde{S}^{(K)}$ une extension de $S^{(K)}$ à $\C^n$ $$S_3+d(\chi\tilde{S}^{(K)})=S_2-d\big((1-\chi)\tilde{S}^{(K)}\big) \mbox{ sur } \stackrel{\circ}{K_1}.$$ On pose $$\tilde{S}_3=S_3+d(\chi\tilde{S}^{(K)}).$$ *Étape 3:* Considérons une suite exhaustive $(K_j)_{j\in\N}$ de compacts de $\C^n\setminus B$. Supposons que $\stackrel{\circ}{K_j}\cup\bar B=\{z\in\C^n\,\: \mid z \mid<\eta_j\}$ où $(\eta_j)_{j\in\N}$ sont des réels tels que $\eta_j <\eta_{j+1}$. Pour $2\leq p\leq 2n-1$, on associe à $(K_j)_{j\in \N}$ grâce aux étapes 1 et 2 une suite de courants $(S_j)_{j\in\N}$ définis dans $K_j$ et prolongeables à $\C^n$ telle que $d S_j=T$ sur $\stackrel{\circ}{K_j}$ et si $j$, $j+1$, $j+2$ sont trois indices consécutifs, $S_{j+2}=S_{j+1}$ sur $\stackrel{\circ}{K_j}$. La suite $(S_j)_{j\in N}$ converge vers un courant $S$ défini sur $\C^n\setminus \bar{B}$ et prolongeable. De plus, $S$ est solution de l’équation $du=T$ dans $\C^n\setminus\bar{B}$. Résolution du $\partial\bar\partial$ pour les courants prolongeables ==================================================================== Tenant compte du th[é]{}or[è]{}me \[thm1\] et des r[é]{}sultats de r[é]{}solution du $\bar{\partial}$ pour les courants prolongeables obtenus par S. Sambou dans [@Samb], on a le th[é]{}or[è]{}me suivant : \[thm3\]$~~ $\ Soit $T$ un $(p,q)$-courant prolongeable d[é]{}fini sur $\C^n\setminus \bar{B}$. Supposons que $d T = 0$; $1\leqslant p \leqslant n$ et $1 \leqslant q \leqslant n$, alors il existe un $(p-1,q-1)$-courant $S$ d[é]{}fini sur $\C^n\setminus \bar{B}$, prolongeable tel que $\partial \bar{\partial} S = T$, pour $2 \leqslant p + q \leqslant 2n-1$. Soit $T$ un $(p, q)$-courant, $1 \leqslant p \leqslant n$ et $1 \leqslant q \leqslant n$, $d$-ferm[é]{} d[é]{}fini sur $\C^n\setminus \bar{B}$ et prolongeable avec $2 \leqslant p + q \leqslant 2n-1$. Puisque le th[é]{}or[è]{}me \[thm1\] nous assure que $\check{{\rm H}}^{p + q} (\C^n\setminus \bar{B})=0$, il existe un courant prolongeable $\mu$ d[é]{}fini sur $\C^n\setminus \bar{B}$ tel que $d \mu = T$. $\mu$ est un $(p + q - 1)$-courant, il se d[é]{}compose en un $(p - 1, q)$-courant $\mu_1$ et en un $(p, q - 1)$-courant $\mu_2$. On a $$d \mu = d (\mu_1 + \mu_2) = d \mu_1 + d \mu_2 = T.$$ Comme $d=\partial+\bar\partial$, on a, pour des raisons de bidegré, $\partial\mu_2=0$ et $\bar\partial\mu_1=0$. On obtient $\mu_1=\bar\partial u_1$ et $\mu_2=\partial u_2$ avec $u_1$ et $u_2$ des courants prolongeables définis sur $\C^n\setminus \bar{B}$, (voir [@Samb], section 3). On a : $$\begin{aligned} T &= &\partial \mu_1 + \bar{\partial} \mu_2\\ &=&\partial \bar{\partial} u_1 + \bar{\partial} \partial u_2\\ &=&\partial \bar{\partial} (u_1 - u_2)\end{aligned}$$ Posons $S = u_1 - u_2$ , $S$ est un $(p - 1, q - 1)$-courant prolongeable d[é]{}fini sur $\C^n\setminus \bar{B}$ tel que $\partial \bar{\partial} S = T$. Résolution du $\partial\bar\partial$ sur une variété analytique complexe ======================================================================== On va maintenant considérer $X$ comme une variété différentiable de dimension $n$. Soit $X$ une variété différentiable de dimension $n$ et $\omega\subset X$ un domaine contractile. On dit que $X$ est une extension contractile de $\Omega$, s’il existe une suite $\left(\Omega_{n} \right)_{n} $ exhaustive de domaines contractiles telle que $$\forall n, \Omega\subset\subset \Omega_{n}\subset\subset X.$$ Quand $X=\mathbb{C}^{n}$, alors $\mathbb{C}^{n}$ est une extension contractile de la boule unité $B$.\ \ On a pour les extensions contractiles, le théorème suivant: \[thm4\]$~~ $\ Soit $X$ une variété analytique complexe de dimension $n$ et soit $D\subset\subset X$ un domaine contractile fortement pseudoconvexe. Supposons que $X$ est une extension $(n-1)$-convexe avec $ H^{j}(\flat D)=0 \quad 2\leqslant j\leqslant 2n-2$ de $D$ et une extension contractile de $D$. Posons $\Omega=X\setminus\bar{D}$. Si $\stackrel{\circ}{\bar{\Omega}}=\Omega$, alors pour tout $(p,q)$ courant $T$ défini sur $\Omega$, $d$-fermé et prolongeable, il existe un $(p-1,q-1)$ courant $S$ défini sur $\Omega$ et prolongeable tel que $\partial\bar{\partial}S=T$ pour $1\leqslant p\leqslant n-1$ et $1\leqslant q\leqslant n-1$. Pour démontrer le théorème \[thm4\], nous avons besoin du lemme suivant : $$\A_c^r(\bar\Omega)\cap\ker d=d\big(\A_c^{r-1}(\bar\Omega)\big) \mbox{ pour } 1\leq r \leq 2n-1.$$ $~~ $\ On a $X=\cup D_{\nu} \quad , D\subset\subset D_{\nu}\subset\subset X$ et $D_{\nu}$ est contractile.\ Si $f\in\A_c^r(\bar{\Omega)}\cap\ker d \quad \exists \nu_{0}\in \mathbb{N}$ tel que $f\in \A_c^r(D_{\nu_{0}})\cap \ker d$. Or $ H^{j}(D_{\nu_{0}})=0 ,\quad \textrm{pour} j\geq 1 $. Par dualité de Poincaré $H^{j}_{c}(D_{\nu_{0}})=0 \quad \textrm{pour} j<2n$. Il existe $g\in \A_c^{r-1}(D_{\nu_{0}})$, donc $g\in \A_c^{r-1}(X)$ telle que $dg=f$.