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tomekkorbak

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pii-pile-chunk3-0-50000

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[ "The activists who championed property tax caps and lawmaker term limits said they planned to begin circulating petitions for a ballot measure that would make the California Legislature a part-time body." ]

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[ "This invention relates generally to phase modulation of a laser beam signal carrier conducted through an optical fiber cable, and is related to the disclosure in my prior copending application, U.S. Ser. ", "No. ", "715,786, filed Mar. 25, 1985, now replaced by continuation application, Ser. ", "No. ", "436,935 filed Nov. 13, 1989 and the disclosures in U.S. Ser. ", "No. ", "613,835, filed May 24, 1984, (now U.S. Pat. ", "No. ", "4,763,030 to Clark et al. ", "issued Aug. 9, 1988) and its parent application, U.S. Ser. ", "No. ", "438,211, filed Nov. 1, 1982, (abandoned), the present application being a continuation-in-part of all of the foregoing applications because of portions of the disclosures therein in common representing my innovative contributions.", "\nIt is generally well known that optical fibers are capable of transmitting information of significantly higher density than electrical conductors because of the high frequency monochromatic beam of coherent light (laser beam) conducted therethrough as the signal carrier. ", "Such high information density transmission has heretofore been limited, as a practical matter, by a relatively narrow bandwidth of the encoding device operatively connected to the laser beam modulator.", "\nModulation of a laser beam conducted through an optical fiber cable was explicitly proposed for encoded signal generating purposes in my prior copending application, Ser. ", "No. ", "715,786, aforementioned, while such purpose was inferentially referred to in U.S. Pat. ", "No. ", "4,763,030 to Clark et al., ", "aforementioned as well as in U.S. Pat. ", "No. ", "4,433,291 to Yariv et al. ", "According to the invention as claimed in my aforementioned prior copending application, Ser. ", "No. ", "715,786, stimulated excitation energy is reflected within a resonance cavity formed between spaced end mirrors within an optical fiber core in order to effect analog frequency modulation of the laser beam carrier by magnetostrictive change in cavity dimension. ", "Modulation encoding data was therefore applied magnetostrictively to the resonance cavity portion of the fiber cable through a conductive coating underlying the outer magnetostrictive sheathing.", "\nAccording to the aforementioned patents to Clark et al. ", "and Yariv et al., ", "phase modulation of a laser beam carrier may be magnetostrictively effected by dimensional change in optical path length caused by strain along a core portion of the fiber cable merely covered by the outer magnetostrictive sheathing. ", "The Clark et al. ", "patent furthermore claims a particular metallic glass composition for the magnetostrictive sheathing that is rendered strain-free by magnetic annealing in order to enhance detection of the magnetic field being sensed as the paramount function of its magnetostrictive activity.", "\nIt is therefore an important object of the present invention to provide a system for more directly and economically modulating a laser beam signal carrier conducted through an optical fiber cable for high density data transmission of signals originating from an encoder having a relatively large bandwidth.", "\nA further object in accordance with the foregoing object is to magnetostrictively modulate a laser beam conducted through an optical fiber cable by encoded control and application of a modulating magnetic field having certain beneficial relationships to the outer magnetostrictive sheathing that is annealed to enhance signal carrier modulation." ]

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[ "Arcobacter cloacae sp. ", "nov. ", "and Arcobacter suis sp. ", "nov., ", "two new species isolated from food and sewage.", "\nThree strains recovered from mussels (F26), sewage (SW28-13(T)) and pork meat (F41(T)) were characterized as Arcobacter. ", "They did not appear to resemble any known species on the basis of their 16S rDNA-RFLP patterns and the rpoB gene analyses. ", "However, strains F26 and SW28-13(T) appeared to be the same species. ", "The 16S rRNA gene sequence similarity of strains SW28-13(T) and F41(T) to the type strains of all other Arcobacter species ranged from 94.1% to 99.6% and 93.4% to 98.8%, respectively. ", "Phenotypic characteristics and the DNA-DNA hybridization (DDH) results showed that they belonged to 2 new Arcobacter species. ", "A multilocus phylogenetic analysis (MLPA) with the concatenated sequences of 5 housekeeping genes (gyrA, atpA, rpoB, gyrB and hsp60) was used for the first time in the genus, showing concordance with the 16S rRNA gene phylogenetic analysis and DDH results. ", "The MALDI-TOF mass spectra also discriminated these strains as two new species. ", "The names proposed for them are Arcobacter cloacae with the type strain SW28-13(T) (=CECT 7834(T)=LMG 26153(T)) and Arcobacter suis with the type strain F41(T) (=CECT 7833(T)=LMG 26152(T))." ]

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[ "JCCA President’s Report\n\nThe cherry blossoms are making an early appearance. ", "The signs of spring are everywhere in Metro Vancouver, including the Annual General Meeting of the Greater Vancouver Japanese Canadian Citizens’ Association which took place on March 14.", "\n\nThere was a good turnout of people, and we were honoured to have Maryka Omatsu, the first Asian female judge in Canada and a key member of the National Association of Japanese Canadians (NAJC) negotiating team who won Redress for Japanese Canadians, attend our AGM. ", "A few people were trying to figure out her identity when outgoing president Derek Iwanaka pointed to a recent copy of The Bulletin magazine with an article and photos of her, and confirmed it really was her in the audience.", "\n\nThe AGM is an opportunity to hear about the work of the JCCA, and what is coming up in the year. ", "The Human Rights Committee (HRC) report to the AGM covered a number of events in the Lower Mainland and on Vancouver Island. ", "One of the highlights was the work at Reconciling Injustices in a Pluralistic Canada. ", "HRC members joined other community leaders in one of the most comprehensive events ever held in Canada to provide knowledge and expertise on the reconciliation of injustice.", "\n\nOther events for the JCCA and HRC included Shinnenkai, Keirokai, the 100th anniversary of the Komagata Maru, 29th Annual Miners Memorial Weekend and 44th Annual Pacific Northwest Labour History Association Conference in Cumberland, Annual Wild Salmon Barbeque at Powell Street Festival, Musubi DIY (Do It Yourself) kit fundraiser, organizing the NAJC AGM and joint events with the Japanese Canadian Young Leaders (JCYL) conference, the world premiere of the Vancouver Asahi film, 25th Annual Women’s Memorial March, opening of the “χ̓əσναʔəμ, τηε χιτψ βεφορε τηε χιτψ” exhibits, and the First Annual JCCA Community Bowl-a-thon Fundraiser.", "\n\nWe thank past board members, Connie Kadota, Gabe Nutley, Paul Esslinger, and Tomiye Ishida for their hard work and dedication to the JCCA. ", "And very special thanks to our past president Derek Iwanaka who gave up valuable family time for us, without complaint. ", "We depended upon his endless energy, support, and he always did the work with incredible grace and a smile. ", "For all of you, we know we continue to have your support and no doubt we will see you at some of the upcoming events. ", "Except this time, you’ll get to enjoy the events as participants, and not have to do all the work behind the scenes.", "\n\nThe enthusiasm and work will continue with a new board, composed of some new directors and some returning directors, who were elected at the AGM. ", "The GVJCCA Board for 2015/2016 includes Chika Buston, May Hamanishi, Judy Hanazawa, Angela Kruger, Greg Masuda, Gary Matson, Yuji Matson, Jack Matsushita, Rachael Nakamura, Lorene Oikawa, Rutsu Shikano, April Shimizu, Kathy Shimizu, Susanne Tabata, and Grace Eiko Thomson. ", "The JCCA is in good hands with the experience and skills of this new board.", "\n\nWe’re also excited to have the Japanese Canadian Young Leaders of Vancouver join the JCCA as a sub-committee. ", "This group of local young leaders came together at last year’s JCYL conference and have continued to meet since then. ", "We’re looking forward to working with their energy and exploring new ideas as we learn from each other.", "\n\nMembers of the board will be busy with a number of upcoming events. ", "We hope to see many from the Japanese Canadian community at Hastings Park on April 26th for the unveiling of four panels introducing the history of Japanese Canadians who were incarcerated at Hastings Park in 1942. ", "The event will include a walking tour and reception. ", "On June 14th, we’ll be practising our swing and having some fun at the 3rd Annual Tonari Gumi and JCCA Golf Tournament. ", "Join us to support Japanese Canadian seniors. ", "Look for more details on these and other events posted in The Bulletin. ", "Happy spring from the GVJCCA Board!" ]

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[ "//---------------------------------------------------------------------------\n// Copyright (c) Microsoft Corporation. ", " All rights reserved.", "\n//\n// This file is automatically generated. ", " Please do not edit it directly.", "\n//\n// File name: D2DBaseTypes.h\n//---------------------------------------------------------------------------\n#pragma once\n\n\n#ifndef _D2DBASETYPES_INCLUDED\n#define _D2DBASETYPES_INCLUDED\n\n#ifndef COM_NO_WINDOWS_H\n#include <windows.h>\n#endif // #ifndef COM_NO_WINDOWS_H\n\n#ifndef D3DCOLORVALUE_DEFINED\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D3DCOLORVALUE\n//\n//------------------------------------------------------------------------------\ntypedef struct D3DCOLORVALUE\n{\n FLOAT r;\n FLOAT g;\n FLOAT b;\n FLOAT a;\n\n} D3DCOLORVALUE;\n\n#define D3DCOLORVALUE_DEFINED\n#endif\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_POINT_2U\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_POINT_2U\n{\n UINT32 x;\n UINT32 y;\n\n} D2D_POINT_2U;\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_POINT_2F\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_POINT_2F\n{\n FLOAT x;\n FLOAT y;\n\n} D2D_POINT_2F;\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_RECT_F\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_RECT_F\n{\n FLOAT left;\n FLOAT top;\n FLOAT right;\n FLOAT bottom;\n\n} D2D_RECT_F;\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_RECT_U\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_RECT_U\n{\n UINT32 left;\n UINT32 top;\n UINT32 right;\n UINT32 bottom;\n\n} D2D_RECT_U;\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_SIZE_F\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_SIZE_F\n{\n FLOAT width;\n FLOAT height;\n\n} D2D_SIZE_F;\n\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_SIZE_U\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_SIZE_U\n{\n UINT32 width;\n UINT32 height;\n\n} D2D_SIZE_U;\n\ntypedef D3DCOLORVALUE D2D_COLOR_F;\n\n//+-----------------------------------------------------------------------------\n//\n// Struct:\n// D2D_MATRIX_3X2_F\n//\n//------------------------------------------------------------------------------\ntypedef struct D2D_MATRIX_3X2_F\n{\n FLOAT _11;\n FLOAT _12;\n FLOAT _21;\n FLOAT _22;\n FLOAT _31;\n FLOAT _32;\n\n} D2D_MATRIX_3X2_F;\n\n#endif // #ifndef _D2DBASETYPES_INCLUDED\n" ]

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[ "/*\n *\n * Copyright 2015 gRPC authors.", "\n *\n * Licensed under the Apache License, Version 2.0 (the \"License\");\n * you may not use this file except in compliance with the License.", "\n * You may obtain a copy of the License at\n *\n * http://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing, software\n * distributed under the License is distributed on an \"AS IS\" BASIS,\n * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n * See the License for the specific language governing permissions and\n * limitations under the License.", "\n *\n */\n\n#ifndef GRPC_CORE_LIB_IOMGR_ENDPOINT_PAIR_H\n#define GRPC_CORE_LIB_IOMGR_ENDPOINT_PAIR_H\n\n#include \"src/core/lib/iomgr/endpoint.h\"\n\ntypedef struct {\n grpc_endpoint *client;\n grpc_endpoint *server;\n} grpc_endpoint_pair;\n\ngrpc_endpoint_pair grpc_iomgr_create_endpoint_pair(const char *name,\n grpc_channel_args *args);\n\n#endif /* GRPC_CORE_LIB_IOMGR_ENDPOINT_PAIR_H */\n" ]

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[ "Gregory Isaacs\n\nOne of Jamaica's most beloved vocalists who was as pertinent in dancehalls as he was in bedrooms, Gregory Isaacs' career stretched over 30 years. ", "From the heady days of reggae through lovers rock, a genre he virtually invented, his talent reached into the modern age. ", "Born in the Fletcher's Land area of Kingston, Jamaica, on July 15, 1951, Isaacs arrived in the music business via the talent show circuit, a tried and true formula for many of the island's budding singing stars. ", "Byron Lee was the first in the industry to spot his talent and brought him and Winston Sinclair into the studio to record the duet \"Another Heartbreak\" in 1968. ", "Sadly, it went nowhere, and Isaacs decided to try his fortunes with a new vocal trio, the Concords. ", "They set up home at Rupie Edwards' Success label, and over the next couple of years released a number of singles, including one with Prince Buster, but none caught the attention of the Jamaican public.", "\n\nIn 1970, the Concords folded and Isaacs struggled on alone. ", "His initial self-productions were similarly unsuccessful, while further cuts with Edwards did no better. ", "Regardless of this poor track record, in 1973 Isaacs set up his own record store and label, African Museum, in partnership with Errol Dunkley, a young singer with a string of hits to his own name. ", "Apparently some of Dunkley's own magic wore off and one of the label's first releases, Isaacs' own self-produced \"My Only Lover,\" was an immediate hit and the floodgates opened wide. ", "Besides African Museum's offerings, Isaacs helped keep the label solvent by recording with virtually every producer on the island for a stream of hits that showed no sign of abating.", "\n\nBetween 1973 and 1976 alone, the singer released more material than most artists do in a lifetime, virtually all of it timeless classics. ", "Isaacs' early albums inevitably gathered up strings of these hits, while usually also including a few new songs. ", "Released in 1975, In Person, for example, features a heavy-hitting collection of successes for producer Alvin Ranglin and was followed up in 1977 by Best Of, Vol. ", "1 and Best Of, Vol. ", "2 in 1981. (", "The Heartbeat label would bundle up this material across three CDs for the U.S. market: My Number One, Love Is Overdue, and The Best Of, Vols. ", "1-2). ", "Similarly, 1976's All I Have Is Love includes a hit-filled package of Sydney Crooks productions. ", "Extra Classic, co-produced by Isaacs, Pete Weston, and Lee Perry, is also stuffed with chartbusters and showcases the singer's deepest roots material. ", "The latter album appeared on African Museum, cut with a diverse range of producers, across three volumes titled Over the Years.", "\n\nIn 1977, the U.K. was treated to an equally dread experience via Mr. Isaacs, released on Dennis Brown's DEB label. (", "Turnabout is fair play and Brown had released several classic albums of his own on African Museum.) ", "By this time, the two polar sides of Isaacs were apparent: the roots singer, whose emotive sufferer's songs and cultural numbers were filled with fire, and the crooning lover, whose passionate declarations of devotion quivered with emotion. ", "Eventually, the vocalist's ties to the lovers rock scene saw his reputation as the Cool Ruler overshadow the equally impassioned roots performer, but his work in the latter half of the '70s shows his heart was true to both. ", "Isaacs was quick to take advantage of the rise of the DJs; producer Ranglin paired him with a string of cutting-edge toasters for another flood of hits, beginning in 1978. ", "It was at this time that he first hooked up with DJ Trinity, a partnership maintained into the next decade across a stream of seminal singles.", "\n\nBy now, Isaacs was too big a talent to ignore, and in 1978 he signed with Virgin's Frontline label. ", "That same year, the singer had a featured role in the classic Rockers movie. ", "Inexplicably, however, as Isaacs was poised on the brink of international success, he failed to set the rest of the world alight. ", "His debut Frontline album, the excellent Cool Ruler, barely ruffled a feather outside Jamaica. ", "It did, however, provide most of the material for Slum: Gregory Isaacs in Dub, which boasted fat rhythms by the Revolutionaries, keyboardist Ansel Collins with Prince Jammy, and Isaacs himself behind the mixing board. ", "Cool Ruler's follow-up, 1979's Soon Forward, was filled with hits that would soon become classics, but also did not make the slightest dent on the world beyond Jamaica. ", "The latter's title track was produced by Sly & Robbie and gave the pair's new Taxi label its first hit. ", "Isaacs cut several more great singles with the team, which were brought together for 1980's Showcase album. ", "Even with Frontline out of the picture, Isaacs continued going from strength to strength. ", "Inking a U.K. deal with the Pre label and with his fortunes secure in Jamaica, the artist continued turning out hit after hit. ", "His Pre debut, The Lonely Lover, and its follow-up, 1981's More Gregory, both boast the Roots Radics and a host of Jamaican hits that range from lovers rock to deep roots and on to the emerging dancehall sound. ", "No wonder the singer was a hands-down success at the first Reggae Sunsplash. ", "It was at this point that Island stepped up to the plate and signed the singer to their Mango imprint.", "\n\nVirgin label head Richard Branson must have cursed his own stupidity, as Isaacs immediately repaid his new label's faith with his biggest hit of all, \"Night Nurse.\" ", "The song titled his Mango debut, another masterpiece, and again featured the steaming Roots Radics. ", "Amazingly, as the song spread around the world, the singer sat whiling his time away in a Jamaican jail as the result of a drug arrest. ", "He was released later in 1982 and immediately entered the studio to record Out Deh with producers Errol Brown and Flabba Holt. ", "Once again able to take the stage, Isaacs played a series of awe-inspiring shows over the next year, captured on both 1983's Live at Reggae Sunsplash and the following year's Live at the Academy Brixton albums. ", "Behind the scenes, Isaacs joined the shadowy conspiracy of vocalists determined to return vocalists to their rightful place in the market by flooding the shops with music. ", "An all-star cast of veteran singers joined the plot, including Dennis Brown, John Holt, Delroy Wilson, and many more, but none would reach the prolificacy of the determined Isaacs.", "\n\nIt's been estimated that the singer released up to 500 albums (including compilations) in Jamaica, the U.K., and the U.S. combined. ", "The singer recorded with anyone and everyone and was just as quick to revise his old songs as create fresh ones. ", "Although none of these are entirely disposable, inevitably the quality of Isaacs full-length work began to decline in the mid-'80s. ", "The Ted Dawson-produced Easy and All I Have Is Love, Love, Love, for example, certainly have their charms, but are hardly crucial. ", "But that didn't mean the hits had dried up. ", "Those 500 records are albums only, not singles, and the shops (and charts) continued to overflow with Isaacs' 45s. ", "And the rise of ragga just added hot new producers to the singer's packed recording diary.", "\n\nIn 1984, producer Prince Jammy, equally intrigued with the changing sounds of dancehall, brought Isaacs into the studio for the superb Let's Go Dancing, while also pairing the singer with Dennis Brown for Two Bad Superstars Meet. ", "The latter proved so popular that a second set, Judge Not, appeared the next year. ", "The two singers dueted again on a track on Isaacs' 1995 solo album, Private Beach Party, which also boasted an exquisite \"Feeling Irie,\" which paired him with Carlene Davis. ", "The album was produced by Gussie Clarke, a man with the determined goal of creating an international crossover sound via his own one-stop operation à la Motown. ", "He hadn't quite succeeded yet, but Private Beach Party helped lay the groundwork.", "\n\nIn 1987 Isaacs collaborated with the equally sweet-singing DJ Sugar Minott for the Double Dose album. ", "Isaacs swiftly found himself a dancehall hero. ", "It was during this period that Isaacs also recorded an album for King Tubby. ", "Warning boasts the magnificent rhythms of the Firehouse Crew, and a dark atmosphere of foreboding slinks through the entire set. ", "It was not released at the time and only came to light after the great man's murder in 1989. ", "By then, Isaacs had already stormed the world, digital or otherwise, with the 1988 Gussie Clarke-produced \"Rumours\" (whose rhythm would launch scores of further version hits, including J.C. Lodge's \"Telephone Love,\" an even bigger smash). ", "The masterful Red Rose for Gregory boasts a clutch of hits beside equally sublime non-45 tracks, all cut for Clarke. ", "The pair's follow-up, 1989's I.O.U., is arguably an even stronger album. ", "That same year, Clarke reunited Isaacs and Brown for the No Contest album. ", "Isaacs continued to cut seminal singles with Clarke, while also recording with a host of other producers. ", "In 1990, the singer joined forces with Niney Holness for the excellent On the Dance Floor album. ", "The next year saw Fatis at the controls for Call Me Collect, which boasts Sly & Robbie and Clevie, while Bobby Digital adds his unique production sound to 1991's Set Me Free. ", "And having inked a deal with RAS in the U.S., that label's head, Doctor Dread, oversaw 1992's memorable Pardon Me. ", "Philip Burrell was in the producer's chair for 1994's Midnight Confidential album.", "\n\nBut there was a slew of lesser titles as well; while Isaacs seemed able to always hit the mark with singles, albums required more effort than he was often willing, or able, to give. ", "No Intention and Boom Shot, both from 1991, are workaday records, with the singer on autopilot. ", "Past & Future sounds promising and features such illustrious guests as Sly & Robbie, J.C. Lodge, Winston Riley, and Boris Gardiner on material both new and old, but it's obvious that no one's heart is really in it, Isaacs' least of all. ", "The patchy Rudie Boo (released by Heartbeat in the U.S. as My Poor Heart) suffers from a similar lack of interest on the singer's part. ", "At least 1993's Unlocked featured a stronger set of songs, but much of Isaacs' releases throughout the '90s were hit-and-miss affairs. ", "Midnight Confidential, for example, is totally disposable, except for the magnificent \"Not Because I Smile.\" ", "Most of the albums frequently revisit older hits, which even at their worst tend to stand out from the newer fare.", "\n\nYounger or less experienced producers were in particular danger, and as the years progressed it was only the toughest and most innovative producers who could coax the best from the singer. ", "Alvin Ranglin, for example, wrung an exquisite set of emotionally riven songs from Isaacs for 1995's Dreaming. ", "Mafia & Fluxy's fat, dubby rhythms inspired one of the singer's best performances in ages for Hold Tight two years later. ", "The wisest course in negotiating one's way through the minefield of latter-day Isaacs is to look at the production credits. ", "If you like the slick production that's the trademark of Bunny Gemini, chances are you'll appreciate 1996's Mr. Cool. ", "Junior Reid likes diversity, and thus, Not a One Man Thing has that in spades, from the slacker-themed \"Big Up Chest\" to a remodeled \"Don't Dis the Dance Hall.\" ", "Steely & Clevie laid down the rhythms for 1998's Hard Core Hits; if you're not a fan of their digitized dancehall mayhem, choose another album. ", "King Jammy is let loose on 1999's Turn Down the Lights, and while not up to the standards of Let's Go Dancing, it's still an enjoyable ride. ", "Joe Gibbs, Errol Thompson, and Sydney Crooks lent their expertise to So Much Love, another one of Isaacs better later offerings.", "\n\nThe singer began the new millennium with aplomb on Father and Son, which, true to the title, features Isaacs and his son Kevin. ", "The duets are gorgeous, while the younger Isaacs is given plenty of room to prove that his talent is equal to his dad's. ", "The next year, I Found Love marked the second time the two worked together. ", "In between times, the singer continued to impress audiences live, and his recorded output continued sporadically during the remainder of the decade. ", "However, by 2007 he had reportedly lost his teeth due to crack cocaine addiction, and he was later diagnosed with lung cancer, which spread and ultimately took his life. ", "Gregory Isaacs died at his home in London on October 25, 2010 at the age of 59." ]

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[ "1. ", "Technical Field\nThe present invention relates to a semiconductor device.", "\n2. ", "Related Art\nA memory device capable of storing data among the semiconductor devices is divided into a volatile memory device and a non-volatile memory device according to maintenance of the data when a power supply is cut. ", "The volatile memory device is a memory device in which data dissipates when the power supply is cut, and dynamic random-access memory (DRAM) and static random-access memory (SRAM) belong to thereto. ", "The non-volatile memory device is a memory device in which stored data is maintained as it is even though the power supply is cut, and a flash memory device belongs thereto.", "\nFor example, in a case of a floating gate-type non-volatile memory device storing data by injecting charges to a floating gate electrode, a program/erase operation is performed by a Fowler-Nordheim tunneling (F-N tunneling), and in this case, a program operation is performed by using a high voltage, such as a program voltage Vpgm and a pass voltage Vpass.", "\nAccordingly, the non-volatile memory device includes a high voltage transistor for transmitting a high program voltage Vpgm or pass voltage Vpass supplied to a global word line.", "\nA semiconductor memory device has the increased number of memory cells disposed within one memory block in order to implement high capacity, and thus the number of word lines connected with the memory cells is gradually increased. ", "Accordingly, the number of high voltage transistors for transmitting an operation voltage to the word lines by connecting the word lines with the global word lines is also increased, thereby causing a problem of an increase in an area." ]

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[ "Numerous strategies have been developed to assist vehicle operators during parking (e.g., reversing) maneuvers. ", "Such vehicle park assist systems may include radar and/or ultrasonic emitters and sensors designed to alert the operator when object(s) are in vehicle's path. ", "One or more visual and/or audio signals may alert the operator of an imminent collision so that appropriate countermeasures may be taken.", "\nAn example of a park assist system is a hybrid ultrasonic and radar backup aid disclosed in U.S. Pat. ", "No. ", "5,754,123 issued to Nashif et al. ", "on May 19, 1998. ", "An apparatus according to the '123 patent includes ultrasonic sensors positioned at the rear of the vehicle providing continuous range information to a control module for objects that are detected as being relatively close to the vehicle. ", "A radar system provides range information to the control module for objects detected beyond the range of the ultrasonic system. ", "At low speeds below a predetermined minimum speed level or when the system is placed in the “park” mode for parking, the radar information is ignored and only the ultrasonic information is used to warn the vehicle operator. ", "At a relatively high threshold backup speed, the vehicle operator is immediately warned to slow down, whether or not an object is detected in the vehicle path. ", "Between the lower and upper threshold speeds, both the ultrasonic system and the radar system are used to continuously range and detect any objects that enter their respective detection fields. ", "The control module causes an alarm device to warn the operator as to how close the vehicle is to the closest object.", "\nAnother example of a park assist system is one disclosed in U.S. Pat. ", "No. ", "6,594,614 issued to Studt et al. ", "on Jul. 15, 2003. ", "A warning system according to the '614 patent scans behind the vehicle with an emitter/sensor system and determines a time-to-collision with the object based on distance to the object and vehicle speed. ", "Based upon the time-to-collision, a simple combination of visual and audio signals is designed to let the operator known of the imminency of a collision with the object so that the operator may react and make appropriate countermeasures.", "\nOther examples of vehicle park assist strategies include those disclosed by U.S. Pat. ", "No. ", "6,446,998 issued to Koenig et al. ", "on Sep. 10, 2002; U.S. Pat. ", "No. ", "6,476,730 issued to Kakinami et al. ", "on Nov. 5, 2002; and U.S. Pat. ", "No. ", "5,754,123 issued to Adachi et al. ", "on Aug. 28, 2001.", "\nAlthough these and other strategies may provide effective assistance to vehicle operators during parking maneuvers, the use of attached vehicle trailers may interfere with the proper function of such warning systems. ", "For example, a trailer attached to a rear portion of the vehicle may inappropriately and continuously activate visual and/or audio signals of an impending collision. ", "To overcome this, vehicles may include a “switch” to deactivate the warning system. ", "The use of a switch may increase the cost and complexity of the warning system and require the operator to manually de-activate and activate system. ", "In some cases, the operator may de-activate the system and then forget to re-activate the system once the trailer is removed. ", "What is needed, then, is a strategy for detecting the presence of a trailer thereby allowing for the automatic deactivation and activation of a park assist system.", "\nTherefore, it would be desirable to provide a trailer detection circuit for a vehicle park assist system that overcomes the aforementioned and other disadvantages." ]

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[ "Fairs & Folk Festivals\n\nLast update: 10/11/2018\n\nAs is well known, the Emilia Romagna Region is a paradise of taste. ", "With its wealth of recognized and certified foods, be it on this side or on the other side of the Sillaro (the River that separates Emilia and Romagna) is really of little importance: your palate will most certainly be satisfied.", "\n\nThe town of Imola marks the beginning of the Romagna part of the region, land of hospitality and ingenuity, where the local cuisine reflects the open and friendly character of its people and the concept of sitting down at the table with friends, drinking and eating well is an absolute necessity.", "\n\nThe kitchen is the domain of “sfoglina” pasta (heir of “azdora”, the stalwart housewife, who presides over the household government and the true symbol of hard work) who, with her experience and skill, prepares quintessential meals in Romagna: such as the traditional minestrina or soup. ", "Even today, according to tradition, the dough is made by hand and rolled out with a rolling pin in order to achieve a uniform thickness and a good degree of “roughness”, which is fundamental to its ability to better accommodate the condiments. ", "As a result, there are many pasta formats with fanciful names: tortellini, cappelletti, ravioli, tagliatelle, strozzapreti, strichetti, quadrettini (little squares), maltagliati, garganelli, just to name the most famous ones.", "\n\nHowever, the minestrina or soup is not the only star of the Imolese table; in fact, every meal worthy of respect requires a good accompaniment of wine. ", "Thanks to its favourable position between the Apennines and the plains, a glorious viticultural tradition has developed here, so much so that the ‘Colli d’Imola’ production can truly boast the title of D.O.C. (Controlled Designation of Origin)\n\nA demonstration of excellence and the viticultural heritage value of the area, in Dozza (a small town located on the hills of Imola) the Emilia Romagna Regional Enoteca was born here. ", "Right here, in the cellars of the Rocca (fortress), they are gathered and made available for purchase, circa 1,000 labels from over 200 producers, selected by a technical committee of sommeliers and industry professionals.", "\n\nIn this gastronomic excursus (narrative digression), one cannot help to mention the “piadina” or flatbread. ", "Famous just about everywhere, it can be enjoyed during meals as a bread substitute, or as a main dish when folded in half and stuffed with meats, cheeses, vegetables and sauces.", "\n\nOne of the most typical fillings and appreciated is the one known as “Squacquerone di Romagna” DOP (fresh soft cheese) and Arugula salad. ", "The piadina or flatbread is well-known throughout the territory, thanks to the many kiosks, where at any time during the day; you can taste this speciality and all its combinations.", "\n\nThe importance that food plays in this area of Italy is known to most and the town of Imola clearly falls into this context. ", "In fact, every year, a festival to promote the culinary culture of this area is organized in the city, a kermesse festival dedicated to a food product to be explored in all of its aspects: the Baccanale or Bacchanal.", "\n\nThis intense love for the table is also accompanied by the handing down of folklore and rural traditions: there are countless festivals and popular festivals that, since ancient times, follow one another, harkening back to a forgotten and by-gone era of traditional dishes." ]

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[ "The Justice Department has opened a probe to investigate child sexual abuse within Pennsylvania's Roman Catholic Church, the Archdiocese of Philadelphia confirmed to Fox News.", "\n\n“The Archdiocese of Philadelphia has received a subpoena issued by a federal grand jury, which requires the production of certain documents,\" a statement read. \"", "The Archdiocese will cooperate with the United States Department of Justice in this matter.”", "\n\nSTUNNING FINDINGS ON REPORT OF CATHOLIC CHURCH ABUSE: PA. ", "PRIESTS MOLESTED MORE THAN 1,000 CHILDREN\n\nFederal prosecutors served subpoenas to the church last week after a grand jury report released in August found priests in the eastern state molested more than 1,000 children.", "\n\nThe Archdiocese of Erie confirmed it has received a subpoena from the Justice Department, and \"its counsel is in conversation\" with federal investigators.", "\n\nHundreds of priests were said to have molested more than 1,000 children — and possibly many more — since the 1940s, and senior church officials allegedly covered up the abuse, according to the report.", "\n\nThe grand jury put the number of abusive clergy at around 300. ", "In nearly all of the cases, the statute of limitations has run out, meaning that criminal charges cannot be filed. ", "More than 100 of the priests are dead, and many others are retired or have been dismissed from the priesthood or put on leave.", "\n\n“Priests were raping little boys and girls, and the men of God who were responsible for them not only did nothing. ", "They hid it all,” Attorney General Josh Shapiro said at a news conference at the time.", "\n\nNow the Justice Department is investigating to see if any federal crimes were committed by priests, bishops, seminarians and others.", "\n\nOPINION: THE CATHOLIC CHURCH IS GUILTY OF A GRAVE MORAL FAILURE FOR ALLOWING MASSIVE SEXUAL ABUSE OF CHILDREN\n\nU.S. Attorney William McSwain, of Philadelphia, demanded bishops turn over any evidence that anyone in their ranks took children across state lines for illicit purposes, sent sexual images or messages via phone or computer, instructed anyone not to contact police, reassigned suspected predators, or used money or other assets as part of the scandal.", "\n\nFox News' Frank Miles and Jake Gibson and The Associated Pres contributed to this report." ]

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[ "Il segreto di Susanna\n\nIl segreto di Susanna (English: Susanna's Secret, German: Susannens Geheimnis) is an intermezzo in one act by Ermanno Wolf-Ferrari to an Italian libretto by Enrico Golisciani. ", "The premiere of the opera was in German, in a translation by Max Kalbeck, at the Hoftheater in Munich on 4 December 1909.", "\n\nRoles\n\nSynopsis\nTime: Early 20th century\nPlace: Piedmont\n\nCount Gil returns home suspecting that he has seen his wife, Susanna, walking alone in the street, something he had forbidden her to do after their wedding. ", "He is relieved when he discovers that she is playing the piano in the living room. ", "However, it was the countess whom he had seen but she returned home shortly before her husband.", "\n\nGil's happiness is short-lived. ", "The room smells of tobacco, and he is surprised since he does not smoke and neither does Susanna, nor the servant, Sante. ", "Suddenly a horrible thought strikes him: is it possible that Susanna is unfaithful to him with a smoker? ", "He speaks with his wife and is soon ashamed of having such suspicions. ", "Gil wants to hug Susanna, but he notices that the tobacco smell comes from Susanna's clothes. ", "She finally admits to having a secret, but does not want to tell him what it is. ", "Gil becomes angry and starts to turn the house upside-down after she locks herself in her bedroom. ", "Finally, as Gil is leaving the house to go to his club, she brings him his umbrella. ", "He softens, they become reconciled, and he exits.", "\n\nAs soon as he leaves the house, she closes the door and opens the small packet she gave to Sante when she came home. ", " She takes out a cigarette and the two smoke. ", "That is her secret! ", "But while she is smoking with Sante, Gil comes back. ", "Smelling the tobacco he starts to search the house for Susanna's lover on the pretext of looking for the umbrella he forgot. ", "Having no success, Gil furiously goes out again and Susanna lights a second cigarette. ", "Once more Gil enters and, this time, he is sure that he will catch her in the act. ", "Trying to seize her hand, he gets burned thus finally unveiling her secret. ", " They forgive each other and swear eternal love while smoking together.", "\n\nRecordings\nThere are eight recordings, including one video. ", "Key to casts (where not written out) is conductor/susanna/gil:\n 1952 - Ester Orel (Susanna), Mario Borriello (Gil); Orchestra Sinfonica di Torino, Alfredo Simonetto (conductor) - Cetra (LP), later licensed to Deutsche Grammophon\n 1954 - Elena Rizzieri (Susanna) Giuseppe Valdengo (Gil); Italian Radio Symphony Orchestra Turin, Angelo Questa (conductor) - Cetra, currently licensed by Warner Music\n 1976 - Maria Chiara (Susanna), Bernd Weikl (Gil), Omar Godknow (Sante); Orchestra of the Royal Opera House Covent Garden, Lamberto Gardelli (conductor) - Decca (LP)\n 1980 - Renata Scotto (Susanna), Renato Bruson (Gil); Philharmonia Orchestra, John Pritchard (conductor) - CBS (LP and CD)\n 1981 - Phelps/Swennes/Potter - live in Bloomington, issued by Indiana University\n 2006 - Haider/Howarth/Ódena - live in Oviedo, issued by Philartis\n 2008 - Petrenko-V/Rodrígues-D/Canturri - live in Liverpool, Avie Records, issued in cooperation with the European Commission\n\nReferences\n Complete Libretto: in Italian and in English\n Amadeus Almanac, accessed 7 September 08\n Warrack, John and West, Ewan (1992), The Oxford Dictionary of Opera, 782 pages, \n\nCategory:Operas by Ermanno Wolf-Ferrari\nCategory:Italian-language operas\nCategory:Operas\nCategory:One-act operas\nCategory:1909 operas" ]

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[ " - 20 = -12*t for t.\n-5\nSuppose 3*c + 14 = -3*l + 5, -5*c - l = 3. ", "Let y = 204 + -201. ", "Suppose 3*t - 8 = -w, 0 = -2*w + y*t - 3 + 10. ", "Solve k - w = -c*k for k.\n5\nSuppose 59 = -3*p - 106. ", "Let m(a) = -4*a**2 + 35*a + 2. ", "Let l be m(10). ", "Let y = l - p. Solve -4*w - 1 - y = 0 for w.\n-2\nSuppose 339*y - 335*y = -q + 1, 5*q - 5 = -2*y. ", "Solve 21*x + 29*x = y for x.\n0\nSuppose -9*k - 21 = -21. ", "Let i(y) = -y**2 - 6*y + 2. ", "Let n be i(-6). ", "Suppose -4*o + 0 = -12. ", "Solve k = o*r + n*r for r.\n0\nSuppose -26*o = 512*o - 19368. ", "Solve 47 = -o*u - 61 for u.\n-3\nLet z be 0 + 6/5*(2520/(-14))/(-3). ", "Solve -11*d - 13*d = z for d.\n-3\nSuppose -2*w = -j - 38, -5*w + 102 = 53*j - 56*j. ", "Suppose a + 4*v = 4, v = -2*a + 4*v + 8. ", "Solve 10*h = a*h - w for h.\n-2\nSuppose n + 3*s = 46, 2*n + s - 96 = -s. ", "Let q = n + -44. ", "Solve q*z + 15 = -0*z for z.\n-3\nSuppose -48 = -3*r - 5*f, 32 = -39*r + 41*r - 5*f. ", "Let q be r/12*(-45)/(-10). ", "Solve -3*y + 21 = q for y.\n5\nSuppose 3*p = 4*m - 23, 14*p = -2*m + 12*p + 8. ", "Suppose -267 = -m*q - 172. ", "Solve -5*b - 4 = -q for b.\n3\nSuppose 4*v = 5*s - 30, 6 = 148*s - 150*s - 2*v. ", "Solve -162 + s = -20*r for r.\n8\nLet v(t) = t - 8. ", "Suppose 1 - 43 = -3*c + u, -3*c + 3*u + 48 = 0. ", "Let k be v(c). ", "Solve -9 = -k*r - 24 for r.\n-3\nLet u(f) = 5*f**3 + 55*f**2 - 8*f - 50. ", "Let p be u(-11). ", "Solve 33*l - 30 = p*l for l.\n-6\nLet t = -245 + 251. ", "Let g(l) = l**2 - 5*l - 1. ", "Let n be g(t). ", "Solve -j + n = 2 for j.\n3\nSuppose -4*l + 15*l + 6721 = 0. ", "Let j = -583 - l. Solve 2*g = 34 - j for g.\n3\nSuppose 0 = -b + y + 4, 2*b = b - 2*y + 1. ", "Suppose u = b + 5. ", "Solve u = 4*g - 0 for g.\n2\nLet d be 2*(2 + (-5)/((-10)/3)). ", "Let l = d + 2. ", "Suppose -n + 3 = 2*n - 2*x, 0 = n + 2*x - l. Solve u = -n*u for u.\n0\nSuppose 4*f + 8 = -6*s + 4*s, -2*f = 5*s - 4. ", "Let o(y) = -30*y + 420. ", "Let t be o(14). ", "Solve s*z + 3*z = t for z.\n0\nSuppose -2*n - 8 = -3*h + 3, -3*h - 5 = 2*n. ", "Let u be h + -9 + (4 - (6 + 2)). ", "Let d be (-3)/(-2)*-1 - u/8. ", "Solve -4*z + 2*z = d for z.\n0\nSuppose 4*j - 3 = -5*d - 1, -6 = -2*d + j. Let m be 378/135 + (-3)/15*-1. ", "Solve 0 = -m*s - 10 - d for s.\n-4\nLet a(w) = -2*w + 4. ", "Let i be a(-1). ", "Suppose -4*d + 8 = 5*r, 3*r - i + 4 = -2*d. ", "Suppose 3*f + 4*l - 41 = 0, 0*f + 2*l = -2*f + 30. ", "Solve 4*p - f = -d for p.\n3\nLet x be (-903)/168 - 3/(-8). ", "Let q(k) = -2*k**2 - 6*k + 9. ", "Let m be q(x). ", "Let h = m + 15. ", "Solve 0 = 2*d + h for d.\n-2\nSuppose 4*a - 10 = -a. ", "Suppose 5*f + u = 28, 28*u = f + 30*u - a. Solve -f = j - 4 for j.\n-2\nLet a = 8988 + -8916. ", "Solve a = -14*n + 16 for n.\n-4\nLet d = 182 + -188. ", "Let s be ((-12)/(6/3))/(d + 4). ", "Solve 3*h + 3 + s = 0 for h.\n-2\nLet x(a) = 7*a + 43. ", "Let p be x(-11). ", "Let s be (-8)/(-12)*-6 - p. Suppose 0*l + s = 3*l - 3*j, -3*l = -4*j - 31. ", "Solve 2*o = -o - l for o.\n-3\nSuppose 0 = -5*n - 13 + 58. ", "Let f be (30/n)/((-1)/3). ", "Let q be (-8)/f - 26/(-5). ", "Solve -2*u + 20 = -q*u for u.\n-5\nLet z be 23/(-115) + (-3421)/(-55). ", "Solve 9*f + z = 80 for f.\n2\nLet j be (((-1)/(-5) - 1) + 2)/((-228)/(-3420)). ", "Solve -j*d + 80 = 8 for d.\n4\nLet y(h) = h**2 + 10*h - 14. ", "Suppose 4*f + 56 - 12 = 0. ", "Let l be y(f). ", "Let i be (-175)/(-55) - 4/(-66)*l. ", "Solve n = -i*n for n.\n0\nLet t be 0 - (-16)/24 - 148/(-24)*2. ", "Solve -41*m + t = -28*m for m.\n1\nSuppose -5*n + 32 = 4*c - 3*c, 5*n + 2 = c. Suppose -37 = -3*p - i, 0 = 2*p - 5*i - 18 - 1. ", "Let t = c - p. Solve 0 = -t*o + 3 + 2 for o.\n1\nLet x = -238 + 278. ", "Solve -22*f + x*f = -126 for f.\n-7\nLet n be 6/((-192)/1928) - 2/(-8). ", "Let b = n - -73. ", "Solve b = 2*o + 5 for o.\n4\nLet l be (188/16 + (2 - 4))*32/6. ", "Solve 18*r = l + 56 for r.\n6\nLet m be 108 - (-6 + 4)*-4. ", "Suppose -231*s + 206*s + m = 0. ", "Solve p - s = -8 for p.\n-4\nLet b(t) = 2*t**3 - 52*t**2 + t - 17. ", "Suppose 4*f = -2*n + 108, 5*f = 6*f - 3*n - 20. ", "Let v be b(f). ", "Solve -7*p = -v*p - 6 for p.\n-3\nSuppose 0 = 4*v - 4*z - 72, -78*v - 2*z + 66 = -74*v. ", "Solve -v*j + 45 = -32*j for j.\n-3\nSuppose 0 = -6*d + d - 20, 26 = t - 5*d. ", "Let r(b) = 103*b + 519. ", "Let x be r(-5). ", "Solve -x*q - t = -2*q for q.\n-3\nLet m be 2 + 3 + -5 + 4 + 0. ", "Let d = -28 + 34. ", "Suppose a - 3*a = -d. ", "Solve m = -a*r - r for r.\n-1\nSuppose -14*d - 598 - 9636 = 0. ", "Let w = -715 - d. Solve -7*s - 51 = -w for s.\n-5\nLet o(g) = -7*g**2 - 15*g - 18. ", "Let i be o(-7). ", "Let w = -252 - i. Solve 0 = -4*v + w - 8 for v.\n-1\nLet y(l) = 2*l**2 + 68*l + 39. ", "Let x be y(-34). ", "Suppose 2*t + 3*a = 7*t - x, 5*a = t - 21. ", "Solve t*k - 29 = 1 for k.\n5\nSuppose 20*g - 158 = 15*g - 8*b, 0 = 2*g + 2*b - 62. ", "Solve -576*a = -581*a - g for a.\n-6\nSuppose -t = -3*t + 5*t. ", "Let g = 103 + -98. ", "Solve t*b - g = 5*b for b.\n-1\nLet r(i) = i**2 - 4*i - 3. ", "Let w be r(-2). ", "Suppose d - w = -2*d. ", "Suppose 0 = -3*c + 221 - 206. ", "Solve 2 + d = c*x for x.\n1\nSuppose -24*j = -21*j - 3. ", "Suppose 3*i = -4*h + 43, 5*h - 61 = -5*i - j. Solve 3*o = h*o + 16 for o.\n-4\nLet a be 0*(3 + -10)/35. ", "Suppose a = m - h - h - 3, h = -4*m + 30. ", "Solve 2*l + m = -3 for l.\n-5\nLet d = 254 - 205. ", "Suppose 5*t = -8*r + 7*r + 35, -4*t + d = 5*r. ", "Solve 4*m + 18 = t for m.\n-3\nSuppose -20 = u - 6*t + t, -3*u + 3*t = 12. ", "Suppose 5*b + q = u, -b + 2*q = -0*q. ", "Let y = b - 0. ", "Solve y = 6*j - j for j.\n0\nLet y(o) = -51*o - 84. ", "Let g be y(-16). ", "Let r = g - 732. ", "Solve 12*t - 6*t - 12 = r for t.\n2\nLet z(c) = -c**3 - 8*c**2 - 12*c + 2. ", "Let p be z(-6). ", "Suppose 0 = b - 2, -n - p*b - 11 = -4*n. ", "Solve 0 = -n*a + 6*a - 4 for a.\n4\nSuppose -3*x = -23 - 16. ", "Suppose 3*b + x + 7 = i, 0 = 3*i + b - 30. ", "Let u = -10 + i. Solve 0 = 2*n - 3 - u for n.\n2\nLet p(c) = -2*c + 22*c - 93 - 11*c. ", "Let i be p(11). ", "Solve -3*h - i = -h for h.\n-3\nLet c = -2 - -5. ", "Suppose -c*b - 4 = -4*b. ", "Suppose -15 = k + 5*m, -4*m - 6 = 3*k - 2*m. ", "Solve k*d = b*d for d.\n0\nSuppose 206*q = 241*q - 245. ", "Solve q*j + 34 - 6 = 0 for j.\n-4\nLet a(g) = g**3 + 5*g + 219. ", "Let j be a(0). ", "Suppose -221*s + 26 = -j*s. ", "Solve 2*v + 11 = s for v.\n1\nLet v(u) = -3*u - 1. ", "Suppose -7*r = -14 - 7. ", "Let g = r + -6. ", "Let b be v(g). ", "Solve 0 = 5*o + 7 + b for o.\n-3\nSuppose -12*w = -8*w - 2*m + 32, 4*w = 5*m - 20. ", "Let q be (-6)/((-12)/w) + 9. ", "Let o be (-8)/6*-3 - 1. ", "Solve -q*v + o = -v for v.\n1\nLet z be 354 - (5 - 6)*(3 - 3). ", "Solve -25*b = 34*b - z for b.\n6\nSuppose 19 = 4*t - 3*t. ", "Let z = 21 - t. Suppose -z*y + 1 = a, 6*a + 3 = -y + 2*a. ", "Solve y = 3*j + 10 for j.\n-3\nLet y be (-4 - (4 - 7))*-3. ", "Let o(m) be the first derivative of 7*m**2/2 - 21*m - 260. ", "Let d be o(y). ", "Solve d*w - 15 = 5*w for w.\n-3\nSuppose 5 - 8 = o. Let h = 3 - o. Let g(r) = -r**2 + 30*r - 223. ", "Let i be g(15). ", "Solve i*x - 12 = h*x for x.\n-3\nSuppose 4*m = -r + 7*m + 3, -5*r + 45 = -5*m. ", "Let u be r/2 + 20/(-20). ", "Solve 0*j + 25 = u*j for j.\n5\nLet v(i) = 27*i**2 - 12*i + 7. ", "Let r be v(4). ", "Suppose 5*s = 436 - r. Solve -s*u - 7 = -2*u for u.\n-1\nSuppose 3*p = -0*p + 5*d + 44, 4*d = 2*p - 32. ", "Suppose -p*s = -12*s + 8. ", "Let o(l) = -l**2 - 10*l - 5. ", "Let a be o(-5). ", "Solve s*b = -3*b + a for b.\n4\nLet g(a) = a**2 - 72*a + 1262. ", "Let h be g(28). ", "Solve -h*t + 32*t = 6 for t.\n3\nLet b(j) = 26*j**2 - 5*j - 14. ", "Let f be b(-2). ", "Let u = f - 88. ", "Suppose 3*h = 8*h + 2*s - 36, -4*s = -u. ", "Solve w - h = -3 for w.\n3\nLet i = -61 - -133. ", "Suppose -66*x - 36 = -i*x. ", "Solve -k + x = k for k.\n3\nLet u be ((-376)/10)/(35/(-25) - -1). ", "Let b = u + -75. ", "Suppose -5*j - 5*q + b = 4, 5*j - 24 = 4*q. ", "Solve v = 3*v + j for v.\n-2\nLet w = 1007 - 767. ", "Suppose -14*b = 10*b - w. Solve -7*x - b = -2*x for x.\n-2\nLet c(h) = 44*h + 1298. ", "Let k be c(-28). ", "Solve -50 = -41*w + k*w for w.\n-2\nLet m be ((-6)/12)/(8/(-48)). ", "Suppose 4*q - 15*f - 26 = -13*f, -m*q + 13 = 5*f. ", "Solve 0 = 5*s + q + 19 for s.\n-5\nLet h(q) be the second derivative of q**5/20 - 4*q**4/3 - 2*q**3 - 36*q**2 - 144*q - 1. ", "Let t be h(17). ", "Solve -t*i + 7*i = -24 for i.\n4\nLet s be -4*(19/(-2) + 6 + -1). ", "Solve 19*i = s*i + 1 for i.\n1\nLet y(a) = 5*a - 148. ", "Let q be y(-17). ", "Let u = 236 + q. Solve 4*s = -5 - u for s.\n-2\nLet t be (-1 - 343/14)/((-15)/40). ", "Solve 52 - t = 4*a for a.\n-4\nSuppose -3*s + 122 = b, 5*s - 5*b = 154 + 56. ", "Solve 57 - s = -16*i for i.\n-1\nLet l(b) = 4*b - 24. ", "Suppose -18*q + 224 = 14*q. ", "Let j be l(q). ", "Solve -j*x - 9 + 21 = 0 for x.\n3\nLet q(c) = c**3 - 19*c**2 - 20*c + 3. ", "Let x be q(20). ", "Suppose -x = -f + 61. ", "Let v = -61 + f. Solve u + v = 6 for u.\n3\nLet r(y) = 5*y**3 + 209*y**2 - 130*y + 138. ", "Let v be r(-42). ", "Solve -56 = 3848*x - v*x for x.\n-4\nLet f(p) be the first derivative of -3*p**2/2 - 47*p + 52. ", "Let k be" ]

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[ "Metaphysical terms in the works of René Guénon\n\nMetaphysical terms in René Guénon's works contains the definition of some metaphysical terms used in René Guénon's writings.", "\n\nIn his metaphysical writings, René Guénon has stated precise definitions concerning key terms in metaphysics. ", "This article summarizes some of them. ", "Guénon's writings make use of words and terms, of fundamental signification, which receive a precise definition throughout his books. ", "These terms and words, although receiving a usual meaning and being used in many branches of human sciences, have, according to René Guénon, lost substantially their original signification (e.g. words such as \"metaphysics\", \"initiation\", \"mysticism\", \"personality\", \"form\", \"matter\"). ", "This article provides the definition given by René Guénon to some of the words used extensively in his works.", "\n\nDefinitions\n\nNotes and references\n\nCategory:Concepts in metaphysics\nCategory:Esotericism" ]

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[ "Flavobacterium frigidarium\n\nFlavobacterium frigidarium is a bacterium. ", "It is an aerobic, psychrophilic, xylanolytic and laminarinolytic bacterium from Antarctica. ", "It is gram-negative, non-motile and yellow-pigmented. ", "Its type strain is A2iT (= ATCC 700810T = NCIMB 13737T).", "\n\nReferences\n\nFurther reading\nHumphry, David Robert. ", "Taxonomy of the psychrophile Flavobacterium frigidarium and the mesophile Cellvibrio japonicus, and comparative analyses of their xylanolytic and laminarinolytic activities. ", "Diss. ", "University of Sunderland, 2003.", "\nWhitman, William B., et al., ", "eds. ", "Bergey’s manual® of systematic bacteriology. ", "Vol. ", "5. ", "Springer, 2012.", "\nVan Trappen, Stefanie. \"", "Diversity of Flavobacterium spp. ", "in polar aquatic environments.\" (", "2009): HASH-0x57f0c78.", "\n\nExternal links\n\nLPSN\nWORMS entry\nType strain of Flavobacterium frigidarium at BacDive - the Bacterial Diversity Metadatabase\n\nCategory:Flavobacteria\nfrigidarium\nCategory:Bacteria described in 2001" ]

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[ "Untitled Document\nThis forum was shut down in 2012 due to a criminal terrorist 'anonymous' hacker attack on the New Nation News Editor.", "\nSince then it has been closed to the public and only a handful of dedicated 'hard core' volunteer reporters have continued to contribute. ", "Any new applicants will be 'security checked'. ", "Thanks for your interest.", "\nThere is no 'freedom of speech' if the rabid far-left and 'powers that be' don't like your viewpoint.", "\n\nSCSO: Father arrested for the murder of 4-month-old baby, mother\nPosted 10:34 am, September 14, 2019\n\nSHELBY CO., ", "Tenn. — The Shelby Count Sheriff’s Office has arrested a man for the murder of a woman and her 4-month-old baby boy.", "\n\nThe Shelby County Sheriff’s Office says that 25-year-old Enoch Turner, who is the father of the 4-month-old baby, has been arrested and charged with numerous felonies, including two counts of first degree murder and aggravated arson.", "\n\nHeather Cook, 32, and her son Bentley were found dead in an apartment on Bennington Circle sometime after 9:30 a.m. Friday morning. ", "Shelby County Fire crews found their bodies while responding to a call of a house fire.", "\n\nDeputies pronounced both of them dead on the scene. ", "Fire marshals later determined that the fire was intentionally set.", "\n\nAccording to an affidavit obtained by WREG, both Cook and the baby were stabbed multiple times.", "\n\nAuthorities say a family told deputies that Turner was the father of baby Bentley, and that Turner and Cook had recently gotten into an argument over custody issues. ", "Family, however, tells WREG that the argument was about child support for Bentley.", "\n\nThe affidavit says that a vehicle tag registered to Turner was spot near Cook’s residence on Friday morning. ", "Deputies located Turner, who agreed to speak with them.", "\n\nAuthorities say that after changing his story several times, Turner admitted to entering Cook’s home through a back window. ", "Turner reportedly claimed that he found them both already dead and fled the scene without calling the police." ]