\ $dg_{\mid D}=0$, si $r=1$ alors $g$ est une constante sur $D$. Si $r>1$, il existe $u$ une $(r-2)$ forme différentielle sur $\bar{D}$ telle que $ g_{\mid D}=du $. Soit $\tilde{u}$ une extension de $u$ à support compact dans $X$, $h=g-d\tilde{u}$ convient. Nous pouvons établir donc la preuve du théorème \[thm4\] $~~ $\ Soit une suite exhaustive de compacts $K_{\nu}$ de $\Omega$. $$K_{\nu}=\bar{D_{\nu}}\setminus \bar{D}$$ et quelque soit $\nu$, $K_\nu$ est un compact d’intérieur non vide. Pour $K$ un compact de $\Omega$, l’opérateur ${\rm L}_T^K$ est bien défini, linéaire et continu, cf. étape 1 de la démonstrations du théorème \[thm1\]. *Étape 1:*\ D’après le théorème de Hahn-Banach, on peut [é]{}tendre ${\rm L}_T^K$ en un op[é]{}rateur lin[é]{}aire et continu : $$\tilde{\rm L}_T^K~: \A_c^{2n-p+1} (\Omega) \to\C$$ qui est linéaire et continu. Donc $\tilde{{\rm L}}_T^K$ est un courant prolongeable défini dans $ \bar\Omega$ et $ d\tilde{\rm L}_T^K = (- 1)^{2n-p} T$ sur $\stackrel{\circ}{K}$ car ${\rm supp}\varphi\subset K$, $$d\varphi \in\A_{c,K}^{2n-p+1}(\Omega)$$ et $$\langle\tilde{{\rm L}}_T^K,d\varphi\rangle=(-1)^{2n-p}\langle T,\varphi\rangle.$$ On pose $S^{(K)}=(-1)^{2n-p}\tilde{{\rm L}}_T^K.$ D’o[ù]{} $S^{(K)} = (- 1)^{2n-p} \tilde{{\rm L}}_T^K $ est un courant prolongeable solution de $d u = T$ sur $K$. *Étape 2:*\ Soit maintenant $K_1$, $K_2$ et $K_3$ trois compacts d’intérieur non vide de $\Omega$ tels que $\stackrel{\circ}{K_1}\subset\subset\stackrel{\circ}{K_2}\subset\subset\stackrel{\circ}{K_3}$ et $\stackrel{\circ}{K_i}\cup \bar D=\{z\in X\,\ ; |z|<\eta_i\}$, $i=1,2,3$. Soit $T$ un courant prolongeable sur $\bar{\Omega}$ tel qu’il existe $S_2$ et $S_3$ deux $(p-1)$ courants définis sur $\stackrel{\circ}{K_2}$ et $\stackrel{\circ}{K_3}$ et prolongeables à $X$ tels que, pour tout indice $i=2,3$, $d S_i=T$ sur $\stackrel{\circ}{K_i}$, alors il existe un courant prolongeable $\tilde{S_3}$ défini sur $\stackrel{\circ}{K_3}$ tel que : $d\tilde{S_3}=T$ sur $\stackrel{\circ}{K_3}$ et $\tilde{S_3}_{|\stackrel{\circ}{K_1}}=(S_2)_{|\stackrel{\circ}{K_1}}$ si $2\leq p.$ En effet, comme $d S_2=T$ sur $\stackrel{\circ}{K_2}$ et $d S_3=T$ sur $\stackrel{\circ}{K_3}$, $d(S_2-S_3)=0$ sur $\stackrel{\circ}{K_2}$. Puisque sur $\stackrel{\circ}{K_2}$, on peut résoudre le $d$ pour les formes différentielles à support compact dans $\stackrel{\circ}{K_2}\cup\,\ \flat D$ de degré $p$ avec $2\leq 2n-p+1\leq 2n-1$ et $d\big[\A_c^{2n-p-1}(\stackrel{\circ}{K_2}\cup\,\ \flat D)\big]$ est fermé dans $\A_c^{2n-p-1}(\stackrel{\circ}{K_2}\cup\,\ \flat D)$, on a d’après l’étape 1 et pour $K$ un compact tel que $\stackrel{\circ}{K_1}\subset\subset K\subset\subset \stackrel{\circ}{K_2}$ un courant $S^{(K)}$ sur $\stackrel{\circ}{K}$ prolongeable à $\stackrel{\circ}{K_2}\cup\bar D$ tel que $S_2-S_3=d S^{(K)}$ sur $\stackrel{\circ}{K}$. Soient $\chi$ une fonction de classe $\CC^\infty$ à support compact dans $\stackrel{\circ}{K}\cup \bar{D}$ qui vaut $1$ dans $K_1$ et $\tilde{S}^{(K)}$ une extension de $S^{(K)}$ à $X$ $$S_3+d(\chi\tilde{S}^{(K)}=S_2-d\big((1-\chi)\tilde{S}^{(K)}\big) \mbox{ sur } \stackrel{\circ}{K_1}.$$ On pose $$\tilde{S}_3=S_3+d(\chi\tilde{S}^{(K)}).$$ *Étape 3:*\ Considérons une suite exhaustive $(K_j)_{j\in\N}$ de compacts de $\Omega$. Supposons que $\stackrel{\circ}{K_j}\cup\bar D=\{z\in X\,\: \mid z \mid<\eta_j\}$ où $(\eta_j)_{j\in\N}$ sont des réels tels que $\eta_j <\eta_{j+1}$. Pour $2\leq p$, on associe à $(K_j)_{j\in \N}$ grâce aux étapes 1 et 2 une suite de courants $(S_j)_{j\in\N}$ définis dans $K_j$ et prolongeables à $X$ telle que $d S_j=T$ sur $\stackrel{\circ}{K_j}$ et si $j$, $j+1$, $j+2$ sont trois indices consécutifs, $S_{j+2}=S_{j+1}$ sur $\stackrel{\circ}{K_j}$. La suite $(S_j)_{j\in N}$ converge vers un courant $S$ défini sur $\Omega $ et prolongeable à $X$. De plus, $S$ est solution de l’équation $d u=T$ dans $\Omega$. *Étape 4 :*\ Soit $T$ un $(p, q)$-courant, $1 \leqslant p \leqslant n$ et $1 \leqslant q \leqslant n$, $d$-ferm[é]{} d[é]{}fini sur $\Omega$ et prolongeable avec $2 \leqslant p + q \leqslant 2n-2$. Puisque le th[é]{}or[è]{}me \[thm1\] nous assure que $\check{{\rm H}}^{p + q} (\Omega)=0$, il existe un courant prolongeable $\mu$ d[é]{}fini sur $\Omega$ tel que $d \mu = T$. $\mu$ est un $(p + q - 1)$-courant, il se d[é]{}compose en un $(p - 1, q)$-courant $\mu_1$ et en un $(p, q - 1)$-courant $\mu_2$. On a $$d \mu = d (\mu_1 + \mu_2) = d \mu_1 + d \mu_2 = T.$$ Comme $d=\partial+\bar\partial$, on a, pour des raisons de bidegré, $\partial\mu_2=0$ et $\bar\partial\mu_1=0$. On obtient $\mu_1=\bar\partial u_1$ et $\mu_2=\partial u_2$ avec $u_1$ et $u_2$ des courants prolongeables définis sur $\Omega$, (voir [@Samb], section 3). On a : $$\begin{aligned} T &= &\partial \mu_1 + \bar{\partial} \mu_2\\ &=&\partial \bar{\partial} u_1 + \bar{\partial} \partial u_2\\ &=&\partial \bar{\partial} (u_1 - u_2)\end{aligned}$$ Posons $S = u_1 - u_2$ , $S$ est un $(p - 1, q - 1)$-courant prolongeable d[é]{}fini sur $\Omega$ tel que $\partial \bar{\partial} S = T$. [33333]{} C. Godbillon. Topologie algébrique, Hermann Paris, 1971. A. Martineau. Distribution et valeurs au bord des fonctions holomorphes. Strasbourg RCP 25 (1966). S. Sambou, E. Bodian, D. Diallo. Résolution du $\partial\bar\partial$ pour les courants prolongeables définis sur la boule euclidienne de $\C^n$. A paraître dans Mathmatical report of royal academy society of Canada. S. Sambou. Résolution du $\bar\partial$ pour les courants prolongeables définis dans un anneau. Annales de la faculté des sciences de Toulouse $6^e$ série, tome 11, 1 (2002), p. 105-129. S. Sambou. Résolution du $\bar\partial$ pour les courants prolongeables. Math. Nachrichten [**235**]{} (2002), pg. 179-190.