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[ "Cancer Medicine 2018; 7(4):1338--1348\n\nIntroduction {#cam41344-sec-0001}\n============\n\nNonsmall cell lung cancer (NSCLC) is the leading cause of cancer‐related death worldwide. ", "The immunosuppressive state is a predominant feature that drives the progression and metastasis of cancer in patients with NSCLC receiving chemotherapy or radiotherapy [1](#cam41344-bib-0001){ref-type=\"ref\"}. ", "Moreover, the immune activity in patients with NSCLC at the clinically detectable stage is mostly suppressed [2](#cam41344-bib-0002){ref-type=\"ref\"}, [3](#cam41344-bib-0003){ref-type=\"ref\"}. ", "Therefore, improving immune function is important for tumor regression in patients with NSCLC.", "\n\nIn contrast to high‐dose radiation (HDR), low‐dose radiation (LDR) has been proven to induce immune enhancement as a consequence of its hormesis effect [4](#cam41344-bib-0004){ref-type=\"ref\"}, [5](#cam41344-bib-0005){ref-type=\"ref\"}, [6](#cam41344-bib-0006){ref-type=\"ref\"}. ", "Radiation hormesis includes the effects of stimulating proliferation in normal cells, increasing lifespan, and enhancing fertility. ", "LDR also induces adaptive responses that protect normal tissues around the tumors from impairment caused by subsequent HDR treatment resulting in increased antioxidant activity and DNA repair capacity, cell cycle redistribution, and susceptibility to apoptosis [4](#cam41344-bib-0004){ref-type=\"ref\"}, [7](#cam41344-bib-0007){ref-type=\"ref\"}. ", "However, these radiation hormesis and adaptive responses do not exist in malignant cells [5](#cam41344-bib-0005){ref-type=\"ref\"}, [8](#cam41344-bib-0008){ref-type=\"ref\"}. ", "Therefore, LDR could be exploited as a synergistic measure in tumor radiotherapy.", "\n\nThe hormesis response in the immune system induced by LDR has been extensively studied. ", "LDR can stimulate both innate and adaptive immune responses [9](#cam41344-bib-0009){ref-type=\"ref\"}. ", "Our previous study showed that LDR can enhance the expansion and cytotoxicity of natural killer (NK) cells in vitro and increase the levels of interferon (IFN)‐*γ* and tumor necrosis factor (TNF)‐*α* in NK culture supernatants [10](#cam41344-bib-0010){ref-type=\"ref\"}. ", "Moreover, LDR can activate dendritic cells and augment T‐cell activation, thereby increasing antibody secretion and enhancing the antibody‐dependent cell‐mediated cytotoxicity response, which may shift naïve helper T cells to Th1 cells [9](#cam41344-bib-0009){ref-type=\"ref\"}, [11](#cam41344-bib-0011){ref-type=\"ref\"}. ", "In this process, responses of T cells to antigens and mitogens are augmented [12](#cam41344-bib-0012){ref-type=\"ref\"} with increased cytokine (IFN‐*γ*, interleukin \\[IL\\]‐2) production, and the number of IL‐2 receptors on the surface of the T cells is also increased [13](#cam41344-bib-0013){ref-type=\"ref\"}. ", "The immunosuppressive regulatory T‐cell (Treg) population is reduced after LDR exposure in tumor‐bearing mice, which may reduce tumor burden and prolong survival [14](#cam41344-bib-0014){ref-type=\"ref\"}, [15](#cam41344-bib-0015){ref-type=\"ref\"}.", "\n\nThe adaptive response of LDR has also been found in the immune system. ", "For example, total‐body LDR exposure induces the adaptive responses of thymocyte apoptosis and cell cycle progression in mice [16](#cam41344-bib-0016){ref-type=\"ref\"}. ", "In vivo LDR treatment protects human B lymphoblasts from subsequent HDR‐induced cell death [17](#cam41344-bib-0017){ref-type=\"ref\"}, and high‐dose *γ*‐radiation‐induced DNA damage could be reduced in human peripheral blood mononuclear cells pretreated with low‐dose *γ*‐radiation [18](#cam41344-bib-0018){ref-type=\"ref\"}.", "\n\nThese observations suggest that LDR may induce antitumor immunity. ", "However, direct evidence demonstrating that immune augmentation is triggered by LDR and contributes to tumor regression is lacking. ", "Thus, an in vivo tumor‐bearing model in normal mice, but not immunodeficient mice, is essential for investigating the role of immunity in LDR‐induced tumor regression. ", "Accordingly, in this study, we established a model in normal C57BL/6 mice that exhibited Lewis lung cancer tumors; the mice received either total‐body LDR or HDR exposure only or sequential exposure to HDR before or after LDR. ", "In this study, HDR was used to destroy the immune function of tumor‐bearing mice; HDR pretreatment before LDR was performed to inversely verify the immune‐enhancing effect of LDR, and LDR pretreatment before HDR was carried out to study the adaptive response of the immune system induced by LDR. ", "The results indicated that LDR‐induced tumor inhibition was dependent on immune enhancement and that the adaptive response of the immune system could be induced by LDR, thereby protecting mice from HDR‐induced immune impairment.", "\n\nMaterials and Methods {#cam41344-sec-0002}\n=====================\n\nCells and cell lines {#cam41344-sec-0003}\n--------------------\n\nC57BL/6 mouse‐derived Lewis lung cancer cells were purchased from the American Type Culture Collection and cultured in Iscove\\'s modified Dulbecco\\'s medium (Gibco, Grand Island, NY) supplemented with 10% fetal bovine serum (FBS; Gibco) and penicillin--streptomycin antibiotics (Invitrogen, Carlsbad, CA). ", "Mouse splenocytes were collected aseptically from spleens of mice by mincing the spleen tissues in a sterile Petri plate, and the erythrocytes were lysed in lysis buffer (10 mmol/L KHCO~3~, 150 mmol/L NH~4~Cl, 10 mmol/L ethylenediaminetetraacetic acid, pH 7.4). ", "Separated splenocytes were cultured in Roswell Park Memorial Institute (RPMI) 1640 medium (Gibco) supplemented with 10% FBS and penicillin--streptomycin antibiotics.", "\n\nMice {#cam41344-sec-0004}\n----\n\nFemale C57BL/6 mice were purchased from the Experimental Animal Center at Norman Bethune Medical College at Jilin University. ", "Mice were housed in a specific pathogen‐free facility. ", "The experimental manipulation of mice was performed according to the National Institute of Health Guide for the Care and Use of Laboratory Animals, with the approval of the Scientific Investigation Board of Science and Technology of Jilin Province.", "\n\nTumor model {#cam41344-sec-0005}\n-----------\n\nThe mouse lung cancer model was established using previously reported methods [19](#cam41344-bib-0019){ref-type=\"ref\"}. ", "Briefly, 6‐ to 8‐week‐old female C57BL/6 mice were inoculated subcutaneously with 1 × 10^6^ Lewis lung cancer cells in 0.2 mL serum‐free medium at the right back near hind leg on day 0. ", "Then, the mice were allocated randomly into five groups; in each group, 10 mice were used for tumor volume and survival analyses, and another 12 mice were used for splenocyte isolation at four time points. ", "Tumor volume (length × width^2 ^× 0.5, in cubic millimeters) was measured every other day once tumors could be observed visually (after day 10). ", "Animal survival was monitored after tumor inoculation.", "\n\nRadiation treatment {#cam41344-sec-0006}\n-------------------\n\nThe mice were subjected to total‐body irradiation using an X‐ray generator (X‐RAD320UMSU). ", "LDR at 75 mGy with a dose rate of 12.5 mGy/min and HDR at 1 Gy with a dose rate of 1 Gy/min were applied in this study. ", "Four cycles of treatment were carried out in each group of tumor‐bearing mice. ", "Briefly, mice in the LDR group received LDR treatment on days 10, 14, 18, and 22 after tumor inoculation; mice in the HDR group received HDR treatment on days 11, 15, 19, and 23; mice in the LDR‐HDR (LDR pretreatment 1 day before HDR) group received LDR on days 10, 14, 18, and 22 and received HDR on days 11, 15, 19, and 23; and mice in the HDR‐LDR (HDR pretreatment 1 day before LDR) group received HDR on days 9, 13, 17, and 21 and LDR on days 10, 14, 18, and 22. ", "Mice in the Sham group were treated similarly except for the radiation. ", "The animal experiment was replicated two times, and representative results are shown.", "\n\nSplenocyte proliferation assay {#cam41344-sec-0007}\n------------------------------\n\nThree tumor‐bearing mice in each group were sacrificed on days 12, 16, 20, and 24 to isolate splenocytes. ", "The proliferation of splenocytes was detected by WST‐1 assays. ", "Briefly, splenocytes were resuspended to a concentration of 2 × 10^6^ cells/mL in RPMI 1640 with 10% FBS and seeded in 96‐well plates. ", "Then, cells were treated with or without concanavalin A (Con A) at a final concentration of 5 *μ*g/mL. After incubation for 48 h at 37°C in an atmosphere containing 5% CO~2~, 20 *μ*L WST‐1 solution (Roche, Mannheim, Germany) was added, and incubation was resumed for an additional 3 h. Then, the plate was shaken for 20 sec and read at 440 nm using a microplate system (BioTek, Winooski, VT, US). ", "Five replicate wells were read. ", "The splenocyte proliferation index was calculated using the following formula: Proliferation index = (OD of the ConA group -- OD of the control group/OD of the control group) × 100%.", "\n\nCytokine measurement {#cam41344-sec-0008}\n--------------------\n\nThe supernatants of splenocytes incubated with ConA were collected after 48 h of culture, and the levels of IL‐1*β*, IL‐2, IFN‐*γ*, TNF‐*α*, and IL‐10 were measured using a mouse cytometric bead array (CBA) kit (BD Biosciences, Bedford, MA, US). ", "Briefly, 50 *μ*L of samples or standard samples (0--5000 pg/mL) were added to a mixture of 50 *μ*L each of capture antibody bead reagent and PE‐conjugated detection antibody. ", "The mixture was then incubated for 2 h at room temperature in the dark and washed to remove unbound detection antibody. ", "Data were acquired using a FACSCalibur flow cytometer (BD Biosciences) and analyzed using CBA software 1.1 (BD Biosciences).", "\n\nSplenocyte cytotoxicity assay {#cam41344-sec-0009}\n-----------------------------\n\nTarget Lewis cells (1 × 10^6^) were labeled with 1 *μ*mol/L calcein AM and incubated for 30 min at 37°C. ", "The labeled cells were then washed twice in phosphate‐buffered saline (PBS) and resuspended to 5 × 10^4^ cells/mL in RPMI 1640 with 5% FBS. ", "Subsequently, 5 × 10^3^ labeled target cells in a 100‐*μ*L volume were plated in 96‐well plates, and mouse splenocytes were added as effector cells to an effector:target (E:T) ratio of 50:1. ", "Cells were then incubated for 4 h at 37°C in an atmosphere containing 5% CO~2~. Next, 100 *μ*L of the supernatant was collected from each well and added to a new 96‐well plate, and the absorbance was measured using a microplate system (BioTek). ", "The excitation wavelength was 485 nm, and the emission wavelength was 528 nm. ", "Spontaneous release was determined by incubating target cells in medium alone, and maximum release was determined by suspending cells with 0.21% Triton X‐100. ", "Splenocyte cytotoxicity was calculated using the following formula: killing efficiency (%) = (experimental release -- spontaneous release)/(maximum release -- spontaneous release) × 100.", "\n\nFlow cytometry {#cam41344-sec-0010}\n--------------\n\nFreshly isolated splenocytes (2 × 10^5^) were stained with peridinin--chlorophyll--protein complex (PerCP)‐labeled anti‐CD3*ε* monoclonal antibodies (mAbs), fluorescein isothiocyanate (FITC)‐labeled anti‐CD4 mAbs, phycoerythrin‐labeled anti‐CD8a mAbs, allophycocyanin‐labeled anti‐NK1.1 mAbs, or FITC‐labeled anti‐CD69b mAbs (BD Biosciences) and incubated for 15 min in the dark at 25°C. ", "The cells were then washed with PBS and analyzed using a FACSCalibur flow cytometer (BD Biosciences). ", "The data were analyzed using FlowJo 7.6 (FlowJo LLC) software.", "\n\nHistopathological and immunohistochemical analyses {#cam41344-sec-0011}\n--------------------------------------------------\n\nOn day 24 after tumor inoculation, three mice in each group were sacrificed, and the tumors were removed. ", "The tumor tissues were then fixed in 4% (w/v) formaldehyde, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E). ", "For immunohistochemical analysis, the sections were deparaffinized, followed by antigen retrieval and blocking. ", "The sections were then stained with anti‐mouse CD3 mAbs (1:500 dilution; Abcam, Cambridge, MA, US). ", "The histopathological and immunohistochemical sections were observed using a microscope (Olympus, Model BX51TF, America, Inc.).", "\n\nStatistical analysis {#cam41344-sec-0012}\n--------------------\n\nTumor growth curves were plotted based on tumor size until mouse death. ", "Differences in tumor size among the various groups were determined by analysis of variance repeated measures test. ", "Statistical significance for the survival of mice was assessed using Kaplan--Meier curves. ", "Unpaired two‐tailed *t*‐tests were applied to analyze cell proliferation, cytotoxicity, and cytokine measurements. ", "Differences with *P* values of less than 0.05 were considered statistically significant. ", "Statistical analyses were performed using SPSS (IBM) and GraphPad Prism (GraphPad Software, Inc.) software.", "\n\nResults {#cam41344-sec-0013}\n=======\n\nTumor growth and survival in radiation‐exposed mice {#cam41344-sec-0014}\n---------------------------------------------------\n\nTo observe the effects of LDR and HDR on tumor growth, female C57BL/6 mice were inoculated with Lewis lung cancer cells at 1 × 10^6^/mouse on day 0 and exposed to LDR or HDR as described above. ", "The tumor volumes of the mice were measured every other day from day 10. ", "As shown in Figure [1](#cam41344-fig-0001){ref-type=\"fig\"}, the tumor volume data revealed that LDR treatment significantly inhibited tumor growth (*P *\\<* *0.05 vs. Sham; Fig.", " [1](#cam41344-fig-0001){ref-type=\"fig\"}A) and prolonged survival of the mice (Fig.", " [1](#cam41344-fig-0001){ref-type=\"fig\"}B). ", "Notably, pretreatment with LDR before HDR significantly inhibited tumor growth and prolonged the survival of mice as well. ", "Although the kinetic curves of tumor growth in the HDR and HDR‐LDR groups were similar to those in the Sham group, the survival of mice in these two groups did not improve, indicating that these two treatment regimens could not inhibit tumor growth.", "\n\n{#cam41344-fig-0001}\n\nAnalysis of the survival data (Fig.", " [1](#cam41344-fig-0001){ref-type=\"fig\"}B) showed that LDR treatment prolonged the survival of tumor‐bearing mice; five of 10 mice lived to day 40. ", "There were three of 10 mice in the LDR‐HDR group and one of 10 mice in the HDR‐LDR group that lived to day 40, whereas all mice in the Sham and HDR groups died by day 31. ", "The median survival times were 28 (Sham), 39.5 (LDR), 32 (LDR‐HDR), 25 (HDR), and 27.5 (HDR‐LDR) days. ", "These results indicated that LDR and LDR pretreatment before HDR inhibited tumor growth and prolonged survival in Lewis lung cancer‐bearing mice, but HDR and HDR pretreatment before LDR did not induce tumor inhibition.", "\n\nLDR increased the mitogen response of splenocytes in tumor‐bearing mice {#cam41344-sec-0015}\n-----------------------------------------------------------------------\n\nOn days 12, 16, 20, and 24, three tumor‐bearing mice in each group were selected randomly and sacrificed, and their spleens were isolated to examine the mitogen responses of splenocytes induced by ConA. The splenocytes were incubated with 5 *μ*g/mL ConA for 48 h, and WST‐1 assays were carried out to determine the splenocyte mitogen response, after which the proliferation index was calculated. ", "The results (Fig.", " [2](#cam41344-fig-0002){ref-type=\"fig\"}) showed that the splenocytes of the mice that received LDR exhibited the highest mitogen response on day 12, 16, 20, and 24; while compared with Sham and LDR, HDR impaired the splenocyte mitogen response or even inhibited splenocyte proliferation after ConA stimulation. ", "Moreover, the results also showed that LDR pretreatment before HDR could protect splenocytes from HDR‐induced severe impairment; the splenocyte proliferation index of mice in the LDR‐HDR group was higher than that in the HDR group, and the mean value on day 16 was even higher than that in the Sham group. ", "However, LDR treatment followed by HDR did not protect splenocytes from impairment from HDR, as the splenocyte proliferation index in the HDR‐LDR group was similar to or only slightly higher than that in the HDR group.", "\n\n{#cam41344-fig-0002}\n\nLDR influenced cytokine production in mouse splenocytes {#cam41344-sec-0016}\n-------------------------------------------------------\n\nAfter incubation with ConA for 48 h, supernatants of the splenocytes were collected, and IL‐1*β*, IL‐2, IFN‐*γ*, TNF‐*α*, and IL‐10 were detected. ", "As shown in Figure [3](#cam41344-fig-0003){ref-type=\"fig\"}, compared with the Sham group, LDR significantly or clearly induced upregulation of the Th1 cytokines IL‐1*β*, IL‐2, IFN‐*γ*, and TNF‐*α* and downregulated IL‐10 production on days 12, 16, and 20, whereas HDR inhibited the production of these cytokines. ", "LDR pretreatment protected the cytokine‐producing ability of splenocytes on days 12, 16, and 20 to some degree; however, this effect did not last up to day 24. ", "In contrast, compared with HDR treatment, HDR‐LDR treatment did not exhibit protective effects on cytokine production.", "\n\n{#cam41344-fig-0003}\n\nLDR‐activated T cells and NK cells {#cam41344-sec-0017}\n----------------------------------\n\nBecause CD69 is an early activation molecule expressed on the surface of cytotoxic leukocytes, we detected CD69 expression in splenic NK cells and CD8^+^ T cells. ", "As shown in Figure [4](#cam41344-fig-0004){ref-type=\"fig\"}, the percentage of CD69^+^ NK cells in mice in the LDR group was significantly higher than that in the Sham group on days 12, 16, 20, and 24, and the percentage of CD69^+^ CD8^+^ T cells in the LDR group was significantly higher than that in the Sham group on days 16 and 20. ", "Similarly, on day 16, the percentage of CD69^+^ NK cells in the LDR‐HDR group was significantly higher than that in the Sham group. ", "However, HDR treatment significantly decreased the percentage of CD69^+^ CD8^+^ T cells on day 24.", "\n\n{#cam41344-fig-0004}\n\nLDR increased cytotoxicity of splenocytes {#cam41344-sec-0018}\n-----------------------------------------\n\nThe splenocytes of tumor‐bearing mice were isolated and incubated with calcein‐stained Lewis lung cancer cells at an E:T ratio of 50:1 for 4 h, and the supernatants were then collected to detect calcein release. ", "As shown in Figure [5](#cam41344-fig-0005){ref-type=\"fig\"}, compared with Sham radiation, LDR effectively increased the cytotoxicity of splenocytes on days 12 and 20, and LDR‐HDR treatment also increased cytotoxicity on day 12. ", "However, HDR treatment significantly inhibited cytotoxicity on day 16.", "\n\n{#cam41344-fig-0005}\n\nPathological changes and CD3^+^ T‐cell infiltration into tumors {#cam41344-sec-0019}\n---------------------------------------------------------------\n\nPathological examination was conducted on day 24 after tumor inoculation. ", "Three mice in each group were killed, and the tumors were isolated and sectioned. ", "The sections were then stained by H&E and anti‐CD3 antibodies for immunohistochemical analysis. ", "As shown in Figure [6](#cam41344-fig-0006){ref-type=\"fig\"}A, massive tumor cell death was observed in the LDR and LDR‐HDR groups, and tumor cell degeneration was induced in the HDR group. ", "Cell division and multinucleated giant cells were observed frequently in the Sham and HDR‐LDR groups, indicating the occurrence of vigorous DNA replication. ", "In immunohistochemical analysis of CD3 staining, many infiltrated T cells were observed in tumor tissues of mice in the LDR and LDR‐HDR groups, and fewer CD3^+^ cells infiltrated in the Sham, HDR, and HDR‐LDR groups, suggesting that LDR could enhance the antitumor immune response in tumor‐bearing mice.", "\n\n{#cam41344-fig-0006}\n\nDiscussion {#cam41344-sec-0020}\n==========\n\nIn this study, a xenograft model was established in normal mice. ", "The advantage of this in vivo model was that it allowed us to explore the participation of the immune system in LDR‐induced tumor inhibition. ", "The LDR‐induced adaptive response of the immune system was also observed through immune impairment induced by subsequent HDR treatment.", "\n\nLDR is known to be associated with the ability to enhance innate and adaptive immunity in tumor‐bearing animals. ", "The data in this study provide direct evidence demonstrating that total‐body LDR exposure can enhance antitumor immunity and inhibit tumor progression in mice, accompanied by induction of adaptive responses in the immune system. ", "Our results demonstrated that the antitumor immunity induced by LDR was mainly related to NK cell and T‐cell activation, as manifested by increased expression of CD69. ", "This was consistent with the results of our previous work showing that LDR augmented the cytotoxicity of NK cells in vitro [10](#cam41344-bib-0010){ref-type=\"ref\"} through increased production of IFN‐*γ*, TNF‐*α*, perforin, and granzymes [20](#cam41344-bib-0020){ref-type=\"ref\"}, [21](#cam41344-bib-0021){ref-type=\"ref\"}. ", "An in vivo study also reported that a single low dose of X‐ray irradiation inhibited tumor metastases and triggered NK cell activity in BALB/C mice with L1 sarcoma. ", "Therefore, the role of NK cells in LDR‐induced tumor inhibition could be determined. ", "T cells are also involved in the immune enhancement induced by LDR, as manifested by augmented proliferation and response to antigenic and mitogenic stimulation and cytokine production [12](#cam41344-bib-0012){ref-type=\"ref\"}, [22](#cam41344-bib-0022){ref-type=\"ref\"}, particularly production of IFN‐*γ* and IL‐2 [23](#cam41344-bib-0023){ref-type=\"ref\"}. ", "Coincidently, in the current study, we found a similar T‐cell reaction induced by LDR, including upregulation of CD69 molecules in T cells, increased cytotoxicity of mouse splenocytes, and increased infiltration of T cells in the tumor tissues. ", "Remarkably, an increase in Th1 cytokine production (IFN‐*γ*, IL‐2, TNF‐*α*, and IL‐1*β*) and a concomitant decrease in Th2 cytokine production (IL‐10) were detected in the splenocyte supernatants of LDR‐treated mice. ", "The switch from Th2 to Th1 cytokine production may be related to the antitumor effects of LDR. ", "We also found that compared with the data for days 12 and 14, LDR‐induced antitumor immunity decreased on day 20 and thereafter, particularly for killing assays and CD69^+^ NK cell and T‐cell percentages, although total survival and tumor growth were improved. ", "Tumors are known to induce immune suppression through multiple mechanisms, facilitating their escape from immune surveillance. ", "Therefore, we speculate that the decreased ability of LDR to induce antitumor immunity may have been related to tumor‐induced immune suppression. ", "During the early stage, when the tumors were small in size, they caused only minor suppression of mouse immunity. ", "Then, as the tumors grew larger after day 20, they caused greater immune impairment, decreasing the ability of LDR to induce antitumor immunity. ", "Such speculation could be supported by a study in the same mouse model showing that generalized T‐cell exhaustion was induced by the tumor 3 weeks after tumor inoculation [24](#cam41344-bib-0024){ref-type=\"ref\"}.", "\n\nTo further validate the involvement of immune enhancement in LDR‐induced tumor inhibition, HDR pretreatment was carried out before LDR treatment to impair the immune function as an inverse validation. ", "The dose of HDR was 1 Gy, which was considered insufficient to directly inhibit tumor growth because the effective dose of radiation to treat Lewis lung cancer in mice is 13 Gy or more [23](#cam41344-bib-0023){ref-type=\"ref\"}, [25](#cam41344-bib-0025){ref-type=\"ref\"}, [26](#cam41344-bib-0026){ref-type=\"ref\"}, [27](#cam41344-bib-0027){ref-type=\"ref\"}. ", "As expected, we found that HDR markedly impaired immune function, resulting in decreased splenocyte proliferation and cytokine production. ", "When HDR pretreatment was administered before LDR, LDR could not induce splenocyte proliferation and cytokine production, and the tumor inhibition effect was not observed. ", "The immunohistochemical analysis of CD3^+^ cell infiltration in tumor tissues also revealed the involvement of immunity in LDR‐induced tumor inhibition. ", "These findings indicated that the antitumor effects of LDR were mediated by enhanced immunity.", "\n\nThe adaptive response of LDR to protect normal tissues from HDR lesions has been observed in many previous studies. ", "For example, 5 cGy pre‐exposure increased the 30‐day survival rate from 30% to 70% in ICR mice exposed to 8 Gy X‐rays [28](#cam41344-bib-0028){ref-type=\"ref\"}; low‐dose pre‐exposure delayed the onset of subsequent HDR exposure‐induced leukemia [29](#cam41344-bib-0029){ref-type=\"ref\"}. ", "The mechanisms of LDR in inducing an adaptive response were found to be related to stimulating the antioxidant response [30](#cam41344-bib-0030){ref-type=\"ref\"}, [31](#cam41344-bib-0031){ref-type=\"ref\"}, DNA damage repair [7](#cam41344-bib-0007){ref-type=\"ref\"}, [32](#cam41344-bib-0032){ref-type=\"ref\"}, [33](#cam41344-bib-0033){ref-type=\"ref\"}, and modifying glucose metabolism [4](#cam41344-bib-0004){ref-type=\"ref\"}, [34](#cam41344-bib-0034){ref-type=\"ref\"}. ", "However, in tumor‐bearing mice, we found that LDR could also induce an adaptive response in the immune system. ", "Although total‐body exposure to 1 Gy HDR four times did not inhibit tumor growth, it did impair mouse immune function. ", "However, we found that 75 mGy LDR pretreatment before 1 Gy HDR ameliorated the HDR‐induced immune impairment and finally tended to inhibit tumor growth and promote survival compared with the Sham and HDR treatment. ", "Moreover, there was more infiltration of CD3^+^ cells in tumor tissues subjected to LDR pretreatment with HDR than in those subjected to HDR treatment alone. ", "Although further studies are needed to elucidate the molecular mechanisms involved in these processes, these findings verified the adaptive response of LDR in the immune system.", "\n\nIn conclusion, the current work demonstrated that the immune system plays a pivotal role in LDR‐induced tumor inhibition, and LDR pretreatment is beneficial to tumor radiation therapy for enhancing antitumor immunity and ameliorating HDR‐induced immune impairment. ", "This may substantially optimize the radiotherapy plan and provide a safer and more effective regimen. ", "However, although our previous study demonstrated that LDR induced NK cell activation in vitro, most likely through the p38 mitogen‐activated protein kinase pathway, the molecular mechanisms of LDR‐induced antitumor immunity enhancement should be explored in greater detail in subsequent in vivo studies. ", "Moreover, the risks of LDR, including the cumulative toxicity of repeated LDR exposure, must be further evaluated.", "\n\nConflict of Interest {#cam41344-sec-0022}\n====================\n\nNo potential conflict of interests was disclosed.", "\n\nWe would like to thank Professor Cai Li for helping in pathological and immunohistochemical analysis and technical support. ", "This study was supported by grants from the National Natural Science Foundation of China (grant no. ", "81672275), the Industrial Research and Development Project of Development and Reform Commission of Jilin Province (grant no. ", "2017C022), the Ministry of Science and Technology of China (grant no. ", "2016YFC1303800), the Key Laboratory Construction Project of Science and Technology Department of Jilin Province (grant no. ", "20170622011JC), the Project of Development and Reform Commission of Jilin Province (grant no. ", "2014N147) to J.W.C., the Fund of the Health and Family Planning Commission of Jilin Province, China (grant no. ", "2016Q035), the Youth Fund of the First Hospital of Jilin University to L.Z., and the Youth Fund of National Natural Science (grant no. ", "81302380) to D.H.Y.\n" ]

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[ "Monday, November 4, 2013\n\nDid Robert Latimer Do The Right Thing? ", "Consider Latimers Action In The Light Of Two Theories(eg.", ",utilitarianism, Virtues Ethics). (", "you Will Have To Do Outside Research To Get The Facts Of The Case Befor You Begin.)", "\n\nBut his carry out was to end her crucifixion , which is better by this take than an inaction of prolonging it , or an inaction of everything (including feeding her- which is static euthanasia ) which would involve led to greater suffering transport death . ", "He simply ended his daughter s sufferingObjections from the utilitarian ViewAssuming that I am slander about my argument from a utilitarian stand would only come from a bewitching utilitarian peck that is non simply concerned with maximising sincere , but also with honoring the sanctity of liveliness . ", "all few utilitarian who fundamentally supports that which spares or maintains the some lives (and minimizes deaths ) would retard Robert Latimer s actions in a negative light , as this cipher would hardly (or non at all ) cope quality of emotional state . ", "But a true , elemental utilitarian view should recognize quality of emotional state , for non only life and death weigh in on maximizing pleasures and stress . ", "A miserable life s founding should negatively doctor some hedonic calculus (a apparatus termed by Jeremy Bentham , which refers to some system of weighing pleasures and pains to steady down what is ruff . ", "So a true utilitarian view would not hold that Latimer s ending a life of suffering was wrong , but quite an that it was virtuously praiseworthyObjections from the Deontological ViewAnyone arguing that Latimer s actions were morally blamable while maintaining a deontological vi ew would also have to deport that his actio! ", "n intended to take a life , rather than save one . ", "But that was not his use . ", "If that was his fix purpose in what he did to his daughter , Tracy , consequently his action was no different from murdering someone in tatty transmission line , which also has the direct intention of come outing . ", "Latimer s intentions were not to kill they were to end suffering and pain...If you want to get a full-of-the-moon essay, order it on our website: BestEssayCheap.com" ]

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[ "28+ Styles Kitchen Dining Chairs Modern\n\nLynea Contemporary Dining Chairs By Domitalia Digsdigs\n\nAbout any of it Kitchen Dining Chairs Modern, develop that photographs listed below are striking you to perfect your project. ", "You might download all these picture from the gallery to make a factor to allow you to create a better decision on your own goals. ", "All pictures listed below are free to talk about with your friends and family.", "\n\nIf you like searching through the latest design magazines for Kitchen Dining Chairs Modern but do not have the full time or budget for a major decoration, we've been providing and easy decorating tips on the best way to give your home an update worthy of a property magazine. ", "The most effective part is why these Kitchen Dining Chairs Modern can mix and match beautifully — play one or even a few together." ]

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[ "CCNU, vinblastine, and delalutin therapy in renal cell carcinoma.", "\nAdvanced renal cell carcinoma is relatively resistant to most adequately evaluated chemotherapeutic agents. ", "The combination of CCNU and vinblastine, which has antitumor activity in a frog renal carcinoma model system, has demonstrated activity in initial studies in man. ", "The current study investigated this combination of drugs together with a progestational agent, Delalutin. ", "Seventeen patients with metastatic renal cell carcinoma were treated with CCNU, vinblastine and Delalutin. ", "There were no objective responses. ", "Four patients with stable disease had a mean survival of 18 months compared to 13 patients with progressive disease who had a mean survival of 5 months. ", "The survival of the four patients with stable disease was in large part due to the slowly progressive natural history of their disease." ]

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[ "SAN FRANCISCO (MarketWatch) -- Past Securities and Exchange Commission probes of Bernard Madoff were incompetent, according to a report issued Wednesday by SEC Inspector General David Kotz. ", "In his report, Kotz said that three agency exams and two investigations failed to uncover Madoff's multibillion-dollar Ponzi scheme despite warning signs. ", "The report, however, found no evidence of improper ties between the SEC and Madoff's firm." ]

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[ "Caladenia subglabriphylla\n\nCaladenia subglabriphylla is a plant in the orchid family Orchidaceae and is endemic to southern Australia. ", "It was first formally described in 2014 by Robert Bates who gave it the name Arachnorchis subglabriphylla and published the description in Australian Orchid Review. ", "In 2015 Mark Clements changed the name to Caladenia subglabriphylla and published the change in American Journal of Botany. ", "The specific epithet (subglabriphylla) is derived from the Latin prefix sub- meaning \"somewhat\" or \"less than\", the word glabrum meaning \"hairless\", \"bald\" or \"smooth\" and the Ancient Greek word phyllon meaning \"leaf\", hence \"almost hairless leaf\".", "\n\nReferences\n\nsubglabriphylla\nCategory:Endemic orchids of Australia\nCategory:Orchids of South Australia\nCategory:Plants described in 2014" ]

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[ "1. ", "Field of the Invention\nThe present invention relates to an improved container, which can be selectively used as a cooler or warmer for food and beverages. ", "More particularly, the present invention relates to a portable container having one or more characteristics that adapt it for use in a motor vehicle and/or dorm room, facilitate its assembly and repair, and/or facilitate its efficient operation.", "\n2. ", "Description of the Related Art\nCoolers are typically in the form of an insulated container which has walls upstanding from a base to define a top opening to which a removable cover is mounted. ", "Thus, such coolers are typically rectangular with two sidewalls and two end walls, and have a pivotal handle assembly mounted to each end wall for carrying the cooler. ", "As such, conventional coolers are intended to be disposed solely on the bottom or back wall, and the lid, whether or not hinged along one edge, is simply interlocked with the container by a friction fit and/or by engagement with pivotally mounted locking carrying handles which selectively engage and hold the lid on the container.", "\nTypically coolers of the type described above are used as ice chests. ", "Thus, when the food and/or beverages are to be kept cool, they are placed in the container and ice is added to the container to keep the food cool. ", "Such ice chests have a number of disadvantages. ", "For example, as the ice melts, water will be present in the base of the container and must be periodically removed. ", "Often, outlet ports are provided in such coolers to allow the melted ice to be drained. ", "Still, for the most part, only hermetically sealed containers can be placed within the container if water damage is to be avoided. ", "Further, to keep the contents cool for an extended period, ice must be repeatedly added.", "\nFurthermore, because ice is required to keep the food and beverages cool, only a relatively small amount of food can actually be stored within a cooler of a given size and the weight of the cooler is significantly increased by the presence of the ice.", "\nIt has been proposed to incorporate within a cooler type container a cooling system so that when the container is coupled to a power source, food and beverages within the cooler will be automatically cooled. ", "With such automatic cooling, there is no need for ice, and thus the container can hold more food and beverages than conventional ice chests of comparable size. ", "The thermoelectric technology which allows a cooling system to be incorporated in a cooler was, to a significant extent, developed by NASA and eliminates the need for bulky compressors and piping. ", "Furthermore, as an alternative to cooling, such newly developed systems can be used to warm foods by reversing the polarity of the power to the system. ", "Because such alternative cooling/heating systems are known a detailed disclosure of the heating/cooling system is omitted herein.", "\nWith the advent of positive cooling or warming within a portable container, there has been a desire to provide a portable food container which can be used both in a conventional ice chest orientation with the lid or door on top and in an end up orientation as a \"college dorm room\", hotel, or office refrigerator/warming oven with a front opening door. ", "A structure of this type is described in U.S. Pat. ", "No. ", "5,319,937, the disclosure of which is hereby incorporated by reference.", "\nWhile portable cooling/warming containers, such as that described in the aforementioned '937 patent, have a number of advantages, that is not to say the improvement thereof is not possible. ", "For example, when a cooler or warmer is used as a top opening ice chest, the cooler itself provides no tray or table top structure other than the top of the top opening lid. ", "Obviously, it is not possible to open the lid while food, beverages, or other items are setting thereupon without displacing the items. ", "Furthermore, when such a thermoelectric unit is used in a motor vehicle, it typically presents an inconvenient and sometimes dangerous interference with passengers or the driver because of the height of the unit and is subject to tipping because of the high center of gravity thereof. ", "In addition, thermoelectric cooler/warmers adapted for use in motor vehicles will typically have a long power cord so that the cooler/warmer may be used in the back seat of a car or in the back of a van while plugged into a cigarette lighter receptacle in the dashboard of the vehicle. ", "It is desirable to have a means for stowing the cord when not in use or stowing excess cord when less than the whole length of cord is needed. ", "One proposal includes cleats for wrapping the cord thereon located within a recess on a lower rear portion of the container. ", "The cleats are not easily accessible and, because they are built within a recess formed on the main body of the container, introduce manufacturing complexities that raise manufacturing costs.", "\nAnother problem encountered with thermoelectric cooling/warming units is that the components of the thermoelectric unit (often known collectively as the \"thermoelectric engine\") are built into portions of the body and/or lid of the cooling/warming unit. ", "Therefore, insertion, removal, and repair of the thermoelectric components comprising the thermoelectric engine can be difficult from a manufacturing and maintenance standpoint. ", "Finally, it is always desirable to maximize the efficiency of a thermoelectric engine, such as that used in a cooling/warming unit." ]

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[ "Q:\n\nDeprecationWarning: Calling an asynchronous function without callback is deprecated with AWS JS SDK\n\nI am trying to use Promises and AWS JS SDK For the first time and I am getting the following error \n\nDeprecationWarning: Calling an asynchronous function without callback is deprecated.", "\n\nI have provided a stack trace below. ", "It appears the error is occurring where I try and use fs.unlink to remove the files I downloaded.", "\nexports.generate = function (req, res) {\n\n if (typeof Promise === 'undefined') {\n AWS.config.setPromisesDependency(require('bluebird'));\n }\n\n var removeBatch = function removeBatch(files) {\n return Promise.all(files.map(function(file) {\n return fs.unlink(file.key);\n }));\n };\n\n var getBatch = function getBatch(files) {\n return Promise.all(files.map(function(file) {\n var params = {\n Bucket: 'my-bucket',\n Key: file.key\n };\n return app.s3.getObject(params).createReadStream().pipe(file.stream);\n }));\n };\n\n var fileNames = ['Original 106fm Logo #268390.jpg', 'test.jpg'];\n var files = fileNames.map(function(fileName) {\n return {\n key: fileName,\n stream: fs.createWriteStream(fileName)\n };\n });\n\n getBatch(files)\n .then(removeBatch.bind(null, files))\n .catch(console.error.bind(console));\n\n}\n\nThis is the stack trace\n(node:63311) [DEP0013] DeprecationWarning: Calling an asynchronous function without callback is deprecated.", "\nat makeCallback (fs.js:127:12)\nat Object.fs.unlink (fs.js:1054:14)\nat /src/splash.js:12:7\nat Array.map (native)\nat removeBatch (/src/splash.js:11:28)\nat <anonymous>\nat process._tickDomainCallback (internal/process/next_tick.js:208:7)\n\nHow do I correctly return a Promise from my removeBatch method?", "\n\nA:\n\nIf you want to use a version of fs.unlink that returns a promise instead of taking a callback then use the mz module like this:\nconst fs = require('mz/fs');\n\nSee the docs:\n\nhttps://www.npmjs.com/package/mz\n\nIt will not only let you do things like this:\nfs.unlink(name)\n .then(() => console.log('Success'))\n .catch(err => console.log('Error:', err));\n\nbut also this inside of async functions:\ntry {\n await fs.unlink(name);\n} catch (e) {\n console.log('Error:', e);\n}\n\nNow, to your question:\n\nHow do I correctly return a Promise from my removeBatch method?", "\n\nWith the mz/fs version of .unlink() it's a one-liner:\nconst removeBatch = files => Promise.all(files.map(file => fs.unlink(file.key));\n\n" ]

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[ "A shipment of protective masks destined for Ontario that was stopped at the U.S.-Canada border on Sunday night is now being released, the province confirmed Monday.", "\n\nOntario Premier Doug Ford said earlier Monday that the shipment contained three million N-95 masks. ", "Ford’s office later clarified that the shipment contained 500,000 masks.", "\n\nIn a one-on-one interview with CityNews Monday morning, Ford warned that if the shipment didn’t go through, Ontario’s frontline health care workers would run out of masks within a week.", "\n\n“We’re getting near the crunch,” Ford said. “", "We’re having a real issue with our U.S. counterparts.”", "\n\nThe premier said he expressed his concerns with the U.S. Trade Ambassador, telling him Ontario is in “desperate need” of the equipment. ", "Prime Minister Justin Trudeau also said he had “productive and positive” conversations with the U.S. regarding the fate of the masks.", "\n\nFord added that the province was exploring other options, including reaching out to contacts in Asia for help.", "\n\nA Woodbridge company is also set to begin production of up to a million masks sometime next week.", "\n\nBREAKING: In one on one interview Premier Ford tells me Ontario will run out of personal protective equipment for health care workers in one week. ", "US stopped shipment from crossing the border yesterday. #", "covid19 ⁦@CityNews⁩ pic.twitter.com/ndR71K0MCt — Cynthia Mulligan (@CityCynthia) April 6, 2020\n\nFord has vocally criticized Trump’s move to halt the shipments, calling it “unacceptable” and vowing to ramp up Ontario’s own manufacturing of personal protective equipment.", "\n\n“When you sit back and you think of your allies and the wars we’ve gone through, and we’ve stood shoulder to shoulder fighting the same enemies. ", "And now we have an enemy and we’re at war and they want to shut things down with their closest ally in the world?” ", "Ford said Saturday from Queen’s Park.", "\n\n“When the cards are down, you see who your friends are, and I think it’s been very clear over the last couple of days who our friends are. ", "You know who our friends are? ", "Every Canadian, look in the mirror, that’s who are our friends are right now.”", "\n\nWatch Premier Ford’s full comments below" ]

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[ "Q:\n\nIncorrect flow of events using FlightJS\n\nI am trying to figure out an issue where a specific div is showing up before an event being fired, specified by FlightJs functions.", "\ndefine([\n 'flight',\n 'mixins/form'\n], function(flight, formMixin) {\n\n function forgotPasswordForm() {\n this.attributes({\n submitButtonSelector: '.btn-submit',\n formSelector: '#forgot-password',\n successMessageSelector: '.success-message',\n successMessageEmailSelector: '.success-message span.success-email',\n emailInputSelector: '#forgot-password #email',\n errorSelector: '#forgot-password .error-message'\n });\n\n this.after('initialize', function() {\n this.on('click', {\n 'submitButtonSelector': this.onSubmitButtonClicked\n });\n this.on('keyup keypress', {\n 'formSelector': this.onFormKeyUp\n });\n });\n\n this.onFormKeyUp = function(event) {\n // Capture and deal with \"Enter\" key being pressed.", "\n var keyCode = event.keyCode || event.which;\n if (keyCode == 13) {\n event.preventDefault();\n this.onSubmitButtonClicked();\n return false;\n }\n };\n\n this.onSubmitButtonClicked = function(event) {\n var email = this.select('emailInputSelector').val();\n if (email.length > 0) {\n this.select('errorSelector').hide();\n this.postForm(this.select('formSelector'))\n // Show success message on error to hide malicious password resetting.", "\n .error(this.showSuccessMessage(email))\n .done(this.showSuccessMessage(email));\n } else {\n this.select('errorSelector').show();\n }\n };\n\n this.showSuccessMessage = function(email) {\n this.select('successMessageSelector').show();\n this.select('successMessageEmailSelector').text(email);\n };\n }\n\n flight.component(forgotPasswordForm, formMixin).attachTo('.forgot-password-form');\n});\n\nAs you can see, after detecting initialization, I specified the on click event for onSubmitButtonClicked.", "\nIn the onSubmitButtonClicked function I collect the field value and pass it to Request handler specified in the mixin 'form' which looks like this:\ndefine([], function() {\n 'use strict';\n\n function formMixin() {\n /*\n * Use an existing form to post data asynchronously, in order to avoid\n * hard coding URLs and data transformation on Javascript.", "\n */\n this.postForm = function($form) {\n return $.ajax({\n type: $form.attr('method'),\n url: $form.attr('action'),\n data: $form.serialize()\n });\n };\n }\n\n return formMixin;\n});\n\nThe issue is that the showSuccessMessage() function is being fired off right after initialization rather that after waiting for Submitbuttonclicked. ", "Is the chaining of the callbacks of error and done incorrect or is there something else wrong with the code ?", "\n\nA:\n\nAssuming that you have a working require.js / webpack config somewhere, you are not using any CSS class to hide the message elements and your markup looks something like this:\n<div class=\"forgot-password-form\">\n <form id=\"forgot-password\" method=\"GET\" \n action=\"https://jsonplaceholder.typicode.com/comments\">\n <input id=\"email\"> \n <div class=\"error-message\">\n Error!", "\n </div>\n </form>\n <button class=\"btn-submit\">\n Submit\n </button>\n\n <div class=\"success-message\">\n Success!", "\n </div>\n</div>\n\nI would say you are only missing to hide the message elements in the initialize event.", "\nIt should look something like this:\n// ...\nthis.after('initialize', function() {\n this.on('click', {\n 'submitButtonSelector': this.onSubmitButtonClicked\n });\n this.on('keyup keypress', {\n 'formSelector': this.onFormKeyUp\n });\n this.select('successMessageSelector').hide();\n this.select('errorSelector').hide();\n});\n// ...\n\nI made a fiddle where you can have a look.", "\n\n" ]

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[ "Q:\n\nfor loop through php array\n\nGuys this is the complete code: \n $response = $this->db->select('DATE(`created_at`) as `day`')->select('MIN(`paid_amount`) as `min_amount`')->select('MAX(`paid_amount`) as `max_amount`')->get('orders');\n\n$nation = array();\nforeach ($response->result() as $row)\n{\n print_r((array)$row);\n array_push($nation, (array)$row);\n}\n\nI got output for print_r shown below :\n Array\n (\n [day] => 2013-03-24\n [min_amount] => 2.00\n [max_amount] => 2.00\n [avg_amount] => 2.000000\n [total_revenue] => 2.00\n [total_orders] => 1\n [total_subscriptions] => 0\n [total_refunds] => 0\n [refunded_amount] => 1.00\n )\n\nI used the below forloop but its not wrking. ", "how to iterate through this array: \nforeach($nation as $key=>$value)\n{\n echo $key;\n}\n\nA:\n\nTry this:\nforeach($nation as $key=>$value)\n{\n echo $key.\" ", "= \".$value;\n echo \"<br />\";\n}\n\nThat should output:\n day = 2013-03-24\n min_amount = 2.00\n max_amount = 2.00\n avg_amount = 2.000000\n total_revenue = 2.00\n total_orders = 1\n total_subscriptions = 0\n total_refunds = 0\n refunded_amount = 1.00\n\nIf nothing is printed out, it means the array $nation is empty. ", "You can also confirm this by \nprint_r($nation);\n\nEDIT\nAfter seeing your updated question, this should do the trick:\nforeach($nation as $array)\n{\n echo $array['day'];\n echo '<br />';\n echo $array['min_amount'];\n echo '<br />';\n .", "\n .", "\n .", "\n and so on\n}\n\n" ]

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[ "Review of microscopic studies on the fetal and neonatal kidney.", "\nThe developing mammalian kidney has been studied by light microscopic, electron microscopic, immunohistochemical, and autoradiographic techniques. ", "The microscopic studies have been conducted on in vivo samples and in vitro samples. ", "The cellular biology and molecular biology of the developmental steps have been clarified, but more investigations are needed. ", "Information has also been collected concerning the influence of the environment on the microscopic development of the kidney." ]

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[ "Q:\n\nHibernate: Multiple FK relationships\n\nI'm kinda stuck defining a Hibernate Entity:\nAssuming I have the following two tables in a database:\n(A)\n\nfromCompany\ntoCompany\nviaCompany\n\n(B)\n\ncompanyID (PK)\ndescription\n\nwhere the elements of (A) point to the primary key of (B); so there are 3 one-to-one relationships between the FKs and the PK.", "\nI assume 3 OneToOne statements with different mappedBy conditions are not the way to go, mh? ", "Has been a long day - I probably just don't get it ;)\nThanks for your help!", "\n\nA:\n\nIf I understood correctly, you want your database to look like this:\ntableA\n- id\n- fromCompanyId (references tableB.id)\n- toCompanyId (references tableB.id)\n- viaCompanyId (references tableB.id)\n\ntableB\n- id\n- description\n\nIf so, you can certainly have this. ", "You just need to override the default column name for the relationship, so that each association have it's own column name instead of falling back to the default name, which would render the three associations with the same name, causing problems.", "\nI don't really agree with OneToOne, but I assume this was a conscious decision. ", "\nSee this:\nhttp://docs.jboss.org/hibernate/annotations/3.5/reference/en/html/entity.html#entity-mapping-association\n\n" ]

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[ "// Distributed memory traversal implementation.", "\n// Author: Gergo Barany\n// $Id: DistributedMemoryAnalysisTemplateDefs.", "C,v 1.1 2008/01/08 02:55:52 dquinlan Exp $\n\n// DQ (9/28/2007): Comment by Gergo to explain nesting problem:\n// The current implementation of DistributedMemoryAnalysisPreTraversal has an issue within\n// AST node types that may be nested within constructs of the same type (basic blocks within\n// basic blocks, function definitions within function definitions etc.). ", "When entering the\n// first scope in the top-down traversal, it is recorded at the end of the funcDecls list.", "\n// The bottom-up pass (in the destroyInheritedValue function) must check that the node it\n// is invoked with is actually that last element of funcDecls -- only then can the inFunc\n// flag be unset and the number of nodes recorded.", "\n// (In case this doesn't work, complain to gergo@llnl.gov.)", "\n\n\n#ifndef DISTRIBUTED_MEMORY_ANALYSIS_IMPLEMENTATION_H\n#define DISTRIBUTED_MEMORY_ANALYSIS_IMPLEMENTATION_H\n\n//#include <mpi.h>\n#include <math.h>\n\n#define DIS_DEBUG_OUTPUT false\n#define RUN_STD true\n#define RUN_DECLARATION false\n#define ALLGATHER_MPI false\n\n// --------------------------------------------------------------------------\n// class DistributedMemoryAnalysisBase -- version by Gergo (based on nodes weight)\n// --------------------------------------------------------------------------\n\ntemplate <class InheritedAttributeType>\nstd::pair<int, int>\nDistributedMemoryAnalysisBase<InheritedAttributeType>::\ncomputeFunctionIndices(\n SgNode *root,\n InheritedAttributeType rootInheritedValue,\n AstTopDownProcessing<InheritedAttributeType> *preTraversal)\n{\n // This function load balances the work assigned to processors. ", " Work is currently\n // assigned to processors on the basis SgFunctionDeclaration (if it is a defining declaration).", "\n\n DistributedMemoryAnalysisPreTraversal<InheritedAttributeType> nodeCounter(preTraversal);\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> starting traversal of nodeCounter (preTraversal)\" << std::endl;\n#endif\n nodeCounter.traverse(root, rootInheritedValue);\n\n funcDecls = nodeCounter.get_funcDecls();\n initialInheritedValues = nodeCounter.get_initialInheritedValues();\n std::vector<size_t> &nodeCounts = nodeCounter.get_nodeCounts();\n std::vector<size_t> &funcWeights = nodeCounter.get_funcWeights();\n ROSE_ASSERT(funcDecls.size() == initialInheritedValues.size());\n ROSE_ASSERT(funcDecls.size() == nodeCounts.size());\n ROSE_ASSERT(funcDecls.size() == funcWeights.size());\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> nr of funcs: \" << funcDecls.size() << \" inheritedValues:\" << initialInheritedValues.size() \n << \" nodeCounts: \" << nodeCounts.size() << std::endl;\n if (funcDecls.size()>0) \n std::cout << \" >>> example entry 0: funcs[0] \" << funcDecls.back() << \" inheritedValues[0]:\" \n << initialInheritedValues.back() << \" nodeCounts[0]: \" << nodeCounts.back() << std::endl;\n std::cout << \" >>> >>>>>>>>>>>>> done traversal of nodeCounter (preTraversal) \\n\\n\\n\" << std::endl;\n#endif\n\n std::vector<size_t>::const_iterator itr;\n size_t totalNodes = 0;\n size_t totalWeight = 0;\n for (itr = nodeCounts.begin(); itr !", "= nodeCounts.end(); ++itr) \n totalNodes += *itr;\n for (itr = funcWeights.begin(); itr !", "= funcWeights.end(); ++itr) \n totalWeight += *itr;\n myNodeCounts = nodeCounts;\n myFuncWeights = funcWeights;\n \n if (DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0)\n {\n nrOfNodes = totalNodes;\n\n//#if DIS_DEBUG_OUTPUT\n std::cout << \"ROOT - splitting functions: \" << funcDecls.size() << \", total nodes: \" << totalNodes\n << \" totalWeight: \" << totalWeight << std::endl;\n//#endif\n }\n\n\n // load balance!!", "\n size_t lo, hi = 0;\n size_t nodesSoFar = 0, nodesOfPredecessors = 0;\n size_t my_lo, my_hi;\n functionsPerProcess.clear();\n for (int rank = 0; rank < processes; rank++)\n {\n const size_t myNodesHigh = (totalNodes / processes + 1) * (rank + 1);\n // set lower limit\n lo = hi;\n nodesOfPredecessors = nodesSoFar;\n size_t myNodes = nodesOfPredecessors + nodeCounts[hi];\n#if DIS_DEBUG_OUTPUT\n std::cout << \"SPLITTING - rank : \" << rank << \" myNodesHigh \" << myNodesHigh << \" myNodes: \" << myNodes\n << \" lo: \" << lo << \" hi: \" << hi << std::endl;\n#endif\n // find upper limit\n for (hi = lo + 1; hi < funcDecls.size(); hi++)\n {\n#if DIS_DEBUG_OUTPUT\n std::cout << \" SPLITTING - func-hi : \" << hi << \" myNodes: \" << myNodes << std::endl;\n std::cout << \" SPLITTING - mynodes > mynodesHigh : \" << myNodes << \" > \" << myNodesHigh << std::endl;\n std::cout << \" SPLITTING - mynodesHigh - myNodes < nodeCounts[\"<<hi<<\"]/2 : \" << (myNodesHigh-myNodes)\n << \" < \" << (nodeCounts[hi]/2) << std::endl;\n#endif\n if (myNodes > myNodesHigh)\n break;\n else if (myNodesHigh - myNodes < nodeCounts[hi] / 2)\n break;\n#if DIS_DEBUG_OUTPUT\n std::cout << \" hi++\" << std::endl;\n#endif\n myNodes += nodeCounts[hi];\n }\n nodesSoFar = myNodes;\n functionsPerProcess.push_back(hi - lo);\n\n // make sure all files have been assigned to some process\n if (rank == processes - 1)\n {\n if (hi !", "= funcDecls.size())\n {\n std::cout << \"hi: \" << hi << \", funcDecls.size(): \" << funcDecls.size() << std::endl;\n std::cout << \"It looks like you asked me to analyze too few functions in too many processes.\"", "\n << std::endl << \" Please give me fewer processes or a larger program to work on.\" ", "<< std::endl;\n }\n ROSE_ASSERT(hi == funcDecls.size());\n }\n\n if (rank == my_rank)\n {\n my_lo = lo;\n my_hi = hi;\n#if DIS_DEBUG_OUTPUT\n std::cout << \"process \" << rank << \": functions [\" << lo << \",\" << hi\n << \"[ for a total of \"\n << myNodes - nodesOfPredecessors\n << \" nodes\" << std::endl;\n#endif\n }\n }\n\n return std::make_pair(my_lo, my_hi);\n}\n\n//compare function for std sort\nstruct SortDescending : public std::binary_function<std::pair<double, size_t>,std::pair<double, size_t>,bool> \n{\n bool operator()(const std::pair<double, size_t>& s1, const std::pair<double, size_t>& s2) const \n {\n return (s1.first > s2.first);\n }\n};\n\ntemplate <class InheritedAttributeType>\nvoid\nDistributedMemoryAnalysisBase<InheritedAttributeType>::\nsortFunctions(std::vector<SgFunctionDeclaration*>& funcDecls, std::vector<InheritedAttributeType>& inheritedValues,\n std::vector<size_t>& nodeCounts, std::vector<size_t>& funcWeights)\n{\n\n std::vector<SgFunctionDeclaration*> funcDecls_temp(funcDecls.size());\n std::vector<InheritedAttributeType> inheritedValues_temp(funcDecls.size());\n std::vector<size_t> nodeCounts_temp(funcDecls.size());\n std::vector<size_t> funcWeights_temp(funcDecls.size());\n\n // std::cout << \"Sorting all functions according to weight...\" << std::endl;\n // sort all the vectors\n std::vector<std::pair<double, size_t> > weights(funcDecls.size());\n for (int i=0; i< (int) funcDecls.size(); i++) {\n double currentWeight = (((double)nodeCounts[i]*funcWeights[i])/(double)funcDecls.size()/100);\n weights[i].first = currentWeight;\n weights[i].second = i;\n }\n std::sort(weights.begin(), weights.end(), SortDescending());\n for (int i=0; i< (int) funcDecls.size(); i++) {\n funcDecls_temp[i]=funcDecls[weights[i].second];\n inheritedValues_temp[i]=inheritedValues[weights[i].second];\n nodeCounts_temp[i]=nodeCounts[weights[i].second];\n funcWeights_temp[i]=funcWeights[weights[i].second];\n if (my_rank==0)\n if (DIS_DEBUG_OUTPUT)\n std::cout << \" function : \" << funcDecls_temp[i]->get_qualified_name().str()\n << \" weight_mul : \" << (weights[i].first) << \" nodes: \" << nodeCounts_temp[i]\n << \" weight : \" << funcWeights_temp[i] << std::endl;\n }\n funcDecls.swap(funcDecls_temp);\n inheritedValues.swap(inheritedValues_temp);\n nodeCounts.swap(nodeCounts_temp);\n funcWeights.swap(funcWeights_temp);\n}\n\n\n\n// --------------------------------------------------------------------------\n// class DistributedMemoryAnalysisBase -- version by tps (based on computation weight -- dynamic algorithm)\n// --------------------------------------------------------------------------\ntemplate <class InheritedAttributeType>\nvoid\nDistributedMemoryAnalysisBase<InheritedAttributeType>::\ncomputeFunctionIndicesPerNode(\n SgNode *root, std::vector<int>& functionToProcessor,\n InheritedAttributeType rootInheritedValue,\n AstTopDownProcessing<InheritedAttributeType> *preTraversal)\n{\n // This function load balances the work assigned to processors. ", " Work is currently\n // assigned to processors on the basis SgFunctionDeclaration (if it is a defining declaration).", "\n\n DistributedMemoryAnalysisPreTraversal<InheritedAttributeType> nodeCounter(preTraversal);\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> starting traversal of nodeCounter (preTraversal)\" << std::endl;\n#endif\n nodeCounter.traverse(root, rootInheritedValue);\n\n funcDecls = nodeCounter.get_funcDecls();\n initialInheritedValues = nodeCounter.get_initialInheritedValues();\n std::vector<size_t> &nodeCounts = nodeCounter.get_nodeCounts();\n std::vector<size_t> &funcWeights = nodeCounter.get_funcWeights();\n ROSE_ASSERT(funcDecls.size() == initialInheritedValues.size());\n ROSE_ASSERT(funcDecls.size() == nodeCounts.size());\n ROSE_ASSERT(funcDecls.size() == funcWeights.size());\n\n sortFunctions(funcDecls, initialInheritedValues, nodeCounts, funcWeights);\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> nr of funcs: \" << funcDecls.size() << \" inheritedValues:\" << initialInheritedValues.size() \n << \" nodeCounts: \" << nodeCounts.size() << std::endl;\n if (funcDecls.size()>0) \n std::cout << \" >>> example entry 0: funcs[0] \" << funcDecls.back() << \" inheritedValues[0]:\" \n << initialInheritedValues.back() << \" nodeCounts[0]: \" << nodeCounts.back() << std::endl;\n std::cout << \" >>> >>>>>>>>>>>>> done traversal of nodeCounter (preTraversal) \\n\\n\\n\" << std::endl;\n#endif\n\n std::vector<size_t>::const_iterator itr, itr2;\n size_t totalNodes = 0;\n double totalWeight = 0;\n for (itr = nodeCounts.begin(), itr2 = funcWeights.begin(); itr !", "= nodeCounts.end(); ++itr, ++itr2) {\n totalNodes += *itr;\n double currentWeight = (((double)(*itr)*(*itr2))/(double)funcDecls.size()/100);\n totalWeight += currentWeight;\n }\n myNodeCounts = nodeCounts;\n myFuncWeights = funcWeights;\n \n if (DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0)\n {\n nrOfNodes = totalNodes;\n\n//#if DIS_DEBUG_OUTPUT\n std::cout << \"ROOT - splitting functions: \" << funcDecls.size() << \", total nodes: \" << totalNodes\n << \" totalWeight: \" << totalWeight << std::endl;\n//#endif\n }\n\n // changed this so it can be used for defuse for all processors\n // int start_rank=1;\n int start_rank=0;\n // std::cerr << \" *********** processes : \" << processes << std::endl;\n // if only one processor is defined then processor 0 does NOT have to do communication\n // and can hence perform the analysis\n if (processes==1)\n start_rank=0;\n // std::vector<int> functionToProcessor;\n double processorWeight[processes];\n int nrOfFunctions[processes];\n for (int rank = 0; rank < processes; rank++) {\n processorWeight[rank] = 0;\n nrOfFunctions[rank]=0;\n }\n for (unsigned int i=0; i< funcDecls.size(); i++) {\n double currentWeight = (((double)nodeCounts[i]*funcWeights[i])/(double)funcDecls.size()/100);\n double min =INFINITY;\n int min_rank=start_rank;\n // find the minimum weight processor\n for (int rank = start_rank; rank < processes; rank++) {\n if (processorWeight[rank]<min) {\n min = processorWeight[rank];\n min_rank = rank;\n }\n }\n processorWeight[min_rank]+=currentWeight;\n functionToProcessor.push_back(min_rank);\n nrOfFunctions[min_rank]+=1;\n if (my_rank ==0 ) {\n if (DIS_DEBUG_OUTPUT)\n std::cout << \" Function per Processor : \" << funcDecls[i]->get_name().str() << \" weight : \" <<\n currentWeight << \"/\" << totalWeight << \" on proc: \" << min_rank << std::endl;\n }\n }\n for (int rank = 0; rank < processes; rank++) {\n if (my_rank ==0 ) {\n std::cerr << \" Processor : \" << rank << \" has \" << nrOfFunctions[rank] <<\n \" functions. ", "Processor weight: \" << processorWeight[rank] << std::endl;\n }\n }\n\n}\n\n\n\n// --------------------------------------------------------------------------\n// class DistributedMemoryTraversal\n// --------------------------------------------------------------------------\n\n\ntemplate <class InheritedAttributeType, class SynthesizedAttributeType>\nvoid\nDistributedMemoryTraversal<InheritedAttributeType, SynthesizedAttributeType>::\nperformAnalysis(SgNode *root, InheritedAttributeType rootInheritedValue,\n AstTopDownProcessing<InheritedAttributeType> *preTraversal,\n AstBottomUpProcessing<SynthesizedAttributeType> *postTraversal)\n{\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> start computeFunctionIndeces\" << std::endl;\n#endif\n /* see what functions to run our analysis on */\n std::pair<int, int> my_limits = computeFunctionIndices(root, rootInheritedValue, preTraversal);\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> done computeFunctionIndeces\\n\\n\\n\" << std::endl;\n#endif\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> start serialize results\" << std::endl;\n#endif\n /* run the analysis on the defining function declarations found above and store the serialized results */\n std::vector<std::pair<int, void *> > serializedResults;\n for (int i = my_limits.first; i < my_limits.second; i++)\n {\n SynthesizedAttributeType result =\n analyzeSubtree(DistributedMemoryAnalysisBase<InheritedAttributeType>::funcDecls[i],\n DistributedMemoryAnalysisBase<InheritedAttributeType>::initialInheritedValues[i]);\n serializedResults.push_back(serializeAttribute(result));\n }\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> done serialize results\\n\" << std::endl;\n#endif\n\n\n\n#if DIS_DEBUG_OUTPUT\n // in the following we only handle certain functions!!", "\n std::cout << \" >>> >>>>>>>>>>>>> start creating buffer\" << std::endl;\n#endif\n /* compute how much total memory our attributes take up, and concatenate the serialized attributes into a single\n * buffer */\n size_t functions = DistributedMemoryAnalysisBase<InheritedAttributeType>::funcDecls.size();\n int myFunctionsPerProcess = DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[\n DistributedMemoryAnalysisBase<InheritedAttributeType>::myID()];\n int *myStateSizes = new int[myFunctionsPerProcess];\n int myTotalSize = 0;\n for (int i = 0; i < myFunctionsPerProcess; i++)\n {\n myStateSizes[i] = serializedResults[i].first;\n myTotalSize += myStateSizes[i];\n }\n unsigned char *myBuffer = new unsigned char[myTotalSize];\n#if DIS_DEBUG_OUTPUT\n // buffer contains inherited values, i.e. the nodeCount per function\n std::cout << \" total buffer size = \" << myTotalSize << \" FunctionsPerProcess: \" << myFunctionsPerProcess << std::endl;\n#endif\n int sizeSoFar = 0;\n for (int i = 0; i < myFunctionsPerProcess; i++)\n {\n std::memcpy(myBuffer + sizeSoFar, serializedResults[i].second, serializedResults[i].first);\n sizeSoFar += serializedResults[i].first;\n // now that we have made a copy of the serialized attribute, we can free the user-allocated memory\n#if DIS_DEBUG_OUTPUT\n std::cout << \" buffer [\"<<i<<\"] = \" << ((char*)serializedResults[i].second)\n << \" myStateSizes[\"<<i<<\"] = \" << myStateSizes[i] << std::endl;\n#endif\n\n deleteSerializedAttribute(serializedResults[i]);\n }\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> end creating buffer\\n\" << std::endl;\n#endif\n\n\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> start communication\" << std::endl;\n#endif\n /* communicate results: first, gather the sizes of the respective states into an array */\n int *stateSizes = NULL;\n int *displacements = NULL;\n if (ALLGATHER_MPI || DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0) {\n displacements = new int[DistributedMemoryAnalysisBase<InheritedAttributeType>::numberOfProcesses()];\n displacements[0] = 0;\n for (int i = 1; i < DistributedMemoryAnalysisBase<InheritedAttributeType>::numberOfProcesses(); i++)\n {\n // Displacements are in units of data elements, not bytes\n displacements[i] = displacements[i-1] + DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[i-1];\n#if DIS_DEBUG_OUTPUT\n std::cout << \" displacements[\"<<i<<\"] = \" << displacements[i] << \" == functionsPerProcess[i] \" << std::endl;\n#endif\n }\n stateSizes = new int[functions];\n }\n\n#if ALLGATHER_MPI\n MPI_Allgatherv(myStateSizes, myFunctionsPerProcess, MPI_INT,\n stateSizes, &DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[0], \n displacements, MPI_INT, MPI_COMM_WORLD);\n#else\n MPI_Gatherv(myStateSizes, myFunctionsPerProcess, MPI_INT,\n stateSizes, &DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[0], \n displacements, MPI_INT, 0, MPI_COMM_WORLD);\n#endif\n\n#if DIS_DEBUG_OUTPUT\n if (ALLGATHER_MPI || DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0) {\n std::cout << \" MPI_Allgatherv: \" << functions << std::endl;\n for (unsigned int k=0; k<functions;k++) {\n std::cout << \" stateSize[\"<<k<<\"] = \" << stateSizes[k] << std::endl;\n }\n }\n#endif\n\n /* from the state sizes communicated above, compute the total buffer size\n * for all concatenated states, and the indices where each part starts */\n int totalSize = 0;\n int *totalStateSizes = NULL;\n unsigned char* recvbuf = NULL;\n if (ALLGATHER_MPI || DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0) {\n totalStateSizes = new int[DistributedMemoryAnalysisBase<InheritedAttributeType>::numberOfProcesses()];\n int j = 0;\n for (int i = 0; i < DistributedMemoryAnalysisBase<InheritedAttributeType>::numberOfProcesses(); i++)\n {\n displacements[i] = totalSize;\n totalStateSizes[i] = 0;\n int j_lim = j + DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[i];\n while (j < j_lim)\n totalStateSizes[i] += stateSizes[j++];\n totalSize += totalStateSizes[i];\n }\n recvbuf = new unsigned char[totalSize];\n }\n\n /* communicate results: gather the actual state information, concatenating\n * it into recvbuf on each process */\n#if ALLGATHER_MPI\n MPI_Allgatherv(myBuffer, myTotalSize, MPI_UNSIGNED_CHAR,\n recvbuf, totalStateSizes, displacements, MPI_UNSIGNED_CHAR,\n MPI_COMM_WORLD);\n#else\n MPI_Gatherv(myBuffer, myTotalSize, MPI_UNSIGNED_CHAR,\n recvbuf, totalStateSizes, displacements, MPI_UNSIGNED_CHAR,\n 0, MPI_COMM_WORLD);\n#endif\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> end communication\\n\\n\" << std::endl;\n#endif\n\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> start deserialize\" << std::endl;\n#endif \n if (ALLGATHER_MPI || DistributedMemoryAnalysisBase<InheritedAttributeType>::myID() == 0) {\n /* unpack the serialized states and store them away for the post traversal to use */\n functionResults.clear();\n \n int j = 0;\n for (int i = 0; i < DistributedMemoryAnalysisBase<InheritedAttributeType>::numberOfProcesses(); i++)\n {\n int j_lim = j + DistributedMemoryAnalysisBase<InheritedAttributeType>::functionsPerProcess[i];\n int sizeSoFar = 0;\n while (j < j_lim)\n {\n std::pair<int, void *> serializedAttribute\n = std::make_pair(stateSizes[j], recvbuf + displacements[i] + sizeSoFar);\n SynthesizedAttributeType attribute = deserializeAttribute(serializedAttribute);\n functionResults.push_back(attribute);\n sizeSoFar += stateSizes[j];\n j++;\n // std::cout << \" getting results \" << std::endl;\n }\n }\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> end deserialize\\n\" << std::endl;\n#endif \n \n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> start postTraversal\" << std::endl;\n#endif \n\n /* perform the post traversal */\n DistributedMemoryAnalysisPostTraversal<SynthesizedAttributeType> postT(postTraversal, functionResults);\n finalResults = postT.traverse(root, false);\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>> >>>>>>>>>>>>> end postTraversal\\n\" << std::endl;\n#endif \n \n /* clean up */\n delete[] stateSizes;\n delete[] totalStateSizes;\n delete[] displacements;\n delete[] recvbuf;\n }\n delete[] myStateSizes;\n delete[] myBuffer;\n}\n\n\n\n\n\n// --------------------------------------------------------------------------\n// class DistributedMemoryAnalysisPreTraversal\n// --------------------------------------------------------------------------\ntemplate <class InheritedAttributeType>\nInheritedAttributeType\nDistributedMemoryAnalysisPreTraversal<InheritedAttributeType>::\nevaluateInheritedAttribute(SgNode *node, InheritedAttributeType inheritedValue)\n{\n // This is the pre-traversal where the load balancing is computed. ", "To change the\n // grainularity from defining function declarations we have to edit all references\n // to SgFunctionDeclaration (just a few places). ", " One way to abstract the details\n // of how the level of gainulatity can be adjusted would be to have the predicate\n // below use a functior passed in from the outside.", "\n\n // An issue might be that nested defining function declaration (such as those that\n // arise in class declarations) might be a problem for this code. ", " This should be \n // tested. ", "A possible solution would be to ignore defining function declaration in \n // classes (SgMemberFunctionDeclaration).", "\n\n // See note from Gergo at the top of the file.", "\n\n // The grainularity must match that of the other implementation in the \n // DistributedMemoryAnalysisPostTraversal.", "\n\n // If we are entering a defining function declaration, start counting\n // nodes and save the function declaration node and the inherited value to\n // be passed to it.", "\n SgFunctionDeclaration *funcDecl = isSgFunctionDeclaration(node);\n#if RUN_STD\n if (funcDecl) {\n std::string funcname = funcDecl->get_name().str();\n #if DIS_DEBUG_OUTPUT\n std::cout << \" >>>> found function : \" << funcname << std::endl;\n #endif\n }\n#else\n if (funcDecl) {\n std::string funcname = funcDecl->get_name().str();\n if (funcname.find(\"__\")!=std::string::npos) {\n stdFunc=true;\n } else {\n stdFunc=false;\n #if DIS_DEBUG_OUTPUT\n std::cout << \" >>>> found function : \" << funcname << std::endl;\n #endif\n }\n }\n if (stdFunc)\n return inheritedValue;\n#endif\n\n#if RUN_DECLARATION\n if (funcDecl)\n#else\n if (funcDecl && funcDecl->get_definingDeclaration() == funcDecl)\n#endif\n {\n inFunc = true;\n nodeCount = 0;\n weightNullDeref = 1;\n weightAssignOp = 1;\n funcDecls.push_back(funcDecl);\n initialInheritedValues.push_back(inheritedValue);\n std::string funcname = funcDecl->get_name().str();\n#if DIS_DEBUG_OUTPUT\n std::cout << \" >>>> found defining function declaration: \" << funcname\n << \" inheritedValue: \" << inheritedValue << std::endl;\n#endif\n }\n\n // If we are not inside any function, evaluate the preTraversal.", "\n // Otherwise, the preTraversal is not to be called, we count the node and\n // return our inheritedValue as a dummy (it is not used anywhere deeper in\n // this subtree).", "\n if (!", "inFunc)\n {\n#if DIS_DEBUG_OUTPUT\n std::cout << \" . ", "outside function : \" << node->class_name() << std::endl;\n#endif\n if (preTraversal !", "= NULL)\n return preTraversal->evaluateInheritedAttribute(node, inheritedValue);\n else\n return inheritedValue;\n }\n else\n {\n#if DIS_DEBUG_OUTPUT\n std::cerr << \" inside function: \" << node->class_name() << \" nodeCount =\" << nodeCount\n << \" depth=\" << inheritedValue << std::endl;\n#endif\n nodeCount++;\n // calculate the weight of the function\n // this weight is mostly used for the def-use checker\n if (isSgNode(node))\n weightAssignOp++;\n // for defuse we weight loops heigher\n if (isSgWhileStmt(node) || isSgForStatement(node)\n || isSgDoWhileStmt(node)) {\n weightAssignOp+=(weightAssignOp)/5;\n }\n // the following weight should be used if null-deref is checked for\n /*\n if (isSgArrowExp(node) || isSgPointerDerefExp(node) ||\n isSgAssignInitializer(node) || isSgFunctionCallExp(node) ) { \n weightNullDeref++;\n } else if (isSgAssignOp(node)) {\n weightAssignOp++;\n }\n */\n return inheritedValue;\n }\n}\n\ntemplate <class InheritedAttributeType>\nvoid\nDistributedMemoryAnalysisPreTraversal<InheritedAttributeType>::\ndestroyInheritedValue(SgNode *node, InheritedAttributeType inheritedValue)\n{\n#if RUN_STD\n#else\n if (stdFunc)\n return ;\n#endif\n\n // If we are outside all functions, the preTraversal computed an\n // inheritedValue before, so give it a chance to destroy it.", "\n if (!", "inFunc && preTraversal !", "= NULL)\n preTraversal->destroyInheritedValue(node, inheritedValue);\n\n // If we are leaving a function, save its number of nodes.", "\n SgFunctionDeclaration *funcDecl = isSgFunctionDeclaration(node);\n#if RUN_DECLARATION\n if (funcDecl)\n#else\n if (funcDecl && funcDecl->get_definingDeclaration() == funcDecl)\n#endif\n {\n // A better implementation would address that the funcDecl should be\n // checked against the funcDecls list. ", " This implementation will \n // likely fail for the case of nested constructs. ", " Both for inherited \n // and synthesised attributes are a likely problem.", "\n\n nodeCounts.push_back(nodeCount);\n // double result = (double)weightAssignOp*(double)1/log((double)weightNullDeref+1);\n // funcWeights.push_back((int)result);\n // funcWeights.push_back(weightAssignOp*weightNullDeref);\n funcWeights.push_back(weightAssignOp);\n // std::cout << \" pushing back func : \" << funcDecl->get_name().str() << \" weightAssignOp : \" << weightAssignOp << \" weightNullDeref : \" << weightNullDeref <<\n // \" 1/log(weightNullDeref) : \" << (1/(log(weightNullDeref))) << \" result = \" << result << std::endl;\n inFunc = false;\n#if DIS_DEBUG_OUTPUT\n std::cout << \" destroying - save nodes \" << nodeCount << std::endl;\n#endif\n }\n}\n\n\n\n\n\n// --------------------------------------------------------------------------\n// class DistributedMemoryAnalysisPostTraversal\n// --------------------------------------------------------------------------\n\n\n//bool\n//DistributedMemoryAnalysisNamespace::postTraversalEvaluateInheritedAttribute(SgNode *node, bool inFunction)\ntemplate <class SynthesizedAttributeType>\nbool\nDistributedMemoryAnalysisPostTraversal<SynthesizedAttributeType>::\nevaluateInheritedAttribute(SgNode *node, bool inFunction)\n{\n SgFunctionDeclaration *funcDecl = isSgFunctionDeclaration(node);\n\n#if RUN_STD\n#else\n std::string funcname=\"\";\n if (funcDecl) {\n funcname = funcDecl->get_name().str();\n if (funcname.find(\"__\")!=std::string::npos) \n stdFunc=true;\n else\n stdFunc=false;\n } \n if (stdFunc)\n return false;\n #if DIS_DEBUG_OUTPUT\n if (funcDecl)\n std::cout << \" >>> postTraversal - inheritedAttribute: found function: \" << funcname << std::endl;\n #endif\n#endif\n #if DIS_DEBUG_OUTPUT\n std::cout << \" postTraversal - inheritedAttribute on node: \" << node->class_name() << \n \" parentEval (inFunction?): \" ", "<< inFunction << std::endl;\n #endif\n\n // Determine from the inherited attribute and the AST node whether this node is inside a defining function declaration.", "\n if (inFunction)\n return true;\n\n // DQ (9/28/2007):\n // This is where the load balancing grainularity is defined and it must match that of the\n // other implementation in the DistributedMemoryAnalysisPreTraversal\n\n#if RUN_DECLARATION\n if (funcDecl)\n#else\n if (funcDecl && funcDecl->get_definingDeclaration() == funcDecl)\n#endif\n return true;\n\n return false;\n}\n\n\n\ntemplate <class SynthesizedAttributeType>\nSynthesizedAttributeType\nDistributedMemoryAnalysisPostTraversal<SynthesizedAttributeType>::\nevaluateSynthesizedAttribute(SgNode *node, bool inFunction,\n DistributedMemoryAnalysisPostTraversal<SynthesizedAttributeType>::SynthesizedAttributesList synAttrs)\n{\n // If this node is the root of a defining function declaration, return the associated analysis result that was passed\n // to our constructor. ", "If this node is within a defining function declaration, we would like to pretend that we are not\n // even here (since this bottom-up pass is not supposed to traverse functions), so we return some default value. ", "If\n // this node is outside of defining function declarations, perform normal bottom-up evaluation.", "\n\n SgFunctionDeclaration *funcDecl = isSgFunctionDeclaration(node);\n#if RUN_STD\n#else\n std::string funcname=\"none\";\n if (funcDecl) {\n funcname = funcDecl->get_name().str();\n if (funcname.find(\"__\")!=std::string::npos) {\n stdFunc=true;\n } else {\n stdFunc=false;\n #if DIS_DEBUG_OUTPUT\n std::cout << \" .. post synthesizedAttribute function: \" << funcname << \" id-nr:\" << functionCounter << std::endl;\n #endif\n }\n }\n if (stdFunc) {\n return defaultSynthesizedAttribute(inFunction);\n } \n#endif\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" post in (NODE): >> \" << node->class_name() << \" currentNode (inFunction?) \" ", "<< inFunction << std::endl;\n#endif\n\n#if RUN_DECLARATION\n if (funcDecl)\n#else\n if (funcDecl && funcDecl->get_definingDeclaration() == funcDecl)\n#endif\n {\n return functionResults[functionCounter++];\n }\n\n if (inFunction)\n {\n if (!", "synAttrs.empty()) {\n SynthesizedAttributeType attr = synAttrs.front(); // this is a default attribute computed somewhere below\n return attr;\n } else {\n return defaultSynthesizedAttribute(inFunction);\n }\n }\n\n#if DIS_DEBUG_OUTPUT\n std::cout << \" ... EVALUATE synthesized Attribute \" << std::endl;\n#endif\n return postTraversal->evaluateSynthesizedAttribute(node, synAttrs);\n}\n\n#endif\n\n\n" ]