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1. Introduction {#sec1-polymers-12-00289} =============== The environmental problems caused by textile printing and dyeing wastewater have become the focus of attention. Typical textile printing and dyeing wastewater usually contains dyes, polyvinyl alcohol (PVA), starch, and so on \[[@B1-polymers-12-00289],[@B2-polymers-12-00289]\]. Some dyes may be further degraded into toxic and carcinogenic substances, which will affect human health \[[@B3-polymers-12-00289]\]. The efficient and complete removal of dyes from effluents is necessary. Starch and PVA in textile printing and dyeing wastewater have a great influence on the reoxygenation behavior of bodies of water. As a result of the high chemical oxygen demand (COD) values and lower biodegradability, PVA is difficult to remove from textile wastewater by simple treatment facilities \[[@B4-polymers-12-00289],[@B5-polymers-12-00289]\]. A lot of technologies, including flocculation, membrane separation, chemical oxidation, and degradation, have been studied for treating dye wastewater \[[@B6-polymers-12-00289],[@B7-polymers-12-00289],[@B8-polymers-12-00289],[@B9-polymers-12-00289]\] or for treating PVA-containing wastewater \[[@B5-polymers-12-00289],[@B10-polymers-12-00289],[@B11-polymers-12-00289],[@B12-polymers-12-00289],[@B13-polymers-12-00289]\], but so far, there have been no reports on the simultaneous removal of dyes, PVA, and starch from textile printing and dyeing wastewater. These methods also have many difficulties for industrial application, due to the high cost of investment and operation, complicated processes, and inability to remove pollutants completely \[[@B5-polymers-12-00289],[@B12-polymers-12-00289],[@B14-polymers-12-00289]\]. By contrast, adsorption is one of the most efficient and reliable textile wastewater treatment techniques \[[@B15-polymers-12-00289],[@B16-polymers-12-00289],[@B17-polymers-12-00289]\], and fixed-bed adsorption is often desired from an industrial point of view, because of its advantages of its 100% pollutant removal ability from wastewater, lower floor space, and lower cost of equipment investment and operation \[[@B18-polymers-12-00289],[@B19-polymers-12-00289],[@B20-polymers-12-00289],[@B21-polymers-12-00289],[@B22-polymers-12-00289]\]. Many studies have been conducted on the dye adsorption properties of various adsorbents used in fixed beds, such as agricultural waste, chitosan-based materials, zeolites, and industrial by-products, etc. \[[@B18-polymers-12-00289],[@B23-polymers-12-00289],[@B24-polymers-12-00289],[@B25-polymers-12-00289]\]; however, these adsorbents usually have defects with a low adsorption capacity. Up until now, activated carbon (AC), although its removal efficiencies for organic dyes are still relatively low \[[@B26-polymers-12-00289],[@B27-polymers-12-00289]\], is still the most commonly used adsorbent for industrial wastewater treatment \[[@B28-polymers-12-00289],[@B29-polymers-12-00289]\]. Therefore, in order to remove dye, polyvinyl alcohol, and starch from textile wastewater simultaneously, it is necessary to develop an efficient and low-cost fixed-bed adsorbent alternative. Starch and its derivatives are of increasing interest because of their higher biodegradability and renewability \[[@B30-polymers-12-00289],[@B31-polymers-12-00289]\]. Cationic starch derivatives with quaternary ammonium groups are commonly prepared through the reaction of starch with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) \[[@B32-polymers-12-00289],[@B33-polymers-12-00289]\]. As a result of the strong quaternary ammonium groups, cationic starch derivatives can adsorb anionic compounds, and have been widely utilized for removing various ions and organic pollutants from wastewater \[[@B34-polymers-12-00289],[@B35-polymers-12-00289],[@B36-polymers-12-00289]\]. PVA possesses hydrophilic, biocompatible, and nontoxic characters. PVA derivatives are important functional polymers, and are widely used in paper, medicine, and water treatment \[[@B37-polymers-12-00289],[@B38-polymers-12-00289],[@B39-polymers-12-00289]\]. Nevertheless, so far, there have been no reports on the synthesis of modified starch/PVA composite microspheres and their applications in textile wastewater treatment. In this paper, the cationic cross-linked starch/PVA composite microspheres (CCSP) were synthesized for the purpose of removing the starch, PVA, and dyes from the textile wastewater concurrently, and their properties were determined. Combined with fixed-bed adsorption techniques, the adsorption capacities of CCSP for treating textile wastewater were investigated. Most importantly, the CCSP used exhibited great sustainable reutilization by converting into regenerated AC, thereby avoiding secondary solid-waste pollution. It is expected that the strategies shown in this work will provide new inspiration and ideas for the development of environmentally-friendly textile wastewater treatment techniques. 2. Materials and Methods {#sec2-polymers-12-00289} ======================== 2.1. Materials {#sec2dot1-polymers-12-00289} -------------- Corn starch containing approximately 71% amylopectin and 29% amylose was supplied by Tianjin Tingfung Starch Development Co., Ltd., Tianjin, China. Polyvinyl alcohol (PVA; 1700 degrees of polymerization, 99% hydrolyzed) was obtained from China Petroleum and Chemical Corporation, Shanghai, China. 