{ "pile_set_name": "Github" }

[ 0, 0.014084507042253521, 0.0027397260273972603, 0, 0, 0.016666666666666666, 0.0035419126328217238, 0, 0.0049435028248587575, 0.010309278350515464, 0.004210526315789474, 0.0037151702786377707, 0, 0, 0.003129890453834116, 0, 0.005221932114882507, 0.0018001800180018, 0.006863780359028511, 0.00490066225165563, 0, 0, 0, 0, 0, 0.02040816326530612, 0, 0, 0.006971340046475601, 0, 0, 0.03389830508474576, 0, 0.005333333333333333, 0, 0.041666666666666664, 0.007352941176470588, 0.0032258064516129032, 0, 0, 0.004235044997353097, 0.006329113924050633, 0.0011627906976744186, 0, 0, 0.007385524372230428, 0.007722007722007722, 0.0023148148148148147 ]

[ "e prime factors of 35315577?", "\n3, 11, 233, 1531\nList the prime factors of 1295301703.", "\n181, 881, 8123\nList the prime factors of 319434845.", "\n5, 17, 127, 233\nList the prime factors of 115226595.", "\n3, 5, 11, 17, 13693\nList the prime factors of 26436779.", "\n59, 71, 6311\nList the prime factors of 10366875.", "\n3, 5, 19, 97\nWhat are the prime factors of 97041452?", "\n2, 24260363\nList the prime factors of 247022700.", "\n2, 3, 5, 269, 3061\nWhat are the prime factors of 10166591?", "\n857, 11863\nWhat are the prime factors of 3602360784?", "\n2, 3, 11, 19, 73, 4919\nList the prime factors of 50989070.", "\n2, 5, 11, 463537\nList the prime factors of 21225162.", "\n2, 3, 7, 107, 4723\nList the prime factors of 150651258.", "\n2, 3, 31, 139, 5827\nWhat are the prime factors of 39499521?", "\n3, 13166507\nWhat are the prime factors of 1027530698?", "\n2, 6977, 73637\nWhat are the prime factors of 1767856355?", "\n5, 47, 7522793\nWhat are the prime factors of 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factors of 36022944.", "\n2, 3, 353, 1063\nWhat are the prime factors of 1905341894?", "\n2, 14747, 64601\nList the prime factors of 25067103.", "\n3, 661, 12641\nList the prime factors of 1678308736.", "\n2, 13, 457, 2207\nWhat are the prime factors of 1416048674?", "\n2, 708024337\nList the prime factors of 2628458480.", "\n2, 5, 19, 1729249\nList the prime factors of 212524340.", "\n2, 5, 7, 127, 11953\nWhat are the prime factors of 8315705029?", "\n8315705029\nWhat are the prime factors of 51806468?", "\n2, 7, 223, 8297\nList the prime factors of 1857439501.", "\n1091, 1702511\nList the prime factors of 232015129.", "\n31, 83, 90173\nList the prime factors of 2259969519.", "\n3, 753323173\nList the prime factors of 2254593295.", "\n5, 17, 19, 1396033\nList the prime factors of 3652981377.", "\n3, 24481, 49739\nList the prime factors of 71370635.", "\n5, 7, 2039161\nList the prime factors of 324827709.", "\n3, 108275903\nList the prime factors of 2447809975.", "\n5, 13, 523, 14401\nWhat are the prime factors of 5704701889?", "\n383, 14894783\nWhat are the prime factors of 52377098?", "\n2, 3511, 7459\nList the prime factors of 211407773.", "\n211407773\nList the prime factors of 58117332.", "\n2, 3, 7, 13, 7603\nList the prime factors of 1888070750.", "\n2, 5, 109, 193, 359\nWhat are the prime factors of 2693409877?", "\n43, 199, 314761\nList the prime factors of 541925682.", "\n2, 3, 107, 844121\nWhat are the prime factors of 89693503?", "\n67, 139, 9631\nWhat are the prime factors of 38650581?", "\n3, 1431503\nWhat are the prime factors of 295668760?", "\n2, 5, 17, 434807\nWhat are the prime factors of 30329722?", "\n2, 15164861\nList the prime factors of 45738589.", "\n13, 3518353\nList the prime factors of 350759985.", "\n3, 5, 239, 97841\nWhat are the prime factors of 402798399?", "\n3, 134266133\nWhat are the prime factors of 32140848?", "\n2, 3, 71, 9431\nList the prime factors of 260133353.", "\n173, 1503661\nList the prime factors of 4384498741.", 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146033\nList the prime factors of 4035580718.", "\n2, 13, 41, 167, 22669\nList the prime factors of 29066051.", "\n7, 71, 233, 251\nWhat are the prime factors of 588114472?", "\n2, 11, 6683119\nList the prime factors of 445579502.", "\n2, 43, 61, 157, 541\nList the prime factors of 6288990009.", "\n3, 59, 35531017\nList the prime factors of 186985072.", "\n2, 11686567\nList the prime factors of 131402277.", "\n3, 29, 283, 593\nList the prime factors of 142002731.", "\n13, 10923287\nList the prime factors of 51604503.", "\n3, 17, 73, 83, 167\nList the prime factors of 120185102.", "\n2, 37, 677, 2399\nList the prime factors of 2706643299.", "\n3, 43, 269, 77999\nWhat are the prime factors of 296790842?", "\n2, 173, 491, 1747\nWhat are the prime factors of 92275306?", "\n2, 46137653\nWhat are the prime factors of 932888709?", "\n3, 83, 1248847\nWhat are the prime factors of 4404519884?", "\n2, 19, 29, 61, 181\nList the prime factors of 2176647377.", "\n17, 128038081\nList the prime factors of 59098567.", "\n11, 5372597\nList the prime factors of 107889430.", "\n2, 5, 11, 67, 14639\nWhat are the prime factors of 1032126?", "\n2, 3, 172021\nWhat are the prime factors of 1407370640?", "\n2, 5, 13, 1353241\nWhat are the prime factors of 548436658?", "\n2, 7, 11, 443, 8039\nWhat are the prime factors of 55855401?", "\n3, 7, 1163, 2287\nList the prime factors of 1591773105.", "\n3, 5, 13, 8162939\nWhat are the prime factors of 591064696?", "\n2, 139, 461, 1153\nWhat are the prime factors of 115212987?", "\n3, 12801443\nList the prime factors of 27888435.", "\n3, 5, 337, 613\nList the prime factors of 31456986.", "\n2, 3, 11, 541, 881\nWhat are the prime factors of 1084427903?", "\n13, 191, 436741\nList the prime factors of 92247634.", "\n2, 317, 145501\nWhat are the prime factors of 75088276?", "\n2, 18772069\nWhat are the prime factors of 216904834?", "\n2, 1471, 73727\nWhat are the prime factors of 110999142?", "\n2, 3, 223, 27653\nList the prime factors of 95073135.", "\n3, 5, 6338209\nWhat are the prime factors of 42124086?", "\n2, 3, 23, 101749\nWhat are the prime factors of 28638836?", "\n2, 59, 121351\nWhat are the prime factors of 239739879?", "\n3, 23, 271, 12821\nList the prime factors of 355061043.", "\n3, 3079, 4271\nWhat are the prime factors of 102858837?", "\n3, 19, 31, 58211\nList the prime factors of 1162579665.", "\n3, 5, 13, 263, 22669\nWhat are the prime factors of 20961547?", "\n89, 235523\nList the prime factors of 374530730.", "\n2, 5, 7, 223, 23993\nWhat are the prime factors of 1173961?", "\n1173961\nList the prime factors of 679463431.", "\n679463431\nList the prime factors of 67504714.", "\n2, 853, 39569\nList the prime factors of 310341962.", "\n2, 7, 3313, 6691\nList the prime factors of 6530843225.", "\n5, 43, 467, 13009\nWhat are the prime factors of 60624393?", "\n3, 263, 76837\nList the prime factors of 167407094.", "\n2, 83703547\nList the prime factors of 1119633218.", "\n2, 11, 29, 1754911\nWhat are the prime factors of 593102990?", "\n2, 5, 59310299\nList the prime factors of 3954650291.", "\n19, 23, 9049543\nList the prime factor" ]

{ "pile_set_name": "DM Mathematics" }

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[ "9800 pro\n\ni recently came across a saphire 9800 pro 256mb agp 8x w/dvi, for 202.00 USD.", "\ni now have a debranded antec 400w PSU. ", "i was wondering what good PSU should i step up to run this card? ", "here is what is currently running:\n3 80mm fans\n1 CoolerMaster Jet Master4\n1 HDD\n1 CDRW drive\n1 Floppy Drive.", "\nATI 9600 SE.", "\nAny Helpful input would be greatly suggested.", "\n\nyou could probably pull of sticking with your current 400w psu. ", "if you really need to replace it i would get a ttgi superflower, something like the one here. ", "super flowers are cheap and very high quality, i have one myself and i would highly recommend it to anyone else.", "\n\nim running 2 hard drives, 5 fans, fan controller and hardcano, 1 cd-rw, floppy, and a 9800 pro all on a 300 watt psu and it works fine. ", "btw i also have the sapphire 9800 pro. ", "got it for $212 total with tax and free shipping on newegg new." ]

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[ "KARACHI: Facebook — one of the world’s largest social media platforms — on Monday blocked Jamaat-i-Islami’s (JI) official and other pages related to the party’s information dissemination, days ahead of its Kashmir March scheduled for Dec 22 in Islamabad, stated a JI spokesman.", "\n\nThe JI spokesman stated that the Facebook administration without any prior notice or warning removed its pages from the platform and also of its leaders, workers and sympathisers who were following the party’s trend for the Kashmir cause.", "\n\n“This is how the Indian lobby is actually manoeuvring at the top in Facebook,” he alleged. “", "The JI, its workers and followers were penalised for raising its voice against Indian atrocities in held-Kashmir. ", "It’s high time the government undertakes tangible and practical measures instead of only issuing statements of condemnation. ", "It’s no more a secret that Facebook allows criticism against Islamic countries but curbs free speech when it comes to India and some other countries,” he added.", "\n\nPublished in Dawn, December 10th, 2019" ]

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[ "Emissive ZnO-graphene quantum dots for white-light-emitting diodes.", "\nHybrid nanostructures combining inorganic materials and graphene are being developed for applications such as fuel cells, batteries, photovoltaics and sensors. ", "However, the absence of a bandgap in graphene has restricted the electrical and optical characteristics of these hybrids, particularly their emissive properties. ", "Here, we use a simple solution method to prepare emissive hybrid quantum dots consisting of a ZnO core wrapped in a shell of single-layer graphene. ", "We then use these quantum dots to make a white-light-emitting diode with a brightness of 798 cd m(-2). ", "The strain introduced by curvature opens an electronic bandgap of 250 meV in the graphene, and two additional blue emission peaks are observed in the luminescent spectrum of the quantum dot. ", "Density functional theory calculations reveal that these additional peaks result from a splitting of the lowest unoccupied orbitals of the graphene into three orbitals with distinct energy levels. ", "White emission is achieved by combining the quantum dots with other emissive materials in a multilayer light-emitting diode." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.", "\nCardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. ", "Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. ", "To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. ", "Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. ", "Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. ", "The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. ", "The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. ", "Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. ", "The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system." ]

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[ "Q:\n\nMySQL is not resolving IP address, but nslookup does resolve\n\nAt work, my team have a MySQL database on a Linux 14.04 box. ", "My team is working on changing the permissions to use hostnames rather than IPs (so that the IT team can do what they want to the network and not worry about breaking our access).", "\nFor example, there would be a user admin@10.10.xxx.xxx that we will want to change to admin@my-ws.co.local. ", "I've been playing around with my user (since I have root and can still log in). ", "After changing the user profile's host from the IP address to the Hostname, Workbench will give the error...\nHOST '10.10.xxx.xxx' is not allowed to connect to this MySQL server\nWhen I log in to the Linux box and use nslookup my-ws.co.local, the response gives me the correct IP address, so I know there no connection issue between the box and the network. ", "And since the response is correct, I am assuming that the internal DNS is working correctly.", "\nChecking the performance_schema.host_cache table, I can see that the IP 10.10.xxx.xxx was not resolved into a host (the HOST column is NULL and the HOST_VALIDATED column is YES).", "\nWhy is MySQL unable to resolve the IP address into the correct hostname, while nslookup works? ", "Is there some setting in MySQL that I need to fix? ", "Do there need to be records in the internal DNS for each workstation of my team?", "\n\nA:\n\nThere's forward lookups, like resolving an A record, and there's reverse lookups, which involve finding a PTR record. ", "They're often paired together on public networks, but remember that one or more A records can point to the same IP but there should be only one reverse PTR record. ", "Additionally, while the PTR record is supposed to be a resolvable address, this may not be the case, the reverse entry might be invalid or resolve to an entirely different address.", "\nUnless you have a resolver for 10.10.in-addr.arpa, which is not normally the case since that's a reserved address space, you cannot reverse lookup the IP back to the hostname.", "\nWith nslookup you can test reverse mapping:\nnslookup 10.10.1.1\n\nWhere that address is whatever you're trying to reverse.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Local Super Bowl TV ratings dip to lowest in 12 years\n\nAfter the Philadelphia Eagles held of the New England Patriots to win their first ever Super Bowl, President Trump congratulated the team on twitter, despite Several Eagles Players already Planning To Skip the White House Visit. ", "For more on the story here is Zachary Devita.", "\nBuzz60\n\nHow would Nick Foles look in an Arizona Cardinals uniform?(Photo: John David Mercer-USA TODAY Sports)" ]

{ "pile_set_name": "Pile-CC" }

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[ "Q:\n\nNSUserDefaults does not in Preferences?", "\n\nAs everybody know, NSUserDefaults is saved in Library/Preferences.", "\nBut....\nAfter I delete com.XXXX.OOO.plist in Library/Preferences/, Xcode still can read Key-Value. ", "Is any other plist at somewhere?", "\nI use Xcode 7.0.1, OS X Yosemite...\n\nA:\n\nI had tried command \ndefaults delete com.XXXX.OOO.plist\n\nor\nrm ~/Library/Preferences/com.", "XXXX.OOO.plist\n\nBut.... it does not work immediately..\nIt has to kill cfprefsd process to refresh NSUserDefaults\nkillall cfprefsd\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "In vitro anticoagulation monitoring of low-molecular-weight heparin.", "\nAlthough low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. ", "We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time. ", "A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. ", "Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. ", "A correlation analysis was made to obtain the regression equation. ", "The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. ", "The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). ", "The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). ", "When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant. ", "The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. ", "The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-IIa activities." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nValidation is not working mvc\n\nI just can`t find out what is wrong. ", "I am trying no to allow setting null values to field, when user tries to do it, it must show message \"*\", and wait for him to set values, but it doesnot work and null values are successfully sent to an action.", "\nModel :\npublic class CompanyMainInfoModel\n{\n public int CompanyId { get; set; }\n\n [Required(ErrorMessage = \"*\")]\n [Display(Name = \"company_name\", ResourceType = typeof(Localization))]\n public string CompanyName { get; set; }\n\n [Required(ErrorMessage = \"*\")]\n [Display(Name = \"company_address\", ResourceType = typeof(Localization))]\n public string CompanyAddress { get; set; }\n\n [Required(ErrorMessage = \"*\")]\n [Display(Name = \"company_director\", ResourceType = typeof(Localization))]\n public string CompanyDirector { get; set; }\n\n [Required(ErrorMessage = \"*\")]\n [Display(Name = \"company_phone\", ResourceType = typeof(Localization))]\n public string CompanyTelephoneNumber { get; set; }\n}\n\nMarkup :\n @model BTGHRM.Models.", "CompanyMainInfoModel\n@{\n Layout = \"~/Views/Shared/_EmployeeMain.cshtml\";\n}\n\n<head>\n <script src=\"~/Scripts/jquery-1.10.2.js\"></script>\n <script src=\"~/Scripts/jquery-ui.js\"></script>\n <script src=\"~/Scripts/jquery.validate.unobtrusive.js\"></script>\n <script src=\"~/Scripts/jquery.validate.js\"></script>\n</head>\n\n<body>\n\n <span class=\"content_h4\">@Resources.", "Localization.company_info</span>\n <br />\n <br />\n\n <div id=\"FormContainer\">\n @Html.", "Partial(\"Partial/_CompanyInfo\", Model)\n </div>\n\n</body>\n\nPartial Markup:\n @model BTGHRM.Models.", "CompanyMainInfoModel\n\n@using (Html.", "BeginForm(\"CompanyInfo\", \"Administration\"))\n{\n <table>\n <tr>\n <td>@Html.", "LabelFor(m => m.CompanyName)</td>\n <td>@Html.", "TextBoxFor(m => m.CompanyName)</td>\n <td>@Html.", "ValidationMessageFor(m => m.CompanyName, \"\" , new { @class=\"text-danger\"})</td>\n </tr>\n <tr>\n <td>@Html.", "LabelFor(m => m.CompanyAddress)</td>\n <td>@Html.", "TextBoxFor(m => m.CompanyAddress)</td>\n <td>@Html.", "ValidationMessageFor(m => m.CompanyAddress, \"\", new { @class = \"text-danger\" })</td>\n </tr>\n <tr>\n <td>@Html.", "LabelFor(m => m.CompanyDirector)</td>\n <td>@Html.", "TextBoxFor(m => m.CompanyDirector)</td>\n <td>@Html.", "ValidationMessageFor(m => m.CompanyDirector, \"\", new { @class = \"text-danger\" })</td>\n </tr>\n <tr>\n <td>@Html.", "LabelFor(m => m.CompanyTelephoneNumber)</td>\n <td>@Html.", "TextBoxFor(m => m.CompanyTelephoneNumber)</td>\n <td>@Html.", "ValidationMessageFor(m => m.CompanyTelephoneNumber, \"\", new { @class = \"text-danger\" })</td>\n </tr>\n </table>\n <input style=\"width:78px\" type=\"submit\" value=@Resources.Localization.save />\n}\n\nAnd despite [Required] it still allows me to set null values to any field.", "\nWhat is wrong with my code?", "\n\nA:\n\nYou have to have unobtrusive scripts enabled in web config\n<add key=\"UnobtrusiveJavaScriptEnabled\" value=\"true\"/>\n\nThen you need to add \n\njquery \njquery.validate.js \njquery.validate.unobtrusive.js\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "× Thanks for reading! ", "Log in to continue. ", "Enjoy more articles by logging in or creating a free account. ", "No credit card required. ", "Log in Sign up {{featured_button_text}}\n\nAn Albany motel owner and manager was found guilty on Thursday of two counts of third-degree sex abuse at the conclusion of his three-day trial in Linn County Circuit Court.", "\n\nDineshkumar Patel faced charges of three counts of first-degree sex abuse. ", "A 12-member jury convicted him of a lesser charge in two of the counts.", "\n\nHe was found not guilty regarding an allegation from 2012, but he was convicted of crimes from 2015 and 2017.", "\n\nThe jury went into deliberations shortly before 5 p.m. on Thursday and the verdict was announced at about 8:15 p.m.\n\nA sentencing date hasn’t been scheduled yet, said a Linn County Circuit Court representative.", "\n\nPatel is the owner of the Budget Inn, 2727 Pacific Blvd. ", "SE.", "\n\nThe victim in the 2017 case, Hayley Crawford of Aumsville, has filed a $500,000 lawsuit against Patel and Budget Inn, saying that she suffered emotional distress, fear and depression after being abused by Patel.", "\n\nIn a separate criminal case, Patel is accused of three counts of second-degree encouraging child sexual abuse. ", "A one-day jury trial in that matter was scheduled to start this week, but has been postponed.", "\n\nKyle Odegard can be contacted at 541-812-6077 or kyle.odegard@lee.net.", "\n\nLove 0 Funny 0 Wow 0 Sad 0 Angry 0\n\nGet local news delivered to your inbox! ", "Subscribe to our Daily Headlines newsletter. ", "Sign up! * ", "I understand and agree that registration on or use of this site constitutes agreement to its user agreement and privacy policy." ]

{ "pile_set_name": "OpenWebText2" }

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[ "Michael Lattke\n\nMichael Stephan Lattke (born 12 May 1942) is a scholar of the New Testament and early Christianity.", "\n\nLattke was born in Stettin, Germany. ", "He was brought up in Solingen and, after attending the Volksschule Wittkuller Straße and Humboldt-Gymnasium before completing his abitur at Gymnasium Schwertstraße, studied at Bonn, Tübingen, Münster, Augsburg and München. ", "In spite of his Roman Catholic background, at Tübingen he also studied Protestant theology, especially under the leading Protestant New Testament scholar Ernst Käsemann. ", "He received the Dipl.-Theol. ", "from Tübingen in 1968, the Dr. theol. ", "from Freiburg in 1974, and the Dr. theol. ", "habil. ", "from Augsburg in 1979.", "\n\nIn 1981 Lattke settled in Brisbane, Australia and began teaching at the University of Queensland, where he also received a D.Litt. ", "in 1992. ", "In 1994 he became professor of New Testament and Early Christianity Studies, and in 1997 he became a senior research fellow of the Australian Research Council. ", "Since October 2007, he has been emeritus professor at the University of Queensland.", "\n\nLattke has published widely on the New Testament, early Christianity, early Judaism, early Christian hymns, and Gnosticism, and he has established himself as the world's foremost authority on the pseudepigraphical Odes of Solomon. ", "In his comprehensive study of the Odes of Solomon, he has argued that the Odes were written originally in Greek. ", "His commentary on the Odes has been translated into English by Marianne Ehrhardt for the Hermeneia series (published 2009 by Fortress Press). ", "He is currently writing a commentary on the Apology of Aristides for the series \"Kommentar zu frühchristlichen Apologeten\" (published by Herder Verlag).", "\n\nIn 2003 the Australian Government awarded Lattke a Centenary Medal for his contribution to the field of early Christian studies, and in 2007 he was presented with the Festschrift, I Sowed Fruits into Hearts (Odes Sol. ", "17:13): Festschrift for Professor Michael Lattke, edited by Pauline Allen, Majella Franzmann and Rick Strelan (Strathfield: St Pauls, 2007).", "\n\nLattke is a member of the Studiorum Novi Testamenti Societas (SNTS), a life member of the Society for the Study of Early Christianity (SSEC), and an Honorary Fellow in the Centre for Early Christian Studies at the Australian Catholic University (ACU).", "\n\nBibliography\nA comprehensive bibliography of Lattke's work is compiled in the Festschrift: I Sowed Fruits into Hearts (Odes Sol. ", "17:13): Festschrift for Professor Michael Lattke, ed. ", "Pauline Allen, Majella Franzmann and Rick Strelan (2007).", "\nEinheit im Wort: Die spezifische Bedeutung von ἀγάπη, ἀγαπᾶν und φιλεῖν im Johannesevangelium (München: Kösel-Verlag, 1975), originally presented as the author's Dr. theol. ", "thesis, Freiburg im Breisgau (1974).", "\nDie Oden Salomos in ihrer Bedeutung für Neues Testament und Gnosis, 4 vols. ", "in 5 (1979–98).", "\nRegister zu Rudolf Bultmanns Glauben und Verstehen, Band I-IV (1984).", "\nHymnus: Materialien zu einer Geschichte der antiken Hymnologie (1991).", "\nCollected Studies in Early Judaism, the New Testament and the Odes of Solomon (1974-1991), (1992) University of Queensland D.Litt. ", "thesis.", "\nOden Salomos (1995).", "\nHerbert Leroy, Jesus: Überlieferung und Deutung, 3rd edition (1999), edited with an introduction and bibliography by Anne Dawson and Michael Lattke.", "\nOden Salomos: Text, Übersetzung, Kommentar, 3 vols. (", "1999-2005).", "\n\"Die Oden Salomos: Einleitungsfragen und Forschungsgeschichte\", Zeitschrift für die neutestamentliche Wissenschaft 98 (2007) 277-307.", "\n\"War der Apologet Aristides ein Mann von Bildung?\", ", "in Frühchristentum und Kultur, ed. ", "Ferdinand R. Prostmeier (2007) 35-74.", "\n\"Druckfehler, Ergänzungen und Verbesserungen im Kommentar zu den Oden Salomos\".", "\n\"Greek Words in the Syriac Text of the Apology of Aristides\", in Malphono w-Rabo d-Malphone: Studies in Honor of Sebastian P. Brock, ed. ", "George A. Kiraz (2008) 383-403.", "\nOdes of Solomon: A Commentary, Translated by Marianne Ehrhardt, Edited by Harold W. Attridge (Hermeneia; Minneapolis: Fortress, 2009).", "\n\"Spuren des Römerbriefs in den Oden Salomos\", in The Letter to the Romans, ed. ", "Udo Schnelle (2009) 543-562.", "\n\"Der Tod Jesu Christi in der Apologie des Aristides. ", "Eine Fallstudie mit forschungsgeschichtlicher Einleitung und Bibliographie\", Early Christianity 1 (2010) 575-601.", "\nDie Oden Salomos: Griechisch-koptisch-syrisch mit deutscher Übersetzung (Darmstadt: WBG, 2011).", "\n\"„Taufe“ und „untertauchen“ in Aphrahats ܬܚܘܝܬܐ (taḥwyāṯā)”, in Ablution, Initiation, and Baptism: Late Antiquity, Early Judaism, and Early Christianity = Waschungen, Initiation und Taufe: Spätantike, Frühes Judentum und Frühes Christentum, ed. ", "David Hellholm, Tor Vegge, Øyvind Norderval, Christer Hellholm (BZNW 176/I–III; Berlin/Boston: De Gruyter, 2011) 1115–38.", "\n\"Eine bemerkenswerte syrische Lesart in Mk 14,25\", Zeitschrift für die neutestamentliche Wissenschaft 104 (2013) 146.", "\nPaul Anton de Lagarde und das Judentum (St Lucia, 2014), 152 pp.", "\n\nReferences\n\nExternal links\n Academia page with publications in pdf\n\nCategory:1942 births\nCategory:Living people\nCategory:20th-century German Catholic theologians\nCategory:21st-century German Catholic theologians\nCategory:Australian historians of religion\nCategory:Australian biblical scholars\nCategory:Roman Catholic biblical scholars\nCategory:New Testament scholars\nCategory:Australian Christian theologians\nCategory:University of Tübingen alumni\nCategory:University of Freiburg alumni\nCategory:University of Augsburg alumni\nCategory:German emigrants to Australia\nCategory:Naturalised citizens of Australia\nCategory:German biblical scholars\nCategory:University of Queensland faculty\nCategory:People from Szczecin\nCategory:German male non-fiction writers" ]

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[ "Q:\n\nWhat is the meaning of \"curl -k -i -X\" in Linux?", "\n\nI have read the man pages of Curl, but I can't understand what those parameters (k, i and X) mean. ", "I see it used in a REST API call, but can someone please explain what those three parameters do? ", "It's not clear in the documentation. ", "\nThank you in advance.", "\n\nA:\n\n-k, --insecure: If you are doing curl to a website which is using a self-signed SSL certificate then curl will give you an error as curl couldn't verify the certificate. ", "In that case, you could use -k or --insecure flag to skip certificate validation. ", " \nExample: \n[root@arif]$ curl --head https://xxx.xxx.xxx.xxx/login\ncurl: (60) Peer's Certificate issuer is not recognized. ", "\nMore details here: http://curl.haxx.se/docs/sslcerts.html \ncurl performs SSL certificate verification by default, using a \n\"bundle\" of Certificate Authority (CA) public keys (CA certs).", "\nIf the default bundle file isn't adequate, you can specify an \nalternate file using the --cacert option.", "\nIf this HTTPS server uses a certificate signed by a CA represented \nin the bundle, the certificate verification probably failed \ndue to a problem with the certificate (it might be expired, \nor the name might not match the domain name in the URL).", "\nIf you'd like to turn off curl's verification of the certificate,\nuse the -k (or --insecure) option.", "\n\n[root@arif]$ curl -k --head https://xxx.xxx.xxx.xxx/login\nHTTP/1.1 302 Moved Temporarily\nDate: Thu, 07 Dec 2017 04:53:44 GMT\nTransfer-Encoding: chunked\nLocation: https://xxx.xxx.xxx.xxx/login \nX-FRAME-OPTIONS: SAMEORIGIN\nSet-Cookie: JSESSIONID=xxxxxxxxxxx; path=/; HttpOnly\n\n-i, --include: This flag will include http header. ", "Usually http header are consist of server name, date, content type etc.", "\nExample: \n[root@arif]$ curl https://google.com\n<HTML><HEAD><meta http-equiv=\"content-type\" content=\"text/html charset=utf-8\">\n <TITLE>301 Moved</TITLE></HEAD><BODY>\n <H1>301 Moved</H1>\n The document has moved\n <A HREF=\"https://www.google.com/\">here</A>.", "\n </BODY></HTML>\n[root@arif]$ curl -i https://google.com\nHTTP/1.1 301 Moved Permanently\nLocation: https://www.google.com/\nContent-Type: text/html; charset=UTF-8\nDate: Thu, 07 Dec 2017 05:13:44 GMT\nExpires: Sat, 06 Jan 2018 05:13:44 GMT\nCache-Control: public, max-age=2592000\nServer: gws\nContent-Length: 220\nX-XSS-Protection: 1; mode=block\nX-Frame-Options: SAMEORIGIN\nAlt-Svc: hq=\":443\"; ma=2592000; quic=51303431; quic=51303339;\nquic=51303338; quic=51303337; quic=51303335,quic=\":443\"; ma=2592000;\nv=\"41,39,38,37,35\"\n<HTML><HEAD><meta http-equiv=\"content-.....\n\n-X, --request: This flag will used to send custom request to the server. ", "Most of the time we do GET, HEAD, and POST. ", "But if you need specific request like PUT, FTP, DELETE then you can use this flag. ", "Following example will send a delete request to the google.com\nExample:\n[root@arif]$ curl -X DELETE google.com\n..........................\n<p><b>405.</b> <ins>That’s an error.</ins>\n<p>The request method <code>DELETE</code> is inappropriate for the URL\n<code>/</code>. ", " <ins>That’s all we know.</ins>`\n\n" ]

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[ "The pathogenesis of pre-eclampsia.", "\nSyncytiotrophoblast normally sheds redundant placental debris into the maternal circulation, a process, which depends on apoptosis. ", "It is renewed from the underlying mononuclear cytotrophoblast. ", "We propose that the continual clearance of this debris from the maternal circulation causes a systemic inflammatory response that is present in all pregnant women in the third trimester. ", "Pre-eclampsia occurs when the systemic inflammatory response decompensates. ", "This may occur if the burden of the debris is abnormally high, or if the woman's response to the process is excessive. ", "There is evidence that oxidative stress in the placenta could lead to an overload of debris by stimulating apoptosis or necrosis or both. ", "Such stress would be most likely with spiral artery disease either from deficient placentation or acute atherosis, In this model, deficient placentation is not the cause of pre-eclampsia but a powerfully predisposing condition." ]

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[ "A structured intentions and action-planning intervention improves weight loss outcomes in a group weight loss program.", "\nTo assess whether forming general behavioral intentions and implementing intentions through action plans promotes weight loss and is moderated by weight loss goals and self-efficacy. ", "A quasi-experimental study comparing change in body mass index (BMI) for 15 months between a behavioral intentions condition (BIC), an implementation intentions condition (IIC), and a comparison condition (CC). ", "Ten-week weight loss program delivered in weekly group meetings at community medical centers. ", "Six hundred thirty-two attendants at the weight loss program (80% of program attendants participated in the study). ", "Weight loss program focused on lifestyle changes, augmented by two experimental conditions (vs. a comparison condition): BIC, intended use of weight loss techniques; IIC, intended use and detailed plans for two techniques. ", "Phone follow-up was conducted 3 and 12 months later. ", "BMI during the program (computed on the basis of weight and height measured on a mechanical medical scale). ", "Experimental manipulations included exposure to list of techniques (BIC/IIC) and structured planning form (IIC); independent variables were assessed with questionnaires (eating self-efficacy, weight loss goal, demographics). ", "Linear mixed models estimating changes in BMI and their interactions with the planning interventions, goals, and self-efficacy. ", "Participants in the BIC and IIC lost 40% more weight during the 10-week program than those in the CC (1.10 and 1.11 BMI points compared with .79; ts < -2.76, ps < .01). ", "Weight loss goals interacted with implementation intentions (t = 2.98, p < .01). ", "Self-efficacy was unrelated to weight loss. ", "No differences were found between conditions at 3 and 12 months after the program. ", "Findings revealed that forming implementation intentions promotes weight loss within a weekly program at a field setting and that its effectiveness depends on initial high goals." ]

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[ "1 of 6 View Caption\n\nMembers of the Mormon Tabernacle Choir are shown at the Capitol in Washington, Jan. 20, 1965 moments before the arrival of Preside Scott Sommerdorf | The Salt Lake Tribune The Mormon Tabernacle Choir sings after LDS President Thomas Monson concluded his remar Leah Hogsten | The Salt Lake Tribune The Mormon Tabernacle Choir performs during the morning session of the 186th Semiannual Gen" ]

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[ "In the case of the death of NYC construction worker Carlos Moncayo, NYCOSH is callling for maximum sentence for Foreman Wilmer Cueva\n\nForeman Wilmer Cueva negligent act caused the death of New York construction worker Carlos Moncayo. ", "Wilmer Cueva, a foreman for Sky Material, an excavation company, was supervising work at a construction site located on 9th Ave in the Meatpacking District in Manhattan.", "\n\nAs the excavation of the site was progressing, Cueva received repeated warnings of imminent danger by an inspector. ", "The trench that had reached 7 feet was not reinforced as it should have been. ", "The NYC construction code requires that any trench reaching 5 feet be reinforced. ", "Cueva ignored the warnings and the code and asked workers to continue to excavate.", "\n\nThe trench was 14 feet and still wasn’t reinforced when it collapsed on Carlos Moncayo. ", "The accident was foreseeable and preventable and Wilmer Cueva acted in a criminal manner. ", "He was was convicted of Criminally Negligent Homicide and Reckless Endangerment by a York State Supreme Court jury. ", "He will be sentenced in December.", "\n\nIn a recent article, the New York Committee for Occupational Safety & Health is calling for a maximum sentence.", "\n\nMoncayo was a Latino worker employed by a non unionized company. ", "Statistics have shown that around 80% of fatal construction accidents occurred on non unionized sites. ", "Among the construction workers killed on the job, 60% of them are Latinos." ]

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[ "Q:\n\nIs mid-water bouyancy a classic example of a balanced but unstable system?", "\n\nI came to this thought experiment as I was pondering good teaching examples of stable and unstable systems. ", " It occurred to me that stable systems are really quite abundant. ", " For a shoot-from-the-hip example, the speed of a car is stable about a given speed given a constant rate of fuel injection, since any perturbation will disappear over time. ", " To be perfectly illustrative, here is a ball on a hill. ", " Note that the forces are balanced in both these cases, but stability is different.", "\n\nNow, the above illustrates the concepts well enough, but I like to present something that's slightly more non-trivial and try to get people to exercise real physical understanding.", "\nConsider:\nA submersible with a compressible cavity. ", " A model sufficient for this will be that of a weight attached to a balloon. ", " Saying it's an airtight bag instead of a balloon might be more straightforward, as it avoids the contribution to pressure from the balloon elasticity itself.", "\n\nI want to make the qualitative argument that given the buoyancy and gravitational forces are balanced at some underwater point (obviously below the surface and above the ocean floor), this point is unstable.", "\nThe logic is that the balloon will increase in volume and decrease in density as it gets closer to the surface, where the pressure is lesser. ", " Correspondingly, increasing depth and pressure contracts the balloon. ", " That means that upward movement causes a net upward force and moving down causes a net downward force. ", " Unstable.", "\n\nSeveral questions\n\nDoes this imply that any submersible (below the surface and above the floor) must actively maintain its depth level? ", " Is the condition associated with this claim that the submersible be more compressible than the liquid? ", " What about a compressible atmosphere?", "\nAre there passive control systems that could maintain a depth setpoint?", "\nWould anyone like to address the problem and questions with equations, derivatives, and all that good stuff?", "\n\nA:\n\nThe assumption here is that the water is more incompressible than a balloon, so that the density variations in the water are less than the density variation in a balloon. ", "This is true for a balloon, but false for a submarine made of steel. ", "The compressibility of steel is roughly 80 times less than the compressibility of water, so if the submarine has thick steel walls, it will make a stable depth equilibrium using bouyancy alone. ", "You can maintain a depth with a submarine by adjusting the density very slightly to the one appropriate for water at a given depth.", "\nFor the balloon, the equilibrium is unstable, but for there to be an equilibrium at all requires that the balloon skin be made of a material significantly denser than water, and the depth where there is balance, the air will be compressed enormously.", "\nEDIT: Submarine compressibility\n(In response to the comments of Zassounotsukushi)\nWhen a submarine is submerged in water, the compressibility is not determined by the bulk compressibility of steel, because the pressure stress has to travel through the much thinner hull to get from one side of the submarine to the other. ", "The actual stress in the hull is increased.", "\nTo see how much it is increased, roughly, consider a model submarine which is a square-box-cylinder, with walls of thickness w and side-length L. The pressure is a flow of momentum per unit length equal to PL from one side (times the length) of the box to the other, through the sides of the wall, and if the thing were perfectly solid, the compressibility would be roughly 80 times less than water.", "\nBut the momentum must flow from right to left through a region of width 2w instead of the full width L, as it would be in a solid steel cylinder, so the actual momentum current in the side of the box is increased by a factor of L/2w. ", "For a round cylinder, up to a factor of order unity (it will be between .5 and 2), the analogous factor is R/w.\nFor a typical submarine, I found a hull width w of 30 cm, while a spatious radius is 6m. The ratio is 1/20, so the submarine is about 20 times more compressible than bulk steel. ", "But this still makes the submarine 4 times less compressible than water, and makes the equilibrium stable. ", "\nSteel balloon\nIn order to make a hollow steel balloon neutrally bouyant, ignoring the density of air, the ratio of unoccupied volume to occupied volume is as the ratio of the density of steel to air volume is as the ratio of the density of steel to water, about 8 to 1. ", "Since this ratio is much smaller than the bulk modulus ratio of 80 to 1, a neutrally bouyant steel balloon will acheive a stable equilibrium. ", "This was the model I originally had in mind for a submarine, and for this model, the walls are extremely thick, and the bulk compressibility is only changed by a factor of order 10 at most, not 80.", "\nBut this model is nonsense: it is assuming an empty submarine! ", "The accurate description is above.", "\n\n" ]

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[ "Annual 3 Chapter 12\n\nWhat Should American Jews Have Done to Rescue Their European Brethren?by Leonard Dinnerstein\n\nAmerican Jewish Commission on the Holocaust. ", "American Jewry During the Holocaust. ", "Submitted by Seymour Maxwell Finger. ", "New York, 1984.", "\n\nIn June 1981 a group of Jews, headed by former United States Supreme Court justice Arthur Goldberg, formed an American Jewish Commission on the Holocaust. ", "Composed of 33 members, including 10 rabbis, eight formerly elected or appointed political officials, a dozen or so Jewish community leaders, and one professor of history, the new commission set out \"to record and publish the truth, as nearly as we would determine it, as to what American Jewish leaders did, and what indeed they might have been able to do in all of the circumstances to mitigate the massive evils of the Holocaust.", "\"1 To that end a professional staff, headed by Ambassador Seymour Maxwell Finger, was put together and individual historians and journalists were asked to do scholarly research on the subject. ", "Their collective findings are reported in Finger's summary and many appendices, which include the original research papers that were done and some miscellaneous material. ", "Together this was printed in 1984 under the title American Jewry During the Holocaust. ", "Most members of the Commission refused to endorse the report, but that fact is buried in one of the bizarrely paginated appendices.2 Another commission member, Elizabeth Holtzman, former Congresswoman and current District Attorney of Kings County (Brooklyn, New York), wrote, \"the creation of the American Jewish Commission on the Holocaust may have given rise to unrealistic expectations that a definitive study would result. ", "No such study did.", "\"3\n\nThat American Jewish politics and personal prejudices affected the formation and ongoing work of the Commission seems certain. ", "When Arthur Goldberg announced the Commission's formation, he indicated that the researchers would delve into the question of what the Jews in the United States knew about Hitler's plans to exterminate the Jews and when they knew it, what American Jewish leaders and organizations did once they received that knowledge, and \"could the persecution of Jews have been limited if American Jews had shown more concern for their coreligionists in Europe and exerted their influence on President Roosevelt and on Congress?\"4\n\nThe framing of the last question suggested that the answer would not reflect well on the actions of American Jewish leaders during World War II in regard to rescue. ", "But in case anyone missed that point, Ambassador (as he likes to be called) Finger emphasized, before the research had even begun, that the findings would be 11 'potentially embarrassing' to some American Jewish groups and are 'likely to be controversial in any case.", "'\"5\n\nDuring the next two-and-a-half years Finger, who is not a trained historian, directed a research staff while members of the Commission, and others, differed over its course and goals. ", "An original financial sponsor, Jack P. Eisner, dissatisfied with what the group appeared to be finding, withdrew from the project, and Goldberg pledged that he would get other funds. ", "One sentence in an early draft of the report, written by researcher Seymour Merlin, who was an outspoken activist for rescue during the war years, read, \"Jewish organizations and their respective leaders were emotionally as well as ideologically so absorbed with their internecine struggles, rivalries and efforts to achieve hegemony in the Jewish community that the perception of the urgency of the rescue was, if not ignored, at least greatly diminished.", "\"6 Apparently, too many Commission members, but not Eisner, objected to both the sentiment and the phrasing, and when that sentence, along with such an abrasive position, was deleted, Eisner and Merlin both left the Commission.7 A revised draft was prepared, and Merlin, without having read it, allowed The New York Times to quote him as saying, \"I don't have to read it to know that the purpose of this report is to whitewash the responsibility and guilt of the Jewish leadership of that time.", "\"8\n\nNaturally, with that kind of background, those who followed the story in The New York Times may have assumed that the work of the Commission did not proceed smoothly, that malcontents chose to air their differences in public, and that the ultimate report would have to be politically acceptable before members of the Commission would give it their stamp of approval. ", "Whatever else might be said on the subject, this is not the kind of process that professional historians engage in when they embark upon their independent endeavors.", "\n\nThe thrust of the report that was finally printed in 1984 (1 gather that no reputable publisher could be found to issue it) is that American Jewry, and specifically American Jewish leaders, did not engage in \"a united, sustained campaign for all out mobilization of American Jews and their organizations on behalf of massive rescue\" during the Holocaust years.9 Whether they could have done more is problematic. ", "But that they should have done more is the theme.", "\n\nAmbassador Finger summarized the events before and during the war, highlighting efforts of American Jewry. ", "What they achieved, Finger notes, \"must not be dismissed as insufficient, particularly in view of their limited power and influence. ", "Indeed, our research indicates that they did more than is generally realized.", "\"10 Among the topics discussed are the inhibiting factors of American antisemitism, the indifference of President Franklin D. Roosevelt and Prime Minister Winston Churchill toward rescue, the hostility of the American State Department, the media's failure to bring more attention to Hitler's atrocities, the American public's reluctance to believe what some Jews said Hitler was actually doing, and so forth.", "\n\nIn a quick first reading one might get the impression that this study was a carefully balanced analysis of what had actually occurred within the ranks of American Jewish leaders and their attempts to save some people from Hitler's ovens. ", "But it is not. ", "Underlying the whole report is an indictment of American Jewish leaders for their timidity, their failure to unite with one another to maximize the possibilities for rescue, their misconception that Hitler and his allies shared the same attitudes toward the Jews, and their early faith that Roosevelt and Churchill really were trying to save those condemned by the Nazis.", "\n\nBy focusing on what America's Jews might have done, or explaining why they did not do more, Finger and the researchers upon whose reports he relied have really missed the eye of the needle. ", "To be sure, in retrospect we see clearly that a greater effort should have been made. ", "And, had all of the options been as easy to see then as they are today, other steps, no doubt, would have been taken.", "\n\nIf any indictment is to be made it should be against President Roosevelt. ", "He knew what was happening and was unwilling to take the necessary political risks that rescue would have entailed. ", "No group could have badgered him to do what he did not want to do. ", "His advisors, Jews and Gentiles alike/ protected him from people he did not want to see. ", "He rarely dealt with rescue because it was not a subject that he chose to entertain. ", "Anyone who knows anything about administration is aware that associates and subordinates who continually bring up topics that the leader cares not to discuss are exiled from the inner circle. ", "What good would it have done if White House advisors like Samuel Rosenman and David Niles had brought unwelcome pressure upon the President? ", "Would they have continued long in close relationship with him?11\n\nThere are many reasons for the failure to rescue the European Jews, but the lack of American Jewish efforts is not among the most salient. ", "Great Britain, in order to placate the Arabs who they feared might align themselves with the Nazis, did not want many more Jews in Palestine. ", "Our State Department supported this position and Roosevelt did not waste much of his political capital trying to countermand it. ", "Besides, the British were urging the United States to alter its extremely tight immigration policy and Roosevelt had little desire to tamper with it.", "\n\nWhile it is quite true that the President could have ordered the State Department and Breckinridge Long, the Assistant Secretary in charge of the Visa Division, to be more lenient and humane in interpreting the law, he failed to do so. ", "In other words, he knew what was being done and did not interfere with the process. ", "Roosevelt did consult with Sam Rayburn, the Speaker of the House of Representatives, and Alben Barkley, the Democratic Senate Majority leader, about admitting more immigrants and/or refugees to the United States, but they told him Congress would never approve of such a proposal.12 He did not press the issue.", "\n\nRoosevelt knew, too, of the depth and intensity of antisernitism throughout the country. ", "He and his key associates were quite sensitive to assaults upon the \"Jew Deal\" and they were not about to provide grist for the mill by making any special efforts to save Jewish refugees. ", "The President maintained that the best way to stop Nazi barbarities was to win the war quickly-and he maintained that stance until his death on 12 April 1945.", "\n\nWhat neither Finger nor any of the other scholars who have written about the United States, Great Britain, and the Holocaust come right out and say is that Roosevelt and Churchill knew the consequences of their inaction. ", "Yet they preferred to let the Jews die rather than stir up dissension within their own countries and among the Arabs, or use the full extent of their powers to save Jewish lives.", "\n\nRoosevelt, especially sensitive to public opinion in the United States, always held his wet finger to the wind. ", "He sensed what the public would support. ", "Only once as President, when he tried to pack the Supreme Court in 1937, did he misjudge popular sentiment. ", "He was a strong and popular President because he led the people in the direction that they wanted to go. ", "He was neither a risk taker nor a Don Quixote fighting windmills. ", "He had no intention of dividing the country and diverting the war effort by going out on a limb to rescue Jews.", "\n\nAnother factor which affected American rescue policies, but which I do not recall Finger discussing, was the conservatism of the 78th Congress, elected in November 1942. ", "The results of that election shocked both the Democrats and neutral observers. ", "The Republicans came within eight votes of capturing control of the House of Representatives and isolationists in both parties grew stronger. ", "This Congress turned out to be the most fractious and conservative legislature with which Roosevelt had to work during his 12 years as President. ", "Members of the conservative coalition (most Republicans and most southern Democrats) spoke out against liberal legislation and policies, and the Ways and Means Committee in the House of Representatives turned down the President's request for broader wartime powers, including the right to suspend federal statutes \"affecting movement of war goods, information and persons into or out of the United States.\" ", "On 13 February 1943 a representative in the British Embassy in Washington sent back a report to his government in London which stated that \"the administration is under fire from many quarters and is showing signs of trimming its sails before the winds of opposition which are blowing strong.", "\"13\n\nThe Senate included vitriolic opponents of the President's internationalism, such as Senators Hiram Johnson (R., California), Henrik Shipstead (R., Minnesota), William Langer (R., North Dakota), Burton K. Wheeler (D., Montana), and Robert R. Reynolds (R., North Carolina). ", "Some of them had been somewhat outspoken in their antisernitic feelings. ", "Tangling with them over the issue of rescuing Jews would have opened up the field for charges that Roosevelt was once again subverting American interests for Jewish causes. ", "Given the tension that already existed between many in Congress and the President, the renewed strength shown by the isolationists after the 1942 elections, and the existing fear that the move toward the right among the electorate portended a postwar shift to Republican isolationism, it becomes easier to understand why Roosevelt refused to make any bold moves toward rescue and why the efforts of American Jews faced steeper hurdles.14\n\nOne must also recognize that millions of Americans would have been equally indifferent to the annihilation of Jews even if they had known all of the details of Auschwitz. ", "Since the beginning of the Spanish Civil War in 1936, Catholics and Catholic publications had railed against the Jews for supporting the Loyalist cause even though Loyalists raped and killed nuns and burned Catholic Churches in Spain.15 The division of American opinion over the Spanish Civil War, in fact, gave impetus to the strongly antisernitic Christian Front in the late 1930s and 1940s, especially in New York and Boston. ", "Furthermore, not only did antisernitic incidents in the United States punctuate the weeks and months of the war, but polls showed that Americans regarded Jews as the greatest menace to this country after the Germans and the Japanese.16\n\nIn addition to the virulent antisemites there were the genteel bigots. ", "Opinion leaders who spoke softly, rarely uttered a vulgarity, and never would have thrown a stone at anyone, nevertheless lived in restricted communities, played golf in exclusive country clubs, and did not hire Jews. ", "These people had what might euphemistically be called \"clout,\" but they certainly had no intention of using it to save Jews and might even have exerted counterpressure had there been visible signs of diverting the war effort. ", "Nor did spokesmen for the major American Protestant denominations or members of the hierarchy of the American Roman Catholic Church speak out for the need to make a special effort to rescue Jews.", "\n\nPerhaps the major reason for the failure to implement rescue was that no country wanted more Jews. ", "Suppose the Jews had been saved? ", "Britain did not want them at home or in Palestine. ", "The United States did not want them. ", "Canada did not want them. ", "Where would they have gone? ", "Critics of the failure to rescue seem unable to come to terms with what was then reality: almost every nation and world leader preferred to ignore the Jews rather than to admit them to their own countries. ", "This is the fact that must be faced, not the lack of vigor on the part of American Jewry. ", "David Wyman, in his book The Abandonment of the Jews (New York, 1984), stated the issue clearly. ", "During the war, he wrote,\n\n... the plain truth is that many Americans were prejudiced against Jews and were unlikely to support measures to help them. ", "Antisemitism had been a significant determinant of America's ungenerous response to the refugee plight before Pearl Harbor. ", "During the war years, it became an important factor in the nation's reaction to the Holocaust.17\n\nThus when Finger writes a report showing how much or how little Jews did to rescue their coreligionists I think he ought to have dwelt more on the context in which they lived and worked. ", "To be sure, he mentions all of the salient points but then goes on to say \"public opinion in both the United States and Britain included not only anti-Semitic elements but many enlightened influences as well, and many non-Jewish as well as Jewish voices in both countries were raised against the official policy of inaction.", "\"18 Finger is, of course, quite right about this. ", "But how influential can dissidents be when a strong President resists their pressure? ", "Protests against the Vietnamese War in the United States began in 1965, grew through 1968, and continued into the early 1970s. ", "President Lyndon B. Johnson chose not to run for office again because of the protests and his successor, Richard Nixon, held well publicized negotiations with the North Vietnamese. ", "But the war did not end until January 1973, with the most massive bombing attack taking place in December 1972. ", "At other periods during our lifetime people have been brutally treated in South Africa, Chile, El Salvador, and other nations. ", "Protest groups in the United States have publicized atrocities in those countries, but their cries have had little effect on American policy. ", "Why, then, should we presume that American Jewish leaders would have been able to arouse an antisernitic public into pressuring President Roosevelt to alter his wartime policies in order to save Jewish lives?", "\n\nHistorians know that events do not occur in a vacuum. ", "A much better analysis of the activities of the Jewish leaders and organizations than Finger's appears in David Wyman's The Abandonment of the Jews. ", "If the Goldberg Commission and Finger had waited, their report, American Jewry During the Holocaust, would have been unnecessary. ", "Wyman puts the American Jews and their efforts into a much broader context, shows what they did try and at which points they were rebuffed, and indicates as well how the confluence of circumstances circumscribed their goals. ", "The Jews tried to have their European brethren rescued, but the prime American Jewish movement was for a Jewish state in Palestine after the war. ", "Maybe they miscalculated; maybe the thrust for rescue should have been more intense. ", "But maybe they were too demoralized, too frightened by the antisernitism that had been growing in the United States since the 1920s, and too insecure to challenge vigorously a popular President in diverting the war effort.", "\n\nFurthermore, too many Jews were frightened by American conditions and felt powerless to do anything about them. ", "Washington newspapers reported an increase in antisernitism in the nation's capital in 1944 and in January 1945, one pleading Jew asked, \"What Can the Jews Do?\":", "\n\nAnti-Sernitism has not yet become a national menace to the United States. ", "It is only at the stage where it is a personal tragedy that humiliates, frightens, and embitters individuals. ", "It is obviously beyond the capabilities of the minority of Jews-the group against whom it is directed-to stop the progress of anti- Semitism here. ", "They are too weak and too few. ", "The greater part of the task of up-rooting anti-Semitism must be done-if at all-by the Gentile majority with the Jewish minority cooperating.19\n\nSuch views permeated the thoughts of many Jews at that time and it reined in any bold efforts that other Jews might have had about mobilizing this nation to rescue coreligionists in Europe.", "\n\nOther factors to which the American Jewish Commission's report fails to give sufficient weight are the divisions in the American Jewish community and the lack of dynamic leadership. ", "Some of the better educated and more articulate Jews like judge Jerome Frank had already committed themselves. ", "On the eve of Pearl Harbor, for example, Frank wrote, \" . . . ", "however much I might be anguished at the plight of the oppressed people in other countries, Jews or Gentiles, I [do] not believe that America should sacrifice its welfare to rescue them.", "\"20 Frank spoke for many Jews who later helped form the anti-Zionist American Council for Judaism in 1943 and whose views received prominence in the pages of The New York Times because its publisher, Arthur Hays Sulzberger, sympathized with the group's position. ", "The Zionists, themselves split into factions, also did not focus on rescue. ", "Although the Zionists certainly did not want to see even one Jew killed, Hitler's policies provided them with the dramatic opening needed to pursue relentlessly their cause for a Jewish state in the Middle East. ", "Their zealousness and commitment in that area led them to call frequently for the opening of the gates to Palestine, but it also clouded their vision and concern for other possible areas of escape for Europe's Jews.", "\n\nAmerica's Jews needed another Louis Marshall, the brilliant head of the American Jewish Committee from 1912 until his death in 1929. ", "Thereafter the Committee, which had been the leading Jewish defense organization to that time, suffered through several weak presidents until the end of the 1940s. ", "Judge Joseph Proskauer, AJC President during the war years, was too concerned about his status as a patriotic American, privy to conversations with State Department officials, to have exerted the kind of direction the Committee had experienced with Marshall at the helm.21\n\nThat is not to say, of course, that no efforts at rescue were made. ", "Finger acknowledges several in his report. ", "The President, State Department officials, and members of Congress were petitioned. ", "A massive rally calling for rescue was held in Madison Square Garden on 1 March 1943. ", "Within 48 hours, however, Roosevelt threw out a placebo of his own and the Jews had to wait before doing much more. ", "The State Department issued a press release announcing that a conference about rescue would be held with the British in the spring. ", "Shortly thereafter the place, too, was made public: Bermuda. ", "Certainly rescue advocates could do little until after the conferees met and announced their decisions. ", "So more time elapsed-with nothing of consequence done and little that rescue advocates could do but wait. ", "People now know that the Bermuda Conference accomplished nothing and wasted everyone's time, but contemporaries were informed by the State Department that \"steps are now being taken to put into effect the recommendations made by the Conference.", "\"22\n\nNot until December 1943, after Breckinridge Long's severely restrictive immigration policies had been exposed, did the Senate Foreign Relations committee call upon Roosevelt to do something to save Hitler's victims. ", "It was a month later that Secretary of the Treasury Henry Morgenthau, Jr., approached Roosevelt about changing our rescue policy. ", "And it was in response to these efforts that Roosevelt established the War Refugee Board. ", "But as Morgenthau confided to his associates, \" . . . ", "the thing that made it possible to get the President really to act on this thing was the Resolution which at least had passed the Senate to form this kind of a War Refugee Board.... I think six months before I could not have done it.", "\"23\n\nEven with the establishment of the War Refugee Board only thousands, not millions, were saved. ", "Roosevelt, shrewd politician that he was, set up the Board but provided insufficient financing for its operations. ", "And then it took him several more months to approve of a shelter in the United States-for 1,000 refugees whose lives were not in danger in Italy. ", "One shelter at Fort Ontario was all that the President would support. ", "He believed the political risks in trying for more outweighed any possible gain. ", "To be sure, the War Refugee Board did save thousands of Hungarian Jews and others as well. ", "But the President was not ready to do anything about rescue before 1944, and unwilling to do more than he did.", "\n\nAnd now I come back to a point already made before that I think needs restatement. ", "How, exactly, does one deal with a leader who does not want to move in a particular direction? ", "Presidents cannot always effectuate their policies, but they certainly have the power to curtail what they do not want done. ", "Administrative officials are always attuned to presidential policies. ", "Sometimes they derail them but more often than not they reflect the will of the leader. ", "American policy in regard to rescue stemmed from Roosevelt and what he considered viable during World War Il. ", "No one should blame the victim. ", "American Jewish leaders of the period were among the victims, not the perpetrators, of this nation's failure to achieve more. ", "The members of the Goldberg Commission probably had high hopes when they agreed to serve. ", "But those hopes were frustrated and ultimately disappointed by the methods used and the results obtained. ", "Elizabeth Holtzman noted that \"commission members had only a limited role in preparing the final report; they never held hearings or took oral testimony.\" ", "The reports and papers commissioned by the staff, Holtzman continued, \"do not provide a comprehensive or final analysis of the response of American Jewish organizations and leaders to the Holocaust and certainly do not provide a definitive evaluation of the response of American Jewry as a whole.", "\"24\n\nComments of another Commission member, Rabbi Morris Sherer, suggest that at the end heated discussions may have occurred among the commissioners and that inadequate direction may have been given earlier to the staff:\n\nThe decision reached at the Commission's final meeting on September 20, 1983, to take no formal action as a Commission to reach joint conclusions or to approve or disapprove the report, was indeed wise as well as just. ", "There is no way that one can reconcile the divergent views of the Commission members about what actually took place in the various circles of American Jewish leadership during the bitter years of the Holocaust. ", "The very fact that the Commission could not unite on a report in itself is clear testimony that the chasm that separates its members is so wide that it is simply not bridgeable.25\n\nRabbi Sherer's remarks remind us of the pitfalls that await a group project when its leaders lack expertise in areas relevant to the enterprise. ", "Whatever accomplishments Arthur Goldberg and Max Finger may otherwise have, they are not in the field of history. ", "Having them supervise and oversee such an important project was equivalent to having the football coach teach high school history.", "\n\nNOTES\n\n1. ", "American Jewry During the Holocaust, p. ii.", "\n\n2. ", "Ibid., ", "appendix 3, p. 15.", "\n\n3. ", "Ibid., ", "appendix 3, p. 14.", "\n\n4. ", "New York Times, 27 Sept. 1981, p. 40.", "\n\n5. ", "Ibid.", "\n\n6. ", "New York Times, 21 Mar. 1984, p. B 4. ", "See also S.E. Peck, \"Campaign for an American Response to the Nazi Holocaust, 1943-1945,\" Journal of Contemporary History 15 (1980): 377.", "\n\n7. ", "New York Times, 9 Mar. 1983, p. B 11.", "\n\n8. ", "Ibid.", "\n\n9. ", "American Jewry During the Holocaust, pp. ", "36-37.", "\n\n10. ", "Ibid.", "\n\n11. ", "Rosenman had been a close advisor to Franklin D. Roosevelt from the time he was Governor of New York (1929-32) until the President's death in 1945. ", "Niles started working for President Roosevelt in 1935 and was officially appointed Special Assistant to the President in 1942. ", "Minority affairs was one of his chief responsibilities, and he had very close relations with officials of the leading Jewish agencies as well as other important American Jews." ]