3-Chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) was obtained from Sigma-Aldrich Chemie Gmbh, Steinheim, Germany. Colour Index (C.I.) Reactive Black 5 and C.I. Reactive Orange 131 were supplied by BASF SE, Ludwigshafen, Germany. Their structures are displayed in [Figure 1](#polymers-12-00289-f001){ref-type="fig"}. The commercial activated carbon (AC) was purchased from Ningxia Huahui Activated Carbon Company (Yinchuan, China), and its methylene blue number was 225.3 mg/g. All of the other chemicals were of analytical grade, obtained from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China), without further purification. 2.2. Preparation of Modified Starch/PVA Composites {#sec2dot2-polymers-12-00289} -------------------------------------------------- Cross-linked cationic PVA (CCP) was obtained by a two-stage process. First, the cationic PVA (CP) was prepared by PVA with CHPTAC, in the presence of sodium hydroxide, at 40 °C for 4 h \[[@B40-polymers-12-00289]\]. In the second step, 7.2 g of Span-80 was added into 100 g of cyclohexane and was stirred, and was then added into 50 g of a cationic PVA aqueous solution (5 wt%). The mixture was homogenized at 6000 r/min by a high-shear dispersion homogenizer for 30 min to form a stable W/O emulsion system. Then, 12 g of a borax solution (2.5 wt%) was dropwise added into the mixture within 30 min, and continued to react for another 4 h at 35 °C. Finally, it was centrifuged, washed with acetone, and dried in an oven at 40 °C. Thus, the CCP microspheres were obtained. The degree of substitution of synthesized CP was 0.24 (2.99 mmol/g of the cationic group content), which was calculated based on the content of the element nitrogen. Cross-linked cationic starch (CCS) and cationic starch (CS) were prepared using borax and CHPTAC as a cross-linking agent and cationic reagent, respectively, in the same way as the above methods. The degree of substitution of the synthesized CS was 0.39 (1.76 mmol/g of the cationic group content), calculated from the nitrogen content. The modified starch/PVA composite sample (denoted as CCSP1) was prepared based on the preparation procedures of CCP, by replacing only the CP with a mixture of CS and CP (CS/CP with a mass ratio of 2:1). The same treatments were repeated in order to obtain the samples of CCSP2 and CCSP3, by changing only the mass ratios of CS/CP from 2:1 to 1:1 and 1:2, respectively. 2.3. Characterization {#sec2dot3-polymers-12-00289} --------------------- The FT-IR spectra of the samples were measured using a Nicolet IS 10 FT-IR spectrophotometer (Nicolet, Madison, Wis., USA). The particle size analyses were carried out using a laser light-scattering-based particle sizer (Rise-2028, Jinan, China), and ethyl alcohol and distilled water were used as the dispersion medium. The sample microtopography was observed using a scanning electron microscope (SEM; JSM-6400, Tokyo, Japan), and the morphology was observed using a transmission electron microscopy (TEM; JEOL JEM-2100F, Tokyo, Japan). The samples were treated with supersonic dispersion before the TEM measurement \[[@B41-polymers-12-00289]\]. The crystalline structure of the samples was examined using powder X-ray diffraction (XRD; DX2700, Dandong, China). The surface charges of the samples were obtained by a Zeta potential analyzer (Malvern-Zetasizer nano ZS, Malvern, UK) under neutral conditions. 2.4. Adsorption Studies {#sec2dot4-polymers-12-00289} ----------------------- The adsorption properties of the samples were investigated using a fixed-bed column (1.2 cm in diameter × 30 cm in height) connected to a spectrophotometer detector. The fixed-bed column was prepared according to the method of Zhang et al. \[[@B42-polymers-12-00289]\]. In view of this, the microsphere samples (CCS, CCP, and the CCSPs) had some of the swelling properties of water absorption, and diatomite or activated carbon were chosen as the filter aid to increase the space velocity of the fixed-bed column. The column was filled with a mixture adsorbent composed of microsphere samples (5 g) and diatomite (5 g; as the filter aid), or a mixture adsorbent composed of microsphere samples (5 g) and activated carbon (5 g), or only 10 g of activated carbon. The microsphere samples, diatomite, and commercial activated carbon were all sieved into a particle size range of 200--300 mesh. The simulated wastewater was continuously fed to the top of the column at a flow rate of 2 mL/min, which was controlled by a peristaltic pump at room temperature. The absorbance readings were taken at set time intervals to analyze the solutions leaving the column. Among these, iodine and potassium iodide solutions and iodine-boric acid solutions were used as color developing agents for solutions containing starch and PVA, respectively. The simulated wastewater used in this study included dye wastewater (0.5 g/L), starch solution (0.1 g/L), PVA solution (0.1 g/L), and simulated textile wastewater (0.5 g/L of Reactive Orange 131, 0.1 g/L of starch, and 0.1 g/L of PVA). The volumes of the completely purified effluent solution were recorded. The adsorption capacities of the adsorbents were calculated based on the volumes of the completely purified effluent. As for the simulated textile wastewater, the adsorption capacity was the sum of the adsorption amount for each component. The effect of the bed height (9.5, 7.6, and 5.7 cm) and flow rate (2, 3, and 4 mL/min) on the column adsorption capacity of the mixture adsorbent (CCSP2 and AC) to treat the textile wastewater was investigated. The effluent solution was analyzed to yield output concentration breakthrough curves. 