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[ "Yahoo Goes Hollywood for CEO\n\nShare\n\nYahoo Goes Hollywood for CEO\n\nTerry Semel, the man Yahoo just tapped to head its global Internet business, said he really wasn't looking for a new job.", "\n\nAfter spending 19 years as chairman and co-CEO of the Warner Brothers media empire, Semel stepped down 14 months ago with plans to spend his time as \"a student of the Internet.\" ", "He put together a private investment fund and spent much of 2000 meeting with Net firms seeking funding.", "\n\n\"I wasn't necessarily looking to be a corporate chairman or CEO again,\" Semel said Tuesday.", "\n\nThat all changed when Yahoo (YHOO) came knocking on his door this spring. ", "Tim Koogle, Yahoo's chairman and CEO of the past six years, announced in March he planned to step down. ", "Yahoo co-founder Jerry Yang said Semel was one of the first candidates the company put on its list of potential successors.", "\n\nYang said the search team focused on Semel largely because they believed his post at Warner Brothers required many of the same skills needed to run a company like Yahoo.", "\n\nBoth companies, he noted, have ample overseas operations and have faced pressure to expand rapidly outside their main area of business. ", "Yang said Semel played an instrumental role in increasing Warner Brothers' total revenue from under $1 billion to close to $11 billion.", "\n\nNumbers aside, Yahoo's selection of Semel also adds a distinctive Hollywood flavor to what has long been a quintessentially Silicon Valley firm. ", "The company also adds an executive who is well known in media and entertainment circles.", "\n\nSemel's 24-year legacy at Warner Brothers is linked closely to that of his longtime business partner, Bob Daly. ", "The two men served as co-chairman and CEOs of the studio until their joint departure in October 1999.", "\n\nUnder their leadership, Warner Brothers branched out into new venues, including the development of a network of Internet sites. ", "Semel and Daly also played a role in launching the WB television network, creating a vast film and television library, and introducing DVD recordings.", "\n\nDuring their tenure, Semel and Daly oversaw a string of high-budget films with star-studded casts that included the Batman and Lethal Weapon series. ", "Under their auspices, the studio also launched three Best Picture Academy Award winners: Chariots of Fire,Driving Miss Daisy and Unforgiven. ", "Their careers at Warner Brothers also included some high-profile flops, including the costly and critically panned 1997 flick The Postman.", "\n\nPerhaps more relevant to his new job is Semel's experience in the Internet business, which has included a few disappointments. ", "One of those was Entertaindom.com, a Web entertainment hub started by Warner Brothers that parent company AOL Time Warner has since shut down. ", "Semel said the site shared the same fate as countless other once-promising Internet ventures that proved to have been launched \"a little too early.\"", "\n\nAnother unfortunate investment was one that Semel made in Digital Entertainment Network, or DEN, which offered original programming online but flamed out in May 2000.", "\n\nBy joining Yahoo, Semel links his fate with a company that has achieved phenomenal success drawing traffic from across the world. ", "In the month of March, Yahoo said it was visited by more than 192 million different users worldwide.", "\n\nHowever, Semel joins the firm at time when Yahoo, along with the rest of its Internet brethren, is facing tough economic conditions. ", "Confronted with shrinking advertising revenues as many of its dot-com customers scale back or shut down, Yahoo reported a loss in its most recent quarter. ", "The company also announced last week that it would lay off approximately 12 percent of its staff.", "\n\nIn comments made during a Tuesday press conference, Semel said Yahoo is facing the kinds of troubles he's familiar with.", "\n\n\"The situation at Warner Brothers in 1980 was quite similar to Yahoo in 2001,\" Semel said. ", "Both companies were aware that their main sources of revenue (movie sales for WB and advertising for Yahoo), were at least temporarily on the decline. ", "Both were under pressure to come up with new money-making strategies. ", "And both were viewed among investors as possible targets for a takeover.", "\n\nYahoo executives skirted the issue of whether the online giant is being eyed as a takeover candidate. ", "However, the company made it clear that whatever happens in the long-term, its executive team is handing over to its new CEO a larger-than-anticipated share of responsibility for running the company.", "\n\nAlthough Yahoo had originally expected to keep Koogle in the chairman's position, it decided to hand that post to Semel. ", "Koogle, who will serve as vice chairman until August and remain on Yahoo's board, said the decision was intended to ensure \"there's absolutely no question about who's running the company.\"", "\n\nYahoo executives also hinted that Semel will be compensated handsomely for his new duties. ", "The incoming CEO purchased one million shares of Yahoo stock and will get an undisclosed salary and stock option package that Yang said \"is consistent with the level being paid to our most senior executives.\"" ]

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[ "On May 23, 2017, New Hampshire wildlife officials announced a plan to euthanize a mother bear and three cubs following increasingly brazen behavior in Hanover neighborhoods near Dartmouth College.", "\n\nThis timeline put the decision, which provoked public outcry, into context by tracking several events before the announcement, including months of warnings for residents to secure bear attractants. ", "As events continued to unfold, ultimately leading to the governor’s intervention, the timeline helped readers follow the developments.", "Click here to view.", "\n\nMany readers were devastated in May 2017 to learn of the closing of Everything But Anchovies in Hanover after 38 years in business. ", "Propelled by social shares from well-known Dartmouth College alumni who considered EBAs to be part of their college experience, the breaking-news scoop I discovered set a record for most hits on a single article.", "\n\nI compiled a sampling of reactions on Storify (click here to view) to complement reporter Jordan Cuddemi’s story, and secured the restaurant’s well-known radio jingle to use in avideo, shot by Jovelle Tamayo and edited by me.", "\n\nWashington, D.C. — After Ruth Heindel and Carissa Aoki had listened to speakers at the Women’s March on Washington for four hours outside the Air and Space Museum on Saturday, the Dartmouth College graduate and post-doctoral ecology students became ecstatic when they learned that organizers were changing the route.", "\n\nIt wasn’t the last-minute change they celebrated, but the reason: The event had drawn so many marchers that they were already filling up the route. ", "They would have to add some new twists and turns to give marchers room to walk.", "\n\n“This felt like a really big deal,” Heindel, 28, said at the march’s conclusion. “", "To feel like I was one of the people in one of those enormous historical photos … and that it was made up of all these individuals.” ", "Continue reading →\n\nLebanon — In a brightly lit conference room last week, more than 20 people — most from the Upper Valley — slowly and silently walked past a long line of large pieces of paper taped on the wall, reading dozens of slurs scrawled in magic marker that are used to stigmatize people with addiction, alcoholism, mental illness and those trying to get sober.", "\n\nThe group, participants in a weeklong course that would teach them how to coach people in addiction recovery, had brainstormed and written the words themselves, in an exercise designed to address stigma.", "\n\nMany wrote from experience: As members of each of those groups, they were familiar with the labels that stuck to them as individuals, sometimes for decades." ]

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[ "Background {#Sec1}\n==========\n\nLumbar back pain, with a lifetime prevalence of about 80 %, leads to enormous direct and indirect costs to the health care system \\[[@CR1]--[@CR3]\\]. ", "It can affect people of all ages and, once ocurred, in many cases is a recurrent condition \\[[@CR4]\\]. ", "While benign and mixed back pain are believed to reach their maximum in the sixth decade of life, it is assumed that severe disabling episodes due to chronic low back pain rise in prevalence with increasing age \\[[@CR5], [@CR6]\\]. ", "Depending on the cause of the patient's complaints, as well as the patient's condition and expectations, therapeutic approaches range from conservative treatment, including physiotherapy with analgesics, orthotics, and local infiltration therapy, to multimodal pain therapy and finally to surgical procedures. ", "Over the past decades, the number of spine surgeries has increased enormously \\[[@CR7]\\]. ", "This is partly because the number of otherwise healthy patients in our ageing society is increasing and better medical care is available, even in rural areas. ", "Moreover, improvements in surgical, perioperative, and anaesthesia techniques have allowed a shift in the threshold of indications for surgery. ", "On the other hand, some authors claim that over the past years, therapeutic strategies have overly focused on surgical treatment, an opinion that seems to be supported by an absolute increase in failure rates after lumbar fusions, followed by adjacent lumbar segment degeneration \\[[@CR8]\\]. ", "Lumbar spine surgery, with its complications, can be contrasted with conservative strategies that also achieve good results \\[[@CR9]\\]. ", "It is therefore of paramount importance to identify patients who will benefit from spine surgery. ", "This is especially so in many cases in which patients' complaints and medical history, together with clinical observations, do not correspond to structural pathological changes found on X-rays or magnetic resonance imaging (MRI).", "\n\nFor this reason, the concept of inpatient gradual diagnostics (IGD) has found widespread use in Germany over the past two decades \\[[@CR10]\\]. ", "Through local administration of analgesic and anti-inflammatory agents to a special area of interest, e.g. facet/sacroiliac joints or the epidural space, the effect of surgery can be temporarily simulated. ", "From the patient's statement about the alleviation of pain, the surgeon can draw conclusions concerning its cause.", "\n\nThe aim of this study was to evaluate the extent to which IGD influences the decision about the nature and scope of surgical treatment strategies, and the way in which it does so, in patients with chronic lumbar back pain.", "\n\nMethods {#Sec2}\n=======\n\nProcedure {#Sec3}\n---------\n\nDuring our spinal consultation, we compare a patient's clinical findings with radiographs (antero-posterior and lateral) and an MRI of the lumbar spine. ", "In cases with a discrepancy between the clinical presentation and the radiological findings in particular, IGD is scheduled to evaluate the possible benefit to the patient from surgical intervention.", "\n\nOn the day that the patient is admitted for IGD, a laboratory blood analysis is performed to rule out possible infection. ", "Over the course of the following days, the patient receives selective infiltrations at loci that, depending on the patient's response to the anti-inflammatory and analgesic drugs, influence the decision of the ensuing treatment strategy. ", "Target sites are mainly the facet joints, epidural space, sacroiliac joints, deep back muscles or the spinal nerve at its exit through the intervertebral foramen. ", "In the case of an epidural injection, for safety reasons, patients are asked to stay in bed for 2 h with their trunk elevated 30°. ", "Injections are performed daily and their effect is registered by repeatedly using the Numeric Pain Rating Scale before and after infiltration to assess pain and enquiring about pain alleviation as a percentage of pain reduction in the back or leg. ", "The surgeon can thus draw conclusions as to the main causes of the patient's pain. ", "At the end of the week, from the synopsis of the responses to the injections, along with the clinical and radiological findings, a well-founded recommendation concerning future treatment is generated.", "\n\nInfiltration technique {#Sec4}\n----------------------\n\nInfiltrations are radiologically guided under a C-arm X-ray unit. ", "The injection technique is based on the recommendations of Theodoridis and Krämer \\[[@CR11], [@CR12]\\]. ", "The analgesic bupivacaine (1 %) and the corticosteroid triamcinolone (10 mg/ml) are injected at the site, the mixture and quantity of which varies, depending on the location being addressed.", "\n\nEvaluation of treatment strategy before and after IGD {#Sec5}\n-----------------------------------------------------\n\nAll patients admitted to our department for IGD from January 2011 to December 2012 (*n* = 116) were selected for retrospective analysis and evaluated by two experienced spine surgeons. ", "The medical letters generated during consultation before admittance to hospital describing the symptoms and the clinical findings were analysed, together with the radiologic images of each patient (X-rays and MRI; if MRI was contraindicated, then myelo-computed tomography was used). ", "The surgeons were asked to determine the orthopaedic course of action they would recommend without the possibility of further evaluation by IGD. ", "Eight weeks later, the same data were presented to the spine surgeons. ", "This time, in addition, the medical reports created at discharge from hospital after IGD were made available. ", "They contained the patients' statements regarding the achieved effect by each of the infiltrations. ", "The spine surgeons were then asked to determine the treatment strategy from the synopsis of all available data; however, they were asked to do this without knowing what their first assessment was for each patient.", "\n\nStatistical analysis {#Sec6}\n--------------------\n\nDistributions of variables within the study groups were assessed by histograms. ", "Because age is non-normally distributed, it is reported as a median (range). ", "Categorical variables are reported as absolute and relative frequencies. ", "The graphic presentation is in the form of histograms and bar diagrams. ", "Statistical analysis was conducted by using IBM SPSS version 22.", "\n\nResults {#Sec7}\n=======\n\nA total of 116 patients were analysed in this study. ", "The median age was 63 years (20--87) and the ratio of men to women was 40:60 (Table [1](#Tab1){ref-type=\"table\"}). ", "Two peak ages could be observed, with a rise in cases at about 50 years, and a second peak at about 70 years (Fig.", " [1a](#Fig1){ref-type=\"fig\"}).Table 1Characteristics of the analysed sample and principal strategies before and after inpatient gradual diagnostics (IGD)CharacteristicsTotalWomenMenStudy group11670 (60 %)46 (40 %)Age, years63 (20--87)61 (35--87)64 (20--82)No surgery (pre/post IGD)33/4321/2512/18Decompression (pre/post IGD)10/74/46/3Fusion (pre/post IGD)65/5740/3525/22Other (pre/post IGD)8/95/63/3Fig. ", "1Analysed sample and treatment strategies. **", "a** Biometric data of the analysed sample. ", "Two thirds of the patients undergoing inpatient gradual diagnostics (IGD) were female. ", "Two major age groups of patients presenting themselves for IGD were observed: a first peak age at about the age of 50, consisting predominantly of women. ", "A second peak age follows at about 70 years with a relatively higher percentage of male patients than at the first peak age. **", "b** The chosen strategy before and after IGD. **", "c** Scope of recommended procedures in terms of included segments in cases of a surgical approach\n\nWithout the information obtained during IGD, a surgical approach had been recommended for 83 of them. ", "For the other 33 patients, conservative strategies had been favoured. ", "A comparison of the recommendations given before IGD with those generated at the end of the inpatient diagnostics shows that the suggested treatment strategy had changed in 39 % of cases. ", "In total, indications for surgery decreased from 83 to 73 cases (12 %), with more conservative approaches recommended instead (Table [2](#Tab2){ref-type=\"table\"}, Fig.", " [1b](#Fig1){ref-type=\"fig\"}). ", "This decrease in surgical procedures can be mostly attributed to a drop in monosegmental procedures, including both fusion and decompression surgery (Fig.", " [1b](#Fig1){ref-type=\"fig\"}, [c](#Fig1){ref-type=\"fig\"}). ", "The number of multisegmental indications changed only slightly. ", "Of the initial 83 indicated operations, 18 (22 %) were rejected after IGD.Table 2Changes of treatment strategy after inpatient gradual diagnostics (IGD)Treatment strategyNumber of cases/ Total casesPercentageStrategy changed through IGD45/11639Strategy unaltered after IGD71/11661No surgery indicated before IGD33/11628Surgery indicated before IGD83/11672Indication for conservative approach confirmed by IGD25/3376Surgery indicated by IGD^a^8/3324Indication for surgery confirmed by IGD65/8378Indication for surgery refused by IGD^b^18/8322Scope of initially suggested surgical procedure extended by IGD (without cases with no indication for surgery before IGD)^c^17/6526Scope of indicated surgical procedure reduced by IGD (without cases with no indication for surgery after IGD)^d^2/653^a^Three two-segment fusions, three one-segment fusions, two one-segment decompressions^b^In two cases, indication for total hip arthroplasty^c^Extension of surgical approach: one segment cranially (*n* = 6), one segment caudally (*n* = 4), one segment cranially and one caudally (*n* = 1), change of decompression to fusion surgery (*n* = 5), monosegmental lumbar fusion in addition to removal of sacroiliac joint screws (*n* = 1)^d^Change of fusion surgery to decompression (*n* = 1), reduction of fusion scope by two segments (*n* = 1)\n\nAt the same time, in about one quarter of these 33 patients in which a conservative approach had been initially suggested, after IGD, a surgical recommendation could be given. ", "It is noteworthy that for the remaining 76 % of these patients (in which a possible surgical intervention had been taken into consideration although not recommended before IGD), a clear statement for conservative treatment and advice against surgery could be formulated after IGD. ", "Changes is treatment strategy were comparable for both peak ages. ", "Individual examples tare given in Figs.", " [2](#Fig2){ref-type=\"fig\"}, [3](#Fig3){ref-type=\"fig\"}, [4](#Fig4){ref-type=\"fig\"} and [5](#Fig5){ref-type=\"fig\"}. ", "Description of cases with a recommended procedure other than simple decompression or primary fusion surgery are in Additional file [1](#MOESM1){ref-type=\"media\"}: Online resource 1.Fig. ", "2Confirmation of an uncertain indication for surgery. **", "a**-**c** T2-weighted magnetic resonance images preoperatively: **a** lumbar sagittal image and **b** axial lumbar image of L4/5 and **c** L5/S1. **", "d** Lateral radiographic image preoperatively and **e** postoperatively. ", "The patient presented with chronic lumbar back and sciatic pain on the right side. ", "Moderate intervertebral disc degeneration was observed between L5 and S1 (Pfirrmann grade 3-4 \\[[@CR13]\\]) and a secondary neuroforaminal stenosis on the right side. ", "Moderate facet joint degeneration was seen at L4/5 (Weishaupt \\[[@CR14], [@CR15]\\] grade 1 right and grade 2 left facet) and L5/S1 (Weishaupt grade 1 right, grade 2 left facet). ", "Recommendation before inpatient gradual diagnostics (IGD): lumbar fusion of L5/S1 with transforaminal lumbar interbody fusion (TLIF). ", "Results obtained during IGD: • epidural injection of L5/S1: 20 % sciatic pain relief. • ", "bilateral facet joint infiltration of L5/S1: 80 % back pain relief. • ", "bilateral sacroiliac joint infiltration: 10 % back pain relief. • ", "iliac crest infiltration at muscular insertion of erector spinae: 80 % pain relief. ", "Recommendation after IGD: lumbar fusion of L5/S1 with TLIF. ", "At 1 year follow-up, the patient reported no painFig. ", "3Extension of surgical scope by one motion segment cranially. **", "a**-**c** T2-weighted magnetic resonance images preoperatively: **a** lumbar sagittal image and **b** axial lumbar image of L4/5 and **c** L5/S1. **", "d** Lateral radiographic image preoperatively and **e** postoperatively. ", "The patient presented with chronic lumbar back pain and sciatic pain on the left side and a sensorimotor deficit of 4/5 on the Medical Research Council scale for muscle power for ankle dorsiflexion, plantarflexion, and toe extension. ", "Advanced intervertebral disc degeneration was observed between L5 and S1 (Pfirrmann grade 4) and a median intervertebral disc protrusion at L5/S1. ", "Mild facet joint degeneration was seen at L4/5 (Weishaupt grade 0 right and grade 1 left facet) and almost no facet joint degeneration at L5/S1 (Weishaupt grade 0 bilaterally). ", "Recommendation before inpatient gradual diagnostics (IGD): Lumbar fusion at L5/S1 with transforaminal lumbar interbody fusion (TLIF). ", "Results obtained during IGD: • bilateral facet joint infiltration of L5/S1: 70 % reduction of back pain. • ", "epidural injection of L5/S1: 40 % improvement of sciatic pain. • ", "bilateral facet joint infiltration of L4/5: 60 % reduction of back pain. ", "Recommendation after IGD: lumbar fusion of L4-S1 with TLIF. ", "At 1 year follow-up, the patient reported no painFig. ", "4Recommendation for conservative treatment. **", "a**-**c** T2-weighted magnetic resonance images preoperatively: **a** lumbar sagittal image and **b** axial lumbar image of L4/5 and **c** L5/S1. **", "d** Lateral radiographic image. ", "The patient presented with predominantly chronic lumbar back pain since childhood and intermittent bilateral sciatic pain. ", "The patient works as a storeman. ", "Advanced intervertebral disc degeneration was observed between L5 and S1 (Pfirrmann grade 4) and mild facet joint degeneration of L4/5 and L5/S1 (Weishaupt grade 1). ", "Before inpatient gradual diagnostics (IGD), a lumbar fusion of L5/S1 with transforaminal lumbar interbody fusion had been discussed. ", "Results obtained during IGD: • epidural injection of L5/S1: 0 % improvement of sciatic pain, 30 % back pain relief. • ", "bilateral facet joint infiltration of L5/S1: 0 % improvement of back and sciatic pain. ", "In view of the lack of response to the infiltrations, further conservative strategy was recommended. ", "Half a year later, the patient had a discectomy of L5/S1 performed in another hospital, with initial good results for a few weeks, followed by a complete clinical relapse. ", "When the patient thereupon presented himself in the department of neurosurgery of our hospital, our colleagues advised against further surgery, independent of our own recommendationFig. ", "5Semirigid inclusion of the cranial motion segment after IGD. **", "a**-**c** T2-weighted magnetic resonance images preoperatively: **a** lumbar sagittal image and **b** axial lumbar image of L3/4 and **c** L4/5. **", "d** Lateral radiographic image preoperatively and **e** postoperatively. ", "The patient presented with chronic lumbar back, strong sciatic pain bilaterally, and a hypoesthesia at the right lateral lower leg. ", "Moderate intervertebral disc degeneration was observed at L3/4 and L5/S1 (Pfirrmann grade 3), advanced degeneration at L4/5 (Pfirrmann grade 4-5), and a neuroforaminal stenosis on the right side due to facet joint hypertrophy and intervertebral disc protrusion (grade 2 according to Lee \\[[@CR16], [@CR17]\\]). ", "Moderate facet joint degeneration was seen at L3/4 and L4/5 (Weishaupt grade 1). ", "Recommendation before inpatient gradual diagnostics (IGD): lumbar fusion of L4/5 with transforaminal lumbar interbody fusion (TLIF). ", "Results obtained during IGD: • bilateral facet joint infiltration of L3/4: 30 % pain relief back pain. • ", "bilateral facet joint infiltration of L4/5: 30 % pain relief back pain. • ", "epidural injection of L4/5: 30 % sciatic pain relief. • ", "bilateral sacroiliac joint infiltration: 0 % pain relief. ", "Although the absolute values for pain relief were only at moderate levels, the patient's walking distance increased dramatically after the infiltrations. ", "Recommendation after IGD: lumbar fusion of L3-5 with TLIF L4/5 and a semirigid instrumentation of L3/4. ", "At the 3-month follow-up, the patient reported considerable pain relief and an increase in walking distance in comparison to that achieved preoperatively\n\nDiscussion {#Sec8}\n==========\n\nIGD is an established concept for determining therapeutic strategies in patients with chronic lumbar back pain, especially in those cases in which symptoms do not correspond to radiomorphological findings. ", "In addition, in multisegment degeneration, IGD is used to assess the necessary surgical scope. ", "IGD leads to significant changes in recommendations for further surgical treatment. ", "In summary, the total number of patients in the current study who were recommended to have surgery was reduced. ", "The chosen operative scope, however, showed a tendency to be slightly more extensive than what would have been the case without IGD. ", "This is, however, probably strongly dependent on the population of patients and the diagnoses that lead to indications for IGD. ", "IGD does not have a therapeutic purpose in itself, but is designed to test different surgical target sites for their aptness for surgery. ", "Pain alleviation is, therefore, only of short duration.", "\n\nRegarding IGD as a concept, the extent to which local infiltrations can temporarily simulate the effect and success of spine surgery needs to be addressed. ", "In our local situation, from our experience, success can be well predicted. ", "For example, a patient with back pain caused by facet joint degeneration of L4/5 who has 100 % relief after facet joint infiltration has a high probability of benefiting from lumbar fusion of L4/5. ", "On the other hand, we often do not know whether the pain is caused only by for example facet joint degeneration seen on MRI and X-rays. ", "It is important to take into consideration that comorbidities such as mental instabilities or other diseases could strongly influence pain before and after surgery. ", "This consideration is, however, much facilitated by IGD because of the intensive doctor-patient relationship and the observations drawn over the course of several days.", "\n\nStudy limitations {#Sec9}\n=================\n\nThe major limitation of this study is the fact that treatment strategies were determined retrospectively. ", "It is possible that interaction with the patient personally might lead to a different recommendation, depending on the physician's personal attitude towards spine surgery. ", "Moreover, even though impressions of the patient's mental and emotional condition are mentioned in our medical reports, a medical report can never replace direct doctor-patient contact. ", "Finally, no intra- or interobserver correlation was performed but recommendations given as a consensus of two experienced spine surgeons. ", "Future studies will have to address this aspect.", "\n\nConclusions {#Sec10}\n===========\n\nIGD is an established concept used to determine therapeutic strategies in patients with chronic lumbar back pain. ", "In our analysed collective, IGD led to highly relevant changes in recommendations for further surgical treatment.", "\n\nAbbreviations {#Sec11}\n=============\n\nALIF, anterior lumbar interbody fusion; IGD, inpatient gradual diagnostics; L, lumbar vertebrae; MRI, magnetic resonance imaging; st. ", "p., status post; Th, thoracic vertebrae; TLIF, transforaminal lumbar interbody fusion\n\nAdditional files {#Sec12}\n================\n\nAdditional file 1: Online resource 1.Description of cases with a recommended procedure other than simple decompression or primary fusion surgery. (", "DOC 33 kb)Additional file 2: Online resource 2.Original data set describing evaluation results before and after IGD. (", "XLSX 36 kb)\n\nWe thank Barbara Every, ELS, of BioMedical Editor, for English language editing. ", "We acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tuebingen.", "\n\nFunding {#FPar1}\n=======\n\nWe acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Tübingen University.", "\n\nAvailability of data and materials {#FPar2}\n==================================\n\nA description of cases with a recommended procedure other than simple decompression or primary fusion surgery is available in Additional file [1](#MOESM1){ref-type=\"media\"}: Online resource 1, the original data set in Additional file [2](#MOESM2){ref-type=\"media\"}: Online resource 2.", "\n\nAuthors' contribution {#FPar3}\n=====================\n\nUH designed the study, wrote the manuscript, helped with the data collection, and performed the statistical analyses. ", "MG designed the study, performed the data collection, and helped to write the manuscript. ", "FM helped with the data collection and wrote the manuscript. ", "All authors read and approved the final manuscript.", "\n\nAuthors' information {#FPar4}\n====================\n\nN/a.\n\nCompeting interests {#FPar5}\n===================\n\nThe authors declare that they have no competing interests.", "\n\nConsent for publication {#FPar6}\n=======================\n\nNot applicable.", "\n\nEthics approval and consent to participate {#FPar7}\n==========================================\n\nFull departmental, institutional and local ethical committee (project number: 328/2016BO2) approvals were obtained for the study. ", "Written informed consent was not required due to the retrospective pseudonymised character of the study.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Introduction {#s1}\n============\n\nChronic kidney disease (CKD) has a high global prevalence worldwide. ", "The prevalence of CKD and end-stage kidney disease (ESKD) increase with age: 27.6% between 60 and 70 years old and 34.3% above 70 years old when taking into account the five stages of CKD ([@B1]).", "\n\nKidney transplantation is the best therapeutic option for ESKD. ", "Results of kidney transplantation in terms of morbidity and mortality, life quality, and cost effectiveness are better as compared to hemodialysis or peritoneal dialysis ([@B2]). ", "However, kidney transplantation, as well as all other solid organ transplantations, is confronted with an organ shortage. ", "To increase the pool of organ donors, the American United Network for Organ Shortage decided to accept organs from Extended Criteria Donors (ECD). ", "The term marginal kidney was replaced by ECD kidney for the first time in 1997 by Kauffman ([@B3]). ", "In 2002, a clear definition was given: ECD are defined by deceased donors aged 60 years or older and 50--59 years old deceased donors with at least two of the three following criteria: cerebrovascular cause of death, terminal serum creatinine higher than 1.5 mg/dl (132.6 μmol/L), or history of hypertension ([@B4], [@B5]). ", "Other definitions and aspects of \"marginal kidneys\" have been studied by different authors such as kidney fibrosis based on histopathology, dual kidney transplantation, donation after cardiac death (DCD), and discarded kidneys ([@B6]--[@B9]). ", "In 2019, in Europe, \\~30% of potential donors are ECD. ", "In North America, \\~24% of potential donors are ECD, and nearly 40% of these kidneys are discarded each year ([@B10]). ", "ECD kidneys do not follow the classical allocation system of standard kidneys and allow to shorten the time on waiting list at the expense of a better graft ([@B11]--[@B13]).", "\n\nMechanisms of Organ Aging {#s2}\n=========================\n\nAging has been described as the decline of physiological integrity due to an accumulation of damages, deterioration of proteins, and organelle functions ([@B14]). ", "We use the term of senescence to relate biological and functional changes in cells due to aging. ", "Senescence, which is a state of permanent cellular cycle arrest, may occur following a decline over time of cell proliferation capacity as shown by Hayflick ([@B15]). ", "Different stimuli may trigger this cellular phenotype such as cells undergoing major DNA damages, telomere dysfunction, and oxidative stress ([@B16]). ", "To prevent the risk of malignant transformation, cells may undergo apoptosis, or become senescent. ", "The senescent state is mediated by two cellular pathways: p53/p21 and p16INK4a/pRB pathways ([@B17]). ", "This phenotype is also a proinflammatory phenotype, with a high level of inflammatory cytokines and chemokines secretion \\[e.g., ", "interleukin (IL)-6, IL-8, IL-1\\]. ", "This induces chronic inflammation in the organs ([@B18]).", "\n\nSenescence in renal cells may be described at different levels using a top--down approach. ", "At a genetic level, Kim et al. ", "described a set of age-related genes (985) in kidneys in 74 healthy patients from 27 to 92 years old ([@B19]). ", "Most of these genes showed increased activity and were shared both in the kidney medulla and cortex. ", "Those age-related genes were also shared in other human tissues. ", "These genes involved in kidney aging are for instance the *mortalin-2*, which encodes the heat shock protein 70. ", "Other genes prevent kidney aging, such as the one encoding the *insulin-like growth factor receptor*. ", "However, it is unclear if senescence and age-related genes activations in the organs are genetically or epigenetically inherited. ", "A recent study assessed aging signature in 563 human kidney transcriptomes using next generation RNA sequencing correlated with genomic data and epigenomic data in kidney and non-renal tissues. ", "Finally, the authors identified a total of 19 kidney age-related genes. ", "Five of them were kidney specific (*EDH3, ERP27, MAP4, PPPAR3C*, and *SNX24*). ", "However, these results are preliminary, and to our knowledge, no other team have reproduced this association. ", "Ten of them were associated with biological and clinical signs of aging. ", "Testis-specific Y-like 5 (*TSPYL5*) was the gene with the most significant association with aging ([@B20]). *", "TSPYL5* is one of the nucleosome proteins and plays a role in transcriptional regulation, cell cycle, and probably in cellular senescence ([@B21], [@B22]).", "\n\nAt a molecular level, many mechanisms of kidney aging have been described and well-reported in the review published by López-Otín et al. ([", "@B14]). ", "One of them implies autophagy dysregulation. ", "Autophagy is a physiological process in which cytoplasmic proteins and organelles are non-selectively degraded. ", "Autophagy is critical for terminally differentiated podocytes that are rarely renewed. ", "Autophagy dysregulation results in the accumulation of intracytoplasmic proteins. ", "This eventually results in podocyte degeneration, responsible for age-related glomerulosclerosis and proteinuria ([@B23]). ", "Another mechanism of kidney aging is the mitochondrial dysfunction theory causing overproduction of reactive oxygen species, oxidative stress, and age-related damages ([@B24]).", "\n\nAt a structural level, aging is related to renal anatomic alterations. ", "Main changes observed in aging kidney are sclerosis (focal and global glomerulosclerosis, tubular atrophy and interstitial fibrosis, arteriosclerosis), nephron hypertrophy, and decline in the number of functional nephrons ([@B25], [@B26]). ", "These modifications lead to renal mass decrease of \\~10% per decade and decrease in plasma flow and tubular damages ([@B27]). ", "The majority of renal cells are permanently renewed, but podocytes have a limited capacity of regeneration due to their terminally differentiation ([@B28], [@B29]). ", "Podocyte senescence largely contributes to renal aging. ", "The cortex shrinks and the medulla increase in size, with an increased number of renal cysts ([@B30]).", "\n\nAt a clinical level, aging leads to glomerular filtration rate (GFR) decline. ", "It has been estimated that, after the fourth decade, a decline of GFR occurs that ranges between 0.63 and 0.75 ml/min/year with kidney aging ([@B26], [@B31]). ", "However, nephrosclerosis and cortical atrophy failed to explain the entirety of the GFR decrease with age ([@B25]).", "\n\nImmunological Aspect of Aging in Kidney Transplant Recipients {#s3}\n=============================================================\n\nAging, in the immunological field, is associated with the concept of immunosenescence, which was based on the clinical reports of a higher incidence of infection and cancer and a lower efficacy of vaccination in older people ([@B32]). ", "In the field of kidney transplantation, older age of recipients is associated with a lower risk of acute rejection as compared to younger recipients ([@B33]). ", "The leading cause of death in old recipient is infection, and death is the leading cause of graft loss ([@B34]). ", "Moreover, Mendonça et al. ", "reported a rate of 37.6% of acute rejection in younger recipients (\\<60 years old) as compared to 22.7% in older (≥60 years old; *p* = 0.01), after a median time of 22 months of follow-up ([@B35]). ", "In larger cohorts, it has been shown that the absolute risk of acute rejection decreases for each decade of recipient age ([@B36]).", "\n\nOn top of aging, kidney transplant recipients suffer from CKDs and ESKD before transplantation. ", "ESKD itself is associated with a higher risk of infections and virus-related cancers as compared to the general population of the same age. ", "In the general population, the absolute rate of cancer mortality increases with age. ", "However, on the contrary, in kidney transplant patients, the excess risk of cancer-related death decreases with age as compared to the general population. ", "Over 65 years, the absolute risk of cancer-related death is 1.7-fold increased in kidney-transplanted recipients as compared to same age non-transplanted population ([@B37]). ", "The mechanism of accelerated immunosenescence in ESKD patients is not clearly understood, but some mechanisms have been assumed: chronic inflammation, oxidative stress, cytomegalovirus (CMV) infection, and epigenetics modifications ([@B38], [@B39]).", "\n\nThe T-cell receptor (TCR) repertoire allows the adaptive immune system to recognize a large number of foreign antigens. ", "The TCR β repertoire is known to decrease almost linearly with age, decreasing from 6.4 × 10^5^ TRBV CDR3 clone types per 10^6^ T cells at the age of 16 years to 3.1 × 10^5^ at the age of 62 years. ", "Although the absolute and relative numbers of total CD3^+^ cells do not differ with age, the percentages of naive CD8^+^ and CD4^+^ cells decrease with age ([@B40]). ", "Huang et al. ", "assessed the factors that may accelerate the TCR β repertoire contraction. ", "They showed that age, CMV infection, and ESKD were significantly and independently associated with a shrinking of the TCR β repertoire ([@B41]). ", "The impact of age on the TCR β repertoire concerned only the CD8^+^ memory T-cell subset but not the naive T-cell subset.", "\n\nOther immune cell compartments appear to be affected by aging ([@B42]). ", "Impaired B-cells proliferation and antibodies production have been reported. ", "The hypothesis put forward may be IL-2 lower production or T-cell/B-cell interaction dysfunction through CD28 downregulation ([@B43], [@B44]). ", "On contrary, immunosenescence is associated with an increase in cytotoxic natural killer cells capacity with aging. ", "Indeed, some authors reported a decrease in CD56^bright^ subset and an increase in CD56^dim^ subset of natural killer cells, which may play a role in graft antibody-mediated rejection ([@B45]).", "\n\nESKD also seems to impact the absolute and relative number of different immune cell subsets. ", "Betjes et al. ", "showed that ESKD was associated with a premature immune system aging, i.e., a lower CD31^+^ naive T-cell number as compared to age-matched healthy individuals and a higher percentage of terminally differentiated activated memory CD8^+^ T cells (TEMRA cells) ([@B46]). ", "ESKD patients may experience an overinduced apoptosis of naive T cells and an insufficient increase in thymic output and compensating proliferation as compared to same aged healthy individuals ([@B46]). ", "Chiu et al. ", "demonstrated how ESKD may accelerate immunosenescence. ", "Indeed, they showed that not only CD8^+^ TEMRA cell frequency was higher in ESKD patients as compared to healthy individuals but also, in multivariate analysis, the level of this senescent phenotype positively correlated with dialysis duration and uremic toxin *p-cresyl* sulfate ([@B47]).", "\n\nModality of ESKD treatment also impacts immunosenescence as hemodialysis was shown to be associated with a higher level of inflammation as compared to peritoneal dialysis. ", "The chronic inflammation and lymphocyte-sustained activation generated in these patients may accelerate immunosenescence by recruiting new T cells, promote stem cell exhaustion, and explain the lower incidence of observed acute rejection in hemodialysis patients, as compared to peritoneal dialysis patients, before transplantation ([@B39]).", "\n\nThe impact of CMV infection on the adaptive immune system homeostasis and immunosenescence is reported in many studies. ", "First, CMV latency is associated with a specific anti-CMV CD8^+^ T-cell repertoire expansion. ", "In healthy donors, using CMV peptides--HLA tetrameric complexes, it has been shown that this subpopulation may reach 10% of CD8^+^ T-cell compartment ([@B48], [@B49]). ", "Posttransplantation, this percentage may reach 18% ([@B50]). ", "This unbalanced expansion due to CMV is considered to be detrimental to the immune system of individuals. ", "Similarly, to ESKD, CMV infection, and/or latency are associated with a decrease in naive CD8^+^ T cells and an accumulation of TEMRA cells. ", "Yang et al. ", "showed that a higher anti-CMV IgG level is associated with a lower percentage of total CD4^+^ and CD8^+^ T cells but a higher percentage of CCR7-CD45RA T cells (TEMRA cells) in hemodialysis patients ([@B51]). ", "These results were comparable to those found in kidney transplant recipients under immunosuppressive regimen. ", "CMV drives a CD8^+^ T-cell expansion especially CD8^+^CD28 null and TEMRA CD8+ T cells ([@B52]).", "\n\nFinally, in older transplant recipients, Schaenman et al. ", "showed a decreased number of naive CD4^+^ and naive CD8^+^ T cells and an increased number of TEMRA cells and senescent KLRG1^+^ T cells as compared to younger recipients ([@B53]).", "\n\nImmunological Aspect of Aging in Kidney Transplant Donors {#s4}\n=========================================================\n\nDonor age appears to be an important prognostic factor of long-term outcome after kidney transplantation ([@B54]). ", "Nevertheless, the donor age criteria may be misleading when assessed alone ([@B55]). ", "In contrast with older recipients, older donors are likely to be more immunogenic. ", "In experimental data, T cells of rats receiving an old graft express a higher level of IFN-γ as compared to those receiving a younger graft. ", "This difference was associated with an accelerated chronic allograft dysfunction ([@B56]). ", "de Fijter et al. ", "assessed in a large cohort of kidney transplant recipients the risk factors of acute rejection ([@B57]). ", "In a multivariate analysis, donor age ≥50 years old, recipient age \\<50 years old, and HLA-DR mismatches were significantly associated with a higher risk of acute rejection (risk ratio = 1.53, 1.34, and 2.28 respectively). ", "Interestingly, the risk of acute rejection in older donors was independent of recipient age suggesting other mechanisms than immunosenescence involved.", "\n\nAged kidneys have an increased susceptibility to ischemia--reperfusion injury (IRI). ", "The presence of senescent cells in older kidney may result in a reduced tissue regeneration and chronic low level of inflammation. ", "Different mechanisms may explain the reduced tolerance to IRI: impairment of mitochondrial functions which results in a decrease in antioxidant defenses, reduced expression of heat shock protein-70 involved in transmitochondrial transport, and telomere shortening contributing to the increase in the process of senescence ([@B58]). ", "Conversely, IRI like hypertension was shown to increase the level of senescence in donor kidney ([@B59]).", "\n\nIn the end, the increased level of inflammation and edema induced by IRI in aged kidneys is the root of a stronger immune response. ", "Indeed, antigen-presenting capacities of dendritic cells seem to increase with age ([@B60]). ", "Nevertheless, regarding dendritic cell functions in aging, little is known currently and data in the literature are controversial ([@B61], [@B62]). ", "Moreover, it was shown that, after acute tubular necrosis, there is an increased expression of HLA molecules in tubular cells and accumulation of inflammatory cells ([@B63]). ", "Clinically, delayed graft function induced by IRI is associated with a 38% increased risk of acute rejection ([@B64]). ", "The impact of IRI on ECD kidneys is significant, and those kidney benefit from machine of perfusion with a lower rate of delayed graft function and higher kidney survival rate as compared to cold storage ([@B65], [@B66]).", "\n\nClinical Results in Recipients of Marginal Kidneys {#s5}\n==================================================\n\nSince the proportions of older patients on the waiting list and ECD have largely increased, many studies assessed the benefit of kidney transplantation in these populations. ", "First, transplantation with kidney from ECD has been associated with a higher survival rate as compared to maintenance of the waiting list in \\>60 years old recipients ([@B67]). ", "In this European study, the 5-year survival rate was 83.6% for recipients of ECD kidney as compared to 67.4% for patients who remained on the waiting list. ", "Recipient\\'s age was the major predictive risk factor of mortality in the early- and late-period posttransplantation with time on dialysis before transplantation and diabetes mellitus ([@B68], [@B69]).", "\n\nOnly few studies assessed the long-term results of recipients receiving a kidney graft from ECD as compared to standard criteria donors (SCDs) ([@B70]). ", "In 2015, Aubert et al. ", "assessed the long-term results of graft survival between ECD and SCD in 2,763 recipients in a French cohort and in a validation cohort. ", "ECD was associated with a lower graft survival \\[hazard ratio (HR) = 1.87 (1.50--2.32), *p* \\< 0.001\\] as compared to SCD at 7 years posttransplantation. ", "In the multivariate Cox analysis, ECD, cold ischemia, and presence of donor-specific alloantibodies (DSA) at transplantation were significantly associated with kidney allograft loss. ", "The model was adjusted on donor type (deceased vs. living), presence of diabetes in donor, graft rank, and number of HLA-A/B/DR mismatches ([@B71]). ", "Recipients of ECD with circulating DSAs at the time of transplantation had the worse kidney graft outcome with a 4.4-fold increased risk of graft loss as compared to those without DSA.", "\n\nIn 2016, Querard et al. ", "conducted a meta-analysis to assess the results of ECD transplantation. ", "From 29 studies, they estimated the non-adjusted pooled risk ratio of patient survival at 5 years at 1.62 (1.18--2.22) and of death-censored graft loss at 1.69 (1.18--2.34) in favor of SCD as compared to ECD ([@B72]). ", "The results largely came from North America studies. ", "Moreover, only a very small number of studies were adjusted with usual confounders. ", "In Europe, the non-adjusted pooled risk ratios were lower than in North America.", "\n\nVan Ittersum et al. ", "published the results of 3,062 kidney recipients after 7.8 years of follow-up in a European population ([@B73]). ", "Six hundred nineteen recipients received an ECD kidney, and 2,443 received a SCD kidney. ", "Recipients from deceased ECD donors had a higher risk of death-censored graft failure \\[HR = 1.92 (1.63--2.26)\\] and death \\[HR = 1.45 (1.26--1.67)\\] as compared to other recipients (deceased donors with SCD criteria and living donors). ", "At 10 years, ECD criteria was associated with an absolute risk of 16.9% for graft lost and 10.1% for death, as compared to SCD. ", "In a subgroup analysis of recipients of the same study, DCD with ECD criteria had the lower graft and patient survival prognosis. ", "Tomita et al. ", "specifically studied ECD after DCD and did not find an increased overall risk of graft loss as compared to SCD. ", "However, the risk of death-censored graft loss was higher in older ECD and donors with an history of hypertension or cerebrovascular events ([@B74]).", "\n\nHowever, some published data report excellent results with ECD transplantation as compared to SCD. ", "In the study of Palkoci et al. ", "50 ECD were compared to 107 ECD kidney recipients. ", "At 1 year, the rate of acute rejection was not statistically different, and at 5 years, the death-censored survival rate was not different (92%, *P* = 0.884) in both groups ([@B75]). ", "Another study conducted by Kim et al., ", "which included 42 ECD and 364 SCD, showed higher serum creatinine level at 12 months in ECD, but the survival rate was similar as compared to SCD ([@B76]).", "\n\nTherapeutic Strategies in ECD Kidney Transplantation {#s6}\n====================================================\n\nDifferent immunosuppressive strategies in ECD recipients may be discussed ([Table 1](#T1){ref-type=\"table\"}). ", "The goal in ECD is to reduce not only the incidence of infections and cancers but also acute rejection in this at-risk population. ", "In induction therapy, rabbit antithymocyte globulin (rATG) has shown lower risk of acute rejection as compared to IL-2 receptor antagonists without an increased risk of death in older recipients and high-risk kidney such as ECD ([@B86]). ", "Steroids maintenance or withdrawal has to be weighed between the higher risk of acute rejection and the risk of side effects in older patients. ", "It was shown that an early steroid withdrawal at the time of first discharge posttransplantation was associated with a better adjusted overall graft survival \\[HR = 1.32 (1.1--1.56), *P* = 0.002) and patient survival \\[HR = 1.46 (1.16--1.83), *P* = 0.001\\] but not death-censored graft survival. ", "In a subgroup analysis, these results were confirmed only in the T-cell-depleting induction treatment (thymoglobulin) group but not in the IL-2 receptor blocker (Basiliximab) group ([@B87]).", "\n\n###### \n\nStudy characteristics of trials evaluating immunosuppressive regimen in expanded criteria donors.", "\n\n --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n **Reference** **Study design** **Results**\n -------------------- ---------------------------------------- ------------------------------------------------------------ -----------------------------------------------------------------------------------------------\n Induction Gill et al. ([", "@B77]) Retrospective.\\ rATG \\> IL2RA/alemtuzumab in terms of rejection rate and graft survival in high-risk patients\n rATG or IL2RA or alemtuzumab\\ \n 14,820 patients \n\n Steroid withdrawal Aull et al. ([", "@B78]) Retrospective.\\ At 5 years:\\\n 634 patients. ", "46% ECD 90.2% patient survival\\\n 87.6% DCGS\\\n 12.8% acute rejection\n\n Segolini et al. ([", "@B79]) 88 ECD\\ At 3 years:\\\n IL2R + MMF + tacrolimus and steroid reducing or withdrawal 13.6% rejection rate\\\n At 4 years:\\\n 96% patient survival\\\n 79% graft survival\n\n Belatacept Durrbach et al. ([", "@B80]) (BENEFIT-EXT) Prospective. ", "543 patients.\\ At 7 years:\\\n Belatacept vs. CsA\\ 73 vs. 78% patient survival\\\n IL2RA + MMF + steroids 88 vs. 81% DCGS\\\n 21 vs. 17% acute rejection\n\n Delayed CNI Stratta et al. ([", "@B81]) Prospective. ", "101 ECD.\\ At 4 years:\\\n ATG or Alemtuzumab + MMF + steroids 12% acute rejection\\\n 93% patient survival\\\n 83% graft survival\n\n Arbogast et al. ([", "@B82]) Prospective. ", "89 ECD.\\ At 5 years:\\\n rATG + MMF + steroids. ", " 24% acute rejection\\\n 88% patient survival\\\n 70% graft survival\n\n mTOR inhibitors Furian et al. ([", "@B83]) Comparative non-randomized.\\ At 1 year:\\\n 31 ECD.\\ 19% acute rejection\\\n rATG + Sirolimus + MMF + steroids 100% patient survival\\\n 97% graft survival\n\n Cruzado et al. ([", "@B84]) Comparative non-randomized. ", "42 ECD.\\ At 3 years:\\\n rATG + Sirolimus + MMF + Steroids 8% acute rejection\\\n 76% patient survival\\\n 90% DCGS\n\n Ferreira et al. ([", "@B85]) Prospective randomized. ", "171 ECD.\\ At 1 year:\\\n rATG + tacrolimus + everolimus + steroids vs. MMF 95 vs. 84% avute rejection 89 vs. 99% DCGS\\\n 90 vs. 99% patient survival\n --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\n*rATG, rabbit antithymoglobulin; IL2RA, IL2 receptor antagonist; ECD, expanded criteria donors; MMF, mycophenolate mofetil; CsA, cyclosporin A; DCGS, death-censored graft survival*.", "\n\nIn the field of kidney transplantation, clinicians seek intensively for new immunosuppressive regimens to avoid calcineurin inhibitors (CNIs) nephrotoxicity. ", "In 2011, the US Food and Drug Administration approved the use of belatacept. ", "This drug is a fusion protein that bind CD80/86 onto antigen-presenting cells and thereby blocks effector T cells by preventing interactions with CD28 ([@B88]). ", "In the BENEFIT-EXT trial, 543 ECD recipients received either cyclosporine- or belatacept-based regimen ([@B80]). ", "At 7 years posttransplantation, mean estimated GFR was 53.9 ± 1.9, 54.2 ± 1.9, and 35.3 ± 2.0 ml/min per 1.73 m^2^ for belatacept more intensive, belatacept less intensive, and cyclosporine groups, respectively (*P* \\< 0.001). ", "This showed the benefit of avoiding CNI nephrotoxicity in those kidneys. ", "Death-censored graft loss and patient survival was similar in all groups except for a higher incidence of posttransplant lymphoproliferative disorders in EBV-negative recipients treated by belatacept. ", "Posttransplantation switch from CNI to belatacept within the first 6 months also seems efficient to improve renal graft function from ECD ([@B89]). ", "Mammalian target of rapamycin (mTOR) inhibitors may also be a valuable option to avoid CNI nephrotoxicity, but large randomized and controlled studies are missing ([@B90]). ", "Most of non-randomized studies showed acceptable results of graft survival and rejection rate with sirolimus or everolimus in CNI minimization strategies ([@B86]). ", "Yet, the benefit of mTOR inhibitors as compared to mycophenolate in ECD patients is controversial ([@B91]). ", "Indeed, despite a lower incidence of CMV infection/disease, Ferreira et al. ", "study was prematurely terminated due to a higher incidence of acute rejection, graft loss, and death in the mTOR inhibitor group, i.e., tacrolimus + everolimus as compared to tacrolimus + MPA ([@B85]).", "\n\nDespite all these clinical results of ECD vs. SCD, kidney transplantation with ECD remains a valuable option. ", "Indeed, in North America, Ojo et al. ", "showed that ECD transplantation improve patient survival over maintenance dialysis treatment with an increase of 5 years in life expectancy ([@B92]). ", "These results were consistent in the European population ([@B67]).", "\n\nRisk Stratification {#s7}\n===================\n\nIn 2009, Rao et al. ", "published the kidney donor risk index based on the Scientific Registry of Transplant recipients in the North American population ([@B93]). ", "The kidney donor risk index appears to be an interesting tool to stratify the risk and estimate outcomes posttransplantation based on 14 donor and transplant factors associated with death and graft failure. ", "This score is currently used in the United States to allocate kidney graft for single kidney transplantation or dual kidney transplantation ([@B94]). ", "KDPI score was assessed also in European cohorts of high-risk donor--recipient pairs and was efficient to improve the graft outcome prediction ([@B95]).", "\n\nIn Europe, the Eurotransplant senior program (ESP) was created to improve transplant allocation and shorten the time on waiting list. ", "It was designed to allocate kidney from ≥65 years old donors to ≥65 years old recipients regardless of HLA matching but with a focus on reducing the cold ischemia time ([@B96]). ", "Frei et al. ", "published the 5-year results of the ESP and showed that death-censored graft survival of ESP patients was similar when compared to old donor giving to other any recipients (67% survival) but was lower as compared to any aged donor giving to old recipients (81%). ", "These results were obtained at the price of higher incidence of acute rejection ([@B97]). ", "Results from the Dutch Organ Transplant Registry, which is part of Eurotransplant and ESP, showed a 5-year death censored graft survival of 83.8% in DBD and 75.3% in DCD ([@B98]). ", "In this old recipient population, delayed graft function was a strong risk factor of death (+40% risk) and of rejection (+57%) and DSA development ([@B99]).", "\n\nConclusions and Perspectives {#s8}\n============================\n\nKidney transplantation of \"marginal donors\" to old recipients implies different specificities: immunosenescence of recipients and higher risk of complications (i.e., infections and cancers), higher immunogenic response of older kidneys and increased susceptibility to IRI, and worse outcome than SCD kidneys. ", "Nevertheless, older patients still benefit from transplantation rather than remaining in the waiting list. ", "New immunosuppressive regimens and strategies such as costimulation blockade, early steroids withdrawal, and CNI minimization strategies may be useful to improve patient and renal outcomes in ECD recipients. ", "The goal in the future will be to minimize CNI-associated toxicity such as nephrotoxicity, cardiovascular morbidity and mortality, and malignancy in the particular population of ECD recipients. ", "To achieve this goal, we need to improve the risk stratification before clinicians allocate a kidney from ECD to an old recipient. ", "New randomized studies need to be done in ECD transplantation.", "\n\nAuthor Contributions {#s9}\n====================\n\nJN performed most of the literature search and wrote the manuscript. ", "TJ, PM, and CS contributed to the literature search and carefully read the manuscript. ", "LR finalized the manuscript.", "\n\nConflict of Interest\n--------------------\n\nThe authors declare that the review was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.", "\n\n[^1]: Edited by: Eric Spierings, Utrecht University, Netherlands\n\n[^2]: Reviewed by: Nicole Andrea Mifsud, Monash University, Australia; Jakob Nilsson, University Hospital Zürich, Switzerland\n\n[^3]: This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "// -*- C++ -*-\n\n// Copyright (C) 2005, 2006, 2009 Free Software Foundation, Inc.\n//\n// This file is part of the GNU ISO C++ Library. ", " This library is free\n// software; you can redistribute it and/or modify it under the terms\n// of the GNU General Public License as published by the Free Software\n// Foundation; either version 3, or (at your option) any later\n// version.", "\n\n// This library is distributed in the hope that it will be useful, but\n// WITHOUT ANY WARRANTY; without even the implied warranty of\n// MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU\n// General Public License for more details.", "\n\n// Under Section 7 of GPL version 3, you are granted additional\n// permissions described in the GCC Runtime Library Exception, version\n// 3.1, as published by the Free Software Foundation.", "\n\n// You should have received a copy of the GNU General Public License and\n// a copy of the GCC Runtime Library Exception along with this program;\n// see the files COPYING3 and COPYING.RUNTIME respectively. ", " If not, see\n// <http://www.gnu.org/licenses/>.", "\n\n// Copyright (C) 2004 Ami Tavory and Vladimir Dreizin, IBM-HRL.", "\n\n// Permission to use, copy, modify, sell, and distribute this software\n// is hereby granted without fee, provided that the above copyright\n// notice appears in all copies, and that both that copyright notice\n// and this permission notice appear in supporting documentation. ", "None\n// of the above authors, nor IBM Haifa Research Laboratories, make any\n// representation about the suitability of this software for any\n// purpose. ", "It is provided \"as is\" without express or implied\n// warranty.", "\n\n/**\n * @file debug_fn_imps.hpp\n * Contains an implementation for binomial_heap_.", "\n */\n\n#ifdef _GLIBCXX_DEBUG\n\nPB_DS_CLASS_T_DEC\nvoid\nPB_DS_CLASS_C_DEC::\nassert_valid() const\n{ base_type::assert_valid(true); }\n\n#endif \n" ]

{ "pile_set_name": "Github" }

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[ "Q:\n\nAzure oauth v2.0 interaction_required error with trusted ip and MFA\n\nI have set up this Azure AD authentication workflow on my web server :\n1 - The user login from this url :\nhttps://login.microsoftonline.com/{tenant_id}/oauth2/v2.0/authorize?", "\n client_id={client_id}\n &redirect_uri=https://example.com/callback\n &scope=openid%20https%3A%2F%2Fgraph.windows.net%2Fuser.read\n &response_mode=query\n &response_type=code\n\n2 - (MFA) The user submit a form with a code received on its phone\n3 - The user is redirected to https://example.com/callback?code={azure_given_code}\n4 - I exchange the {azure_given_code} for a token via the following POST request server side :\nPOST https://login.microsoftonline.com/{tenant_id}/oauth2/token\n\n{\n \"client_id\": \"{client_id}\",\n \"client_secret\": \"{client_secret}\",\n \"code\": \"{azure_given_code}\",\n \"grant_type\": \"authorization_code\",\n \"redirect_uri\": \"https://example.com/callback\"\n}\n\n5 - I receive an access token and can retrieve the logged-in user from this url, again, server side :\nhttps://graph.windows.net/me?api-version=1.6\n\nI added our office ip address to the trusted ip list so that users can bypass MFA when connecting from our network.", "\nEverything works fine if I am doing this workflow outside of the office network (from an untrusted ip that triggers MFA).", "\nBut with my office ip, the step 2 is bypassed (as expected) and at step 3 I get the following error :\n{\n \"error\": \"interaction_required\",\n \"error_description\": \"AADSTS50076: Due to a configuration change made by your administrator, or because you moved to a new location, you must use multi-factor authentication to access …\", \"error_codes\": [50076],\n \"timestamp\": \"2020-03-13 12:54:58Z\",\n \"trace_id\": '...'\n}\n\nWhat am I missing here to have this workflow working in both case (from a trusted and untrusted ip) ?", "\nI am really stuck with this issue, many thanks for your help.", "\n\nA:\n\nHere is how I solved my problem.", "\nWhen the user is redirected to the login url https://login.microsoftonline.com/{tenant_id}/oauth2/v2.0/authorize?... ", "his IP is used to determine whether or not he can bypass the MFA according to trusted ip rules.", "\nThen when the azure_given_code is retrieved, the request for the token is made server side, using the server IP which is the cause of the error (server IP is not a trusted one).", "\nDoing the POST https://login.microsoftonline.com/{tenant_id}/oauth2/token client side did solve the issue since the IP used for the request is a trusted one.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Talk To Us!", "\n\nGluten Free Restaurant Guide from Triumph Dining: A Must Have for Gluten Free Dining!", "\n\nWouldn't it be great if there was a comprehensive GLUTEN FREE RESTAURANT GUIDE that you could refer too before going out to eat?", "\n\nDo you find yourself struggling to find reliable gluten free restaurants even in your home town...or when you travel on business....or when you travel on vacation?", "\nWell, struggle no longer!!! ", "There is an excellent, comprehensive gluten free resturant guide that will eliminate your struggle to find restaurants that cater to gluten free customers!", "\n\nThe guide I am talking about and I am personally recommending is from Triumph Dining and the name of the book is \"The Essential Gluten Free Restaurant Guide 5th Edition\".", "\n\nWHY DO I RECOMMEND THIS AWESOME GUIDE?", "\n\nBecause it includes a list over 6,500 restaurants that either has a full gluten free menu or offers gluten free food options.", "\n\nI own this guide and I use it all the time. ", "I travel on business and I take it with me. ", "When I go on vacation to a different city, it never leave home without it!", "\n\nI even use it for local restuarants. ", "It is the best guide out there without question!", "\n\nHere are some of the highlights of the guide:\n\n* Gluten free menus for 120 National and Regional restaurant chains.", "\n\n* Lists gluten free restuarants by major city in the each of the 50 states in the U.S. incuding Washington DC.", "\n\n* Restaurants are catergorized with 4 symbols:\n\n1. ", "A gluten free menu is available.", "\n\n2. ", "It has gluten free specialty items.", "\n\n3. ", "It is a chain restaurant which actually has the gluten free menu included in section 3 of the book.", "\n\n4. ", "It is a 100% gluten free establishment...no gluten on site.", "\n\nSO HOW CAN YOU GET THIS AWESOME ONE-OF-A-KIND, FULLY TRUSTED, COMPREHENSIVE GLUTEN FREE RESTAURANT GUIDE???", "\n\nJust click on the banner below and it will take you to the TriumphDining website where you can purchase this well researched book for less than $25! ", "That's it, under $25!!.", "\n\nVery reasonable price for a book that has spent numerous hours of time researching and interviewing over 6,500 restaurants!.", "\n\nThis book also includes over 450 pages of information that really help us speed up the process of finding GF restaurants...it has already been done for us in this guide!", "\n\nClick this banner to go to the Truimph Dining website to order your guide and read other reviews:\n\nOther products that you can get from Triumph Dining are Triumph Dining Cards." ]

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[ "If you want to put your best gardening foot forward this spring, it is important to take your first steps in the right direction. ", "Decisions you make in early spring have enormous impact on the health and appearance of your garden later in the season. ", "To help you plant smart, we've compiled a list of 10 tech gadgets that can make your thumb a little greener. ", "These tools use the latest technology and science to help you analyze, monitor, and tend to your plants. ", "Check out this collection of smart tech, from pollen extractors to weather forecasters, that can help make this year's garden your best ever." ]

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[ "Wu S, Wei Z, Greene CM, et al. ", "Mortality burden from seasonal influenza and 2009 H1N1 pandemic influenza in Beijing, China, 2007‐2013. ", "Influenza Other Respi Viruses. ", "2018;12:88--97. ", "<https://doi.org/10.1111/irv.12515>\n\n**Funding information**\n\nThis work was supported by Expanding the Use of Seasonal Influenza Vaccine in Public Health Programs in China (1U51IP000819‐01), Beijing Science and Technology Planning Project (D141100003114002), The Capital Health Research and Development of Special (2014‐1‐1011), Beijing Talents Fund (2014000021223ZK36) and Beijing Health System High Level Health Technology Talent Cultivation Plan (2013‐3‐098). ", "APC for this article is funded by World Health Organization (WHO).", "\n\nShuangsheng Wu and Zaihua Wei contributed equally to this article.", "\n\nThe copyright line for this article was changed on 25 January 2018 after original online publication\n\n\\[Correction added on 25 January 2018, after first online publication: Funding information has been updated.\\]\n\n1. ", "INTRODUCTION {#irv12515-sec-0005}\n===============\n\nInfluenza is a major cause of global morbidity and mortality each year, especially among older adults and those with chronic diseases.[1](#irv12515-bib-0001){ref-type=\"ref\"} Although several statistical models have estimated the mortality burden of influenza,[2](#irv12515-bib-0002){ref-type=\"ref\"} few have focused on mainland China,[3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"} and information on mortality burden in northern China is especially limited. ", "Considering the diverse seasonality patterns,[6](#irv12515-bib-0006){ref-type=\"ref\"} income levels and healthcare access across China, mortality burden may vary by region.", "\n\nBeijing, the capital of China, is located in northern China. ", "With a resident population of nearly 20 million in 2010, it is one of the most populous cities in the world. ", "During the 2009 H1N1 pandemic, only 10 844 laboratory‐confirmed cases of influenza A(H1N1)pdm09 and 69 deaths were reported in Beijing.[7](#irv12515-bib-0007){ref-type=\"ref\"} These numbers solely represent laboratory‐confirmed influenza deaths and not decedents who might have died because of pandemic influenza but were never tested.[3](#irv12515-bib-0003){ref-type=\"ref\"} A mathematical modeling study estimated that the likely number of influenza A (H1N1)pdm09 infections in Beijing was 1.8 million during the pandemic period.[8](#irv12515-bib-0008){ref-type=\"ref\"} To date, no study has estimated the likely number of influenza A(H1N1)pdm09‐associated deaths in Beijing.", "\n\nSince 2007, the Beijing Municipal Government has provided seasonal influenza vaccination to priority populations, including adults ≥60 years of age and primary and middle school students, free of charge between September and November each year prior to the start of typical influenza virus circulation. ", "Beijing also conducted influenza A(H1N1)pdm09 vaccination campaigns during the pandemic period.[9](#irv12515-bib-0009){ref-type=\"ref\"} These programs were implemented in the absence of local data on influenza‐associated mortality burden because there was concern that this novel virus could have substantial burden on the population\\'s health. ", "Influenza mortality burden data allow programs to determine the potential impact of influenza vaccination and inform investments in prevention strategies. ", "In this study, we modeled mortality data obtained from a representative mortality register system, combined with weekly influenza virus surveillance data, to provide estimates of the mortality impact associated with seasonal influenza and the influenza A(H1N1)pdm09 virus during the pandemic period by specific death categories, age groups, and influenza virus type and subtype in Beijing from 2007 to 2013.", "\n\n2. ", "METHODS {#irv12515-sec-0006}\n==========\n\n2.1. ", "Population data {#irv12515-sec-0007}\n--------------------\n\nWe obtained annual population data from the National Population Census in Beijing, China.[10](#irv12515-bib-0010){ref-type=\"ref\"} In 2010, the total population of Beijing was nearly 20 million, of which 12‐13 million were registered residents of Beijing. ", "The remaining 7‐8 million persons were classified as \"migrants\" who are not registered residents of Beijing. ", "In this study, we used population data of registered populations only to calculate the annual mortality rates.", "\n\n2.2. ", "Mortality data {#irv12515-sec-0008}\n-------------------\n\nLocal regulation requires that all deaths in Beijing are registered in the Mortality Register and Surveillance System, managed by Beijing Center for Disease Control and Prevention (BJCDC). ", "We were unable to obtain reliable mortality data among migrants, as both Chinese culture and high medical expenses compel a large proportion of migrants to return to their home provinces when they are severely ill, and therefore, the majority of migrants do not die in Beijing and are not registered in the BJCDC Mortality Register and Surveillance system. ", "In this study, we obtained weekly electronic mortality data for the registered Beijing population from 2007 to 2013, covering the influenza seasons of 2007/2008 to 2012/2013. ", "We defined an influenza season as the period ranging from the 27th week in 1 year to the 26th week in the next year, based on influenza surveillance data.[11](#irv12515-bib-0011){ref-type=\"ref\"} The registration system categorized weekly numbers of deaths into two underlying causes of death according to the International Classification of Disease, Tenth Revision \\[ICD‐10\\]: respiratory (ICD‐10 codes J00‐99) and circulatory diseases (ICD‐10 codes I00‐99) (respiratory and circulatory: R&C), and all‐cause deaths (including both respiratory and circulatory deaths which have been previously been associated with influenza‐associated deaths).[2](#irv12515-bib-0002){ref-type=\"ref\"}, [3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"}, [6](#irv12515-bib-0006){ref-type=\"ref\"} Two age groups were considered: \\<65 years and ≥65 years.", "\n\n2.3. ", "Influenza virology data {#irv12515-sec-0009}\n----------------------------\n\nWe obtained influenza virology data from the Beijing influenza surveillance system from seasons 2007/2008 to 2012/2013. ", "The influenza surveillance system, designed and managed by BJCDC, included 14 sentinel hospitals in 2007, 17 hospitals in 2008, 20 hospitals in 2011, and 23 hospitals in 2012. ", "In this system, clinicians of surveillance clinics in internal medicine, the emergency department, the fever clinic, and the pediatric clinic were required to diagnose all influenza‐like illness (ILI) cases (patients presenting with fever ≥38°C and cough or sore throat) and to record the weekly numbers of ILI outpatient visits throughout the year. ", "Trained clinicians collected pharyngeal swab specimens from a convenience sample of 10‐20 ILI case‐patients per sentinel hospital per week. ", "Specimens were sent to local CDC laboratories to test for influenza by cell culture. ", "A more detailed description of the surveillance was published in a previous study.[12](#irv12515-bib-0012){ref-type=\"ref\"}\n\n2.4. ", "Statistical model {#irv12515-sec-0010}\n----------------------\n\nA negative binomial model was applied to estimate influenza‐associated excess mortality, using age‐specific weekly mortality data as the outcome and proportions of specimens positive for influenza by type/subtype (not age‐specific) as the predictor variables.[3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"} Models included virology surveillance time series data, as well as time terms to account for the weeks in the model and harmonic terms to account for the cyclical pattern in deaths. ", "Because of the lack of respiratory syncytial virus virology data in Beijing, we did not include this pathogen in the model.", "\n\nNegative Binomial models were fit separately for the two outcomes (all‐cause and respiratory and circulatory deaths) and age groups (aged \\<65 years and ≥65 years) using a log link function. ", "The final models were selected by evaluating the AIC/BIC values in combination with the statistical significance of the viral surveillance terms and the harmonic and time terms (for baseline estimation) for each of the models examined (Table [S1](#irv12515-sup-0001){ref-type=\"supplementary-material\"}). ", "Further, we decided to choose the same model for each age group and outcome based on the evaluation of the separate models. ", "We chose to use the same model for each age group for ease of interpretation and better comparison of estimates and methods. ", "The final model selected for both all‐cause and respiratory and circulatory deaths was as follows: $$\\begin{array}{cl}\n{Y_{t}\\, = \\,} & {\\alpha\\, exp\\,\\{\\beta_{0}\\, + \\,\\beta_{1}{\\lbrack t\\rbrack}\\, + \\,\\beta_{2}{\\lbrack t^{2}\\rbrack}\\, + \\,\\beta_{3}{\\lbrack\\sin{\\lbrack{(2\\pi t)}/{(365.25/7)}\\rbrack}\\rbrack}} \\\\\n & {\\, + \\,\\beta_{4}{\\lbrack\\cos{\\lbrack{(2\\pi t)}/{(365.25/7)}\\rbrack}\\rbrack}\\, + \\,\\beta_{5}{\\lbrack A{(\\text{H1N1})}_{t}\\rbrack}} \\\\\n & {\\, + \\,\\beta_{6}{\\lbrack A{(\\text{H3N2})}_{t}\\rbrack}\\, + \\,\\beta_{7}{\\lbrack B_{t}\\rbrack}\\, + \\,\\beta_{8}{\\lbrack A{(\\text{H1N1})}pdm_{t}\\rbrack}\\, + \\, e_{t}\\}} \\\\\n\\end{array}$$\n\nY~t~ is the weekly variable for the time series from 2007/2008 to 2012/2013 (1‐312) and represents age‐specific weekly number of deaths, α is the offset term equal to the log of the age‐specific population size, β~0~ represents the intercept, β~1~ and β~2~ account for the linear and quadratic time trends, β~3~ and β~4~ account for cyclical secular trends, and β~5~ through β~8~ represent coefficients associated with the weekly proportion of specimens testing positive for each influenza subtype. ", "Further explanation of our model selection is available in Table [S1](#irv12515-sup-0001){ref-type=\"supplementary-material\"}.", "\n\nThe number of deaths attributed to influenza was calculated as the difference between the predicted influenza‐associated deaths from the full model and the predicted baseline deaths (from the model when the co‐variables for influenza subtype were set to zero). ", "Confidence intervals were generated for excess mortality estimates based on the confidence intervals of the model predictions. ", "Age‐specific excess mortality rates were calculated from the estimated number of deaths attributed to influenza divided by population from the National Population Census in Beijing, China.[10](#irv12515-bib-0010){ref-type=\"ref\"} All the statistical analyses were carried out using SAS University Edition (SAS Institute Inc., Cary, NC, USA). ", "A *P* value \\< .05 was considered to be statistically significant.", "\n\n2.5. ", "Ethics approval {#irv12515-sec-0011}\n--------------------\n\nStudy approval was obtained from the Institutional Review Board and Human Research Ethics Committee of BJCDC.", "\n\n3. ", "RESULTS {#irv12515-sec-0012}\n==========\n\n3.1. ", "Mortality data reported from the Mortality Register and Surveillance System and influenza virus activity, from season 2007/2008 to 2012/2013 {#irv12515-sec-0013}\n-------------------------------------------------------------------------------------------------------------------------------------------------\n\nFor the influenza seasons 2007/2008 to 2012/2013, the annual all‐cause mortality rate ranged from 581.7 to 602.6 per 100 000 persons for all ages, and 3238.9 to 3394.3 per 100 000 for adults aged ≥65 years. ", "Adults aged ≥65 years accounted for 76% of all‐cause deaths among all ages. ", "R&C causes represented 58% of all deaths. ", "The annual R&C mortality rate ranged from 335.8 to 346.9 per 100 000 persons for all ages and 2050.0 to 2221.0 per 100 000 for adults aged ≥65 years. ", "Adults aged ≥65 years accounted for 84% of R&C deaths among all ages (Table [1](#irv12515-tbl-0001){ref-type=\"table-wrap\"}).", "\n\n###### \n\nMortality rates (per 100 000 persons) reported from the Mortality Register and Surveillance System by age, Beijing 2007/2008 to 2012/2013 influenza seasons\n\n All ages Adults aged ≥65 y (% of deaths among all age) \n ----------- ------------ ----------------------------------------------- -------------- ----------- --------------- ---------------\n 2007/2008 12 047 617 581.7 343.4 (59) 1 560 836 3394.3 (75.6) 2221 (83.8)\n 2008/2009 12 208 706 575 335.8 (58.4) 1 614 871 3292.6 (75.7) 2113.7 (83.3)\n 2009/2010 12 375 798 602.6 354.2 (58.8) 1 664 285 3388.4 (75.6) 2196.3 (83.4)\n 2010/2011 12 518 114 593.5 346.9 (58.4) 1 707 318 3329.7 (76.5) 2143.8 (84.3)\n 2011/2012 12 678 603 595.3 340.8 (57.2) 1 764 450 3274.3 (76.5) 2064.0 (84.3)\n 2012/2013 12 876 915 601.9 346.2 (57.5) 1 840 459 3238.9 (76.9) 2050.0 (84.6)\n\nR&C, Respiratory and circulatory diseases.", "\n\nJohn Wiley & Sons, Ltd\n\nDuring the 6‐year study period, a total of 60 795 specimens were tested for influenza virus. ", "An average of 15.4% specimens tested positive for influenza for the entire time series. ", "Influenza A(H1N1), A(H1N1)pdm09, and A(H3N2) were each the predominant subtype in one season (2008/2009, 2009/2010, and 2010/2011, respectively), while influenza B predominated in 2 seasons (2007/2008 and 2011/2012), and A(H1N1)pdm09 and A(H3N2) co‐circulated in the 2012/2013 season (Figure [1](#irv12515-fig-0001){ref-type=\"fig\"}). ", "Influenza virus activity and mortality both peaked in the winter months of December‐February during the non‐pandemic period and from November of 2009 to February of 2010 during the pandemic period (Figure [1](#irv12515-fig-0001){ref-type=\"fig\"}).", "\n\n{#irv12515-fig-0001}\n\n3.2. ", "Estimates of influenza‐associated deaths, from season 2007/2008 to 2012/2013 {#irv12515-sec-0014}\n---------------------------------------------------------------------------------\n\nFigure [2](#irv12515-fig-0002){ref-type=\"fig\"} presents the weekly time series of observed, predicted, and baseline mortality using a negative binomial regression model. ", "The predicted values fit well with the observed data.", "\n\n{#irv12515-fig-0002}\n\nFor all ages, there was year‐to‐year variability in the annual number of influenza‐associated all‐cause deaths, and the mean number of deaths from 2007/2008 to 2012/2013 was 2375(95% confidence interval \\[CI\\] 1002‐8688), with a rate of 19.1 (CI 8.1‐69.9) deaths per 100 000 persons (Table [2](#irv12515-tbl-0002){ref-type=\"table-wrap\"}). ", "Most (81%) influenza‐associated all‐cause deaths occurred among adults aged ≥65 years, and the rate in this age group was higher than the rate among those aged \\<65 years (113.6 \\[CI 49.5‐397.4\\] versus 4.4 \\[CI 1.7‐18.6\\] per 100 000, *P* \\< .05). ", "There were, on average, 1873 (CI 818‐6684) influenza‐associated R&C deaths per year, with a rate of 15.1 (CI 6.6‐53.8) per 100 000. ", "Influenza‐associated R&C mortality varied by season (ranged from 8.9 \\[CI 1.7‐48.1\\] to 23.2 \\[CI 10.5‐64\\] per 100 000) and 87% of deaths occurred in those aged ≥65 years.", "\n\n###### \n\nInfluenza‐associated excess deaths and influenza‐associated death rates (per 100 000 persons) by age, Beijing, 2007/2008 to 2012/2013\n\n Season Influenza‐associated excess deaths Influenza‐associated death rates \n -------------------------------------------------------------- ------------------------------------ ---------------------------------- ---- ------------------ --------------------- ----------------\n All‐cause \n 2007/2008 3039 (1788‐9984) 2562 (1579‐7803) 84 25.2 (14.8‐82.9) 164.1 (101.2‐499.9) 4.5 (2‐20.8)\n 2008/2009 1532 (317‐7787) 1292 (286‐6000) 84 12.5 (2.6‐63.8) 80 (17.7‐371.5) 2.3 (0.3‐16.9)\n 2009/2010 3576 (1544‐10126) 2610 (1039‐7549) 73 28.9 (12.5‐81.8) 156.8 (62.4‐453.6) 9 (4.7‐24.1)\n 2010/2011 2101 (707‐7740) 1670 (591‐5950) 79 16.8 (5.6‐61.8) 97.8 (34.6‐348.5) 4 (1.1‐16.6)\n 2011/2012 2225 (1304‐8093) 1893 (1164‐6371) 85 17.5 (10.3‐63.8) 107.3 (66‐361.1) 3 (1.3‐15.8)\n 2012/2013 1777 (350‐8396) 1391 (280‐6432) 78 13.8 (2.7‐65.2) 75.6 (15.2‐349.5) 3.5 (0.6‐17.8)\n Mean (all years) 2375 (1002‐8688) 2375 (1002‐8688) 81 19.1 (8.1‐69.9) 113.6 (49.5‐397.4) 4.4 (1.7‐18.6)\n Mean (seasonal years[c](#irv12515-note-0007){ref-type=\"fn\"}) 2135 (893‐8400) 2135 (893‐8400) 82 17.2 (7.2‐67.5) 105 (46.9‐386.1) 3.5 (0.9‐14.6)\n R&C \n 2007/2008 2194 (1344‐6467) 2194 (1344‐6467) 91 20.1 (11.6‐64.7) 140.6 (86.1‐414.3) 2.1 (0.6‐12.7)\n 2008/2009 957 (201‐4747) 957 (201‐4747) 88 8.9 (1.7‐48.1) 59.3 (12.4‐294) 1.2 (0.1‐10.7)\n 2009/2010 2284 (995‐6271) 2284 (995‐6271) 79 23.2 (10.5‐64) 137.2 (59.8‐376.8) 5.5 (2.9‐15.4)\n 2010/2011 1489 (613‐4907) 1489 (613‐4907) 86 13.8 (5.3‐48.1) 87.2 (35.9‐287.4) 2.2 (0.5‐10.3)\n 2011/2012 1524 (931‐5061) 1524 (931‐5061) 92 13.1 (7.6‐47.9) 86.4 (52.8‐286.8) 1.3 (0.3‐9.3)\n 2012/2013 1248 (329‐5215) 1248 (329‐5215) 85 11.4 (2.8‐49.9) 67.8 (17.9‐283.4) 2 (0.3‐10.9)\n Mean (all years) 1873 (818‐6684) 1616 (736‐5445) 87 15.1 (6.6‐53.8) 96.4 (44.1‐323.8) 2.4 (0.8‐11.5)\n Mean (seasonal years[c](#irv12515-note-0007){ref-type=\"fn\"}) 1673 (721‐6437) 1482 (684‐5279) 88 13.5 (5.8‐51.7) 88.2 (41‐313.2) 1.8 (0.3‐9)\n\nCI, 95% confidence interval; R&C, Respiratory and circulatory diseases.", "\n\nThe sum of the estimates of influenza‐associated deaths for persons aged ≥65 y and persons aged\\<65 y.\n\n\\% of all ages = Influenza‐associated excess deaths for persons aged ≥65 y ÷ Influenza‐associated excess deaths for all ages.", "\n\nseasonal years: all years excluding 2009/2010.", "\n\nJohn Wiley & Sons, Ltd\n\nTable [3](#irv12515-tbl-0003){ref-type=\"table-wrap\"} lists influenza death rates by virus type/subtype from season 2007/2008 to 2012/2013. ", "For all ages, the mortality rate associated with influenza B was 7.7 (CI 4.6‐20.3) per 100 000 persons per season for all‐cause mortality, followed by A(H1N1)pdm09 (7.1 \\[CI 4.1‐19.3\\] per 100 000 for 2009/2010‐2012/2013) and A(H3N2) (5.6 \\[CI 1.4‐18.3\\] per 100 000). ", "Influenza B caused the highest mortality burden (20.5 \\[CI 14.2‐34.9\\] per 100 000) when influenza B virus predominated in 2007/2008. ", "A similar pattern was observed among both those aged \\<65 years and those aged ≥65 years, and also within all respiratory and circulatory deaths (Table [4](#irv12515-tbl-0004){ref-type=\"table-wrap\"}).", "\n\n###### \n\nInfluenza‐associated death rates (per 100 000 persons) by virus subtype, Beijing, 2007/2008 to 2012/2013\n\n Season All Rates (% of deaths) by virus subtypes The predominant virus circulating \n -------------------------------------------------------------- ------ --------------------------------------- ----------------------------------- ------------- --------------------------------------------------- ---------------------\n All‐cause \n 2007/2008 25.2 0.1 (0.3) 4.6 (18.3) 20.5 (81.4) 0 (0) B\n 2008/2009 12.5 6.4 (51) 2.2 (17.4) 4 (31.5) 0 (0) A(H1N1)\n 2009/2010 28.9 0.3 (0.9) 6 (20.7) 2.7 (9.5) 19.9 (68.9) A(H1N1)pdm\n 2010/2011 16.8 0 (0.1) 10.3 (61.3) 2.9 (17.6) 3.5 (21.1) A(H3N2)\n 2011/2012 17.5 0 (0) 1.9 (11.1) 15.6 (88.8) 0 (0.1) B\n 2012/2013 13.8 0 (0) 8.7 (63) 0.2 (1.2) 4.9 (35.8) A(H1N1)pdm, A(H3N2)\n Mean (all years) 19.1 1.1 (8.7) 5.6 (32) 7.7 (38.3) 7.1 (36.6)[a](#irv12515-note-0010){ref-type=\"fn\"} \n Mean (seasonal years[b](#irv12515-note-0011){ref-type=\"fn\"}) 17.2 1.3 (5.2) 5.5 (32.6) 8.6 (49.9) 2.8 (17.7)[a](#irv12515-note-0010){ref-type=\"fn\"} \n R&C \n 2007/2008 20.1 0.1 (0.3) 4.1 (20.6) 15.9 (79.1) 0 (0) B\n 2008/2009 8.9 4.2 (46.9) 1.9 (21.3) 2.8 (31.9) 0 (0) A(H1N1)\n 2009/2010 23.2 0.1 (0.6) 5 (21.7) 2.1 (8.8) 16 (68.9) A(H1N1)pdm\n 2010/2011 13.8 0 (0.1) 8.8 (64) 2.1 (15.3) 2.8 (20.7) A(H3N2)\n 2011/2012 13.1 0 (0) 1.6 (12.3) 11.5 (87.7) 0 (0) B\n 2012/2013 11.4 0 (0) 7.4 (64.9) 0.1 (0.9) 3.9 (34.2) A(H1N1)pdm, A(H3N2)\n Mean (all years) 15.1 0.7 (8) 4.8 (34.1) 5.7 (37.3) 5.7 (36.7)[a](#irv12515-note-0010){ref-type=\"fn\"} \n Mean (seasonal years[b](#irv12515-note-0011){ref-type=\"fn\"}) 13.5 0.5 (6.2) 4.7 (35.8) 6.5 (47.8) 2.3 (17.7)[a](#irv12515-note-0010){ref-type=\"fn\"} \n\nNumber (proportion) presented.", "\n\nR&C, Respiratory and circulatory diseases.", "\n\nEstimates for seasons 2009 to 2013.", "\n\nseasonal years: all years excluding 2009/2010.", "\n\nJohn Wiley & Sons, Ltd\n\n###### \n\nInfluenza‐associated death rates (per 100 000 persons) by virus subtype and by age group, Beijing, 2007/2008 to 2012/2013\n\n Season Age ≥65 y Age \\<65 y \n -------------------------------------------------------------- ----------- ------------- ------------- -------------- ---------------------------------------------------- ----- ------------ ------------ ------------ ---------------------------------------------------\n All‐cause \n 2007/2008 164.1 0.6 (0.4) 29 (17.6) 134.6 (82) 0 (0) 4.5 0 (0.2) 1 (21.6) 3.6 (78.2) 0 (0)\n 2008/2009 80.0 41.4 (51.8) 13.5 (16.9) 25.1 (31.3) 0 (0) 2.3 1.1 (47.1) 0.5 (20.4) 0.7 (32.5) 0 (0)\n 2009/2010 156.8 1.7 (1.1) 36 (23) 17.2 (11) 101.8 (64.9) 9.0 0 (0.2) 1.3 (14.8) 0.5 (5.4) 7.2 (79.6)\n 2010/2011 97.8 0.1 (0.1) 61.4 (62.8) 18.2 (18.6) 18 (18.4) 4.0 0 (0) 2.2 (55.2) 0.5 (13.5) 1.2 (31.3)\n 2011/2012 107.3 0.1 (0.1) 11.4 (10.7) 95.7 (89.2) 0.1 (0.1) 3.0 0 (0) 0.4 (13.3) 2.6 (86.7) 0 (0)\n 2012/2013 75.6 0 (0) 50 (66.1) 1 (1.4) 24.6 (32.5) 3.5 0 (0) 1.8 (51.8) 0 (0.5) 1.7 (47.7)\n Mean(all years) 113.6 7.3 (8.9) 33.6 (32.8) 48.6 (38.9) 36.2 (32.5)[a](#irv12515-note-0014){ref-type=\"fn\"} 4.4 0.2 (7.9) 1.2 (29.5) 1.3 (36.1) 2.5 (39.6)[a](#irv12515-note-0014){ref-type=\"fn\"}\n Mean (seasonal years[b](#irv12515-note-0015){ref-type=\"fn\"}) 105.0 8.4 (7.7) 33.1 (32.3) 54.9 (51.4) 14.2 (15.4)[a](#irv12515-note-0014){ref-type=\"fn\"} 3.5 0.2 (6.1) 1.2 (34) 1.5 (42.8) 1.0 (26.3)[a](#irv12515-note-0014){ref-type=\"fn\"}\n R&C \n 2007/2008 140.6 0.4 (0.3) 28.3 (20.1) 111.8 (79.5) 0 (0) 2.1 0 (0.4) 0.5 (24.6) 1.6 (75) 0 (0)\n 2008/2009 59.3 27.1 (45.8) 12.7 (21.4) 19.4 (32.8) 0 (0) 1.2 0.7 (55) 0.2 (20.2) 0.3 (24.8) 0 (0)\n 2009/2010 137.2 1 (0.7) 33 (24.1) 13.9 (10.1) 89.3 (65.1) 5.5 0 (0) 0.7 (12.5) 0.2 (3.9) 4.6 (83.6)\n 2010/2011 87.2 0.1 (0.1) 57.1 (65.5) 14.1 (16.2) 15.9 (18.3) 2.2 0 (0) 1.2 (54.3) 0.2 (9.8) 0.8 (35.9)\n 2011/2012 86.4 0 (0) 10.4 (12.1) 75.9 (87.9) 0 (0) 1.3 0 (0) 0.2 (14.9) 1.1 (85.1) 0 (0)\n 2012/2013 67.8 0 (0) 46.1 (67.9) 0.7 (1) 21 (31) 2.0 0 (0) 1 (48.2) 0 (0) 1.1 (51.8)\n Mean (all years) 96.4 4.8 (7.8) 31.3 (35.2) 39.3 (37.9) 31.6 (32.8)[a](#irv12515-note-0014){ref-type=\"fn\"} 2.4 0.1 (9.2) 0.6 (29.1) 0.6 (33.1) 1.6 (42.8)[a](#irv12515-note-0014){ref-type=\"fn\"}\n Mean (seasonal years[b](#irv12515-note-0015){ref-type=\"fn\"}) 88.2 5.5 (6) 30.9 (35.8) 44.4 (49.2) 12.3 (15.5)[a](#irv12515-note-0014){ref-type=\"fn\"} 1.8 0.1 (7.6) 0.6 (35.4) 0.6 (36) 0.6 (29.2)[a](#irv12515-note-0014){ref-type=\"fn\"}\n\nNumber (proportion) presented.", "\n\nR&C, Respiratory and circulatory diseases.", "\n\nEstimates for seasons 2009 to 2013.", "\n\nseasonal years: all years excluding 2009/2010.", "\n\nJohn Wiley & Sons, Ltd\n\n3.3. ", "Comparisons of mortality burden between seasonal epidemics and the influenza A(H1N1)pdm09 pandemic period {#irv12515-sec-0015}\n--------------------------------------------------------------------------------------------------------------\n\nTable [5](#irv12515-tbl-0005){ref-type=\"table-wrap\"} shows comparisons of mortality burden between seasonal epidemics and the influenza A(H1N1)pdm09 pandemic period from this study and previous studies. ", "The all‐cause mortality rate associated with the influenza A(H1N1)pdm09 was comparable to the mortality rate of seasonal influenza during the non‐pandemic seasons (19.9 \\[CI 10.4‐33.1\\] vs 17.2 \\[CI 7.2‐67.5\\] per 100 000). ", "The mortality impact of the influenza A(H1N1)pdm09 was about double that of seasonal epidemics in non‐pandemic seasons among persons aged \\<65 years (7.2 \\[CI 4.4‐10.9\\] vs 3.5 \\[CI 0.9‐14.6\\] per 100 000), but almost equal among older adults (101.8 \\[CI 48.4‐175.9\\] vs 105 \\[CI 46.9‐386.1\\] per 100 000). ", "However, the differences did not reach statistical significance (*P* \\> .05). ", "Persons aged \\<65 years represented a greater proportion of all deaths during the influenza A(H1N1)pdm09 pandemic period than during the seasonal epidemics (27.0% vs 17.7%, *P* \\< .05). ", "A similar mortality burden age shift toward persons \\<65 years of age was also observed for respiratory and circulatory deaths.", "\n\n###### \n\nComparisons of influenza‐associated death rates (per 100 000 persons) by age and death category in this study with previous studies from China\n\n Model[a](#irv12515-note-0017){ref-type=\"fn\"} Study period All ages Age ≥65 y Age \\<65 y \\% of deaths in age \\<65 y[b](#irv12515-note-0018){ref-type=\"fn\"}\n --------------------------------------------------------------- ---------------------------------------------- -------------- ------------------ --------------------- ----------------- -------------------------------------------------------------------\n All deaths: seasonal \n China(Beijing, this study) NB 2007‐2013 17.2 (7.2‐67.5) 105 (46.9‐386.1) 3.5 (0.9‐14.6) 17.7\n China(Northern cities)[3](#irv12515-bib-0003){ref-type=\"ref\"} NB 2003‐2008 18 (10.9‐32.7) 150.8 (66.2‐502.5) 1.3 6.3\n China(Southern cities)[3](#irv12515-bib-0003){ref-type=\"ref\"} NB 2003‐2008 11.3 (1.4‐50.4) 75.4 (11.0‐313.6) 1.8 13.7\n China[4](#irv12515-bib-0004){ref-type=\"ref\"} NB 2004‐2010 15.1 (6.3‐48.9) 145.5 (95.8‐227.3) 3.7 (1.2‐14.8) 22.4\n China(Guangzhou city)[13](#irv12515-bib-0013){ref-type=\"ref\"} P 2004‐2006 10.6 (0.6‐17.3) 111.3 (19.4‐203.2) ‐ ‐\n China(Guangzhou city)[5](#irv12515-bib-0005){ref-type=\"ref\"} NB 2010‐2012 14.7 (12.1‐17.3) 185.6 (152.5‐218.7) 2.5 (2‐3) 34.8\n Hong Kong, China[14](#irv12515-bib-0014){ref-type=\"ref\"} P 1996‐1999 16.4 (9.4‐23.3) 136.1 (83.7‐188.4) 11.8 (3.8‐20.1) 21.2\n Hong Kong, China[13](#irv12515-bib-0013){ref-type=\"ref\"} P 2004‐2006 13.4 (5.4‐20.9) 103.7 (40.2‐117.1) ‐ ‐\n All deaths: 2009 pandemic \n China(Beijing, this study) NB 2007‐2013 19.9 (10.4‐33.1) 101.8 (48.4‐175.9) 7.2 (4.4‐10.9) 27.0\n China[4](#irv12515-bib-0004){ref-type=\"ref\"} NB 2004‐2010 13.8 (6.3‐28.1) 125.8 (59.3‐250.2) 3.9 (1.7‐8.6) 26.3\n Hong Kong, China[15](#irv12515-bib-0015){ref-type=\"ref\"} P 1998‐2009 1.8 (0‐3.7) ‐ ‐ 8.7\n R&C Deaths: Seasonal \n China(Beijing, this study) NB 2007‐2013 13.5 (5.8‐51.7) 88.2 (41‐313.2) 1.8 (0.3‐9) 11.7\n China(Northern cities)[3](#irv12515-bib-0003){ref-type=\"ref\"} NB 2003‐2008 12.4 (7.4‐22.2) 106 (46.7‐344.1) 0.6 4.3\n China(Southern cities)[3](#irv12515-bib-0003){ref-type=\"ref\"} NB 2003‐2008 8.8 (1.8‐35.1) 64.3 (14.0‐243.7) 0.6 6\n China[4](#irv12515-bib-0004){ref-type=\"ref\"} NB 2004‐2010 11.1 (5‐32.2) 117.8 (54.8‐329.3) 1.7 (0.6‐6.1) 14.5\n China(Guangzhou city)[13](#irv12515-bib-0013){ref-type=\"ref\"} P 2004‐2006 9.9 (2‐17.6) 104.1 (27.5‐177.5) ‐ ‐\n China(Guangzhou city)[5](#irv12515-bib-0005){ref-type=\"ref\"} NB 2010‐2012 11.4 (9.4‐13.4) 146.9 (120.7‐173) 1.7 (1.4‐2) 18\n Hong Kong, China[14](#irv12515-bib-0014){ref-type=\"ref\"} P 1996‐1999 12.4 (7.7‐17.1) 102.4 (61.2‐142.7) 7.3 (3.1‐11.4) 17.2\n Hong Kong, China[13](#irv12515-bib-0013){ref-type=\"ref\"} P 2004‐2006 9.5 (4.5‐14.6) 78.7 (40.2‐117.1) ‐ ‐\n R&C deaths: 2009 pandemic \n China(Beijing, this study) NB 2007‐2013 16 (8.6‐26.2) 89.3 (45.5‐149.3) 4.6 (2.8‐7.1) 20.6\n China[4](#irv12515-bib-0004){ref-type=\"ref\"} NB 2004‐2010 9.4 (4.6‐18.6) 94.6 (44.5‐187.1) 2 (1‐3.8) 19\n Hong Kong, China[15](#irv12515-bib-0015){ref-type=\"ref\"} P 1998‐2009 1.6 (0.4‐2.9) ‐ ‐ 15.7\n\nrate (95% confidence interval) presented.", "\n\nNB denotes negative binomial model; P denotes Poisson model.", "\n\n\\% of deaths in persons aged\\<65 years was a calculation of estimated numbers of influenza.", "\n\nJohn Wiley & Sons, Ltd\n\n4. ", "DISCUSSION {#irv12515-sec-0016}\n=============\n\nThis study estimated the mortality burden of seasonal influenza 2007/2008‐2012/2013 and influenza A(H1N1)pdm09 in Beijing based on robust vital statistics and mortality data. ", "We estimated an average of 2375 (CI 1002‐8688) influenza‐associated all‐cause deaths per year, accounting for 3% (CI 2‐4%) of all reported deaths from the Mortality Register and Surveillance System. ", "All‐cause mortality rates associated with influenza A(H1N1)pdm09 and seasonal influenza 2007/2008‐2012/2013 were 19.9 (CI 10.4‐33.1) and 17.2 (CI 7.2‐67.5) per 100 000 persons, respectively.", "\n\nOur estimates are consistent with previous studies that have shown that the majority of influenza‐associated deaths occurred in persons aged ≥65 years (Table [5](#irv12515-tbl-0005){ref-type=\"table-wrap\"}).[3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"}, [13](#irv12515-bib-0013){ref-type=\"ref\"}, [14](#irv12515-bib-0014){ref-type=\"ref\"}, [15](#irv12515-bib-0015){ref-type=\"ref\"}, [16](#irv12515-bib-0016){ref-type=\"ref\"}, [17](#irv12515-bib-0017){ref-type=\"ref\"}, [18](#irv12515-bib-0018){ref-type=\"ref\"}, [19](#irv12515-bib-0019){ref-type=\"ref\"}, [20](#irv12515-bib-0020){ref-type=\"ref\"}, [21](#irv12515-bib-0021){ref-type=\"ref\"}, [22](#irv12515-bib-0022){ref-type=\"ref\"}, [23](#irv12515-bib-0023){ref-type=\"ref\"} Notably, our study observed that influenza B caused the highest burden (20.5 \\[CI 14.2‐34.9\\] per 100 000) when influenza B virus predominated in 2007/2008. ", "This mortality pattern is consistent with those described in studies conducted by China CDC and Guangzhou CDC,[3](#irv12515-bib-0003){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"} but differs from studies conducted in other regions such as Hong Kong,[14](#irv12515-bib-0014){ref-type=\"ref\"} Singapore,[16](#irv12515-bib-0016){ref-type=\"ref\"} Thailand,[17](#irv12515-bib-0017){ref-type=\"ref\"} United States,[18](#irv12515-bib-0018){ref-type=\"ref\"}, [19](#irv12515-bib-0019){ref-type=\"ref\"} and New Zealand,[23](#irv12515-bib-0023){ref-type=\"ref\"} where the highest death rates were associated with influenza A(H3N2). ", "In addition, the highest mortality burden was not observed in 2011/2012 when influenza B also predominated in Beijing. ", "In 2007/2008, the circulating influenza B viruses originated from the B/Yamagata/16/88 lineage and did not match the vaccine strain, which originated from a different and antigenically distinct lineage of influenza B virus (B/Victoria/2/87).[24](#irv12515-bib-0024){ref-type=\"ref\"} The mismatch of the influenza B strain included in the Northern Hemisphere vaccine with the circulating influenza B strain had a negative impact on the effectiveness of the vaccine in the targeted population.[25](#irv12515-bib-0025){ref-type=\"ref\"} In contrast, the 2012/2013 influenza vaccine was moderately effective against influenza B.[26](#irv12515-bib-0026){ref-type=\"ref\"} Thus, the very low vaccine effectiveness may have led to a higher influenza B infection incidence and mortality in 2007/2008.", "\n\nOur findings for the all‐age mortality burden of seasonal influenza are comparable with previous studies derived from similar approaches in China (Table [5](#irv12515-tbl-0005){ref-type=\"table-wrap\"}) [3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"} and other areas, such as Hong Kong,[14](#irv12515-bib-0014){ref-type=\"ref\"} Singapore,[16](#irv12515-bib-0016){ref-type=\"ref\"} USA,[18](#irv12515-bib-0018){ref-type=\"ref\"} and Mexico.[20](#irv12515-bib-0020){ref-type=\"ref\"} For adults aged ≥65 years, however, our estimate is lower than previous estimates made for China overall, 3 northern cities in China, and a southern city in China (105 \\[46.9‐386.1\\] vs 145.5 \\[95.8‐227.3\\], 150.8 \\[66.2‐502.5\\], and 185.6 \\[152.5‐218.7\\] per 100 000, respectively).[3](#irv12515-bib-0003){ref-type=\"ref\"}, [4](#irv12515-bib-0004){ref-type=\"ref\"}, [5](#irv12515-bib-0005){ref-type=\"ref\"} One explanation for this lower burden of seasonal influenza mortality among older adults in Beijing may be the higher seasonal influenza vaccine coverage among older adults in Beijing compared with older adults in the rest of China. ", "Since 2007, the Beijing Municipal Government has provided annual seasonal influenza vaccination to older adults free of charge, and the vaccine coverage rate for this population in season 2010/2011 was 43%.[9](#irv12515-bib-0009){ref-type=\"ref\"} In most regions of China, older adults must pay for the seasonal influenza vaccine out of pocket, leading to very low vaccine coverage. ", "One study estimated that the vaccine coverage in the Chinese population overall was only 2% in 2009.[27](#irv12515-bib-0027){ref-type=\"ref\"} Second, as the largest proportion of influenza‐associated deaths among older adults is among those aged ≥75 years,[18](#irv12515-bib-0018){ref-type=\"ref\"} different age distributions across regions may contribute to differences in influenza‐associated mortality burden. ", "Beijing is a large city with a very high population aging rate that has reached the average level of developed countries.[28](#irv12515-bib-0028){ref-type=\"ref\"} A higher proportion of adults aged ≥75 years in Beijing may contribute to a higher mortality burden among all adults aged ≥65 years. ", "However, as Beijing is also one of the most developed regions in China, on average, its residents have higher socioeconomic status and better access to health care than residents in other Chinese regions which, in turn, may contribute to a lower mortality burden among older adults.", "\n\nWe estimated that the all‐cause mortality rate associated with influenza A(H1N1)pdm09 was comparable to the mortality impact of seasonal epidemics during the non‐pandemic seasons (19.9 vs 17.2 per 100 000). ", "Although the influenza A(H1N1)pdm09 mortality rate in this study is similar to that estimated by another study in China,[4](#irv12515-bib-0004){ref-type=\"ref\"} it is lower than the rate described in Mexico,[20](#irv12515-bib-0020){ref-type=\"ref\"} and higher than rates estimated in the United States.[29](#irv12515-bib-0029){ref-type=\"ref\"} The case fatality rate of pH1N1 infection during the pandemic was higher in Mexico than in Beijing (1.2% vs 0.6%),[30](#irv12515-bib-0030){ref-type=\"ref\"} contributing to the higher influenza A(H1N1)pdm09 mortality rate described in Mexico. ", "Many factors may have contributed to the regional difference in the mortality impact of the pandemic virus between Mexico and Beijing, including epidemic intensity, use of influenza vaccine and antiviral drugs, and healthcare access. ", "Meanwhile, the lower rates described in the United States may have been associated with the higher vaccination coverage for influenza A(H1N1)pdm09 achieved in the United States compared with Beijing (20% vs 13%, respectively).[31](#irv12515-bib-0031){ref-type=\"ref\"}, [32](#irv12515-bib-0032){ref-type=\"ref\"} Finally, treatment factors may have contributed to different pandemic mortality rates in the United States and Beijing. ", "Due to limited supply of antiviral drugs in Beijing, most patients with mild influenza illness did not take neuraminidase inhibitors within 48 hours of illness onset, increasing the likelihood of severe or fatal outcomes.[7](#irv12515-bib-0007){ref-type=\"ref\"} In addition, although approximately 80% of patients with severe illness from influenza A(H1N1)pdm09 in Beijing were treated with neuraminidase inhibitors at some point during the course of their illness, in most cases, treatment was not initiated within 48 hours of illness onset.[7](#irv12515-bib-0007){ref-type=\"ref\"}\n\nConsistent with studies conducted in other countries, our study found that, compared with seasonal epidemics, there was an \"age shift\" in age‐specific mortality burden toward persons \\<65 years of age during the influenza A(H1N1)pdm09 pandemic period.[4](#irv12515-bib-0004){ref-type=\"ref\"}, [20](#irv12515-bib-0020){ref-type=\"ref\"}, [29](#irv12515-bib-0029){ref-type=\"ref\"}, [33](#irv12515-bib-0033){ref-type=\"ref\"}, [34](#irv12515-bib-0034){ref-type=\"ref\"}, [35](#irv12515-bib-0035){ref-type=\"ref\"}, [36](#irv12515-bib-0036){ref-type=\"ref\"} A previous meta‐analysis from 27 studies showed that the influenza A(H1N1)pdm09 cumulative incidence varied significantly by age with much higher incidence in younger people.[37](#irv12515-bib-0037){ref-type=\"ref\"} In addition, a study comparing seasonal influenza and influenza A(H1N1)pdm09 demonstrated that younger people had 2‐4 times the risk of severe outcomes from influenza A(H1N1)pdm09 than persons of the same ages with seasonal influenza.[38](#irv12515-bib-0038){ref-type=\"ref\"} These findings suggest that prevention and control measures during pandemics may need to target younger adults who are not considered high risk during seasonal epidemics.", "\n\nThis study has several limitations. ", "First, although underreporting of deaths in Beijing is low when compared to China overall (4‐7% vs 17%),[39](#irv12515-bib-0039){ref-type=\"ref\"}, [40](#irv12515-bib-0040){ref-type=\"ref\"}, [41](#irv12515-bib-0041){ref-type=\"ref\"} it is possible that underreporting still led to an underestimation of influenza mortality. ", "Second, because Beijing does not have access to local respiratory syncytial virus (RSV) virology data, we were unable to control for RSV co‐circulation. ", "As RSV is associated with substantial mortality,[18](#irv12515-bib-0018){ref-type=\"ref\"} not accounting for RSV may have inflated our influenza‐related mortality burden estimate. ", "While it is possible that our estimates might be an overestimate of influenza‐associated deaths, the inclusion of viral surveillance terms significantly reduces the chance of overestimation. ", "Prior to including these terms, we evaluated the surveillance data to ensure that it was robust and did not show instances of bias due to few specimens being collected. ", "We also compared our viral surveillance data to the national system which showed a similar pattern in influenza virus circulation for the northern region of China. ", "Third, we did not have the sample size available to obtain reliable estimates within more refined age categories. ", "There were also several factors that may contribute to deaths in Beijing that we were unable to include in our model, such as air quality, which is particularly poor in Beijing especially when compared to cities outside of China. ", "Finally, our estimates were based on an ecological study design, and therefore, we cannot confirm a causal relationship between influenza activity and our estimates of mortality burden.", "\n\n5. ", "CONCLUSIONS {#irv12515-sec-0017}\n==============\n\nOur study demonstrates a substantial influenza‐related mortality burden in Beijing, China from 2007/2008 to 2012/2013, especially among older adults. ", "Influenza B caused highest mortality when influenza B virus was the predominant circulating virus in 2007/2008. ", "Although this study did not find any increase in all‐age influenza‐associated mortality during the influenza A(H1N1)pdm09 pandemic period, the mortality burden in 2009/2010 increased among persons aged \\<65 years. ", "These findings inform local influenza prevention and control strategies. ", "First, the results support policies that give priority to older adults for seasonal influenza vaccination as they have done since 2007, and efforts to identify strategies to increase vaccine coverage in this population at highest risk for seasonal influenza‐related mortality. ", "Second, the increased influenza‐associated mortality rates among persons \\<65 years of age during the influenza A(H1N1)pdm09 pandemic period suggest that the most effective pandemic vaccination strategies may differ from those used for seasonal influenza; it is important to identify and vaccinate populations at highest risk for morbidity and mortality during each pandemic.", "\n\nCONFLICT OF INTEREST {#irv12515-sec-0019}\n====================\n\nThe authors declare that they have no competing interests.", "\n\nAUTHORS' CONTRIBUTION {#irv12515-sec-0020}\n=====================\n\nWS, WZ, YP, and WQ designed the study; WS and SJ performed the data collection; WQ and WZ coordinated and supervised the data collection; WS analyzed the data; WS, YP, CG, SY, and AI participated in the interpretation of data; WS drafted the initial manuscript; WS, CG, SY, and AI revised the manuscript. ", "All authors have read and approved the final version of the manuscript.", "\n\nSupporting information\n======================\n\n###### \n\n \n\n###### \n\nClick here for additional data file.", "\n\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the United States Centers for Disease Control and Prevention.", "\n" ]

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[ "(NaturalNews) In a stunning interview with Truthout's Martha Rosenberg, former FDA drug reviewer, Ronald Cavanaugh, exposes the FDA as a relentless criminal mafia protecting its client, Big Pharma, with a host of mob strategies.", "Cavanaugh: \"...widespread racketeering, including witness tampering and witness retaliation.", "\"\"I was threatened with prison.", "\"\"One [FDA] manager threatened my children... I was afraid that I could be killed for talking to Congress and criminal investigators.", "\"Cavanaugh reviewed new drug applications made to the FDA by pharmaceutical companies. ", "He was one of the holdouts at the Agency who insisted that the drugs had to be safe and effective before being released to the public.", "But honest appraisal wasn't part of the FDA culture, and Cavanaugh swam against the tide, until he realized his life and the life of his children was on the line.", "What was his secret task at the FDA? \"", "Drug reviewers were clearly told not to question drug companies and that our job was to approve drugs.\" ", "In other words, rubber stamp them. ", "Say the drugs were safe and effective when they were not.", "Cavanaugh's revelations are astonishing. ", "He recalls a meeting where a drug-company representative flat-out stated that his company had paid the FDA for a new-drug approval. ", "Paid for it. ", "As in bribe.", "He remarks that the drug pyridostigmine, given to US troops to prevent the later effects of nerve gas, \"actually increased the lethality\" of certain nerve agents.", "Cavanaugh recalls being given records of safety data on a drug---and then his bosses told him which sections not to read. ", "Obviously, they knew the drug was dangerous and they knew exactly where, in the reports, that fact would be revealed.", "Read the entire landmark interview for yourself and see what the FDA really is. ", "We are not dealing with isolated incidents of cheating and lying. ", "We are not dealing with a few isolated bought-off FDA employees. ", "The situation at the FDA isn't correctable with a few firings. ", "This is an ongoing criminal enterprise, and any government official, serving in any capacity, who has become aware of it and has not taken action, is an accessory to mass poisoning of the population.", "Twelve years ago, the cat was let out of the bag. ", "Dr. Barbara Starfield, writing in the Journal of the American Medical Association, on July 26, 2000, in a review titled, \"Is US health really the best in the world,\" exposed the fact that FDA-approved medical drugs kill 106,000 Americans per year.", "In interviewing her, I discovered that she had never been approached by any federal agency to help remedy this tragedy. ", "Nor had the federal government taken any steps on its own to stop the dying.", "Jon RappoportThe author of an explosive collection, THE MATRIX REVEALED, Jon was a candidate for a US Congressional seat in the 29th District of California. ", "Nominated for a Pulitzer Prize, he has worked as an investigative reporter for 30 years, writing articles on politics, medicine, and health for CBS Healthwatch, LA Weekly, Spin Magazine, Stern, and other newspapers and magazines in the US and Europe. ", "Jon has delivered lectures and seminars on global politics, health, logic, and creative power to audiences around the world.", "The author of an explosive new collection, THE MATRIX REVEALED, Jonwas a candidate for a US Congressional seat in the 29th District ofCalifornia. ", "Nominated for a Pulitzer Prize, he has worked as aninvestigative reporter for 30 years, writing articles on politics,medicine, and health for CBS Healthwatch, LA Weekly, Spin Magazine,Stern, and other newspapers and magazines in the US and Europe. ", "Jonhas delivered lectures and seminars on global politics, health, logic,and creative power to audiences around the world." ]