2.5. The Recycle of Disabled Adsorbent {#sec2dot5-polymers-12-00289} -------------------------------------- After adsorption, the disabled mixture adsorbent was recycled as follows. First, the disabled adsorbent was dried at 110 °C for 12 h under an air atmosphere, and then carbonized at 350 °C for 3 h under an N~2~ atmosphere. Next, the carbon spheres were impregnated with the activating agent KOH \[[@B43-polymers-12-00289]\], and the activation process was carried out at 850 °C for 2 h under an N~2~ atmosphere. The obtained material, signed as regenerated activated carbon (RAC), was washed with diluted HCl and deionized water separately, and finally dried. The schematic representation of the adsorption-recycle process is shown in [Figure 2](#polymers-12-00289-f002){ref-type="fig"}. 3. Results {#sec3-polymers-12-00289} ========== 3.1. FT-IR Analysis {#sec3dot1-polymers-12-00289} ------------------- The FT-IR spectra of samples are shown in [Figure 3](#polymers-12-00289-f003){ref-type="fig"}(1). It can be seen that the main absorption bands for CCSP2, as depicted in curve c, were found at 3396, 2931, 1444, and 1027 cm^−1^. The peak at 3396 cm^−1^ was attributed to the stretching vibration of hydroxyl. The peak at 2931 cm^−1^ was caused by the stretching vibration of C--H. The peak at 1027 cm^−1^ was attributed to the stretching vibration of C--O--C. The peak at 1444 cm^−1^ was assigned to the bending vibration of C--N \[[@B32-polymers-12-00289],[@B44-polymers-12-00289]\]. For the FT-IR spectra of (a) CCS, the peaks at 3404, 2926, and 1018 cm^−1^ were attributed to the stretching vibration of O--H, C--H, and C--O--C, respectively. The peak at 1430 cm^−1^ in curve b (CCP) was similarly assigned to the bending vibration of C--N. The FT-IR spectra of the mixture adsorbent composed of CCSP and AC before and after treating the textile wastewater are shown in [Figure 3](#polymers-12-00289-f003){ref-type="fig"}(2); it can be seen that the characteristic peak of the hydroxyl group (3419 cm^−1^) was enhanced relatively after treating the textile wastewater, and the peak at 1475 cm^−1^ confirmed the existence of azo groups in the dye molecules. 3.2. XRD Analysis {#sec3dot2-polymers-12-00289} ----------------- As shown in [Figure 4](#polymers-12-00289-f004){ref-type="fig"}, it can be clearly seen that corn starch exhibited a typical A-type XRD pattern \[[@B45-polymers-12-00289]\], and strong diffraction bands centered at about 15°, 17°, 18°, and 23° (2*θ* degrees). However, the XRD pattern of CCS had only a dispersed broad peak, and the crystallization peaks of starch disappeared (see curve c), indicating that the modification could inhibit the crystallization of starch molecules \[[@B45-polymers-12-00289]\]. As for PVA, the intensity of its crystallization peak also significantly decreased after cross-linking and cationic modification. The XRD pattern of CCSP2 was similar to that of CCP. 3.3. SEM and TEM Analysis {#sec3dot3-polymers-12-00289} ------------------------- From the SEM images ([Figure 5](#polymers-12-00289-f005){ref-type="fig"}a--e), the particle sizes of CCS were larger than those of the other four samples. The morphology of most of the CCP was shaped with a good sphericity, although some particles congregated together. It can be obviously seen that the particle sizes of the CCSPs were all larger than that of CCP, but smaller than that of CCS, and gradually increased with the dosage increase of cationic starch in its preparation. This result was in good agreement with the analysis of the TEM images (see [Figure 5](#polymers-12-00289-f005){ref-type="fig"}f--h). 3.4. Particle Size Analysis {#sec3dot4-polymers-12-00289} --------------------------- The particle size distributions of CCS, CCP, and the CCSPs are shown in [Figure 6](#polymers-12-00289-f006){ref-type="fig"}. From [Figure 6](#polymers-12-00289-f006){ref-type="fig"}, no matter whether using ethyl alcohol or distilled water as the dispersion medium, the average diameter of CCS was the largest, while the average diameter of CCP was the smallest out of the five samples. This result was in good agreement with the morphology analyses of the samples (see [Figure 5](#polymers-12-00289-f005){ref-type="fig"}). The average diameters of the five kinds of microsphere samples all increased obviously when the dispersion medium was changed from ethyl alcohol to distilled water, indicating that CCS, CCP, and the CCSPs all had some of the swelling properties of water absorption. This result meant that the microsphere samples should be used together with filter aids (diatomite or activated carbon) in the column adsorption process. 3.5. Application in Wastewater Treatment {#sec3dot5-polymers-12-00289} ---------------------------------------- The adsorption properties of the samples were investigated using the fixed-bed column. Previous research has shown that the cationic group built-in CCS molecule could interact with dye molecules in wastewater via charge neutralization \[[@B46-polymers-12-00289]\]. The results of the fixed-bed column adsorption experiments are shown in [Table 1](#polymers-12-00289-t001){ref-type="table"}. Among these, the adsorption capacities of CCS, CCP, the CCSPs were calculated by subtracting the adsorption capacity of diatomite from that of the corresponding mixture adsorbents. From [Table 1](#polymers-12-00289-t001){ref-type="table"}, CCS, CCP, and the CCSPs all had a much larger adsorption capacity than that of AC when treating simulated dye wastewater, and CCP had the largest dye adsorption capacity, owing to its highest cationic group content. Meanwhile, they all had a smaller adsorption capacity than that of AC when treating a starch or PVA solution. CCS had a better adsorption capacity than that of CCP and the CCSPs when treating a starch solution, but CCP had a better adsorption capacity than that of CCS and CCSPs when treating a PVA solution. All of the CCSPs had a larger adsorption capacity than that of CCS, and had a smaller adsorption capacity than that of CCP when treating the simulated dye wastewater and PVA solution. Inversely, all of the CCSPs had a smaller adsorption capacity than that of CCS, and had a larger adsorption capacity than that of CCP when treating a starch solution. The composition of the CCSPs had a great influence on their adsorption capacity. The adsorption capacities of the CCSPs for Reactive Black 5, Reactive Orange 131, and PVA all gradually increased with the dosage increase of cationic PVA in their preparation, but decreased for starch. These results indicated that the adsorption capacities of the CCSPs could be developed based on the respective advantages of CCS and CCP when they were used to treat practical textile wastewater. Compared with CCS and CCP, the adsorption capacity of the CCSPs increased significantly when treating simulated textile wastewater. The adsorption capacities of the CCSPs were over 10 times larger than that of the commercial activated carbon (AC) when treating dye wastewater. According the zeta potential analysis (see [Table 2](#polymers-12-00289-t002){ref-type="table"}), the surfaces of the CCSPs all possessed a high positive charge, whereas the dye molecules had negative charges in the solutions. This means an electrostatic interaction between the cationic group built-in CCSP and dye molecules there should exist \[[@B46-polymers-12-00289]\]. In addition, CCSP had quite a similar molecular structure, with both the starch and PVA molecules, indicating that a hydrogen bonding mechanism might also exist. Therefore, the electrostatic interaction and hydrogen-binding interaction might be the main adsorption mechanisms of CCSP for treating textile wastewater. It is worthwhile to note that the mixture adsorbent composed of CCSP2 and AC (1:1 in weight) had the largest adsorption capacity compared with the other adsorbents when treating the simulated textile wastewater, which indicated that the combination of AC and CCSP2 could show an obvious synergetic effect on each other for adsorption, and that the starch, PVA, and dyes could be removed effectively from the simulated textile wastewater simultaneously. The effect of the bed height and flow rate on the adsorption capacity of the mixture adsorbent (CCSP2 and AC) to treat the textile wastewater was investigated, and the results are shown in [Table 3](#polymers-12-00289-t003){ref-type="table"}. It can be found that the column adsorption performance of the mixture adsorbent could be enhanced at a higher bed height and lower flow rate. The reason for this could be that the residence time of the adsorbate molecules in fixed-bed columns could be longer at the higher bed height and at the lower flow rate, and more adsorbate molecules would establish the adsorption equilibrium in the column \[[@B18-polymers-12-00289],[@B25-polymers-12-00289]\]. As shown in [Figure 7](#polymers-12-00289-f007){ref-type="fig"}, the breakthrough curves of the dye, starch, and PVA were diverse from each other, and the breakthrough point, defined as the point at which the pollutant concentration (any one of starch, or PVA, or dyes) of the effluent reached to above zero, of the starch first appeared, while at this point, the mixture adsorbent still had a high adsorption capacity to the dye and PVA. This result indicated that it could obtain the higher adsorption ability for treating textile wastewater by adjusting the composition of the mixture adsorbent based on the breakthrough curves of the adsorbates. 