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[ "The online version of this article (doi:10.1186/1559-4106-8-10) contains supplementary material, which is available to authorized users.", "\n\nThe authors declare that they have no competing interests.", "\n\nGRL and JC carried out the modeling of the DNA encapsulated in HAp and quantum mechanical calculations. ", "GRL and OB conducted simulations related with the nucleation of calcium phosphate at a DNA template. ", "JP assisted in modeling, simulations and discussion. ", "PT and CA developed the analyses and discussion of results. ", "CA drafted the manuscript. ", "All authors read and approved the final manuscript.", "\n\nBackground {#Sec1_8}\n==========\n\nHydroxyapatite (HAp), a mineral with formula Ca~10~(PO~4~)~6~(OH)~2~ and hexagonal symmetry, is the most stable form of calcium phosphate at room temperature and in the pH range of 4--12 \\[[@CR1_8]\\]. ", "This mineral, which is the main component of bones and teeth, is considered as an important biomaterial since several decades ago \\[[@CR2_8]\\]. ", "Thus, due to both its outstanding biological responses to the physiological environment and its very close similarity to natural bone structure, HAp is currently applied in biomedicine. ", "For example, it is used as a bioactive and osteoconductive bone substitute material in clinical surgery \\[[@CR3_8], [@CR4_8]\\], and as a system for the delivery of antitumor agents and antibodies in the treatment of cancer \\[[@CR5_8]--[@CR7_8]\\]. ", "Furthermore, as HAp also has the advantage of absorbability and high binding affinity with a variety of molecules, it has been also used as a purification platform. ", "For example, HAp is applied for the removal of heavy atoms from waste water \\[[@CR8_8]\\], and for the separation, extraction and purification of proteins \\[[@CR9_8]\\] and DNA \\[[@CR10_8]\\].", "\n\nDNA/HAp biominerals formed by the combination of DNA with a HAp matrix can be viewed from different perspectives. ", "The first refers to the fact that therapeutic DNA is encapsulated in HAp nanoparticles for its subsequent transfection into living cells (*e.g.* liver cells, fibroblasts, osteoblasts and tumor cells) \\[[@CR5_8]--[@CR7_8], [@CR11_8], [@CR12_8]\\]. ", "Specifically, HAp nanoparticles with embedded DNA chains can be obtained using different approaches, even though the more popular are those based on the *in situ* precipitation of the inorganic salt in presence of DNA \\[[@CR13_8], [@CR14_8]\\] and on the use of a HAp core that is coated using colloidal solutions to give a multi-shell particle \\[[@CR7_8]\\]. ", "Nanostructured HAp has been shown to be superior for the transfection to other gene delivery methods in terms of immunogenicity and toxicity (*i.e.* safety) \\[[@CR15_8]\\]. ", "Moreover, the transfection efficiency can be stabilized and enhanced by modulating properties such as extent of DNA binding and encapsulation, particle size, and dissolution behavior of the HAp phases \\[[@CR15_8], [@CR16_8]\\]. ", "The interaction between the two entities of the biomineral has been proposed to occur because of the affinity between the calcium of HAp and the phosphate backbone of DNA \\[[@CR17_8]--[@CR20_8]\\]. ", "It should be noted that this proposal makes the nucleotide sequence of DNA unimportant, whereas its length takes major importance.", "\n\nAnother perspective is the one reported by Kostetsky \\[[@CR21_8]\\], who observed that the period of translation along the *c*-axis of the HAp lattice, 3.4 Å, is relatively similar to the period of the DNA double helix. ", "This feature combined with the fact that the phosphate groups of HAp are able to catalyze the abiogenic synthesis of: D-riboses from ammonia, methane and water \\[[@CR22_8], [@CR23_8]\\]; nucleotides from nucleosides condensing agents and ammonium oxalate \\[[@CR24_8]\\]; and polynucleotides with a 3^′^,5^′^-phosphodiether bond \\[[@CR24_8]\\] under conditions similar to those of primeval Earth, led Kostetsky to propose a model for the synthesis of DNA through the interaction of its different elements with the lattice of HAp mineral \\[[@CR25_8]\\]. ", "According to this model, the DNA double helix is embedded into the crystalline network of HAp forming a biomineral similar to that obtained by encapsulating therapeutic DNA into HAp nanoparticles.", "\n\nOn the other hand, in a very recent study Gerdon and co-workers \\[[@CR26_8]\\] demonstrated the ability of DNA to template the mineralization of calcium phosphate. ", "These authors developed a quartz crystal microbalance sensor for the quantification of HAp formation and the assessment of DNA as a template molecule. ", "The results, which were also supported by optical density and dynamic light scattering measures, FTIR spectroscopy and scanning electron microscopy, suggested that DNA sequesters calcium and phosphate ions, thereby supersaturating the microenvironment and acting as a scaffold on which mineral forms \\[[@CR26_8]\\]. ", "Moreover, small differences in DNA length, hybridization, and secondary structure were found to provoke differences in affinity for HAp and appear to influence mineralization.", "\n\nIn this work we have used molecular modeling tools to investigate the structure of DNA/HAp biominerals, in which single stranded (ss) and double stranded (ds) DNA are embedded into HAp nanopores. ", "We have focused our analyses on the following aspects: (i) the smallest nanopore size required for the accommodation of ds DNA arranged in the typical B structure \\[[@CR27_8]\\] (ds B-DNA) during the encapsulation process; (ii) the strain induced by the HAp crystalline field into the B-DNA structure; (iii) the importance of the chemical nature of the inorganic part of the biomineral in the DNA, which has been investigated by comparing DNA/HAp with the biomineral constructed by combining DNA with fluoroapatite \\[Ca~10~(PO~4~)~6~F~2~, abbreviated FAp\\], hereafter denoted DNA/FAp; (iv) the encapsulation of ss DNA in terms of molecular strain and relative stability with respect to ds DNA; and (v) the stability of HAp crystals formed around the ds B-DNA core. ", "Furthermore, in order to contribute to a better understanding of the interaction of B-DNA with HAp at the atomic level, we have performed a simulation study of the nucleation and crystal growth of HAp at the ds B-DNA matrix. ", "More specifically, we have used Molecular Dynamic (MD) simulations to provide detailed atomistic models for the initial stages of nucleation and cluster formation of calcium phosphate at a B-DNA molecule. ", "The rest of the paper has been organized as follows. ", "In the next section, we briefly summarize the main characteristics of the crystal structures of natural HAp and FAp, and the chemical structures of the three B-DNA duplexes studied in this work. ", "After this, the strategy and computational details used for both the encapsulation of DNA in apatites and the early processes in the nucleation of HAp at a B-DNA template are described. ", "The results have been organized in several sub-sections, which are devoted to the encapsulation of ds and ss DNA in both HAp and FAp, the validation of the force-field to reproduce organic···inorganic interactions in biominerals, and both the modeling and dynamics of HAp crystals growth around the ds B-DNA template. ", "Finally, conclusions are summarized in the last section of the article.", "\n\nStructures of apatites and DNA {#Sec2_8}\n------------------------------\n\nNatural HAp has a hexagonal crystal structure with space group P6~3~/m and periods *a*=*b*= 9.42 Å, and *c*= 6.87 Å. The total number of atoms in the unit cell is 44, even though it only contains seven symmetrically independent atoms: two calcium ions, one forming single atomic columns parallel to the *c* axis (Ca~I~) and the other surrounding the hexagonal channel of hydroxyl in groups of the three calcium atoms at different heights (Ca~II~); one phosphor and three oxygen atoms (P, O~I~, O~II~ and O~III~) forming PO~4~ tetrahedral units; and the O(H) ions disordered along *c* about the mirror plane at *z*= ¼. The occupancy of the OH^-^ sites was 50%, as necessary in a P6~3~/m. ", "FAp shows a very similar crystal structure with 42 atoms in the P6~3~/m hexagonal cell (*a*= *b*= 9.40 Å, *c* = 6.88 Å) \\[[@CR28_8]\\]. ", "In this case, the OH^-^ ions of HAp are replaced by F^-^, which are located on the *c*-axis. ", "The Additional file [1](#MOESM1_8){ref-type=\"media\"}: provides the positions of the non-equivalent atoms used to construct HAp and FAp for the modeling of the biominerals, and the projections of the HAp unit cells.", "\n\nThree different ds dodecamers, which adopt a B-DNA double helix, have been examined. ", "The chemical structures of the three duplexes, hereafter denoted **I**, **II** and **III**, are 5^′^-CGCGAATTCGCG-3^′^, 5^′^-GCGAGATCTGCG-3^′^ and 5^′^-CGCGAATTC^\\*^GCG-3^′^, respectively. ", "Sequence **I** is known as the Dickerson's dodecamer \\[[@CR29_8]\\] and consists in a well-known sequence with three primary characteristic tracts: CG, AA and TT. ", "Sequence **II** is a conventional sequence that becomes involved in different cellular processes, including carcinogenic ones \\[[@CR30_8]\\]. ", "Finally, **III** involves methylation of the C5 position of cytidine base, identified as C^\\*^\\[[@CR31_8]\\]. ", "This methylation is known to suppress hydrolysis by *Eco*RI restriction enzyme. ", "The 3D structure of the three dodecamers was studied in solution and/or solid state \\[[@CR29_8]--[@CR32_8]\\], a B-DNA arrangement being observed in all cases. ", "Details of the ds B-DNA structure are given in the The Additional file [1](#MOESM1_8){ref-type=\"media\"}: On the other hand, ss DNAs were constructed by removing one of the strands from the three selected duplexes.", "\n\nEncapsulation of DNA in apatites and nucleation of HAp {#Sec3_8}\n------------------------------------------------------\n\nGiving the hexagonal symmetry of the two investigated apatites and the molecular dimensions of the B-DNA dodecamers, HAp and FAp models (super-cells) were constructed considering 6×6×7 unit cells. ", "After this, a hole was generated in the center of each super-cell, the dimensions of such hole being defined by the ds B-DNA (*i.e.* steric conflicts between the apatite atoms and the B-DNA were not allowed). ", "After several trials, we found that a hole of 2×2×7 units cells (Figure [1](#Fig1){ref-type=\"fig\"}a) was the minimum required to accommodate the double helix without severe steric contacts. ", "In order to completely avoid unfavorable steric interactions between the apatite and the biomolecule, some additional atoms and groups of atoms were translated at their border regions (Figure [1](#Fig1){ref-type=\"fig\"}b) allowing us to maintain the electroneutrality of the super-cells. ", "The side length of this hole is 19 Å and its angle γ is 120°. ", "The resulting models (*i.e.* super-cells with a hole of appropriated dimensions at the center) consist of 9856 and 9408 atoms for HAp and FAp, respectively.", "Figure 1**(a) Simplified scheme of the HAp and FAp super-cells and the hole used to encapsulate ds B-DNA.** (**", "b**) Atomistic depiction of the FAp super-cell projected onto the (001) plane showing the atoms (blue arrows) and groups of atoms (blue arrows and circles) translated to the border regions of the super-cell. (**", "c**) Graphical representation of the system used to investigate the initial stages HAp nucleation and growth at a B-DNA in aqueous solution: Dickerson's dodecamer double helix in the center of the simulation box, which also contains water solvent molecules and Ca^2 +^, and OH^--^ ions.", "\n\nThe atomic coordinates for the ds DNAs were generated using the NAB (Nucleic Acid Builder) program of the AMBER software \\[[@CR33_8]\\], which constructed the double helix in the canonical B form. ", "In order to maintain the electrical neutrality of the system, Ca^2+^ ions were put at the minor groove of the double helix, as is frequently observed by X-ray diffraction \\[[@CR34_8]--[@CR36_8]\\]. ", "The positions of these ions were optimized by energy minimization while the coordinates of the rest of the atoms of the system were kept fixed. ", "Models for encapsulated ss DNAs were constructed by removing one of the two strands from the ds B-DNAs embedded in HAp or FAp. ", "In these cases, Ca^2+^ ions were put at random positions around the backbone phosphate groups and subsequently optimized by energy minimization.", "\n\nThe simulation system used to investigate the initial stages of nucleation and cluster formation of calcium phosphate at a B-DNA double helix consisted of the Dickerson's dodecamer duplex (**I**), which was located at the center of the simulation box, 945 Ca^2+^ ions, 567 ions, 189 OH^--^ ions, and 29560 water molecules (Figure [1](#Fig1){ref-type=\"fig\"}c). ", "In order to provide a comprehensive view of the templating role of the double helix, additional simulations of the same system but without B-DNA were carried out. ", "Several factors are expected to affect the nucleation and growth of the HAp at the B-DNA, ionic concentration being among them. ", "We are aware that the concentration of ions in the simulation systems is higher than in biological conditions. ", "However, modeling much lower concentrations would require computationally prohibitively large simulation boxes. ", "Furthermore, increasing the ion concentration is a practical way to accelerate the simulation of HAp nucleation and growth \\[[@CR37_8], [@CR38_8]\\].", "\n\nMethods {#Sec4_8}\n=======\n\nEncapsulation of DNA {#Sec5_8}\n--------------------\n\nIn order to relax and investigate the stability of the models constructed in the previous section, molecular mechanics calculations based on both energy minimization and MD simulations were applied using the NAMD 2.6 program \\[[@CR39_8]\\]. ", "Initially, all the models were minimized by applying 5×10^3^ steps of steepest descent to relax the more important conformational and structural tensions. ", "Then, a MD run of 3.0 ns in the NVT ensemble (constant number of particles, volume and temperature) at 298 K was carried out to equilibrate the systems and eliminate small structural tensions. ", "After such thermal relaxation, the saved coordinates were submitted to a new energy minimization by applying 5×10^3^ steps of steepest descent. ", "In both energy minimizations and MD simulation, atoms contained in ds and ss DNAs were the only ones allowed to move from their positions, the coordinates of the mineral being kept fixed at their crystallographic positions in all cases. ", "It should be emphasized that all the systems were calculated in triplicate considering starting points that differ in the orientation of the DNA with respect to the apatite.", "\n\nThe potential energy was computed using the Amber force-field \\[[@CR40_8], [@CR41_8]\\]. ", "All force-field parameters for DNA as well as the phosphate and hydroxyl groups of apatites were extracted from Amber ff03 \\[[@CR42_8]\\]. ", "This is a variant of Amber ff99 \\[[@CR43_8]\\] in which charges and main chain torsion potentials have been re-derived from quantum mechanical calculations in solution. ", "It should be noted that the ff03 parameters are identical to the ff99-SB \\[[@CR44_8]\\] ones for nucleic acids, phosphate and hydroxyl groups. ", "Force-field parameters of Ca^2+^ and F^-^ were extracted from the works reported by Bradbrook *et al.*\\[[@CR45_8]\\] and Dang \\[[@CR46_8]\\], respectively (see The Additional file [1](#MOESM1_8){ref-type=\"media\"}).", "\n\nThe geometric distortion induced by the apatite in the secondary structure of DNA (Δτ) has been measured as an energy penalty in the bonding contributions using Eqn 1:\n\nwhere Δ*E*~*str*~, Δ*E*~*bnd*~ and Δ*E*~*tor*~ refer to the differences in the stretching, bending and torsional energies, respectively. ", "It should be remarked that Δτ exclusively refers to the geometric stress of the double helix, the omission of non-bonding contributions in Eqn 1 allowing us to avoid masking effects associated with strong electrostatic interactions. ", "These differences were calculated by subtracting the energy values associated with the relaxed structure (*i*.*e*. ", "the structure obtained for the DNA embedded in apatite after relaxation by energy minimization and MD simulations) and canonical B-form of DNA (*i*.*e*. ", "the structure directly provided by the NAB module). ", "It should be noted that Δτ accounts for the structural stress induced by the apatite atoms in DNA.", "\n\nValidation of the force-field {#Sec6_8}\n-----------------------------\n\nThe reliability of the force-field parameters used in this work to reproduce apatite···DNA interactions in biominerals has been evaluated by comparing the interaction energies derived from molecular mechanics and quantum mechanics calculations. ", "A total of 22 small model complexes containing a fragment of DNA and a fragment of apatite were taken from the modeled biominerals. ", "These complexes, which involved a number of atoms ranging from 53 to 98, were selected to cover the modeling of both attractive and repulsive interactions. ", "The interaction energies, which were estimated as the difference between the total energy of the complex and the energies of the isolated fragments, were calculated using both the AMBER force-field and the B3LYP/6-31G(d) \\[[@CR46_8]--[@CR48_8]\\] quantum mechanical method. ", "The basis set superposition error (BSSE) of the interaction energies calculated at the B3LYP/6-31G(d) level was corrected using the counterpoise (CP) method \\[[@CR49_8]\\]. ", "All quantum mechanical calculations were performed using the Gaussian 09 computer program \\[[@CR50_8]\\].", "\n\nNucleation of HAp {#Sec7_8}\n-----------------\n\nMD simulations in NPT conditions (constant number of particles, temperature of 298 K and pressure of 1 atm) were performed using the NAMD 2.6 \\[[@CR39_8]\\] code to investigate the process of formation and growth of HAp around ds B-DNA molecule in a bath of water molecules. ", "Before the incorporation of DNA, the density of the water in the simulation box was 1.00 g/cm^3^ at a temperature of 298 K. The force-field parameters for DNA, phosphate and hydroxyl groups, and Ca^2+^ were identical to those for the encapsulation study. ", "The water molecules were represented using the TIP3P model \\[[@CR51_8]\\]. ", "The initial simulation box (92.0×91.5×108.0 Å^3^) was equilibrated using the following strategy. ", "Before any MD trajectory was run, 5×10^3^ steps of energy minimization were performed in order to relax conformational and structural tensions. ", "Next, different consecutive rounds of short MD runs were performed in order to equilibrate the density, temperature, and pressure. ", "First, solvent and ions were thermally relaxed by three consecutives runs, while the B-DNA was kept frozen: 0.5 ns of NVT-MD at 500 K were used to homogeneously distribute the solvent and ions in the box. ", "After this, 0.5 ns of isothermal (298 K) and 0.5 ns isobaric (1 atm and 298 K) relaxation were run. ", "Finally, all the atoms of the system were submitted to 0.15 ns of steady heating until the target temperature was reached (298 K), 0.25 ns of NVT-MD at 298 K (thermal equilibration) followed by 0.5 ns of density relaxation (NPT-MD).", "\n\nAtom pair distance cut-offs were applied at 16.0 Å to compute the van der Waals interactions. ", "In order to avoid discontinuities in the Lennard-Jones potential, a switch function was applied to allow a continuous decay of the energy when the atom pair distances are larger than 14.0 Å. For electrostatic interactions, we computed the non-truncated electrostatic potential throughout Ewald Summations \\[[@CR52_8]\\]. ", "The real space term was determined by the van der Waals cut-off (16 Å), while the reciprocal term was estimated by interpolation of the effective charge into a charge mesh with a grid thickness of 5 points per volume unit, *i*.*e*. ", "Particle-Mesh Ewald (PME) method \\[[@CR52_8]\\]. ", "Both temperature and pressure were controlled by the weak coupling method, the Berendsen thermobarostat \\[[@CR53_8]\\]. ", "The relaxation times used for the coupling were 1 and 10 ps for temperature and pressure, respectively. ", "Bond lengths were constrained using the SHAKE algorithm \\[[@CR54_8]\\] with a numerical integration step of 1 fs. ", "Periodic boundary conditions were applied using the nearest image convention, and the nonbonded pair list was updated every 1000 steps (1 ps). ", "The end of the density relaxation simulation was the starting point of the 10 ns production simulations presented in this work. ", "The coordinates of all the production runs were saved every 500 steps (1 ps intervals).", "\n\nResults and discussion {#Sec8_8}\n======================\n\nEmbedding double stranded B-DNA in hydroxyapatite {#Sec9_8}\n-------------------------------------------------\n\nFigure [2](#Fig2){ref-type=\"fig\"}a represents the structure of Dickerson's dodecamer (sequence **I**) embedded in HAp before relaxation. ", "As it can be seen, the B-DNA occupies practically the whole pore, indicating that its dimensions are appropriated to accommodate the double helix. ", "Figure [2](#Fig2){ref-type=\"fig\"}b depicts the double helix after complete relaxation through energy minimizations and MD. ", "Although interactions with HAp atoms induce some distortions in the backbone of B-DNA, both the intra-strand stacking and the inter-strand hydrogen bonds are clearly preserved. ", "The influence of the sequence on the B-DNA distortion induced by the mineral was examined by considering the double helices of **II** and **III** embedded in the same pore of HAp. ", "Inspection of the relaxed structures, which are also included in Figure [2](#Fig2){ref-type=\"fig\"}b, indicates that, as observed for **I**, apparently the initial double helices do not undergo significant distortions. ", "This result is fully consistent with previous suggestions, which attributed the binding between HAp and ds DNA to the attractive interaction between the Ca^2+^ ions of the former and the PO~4~^3-^ groups of the latter \\[[@CR17_8]--[@CR20_8]\\]. ", "According to this feature, the role of the nucleotide sequence is relatively unimportant and the stability of the B-DNA inside the pore is essentially due to the dimensions of the latter.", "Figure 2(**a**) **Equatorial perspective of the B-DNA double helix (I) embedded in HAp before relaxation.** (**", "b**) Axial perspective of the double helix of **I**, **II** and **III** after relaxation.", "\n\nThe distortion induced by the mineral in the double helix of each of the three investigated sequences was quantified using the parameters displayed in Table [1](#Tab1){ref-type=\"table\"}, which correspond to: (*i*) Δτ, which measures energy differences of the bonding contributions (Eqn 1); (*ii*) the root mean square deviation (RMSD) between the canonical double helix (*i*.*e*. ", "the starting structure) and the relaxed double helix; and (*iii*) the inter-chain distance (IC) measured with respect to the centers of mass of each strand. ", "Interestingly, the Δτ obtained for **I** was one order of magnitude higher than for **II** and **III**, even though the difference between the bonding contributions was attractive in all cases. ", "Thus, distortion of the backbone produces an energy penalty in the torsional energy but favorable stretching and, especially, bending contributions, resulting in an attractive Δτ value. ", "However, the unfavorable torsional energy contributions, which reflect the conformational distortions induced by the mineral in the canonical B-DNA, are relatively small. ", "The RMSDs ranged from 1.7 to 4.2 Å, which are relatively low considering that they were derived using all the atoms of ds DNA. ", "Finally, the IC showed very small distortions (*i*.*e*. ", "ranging from −0.5 to +2.8 Å) since the IC of the starting structures varied from 19.0 to 20.3 Å, depending on the sequence.", "Table 1**Stress induced by the minerals in the DNA molecules (Δτ; in kcal/mol), stretching, bending and torsional contributions to the stress (Δ*E***~***str***~**, Δ*E***~***bnd***~**and Δ*E***~***tor***~***,*respectively), inter-chain distance (IC; in Å) and root mean square deviations (RMSD; in Å) between the initial and the relaxed conformations of the biomolecule for different systems encapsulated in HAp and FAp**Δτ ^a^Δ***E***~***str***~Δ***E***~***bnd***~Δ***E***~***tor***~IC ^b^RMSD ^c^HAp···ds B-DNA**I**−277−32−291+4622.83.5**II**−2460−311−2160+1119.81.7**III**−1975−228−1903+15618.74.2FAp···ds B-DNA**I**+698+961−385+12217.69.7HAp···ss DNA**I**−239−22−236+19.2-10.3FAp···ss DNA**I**−204−18−234+48-11.1^a^ Eqn (1). ", "^b^ Calculated with respect to the center of masses of each strand. ", "^c^ The RMSD was calculated considering all the atoms of the duplexes.", "\n\nThe overall of these results indicates that the cavity displayed in Figure [1](#Fig1){ref-type=\"fig\"}b allows encapsulate B-DNA double helices without produce mineral-induced stress. ", "Moreover, the dimensions of the pore combined with the crucial role played by the Ca^2+^ are appropriated to avoid any dependence on the nucleotide sequence. ", "Accurate definition of the cavity is provided by the maximum distances between pairs of atoms of the mineral at the internal diagonals of the pore, which are 30.5 and 21.1 Å.\n\nEmbedding double stranded B-DNA in fluoroapatite {#Sec10_8}\n------------------------------------------------\n\nRelaxation of ds Dickerson's dodecamer embedded in FAp led to the structure displayed in Figure [3](#Fig3){ref-type=\"fig\"}a. ", "Although the general shape of the double helix is retained after energy minimizations and MD, it underwent geometric distortions that affected significantly both the inter-strand hydrogen bonds and the intra-strand π-stacking. ", "Thus, the RMSD calculated with respect to the canonical B-DNA used as starting point was 9.7 Å (Table [1](#Tab1){ref-type=\"table\"}), this value being significantly higher than those obtained for complexes with HAp. ", "Moreover, the energy penalty is repulsive, Δτ= 698 kcal/mol, evidencing the significant geometric stress induced by FAp in the double helix. ", "This stress is essentially concentrated in the bond lengths, the Δ*E*~*str*~ being not only repulsive but also significantly higher than the Δ*E*~*bnd*~ and Δ*E*~*tor*~ contributions. ", "Finally, it should be noted that the repulsive interactions between the FAp and the double helix produces a significant reduction in the IC with respect to the initial value. ", "Thus, the distance between the centers of masses of the two strands in the canonical B-DNA form of **I** was 20.0 Å, decreasing to 17.6 Å after relaxation inside of the FAp pore. ", "This contraction is in opposition with the expansion of 2.8 Å observed when **I** was embedded in HAp, reflecting the repulsive force exerted by fluorine atoms of FAp in the double helix.", "Figure 3Axial perspectives of (a) the double helix of I before and after relaxation in FAp and of (b) a single strand of I before and after relaxation in FAp (top) and HAp (down).", "\n\nEmbedding single stranded DNA in apatites {#Sec11_8}\n-----------------------------------------\n\nAs expected, ss DNA molecules encapsulated in HAp and FAp underwent drastic conformational changes upon relaxation. ", "Obviously, this should be attributed to the lack of inter-strand hydrogen bonding, which facilitates the distortions induced by the interactions with the mineral. ", "Figure [3](#Fig3){ref-type=\"fig\"}b reflects such important variations for ss-**I**. ", "The RMSD obtained for the strand encapsulated in HAp and FAp after relaxation is 10.3 and 11.1 Å, respectively, suggesting that distortions are similar in both cases. ", "The latter is corroborated by Δτ values (Table [1](#Tab1){ref-type=\"table\"}). ", "Thus, the pore is large enough to minimize repulsive interactions, independently of the composition of the mineral, through the complete conformational reorganization of the biomolecule. ", "The relaxed conformation displayed in Figure [3](#Fig3){ref-type=\"fig\"}b should be simply considered as one of the many possible disordered conformational states of the ss DNA molecules (*i*.*e*. ", "the pore allows multiple disordered conformational states for the DNA strand, as was observed during the MD simulation). ", "Similar results were obtained for ss-**II** and ss-**III** (not shown).", "\n\nValidation of the force-field {#Sec12_8}\n-----------------------------\n\nWe are aware that the molecular mechanics calculations presented in the above sub-sections were carried out using force-field parameters that were not explicitly designed to investigate the inorganic···organic interactions found in biominerals. ", "Specifically, the parameters used to simulate the phosphate and hydroxyl groups of apatites were extracted from Amber ff03 \\[[@CR41_8]\\], which was explicitly developed to study the dynamics of proteins and nucleic acid in condensed phases, while those used for Ca^2+^ and F^-^ were set to study the crystallographic structure of monosaccharides \\[[@CR44_8]\\] and the solvation of LiF in polarizable water \\[[@CR45_8]\\], respectively. ", "Before to investigate the nucleation of HAp at a B-DNA double helix, we performed quantum mechanical calculations on model systems to demonstrate that such force-field parameters satisfactorily reproduce inorganic···organic interactions. ", "A total of 22 model complexes, each containing a fragment of HAp and a fragment of B-DNA, were taken from the model obtained for **I** embedded in the mineral. ", "These model complexes were selected to cover a wide range of interactions, both attractive and repulsive. ", "The interaction between the HAp and B-DNA fragments was calculated for all the complexes using both the force-field potential (ΔE^FF,i^) and the B3LYP/6-31G(d) quantum mechanical method (ΔE^QM,i^), the CP procedure being applied in the latter to correct the BSSE.", "\n\nThe ΔE^QM,i^ against ΔE^FF,i^ values range from 11.7 to −17.1 kcal/mol and from 11.3 to −14.8 kcal/mol, respectively. ", "Figure [4](#Fig4){ref-type=\"fig\"}, which represents ΔE^QM,i^ against ΔE^FF,i^, evidences a close agreement between the force-field and quantum mechanical estimates. ", "Thus, the root mean square deviation between the interaction energies provided by the two methodologies only amounts 1.6 kcal/mol, while the ratio ΔE^FF,i^/ΔE^QM,i^ and the regression coefficient R^2^ are 0.93 and 0.950, respectively. ", "These results demonstrate the ability of the force-field parameters used in this work to reproduce inorganic···organic interactions in biominerals with an accuracy better than expected.", "Figure 4**Representation of the interaction energies calculated for inorganic···organic model complexes using quantum mechanical calculations at the B3LYP/6-31G(d) level (ΔE**^**QM,i**^**) and the AMBER force-field (ΔE**^**FF,i**^**).**", "\n\nNucleation of apatites using B-DNA {#Sec13_8}\n----------------------------------\n\nDetailed comparison of B-DNA and apatites structures allowed us to identify a plane defined by four phosphate groups that are located at similar distances in the two systems (Figure [5](#Fig5){ref-type=\"fig\"}). ", "Specifically, for HAp / FAp such plane is defined by *u*= 6.87 / 6.88 Å (*i*.*e*. ", "the crystallographic parameter c) and *v*= 11.66 / 11.62 Å, with an angle γ of 120º; while some variability is observed for B-DNA depending on the sequence. ", "Thus, the average values of the sides are *u*= 6.72 Å and *v*= 13.75 Å, the largest variability being shown by the angle with values ranging from 108° to 141°.Figure 5Isomorphic planes identified in (a) the double helix of B-DNA and (b) HAp.", "\n\nStarting from the plane identified in sequence **I**, HAp and FAp models were generated from the phosphate groups located at such plane and growing the crystal through the positional parameters displayed in The Additional file [1](#MOESM1_8){ref-type=\"media\"}: Table S1. ", "Accordingly, the four phosphate of the plane identified in B-DNA, as displayed in Figure [5](#Fig5){ref-type=\"fig\"}a, were embedded into the apatite crystal. ", "The latter growing process is schematized in Figure [6](#Fig6){ref-type=\"fig\"}a for HAp, while Figure [6](#Fig6){ref-type=\"fig\"}b displays the resulting structure viewed from a perspective in front of the B-DNA. ", "In order to make understandable the procedure used to build the models, Figure [6](#Fig6){ref-type=\"fig\"} illustrates the procedure considering a single plane of phosphates. ", "The same procedure was applied to build the crystal FAp model (not shown). ", "As suggested from the comparison displayed in Figure [5](#Fig5){ref-type=\"fig\"}, we corroborated that the geometric position of the phosphate groups of ds B-DNA is suitable to grow both HAp and FAp crystals. ", "This feature allowed us to conclude that, from a geometric point of view, such biomolecule may act as nucleating agent of the mineral. ", "However, an energy analysis is also required to provide a complete evaluation of this nucleation in the biomineral.", "Figure 6(**a**) **Growing process of HAp using the double helix of B-DNAas a nucleating agent and** (**b**) **biomineral obtained such growing mechanism.**", "\n\nFigure [7](#Fig7){ref-type=\"fig\"} compares the variation of the total energy, which is clearly dominated by the electrostatic contribution, of the two biominerals with those of the two minerals as the size of the crystal grows (*i*.*e*. ", "increasing thickness). ", "It should be noted that biominerals refer to the apatite crystals grown around a B-DNA molecule, which is used as a template (*i*.*e*. ", "B-DNA/HAp and B-DNA/FAp) while minerals correspond to pure apatite crystals (*i*.*e*. ", "HAp and FAp without B-DNA). ", "Also, the size or thickness of the crystal is represented by a cutoff distance defined with respect to the center of masses of the phosphate groups belonging to the planes used to nucleate the crystals. ", "The energy profiles obtained for B-DNA/HAp and HAp, which are practically identical (Figure [7](#Fig7){ref-type=\"fig\"}a), clearly reflect the lack of influence of the double helix DNA on the energy of the system from the first steps of mineralization (*i*.*e*. ", "mineral thickness \\< 10 Å). ", "The pattern for B-DNA/FAp and FAp is fairly similar but there is an energetic mismatch between the biomineral and the mineral (Figure [7](#Fig7){ref-type=\"fig\"}b), which suggests a stronger distortion of the ds DNA. ", "These results are in agreement with those provided above, which evidenced that FAp distorts more severely the double helix of B-DNA than HAp.", "Figure 7**Variation of the total energy (E**~**T**~**) against the distance from the center of masses of B-DNA for the biomineral and mineral of (a) HAp and (b) FAp.**", "\n\nDynamics of the initial stages of nucleation of apatites at B-DNA {#Sec14_8}\n-----------------------------------------------------------------\n\nIn order to simulate the early formation and growing of calcium phosphate clusters in the nucleation of HAp at B-DNA double helix template, MD simulations of two systems based on stoichiometric aqueous solutions of Ca^2 +^, and OH^--^ ions were carried out. ", "In the first system, hereafter denoted HAp/DNA, a double helix B-DNA molecule was immersed in the stoichiometric solution described in the Methods section. ", "The second system, hereafter denoted HAp, no DNA was incorporated to the water box thus remaining the Ca^2 +^, and OH^--^ ions. ", "The analysis of the results was performed on the bases of a 10 ns production run (*i*.*e*. ", "the trajectory after equilibration of the density, temperature, and pressure; see Methods section) in the NPT ensemble. ", "It is worth noting that these simulations are two times larger than those used to examine the early stages of nucleation of HAp at a collagen template \\[[@CR39_8]\\] and, therefore, the clustering process is expected to occur within such time scale.", "\n\nFigure [8](#Fig8){ref-type=\"fig\"} compares the radial distribution functions (RDF) of Ca^2 +^*···*OH^--^ and pairs obtained from HAp and HAp/DNA simulations. ", "As it can be seen, the B-DNA template does not have any significant effect in the RDF of the Ca^2 +^*···*OH^--^ pair at distances smaller than 4.5 Å, even though the peaks centered at 5.45 and 6.18 Å are more pronounced in the HAp/DNA system than in the HAp ones. ", "The latter feature indicates that the clustering is higher in the former than in the latter. ", "Differences are more pronounced, especially at short distances, in the RDFs calculated for the pair in HAp and HAp/DNA. ", "Thus, for the HAp system the first peak appears at 4.22 Å, whereas two well-defined sharp peaks centered at 3.14 and 3.82 Å are clearly identified for the HAp/DNA one. ", "This is consistent with the growing of embryonic clusters in the latter system. ", "Inspection of atomistic configurations extracted from the dynamics indicates that peaks identified for the pair at distances lower than 4 Å correspond to groups surrounded by several (frequently 3) Ca^2+^ atoms.", "Figure 8**Radial distribution functions of** Ca^2 +^*···*OH^--^**andpairs calculated for HAp and HAp/DNA systems.** ", "Both general and detailed views are displayed.", "\n\nThe nucleation of HAp at the DNA molecule is clearly corroborated in Figure [9](#Fig9){ref-type=\"fig\"}, which represents the RDF of and pairs (where corresponds to the phosphate group of DNA). ", "As it can be seen, the profile shows a peak at 2.58 Å, indicating that the groups of B-DNA are coordinated with Ca^2+^ forming stable ion complexes. ", "Although the role of Ca^2+^ in this complexes may be initially reduced to that of a simple counterion, the peaks observed at 3.14 and 3.84 Å in the RDF can be only attributed to the nucleation of inorganic crystals at the biomolecule template. ", "Thus, MD simulations reflect that the phosphate groups of DNA interact with Ca^2+^ to form ion complexes, which subsequently coordinate with groups of the solution giving place to the stabilization of calcium phosphate clusters at the template. ", "Electrostatic attractions between Ca^2+^ and the phosphate groups of both the DNA and the solution were crucial for the nucleation of the crystals at the template surface. ", "On the other hand, the RDF suggests that the role of the OH^--^·is much less decisive in the formation of clusters at the B-DNA surface. ", "Thus, although the profile shows a very broad peak centered at 3.28 Å, it is very poorly defined indicating that the OH^--^ anions are incorporated only occasionally to the calcium phosphate clusters formed at the surface of the B-DNA. ", "Accordingly, the combination of the and Ca^2 +^*···*OH^--^ RDFs (Figures [8](#Fig8){ref-type=\"fig\"} and [9](#Fig9){ref-type=\"fig\"}, respectively) evidences that the OH^--^remain essentially at the bulk forming complexes and clusters with Ca^2+^. It should be remarked that the low relevance of the OH^--^ anions in the formation of clusters to nucleate HAp crystal at the B-DNA surface is fully consistent with experimental observations. ", "Thus, Tarasevich *et al.*\\[[@CR55_8]\\] reported that the calcium phosphate clusters act as precursors of HAp (*i.e.* typically octacalcium phosphate) do not incorporate OH^--^ groups.", "Figure 9**Radial distribution functions ofandpairs calculated for HAp/DNA.** ", "Both general and detailed views are displayed.", "\n\nConclusions {#Sec15_8}\n===========\n\nIn this study, biominerals made of apatite and DNA have been modeled at the atomistic level. ", "The aims of the work were to provide understanding of the influence of the mineral on the conformation of the biomolecule and to determine the possible role of the latter as nucleating agent of the mineral. ", "Encapsulation of the B-DNA double helix in rhombohedric pores (γ= 120°) of HAp does not induce significant structural distortions in the biomolecule. ", "This observation has been found to be independent of the DNA sequence, which has been attributed to the strong stabilizing interactions between the Ca^2+^ atoms of HAp and the phosphate groups of DNA. ", "The minimum dimensions of the pore needed to encapsulate B-DNA are defined by the maximum distances between atoms of the mineral at the internal diagonals, which are 30.5 and 21.1 Å. This result is fully consistent with experimental investigations devoted to encapsulate DNA into HAp nanoparticles, which show a relatively high loading capacity through their pores. ", "The structural stability of the encapsulated double helix is an important finding that offers new possibilities for the design of efficient therapeutic biomedical applications. ", "These results are particularly relevant considering recent findings like the mechanism used by carcinogenic cells to capture HAp nanoparticles \\[[@CR56_8]\\].", "\n\nOn the other hand, the mechanism proposed for the growing of apatite crystals using the double helix of B-DNA as nucleating agent represents an alternative to classical encapsulation processes (*i.e.* loading of biomolecules at the nanopores and/or the surface). ", "Thus, the controlled formation of biominerals (*i.e.* porous nanoparticles of mineral growing from biomolecules) combined with conventional encapsulation approaches may be used to design therapies with higher efficacy and durability. ", "MD simulations have been used to investigate the initial stages of nucleation and cluster formation of calcium phosphate at a B-DNA double helix in aqueous solution. ", "At room temperature, calcium ions interact with DNA phosphates to form ion complexes, but attracted by electrostatic forces, they coordinate to and other calcium ions starting the formation of clusters. ", "Finally, it should be mentioned that this growing mechanism of the biomineral is compatible with the theory and models proposed by Kostetsky \\[[@CR21_8]\\] to explain the origin of organic matter and life on the Earth.", "\n\n {#AppESM1_8}\n\n {#SecESM1_8}\n\nAdditional file 1: Table S1: Positional parameters used to construct the crystal structures of natural HAp and FAp. **", "Table S2.** ", "Force-field parameters for Ca^2+^ and F^-^. **Figure S1.** ", "Schematic depiction of the unit cell of the investigated apatites (left) projected onto the (001) and (010) planes (top and down, respectively). ", "The hexagonal symmetry is evidenced in the picture at the right, which shows four unit cells projected onto the (001) plane. **", "Figure S2.** ", "Structure of B-DNA. ", "The double helix is right-handed and makes a turn every 3.4 nm, the distance between two neighboring base pairs being 0.34 nm. ", "Accordingly, there are about 10 nucleotides per turn. ", "The intertwined strands make two grooves of different widths, referred as the *major groove* and *minor groove*. (", "DOC 735 KB)\n\nThis work was supported by B. Braun Surgical S.A. through a joint research agreement with UPC. ", "Special thanks to Mr. M. Jiménez for believing in the idea and funding the project. ", "Authors thank J.F. Julián, J. Navinés, J.R. Grifols, C. Colomer, L.F. del Castillo, S. Santos and J.M. Turon for their contributions to the conceptual framework of the work. ", "This work is integrated within a wider research project supported by B. Braun Surgical S.A., UPC, Institut de Ciencies Fotòniques (ICFO), and the Institut Català de la Salut (ICS) through the H. A. Germans Trias i Pujol and H. U. Vall d'Hebron, MICINN-FEDER funds (MAT2012-34498), and by the Generalitat de Catalunya (2009SGR925 and XRQTC). ", "Authors are indebted to the Centre de Supercomputació de Catalunya (CESCA) for computational facilities. ", "Support for the research of C.A. was received through the \"ICREA Academia\".", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\n$O(\\frac{\\log n}{\\log \\log n})$ algorithm for the prefix parity problem\n\nThe prefix parity problem can be defined as follows. ", "You are given a string $S$ of length $n$ and initially every character is $0$. Then you want to build a data structure that can support updates such as follows. ", "\n\nFor a given $i$ change $S[i]$ to either $0$ or $1$\nfor a given $i$ find the parity of $S[1]+S[2]+...+S[i]$.\n\nFrom the top of my head, there is a solution that can support these type of queries in $O(\\log n)$ time, while only using linear space and linear preprocessing time to build the data structure. ", "The idea is to build a complete binary search tree on top of the string where the leafs correspond to individual characters of $S$ and in every internal node we store the sum of all the characters that are leafs in the sub tree defined by that node. ", "In this way we can trivially support both of the updates in $O(\\log n)$ time.", "\nHowever, I found a paper proving a lower bound for this problem, stating that you can not do better than $O(\\frac{\\log n}{\\log \\log n})$ for the updates, and I also found the following paper http://link.springer.com/chapter/10.1007%2F3-540-51542-9_5, and a direct link to the pdf, giving an algorithm achieving that bound, thus being optimal. ", "\nI would like to understand this algorithm however the explanation is like 1 page, and a lot of details are missing.", "\nSo I was wondering if there is any other source on this problem, because I find it very hard to find any, or is this is the only source available?", "\nthank you in advance\n\nA:\n\nI did a quick read over the paper you linked. ", "Based on the ideas given in that paper, here's a simple data structure that obtains an $O(\\frac{\\log n}{\\log\\log n})$ time bound on each operation.", "\nYou mentioned in your question that you can use balanced, augmented trees to speed this up. ", "In particular, if you have a binary tree and augment each node with the parity of its left subtree, then you can do updates and lookups in time $O(\\log n)$ each. ", "That's fast, but not fast enough.", "\nNow, consider the following generalization of your idea. ", "Suppose that instead of using a binary tree, we use a multiway tree with branching factor $k$. We augment each key in each node with the parity of the all the subtrees preceding it (this generalizes the idea of storing the parity of the left subtree). ", "Now, let's think about how we'd do a lookup or update in this tree. ", "To do a lookup, we use a slightly modified version of the binary tree lookup algorithm from before: walk from the top of the tree down to the bottom, at each step accumulating the parity of the subtree purely to the left of each node. ", "The height of the tree in this case will be $O(\\log_k n)$ and we do $O(1)$ work per node, so the cost of doing a lookup will be $O(\\log_k n)$.\nHowever, with this setup, the cost of doing an update increases. ", "In particular, if we change the parity of an element, we need to walk up from the bottom of the tree to the top, changing the stored parity of every key in every node on the path upward. ", "There are $k$ keys per node and $O(\\log_k n)$ nodes on the path upward from the leaves, so the cost of performing an operation like this will be $O(k \\log_k n) = O(\\frac{k}{\\log k} \\log n)$, which is too slow. ", "If we could somehow eliminate this extra $k$ term, then we'd be in business.", "\nThe insight the paper has is the following. ", "If you think about our initial problem, we had an array of size $n$ and wanted to be able to compute prefix parities. ", "We now have a $k$-ary tree where, at each node, we need to be able to solve the prefix parity problem on arrays of size $k$ each, since each node caches information about the layers below it. ", "In the above data structure, we solved the prefix parity problem at each node by just storing an array of the prefix parities, which means that if we need to perform an update, the cost is $O(k)$. The paper's insight is that by using a more clever data structure at each node, you can perform these updates significantly more efficiently.", "\nIn particular, the paper makes the following insight. ", "Let's suppose that $k$ is \"small,\" for some definition of small that we'll pick later. ", "If you want to solve the prefix parity problem on an array of size $k$, then there are only $2^k$ different possible bit arrays of length $k$. Additionally, there are only $k$ possible lookup queries you could make on a bit array of size $k$. As a result, the number of possible combinations of an array and a query is $k 2^k$. If we pick $k$ to be small enough, we can make this quantity so small that it becomes feasible to precompute the result of every possible array and every possible query. ", "If we do that, then we can update our data structure as follows. ", "In each node of the $k$-way tree, rather than having each key store the parity of its left subtree, we instead store an array of $k$ bits, one for each key in the node. ", "When we want to find the parity of all the nodes to the left of the $i$th child, we just do a lookup in a table indexed by those $k$ bits (treated as an integer) and the index $i$. Provided we can compute this table fast enough, this means that doing a prefix parity query will still take time $O(\\log_k n)$, but now updates take time $O(\\log_k n)$ as well because the cost of a prefix parity query on a given node will be $O(1)$.\nThe authors of the paper noticed that if you pick $k = \\frac{\\lg n}{2}$, then the number of possible queries that can be made is $\\frac{\\lg n}{2} 2^{\\frac{\\lg n}{2}} = \\frac{\\lg n}{2} \\sqrt{n} = o(n)$. Additionally, the cost of performing any operation on the resulting tree will be $O(\\log_k n) = O(\\frac{\\log n}{\\log \\frac{\\lg n}{2}}) = O(\\frac{\\log n}{\\log \\log n})$. The catch is that you now need to do $o(n)$ precomputation at the start of setting up the data structure. ", "The authors give a way to amortize this cost away by using a different data structure for the initial queries until enough work has been done to justify performing the work necessary to set up the table, though you could argue that you need to spend $O(n)$ time building up the tree in the first place and that this won't affect the overall runtime.", "\nSo, in summary, the idea is the following:\n\nInstead of using an augmented binary tree, use an augmented $k$-ary tree.", "\nNotice that with small $k$, all possible $k$-bit lists and queries on those lists can be precomputed.", "\nUse this precomputed data structure at each node in the tree.", "\nChoose $k = \\frac{\\lg n}{2}$ to make the tree height, and, therefore, the cost per operations, $O(\\frac{\\log n}{\\log \\log n})$.\nAvoid the upfront precomputation cost by using a temporary replacement data structure in each node until the precomputation becomes worthwhile.", "\n\nAll in all, it's a clever data structure. ", "Thanks for asking this question and linking it - I learned a lot in the process! ", "\nAs an addendum, many of the techniques that went into this data structure are common strategies for speeding up seemingly optimal solutions. ", "The idea of precomputing all possible queries on objects of a small size is often called the Method of Four Russians and can be seen in other data structures like the Fischer-Heun data structure for range minimum queries or the decremental algorithm for tree connectivity. ", "Similarly, the technique of using augmented balanced multiway trees with a logarithmic branching factor comes up in other contexts, like the original deterministic data structure for dynamic graph connectivity, where such an approach is used to speed up connectivity queries from $O(\\log n)$ to $O(\\frac{\\log n}{\\log \\log n})$.\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "[The melatonin influences on neutrophils/lymphocytes ratio of mammals blood depends on age of animals].", "\nThe influence of melatonin on age dynamics of neutrophils and lymphocytes in blood of laboratory rats kept under different light conditions and predatory mammals--farmer silver fox, raccoon dog kept under natural light (NL) was investigated. ", "The decrease of lymphocyte level, increase neutrophils content and alteration of neutrophils/lymphocytes ratio of aged rats (24 months) kept under natural light (NL) and standard light (LD) and adult silver foxes (2-5 years) kept under natural light in comparison with juvenile animals were detected. ", "The reduced lymphocytes level and increased neutrophil level in rats under constant light (LL) were revealed in younger ages. ", "The melatonin effect was detected in aged rats and adult silver foxes and not observed in juvenile animals." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nComputing Wheel Torque From Engine Torque\n\nIt seems possible to obtain engine torque and RPM from a truck CAN bus. ", "I'd like to estimate tractive force at the wheels given these two values.", "\nHow should I go about computing torque at the wheels? ", "Wouldn't I need gear ratio, which doesn't seem obtainable from the CAN bus?", "\n(also asked this question on physics.stackexchange)\n\nA:\n\nThe basics are quite simple. ", "\nThe motor generates a certain torque N and a certain power P at a given RPM. ", "Further more, the relation between power and torque is:\nP = C * N * RPM\n\nwhere C is a constant to convert all that odd units. ", "For N, P in SI units, it is \nC = pi / 30\n\nNeglecting any losses, Power is conserved from the motor to the wheels so you can say\nC * N_motor * RPM_motor = C* N_wheel * RPM_wheel\n\nN_wheel = N_motor * RPM_motor / RPM_wheel \n\nThe RPM of the wheel can easily be derived from speed and the rolling circumference of the wheel R_wheel. (", "Keep in mind, the rolling circumference is smaller than the geometrical circumference, as the tire is flexible.", "\nSince you are more interested in the tractive force F_wheel, it is\nN_wheel = F_wheel * R_wheel\n\nand so\nF_wheel = N_motor * RPM_motor / (RPM_wheel * R_wheel)\n\nAs it's also v = pi * RPM_wheel * R_wheel / 30 (velocity in m/s) you can write\nF_wheel = N_motor * RPM_motor * pi / (v * 30)\n\nThis means, if you really have the torque the motor currently delivers, the RPM of the motor and the speed of the truck, you can calculate the total force applied to the street.", "\nIt's strange that gear ratios don't appear, but they are hidden in the ratio RPM_motor / RPM_wheel or RPM_motor / v.\n\nIn reality, there are lots of non neglible losses, as Paulster2 wrote in his comment. ", "\nEvery bearing and every gear wheel has some friction, taking away some torque and power. ", "If this torque is constant, the power loss will be linear to the RPM of this part, but usually, torque will increase with RPM, so the power loss grows even faster with RPM.", "\nThis means the loss is not constant, it varies with RPM and gear!", "\nOne interesting fact: A clutch transfers power / torque by friction. ", "For a slipping clutch, torque is the same on both shafts, but power is lost due to the difference in RPM...\n\nAnd to make it clear again: You do need the measured torque from the motor, max torque at given RPM is not what you need.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "a*p**2 + h - 1\nWhat is the derivative of -572*r*w**2 + 2*r*w + 711*w**2 wrt r?", "\n-572*w**2 + 2*w\nWhat is the second derivative of -3845*f**2 - 357*f wrt f?", "\n-7690\nFind the third derivative of d*w**5 - 6*d*w**3 + 18*d*w**2 - 5*w**5 - 8*w**2 wrt w.\n60*d*w**2 - 36*d - 300*w**2\nWhat is the second derivative of -217*y**3 - 811*y wrt y?", "\n-1302*y\nFind the second derivative of m**2*n**2*x**2 - 3*m**2*n**2 - 2*m**2 - 5*n**2*x**2 - 2*n*x**2 + n + 7 wrt n.\n2*m**2*x**2 - 6*m**2 - 10*x**2\nFind the first derivative of 4*s**4 + 3*s**3 + 8269 wrt s.\n16*s**3 + 9*s**2\nWhat is the first derivative of -74*k - 329?", "\n-74\nDifferentiate 2*a**3*m*o**3 - 3*a**3*m*o**2 - 54*a**3*o + a**3 + 2*a**2*o**3 wrt m.\n2*a**3*o**3 - 3*a**3*o**2\nFind the second derivative of -848*a**3*u**3 - 3*a*u**3 + 35*a wrt a.\n-5088*a*u**3\nWhat is the third derivative of -83*d**4 - 5*d**3 + 216*d**2 - d?", "\n-1992*d - 30\nWhat is the derivative of -6*p**3*x**3 - 2*p**3 + 495*x**3 wrt p?", "\n-18*p**2*x**3 - 6*p**2\nFind the third derivative of 2*c*d**4*k + 4*c*d**3 - 21*c*d**2*k - 4*c*d**2 - 3*c*d - 12*d**4*k wrt d.\n48*c*d*k + 24*c - 288*d*k\nDifferentiate 4*m**3 + 57*m**2*w**3 + 3*w**3 + 79 with respect to m.\n12*m**2 + 114*m*w**3\nFind the second derivative of 20*c**4 - 2*c**3 + 10*c**2 - c - 442.", "\n240*c**2 - 12*c + 20\nWhat is the second derivative of -13772*m**3 + 26025*m wrt m?", "\n-82632*m\nFind the second derivative of -92*l*n**4 + 5*l + n**4 + 3*n**2 - 75*n wrt n.\n-1104*l*n**2 + 12*n**2 + 6\nFind the second derivative of -71*g**3*y**3 + 2*g**3*y - 47*g*y**2 - g - y**3 - 4059*y wrt y.\n-426*g**3*y - 94*g - 6*y\nFind the second derivative of -6462*b**3 + 403*b + 3 wrt b.\n-38772*b\nFind the first derivative of f**2*y**2 - f**2*y + 5*f**2 + 2*y**2 + 102*y wrt f.\n2*f*y**2 - 2*f*y + 10*f\nFind the first derivative of -6*k**3*o + 4*k**3*y**2 + 258*k**3 - 72*k*o*y**2 wrt o.\n-6*k**3 - 72*k*y**2\nFind the second derivative of 2*x**5 - 40*x**3 - x + 72 wrt x.\n40*x**3 - 240*x\nWhat is the first derivative of 48*w**4 - 2*w**2 + 374 wrt w?", "\n192*w**3 - 4*w\nFind the third derivative of 4195*r**6 - r**2 - 19*r - 1 wrt r.\n503400*r**3\nDifferentiate 670*c*p**3 + c + p**3 + 2*p - 1260 wrt p.\n2010*c*p**2 + 3*p**2 + 2\nFind the second derivative of -69*c**3 - c**2 + 929*c wrt c.\n-414*c - 2\nWhat is the derivative of 13*s**2*v**4 + 4*s**2*v + 169*s**2 wrt v?", "\n52*s**2*v**3 + 4*s**2\nDifferentiate -3*a**3*p*v**2 - a**3*v + 160*a**2*p*v**3 + a**2*v**3 - 597*a*v wrt p.\n-3*a**3*v**2 + 160*a**2*v**3\nDifferentiate -1550*j**2 - 8761.", "\n-3100*j\nWhat is the first derivative of -172*d**3*w - 2*d**3*x + 1143*w*x wrt x?", "\n-2*d**3 + 1143*w\nDifferentiate 2*k**3 + 301*k**2 - 2265 wrt k.\n6*k**2 + 602*k\nWhat is the third derivative of 2*w**5 + 32*w**4*y - w**3*y**3 - 25*w**2*y**3 - 2*w**2*y**2 + 3*w**2*y wrt w?", "\n120*w**2 + 768*w*y - 6*y**3\nWhat is the derivative of -178*m**4 + 3*m**2 - 536 wrt m?", "\n-712*m**3 + 6*m\nFind the second derivative of -2*b**3*r**2 + 1114*b**3*r - 1735*b*r**2 - 4*r**2 - r wrt r.\n-4*b**3 - 3470*b - 8\nFind the second derivative of -86*q**4 - 2*q**2 + 1685*q wrt q.\n-1032*q**2 - 4\nFind the third derivative of 34*h**3*q**2 - 17*h**3 + h**2 + 5*h*q**2 - 6*h wrt h.\n204*q**2 - 102\nWhat is the derivative of 2*j**2*r - 4*j**2*w + 7*j*r*w + 12*r*w + w - 4 wrt j?", "\n4*j*r - 8*j*w + 7*r*w\nWhat is the second derivative of 4311*p**2 + 3*p + 1719?", "\n8622\nFind the third derivative of -f**3*w**5 + 1337*f**3*w**4 + 1835*f**3*w**2 - f**3 wrt w.\n-60*f**3*w**2 + 32088*f**3*w\nWhat is the first derivative of -2*h**4 + 701*h**3 + 121?", "\n-8*h**3 + 2103*h**2\nFind the second derivative of 32*g**3*u**2 + 2*g**3*u - 20*g**2*u**3 - 34*g*u**3 - 2*g*u + 4*u wrt g.\n192*g*u**2 + 12*g*u - 40*u**3\nWhat is the derivative of -c**3*x*y**2 - 117*c**3*y**3 + 4*c**3*y + 270*x*y**3 + x wrt x?", "\n-c**3*y**2 + 270*y**3 + 1\nFind the third derivative of 30*j**4 + 2*j**3 + 34*j**2.", "\n720*j + 12\nWhat is the first derivative of -281*m**2 - 3*m + 967 wrt m?", "\n-562*m - 3\nWhat is the derivative of -71*n**2 - 8*n - 742 wrt n?", "\n-142*n - 8\nWhat is the second derivative of -5*h**5 + 92*h**4 - h**2 - 11562*h wrt h?", "\n-100*h**3 + 1104*h**2 - 2\nWhat is the third derivative of 120*n**3 + 88*n**2 wrt n?", "\n720\nFind the second derivative of b*u**3*w - 35*b*u**2*w - b*u - 46*u**5 + 15*u*w - 25*u wrt u.\n6*b*u*w - 70*b*w - 920*u**3\nWhat is the third derivative of -2*q**3*r**4 - 2*q**3*r**2 + q**3*r + 353*q*r**4 - 2*q*r wrt r?", "\n-48*q**3*r + 8472*q*r\nWhat is the third derivative of 2*v**6 - 81*v**4 + 2*v**2 - 147*v?", "\n240*v**3 - 1944*v\nWhat is the derivative of 12*j**3*r**2 - j**3 + 3*j*r - 13*j wrt r?", "\n24*j**3*r + 3*j\nFind the second derivative of -1883*s**2 - s + 999 wrt s.\n-3766\nDifferentiate -15*c**2*d**3 + 2*c**2*d**2 - 102*c**2 with respect to d.\n-45*c**2*d**2 + 4*c**2*d\nFind the first derivative of -30*i**4 + 3*i**2 - 2067.", "\n-120*i**3 + 6*i\nDifferentiate 6181*g**4 + 7933.", "\n24724*g**3\nWhat is the third derivative of 2*o*t**3*y**3 + 1073*o*t**3*y - 176*o*t*y**3 - o*t + 3*t**3*y**3 - 2*t**3*y**2 wrt y?", "\n12*o*t**3 - 1056*o*t + 18*t**3\nDifferentiate 67*z**4 - 44*z**3 - z**2 - 10202 wrt z.\n268*z**3 - 132*z**2 - 2*z\nWhat is the second derivative of -52*f**2*o**4 + 33*f**2*o + f*o - 2*o wrt o?", "\n-624*f**2*o**2\nDifferentiate -3*p**4 + p**3*w*x - 91*p*x + 402*w*x - x with respect to p.\n-12*p**3 + 3*p**2*w*x - 91*x\nDifferentiate -216*w**2*z + 2*w*z**2 - 13*z**2 - 12 wrt w.\n-432*w*z + 2*z**2\nFind the third derivative of -3*h**2*w**3 - 5*h**2*w**2 + 2*h**2*w - 39*h*w**3 + 20*h - 2*w**4 wrt w.\n-18*h**2 - 234*h - 48*w\nWhat is the second derivative of 24*c**4 + 10*c**2 + 473*c?", "\n288*c**2 + 20\nFind the second derivative of 2*d**3 - 35*d**2 + 2*d - 175.", "\n12*d - 70\nWhat is the derivative of 846*m**3 + 1766?", "\n2538*m**2\nFind the third derivative of -13*d**3*g*m**2*z**3 - d**3*g*z**3 + 19*d**3*z**2 - g*m*z + m**2*z**2 + 3*z**2 wrt z.\n-78*d**3*g*m**2 - 6*d**3*g\nWhat is the third derivative of 13*p**6 - 12*p**5 + 5*p**4 + 19*p**2 - p - 8 wrt p?", "\n1560*p**3 - 720*p**2 + 120*p\nFind the second derivative of 22*c**3*u**2 + 271*c**3*u + 4*c**2*u**2 - c - 20*u**2 + u wrt u.\n44*c**3 + 8*c**2 - 40\nFind the first derivative of 182*g**3 + 114.", "\n546*g**2\nFind the third derivative of 1384*f**5 + 3*f**4 - 5157*f**2.", "\n83040*f**2 + 72*f\nWhat is the second derivative of 33*c**4 + 46*c**2 - c + 1135 wrt c?", "\n396*c**2 + 92\nWhat is the second derivative of -49*o*p*x**3 + 3*o*p*x + 2*o*p + 3*p*x**3 - 2*p wrt x?", "\n-294*o*p*x + 18*p*x\nWhat is the derivative of -9*i*m**4 - 8*i*m**3 - 1074*i wrt m?", "\n-36*i*m**3 - 24*i*m**2\nFind the third derivative of i**5 + 2*i**4 - 3940*i**2.", "\n60*i**2 + 48*i\nWhat is the third derivative of 9*f*i*l**3 - 2*f*i*l**2 + 6*f*i*l + 10*f*l**3 + 4*i + l**2 wrt l?", "\n54*f*i + 60*f\nWhat is the second derivative of 2*m*s**2 + 315*m*s - 2*m + 21*s**2 wrt s?", "\n4*m + 42\nFind the first derivative of 507*g + 546.", "\n507\nWhat is the derivative of -25*o*u**3 - 245*u**3 + u**2 wrt o?", "\n-25*u**3\nFind the second derivative of -2774*h**4 + 4*h - 69.", "\n-33288*h**2\nDifferentiate 15*f**3*p**2 - 2*f**3*p - 423*f**3 - 3*f**2*p**2 wrt p.\n30*f**3*p - 2*f**3 - 6*f**2*p\nDifferentiate 3*o*w - 155*o + w**3 wrt w.\n3*o + 3*w**2\nDifferentiate 2*f*n**3 - 6*f*n*y + 3*f*y + 27*n**3 + 2*n**2 - 12*y wrt f.\n2*n**3 - 6*n*y + 3*y\nDifferentiate -j*n*x**3 + 5*j*n*x + 11*j*n + 8*j + 6*x**2 with respect to x.\n-3*j*n*x**2 + 5*j*n + 12*x\nFind the second derivative of -323*u**3 - 133*u wrt u.\n-1938*u\nDifferentiate -b**2 - 1367*b*x - 107*x + 46 with respect to b.\n-2*b - 1367*x\nWhat is the third derivative of g**3*u**2*v + 6*g**3*u**2 - 29*g**3*v**3 - 21*g**2*u**2*v + 114*g**2*u*v**3 - 2*g*u*v**3 wrt g?", "\n6*u**2*v + 36*u**2 - 174*v**3\nWhat is the second derivative of 5*p*x**2*y + 2*p*x**2 - 2*p*x*y**2 - 438*p*y**3 - 3*x**2*y**3 + 38*x**2*y + 10*x*y**2 wrt x?", "\n10*p*y + 4*p - 6*y**3 + 76*y\nWhat is the third derivative of 2*f**6 + 129*f**4 - 423*f**2 wrt f?", "\n240*f**3 + 3096*f\nWhat is the third derivative of 78*n**3*q**3 - 12*n**2*q**3 + 2*n**2*q - 2*n*q**3 wrt n?", "\n468*q**3\nWhat is the third derivative of b*t**5 - b*t**2 - 17*b*t - 65*t**3 wrt t?", "\n60*b*t**2 - 390\nDifferentiate -11*s*x**2 + s*x - 59*x**2 wrt s.\n-11*x**2 + x\nFind the first derivative of -1642*g**3 + 3556.", "\n-4926*g**2\nDifferentiate -15*k**2*q**3 - 72*k**2 + 80*k*q**4 + k - 2 wrt q.\n-45*k**2*q**2 + 320*k*q**3\nWhat is the first derivative of 31*n**2*w**3 + n**2*w + 358*n" ]

{ "pile_set_name": "DM Mathematics" }

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[ "/*\n Copyright (c) 2013 yvt\n\n This file is part of OpenSpades.", "\n\n OpenSpades is free software: you can redistribute it and/or modify\n it under the terms of the GNU General Public License as published by\n the Free Software Foundation, either version 3 of the License, or\n (at your option) any later version.", "\n\n OpenSpades is distributed in the hope that it will be useful,\n but WITHOUT ANY WARRANTY; without even the implied warranty of\n MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n GNU General Public License for more details.", "\n\n You should have received a copy of the GNU General Public License\n along with OpenSpades. ", " If not, see <http://www.gnu.org/licenses/>.", "\n\n */\n\n#include <cstdint>\n\n#include \"IGLDevice.h\"\n#include \"IGLShadowMapRenderer.h\"\n\nnamespace spades {\n\tnamespace draw {\n\t\tclass GLRenderer;\n\t\tclass GLShadowShader;\n\t\tclass GLSettings;\n\t\tclass GLSparseShadowMapRenderer : public IGLShadowMapRenderer {\n\t\t\tfriend class GLShadowMapShader;\n\t\t\tfriend class GLShadowShader;\n\n\t\t\tstruct ModelRenderer;\n\t\t\tstruct Internal;\n\n\t\t\tenum { Tiles = 64 };\n\n\t\t\tIGLDevice *device;\n\t\t\tGLSettings &settings;\n\n\t\t\tint textureSize;\n\t\t\tint minLod;\n\t\t\tint maxLod;\n\n\t\t\tuint32_t pagetable[Tiles][Tiles];\n\n\t\t\tIGLDevice::UInteger framebuffer;\n\t\t\tIGLDevice::UInteger texture;\n\t\t\tIGLDevice::UInteger pagetableTexture;\n\n\t\t\t// not used, but required\n\t\t\tIGLDevice::UInteger colorTexture;\n\n\t\t\tMatrix4 matrix;\n\t\t\tOBB3 obb;\n\t\t\tfloat vpWidth, vpHeight; // used for culling\n\n\t\t\tvoid BuildMatrix(float near, float far);\n\n\t\tprotected:\n\t\t\tvoid RenderShadowMapPass() override;\n\n\t\tpublic:\n\t\t\tGLSparseShadowMapRenderer(GLRenderer *);\n\t\t\t~GLSparseShadowMapRenderer();\n\t\t\tvoid Render() override;\n\n\t\t\tbool Cull(const AABB3 &) override;\n\t\t\tbool SphereCull(const Vector3 &center, float rad) override;\n\t\t};\n\t}\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Quantitative office perimetry.", "\nThis study presents a preliminary comparison of six commercially-available automated threshold static parameters, consisting of three projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) and three light-emitting diode (LED) perimeters (Dicon 2000, Fieldmaster 50, and Digilab 350). ", "Eighteen individuals were included in the study: 6 normal observers (31-58 years old), six patients with glaucomatous field loss in both eyes (55-70 years old), and six patients with neuro-ophthalmologic or retinal visual field abnormalities in both eyes (12-61 years old). ", "Three aspects of quantitative testing were evaluated: (1) the patients' and normal observers' acceptance and subjective impressions of the test procedure; (2) the technician's ease of operating the device and related tasks; and (3) practitioner-oriented considerations such as test-retest reliability, comparability of test results and testing time. ", "Our results showed that no device was clearly superior to the others in all respects. ", "Patients were most favorably impressed with the Octopus 500, Squid, and the Fieldmaster 50, while technician impressions were most favorable to the Humphrey Field Analyzer and the Squid. ", "The projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) were the easiest to perform cross-comparisons of test results, although there was considerable variation in the clarity of data interpretation from one case to another. ", "Test-retest reliability and the time of testing varied among the six automated perimeters." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "1. ", "Introduction {#sec1}\n===============\n\nThe branchial arches give rise to specific derivatives, which for the fourth arch include the laryngeal cartilages, the laryngeal and pharyngeal muscles, the superior laryngeal nerve, the left thoracic aorta, the right proximal subclavian artery, the interfollicular cells of the thyroid, and the superior parathyroid glands \\[[@B1]\\].", "\n\nCongenital fourth branchial arch anomalies are uncommon entities. ", "They typically present as a cervical inflammatory process primarily affecting children. ", "Acute suppurative thyroiditis is a common presentation for this pathology (45%). ", "Almost all cases of these anomalies are described only in case reports (526 cases were found in the literature) \\[[@B2]\\].", "\n\nMultiple diagnostic and treatment options have been described with a large variety in outcomes.", "\n\nThe first published description of a branchial cleft lesion was in 1832 by Ascherson \\[[@B3]\\]. ", "The prevalence of fourth arch anomalies is 1% to 4% of all branchial anomalies \\[[@B4]\\].", "\n\nWe report a clinical case of a recurrent left-side cervical abscess in a young woman due to a residual fistula between the pyriform sinus and the thyroid lobule on the left side. ", "She had been operated for an excision of a cervical cyst in the left side 6 years before with an initial diagnosis of a fourth branchial anomaly.", "\n\n2. ", "Clinical Case {#sec2}\n================\n\nA 20-year-old woman presented in January 2013 with an inflammatory left-side cervical swelling. ", "She had been in a good general condition and only experienced an excision of a left-side cervical cyst 6 years before with an initial diagnosis of a fourth branchial arch anomaly. ", "The follow-up did not show any recurrence or inflammatory process during the last 6 years. ", "The clinical examination showed a left-side inflammatory and painful cervical swelling without evidence of external skin fistula or spontaneous discharge of pus. ", "She had no dyspnea or dysphagia. ", "The ENT examination did not show any pathological signs in the oropharynx, hypopharynx, or larynx. ", "The biological findings showed an acute inflammatory syndrome with leukocytosis and elevated CRP. ", "A cervical CT-scan showed a multilobulated liquid formation in the left lateral cervical region, measuring 29 × 15 × 55 mm, in contact with the left thyroid lobule, as well as the presence of a fistula tract between the thyroid lobule and the pyriform sinus on the left side (Figures [1](#fig1){ref-type=\"fig\"} and [2](#fig2){ref-type=\"fig\"}).", "\n\nA surgical drainage of the abscess was done, followed by an antibiotic treatment of amoxicillin-clavulanic acid with a dose of 1 gr three times per day for 14 days ([Figure 3](#fig3){ref-type=\"fig\"}).", "\n\nThe 2-month postoperative follow-up showed good healing of the cervical wound without any signs of recurrence. ", "An MRI was done 3 months after the surgery and showed a diffuse inflammation in the left cervical region without abscess formation and a fistula tract at the level of the hypopharynx on the left side ([Figure 4](#fig4){ref-type=\"fig\"}).", "\n\nA complete surgical treatment including the resection of the fistula tract and left thyroid lobule combined with endoscopic control of the fistula in the left pyriform sinus was proposed to the patient; unfortunately, she refused the surgery at that time. ", "Five months later, she presented a recurrence of a cervical abscess on the left side. ", "A cervical CT-scan showed an abscess with a fistula on the left side of the neck ([Figure 5](#fig5){ref-type=\"fig\"}). ", "A second surgical drainage was done, followed by an antibiotic therapy for a period of 14 days.", "\n\nA complete surgical treatment was performed 2 months later. ", "The intraoperative endoscopy showed a fistula orifice in the apex of the left piriform sinus. ", "An endoscopic cauterization of the fistula in the left piriform sinus was done (Figures [6](#fig6){ref-type=\"fig\"} and [7](#fig7){ref-type=\"fig\"}). ", "A left-side cervicotomy was performed with a complete excision of the fistula tract, left thyroid lobule, and all the inflammatory tissues with multiples lymph nodes ([Figure 8](#fig8){ref-type=\"fig\"}: fistula\\'s tracts between the left thyroid nodule and the pharynx). ", "The surgery was followed by an antibiotic treatment. ", "The postoperative follow-up showed a good healing of the wound, no symptoms of thyroid gland dysfunctions or any other complications.", "\n\n3. ", "Discussion {#sec3}\n=============\n\nMost fourth branchial arch anomalies are diagnosed in childhood. ", "The great majority of cases occur on the left side and most commonly present either as acute suppurative thyroiditis or neck abscess. ", "Respiratory distress could be a clinical presentation for these anomalies in neonates. ", "In the 518 cases found in the literature in which the patient\\'s age was reported, 45 occurred in neonates and 29 (64%) of these presented with respiratory distress \\[[@B2]\\].", "\n\nFourth branchial arch anomalies represent vestiges of a sinus tract, originating from the apex of the pyriform sinus \\[[@B5]\\]. ", "Some authors group third and fourth arch fistulas generically as pyriform sinus tracts or pyriform fossa lesions \\[[@B6], [@B7]\\]. ", "But anatomically, these two types of anomalies are distinct: the tract of the third branchial arch anomalies originates from the base of the pyriform sinus and the tract of the fourth branchial arch anomalies originates from the apex of the pyriform sinus \\[[@B5]\\].", "\n\nThe clinical presentation of fourth branchial arch anomalies varies with age. ", "A respiratory distress is the usual clinical presentation in neonates. ", "Cervical cutaneous fistulas develop only in late childhood. ", "Acute suppurative thyroiditis is a late clinical presentation. ", "Cases of mediastinal abscess of fourth branchial arch origin have been reported \\[[@B8], [@B9]\\].", "\n\nThe left side predominance of the disease might be because of the more complex and extended pathway of the fourth branchial tract on the left side \\[[@B10]\\].", "\n\nIn a meta-analysis of 526 cases published in a literature, the fourth branchial arch anomalies were almost always located on the left side (94%) and generally presented as acute suppurative thyroiditis (45%) or recurrent neck abscess (42%) \\[[@B2]\\].", "\n\nA large variety of diagnostic procedures have been described. ", "The barium esophagogram may fail to demonstrate a sinus tract during acute inflammation \\[[@B4]\\]. ", "In contrast, direct laryngoscopy can be performed during an acute episode and can achieve several targets \\[[@B11]\\]. ", "Magnetic resonance imaging is especially useful for detecting cystic anomalies of the sinus tract. ", "The use of Valsalva maneuver during CT-scan or barium swallow may help to open the sinus tract and make it more readily visible \\[[@B12], [@B13]\\]. ", "The meta-analysis of 526 cases showed that the barium esophagogram and direct laryngoscopy were the most useful diagnostic tools (74% and 45% of cases) \\[[@B2]\\].", "\n\nThe treatment options are multiple. ", "Incision and drainage is frequently performed but carries a high recurrence rate. ", "By contrast, open neck surgery, especially when combined with partial thyroidectomy, has the lowest recurrence rate but yields a higher rate of complications in infants and small children \\[[@B2]\\], with more risk of injury to the cervical neurovascular structures related to the small neck in this age. ", "Endoscopic treatment represents a minimally invasive technique using cauterization to obliterate the internal opening of a pyriform sinus tract \\[[@B14]\\]. ", "The meta-analysis of 526 cases described recurrence rates: incision-drainage, 89%; open neck surgery and tract excision, 15%; endoscopic cauterization of the sinus tract opening, 15%; and open neck surgery with partial thyroidectomy, 8% \\[[@B2]\\].", "\n\nIn our case, the 2 episodes of acute inflammation presented as left sided neck abscess without signs of thyroiditis and were treated by incision-drainage followed by antibiotic therapy. ", "After the acute phase, open neck surgery with complete excision of the fistula\\'s tract combined with left side partial thyroidectomy and cauterization of the internal opening of the left pyriform sinus tract by endoscopic approach were performed. ", "No complications or recurrence of inflammation was noted in the postoperative follow-up. ", "The patient had no difficulties with swallowing. ", "A postoperative indirect laryngoscopy showed normal vocal cord mobility and absence of edema in the pyriform sinus. ", "We noted good healing of the cervical wound.", "\n\n4. ", "Conclusion {#sec4}\n=============\n\nFourth branchial arch anomalies are more common than previously suspected. ", "The usual clinical presentations of these anomalies are recurrent neck abscess, acute suppurative thyroiditis, and respiratory distress in neonatal period. ", "Complete excision of the fistula tract during a quiescent period combined with partial thyroidectomy appears to be the treatment of choice with a lower recurrence rate. ", "This surgery is recommended for patients older than age 8 to minimize complications. ", "Before the age of 8, a medical treatment is recommended. ", "Endoscopic cauterization can be an effective alternative strategy with an outcome similar to open surgery.", "\n\nConsent\n=======\n\nThe authors have received the patient's permission to publish all photos.", "\n\nConflict of Interests\n=====================\n\nThe authors declare that they have no conflict of interests.", "\n\n{#fig1}\n\n{#fig2}\n\n{#fig3}\n\n{#fig4}\n\n{#fig5}\n\n{#fig6}\n\n{#fig7}\n\n{#fig8}\n\n[^1]: Academic Editor: Abrão Rapoport\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Q:\n\nHow do I enumerate a multidimensional associative array?", "\n\nI'll be the first to admit that PHP is not my forte and this array is starting to drive me nuts.", "\nThis is the array I'm attempting to enumerate:\n// array containing the site menu\n$sitemap = array(\n array( 'Title' => 'menu01',\n 'Description' => 'menu01_description', \n 'Address' => 'http://localhost/site.php?page=menu01',\n ),\n array( 'Title' => 'menu02',\n 'Description' => 'menu02_description', \n 'Address' => 'http://localhost/site.php?page=menu02',\n ),\n array( 'Title' => 'menu03',\n 'Description' => 'menu03_description', \n 'Address' => 'http://localhost/site.php?page=menu03',\n )\n);\n\nRight now I'm operating under the assumption that I need to use a foreach loop to enumerate the contents of my array. ", "\nThis is the function I'm currently trying to implement, but it keeps returning an error stating that my arguments are not valid.", "\nfunction GenerateMenu(){\n $output = \"<ul>\";\n\n foreach ($sitemap as $menuitem => $value){\n if ($page == $value[\"Title\"]){\n $output .= '<li class=\"active\">';\n }\n else {\n $output .= '<li>';\n }\n\n $output .= '<a href=\"' . ", "$value['Address'] . '\"", ">' . ", "$value['Description'] . '", "</a><li>';\n }\n\n $output .= \"</ul>\";\n return $output;\n}\n\nWhy are my arguments invalid? ", "What best way to print my array?", "\n\nA:\n\nYou forgot to specify/pass $page and $sitemap. ", "Where do that variables come from?", "\nTry pass it to your function:\nfunction GenerateMenu($sitemap, $page) {\n // …\n}\n\nThen you can call it like this:\n$sitemap = array(\n // …\n);\n$page = 'menu01'\necho GenerateMenu($sitemap, $page);\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "1. ", "Field of the Invention\nThe present invention generally relates to projection and display systems, and more particularly to an overhead projector having a computer integrated therein with several output ports for external devices, and having a unique interface card which electronically connects the overhead projector to a liquid crystal display panel and simultaneously aligns the panel with the stage of the overhead projector. ", "The panel may be slidably or pivotally attached to the overhead projector.", "\n2. ", "Description of the Prior Art\nOverhead projectors (OHP's) are known in the art, and generally consist of a base having a stage area, a light source to illuminate the stage, and a projector head which houses mirrors and lenses designed to project any image placed on the stage area onto a display screen. ", "OHP's may be either transmissive or reflective. ", "In a transmissive OHP, the light source is under the stage area, i.e., opposite the side of the projector head. ", "In a reflective OHP, the light source is above the stage area, typically near or even in the projector head, and the stage has a mirror-like surface to reflect the light back toward the head.", "\nUse of OHP's has recently expanded from the traditional projection of images printed on transparent films, to the projection of images which are stored in machine-readable form (e.g., on magnetic or optical disks) and which are presented by means of a light-transmissive liquid crystal display (LCD) panel which is laid on the stage of the OHP. ", "Exemplary LCD/OHP arrangements are shown in U.S. Pat. ", "Nos. ", "4,846,694 and 4,944,578. ", "In these patents, the LCD panels are controlled by external processors, such as a personal computer (PC). ", "This type of system enhances the use of an OHP since the LCD controller may simultaneously direct the video output to other viewing devices, such as television monitors, which may be placed at several stations among the audience.", "\nSeveral problems have arisen, however, in the use of LCD panels with OHP's. ", "Foremost among these is the difficulty of storing and transporting the PC which controls the LCD panel, and connecting the PC to the panel. ", "Three alternative systems have been devised to overcome this problem. ", "The first system simply provides a portable \"black box,\" much more compact than a normal PC and having simplified user inputs, which contains the minimum electronic components necessary to control the LCD panel, such as a microprocessor, memory storage and a monitor output port. ", "An example of such a system is VIDEOSHOW (a trademark of General Parametrics Corp. of Berkeley, Calif.), wherein the graphic images are prepared at a normal PC, and then transferred to a magnetic (floppy) diskette which may be placed in the portable unit. ", "The second system similarly incorporates certain components into the LCD panel, instead of the OHP. ", "An example of an LCD panel having a microprocessor and memory means for storing images is disclosed in European Patent Application No. ", "89114916.3.", "\nA third system for simplifying the LCD/OHP combination integrates certain computer components within the OHP. ", "An example of this type of system is found in U.S. Pat. ", "No. ", "4,882,599. ", "This design, however, suffers from the drawback of the processor being limited to the single purpose of controlling the LCD panel. ", "In other words, it is impossible to adapt the integrated OHP-computer for other uses such as remote communications, printing, etc. ", "More generally, these functions are unavailable due to the lack of any external ports for connection of peripherals, such as a modem, printer, mouse, etc. ", "Another disadvantage is that these systems do not support direct digital drive (for VGA-compatible panels), so that video signals must be converted from digital to analog and then back to digital again to interface to the LCD. ", "Also, prior art OHP-computers are not compatible with conventional PC operating systems, such as PC-DOS, OS/2 (trademarks of International Business Machines), MS-DOS (a trademark of Microsoft Corp.), DR DOS (a trademark of Digital Research, Inc.), or MACINTOSH system (a trademark of Apple Computers, Inc.), additionally limiting their usefulness.", "\nA further inconvenience of using an LCD panel with an OHP relates to the physical attachment of the panel to the OHP, and the electrical connections between the panel, its controller, and the OHP. ", "Those skilled in the art will appreciate the importance of properly aligning the LCD panel with the stage of the overhead projector. ", "Misalignment can result in lower light transmission through the panel, leading to an inferior projected image, and heat management problems; this is particularly critical in stacked panel designs which are subject to parallax problems, and also when special optical components, such as fresnel lenses, are used with the OHP. ", "While it is not terribly difficult to properly align a portable LCD panel on an OHP, the fumbling that often occurs in this step adversely detracts from the presentation, and this problem can be amplified depending upon the particular dimensions of the LCD panel and OHP being used. ", "With respect to the problem of electrical interconnection, anyone who has made a presentation with an LCD/OHP system has experienced the confusion of trying to connect the various cables needed for power, video, LCD control and other accessories. ", "This confusion leads not only to delays, but also presents a possible hazard of electrical shock to a user or damage to the equipment if the cabling is not properly connected. ", "Additionally, the user must insure that the proper cables (i.e., terminal connectors) are provided for the particular computer/LCD ports being used.", "\nThe problems mentioned in the foregoing paragraph are avoided in systems wherein the LCD panel is permanently integrated with the OHP. ", "See, e.g., U.S. Pat. ", "Nos. ", "4,763,993 (FIG. ", "4b) and 4,880,303. ", "The first of these devices, however, is less desirable since the LCD panel always remains in the optical projection path, even when a transparency, rather than the LCD panel, is being used to provide the image. ", "This in turn results in lower light transmission (due to the use of polarizers in the LCD panel) and hence poorer contrast in the projected image. ", "In the second of these devices, although the LCD panel can be hinged upwardly out of the optical projection path, its attachment to the OHP still leads to storage and transportation problems and, in both devices, the LCD panel is not removable and so cannot be used with other systems. ", "The latter aspect of these devices can be considerably frustrating, e.g., when the LCD panel is properly functioning but the OHP is nonfunctional, which may have many causes including breakdown of electrical components/connections in the OHP, or breakage of optical components such as the lamp or lenses. ", "Another disadvantage of the last two mentioned patents is that, when the LCD panel is moved to its upper position out of the optical projection path, it presents an obstruction which may prevent certain viewers in the audience from being able to see the projected image. ", "The simplest solution to this problem is to make the LCD panel completely removable, but this solution leads back to the aforementioned problems of panel storage and cable interconnection. ", "It would, therefore, be desirable and advantageous to devise an LCD/OHP system which would overcome all of the above limitations, particularly one which is easily adapted for use with either transparencies or an LCD panel, which provides means for conveniently storing the panel in a position which does not obstruct the projection screen from any viewing angle and further provides means for conveniently connecting the panel to the computer or controller." ]

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[ "Pages\n\nMonday, July 21, 2014\n\nIn Defense of Trophy Hunting\n\nI’m not a hunter, but I’m tempted to become one just to\nstand in solidarity with people – young women especially – who have recently\nbecome the targets themselves of vile anti-hunting hysteria.", "\n\nFirst, a 19-year-old Texas Tech cheerleader named Kendall\nJones roused a firestorm of social media anger after posting on Facebook pics\nof her posed with her legally acquired big game trophies. ", "After taking heat\nfrom accusations of animal cruelty, Jones replied,\n“The rhino was a green hunt, meaning it was darted and immobilized in order to\ndraw blood for testing, DNA profiling, microchipping the horn and treating a\nmassive leg injury most likely caused by lions.” ", "A lion she brought down\nwith a bow (!) ", "was within a game reserve: “Controlling the male lion population\nis important within large fenced areas like these in order to make sure the\ncubs have a high survival rate.”", "\n\nAs for the leopard pic, “this was a free ranging leopard in\nZimbabwe on communal land,” Jones wrote. “", "The money for the permit goes to the\ncommunal council and to their village people... Leopard populations have to be\ncontrolled in certain areas. ", "So yes, my efforts do go to conservation efforts\nand are all fair chase, not canned hunts.”", "\n\nShe also explained that meat from some hunts feeds local villagers:\n\nAnd for all that want to say stuff\nabout hunting is for food all the other animals go to the local villagers that\nare just trying to get meat! ", "These people only get meat when an animal is shot,\nthey aren’t privileged enough to go to the local grocery store and pay $20 for\nsome steaks! ", "And another thing is that this elephant’s trunk had been caught in\na snare put out by poachers!", "\n\nNevertheless, predictable internet outrage continued. ", "Facebook\nremoved the pics after tens of thousands of complaints. ", "She was verbally\nassaulted on social media. ", "One lunatic who fancies himself a future Congressman\n(I won’t mention his name because he’s a pathetic attention hound) even claimed\nthat “she deserves to be a target” and offered $100,000 for nude photos of\nJones or other salacious information. “", "Does #KendallJones use vegetables as sex\ntoys?” ", "he tweeted. “", "Does she enjoy being spanked? ", "We want to know.”", "\n\nNext, a 17-year-old Belgian soccer fan named Axelle\nDespiegelaere, who actually scored a modeling gig with L’Oreal after becoming\nthe focus of World Cup attention, immediately lost\nthat gig when her hunting photos\nshowed up on Facebook. ", "Again the social media hatred flew, and she was labeled “evil”\nand a “serial killer.” ", "After the teen appeared in a promo video which has since\nbeen removed from the company’s website, L’Oreal claimed that her “contract has\nnow been completed” and she will no longer be representing the company. ", "Then it\nfelt compelled to pacify animal activists further by reminding them that\nL’Oreal “no longer tests on animals, anywhere in the world.”", "\n\nI hope Despiegelaere gets picked up for another contract\nelsewhere. ", "If a modeling company and its customers are so concerned about\npolitically correct objections to the disgusting habits of their\nrepresentatives, perhaps they should demand that their models stop smoking\n(insert record scratch). ", "Watch how fast that shuts down the entire fashion\nindustry.", "\n\nThe hysteria reached, well, hysterical proportions when an\nold photo\nsurfaced on Facebook of a grinning Steven Spielberg posed in front of an\napparently freshly killed triceratops\n– from the set of Jurassic Park. ", "That\nattracted anti-hunting ire as well. ", "One\nFacebooker ranted (language warning):\n\nHe’s a disgusting inhumane prick Id\nlove to see these hunters be stopped…I think zoos are the best way to keep\nthese innocent animals safe…assholes like this piece of s**t are going into\nthese beautiful animals HOME and killing them…its no different than someone\ncoming into your home and murdering you … . ", "Steven Spielberg I’m disappointed\nin you…I’m not watching any of your movies again ANIMAL KILLER\n\nRecently I took my young daughter to Los Angeles’ Natural\nHistory Museum, which has an extensive and dramatic collection of dinosaur\nrelics. ", "She isn’t familiar with Spielberg, but she loves triceratops, and even at four years old she knows that\nthey’re long extinct.", "\n\nI appreciate that many are\ndisgusted by trophy hunting; it’s certainly not my thing. ", "But whatever your\nstand, the teens mentioned above hunted legally and even socially and\nenvironmentally responsibly. ", "They and others don’t deserve to be the “targets”\nof irrational personal attacks or to lose jobs for which hunting isn’t even relevant.", "\n\nAbout Me\n\nMark is the editor of TruthRevolt and a Shillman Journalism Fellow at the David Horowitz Freedom Center. ", "He writes about culture and politics for Acculturated, FrontPage Magazine, The Federalist, The New Criterion, and elsewhere. ", "He has made television appearances on CNN, Glenn Beck and elsewhere, as well as many radio and public appearances.", "\nMark has worked on numerous films including co-writing the award-winning documentary “Jihad in America: The Grand Deception.”", "\nHe is currently adapting a book for the big screen and writing one of his own for Templeton Press." ]

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[ "Black phosphorus (BP) is a layered allotrope of phosphorus, which crystallizes into an orthorhombic lattice.^[@ref1]^ Weakly bound phosphorene layers are vertically stacked in an arrangement analogous to graphite; in contrast, however, each phosphorene layer possesses two planes of phosphorus atoms bonded though *sp*^3^ orbitals. ", "This leaves two electrons per phosphorus atom paired, yet unbonded.^[@ref2],[@ref3]^ The 1D buckling and lone-pair electronic configuration result in an electronic band gap for bulk black phosphorus of 0.3 eV,^[@ref1]^ which is predicted to be dramatically enhanced in the single layer limit (∼1.5--2 eV) due to the suppression of interlayer interactions.^[@ref4],[@ref5]^ This strong variation in the electronic structure allows for optical identification of variations in layer thickness,^[@ref6],[@ref7]^ which, in addition to the high carrier mobility, make black phosphorus extremely promising for device applications based on 2D layered materials.^[@ref8]−[@ref13]^ Furthermore, black phosphorus contains an additional distinction: a strongly anisotropic band structure along the principle direction Γ--X compared to Γ--Y, which can be characterized by two free electron-like bands with starkly different effective masses.^[@ref14],[@ref15]^ To date, measurable anisotropies have been reported for in-plane carrier mobility, optical extinction, thermal transport, and plasmon dispersion.^[@ref14],[@ref16]−[@ref19]^\n\nIn addition to device applications, it has been proposed that the band structure of black phosphorus can be manipulated by strain or electric fields toward a superconducting phase transition^[@ref20],[@ref21]^ or a Lifshitz topological transition.^[@ref15],[@ref22]−[@ref24]^ The first experimental work to this end used surface alkali metals to controllably close the band gap and demonstrate a semimetal transition in which one of the two free electron bands transformed into a Dirac-like band.^[@ref25],[@ref26]^ This opens up the possibility of controlling both the topology and band gap of black phosphorus based on surface electric fields.", "\n\nHowever, unlike graphene, MoS~2~, or WS~2~, black phosphorus is extremely reactive, making its electronic properties sensitive to ambient conditions.^[@ref27],[@ref28]^ This motivates a careful understanding of the intrinsic doping of black phosphorus and how native defects modify the band structure.^[@ref29]−[@ref32]^ Scanning tunneling microscopy/spectroscopy (STM/STS) has been used to characterize the intrinsic band gap of bulk black phosphorus in ultrahigh vacuum, but conflicting values have been reported.^[@ref33],[@ref34]^ Here, we characterize the structural and electronic properties of black phosphorus and the influence of inherent single vacancies on those properties, utilizing a combination of low temperature STM/STS with electronic structure calculations. ", "We illustrate that black phosphorus is *p*-doped with a band gap of ∼0.3 eV; this doping is facilitated by single vacancies, which are characterized by an anisotropic charge density and in-gap resonance states near the valence band edge. ", "Combining tight-binding calculations with atomic-scale STM/STS, we identify the structure of these vacancies as well as depth profile them, correlating their electronic properties near the band gap with their depth from the surface. ", "Moreover, we demonstrate via quasiparticle interference that these vacancies act as strong scattering centers illuminating the anisotropic band structure.", "\n\nBlack phosphorus cleaves along the \\[001\\] direction due to weak van der Waals interactions; the STM image in [Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}a shows the resultant atomic structure after cleaving *in situ*, which leaves a macroscopically flat black phosphorus (001) surface. ", "Constant-current STM images reveal zigzag rows (along the \\[010\\] or zigzag direction), which correspond to the upper plane of phosphorus atoms (light orange atoms in [Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}b) in the topmost layer of the buckled rhombohedral structure. ", "As each phosphorus atom contains a lone pair of nonbonding electrons, the charge density per atom extends quite far into the vacuum, leading to the significant (0.02 nm) atomic corrugation observed in the STM topography. ", "The crystal structure yields two mirror-symmetric sublattices, which we label A and B in [Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}b, within each \\[010\\]-oriented atomic row. ", "In general, both sublattice sites appear equivalent in STM ([Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}c), except in the vicinity of a defect. ", "A close examination of the atomic structure ([Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}c) enables the determination of the lattice parameters within the (001) plane: *a* = 0.32 nm and *c* = 0.44 nm. ", "These parameters are consistent with previous experimental and theoretical studies of unstrained black phosphorus.^[@ref1],[@ref35]^ A FFT of the atomic resolved image in [Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}a ([Figure [1](#fig1){ref-type=\"fig\"}](#fig1){ref-type=\"fig\"}d) allows for the identification of the high-symmetry points of the topmost layer, where we adopt the convention denoting the real-space \\[100\\] direction as armchair and \\[010\\] as zigzag.", "\n\n{#fig1}\n\nTo understand the electronic properties of black phosphorus, STS was performed to characterize the band gap. ", "Using the analysis shown in [Figure S1](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf) for *n* = 48 individual measurements, we estimate *E*~g~ = 0.317 ± 0.036 eV. This band gap is consistent with previous large-area measurements on bulk black phosphorus crystals (0.31--0.35 eV).^[@ref1]^ Scanning tunneling spectroscopy further illustrates that the Fermi level (*E*~F~) generally resides within ±30 mV of the valence band edge ([Figure S2](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)); considering the band gap, this indicates that black phosphorus is strongly *p*-doped without deliberate modification. ", "To elucidate the origin of this intrinsic *p*-doping, we investigate below the structural and electronic properties of the atomic-scale defects in black phosphorus.", "\n\n[Figure [2](#fig2){ref-type=\"fig\"}](#fig2){ref-type=\"fig\"}a shows a representative large-area constant-current image of black phosphorus near the valence band edge. ", "The surface is decorated with a low density of characteristic, elongated, dumbbell-shaped protrusions, which exhibit enhanced charge density along the \\[100\\] (armchair) direction. ", "As these features are present after cleaving in ultrahigh vacuum, we associate them with native defects in the black phosphorus crystal. ", "Line profiles across these defects, shown in the upper left inset of [Figure [2](#fig2){ref-type=\"fig\"}](#fig2){ref-type=\"fig\"}a, reveal that measured heights of the defects range from 0.01 to 0.2 nm above the pristine surface, spanning nearly an order of magnitude greater than the intrinsic corrugation of the atomic lattice. ", "The monotonic changes in apparent height ([Figure [3](#fig3){ref-type=\"fig\"}](#fig3){ref-type=\"fig\"}) are consistent with STM studies of defects at various heights beneath the surface of III--V semiconductors,^[@ref36]−[@ref39]^ as well as in various layered compounds.^[@ref40],[@ref41]^ We discuss the depth profiling of the defects in more detail later.", "\n\n{#fig2}\n\n{#fig3}\n\nAtomic-scale characterization of the observed dumbbell structures is shown in [Figure [2](#fig2){ref-type=\"fig\"}](#fig2){ref-type=\"fig\"}b,c, for two different depths below the surface. ", "Close examination of these images reveals that the two dumbbell structures can be transposed onto one another through a reflection along \\[010\\] (see also [Figure S3--S4](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "Utilizing tight-binding calculations, we investigate the resultant charge density associated with midgap states near single vacancies ([Figure [2](#fig2){ref-type=\"fig\"}](#fig2){ref-type=\"fig\"}d,e) in the uppermost layer at both sublattice positions (A, B). ", "The calculations qualitatively reproduce the highly anisotropic charge density seen in STM images ([Figure S5](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)), as well as a sublattice-dependent orientation of the charge density. ", "By comparing the curvature near the defect center, each experimentally observed dumbbell structure can be directly assigned to a vacancy at a particular sublattice. ", "Therefore, we refer to the vacancies at sublattice A and B, as vacancy A and B, respectively. ", "Furthermore, tight-binding calculations show that vacancies below the first layer maintain the dumbbell defect shape, but have diminished intensity with respect to vacancies in the surface layer ([Figure S6](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "In reproducing key experimental observations, tight-binding calculations reveal that it is possible to trace each observed defect to a particular depth below the surface as well as the atomic sublattice within that layer.", "\n\nIn order to thoroughly understand the relationship between the experimentally determined apparent height and the vacancy depth below the surface, over 100 vacancies were characterized according to their sublattice location and constant-current height profile. ", "This analysis, with the index sorted according to apparent height, is presented in [Figure [3](#fig3){ref-type=\"fig\"}](#fig3){ref-type=\"fig\"} for both vacancy types. ", "From the total number of characterized vacancies, we observe vacancy B nearly twice as frequently as vacancy A. The plots in [Figure [3](#fig3){ref-type=\"fig\"}](#fig3){ref-type=\"fig\"} display the mean intensity extracted from line profiles of the apparent height (illustrated in the insets) for (1) both sides of the vacancy (red/blue), (2) the left side (gray square), (3) and the right side (black diamond). ", "Clear trends emerge in the apparent height for vacancy A, seen in the step-like features at approximately 0.01, 0.04, 0.07, and 0.10 nm. ", "The plateaus are attributed to vacancies residing in discrete layers below the surface, which we label by increasing number with increasing depth underneath the surface, with the label 0 referring to vacancies in the surface layer. ", "Furthermore, a majority of A vacancies exhibited an enhanced intensity on the left region of the charge density compared to the right, with asymmetry between regions decreasing with increasing depth below the surface. ", "Height plateaus for vacancy B are not readily identifiable in [Figure [3](#fig3){ref-type=\"fig\"}](#fig3){ref-type=\"fig\"}b; however, there is a height dependent trend in the d*I*/d*V* spectra, as we show below ([Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}a and [Figure S6](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)), similar to vacancy A, which we believe is related to the specific layer assignment. ", "The preference of vacancy B compared to vacancy A, combined with the differences in their height profiles indicates that the symmetry of the A--B sublattices is broken near the surface at the vacancy site. ", "We attribute this trend to surface relaxation effects, which may relax the two sublattices asymmetrically at the vacancy site near the surface. ", "While the symmetry breaking of the A--B sublattices may be due to vertical relaxation, we note that we cannot rule out a small vertical relaxation for deeper vacancies, which show A--B sublattice symmetry.", "\n\n![", "Tunneling spectroscopy of the depth dependence and spatial variation for both vacancy types taken at red circles. (", "a,b) Representative tunneling spectra sorted by decreasing apparent height (*h*) according to progressive blue scale in the middle for (a) vacancy A and (b) vacancy B taken at the position of the red dot as denoted in the inset. ", "All apparent heights are within ±0.01 nm, except for the *h* = 0.165 nm, which is ±0.02 nm. (", "c,d) Spatially resolved tunneling spectra taken for vacancy B (*h* = 0.150 nm) along: (c) \\[100\\] (armchair) direction over a total length of 20 nm and (d) along \\[010\\] (zigzag) direction over a total length of 10 nm. ", "Stabilization conditions for all spectra: *V*~s~ = 0.35 V, *I*~t~ = 200--400 pA. The red spectra were taken at the red point in the inset.](nl-2017-00766a_0004){#fig4}\n\nTo correlate the electronic properties of each vacancy type with their depth from the surface, spatially resolved tunneling spectroscopy was performed for vacancies at various depths from the surface ([Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}). ", "All spectra for both vacancy types taken near the center of the vacancy share two key departures from the pristine band gap spectrum (gray curve at the bottom of [Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}a,b): (a) spectral resonance(s) emerge in all curves near *E*~F~ and (b) nonzero tunneling conductance is measured throughout most of the bulk band gap in the proximity of the vacancy (see [Figure S7](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "Moreover, the spectra ([Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}a,b) clearly show a phenomenological trend with respect to the resonance states near *E*~F~. The upper curves (*h* \\> 0.06 nm) show two distinct spectral features split (not necessarily equivalently) about the Fermi level. ", "For both vacancy types, these split peaks are seen for vacancies near the surface, whereas deeper vacancies converge to a single spectral resonance slightly above *E*~F~ (see also [Figure S8](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "Furthermore, while the absolute energy of the double-resonance structure for vacancy B varies, the separation between the resonance features is nearly constant with a value of approximately 27 ± 3 mV. The rigid separation likely originates from the monovalent nature of single vacancies, while the absolute position of spectral features can be influenced by the depth from the surface and the surrounding environment. ", "Additionally, the relative intensity of the spectral peaks varies with the precise measurement position (see [Figure S9](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "It is important to note that we do not observe any significant effects of tip-induced band bending ([Figure S10](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)), most likely due to the pinning of the valence band. ", "At *h* \\< 0.05 nm, the spectra for vacancies A and B merge to a single resonance at 9 ± 2 mV. This further indicates that the symmetry between both sublattices may be broken by surface relaxation for vacancies at or near the surface (e.g., 0L--2L), and this symmetry is restored in the bulk. ", "These spectral features reveal that the atomic vacancies host shallow donor states, which contribute to the inherent *p*-doping and lead to electrical conduction within the band gap.", "\n\nSpatially resolved STS can also be utilized to map the lateral variation of the observed spectral features. ", "The line spectra in [Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}c show that the spectral resonances near the Fermi level are localized to the topographically bright dumbbell regions (red point in inset and red curve, see also [Figure S7](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf)). ", "Such resonance states are observable as far as 5 nm from the vacancy site along \\[100\\]. ", "In the direction of \\[010\\] ([Figure [4](#fig4){ref-type=\"fig\"}](#fig4){ref-type=\"fig\"}d), however, the resonance states decay much faster, generally within 2 nm of the vacancy site. ", "The strong wave function anisotropy likely stems from the drastic differences in the effective masses of the valence band along Γ--X and Γ--Y. The full spatial profile of the differential tunneling conductance is shown in [Figure S7](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf), at energies both off and on resonance.", "\n\nThe anisotropic nature of the black phosphorus band structure is strongly pronounced in quasiparticle interference (QPI) near the vacancy sites.^[@ref42],[@ref43]^[Figure [5](#fig5){ref-type=\"fig\"}](#fig5){ref-type=\"fig\"}a shows a constant-current d*I*/d*V* image acquired at *V*~S~ = −0.6 V near several vacancies with varying depth from the surface. ", "Clear oscillations are observed around each vacancy, with a much stronger intensity along \\[100\\] compared to \\[010\\]. ", "This asymmetric scattering pattern is a signature of the anisotropy of the valence bands near the Fermi edge, giving rise to nesting of the quasiparticle scattering vectors. ", "This asymmetry can be clearly traced in the Fourier transform of the d*I*/d*V* map ([Figure [5](#fig5){ref-type=\"fig\"}](#fig5){ref-type=\"fig\"}b), where higher intensity is seen for vectors oriented along the Γ--X direction. ", "The edge of the Brillouin zone (BZ) is also highlighted with a green rectangle for reference. ", "As seen in the calculated constant energy contours in [Figure [5](#fig5){ref-type=\"fig\"}](#fig5){ref-type=\"fig\"}d (progressive ellipses around Γ, see [Figure S9](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf) for cuts on the band structure), the shape of the valence band is strongly ellipsoidal near *E*~F~. This ellipticity causes an imbalance of available scattering vectors in the Γ--X versus Γ--Y directions leading to more prominent carrier scattering along \\[100\\]. ", "As the calculations reveal, the constant energy contours become more circular at increasing negative energies, which weakens the nesting condition and results in stronger intensity fringes along \\[010\\], as shown in [Figure [5](#fig5){ref-type=\"fig\"}](#fig5){ref-type=\"fig\"}c.", "\n\n{#fig5}\n\nIn conclusion, we have characterized the structural and electronic properties of inherent single vacancies in black phosphorus. ", "We illustrate that vacancies exhibit a highly anisotropic and delocalized charge density. ", "Moreover, intrinsic vacancies possess in-gap resonance states near the valence band edge, which strongly perturb the bulk band gap. ", "Therefore, we conclude that intrinsic vacancies contribute to the observed strong *p*-doping of black phosphorus. ", "This work motivates further studies of the bulk doping to conclude if intrinsic vacancies are solely responsible for the observed strong *p*-doping. ", "We further reveal that these single vacancies serve as strong scattering centers, as seen in quasiparticle interference near the observed vacancy sites. ", "This study provides fundamental insight into the influence of intrinsic point defects on the electronic properties of black phosphorus, which is crucial for future developments of black phosphorus technologies. ", "Moreover, the recent findings of magnetic vacancies in graphene and indications of magnetism in black phosphorus vacancies,^[@ref32]^ make this an interesting platform to study magnetic ordering in *sp*-driven systems.^[@ref44]^\n\nExperimental Methods {#sec2}\n====================\n\nSTM/STS measurements were carried out on a commercial Omicron low-temperature STM with a base temperature of 4.6 K, operating in ultrahigh vacuum (\\<1 × 10^--10^ mbar), with the bias applied to the sample. ", "Etched W tips were utilized for these measurements and were treated *in situ* by electron bombardment, field emission, as well as dipped and characterized on clean Au surface. ", "Scanning tunneling spectroscopy was performed using a lock-in technique to directly measure d*I*/d*V*, with a modulation frequency of *f*~mod~ = 4.2 kHz and amplitude of *V*~mod~ = 5 mV. Black phosphorus crystals were provided by HQ graphene and stored in vacuum at a temperature less than 25 °C, cleaved under ultrahigh vacuum conditions at pressures below 1 × 10^--9^ mbar, and immediately transferred to the microscope for *in situ* characterization.", "\n\nTheoretical Calculations {#sec2.1}\n========================\n\nTheoretical calculations were based on the tight-binding model proposed for multilayer BP in ref ([@ref5]). ", "To model structural defects, we considered a missing atom in a three-layer supercell with dimensions (16*a* × 12*c*) ≈ (52.5 × 53.0) Å and performed exact diagonalization of the tight-binding Hamiltonian. ", "Wave functions of a defect state were represented as Ψ(r) = Σ~i~*c*~i~ · φ(*r*), where *c*~i~ is the contribution of the *i*th atom given by the corresponding eigenvector of the Hamiltonian, and φ(*r*) is the cubic harmonic representing the 3p~*z*~-like orbital of P atoms, being the basis functions of the Hamiltonian. ", "Constant energy contours appearing in [Figure [5](#fig5){ref-type=\"fig\"}](#fig5){ref-type=\"fig\"}d were extracted directly from first-principles GW calculations performed in ref ([@ref5]).", "\n\nThe Supporting Information is available free of charge on the [ACS Publications website](http://pubs.acs.org) at DOI: [10.1021/acs.nanolett.7b00766](http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.7b00766).Additional information includes band gap determination and statistics, detailed examination of defect anisotropy, extended tight-binding results, spatial profiles of defect-related in-gap conduction, representative depth dependent d*I*/d*V* spectra, spatial variation in d*I*/d*V* spectra, height-dependent d*I*/d*V* spectra, and the calculated band structure of black phosphorus ([PDF](http://pubs.acs.org/doi/suppl/10.1021/acs.nanolett.7b00766/suppl_file/nl7b00766_si_001.pdf))\n\nSupplementary Material\n======================\n\n###### \n\nnl7b00766_si_001.pdf\n\nThe authors declare no competing financial interest.", "\n\nB.K., N.H., and A.A.K. acknowledge financial support from the Emmy Noether Program (KH324/1-1) via the Deutsche Forschungsgemeinschaft, and the Foundation of Fundamental Research on Matter (FOM), which is part of The Netherlands Organization for Scientific Research (NWO). ", "B.K., N.H., and A.A.K. also acknowledge the VIDI project: 'Manipulating the interplay between superconductivity and chiral magnetism at the single atom level' with project number 680-47-534 which is financed by NWO. ", "N.H. and A.A.K. also acknowledge support from the Alexander von Humboldt foundation via the Feodor Lynen Research Fellowship. ", "A.N.R. and M.I.K. acknowledge support from the European Union's Horizon 2020 Programme under Grant No. ", "696656 Graphene Core1. ", "A.A.K. would also like to acknowledge scientific discussions with Alexander Grueneis and Daniel Wegner.", "\n" ]

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[ "A Chinese hot pot restaurant has been forced to close its doors after an all-you-can-eat deal left it more than $100,000 in debt.", "\n\nKey points: Restaurant fails to anticipate demand for $25, month-long all-you-can-eat deal\n\nRestaurant fails to anticipate demand for $25, month-long all-you-can-eat deal Went bankrupt inside of two weeks after more than 500 people came every day\n\nWent bankrupt inside of two weeks after more than 500 people came every day The owner admits they weren't great at management after ending up $100,000 in debt\n\nJiamener restaurant in the city of Chengdu shut its doors for good last week after customers took advantage of a $25 all-you-can-eat deal, the Chengdu Economic Daily reported.", "\n\nCustomers paid the fee and received a membership card that entitled them to unlimited food for the month.", "\n\nSome customers reportedly shared their card around with family and friends, drastically increasing the volume of meals being consumed on a single purchase.", "\n\nThe neighbourhood restaurant never made it through the first month of the promotion, after it began receiving in excess of 500 customers a day after the deal commenced, with long queues forming before the doors opened and lasting till late into the evening past closing times.", "\n\nChinese social media lit up after the news of the restaurant closure broke.", "\n\n\"This [restaurant owner] is really careless, didn't think through,\" Weibo user Si Yan Du Bu said.", "\n\nAnother user, Shao Xingfeng, added: \"The owner gets himself out of business.", "\n\n\"You would not dare to play this kind of thinking in China.", "\n\n\"[Customers] can eat till you're bankrupt.\"", "\n\nAnother user who went by the name \"Come to shout together GY\" said: \"Never underestimate our Chinese appetite!\"", "\n\nA Weibo user's photo of the unfortunate restaurant, now quiet. ( ", "Weibo )\n\nOwner blames lack of business skill\n\nOwners told the publication they anticipated losing some money, but thought they could accumulate more repeat customers in the process.", "\n\nThey also said they hoped to lower overall costs with other suppliers once they increased the volumes on their own food purchases.", "\n\nCo-owner Su Jie said the main problem was a lack of business acumen on the part of owners, who had only opened the restaurant in December.", "\n\n\"The uncivilised behaviour of the diners was secondary — the main problem was our poor management,\" he told the Chengdu Economic Daily.", "\n\nHot pot is very popular in Chengdu, which has a population of more than 10 million people.", "\n\nIt is estimated there are about 20,000 hot pot restaurants dotted across the city.", "\n\nAccording to data released by China's internet giant Sina, Chengdu residents spent $3 billion eating at hotpot restaurants in 2016 — more than $800 per person." ]

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[ "**What was known?**", "\n\nThe rhinosporidiosis with disseminated is very rare phenomenon. ", "Very few literature supports for FNAC as diagnostic tool in such cases. ", "In these reported cases, patients are known case of nasal or ocular rhinosporidiosis with dissemination detected by FNAC.", "\n\nIntroduction {#sec1-1}\n============\n\nRhinosporidiosis is a chronic granulomatous lesion caused by *Rhinosporidium seeberi*.\\[[@ref1][@ref2][@ref3]\\] Clinically, rhinosporidiosis presents as pedunculated polypoidal soft tissue mass. ", "Nose and nasopharynx are the most common sites involved, accounting for more than 70% cases. ", "Ocular lesions, particularly of the conjunctiva and lacrimal sac, account for 15% cases.\\[[@ref2][@ref3]\\] Rare sites of involvement are lips, palate, uvula, maxillary antrum, epiglottis, larynx, trachea, bronchus, ear, scalp, vulva, penis, rectum and skin. ", "Rarely, disseminated infections are also reported involving limbs, trunk and viscera especially in the immunocompromised patients.\\[[@ref2][@ref3][@ref4]\\] Presenting as cutaneous and subcutaneous mass is extremely rare.\\[[@ref3][@ref4]\\] We describe a case of FNA cytology experience of rhinosporidiosis occurring as a soft tissue mass in the right mid thigh region.", "\n\nCase Report {#sec1-2}\n===========\n\nA 71-year-old male presented with multiple subcutaneous soft tissue mass lesions in the postero medial aspect of mid right thigh region since 2 weeks. ", "Local examination revealed multiple firm to hard mass with skin over the swelling being unremarkable \\[[Figure 1a](#F1){ref-type=\"fig\"}\\]. ", "CT of the right thigh showed a heterogeneous lesion with infiltrative margins in the thigh. ", "Clinically soft tissue sarcoma was considered. ", "Routine hematological and biochemical investigations were unremarkable. ", "HIV and HBs Ag tests were nonreactive. ", "Diagnostic FNAC was performed showing numerous mature and immature sporangias with giant cell reaction \\[Figure [1c](#F1){ref-type=\"fig\"} and [d](#F1){ref-type=\"fig\"}\\]. ", "Intraoperatively, the mass was irregular and nodular grey white \\[[Figure 1b](#F1){ref-type=\"fig\"}\\]. ", "An excision biopsy showed multiple grey white masses with cystic and mucoid areas \\[[Figure 2a](#F2){ref-type=\"fig\"}\\]. ", "Histopathology confirmed the rhinosporidiosis with numerous mature and immature sporangia surrounded by dense inflammatory response \\[[Figure 2b](#F2){ref-type=\"fig\"}\\]. ", "Complete ENT examination revealed no obvious rhinosporidial lesion. ", "The patient is under regular follow up since 1 year without any evidence of recurrence.", "\n\n![(", "a) Clinical photograph showing nodular mass in subcutaneous plane in the thigh (b) Intraoperatively nodular grey white mass in the subcutaneous plane (c) Lesional aspiration showing many mature sporangia with endospores in background \\[Papanicolou stain, ×400\\] (d) Lesional aspiration showing many mature and immature sporangia \\[Papanicolou stain, ×400\\]](IJD-60-215e-g001){#F1}\n\n![(", "a) Gross specimen showing multiple grey white masses with cystic and mucoid areas (b) Histopathology showing with hyperplastic epithelium and immature spornagias with giant cell reaction \\[H and E, ×400\\]](IJD-60-215e-g002){#F2}\n\nDiscussion {#sec1-3}\n==========\n\nRhinosporidiosis is a rare disease, known for many years and first described in argentina.\\[[@ref1][@ref3]\\] The mode of infection from the natural aquatic habitat of *R. seeberi* is through the traumatized epithelium.\\[[@ref2][@ref3][@ref4]\\] It is an aquatic protozoan and recent taxonomy suggests it is now a new eukaryotic group of protists known as Mesomycetozoa. ", "Ahluwalia *et al*. ", "suggested the cyanobacterium Microcystis aerogenosa as the causative agent which has been isolated from clinical samples as well as water samples in which patients are taking bath.\\[[@ref5][@ref6]\\] There is evidence for hematogeneous spread of rhinosporidiosis to anatomically distant sites especially in immunocompromised individuals.\\[[@ref2]\\] However in our case, HIV was nonreactive and mode of dissemination to a distant site is obscure.", "\n\nA typical polypoid appearance of the lesions often helps in correct preoperative diagnosis. ", "However, atypical presentations may cause confusion with soft tissue tumors or papillomas.\\[[@ref2][@ref4][@ref5]\\] Aspiration cytology can be helpful in these cases.\\[[@ref2][@ref3][@ref5]\\] Microscopically, demonstration of endospores of 5-10 μm and sporangium of 50-1000 μm in the cytological smears clinches the diagnosis. ", "Background shows granulomatous reaction. ", "The endospores may be confused with epithelial cells. ", "The PAS stain is used to discriminate between endospores and epithelial cells, in which the residual cytoplasm and large nuclei can sometime simulate the residual mucoid sporangial material around the endospores.\\[[@ref2][@ref4][@ref5]\\] In our case, aspiration cytology was classical of rhinosporidiosis and hence PAS stain was not performed.", "\n\n*R. seeberi* should be distinguished from *Coccidioides immitis*.\\[[@ref2][@ref3][@ref4]\\] The latter has similar mature stages represented by large, thick-walled, spherical structures containing endospores, but the spherules are smaller (diameter of 20-80 μm versus 50-1000 μm) and contain small endospores (diameter of 2-4 μm).\\[[@ref1][@ref3][@ref4]\\]\n\nThe definitive diagnosis of rhinosporidiosis is by histopathology on biopsied or resected tissues, with the demonstration of sporangia and endospores.\\[[@ref2][@ref4][@ref5]\\] The sporangia are large, thick-walled spherical structures with endospores seen in a fibromyxomatous or fibrous stroma containing chronic inflammatory cells, which include macrophages and lymphocytes. ", "Each mature sporangium contains an operculum or pore through which the endospores are extruded.\\[[@ref2][@ref4][@ref5]\\] Our case also showed similar histopathological finding.", "\n\nThe only curative approach is the surgical excision combined with electro coagulation.\\[[@ref2][@ref4][@ref5]\\] There is no demonstrated efficacy in using antifungal and/or antimicrobial drugs. ", "Recurrence, dissemination and local secondary bacterial infections are the most frequent complications. ", "Dapsone, ketconazole, ciprofloxacin and amphotericin have been tried with varied success.\\[[@ref3][@ref4][@ref5]\\] Our case was managed with surgical excision and on 1 year of follow up no evidence of recurrence was noted.", "\n\nConclusion {#sec1-4}\n==========\n\nThe FNAC diagnosis of rhinosporidiosis is specific. ", "It can be diagnosed cytologically from its morphological features similar to histopathology. ", "Preoperative diagnosis is possible even in cases with unusual clinical presentations.", "\n\n**What is new?**", "\n\nThe disseminated rhinosporidiosis without nasal or ocular lesion is very rare phenomenon and diagnosing such cases by FNAC is very challenging. ", "Our case is of first of its kind in the literature\n\n**Source of support:** Nil\n\n**Conflict of Interest:** Nil.", "\n" ]

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[ "The antinociceptive effect of moclobemide on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy.", "\nThe aim of our study was to investigate the antinociceptive activity of moclobemide on the vocalization threshold to paw pressure in a rat model of unilateral mononeuropathy. ", "The neuropathy was produced by ligation of the sciatic nerve and nociceptive thresholds were determined 15-21 days after surgery by a modification of the Randall-Sellito method. ", "Group 1 (n= 10) received 0.2 ml peroral (p.o.) ", "saline, Group 2 (n= 10) 5 mg x kg(-1), Group 3 (n= 10) 10 mg x kg(-1) and Group 4 (n= 10) 20 mg x kg(-1) p.o. ", "moclobemide. ", "Nociceptive pressure thresholds were then measured every 20 minutes after drug administration. ", "Analysis of variance, Tukey's test and a paired Student's t-test were employed for statistical analysis. ", "The perorally administered moclobemide (5, 10 and 20 mg x kg(-1)) produced an antinociceptive effect on both lesioned and non-lesioned hind paws ( P< 0.05). ", "However, the analgesic effect on the lesioned paw was significantly more potent than the non-lesioned paw. ", "The peak value ( p) remained constant while the maximal increment between the control threshold and the peak value ( I(max)) was significantly more pronounced for the lesioned paw ( P< 0.001). ", "The results of this study may suggest that moclobemide can be a therapeutic alternative to treat some clinical symptoms in peripheral neuropathic conditions." ]

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[ "Q:\n\nAccounts with many-to-many relationship with accounts -- how to create a report on contacts\n\nI'm setting up an org that has a many-to-many relationship between \"buyers\" and \"sellers.\" ", " I'm using the Account object for both buyers and sellers and set the Type field picklist to have the choices \"buyer\" or \"seller.\" ", " Then, in order to complete the many-to-many relationship, I created a junction object called \"Relationship\" with two lookup fields: \"Buyer\" and \"Seller.\" ", " This works fine on the account level -- if BuyerA has relationships with Seller1 and Seller2, then the record for BuyerA has the relationship related list populated with Seller1 and Seller2, and so forth.", "\nHowever, I want to be able to create a report that goes down to the contact level: For instance, I'd like to be able to have the report show all Seller contacts for BuyerA. So, if BuyerA has relationships with Seller1 and Seller2, and Seller1 has contacts ContactS1a and ContactS1b, and Seller2 has contacts ContactS2a and ContactS2b, the report filtered on BuyerA should show: ContactS1a, ContactS1b, ContactS2a, and ContactS2b. ", " A further requirement is that the report needs to be exportable, so I can't use a joined report.", "\nIs it possible to do this with standard or custom Salesforce reports? ", " If so, how might I go about it -- I've tried every angle...custom reports, cross-joins, etc., ", "but can't seem to get the results I need.", "\nAlternatively, is the basic relationship structure flawed? ", " Should I be using a custom object for buyers or sellers and not try to use the account object for both?", "\nEdit: Here is a barebones sketch of the schema. ", " And, if it helps at all to understand my situation, here's what the query for the report would look like in MSSQL:\nSELECT c.*\n FROM Account a\n JOIN Relationship r ON r.BuyerId = a.Id\n JOIN Account a2 ON a2.Id = r.SellerId\n JOIN Contact c ON c.AccountId = a2.Id\n WHERE a.Name = 'BuyerA'\n\nA:\n\nIt's a few months later and I finally found the solution to this problem -- and it turns out it's already built into Salesforce (although I believe it's only available in the enterprise edition and above): Partner Portals. ", " You don't actually have to use the core partner portal functionality, but by activating the Partner object, you automatically get a many-to-many relationship between accounts (which is exactly what I wanted). ", " Here's what I did:\nTurn on the Partner object: Setup > Customize > Partners > Settings; then check the box to enable partners and hit save. ", "\nAdd the Partner Account field to the Account Layout: Setup > Customize > Accounts > Page Layouts; edit the default page layout and just drag the Partner Account field somewhere. ", " It’s actually not editable, but I guess it’s nice to see…or maybe making it visible triggers its functionality (not sure).", "\nTo make an account a partner account, you must first create it and save it, and then you'll see a button that says “Manage External Account”; click on it an select “Enable As Partner” – now the Partner Account checkbox will be checked.", "\nThen, the way you link an account with a partner account is you scroll down to the bottom of the account page to Partners related list. ", " Click on “New” and select a partner account, give it a role, and save.", "\nIf you want to then run a report showing all contacts for a specific account's partners, you'll need to create a custom report with the primary object being accounts, the secondary object being partners, and the tertiary object being contacts. ", " When you run the report, filter it by the original account, and you'll see all contacts for that account's partners! ", "\n\n" ]

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[ "\n\n(written from a Production point of view Real World article\n\nFor the TOS episode with a similar title, please see \" Wink of an Eye \".", "\n\nOver time and generations, a world tries to uncover the mystery of a strange object in the sky.", "\n\nContents show]\n\nSummary\n\nTeaser\n\nThe USS Voyager approaches a planet rotating 58 times per minute and, while investigating, the ship enters a gravimetric gradient pulling it into a geosynchronous orbit in which the crew becomes trapped. ", "On the planet, a native is then seen preparing an altar. ", "Just then, an earthquake occurs, and the native sees a new star in the sky, which is Voyager.", "\n\nAct One\n\nThe civilization, who had been worshiping a deity called Tahal, is confused at the situation. ", "Another of the natives comes to interpret that there is a new deity wishing to be worshiped, orders a new altar to be made for it, and promises allegiance to the new one, calling it Ground Shaker.", "\n\nThe tachyon core of the planet has created a differential in space-time, meaning that time passes much more quickly on the planet than in the rest of space. ", "Within \"moments\" of Voyager's arrival and entrapment many years have passed on the surface. ", "The initial entry into orbit coincides with an earthquake interpreted by the inhabitants as an act of a new deity, the Voyager ship appearing as a new bright star in the sky. ", "Chakotay asks B'Elanna Torres to reconfigure a class 5 probe to take pictures every ten milliseconds, and to take surveys of the planet to help try to get Voyager out of orbit. ", "Chakotay goes on to say that this could be the best anthropological find ever; it is one thing to dig and find the history, but to watch the civilization develop before your eyes is another thing entirely. ", "After Torres tells Chakotay that it could take a few hours to reconfigure the probe, he says that they might miss the rise and fall of a civilization. ", "Torres reassures him that they'll just have to watch the next one.", "\n\nAs time passes, the planet's inhabitants quickly change to a pre-medieval level of technology. ", "An old teacher climbs a hill to one of his former students who is now a protector. ", "He believes the star is from another civilization like theirs, and the Ground Shaker their protector, like himself. ", "He intends to send a letter via hot air balloon, and has the teacher write a note for him, asking him to stop shaking the ground.", "\n\nAct Two\n\nTorres and Chakotay are fascinated as they observe scans from the probe indicating that the civilization has entered an industrial age, creating roads and more fortified buildings than normal for a civilization in that stage. ", "Furthermore, they can tell the frequency of the earthquakes. ", "The probe, however, soon decays and disintegrates in the atmosphere, as it's operating in the space-time of the planet, equivalent to over 200 years. ", "Chakotay surmises that the civilization is advanced enough that it should be observing Voyager.", "\n\nOn the planet, an astronomical observatory exists. ", "A scientist there is able to observe Voyager through its telescope and is trying to contact it through radio transmissions, however, it is not responding, to both him and his tired assistant's dismay. ", "They are trying one last time before calling it a day when the assistant suggests a personal message in addition to mathematical sequences and constants.", "\n\nIn astrometrics, Seven of Nine detects the transmission and Chakotay recognizes they need to slow down the frequency to interpret it. ", "In the message, the astronomer explains the culture and mythology of the planet's people. ", "In a senior staff briefing, the crew listens to the message. ", "For centuries the society lives with the constant ground-shaking effect brought about by Voyager and its effects on the natural poles and rotation of the planet. ", "Cautious about first contact with a pre-warp society and aware of the accelerated aging causing by the time differential, Captain Janeway employs The Doctor to beam to the planet on an undercover mission to gather data in an effort to find a way for Voyager to escape orbit. ", "As Janeway and Torres prepare to beam him back, the signal is lost.", "\n\nAct Three\n\nBy the time The Doctor is successfully located and beamed back on board, three years have passed on the planet. ", "Overjoyed to see them, he explains that Voyager has been a catalyst for invention and that a space race is in progress to make contact. ", "Voyager is also used as a catalyst for religion, music, art, and even children's toys. ", "He tells the captain that his roommate, with whom he shared an apartment, even composed an aria about Voyager. ", "He said the apartment was destroyed by a rival state's cannon shells when they started a war with the one he was in. ", "The Doctor goes on to explain that the war was finished in \"a matter of weeks\" when a new treaty was signed.", "\n\nHe also informs Janeway that he has committed to memory the last three hundred years of meteorological records and some seismic analysis from the planet. ", "Using The Doctor's data, the crew attempts an escape, but after only fifty meters of ascent, seismic activity increases and the exercise is aborted. ", "In the meantime, a space capsule from the planet's surface reaches Voyager and its two-person crew find the crew in what appears to be some form of stasis; the time differential causes them to observe only microseconds passing on board the ship while they experience several minutes. ", "When they reach the bridge, they witness Neelix in the middle of pouring Janeway some coffee and realize it is not stasis they are witnessing, but a time differential. ", "Right after, they enter Voyager's time-frame and collapse, to the surprise of the bridge crew. ", "Janeway immediately calls for medical emergency.", "\n\nAct Four\n\nIn sickbay, The Doctor was able to save the pilot, Gotana-Retz, while the commander, Terrina, does not survive the transition. ", "The Doctor notes that, given his extensive knowledge of local physiology, he is as good as Retz' family doctor. ", "Retz is revived in sickbay in the company of Janeway and The Doctor. ", "After hearing the news of his fallen comrade, he informs Janeway that he is beginning to understand the time differential between his world and Voyager. ", "Janeway explains the difference in time to Retz in greater detail, to which he asks, \"So you really haven't been watching us for centuries?\" ", "Captain Janeway replies \"Actually, we just got here. ", "And we're hoping you can help us find a way to leave.\"", "\n\nLater, Gotana-Retz meets with Janeway in her ready room. ", "Retz realizes that everyone he knew when he left his planet is long dead. ", "He tells the Captain that although he is an accomplished pilot, he lacks the courage of his associates and they made a mistake choosing him. ", "Janeway disagrees, telling Retz that for someone whose life has been turned upside down, he is handling it well. ", "Retz reminisces and tells Janeway that when he was a child lying in his crib, his first memory was not of his mother's face, but of the sky ship toy hanging above, and now he is the only one of his kind to know its true name: Voyager. ", "It is obvious that he, much like the rest of his species, has always fantasized about what the sky ship is really like. ", "Retz then wonders if Voyager will be the last thing he will ever see. ", "The captain informs him that she has no intention of keeping him aboard against his will, but warns that the longer he stays, the harder it could become for him to return home.", "\n\nRetz takes a moment to think about this and begins to sing in nostalgic reflection, \"Star of the night, star of the day, come to take my tears away. ", "Make my life always bright.\" ", "As he trails off, he tells Janeway that it's a child's prayer to Voyager. ", "The captain hopes that Retz is not too disappointed in discovering that Voyager is merely a starship. ", "Retz replies, \"How often does your very first dream come true?\" ", "And although every minute spent aboard means that months and even years pass on the surface, he agrees to help the crew interpret The Doctor's data and find a way to break orbit.", "\n\nAs Seven scans the surface she detects warp experimentation. ", "Soon after, Voyager is being attacked by antimatter torpedoes and a tricobalt device.", "\n\nAct Five\n\nThe weapons are soon causing major damage to Voyager's shields, so Janeway convinces Retz to go back to the planet to convince his people the ship is not a threat. ", "He agrees, and returns to his planet with Voyager's specifications, with Janeway hoping he can convince his planet's rulers to stop the attacks and help them leave orbit. ", "Before the pilot leaves, The Doctor tells him that, when he was living on the planet, he had a son who was probably long dead by this point. ", "He asks the pilot to contact the members of his son's family to tell them about him. ", "The pilot asks how The Doctor could have a son, as he is a hologram, The Doctor just answers \"it's a long story.\"", "\n\nAfter more attacks and a planet's year since the pilot returned, two ships appear next to Voyager and deploy a tractor beam to pull it clear. ", "Using a temporal compensator invented on his planet, Gotana-Retz returns one last time to say goodbye before the sky ship leaves forever.", "\n\nFinally, Gotana-Retz, now an old man, sits on a hillside and gazes wistfully into the sky as the star that is Voyager winks out and vanishes. ", "The hillside now overlooks a vast technological metropolis.", "\n\nMemorable quotes\n\n\"How does this sound? '", "The Weird Planet Where Time Moved Very Fast and So Did the People Who Lived There,' by Naomi Wildman…\"\n\n\"Your title is verbose. ", "I suggest you try to condense it.\"", "\n\n\"The Weird Planet\"\n\n\"Better, but it lacks precision. '", "The Weird Planet Displaced in Time'\"\n\n\"Perfect!\"", "\n\n\n\n- Naomi Wildman and Seven of Nine, discussing the title of Naomi's astronomy essay\n\n\n\n\"That's one planet that never showed up on the multiple choice exam.\"", "\n\n- Tom Paris\n\n\n\n\"If there's an intelligent species down there, we'll be able to track their development, not just for days or weeks, but for centuries.\"", "\n\n- Chakotay\n\n\n\n\"We might miss the rise and fall of a civilization.\"", "\n\n\"So, we'll watch the next one.\"", "\n\n- Chakotay and B'Elanna Torres\n\n\n\n\"What should I say?\"", "\n\n\"Oh…glad to meet you. ", "Where are you from? ", "Please stop shaking our planet.\"", "\n\n- Astronomer and Technician\n\n\n\n\"What if they're big purple blobs of protoplasm?\"", "\n\n\"Then you'll be the best-looking blob on the planet.\"", "\n\n\n\n- The Doctor and Janeway\n\n\n\n\"Captain, isn't it time we returned fire?\"", "\n\n\"We've done enough damage to these people over the last thousand years.\"", "\n\n- Tom Paris and Chakotay\n\n\n\n\"You're the best pilot we have, that's why you're on this mission. ", "This is no different than flying your favorite…\"\n\n\"Oh, it's different!\"", "\n\n\"I can't argue with that.\"", "\n\n- Terrina and Gotana-Retz\n\n\n\n\"Jason? ", "An unusual name.\"", "\n\n\"Yes. ", "He was my… son.\"", "\n\n\"But you're a hologram.\"", "\n\n\"lt's a long story.\"", "\n\n- Gotana-Retz and The Doctor\n\n\n\n\"If you've ever wanted to report more than the weather, now is your chance. ", "Tell them to clear Central Lake of all traffic: Orbital 1 is coming in for a landing.\"", "\n\n- Gotana-Retz, to the weather coordinator for Station 004\n\nBackground information\n\nContinuity and trivia\n\nOne day on the planet is slightly more than one second long (1.03 seconds) in normal time, so three years on the planet would only be 18.9 minutes in normal time. ", "This would mean that a hundred years on the planet would pass every 10.45 hours. ", "Since Voyager seems to have been in orbit for centuries of planetary time it is likely that the episode takes place over a few days of time for the crew.", "\n\nseems to have been in orbit for centuries of planetary time it is likely that the episode takes place over a few days of time for the crew. ", "This episode contains a scene in which a member of an alien species writes in English using a pen and ink. ", "This is unusual considering most alien writing depicted in Star Trek is made up of alien-looking characters.", "\n\nis made up of alien-looking characters. ", "Although Tuvok describes the planet as having a high rate of rotation \"like a quasar\", this property more accurately describes a pulsar.", "\n\nStar Trek: The Original Series had an episode entitled \" Wink of an Eye \" where Scalosians, moving too fast to be seen or heard (other than a faint buzzing sound), board the USS Enterprise and abduct Captain James T. Kirk.", "\n\nVideo and DVD releases\n\nStarring\n\nAlso starring\n\nGuest star\n\nCo-stars\n\nUncredited co-stars\n\nStand-ins\n\nReferences\n\nacceleration; almanac; altar; ammonium; amplitude modulation; anthropology; antimatter torpedo; aria; astronomy; Astronomer's grandfather; athlete; Belief system; cannon; carbon monoxide; carrier wave; Central Lake; Central Protectorate; class V planetary probe; coastline; concert hall; confinement beam; crib; Darek; decayed orbit; disorientation; docking port; doppler component; display buffer; dwarf star; elemental constant; epidermal; exile; family doctor; fire-fruit; frequency; god; Gotana-Retz' mother; gravimetric gradient; \"Ground Shaker\"; hemisphere; high orbit; holomatrix; hot air balloon; internal combustion; iron; Jefferies tube; Kelemane's planet; Kelemane's planet sport; Kelemane's species; Kelemane; kilometer; Klingon; lake; Lakeside; Launch Control/Tactical Command Center; logic; low orbit; lyric; Mareeza; mathematical constant; medical journal; meter; Milky Way Galaxy; Mountain; multiple-choice exam; mythology; numerical sequence; observatory; opera house; orbit; Orbital 1; palace; pat on the back; pre-warp society; Prime Directive; prime number; Protector; protoplasm; purple; quasar; radio transmission; Red River; religion; roommate; shooting star; \"Sky Ship\"; Sky Ship Friends; state; Station 004; surface; synchronous orbit; Tabreez, Jason; tachyon; Tactical Air Command; Tahal; technology; telescope; temporal compensator; temporal field; time frame; Torelius; tricobalt device; ultra-high frequency; warp-capable civilization; weather; weather coordinator; Weird Planet Displaced in Time, The\n\n\n\n" ]