3.6. The Recycle of Disabled Adsorbent {#sec3dot6-polymers-12-00289} -------------------------------------- After treating the simulated textile wastewater, the particle surfaces of the mixture adsorbent composed of CCSP and AC would gather a large amount of starch, PVA, and dyes. It was difficult to be regenerated by the conventional desorption methods. In order to avoid producing solid waste, a chemical activation process was carried out to convert these disabled adsorbents into regenerated activated carbon. The SEM images of the original activated carbon (AC) and the regenerated activated carbon (RAC) that came from the disabled mixture adsorbent composed of CCSP2 and AC (mass ratio of 1:1) are shown in [Figure 8](#polymers-12-00289-f008){ref-type="fig"}. As can be seen from [Figure 8](#polymers-12-00289-f008){ref-type="fig"}, significant differences in the morphology of the RAC and AC were observed. The average particle size of the RAC was obviously smaller than that of the AC, and some honeycomb-shaped porous carbons were developed after carbonization. The Brunauer-Emmett-Teller (BET) data (see [Table 4](#polymers-12-00289-t004){ref-type="table"}) showed that the RAC had a larger surface area and pore volume than that of AC. This result indicated that the starch and PVA in CCSP2 should be converted into biomass carbon and porous carbon after carbonization \[[@B47-polymers-12-00289],[@B48-polymers-12-00289]\]. It is worth mentioning that the adsorption capacity of RAC on the simulated textile wastewater was higher than that of the original activated carbon, no matter whether used alone or in combination with CCSP2 (see [Figure 9](#polymers-12-00289-f009){ref-type="fig"}). This result indicated that the mixture adsorbent composed of CCSP2 and AC exhibited the advantages of a high adsorption capacity, recycling ability, and no solid waste when it was used as the adsorbent of the fixed-bed to treat the simulated textile wastewater. 4. Conclusions {#sec4-polymers-12-00289} ============== A novel modified starch/polyvinyl alcohol composite (CCSP) was prepared and employed as a highly efficient adsorbent for textile wastewater treatment. The CCSP was shaped with sphericity, and had some of the swelling properties of water absorption and a lower crystallinity. The dye adsorption capacity of CCSP was much larger than that of AC. The mixture adsorbent composed of CCSP and AC could make full use of the respective advantages of its components, and could remove starch, PVA, and dyes from the textile wastewater simultaneously, combined with the fixed-bed adsorption technique. The fixed-bed column adsorption process could be influenced by the bed height and flow rate. After adsorption, the disabled mixture adsorbent was converted into regenerated activated carbon for sustainable use by the chemical activation process, and the regenerated activated carbon had a higher adsorption capacity to the textile wastewater than AC. The developed method, through fixed-bed adsorption using CCSP, would be an excellent green textile wastewater treatment, on account of the high adsorption capacity, recycling ability, and no solid waste. Methodology, W.W. and X.Y.; formal analysis, X.L.; investigation, K.X.; data curation, K.X., W.W., and X.Y.; writing (original draft preparation), K.X.; writing (review and editing), X.Z. All authors have read and agreed to the published version of the manuscript. This research was financially supported by the Major Science and Technology Innovation Project of Shandong (no. 2019JZZY010507), the National Natural Science Foundation of China (no. 21808115), and the China Postdoctoral Science Foundation (no. 2019T120571 and no. 2018M632623). The authors declare no conflict of interest. ![Chemical structure of the anionic dyes used in this study.](polymers-12-00289-g001){#polymers-12-00289-f001} ![Schematic representation of the adsorption-recycle process. PVA---polyvinyl alcohol; CHPTAC---3-chloro-2-hydroxypropyltrimethylammonium chloride.](polymers-12-00289-g002){#polymers-12-00289-f002} ![(**1**) The FT-IR spectra of (**a**) cross-linked cationic starch (CCS), (**b**) cross-linked cationic PVA (CCP), and (**c**) CCSP with a mass ratio of CS/CP of 1:1 (CCSP2). (**2**) The FT-IR spectra of the mixture adsorbent was composed of CCSP2 and activated carbon (AC), (**a**) before and (**b**) after treating the textile wastewater.](polymers-12-00289-g003){#polymers-12-00289-f003} ![The XRD patterns of (**a**) starch, (**b**) PVA, (**c**) CCS, (**d**) CCP, and (**e**) CCSP2.](polymers-12-00289-g004){#polymers-12-00289-f004} ![SEM images of (**a**) CCS, (**b**) CCP, (**c**) CCSP1, (**d**) CCSP2, and (**e**) CCSP with a mass ratio of CS/CP of 1:2 (CCSP3). TEM images of (**f**) CCSP1, (**g**) CCSP2, and (**h**) CCSP3.](polymers-12-00289-g005){#polymers-12-00289-f005} ![Particle size distribution of samples by using (**a**) ethyl alcohol or (**b**) distilled water as the dispersion medium.](polymers-12-00289-g006){#polymers-12-00289-f006} ![Breakthrough curves in the fixed-bed column. Experimental operating conditions: the mixture adsorbent composed of CCSP2 and AC (mass ratio of 1:1; 10 g), flow rate = 2 mL/min.](polymers-12-00289-g007){#polymers-12-00289-f007} ![SEM images of the AC (**a~1~** and **a~2~**) and regenerated activated carbon (**b~1~** and **b~2~**).](polymers-12-00289-g008){#polymers-12-00289-f008} ![The adsorption capacities of the AC and RAC to the simulated textile wastewater in column.](polymers-12-00289-g009){#polymers-12-00289-f009} polymers-12-00289-t001_Table 1 ###### The results of the fixed-bed column adsorption experiments. Simulated Wastewater Solutions The Adsorption Capacity (mg/g) -------------------------------- -------------------------------- ------- ------- ------- ------- ------ ------- Reactive Black 5 572.0 693.5 605.0 629.5 661.0 54.0 378.0 Reactive Orange 131 494.0 605.5 539.0 560.0 573.5 48.0 340.5 Starch solution 12.4 9.3 11.4 10.6 9.9 16.2 14.4 PVA solution 7.7 16.2 10.1 13.4 15.1 19.6 17.7 Textile wastewater 40.6 52.5 68.6 73.5 60.9 56.7 93.1 polymers-12-00289-t002_Table 2 ###### The zeta potential of the prepared microspheres. Adsorbents Zeta Potential (mV) ------------ --------------------- CCS 20.3 CCP 30.4 CCSP1 22.7 CCSP2 26.2 CCSP3 28.1 polymers-12-00289-t003_Table 3 ###### Effect of bed height and flow rate on the column adsorption capacity of the mixture adsorbent (CCSP2 and AC) to treat the textile wastewater. Bed Height (cm) Flow Rate (mL/min) The Adsorption Capacity (mg/g) ----------------- -------------------- -------------------------------- 9.5 (10g) 2 93.1 7.6 (8g) 2 88.9 5.7 (6g) 2 80.5 9.5 (10g) 3 86.8 9.5 (10g) 4 77.0 polymers-12-00289-t004_Table 4 ###### Characterization of the regenerated activated carbon (RAC) and AC. Characterization BET Surface Area (m^2^/g) Pore Volume (cm^3^/g) Average Pore Diameter (nm) ------------------ --------------------------- ----------------------- ---------------------------- AC 386 0.39 4.12 RAC 581 0.53 3.13
{ "pile_set_name": "PubMed Central" }
昨年10月に脊髄損傷の大ケガを負い、手術を受けて長期のリハビリの末に復帰を果たした気象予報士の木原実さん(58)が27日、自身のブログを更新。負傷からちょうど1年目にあたって自身のMRI画像を公開した。 「あれから1年」とのタイトルでブログを更新した木原さん。「2017年10月27日。あの日、救急車で運び込まれた東京医大へ今日検診に行きました」と検診を受けて来たことを報告し「ちょうど一年。これは怪我をした日の画像。左が体の正面で右が背中側。上が頭蓋骨。でそこから4つ目の頸骨と五つ目の頚骨がずれている首のMRI画像です」と大きくずれていることが鮮明なMRI画像を公開。「気持ち悪かったらごめんなさい」と一言添えた。 手術後は動かない手が痛み、看護師を何度も呼んではさすってもらったことも。痛み止めの鎮静剤の副作用なのか「集中治療室の天井を錦絵の大名行列が動いていたり時計の文字盤がぐるぐるまわったり点滴のパイプにポリ袋がたくさん絡みついて見えたり」とおかしな幻覚にも苦しんだという。 「それから病院を移って5ヶ月のリハビリ。退院、仕事に復帰して7ヶ月。そしてちょうど一年。書かずにはいられなくてキーボードを叩きました」と、今回のブログを書くこと、そしてMRI画像を公開した思いを明かした木原さん。 「いつか忘れることが怖いからこのことを忘れないためにもここに書き残しておきます」とし、「一人ではどうしようもないことを大勢の人がなんとかしてくれたことを。寂しい気持ちを温めてくれたたくさんの人の言葉を。決して忘れないように。『ありがとう』そして立場が変わったら僕がもらったものを必ずお返ししますから。決して忘れないように。ここに記す。2018年10月27日」とケガからちょうど1年後の日付を刻んでブログを締めくくった。
{ "pile_set_name": "OpenWebText2" }
Q: Controller is not detecting Model Here in my Project Controller is not detecting Model.Am using ASP.net MVC3 ,Visual Studio 2010 But my other projects are working as well.How can i rectify this. I have re-installed VS2010 2 times but its working for this project. Here is my Controller Code using System; using System.Collections.Generic; using System.Linq; using System.Web; using System.Web.Mvc; using System.Web.Security; namespace OfficeAuto.Controllers { public class LoginController : Controller { public ActionResult Index() { return View(); } [HttpPost] public ActionResult Index(LoginModel model) { if (ModelState.IsValid) { if (DataAccess.DAL.UserIsValid(model.UserName, model.Password)) { FormsAuthentication.SetAuthCookie(model.UserName, false); return RedirectToAction("Index", "Home"); } else { ModelState.AddModelError("", "Invalid Username or Password"); } } return View(); } public ActionResult FranchIndex() { return View(); } } } A: It's a simple mistake; not a big problem You didn't add your Model reference: using OfficeAuto.Models;
{ "pile_set_name": "StackExchange" }
Two principles for adjusting the circumferential register in rotary printing machines are known from the prior art: first, a rotary shift of the forme cylinders via a planetary gear, or second, an axial shift of helical gears in the drive trains. However, it is known per se that planetary gears necessitate an expensive gear mechanism. On the other hand, in apparatus with helical gears, usually only a relatively coarse adjustment is usually possible. Furthermore, the problem generally arises in these geared mechanisms either that there is a great amount of play, or if they are designed for play-free operation then that they are extremely expensive to manufacture.
{ "pile_set_name": "USPTO Backgrounds" }
Development of an Automatic Diagnostic Algorithm for Pediatric Otitis Media. The artificial intelligence and image processing technology can develop automatic diagnostic algorithm for pediatric otitis media (OM) with accuracy comparable to that from well-trained otologists. OM is a public health issue that occurs commonly in pediatric population. Caring for OM may incur significant indirect cost that stems mainly from loss of school or working days seeking for medical consultation. It makes great sense for the homecare of OM. In this study, we aim to develop an automatic diagnostic algorithm for pediatric OM. A total of 1,230 otoscopic images were collected. Among them, 214 images diagnosed of acute otitis media (AOM) and otitis media with effusion (OME) are used as the database for image classification in this study. For the OM image classification system, the image database is randomly partitioned into the test and train subsets. Of each image in the train and test sets, the desired eardrum image region is first segmented, then multiple image features such as color, and shape are extracted. The multitask joint sparse representation-based classification to combine different features of the OM image is used for classification. The multitask joint sparse representation algorithm was applied for the classification of the AOM and OME images. The approach is able to differentiate the OME from AOM images and achieves the classification accuracy as high as 91.41%. Our results demonstrated that this automatic diagnosis algorithm has acceptable accuracy to diagnose pediatric OM. The cost-effective algorithm can assist parents for early detection and continuous monitoring at home to decrease consequence of the disease.
{ "pile_set_name": "PubMed Abstracts" }