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[ "The split-decision victory of Timothy Bradley over Manny Pacquiao on Saturday at the MGM Grand Garden Arena in Las Vegas has left promoter Bob Arum fuming angry, insisting there would be no rematch unless Nevada attorney general Catherine Cortez Masto launches an investigation.", "\n\nFans and members of the media have been accusing Arum of somehow rigging the match. ", "Bob Arum had the following comments:\n\n“I want to investigate whether there was any undue influence, whether the Nevada Athletic Commission gave any particular instruction and how they came to this conclusion.”", "\n\nHe continues to express his feelings that Manny Pacquiao had won the fight even the day after the fight, his decision remained unchanged.", "\n\n“If this was a subjective view that each of the judges honestly held, OK. ", "I would still disagree, but then we’re off the hook in terms of there being no conspiracy. ", "But there needs to be an independent investigation because it strains credulity that an event everybody saw as so one-sided one way all three judges saw it as close. ", "It strains credulity.”", "\n\nTimothy Bradley won Manny Pacquiao‘s WBO World Welterweight Championship form the decisions of C.J. Ross and Duane Ford scoring the fight 115-133 for Bradley and judge Jerry Roth scoring the fight 115-113 Pacquiao.", "\n\nThere are a select few individuals in the boxing community who believe that Bradley deserved the victory; a good portion of the boxing world scored the fight in favour of Pacquiao.", "\n\nRegardless of the outcome and despite all the controversy, the outcome is not going to change; Bradley won the fight.", "\n\nWhether this scratch on Pacquiao’s record will oust him from his shared position atop the rankings, action is inevitable.", "\n\nCheck out whole the fight below and tell us who you think won the fight on Twitter @EliteSportsBlog" ]

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[ "[The interhemispheric brain asymmetry of the rabbit in a state of \"animal hypnosis\"].", "\nBy the method of forced immobilization the rabbits were brought into the state of \"animal hypnosis\" (immobilization reflex), and their ECoG was recorded, which was further processed on the computer. ", "It was found that during hypnosis a functional interhemispheric brain asymmetry was developed in rabbits with activity predominance in the right hemisphere. ", "The \"animal hypnosis\" is a phasic process: in the ECoG of the rabbit under hypnosis a regular alternation of delta and theta activity takes place. ", "Electrophysiological reconstructions in the rabbit brain during the change of its functional state correlate with the brain thermal reactions, revealed earlier." ]

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[ "DIY\n\nVTI is FSC® certified\n\nFSC (Forest Stewardship Council) is a collaborative venture of equals involving various forestry stakeholders who have come to a consensus on guidelines for sustainable forestry. ", "FSC respects the financial, social and natural interests.", "\n\nBeing FSC certified means the factory is able to document the specific origin of the raw timber has been used in the production of the various orders. ", "We are able to trace the raw timber from raw timber reception all the way through production to packaging and delivery." ]

{ "pile_set_name": "Pile-CC" }

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[ "29 U.S. Code § 1103 - Establishment of trust\n\nExcept as provided in subsection (b) of this section, all assets of an employee benefit plan shall be held in trust by one or more trustees. ", "Such trustee or trustees shall be either named in the trust instrument or in the plan instrument described in section\n1102(a) of this title or appointed by a person who is a named fiduciary, and upon acceptance of being named or appointed, the trustee or trustees shall have exclusive authority and discretion to manage and control the assets of the plan, except to the extent that—\n\n(1)the plan expressly provides that the trustee or trustees are subject to the direction of a named fiduciary who is not a trustee, in which case the trustees shall be subject to proper directions of such fiduciary which are made in accordance with the terms of the plan and which are not contrary to this chapter, or\n\n(2)authority to manage, acquire, or dispose of assets of the plan is delegated to one or more investment managers pursuant to section\n1102(c)(3) of this title.", "\n\n(b) Exceptions\n\nThe requirements of subsection (a) of this section shall not apply—\n\n(1)to any assets of a plan which consist of insurance contracts or policies issued by an insurance company qualified to do business in a State;\n\n(2)to any assets of such an insurance company or any assets of a plan which are held by such an insurance company;\n\n(3)to a plan—\n\n(A)some or all of the participants of which are employees described in section\n401(c)(1) of title\n26; or\n\n(B)which consists of one or more individual retirement accounts described in section\n408 of title\n26;\n\nto the extent that such plan’s assets are held in one or more custodial accounts which qualify under section\n401(f) or\n408(h) of title\n26, whichever is applicable.", "\n\n(4)to a plan which the Secretary exempts from the requirement of subsection (a) of this section and which is not subject to any of the following provisions of this chapter—\n\n(A)part 2 of this subtitle,\n\n(B)part 3 of this subtitle, or\n\n(C)subchapter III of this chapter; or\n\n(5)to a contract established and maintained under section\n403(b) of title\n26 to the extent that the assets of the contract are held in one or more custodial accounts pursuant to section\n403(b)(7) of title\n26.", "\n\n(6)Any plan, fund or program under which an employer, all of whose stock is directly or indirectly owned by employees, former employees or their beneficiaries, proposes through an unfunded arrangement to compensate retired employees for benefits which were forfeited by such employees under a pension plan maintained by a former employer prior to the date such pension plan became subject to this chapter.", "\n\n(c) Assets of plan not to inure to benefit of employer; allowable purposes of holding plan assets\n\n(1)Except as provided in paragraph (2), (3), or (4) or subsection (d) of this section, or under sections\n1342 and\n1344 of this title (relating to termination of insured plans), or under section\n420 of title\n26 (as in effect on July 6, 2012), the assets of a plan shall never inure to the benefit of any employer and shall be held for the exclusive purposes of providing benefits to participants in the plan and their beneficiaries and defraying reasonable expenses of administering the plan.", "\n\n(2)\n\n(A)In the case of a contribution, or a payment of withdrawal liability under part 1 of subtitle E of subchapter III of this chapter—\n\n(i)if such contribution or payment is made by an employer to a plan (other than a multiemployer plan) by a mistake of fact, paragraph (1) shall not prohibit the return of such contribution to the employer within one year after the payment of the contribution, and\n\n(ii)if such contribution or payment is made by an employer to a multiemployer plan by a mistake of fact or law (other than a mistake relating to whether the plan is described in section\n401(a) of title\n26 or the trust which is part of such plan is exempt from taxation under section\n501(a) of title\n26), paragraph (1) shall not prohibit the return of such contribution or payment to the employer within 6 months after the plan administrator determines that the contribution was made by such a mistake.", "\n\n(B)If a contribution is conditioned on initial qualification of the plan under section\n401 or\n403(a) of title\n26, and if the plan receives an adverse determination with respect to its initial qualification, then paragraph (1) shall not prohibit the return of such contribution to the employer within one year after such determination, but only if the application for the determination is made by the time prescribed by law for filing the employer’s return for the taxable year in which such plan was adopted, or such later date as the Secretary of the Treasury may prescribe.", "\n\n(C)If a contribution is conditioned upon the deductibility of the contribution under section\n404 of title\n26, then, to the extent the deduction is disallowed, paragraph (1) shall not prohibit the return to the employer of such contribution (to the extent disallowed) within one year after the disallowance of the deduction.", "\n\n(3)In the case of a withdrawal liability payment which has been determined to be an overpayment, paragraph (1) shall not prohibit the return of such payment to the employer within 6 months after the date of such determination.", "\n\n(d) Termination of plan\n\n(1)Upon termination of a pension plan to which section\n1321 of this title does not apply at the time of termination and to which this part applies (other than a plan to which no employer contributions have been made) the assets of the plan shall be allocated in accordance with the provisions of section\n1344 of this title, except as otherwise provided in regulations of the Secretary.", "\n\n(2)The assets of a welfare plan which terminates shall be distributed in accordance with the terms of the plan, except as otherwise provided in regulations of the Secretary.", "\n\nThis chapter, referred to in subsecs. (", "a)(1) and (b)(4), (6), was in the original “this Act”, meaning Pub. ", "L. 93–406, known as the Employee Retirement Income Security Act of 1974. ", "Titles I, III, and IV of such Act are classified principally to this chapter. ", "For complete classification of this Act to the Code, see Short Title note set out under section\n1001 of this title and Tables.", "\n\nSubsec. (", "b)(3). ", "Pub. ", "L. 101–239, § 7894(e)(3), redesignated cls. (", "i) and (ii) as subpars. (", "A) and (B), respectively, struck out “, to the extent that such plan’s assets are held in one or more custodial accounts which qualify under section\n401(f) or\n408(h) of title\n26, whichever is applicable” before the semicolon in subpar. (", "B), and inserted concluding provision “to the extent that such plan’s assets are held in one or more custodial accounts which qualify under section\n401(f) or\n408(h) of title\n26, whichever is applicable.”", "\n\nSubsec. (", "c)(2)(A). ", "Pub. ", "L. 101–239, § 7894(e)(1)(A), in introductory provisions, made technical amendment to reference to part 1 of subtitle E of subchapter III of this chapter to correct reference to corresponding part of original Act, requiring no change in text, and in cls. (", "i) and (ii), inserted “if such contribution or payment is” before “made by an employer”.", "\n\nSubsec. (", "c)(3), (4). ", "Pub. ", "L. 101–239, § 7881(k), redesignated par. (", "4) as (3) and struck out former par. (", "3) which read as follows: “In the case of a contribution which would otherwise be an excess contribution (as defined in section\n4979(c) of title\n26) paragraph (1) shall not prohibit a correcting distribution with respect to such contribution from the plan to the employer to the extent permitted in such section to avoid payment of an excise tax on excess contributions under such section.”", "\n\n1987—Subsec. (", "c)(2)(B). ", "Pub. ", "L. 100–203, § 9343(c)(1), amended subpar. (", "B) generally. ", "Prior to amendment, subpar. (", "B) read as follows: “If a contribution is conditioned on qualification of the plan under section\n401,\n403(a), or\n405(a) of title\n26, and if the plan does not qualify, then paragraph (1) shall not prohibit the return of such contributions to the employer within one year after the date of denial of qualification of the plan.”", "\n\nSubsec. (", "c)(2)(A). ", "Pub. ", "L. 96–364, § 410(a), substituted provisions relating to contributions or payments of withdrawal liability under part 1 of subtitle E of subchapter III of this chapter made by an employer to a plan by a mistake of fact, and by an employer to a multiemployer plan by a mistake of fact or law, for provisions relating to contributions made by an employer by a mistake of fact.", "\n\nAmendment by Pub. ", "L. 106–170applicable to qualified transfers occurring after Dec. 17, 1999, see section 535(c)(1) ofPub. ", "L. 106–170, set out as a note under section\n420 of Title\n26, Internal Revenue Code.", "\n\nEffective Date of 1990 Amendment\n\nAmendment by Pub. ", "L. 101–508applicable to qualified transfers under section\n420 of title\n26 made after Nov. 5, 1990, see section 12012(e) ofPub. ", "L. 101–508, set out as a note under section\n1021 of this title.", "\n\nEffective Date of 1989 Amendment\n\nAmendment by section 7881(k) ofPub. ", "L. 101–239effective, except as otherwise provided, as if included in the provision of the Pension Protection Act, Pub. ", "L. 100–203, §§ 9302–9346, to which such amendment relates, see section 7882 ofPub. ", "L. 101–239, set out as a note under section\n401 of Title\n26, Internal Revenue Code.", "\n\nAmendment by section 7891(a)(1) ofPub. ", "L. 101–239effective, except as otherwise provided, as if included in the provision of the Tax Reform Act of 1986, Pub. ", "L. 99–514, to which such amendment relates, see section 7891(f) ofPub. ", "L. 101–239, set out as a note under section\n1002 of this title.", "\n\nSection 7894(e)(1)(B) ofPub. ", "L. 101–239provided that: “The amendments made by subparagraph (A) [amending this section] shall take effect as if included in section 410 of the Multiemployer Pension Plan Amendments Act of 1980 [Pub. ", "L. 96–364].”", "\n\nAmendment by section 7894(e)(3) ofPub. ", "L. 101–239effective, except as otherwise provided, as if originally included in the provision of the Employee Retirement Income Security Act of 1974, Pub. ", "L. 93–406, to which such amendment relates, see section 7894(i) ofPub. ", "L. 101–239, set out as a note under section\n1002 of this title.", "\n\nAmendment by section 410(a) ofPub. ", "L. 96–364effective Jan. 1, 1975, except with respect to contributions received by a collectively bargained plan maintained by more than one employer before Sept. 26, 1980, see section 410(c) ofPub. ", "L. 96–364, set out as a note under section\n401 of Title\n26, Internal Revenue Code.", "\n\nRegulations\n\nSecretary authorized, effective Sept. 2, 1974, to promulgate regulations wherever provisions of this part call for the promulgation of regulations, see sections\n1031 and\n1114 of this title.", "\n\nApplicability of Amendments by Subtitles A and B of Title I of Pub. ", "L. 109–280\n\nFor special rules on applicability of amendments by subtitles A (§§ 101–108) and B (§§ 111–116) of title I of Pub. ", "L. 109–280to certain eligible cooperative plans, PBGC settlement plans, and eligible government contractor plans, see sections 104, 105, and 106 ofPub. ", "L. 109–280, set out as notes under section\n401 of Title\n26, Internal Revenue Code." ]

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[ "The present invention concerns tetrahydro xcex3-carbolines having a broad therapeutic potential. ", "It further relates to their preparation, compositions comprising them and their use as a medicine.", "\nU.S. Pat. ", "No. ", "4,636,563, published on Jan. 13, 1987, and U.S. Pat. ", "No. ", "4,672,117, published on Jun. 9, 1987, disclose 2-(heteroaryl-alkyl)-tetrahydro-xcex3 carbolines having antipsychotic activity. ", "EP-A-0,705,832, published on Apr. 10, 1996, discloses 1,2,3,4-terahydro-9H-pyrido3,4-b]indolyl-alkyl-1,3-dihydro-2H-benzimidazolones as serotonergic modulators.", "\nThe compounds of the present invention are novel and have an interesting broad-spectrum receptor-binding profile. ", "In comparison to the structurally related known compounds, they surprisingly exhibit a greater therapeutic breadth.", "\nThe present invention concerns the compounds of formula \nthe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein:\nR1 is hydrogen, C1-6alkyl, aryl or C1-6alkyl substituted with aryl;\nR2 is each independently a halogen, hydroxy, C1-6alkyl, C1-6alkyloxy or nitro;\nn is 0, 1, 2 or 3;\nAlk is C1-6alkanediyl;\nD is 2(3H)benzoxazolone-3-yl or a radical of formula \nxe2x80x83wherein\neach X independently represents O, S or NR12;\nR3 is hydrogen, C1-6alkyl, aryl or arylC1-6alkyl;\nR4 is hydrogen, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, mono- or di(C1-6alkyl)amino or mono- or di(arylC1-6alkyl)amino;\nR5, R6, R7, R10, R11 and R12 each independently are hydrogen or C1-6alkyl;\nR8 and R9 each independently are hydrogen, C1-6alkyl or aryl; or\nR4 and R5 taken together may form a bivalent radical xe2x80x94R4xe2x80x94R5xe2x80x94 of formula \nxe2x80x83wherein one or two hydrogen atoms of said radicals (a-1) to (a-5) each independently may be replaced by halogen, C1-6alkyl, arylC1-6alkyl, trifluoromethyl, amino, hydroxy, C1-6alkyloxy or C1-6alkylcarbonyloxy; or where possible, two geminal hydrogen atoms may be replaced by C1-6alkylidene or arylC1-6alkylidene; or\nxe2x80x94R4xe2x80x94R5xe2x80x94 may also be \nxe2x80x83wherein one or where possible two or three hydrogen atoms in said radicals (a-6) to (a-14) each independently may be replaced by C1-6alkyl or aryl; and\naryl is phenyl or phenyl substituted with a halogen or C1-6alkyl.", "\nAs used in the foregoing definitions the term halogen is generic to fluoro, chloro, bromo and iodo. ", "The term C1-4alkyl defines straight and branched saturated hydrocarbons, having from 1 to 4 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylethyl, 1,1-dimethylethyl, 2-methylpropyl and the like. ", "The term C1-6alkyl is meant to include C1-6alkyl and the higher homologues thereof having 5 or 6 carbon atoms such as, for example, pentyl, hexyl or the like. ", "The term C1-10alkyl is meant to include C1-6alkyl radicals and the higher homologues thereof having 7 to 10 carbon atoms such as, for example, heptyl, octyl, nonyl, decyl and the like. ", "The term C1-4alkanediyl defines bivalent straight or branch chained alkanediyl radicals having from 1 to 4 carbon atoms such as, for example, methylene, 1,2-ethanediyl, 1,3-propanediyl, 1,4-butanediyl and the like; the term C1-6alkanediyl is meant to include C1-4alkanediyl and the higher homologues thereof having 5 or 6 carbon atoms such as, for example, 1,5-pentanediyl, 1,6-hexanediyl and the like; the term C1-6alkylidene defines bivalent straight or branch chained alkylidene radicals having from 1 to 6 carbon atoms such as, for example, methylene, ethylidene, 1-propylidene, 1-butylidene, 1-pentylidene, 1-hexylidene and the like.", "\nAlso as used hereinafter, the term benzyl refers to phenylmethyl. ", "Other names for the term xcex3-carboline are 5H-pyrido[4,3-b]indole, 3-azacarbazole and 3-azarbazole.", "\nThe addition salts as mentioned herein are meant to comprise the therapeutically active addition salt forms which the compounds of formula (I) are able to form with appropriate acids, such as, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclamic, salicylic, p-amino-salicylic, pamoic and the like acids.", "\nThe pharmaceutically acceptable addition salts as mentioned hereinabove are also meant to comprise the therapeutically active non-toxic base, in particular, a metal or amine addition salt forms which the compounds of formula (I) are able to form. ", "Said salts can conveniently be obtained by treating the compounds of formula (I) containing acidic hydrogen atoms with appropriate organic and inorganic bases such as, for example, the ammonium salts, the alkali and earth alkaline metal salts, e.g. the lithium, sodium, potassium, magnesium, calcium salts and the like, salts with organic bases, e.g. the benzathine, N-methyl-D-glucamine, hydrabamine salts, and salts with amino acids such as, for example, arginine, lysine and the like.", "\nConversely said salt forms can be converted by treatment with an appropriate base or acid into the free acid or base form.", "\nThe term addition salt as used hereinabove also comprises the solvates which the compounds of formula (I) are able to form and said solvates are meant to be included within the scope of the present invention. ", "Examples of such solvates are, e.g. the hydrates, alcoholates and the like.", "\nThe N-oxide forms of the compounds of formula (I) are meant to comprise those compounds of formula (I) wherein one or several nitrogen atoms are oxidized to the so-called N-oxide.", "\nThe term stereochemically isomeric forms as used herein defines all the possible isomeric forms in which the compounds of formula (I) may occur. ", "Unless otherwise mentioned or indicated, the chemical designation of compounds denotes the mixture of all possible stereochemically isomeric forms, said mixtures containing all diastereomers and enantiomers of the basic molecular structure.", "\nSome of the compounds of formula (I) may also exist in their tautomeric forms. ", "Such forms although not explicitly indicated in the above formula are intended to be included within the scope of the present invention.", "\nWhenever used hereinafter, the term compounds of formula (I) is meant to include also the N-oxide forms, the pharmaceutically acceptable addition salts and all stereoisomeric forms.", "\nA special group of compounds includes those compounds of formula (I) wherein one or more of the following restrictions apply:\n1) R2 is halogen, hydroxy, C1-6alkyl or C1-6alkyloxy;\n2) n is 0 or 1;\n3) Alk is C1-4alkanediyl; preferably, Alk is 1,2-ethanediyl;\n4) D is a radical of formula (a) wherein R3 is C1-6alkyl, aryl or arylC1-6alkyl; R4 is amino, mono- or di(C1-6alkyl)amino, or mono- or di(arylC1-6alkyl)amino; or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2) or (a-5) wherein one or two hydrogen atoms each independently may be replaced by halogen, C1-6alkyl, trifluoromethyl or C1-6alkyloxy, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-6), (a-7), (a-8), (a-11), (a-13) or (a-14) wherein one or where possible two hydrogen atoms each independently may be replaced by C1-6alkyl;\n5) D is a radical of formula (b) and R6 and R7 are suitably methyl;\n6) D is a radical of formula (c) and R8 is suitably hydrogen, methyl or phenyl;\n7) D is a radical of formula (d) wherein R9 is aryl; and suitably, R9 is 4-fluoro-phenyl, and the piperidine ring is connected in the 3- or 4-position to the remainder of the molecule;\n8) D is a radical of formula (e) wherein X is S or NH and R10 is hydrogen; or\n9) D is a radical of formula (f) wherein X is S or NCH3.", "\nIn case n is 1, the R2 substituent is suitably positioned in the 6-, 7- or 8-position of the xcex3-carboline moiety, preferably in the 7- or 8-position, and R2 is preferably chloro, fluoro, methyl, hydroxy or methoxy.", "\nSuitably, D is a radical of formula (a), (d), (e) or (f).", "\nAn interesting group of compounds includes those compounds of formula (I) wherein R1 is hydrogen or aryl; R2 is halogen or C1-6alkyl; n is 0 or 1; Alk is C1-4alkanediyl; D is a radical of formula (a) or (e), especially a radical of formula (a) wherein R3 is C1-6alkyl and xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2), (a-5), (a-6), (a-7) or (a-8) wherein one or where possible two hydrogen atoms each independently may be replaced by C1-6alkyl, or a radical of formula (e) wherein X is S and R10 is hydrogen.", "\nAnother interesting group of compounds includes those compounds of formula (I) wherein R1 is hydrogen or C1-6alkyl; R2 is halogen, C1-6alkyl or C1-6alkyloxy; n is 0 or 1; Alk is C1-4alkanediyl; D is a radical of formula (a) or (f), especially a radical of formula (a) wherein R4 is amino, mono- or di(C1-6alkyl)amino or mono- or di(arylC1-6alkyl)amino, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2), (a-5), (a-6), (a-7), (a-8) or (a-11) wherein one or where possible two hydrogen atoms each independently may be replaced by C1-6alkyl or a radical of formula (f) wherein X is NR12.", "\nYet another interesting group of compounds includes those compounds of formula (I) wherein R2 is halogen, hydroxy, C1-6alkyl or C1-6alkyloxy; n is 0 or 1, Alk is C1-4alkanediyl; D is a radical of formula (a), (e) or (f), especially a radical of formula (a) wherein R3 is C1-6alkyl, R4 is amino, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2) or (a-5) wherein one or two hydrogen atoms each independently may be replaced by halogen, C1-6alkyl, trifluoromethyl or C1-6alkyloxy, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-6), (a-7), (a-8), (a-11), (a-13) or (a-14) wherein one or where possible two hydrogen atoms each independently may be replaced by C1-6alkyl, or a radical of formula (e) wherein X is S or NR12 and R10 is hydrogen, or a radical of formula (f) wherein X is S or NR12.", "\nStill another interesting group of compounds includes those compounds of formula (I) wherein R1 is hydrogen, C1-6alkyl or aryl; R2 is halogen, C1-6alkyl or C1-6alkyloxy; n is 0 or 1; Alk is C1-4alkanediyl; D is a radical of formula (a), (d) or (e), especially a radical of formula (a) wherein R3 is C1-6alkyl or arylC1-6alkyl, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-5) wherein one or two hydrogen atoms each independently may be replaced by a halogen, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-6) or (a-8), or a radical of formula (d) wherein R9 is aryl, or a radical of formula (e) wherein X is S or NR12 and R10 is hydrogen.", "\nParticular compounds are those compounds of formula (I) wherein R1 is hydrogen; n is 0 or n is 1 whereby R2 is a halogen, C1-6alkyl, or C1-6alkoxy; Alk is 1,2-ethanediyl and D is a radical of formula (a) or (f), especially a radical of formula (a) wherein R3 is C1-6alkyl, R4 is amino, R5 is C1-6alkyl, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2), (a-5), (a-6), (a-7), (a-8) or (a-11) wherein one hydrogen atom may be replaced by C1-6alkyl, or a radical of formula (f) wherein X is NR12 and R11 is C1-6alkyl; more in particular, wherein R1 is hydrogen; n is 0 or n is 1 whereby R2 is a chloro, methyl, or methoxy; Alk is 1,2-ethanediyl and D is a radical of formula (a) wherein R3 is methyl, R4 is amino, R5 is methyl, or xe2x80x94R4xe2x80x94R5xe2x80x94 is a radical of formula (a-2), (a-5), (a-6), (a-7), (a-8) or (a-11) wherein one hydrogen atom may be replaced by methyl, or D is a radical of formula (f) wherein X is Nxe2x80x94CH3 and R11 is methyl.", "\nOther particularly interesting compounds are those compounds of formula (I) wherein R1 is hydrogen; n is 0 or n is 1 whereby R2 is a halogen or C1-6alkyl; Alk is 1,2-ethanediyl and D is a radical of formula (a), especially a radical of formula (a) wherein R3 is C1-6alkyl, R4 and R5 are taken together to form xe2x80x94R4xe2x80x94R5xe2x80x94 of formula (a-2), (a-5), (a-6), (a-7) or (a-8) wherein one hydrogen atom may be replaced by C1-6alkyl; more in particular, wherein R1 is hydrogen; n is 0 or n is 1 whereby R2 is a chloro, fluoro or methyl; Alk is 1,2-ethanediyl and D is a radical of formula (a) wherein R3 is methyl, R4 and R5 are taken together to form xe2x80x94R4xe2x80x94R5xe2x80x94 of formula (a-2), (a-5), (a-6), (a-7) or (a-8) wherein one hydrogen atom may be replaced by methyl.", "\nA preferred set of compounds includes those compounds of formula (I) wherein R1 is hydrogen, methyl, n-butyl, phenyl, benzyl or 4-fluoro-phenyl.", "\nThe compounds of formula (I) can generally be prepared by N-alkylating a 1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole derivative of formula (II) with an alkylating reagent of formula (III) following the procedure described in EP-A-0,037,265, EP-A-0,070,053, EP-A-0,196,132 and in EP-A-0,378,255. ", "\nIn particular, intermediate (II) wherein W1 represents an appropriate reactive leaving group such as, for example, a halogen, e.g. chloro, bromo or iodo; a sulfonyloxy, e.g. methanesulfonyloxy, toluenesulfonyloxy, may be reacted with an intermediate of formula (II) in a reaction-inert solvent such as, for example, N,N-dimethylformamide or methylisobutylketon, in the presence of a suitable base such as, for example, sodiumcarbonate or triethylamine, and optionally in the presence of a catalyst such as, for example, potassium iodide.", "\nIn this and the following reactions, the reaction products may be isolated from the reaction medium and, if necessary, further purified according to methodologies generally known in the art such as extraction, crystallization, trituration and chromatography.", "\nThe compounds of formula (I) wherein D is a radical of formula (e), being represented by formula (I-e), may be prepared by N-acylating an intermediate of formula (IV) with an acyl derivative of formula (V) wherein W2 is an appropriate reactive leaving group such as, for example, a halogen, in a reaction-inert solvent such as, for example, chloroform, in the presence of a suitable base such as, for example, sodium carbonate or triethylamine. ", "\nThe compounds of formula (I) wherein D is a radical of formula (f), being represented by formula (I-f), can be prepared by N-alkylating an amine of formula (VI) with an intermediate of formula (VII) wherein W3 is an appropriate reactive leaving group such as, for example, a halogen, in a reaction-inert solvent such as, for example, ethanol or toluene, in the presence of a suitable base such as, for example, sodiumbicarbonate or sodiumcarbonate. ", "\nAlternatively, intermediates (VI) may be N-alkylated with intermediates (VII) in the presence of copper.", "\nThe compounds of formula (I) may be converted into each other following art-known functional group transformation reactions.", "\nThe compounds of formula (I) may also be converted to the corresponding N-oxide forms following art-known procedures for converting a trivalent nitrogen into its N-oxide form. ", "Said N-oxidation reaction may generally be carried out by reacting the starting material of formula (I) with an appropriate organic or inorganic peroxide. ", "Appropriate inorganic peroxides comprise, for example, hydrogen peroxide, alkali metal or earth alkaline metal peroxides, e.g. sodium peroxide, potassium peroxide; appropriate organic peroxides may comprise peroxy acids such as, for example, benzenecarboperoxoic acid or halo substituted benzenecarboperoxoic acid, e.g. 3-chlorobenzenecarboperoxoic acid, peroxoalkanoic acids, e.g. peroxoacetic acid, alkylhydroperoxides, e.g. tert-butyl hydroperoxide. ", "Suitable solvents are, for example, water, lower alkanols, e.g. ethanol and the like, hydrocarbons, e.g. toluene, ketones, e.g. 2-butanone, halogenated hydrocarbons, e.g. dichloromethane, and mixtures of such solvents.", "\nA number of intermediates and starting materials are commercially available or are known compounds which may be prepared according to art-known methodologies.", "\nFor example, some of the intermediates of formula (III) and their preparations are described in EP-A-0,037,265, EP-A-0,070,053, EP-A-0,196,132 and in EP-A-0,378,255.", "\nIntermediates of formula (II) wherein R1 is hydrogen, said intermediates being represented by formula (II-a), can generally be prepared by reacting an intermediate of formula (VIII) wherein P is a protective group such as, for example, an alkyloxycarbonyl group, with an intermediate of formula (IX) in a reaction-inert solvent, thus forming an intermediate of formula (X), and subsequently removing the protective group using art-known techniques such as, for instance, mixing the intermediate of formula (X) with potassium hydroxide in 2-propanol. ", "Alternatively, the intermediate of formula (X) may be further reacted with a reagent of formula (XI) wherein R1xe2x80x2 is the same as R1 but other than hydrogen and W4 is a suitable leaving group such as, for example, a halogen, in a suitable solvent such as, for example, hexamethylphosphorous triamide and the like, in the presence of an appropriate base such as, for example, sodium hydride, thus forming an intermediate of formula (XII) which may subsequently be deprotected using art-known techniques resulting in a compound of formula (II) wherein R1 is other than hydrogen, said compounds being represented by formula (II-b). ", "\nIntermediates of formula (IV) can be prepared by N-alkylating an intermediate of formula (II) with an intermediate of formula (XIII) wherein P is a protective group such as, for example, an alkyloxycarbonyl group, and W5 is a suitable leaving group such as, for example, a p-toluenesulfonyloxy group and the like, in a reaction-inert solvent such as, for example, N,N-dimethylformamide, and in the presence of a suitable base such as, for example, sodium carbonate. ", "The thus formed intermediate may be deprotected using art-known deprotection techniques. ", "\nIntermediates of formula (VI) may be prepared by N-alkylating an intermediate of formula (II) with an intermediate of formula (XIV) wherein P is a protective group such as, for example, an alkyloxycarbonyl group, and W6 is a suitable leaving group such as, for example, a halogen, in a reaction-inert solvent such as, for example, methylisobutylketon, in the presence of a suitable base such as, for example, sodium carbonate, and optionally in the presence of a catalyst such as, for instance, potassium iodide. ", "The thus formed intermediate may be deprotected using art-known deprotection techniques. ", "\nIntermediates of formula (VI) wherein Alk is 1,3-propanediyl and R11 is hydrogen, said intermediates being represented by formula (VI-3) may suitably be prepared by reacting an intermediate of formula (II) with acrylonitrile in a reaction-inert solvent such as, for example, 2-propanol, and in the presence of a suitable catalyst such as, for example, a quaternary ammonium compound, e.g. Aliquat 336, thus forming a nitrile derivative of formula (XV) which may subsequently be reduced to the corresponding amine derivative using art-known reduction techniques as there are, for example, the use of hydrogen with Raney Nickel as a catalyst in methanol, optionally in the presence of ammonia. ", "\nIntermediates of formula (VI) wherein Alk is 1,4-butanediyl and R11 is hydrogen, said intermediates being represented by formula (VI-4) may suitably be prepared by reacting an intermediate of formula (II) with an intermediate of formula (XVI) wherein W7 is a suitable leaving group such as, for example a halogen, in a reaction-inert solvent such as, for example, methylisobutylketon, and in the presence of a suitable base such as, for example, sodium carbonate, and optionally in the presence of a catalyst such as, for instance, potassium iodide, thus forming a nitrile derivative of formula (XVII) which may subsequently be reduced to the corresponding amine derivative using art-known reduction techniques as there are, for example, the use of hydrogen with Raney Nickel as a catalyst in methanol, optionally in the presence of ammonia. ", "\nSome of the compounds of formula (I) and some of the intermediates in the present invention contain at least one asymmetric carbon atom. ", "Pure stereochemically isomeric forms of said compounds and said intermediates can be obtained by the application of art-known procedures. ", "For example, diastereoisomers can be separated by physical methods such as selective crystallization or chromatographic techniques, e.g. counter current distribution, liquid chromatography and the like methods. ", "Enantiomers can be obtained from racemic mixtures by first converting said racemic mixtures with suitable resolving agents such as, for example, chiral acids, to mixtures of diastereomeric salts or compounds; then physically separating said mixtures of diastereomeric salts or compounds by, for example, selective crystallization or chromatographic techniques, e.g. liquid chromatography and the like methods; and finally converting said separated diastereomeric salts or compounds into the corresponding enantiomers.", "\nPure stereochemically isomeric forms of the compounds of formula (I) may also be obtained from the pure stereochemically isomeric forms of the appropriate intermediates and starting materials, provided that the intervening reactions occur stereospecifically. ", "The pure and mixed stereochemically isomeric forms of the compounds of formula (I) are intended to be embraced within the scope of the present invention.", "\nThe compounds of formula (I), their pharmaceutically acceptable addition salts, stereochemically isomeric forms, or N-oxide forms thereof, all show a particular affinity for serotonin receptors, such as, 5-hydroxytryptamine receptors of the 5HT1- and 5-HT2-type, and have an antagonistic, partially antagonistic or agonistic effect thereon. ", "Apart from their serotonergic receptor affinity, the present compounds also bind as ligands on the xcex12- or dopamine receptors, or selectively inhibit serotonin reuptake. ", "This broad-spectrum receptor-binding profile of the present compounds gives them a great therapeutic breadth. ", "They are useful in controlling diseases which are characterized by disturbances of the serotonergic system, in particular with involvement of 5HT2-type receptors. ", "They are therefore suitable for treating disorders of the central nervous system including psychotic disorders such as, e.g. schizophrenia, tension and depression states, neuroses, psychoses, bipolar disorders, aggressive behaviour, anxiety and the like. ", "Further, serotonin is a potent broncho- and vasoconstrictor and thus the present compounds acting as antagonists on the serotonin receptors may also be used against hypertension and vascular disorders such as, migraine and migraine related disorders. ", "Compounds controlling the serotonergic system have been associated with a number of other properties such as, the suppression of appetite and promotion of weight loss, which may prove effective in combatting obesity; the alleviation of withdrawal symptoms in addicts trying to discontinue drinking and smoking habits; and also with gastrointestinal disorders such as, e.g. colonkinetic disturbances.", "\nAlso the inhibitory activity of a particular group of the present compounds on the reuptake of serotonin contributes to the effectiveness to treat tension and depression states.", "\nAn additional feature of the present compounds is that they have central xcex12-adrenoceptor antagonistic activity. ", "Central xcex12-adrenoceptor antagonists are known to increase noradrenaline release by blocking presynaptic xcex12-receptors which exert an inhibiting control over the release of the neurotransmitter. ", "By increasing the noradrenaline concentrations, xcex12-antagonists can be used particularly for the treatment or prophylaxis of depression, and are also potentially useful in the treatment of Alzheimer\"\"s disease and dementia as it is known that xcex12-antagonists promote the release of acetylcholine (Tellez et al. ", "1997, J. Neurochem. ", "68:778-785).", "\nA particular group of the present compounds exhibits. ", "a pronounced affinity for dopaminergic receptors which in combination with an affinity for serotonergic receptors is of therapeutic significance in the treatment of psychosis.", "\nThe 5-HT2 receptor-binding profile of the compounds of formula (I) is discussed in the pharmacological example C.1. ", "The binding profile for other recptors such as, the xcex12-adrenergic or the dopaminergic receptors, may be demonstrated using analogous radioligand binding studies. ", "Further, the serotonergic properties of the present compounds may be evidenced by the xe2x80x9capomorphine, tryptamine, norepinephrine (ATN) test in ratsxe2x80x9d, described in Arch. ", "Int. ", "Pharmacodyn., ", "227, 238-253 (1977).", "\nThe present invention thus relates to compounds of formula (I) as defined hereinabove for use as a medicine. ", "Also, the present invention relates to the use of the present compounds for the manufacture of a medicament for treating depression, anxiety and psychosis.", "\nIn view of the usefulness of the subject compounds in the treatment or prevention of the above-mentioned disorders, the present invention provides a method of treating warm-blooded animals suffering from such disorders, in particular depression, anxiety and psychosis, said method comprising the systemic administration of a therapeutic effective amount of a compound of formula (I), a N-oxide or a pharmaceutically acceptable addition salt thereof, effective in treating disorders associated with the serotonergic system\nIn general it is contemplated that an effective therapeutic daily amount would be from about 0.01 mg/kg to about 4 mg/kg body weight. ", "The exact dosage to be used in the treatment of any of the above-mentioned disorders must be subjectively determined by the attending physician. ", "The variables involved include the severity of the disorder and the size, age and response pattern of the patient.", "\nFor administration purposes, the subject compounds may be formulated into various pharmaceutical compositions comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound of formula (I). ", "To prepare the pharmaceutical compositions of this invention, an effective amount of the particular compound, in addition salt or in free acid or base form, as the active ingredient is combined in intimate admixture with a pharmaceutically acceptable carrier, which may take a wide variety of forms depending on the form of preparation desired for administration. ", "These pharmaceutical compositions are desirably in unitary dosage form suitable, preferably, for administration orally, percutaneously, or by parenteral injection. ", "For example, in preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed, such as, for example, water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, syrups, elixirs and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, disintegrating agents and the like in the case of powders, pills, capsules and tablets. ", "Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. ", "For parenteral compositions, the carrier will usually comprise sterile water, at least in large part, though other ingredients, for example, to aid solubility, may be included. ", "Injectable solutions, for example, may be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution. ", "Injectable solutions containing compounds of formula (I) may be formulated in an oil for prolonged action. ", "Appropriate oils for this purpose are, for example, peanut oil, sesame oil, cottonseed oil, corn oil, soy bean oil, synthetic glycerol esters of long chain fatty acids and mixtures of these and other oils. ", "Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed. ", "In the compositions suitable for percutaneous administration, the carrier optionally comprises a penetration enhancing agent and/or a suitable wettable agent, optionally combined with suitable additives of any nature in minor proportions, which additives do not cause any significant deleterious effects on the skin. ", "Said additives may facilitate the administration to the skin and/or may be helpful for preparing the desired compositions. ", "These compositions may be administered in various ways, e.g., as a transdermal patch, as a spot-on or as an ointment. ", "Addition salts of (I) due to their increased water solubility over the corresponding free base or free acid form, are obviously more suitable in the preparation of aqueous compositions.", "\nIt is especially advantageous to formulate the aforementioned pharmaceutical compositions in dosage unit form for ease of administration and uniformity of dosage. ", "Dosage unit form as used in the specification and claims herein refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect, in association with the required pharmaceutical carrier. ", "Examples of such dosage unit forms are tablets (including scored or coated tablets), capsules, pills, powder packets, wafers, injectable solutions or suspensions, teaspoonfuls, tablespoonfuls and the like, and segregated multiples thereof." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Lay theories of the causes of alcoholism.", "\nThis paper investigates the range, structure and determinants of lay people's implicit theories of alcoholism. ", "The different explicit medical and psychological theories are reviewed as are studies on lay beliefs about alcoholism and heavy drinking. ", "After a number of interviews in which people were asked to list what they believed to be the major causes of alcoholism, 265 people completed a questionnaire in which they rated 30 explanations for their importance in explaining the causes of alcoholism. ", "Females more than males believed alcoholics to be socially inadequate and anxious and that there was too much social pressure and not enough prohibitions against drinking. ", "Middle-aged rather than younger or older people tended to explain alcoholism in terms of poor education, social and cultural pressures and biological or genetic mechanisms. ", "However, there were few differences in the ratings of heavy, moderate, light and non-drinkers. ", "Factor analysis revealed six factors labelled psychological stress, personal and social problems, psychoanalytic theories, sociocultural explanations, biological or genetic explanations and social desirability or pressure. ", "The results are discussed in terms of the research on lay understandings of psychological and medical phenomena, and the relationship between explicit and implicit theories." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "unit notifier;\n\n{$mode objfpc}{$H+}\n(* A trivial unit that uses libnotify on Linux and a timed out TPopupNotify on other platforms.", "\n\n Does very little, on linux it just calls libnotify, https://github.com/ik5/libnotify-fpc\n On Non-Linux, it calls TPopupNotifier, sets a timer and removes the Popup after the set\n time (in mS). ", " In both cases, it then destroys itself !", "\n\n Yes, you call create but YOU DO NOT FREE it !", "\n\n To use it, grab libnotify.pas, add it and this unit to your Lazarus project and do\n something like this -\n\n procedure TForm1.Button2Click(Sender: TObject);\n var\n Notifier : TNotifier;\n begin\n Notifier := TNotifier.", "Create;\n Notifier.", "ShowTheMessage('This is Title', 'and this is the message', 15000); // 15 seconds\n // Note, don't free it, it frees itself.", "\n end;\n\n On Linux, multitheading must be enabled, in the project (lpr) file, add\n {$DEFINE UseCThreads} immediatly above the first \"uses\" line.", "\n\n On Linux, to compile you need the dev version of libnotify but at run time all\n that is needed is libnotify and it appears to be installed on most if not all distros.", "\n\n On tomboy-ng, my model is that \"oh, you might like to know\" type notifications take the common\n 6 seconds. ", "Things the end user might really need to know, such as sync drive not being available\n I give 12 seconds. ", "Something, really urgent (I don't have any) might get longer. ", "Its incorrect\n to leave messages that really don't need user action there for very long.", "\n\n --------- License --------------\n\n Copyright (C) 2020 David Bannon\n\n This library is free software; you can redistribute it and/or modify it\n under the terms of the GNU Library General Public License as published by\n the Free Software Foundation; either version 2 of the License, or (at your\n option) any later version.", "\n\n This program is distributed in the hope that it will be useful, but WITHOUT\n ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or\n FITNESS FOR A PARTICULAR PURPOSE. ", "See the GNU Library General Public License\n for more details.", "\n\n You should have received a copy of the GNU Library General Public License\n along with this library; if not, write to the Free Software Foundation,\n Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA.", "\n*)\n\ninterface\n\nuses\n Classes, SysUtils, fpTimer{$ifdef Linux}, libnotify{$else}, PopupNotifier {$endif} ;\n\nType\n\n{ TNotifier }\n\n TNotifier = class\n\n private\n {$ifdef LINUX}\n LNotifier : PNotifyNotification;\n {$else}\n LocalTimer : TFPTimer;\n PopupNotifier: TPopupNotifier;\n procedure TimerFinished( Sender : TObject );\n {$endif}\n public\n procedure ShowTheMessage(const Title, Message : string; ShowTime : integer = 6000);\n destructor Destroy; Override;\n constructor Create();\nend;\n\nimplementation\n\n\n\nprocedure TNotifier.", "ShowTheMessage(const Title, Message : string; ShowTime : integer);\nbegin\n {$ifdef LINUX}\n notify_init(argv[0]);\n LNotifier := notify_notification_new (pchar(Title), pchar(Message), pchar('dialog-information'));\n notify_notification_set_timeout(LNotifier, ShowTime); // figure is mS\n notify_notification_show (LNotifier, nil);\n notify_uninit;\n Destroy;\n // Should also check for errors and use TPopupNotifier if Notify won't work\n // But that will have to wait until I find a Linux where it does not work .....\n {$else}\n // Non Linux must use TPopupNotifier\n PopupNotifier := TPopupNotifier.", "Create(nil);\n PopupNotifier.", "Text := Message;\n PopupNotifier.", "Title := Title;\n PopupNotifier.show;\n LocalTimer := TFPTimer.create(nil);\n LocalTimer.", "Interval := ShowTime;\n LocalTimer.", "OnTimer:= @TimerFinished;\n LocalTimer.", "Enabled := True;\n {$endif}\nend;\n\n{$ifndef LINUX}\nprocedure TNotifier.", "TimerFinished( Sender : TObject );\nbegin\n // writeln('Timer finished');\n LocalTimer.", "Enabled := false;\n PopupNotifier.hide;\n Destroy;\nend;\n{$endif}\n\ndestructor TNotifier.", "Destroy;\nbegin\n {$ifndef LINUX}\n freeandnil(PopupNotifier);\n freeandnil(LocalTimer);\n {$endif}\n inherited Destroy;\nend;\n\nconstructor TNotifier.", "Create();\nbegin\n inherited Create();\nend;\n\nend.", "\n\n" ]

{ "pile_set_name": "Github" }

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[ "---\ntitle: 源自定义（WCF 数据服务）\nms.date: 03/30/2017\ndev_langs:\n- csharp\n- vb\nhelpviewer_keywords:\n- WCF Data Services, feeds\n- WCF Data Services, Atom protocol\n- Atom Publishing Protocol [WCF Data Services]\n- WCF Data Services, customizing feeds\nms.assetid: 0d1a39bc-6462-4683-bd7d-e74e0fd28a85\nms.openlocfilehash: bf25737d98a880ac720318de18b687b4df5b0708\nms.sourcegitcommit: 5b475c1855b32cf78d2d1bbb4295e4c236f39464\nms.translationtype: MT\nms.contentlocale: zh-CN\nms.lasthandoff: 09/24/2020\nms.locfileid: \"91172627\"\n---\n# <a name=\"feed-customization-wcf-data-services\"></a>源自定义（WCF 数据服务）\n\nWCF 数据服务使用 Open Data Protocol (OData) 将数据公开为源。 ", "OData 支持用于数据馈送的 Atom 和 JavaScript 对象表示法 (JSON) 格式。 ", "使用 Atom 馈送时，OData 提供一种标准方法，用于将数据（如实体和关系）序列化为可包含在 HTTP 消息正文中的 XML 格式。 ", "OData 定义实体中包含的数据与 Atom 元素之间的默认实体属性映射。 ", "有关详细信息，请参阅 [OData： Atom 格式](https://www.odata.org/documentation/odata-version-2-0/atom-format/)。 ", " \n \n 您的应用程序方案可能要求以自定义方式而非标准源格式序列化数据服务返回的属性数据。 ", "使用 OData，你可以在数据馈送中自定义序列化，以便可以将实体的属性映射到某个条目的未使用的元素和属性，或者映射到源中条目的自定义元素。 ", " \n \n> [!", "NOTE]\n> 只有 Atom 馈送才支持源自定义。 ", "当为返回的源请求 JSON 格式时，不会返回自定义源。 ", " \n \n 使用 WCF 数据服务，可以通过手动将属性应用于数据模型中的实体类型，为 Atom 有效负载定义备用实体属性映射。 ", "数据服务的数据源提供程序确定应当如何应用这些特性。 ", " \n \n> [!", "IMPORTANT]\n> 定义自定义源时，必须保证已定义自定义映射的所有实体属性都包含在投影中。 ", "如果投影中不包含某个已映射的实体属性，则可能会丢失数据。 ", "有关详细信息，请参阅 [查询投影](query-projections-wcf-data-services.md)。 ", " \n \n## <a name=\"customizing-feeds-with-the-entity-framework-provider\"></a>使用实体框架提供程序自定义源 \n\n 在 .edmx 文件中，用于实体框架提供程序的数据模型以 XML 格式表示。 ", "在这种情况下，用于定义自定义源的特性将会添加到表示数据模型中的实体类型和属性的 `EntityType` 和 `Property` 元素中。 ", "这些源自定义属性未定义为[ \\[ MC-CSDL \\] ：概念架构定义文件格式](/openspecs/windows_protocols/mc-csdl/c03ad8c3-e8b7-4306-af96-a9e52bb3df12)，这是实体框架提供程序用于定义数据模型的格式。 ", "因此，必须在某个特定的架构命名空间中声明源自定义特性，此架构命名空间应按 `m=\"http://schemas.microsoft.com/ado/2007/08/dataservices/metadata\"` 格式定义。 ", "以下 XML 片段显示应用于 `Property` 实体类型的 `Products` 元素的源自定义特性，这些特性定义 `ProductName`、`ReorderLevel` 和 `UnitsInStock` 属性。 ", " \n \n [!", "code-xml[Astoria Custom Feeds#EdmFeedAttributes](../../../../samples/snippets/xml/VS_Snippets_Misc/astoria_custom_feeds/xml/northwind.csdl#edmfeedattributes)] \n \n 这些特性为 `Products` 实体集生成以下自定义数据源。 ", "在自定义数据源中，`ProductName` 属性值同时显示在 `author` 元素以及 `ProductName` 属性元素中，`UnitsInStock` 属性显示在具有其自己的唯一命名空间并且其 `ReorderLevel` 属性作为特性的自定义元素中： \n \n [!", "code-xml[Astoria Custom Feeds#EdmFeedResultProduct](../../../../samples/snippets/xml/VS_Snippets_Misc/astoria_custom_feeds/xml/edmfeedresult.xml#edmfeedresultproduct)] \n \n 有关详细信息，请参阅 [如何：利用实体框架提供程序自定义源](how-to-customize-feeds-with-ef-provider-wcf-data-services.md)。 ", " \n \n> [!", "NOTE]\n> 由于实体设计器不支持数据模型扩展，因此必须手动修改包含数据模型的 XML 文件。 ", "有关实体数据模型工具生成的 .edmx 文件的详细信息，请参阅实体框架) 中的 [.Edmx 文件概述 (](/previous-versions/dotnet/netframework-4.0/cc982042(v=vs.100))。 ", " \n \n### <a name=\"custom-feed-attributes\"></a>自定义源特性 \n\n 下表列出了一些 XML 特性，这些特性自定义可添加到用于定义数据模型的概念架构定义语言 (CSDL) 的源。 ", "这些特性等效于用于反射提供程序的 <xref:System.", "Data.", "Services.", "Common.", "EntityPropertyMappingAttribute> 的属性。 ", " \n \n|属性名称|描述| \n|--------------------|-----------------| \n|`FC_ContentKind`|指示内容类型。 ", "以下关键字定义联合内容类型。<br /><br /> `text:` 属性值在源中显示为文本。<br /><br /> `html:` 属性值在源中显示为 HTML。<br /><br /> `xhtml:` 属性值在源中显示为 XML 格式的 HTML。<br /><br /> 这些关键字等效于用于反射提供程序的 <xref:System.", "Data.", "Services.", "Common.", "SyndicationTextContentKind> 枚举的值。<br /><br /> 如果使用了 `FC_NsPrefix` 和 `FC_NsUri` 特性，则不支持此特性。<br /><br /> 为 `xhtml` 特性指定值 `FC_ContentKind` 时，必须确保该属性值包含格式正确的 XML。 ", "数据服务返回值，但不执行任何转换。 ", "还必须确保返回的 XML 中任何 XML 元素前缀在映射的源中定义了命名空间 URI 和前缀。| \n|`FC_KeepInContent`|指示是否应将引用的属性值包含到源的内容部分和映射的位置中。 ", "有效值为 `true` 和 `false`。 ", "若要使结果源与 WCF 数据服务早期版本向后兼容，请将值指定 `true` 为以确保该值包含在源的内容部分中。| \n|`FC_NsPrefix`|非联合映射中的 XML 元素的命名空间前缀。 ", "此特性必须与 `FC_NsUri` 特性一起使用，但不能与 `FC_ContentKind` 特性一起使用。| \n|`FC_NsUri`|非联合映射中的 XML 元素的命名空间 URI。 ", "此特性必须与 `FC_NsPrefix` 特性一起使用，但不能与 `FC_ContentKind` 特性一起使用。| \n|`FC_SourcePath`|应用此源映射规则的实体属性的路径。 ", "仅当在 `EntityType` 元素中使用时，才支持此特性。<br /><br /> <xref:System.", "Data.", "Services.", "Common.", "EntityPropertyMappingAttribute.", "SourcePath%2A> 属性无法直接引用复杂类型。 ", "对于复杂类型，必须使用路径表达式，在此路径表达式中，使用反斜杠 (`/`) 字符分隔属性名称。 ", "例如，对于 `Person` 具有整数属性 `Age` 和复杂属性的实体类型，允许使用以下值：<br /><br /> `Address`:<br /><br /> `Age`<br /><br /> `Address/Street`<br /><br /> 不能将 <xref:System.", "Data.", "Services.", "Common.", "EntityPropertyMappingAttribute.", "SourcePath%2A> 属性设置为包含空格或在属性名称中无效的任何其他字符的值。| \n|`FC_TargetPath`|属性将映射到的结果源中的目标元素的名称。 ", "此元素可以是按 Atom 规范定义的元素，也可以是自定义元素。<br /><br /> 以下关键字是指向 OData 源中特定位置的预定义联合目标路径值。<br /><br /> `SyndicationAuthorEmail:``atom:email`元素的子元素 `atom:author` 。", "<br /><br /> `SyndicationAuthorName:``atom:name`元素的子元素 `atom:author` 。", "<br /><br /> `SyndicationAuthorUri:``atom:uri`元素的子元素 `atom:author` 。", "<br /><br /> `SyndicationContributorEmail:``atom:email`元素的子元素 `atom:contributor` 。", "<br /><br /> `SyndicationContributorName:``atom:name`元素的子元素 `atom:contributor` 。", "<br /><br /> `SyndicationContributorUri:``atom:uri`元素的子元素 `atom:contributor` 。", "<br /><br /> `SyndicationCustomProperty:` 自定义属性元素。 ", "映射到自定义元素时，目标必须是路径表达式，在此路径表达式中，使用反斜杠 (`/`) 分隔嵌套元素，并使用 `@` 指定特性。 ", "在以下示例中，字符串 `UnitsInStock/@ReorderLevel` 将属性值映射到根项元素的 `ReorderLevel` 子元素上的 `UnitsInStock` 特性。<br /><br /> `<Property Name=\"ReorderLevel\" Type=\"Int16\" m:FC_TargetPath=\"UnitsInStock/@ReorderLevel\" m:FC_NsPrefix=\"Northwind\" m:FC_NsUri=\"http://schemas.examples.microsoft.com/dataservices\" m:FC_KeepInContent=\"false\" />`<br /><br /> 如果目标是自定义元素名称，还必须指定 `FC_NsPrefix` 和 `FC_NsUri` 特性。<br /><br /> `SyndicationPublished:``atom:published`元素。<br /><br /> `SyndicationRights:``atom:rights`元素。<br /><br /> `SyndicationSummary:``atom:summary`元素。<br /><br /> `SyndicationTitle:``atom:title`元素。<br /><br /> `SyndicationUpdated:``atom:updated`元素。<br /><br /> 这些关键字等效于用于反射提供程序的 <xref:System.", "Data.", "Services.", "Common.", "SyndicationItemProperty> 枚举的值。| \n \n> [!", "NOTE]\n> 特性名称和值是区分大小写的。 ", "特性可以应用于 `EntityType` 元素，也可以应用于一个或多个 `Property` 元素，但不能同时应用于二者。 ", " \n \n## <a name=\"customizing-feeds-with-the-reflection-provider\"></a>使用反射提供程序自定义源 \n\n 若要为使用反射提供程序实现的数据模型自定义源，请将 <xref:System.", "Data.", "Services.", "Common.", "EntityPropertyMappingAttribute> 特性的一个或多个实例添加到表示数据模型中的实体类型的类中。 ", "<xref:System.", "Data.", "Services.", "Common.", "EntityPropertyMappingAttribute> 类的属性对应于在上一节中介绍的源自定义特性。 ", "以下是 `Order` 类型的声明示例，该示例为两个属性定义了自定义源映射。 ", " \n \n> [!", "NOTE]\n> 主题 [如何：使用反射提供程序创建数据服务](create-a-data-service-using-rp-wcf-data-services.md)中定义了此示例的数据模型。 ", " \n \n [!", "code-csharp[Astoria Custom Feeds#CustomOrderFeed](../../../../samples/snippets/csharp/VS_Snippets_Misc/astoria_custom_feeds/cs/orderitems.svc.cs#customorderfeed)]\n [!", "code-vb[Astoria Custom Feeds#CustomOrderFeed](../../../../samples/snippets/visualbasic/VS_Snippets_Misc/astoria_custom_feeds/vb/orderitems.svc.vb#customorderfeed)] \n \n 这些特性为 `Orders` 实体集生成以下自定义数据源。 ", "在此自定义源中， `OrderId` 属性值仅显示在 `title` 的元素中， `entry` `Customer` 属性值同时显示在 `author` 元素和 `Customer` 属性元素中： \n \n [!", "code-xml[Astoria Custom Feeds#IQueryableFeedResult](../../../../samples/snippets/xml/VS_Snippets_Misc/astoria_custom_feeds/xml/iqueryablefeedresult.xml#iqueryablefeedresult)] \n \n 有关详细信息，请参阅 [如何：用反射提供程序自定义源](how-to-customize-feeds-with-the-reflection-provider-wcf-data-services.md)。 ", " \n \n## <a name=\"customizing-feeds-with-a-custom-data-service-provider\"></a>使用自定义数据服务提供程序自定义源 \n\n 通过对表示数据模型中实体类型的 <xref:System.", "Data.", "Services.", "Providers.", "ResourceType.", "AddEntityPropertyMappingAttribute%2A> 调用 <xref:System.", "Data.", "Services.", "Providers.", "ResourceType>，可以为资源类型定义通过使用自定义数据服务提供程序定义的数据模型的源自定义。 ", "有关详细信息，请参阅 [自定义数据服务提供程序](custom-data-service-providers-wcf-data-services.md)。 ", " \n \n## <a name=\"consuming-custom-feeds\"></a>使用自定义源 \n\n 当应用程序直接使用 OData 源时，它必须能够处理返回的源中的任何自定义元素和特性。 ", "如果已在数据模型中实现自定义源，不管数据服务提供程序如何，`$metadata` 终结点都会返回自定义源信息，并作为数据服务返回的 CSDL 中的自定义源特性。 ", "使用 **添加服务引用** 对话框或 [datasvcutil.exe](wcf-data-service-client-utility-datasvcutil-exe.md) 工具生成客户端数据服务类时，将使用自定义的源属性来保证正确处理对数据服务的请求和响应。 ", " \n \n## <a name=\"feed-customization-considerations\"></a>源自定义注意事项 \n\n 定义自定义源映射时，应考虑下列事项。 ", " \n \n- 当源中的映射元素仅包含空白时，WCF 数据服务客户端将源中的映射元素视为空。 ", "因此，仅包含空白的映射元素在具有相同空白的客户端上不具体化。 ", "若要在客户端上保留此空格，必须 `KeepInContext` `true` 在 \"源映射\" 属性中将的值设置为。 ", " \n \n## <a name=\"versioning-requirements\"></a>版本控制要求 \n\n 源自定义具有以下 OData 协议版本要求： \n \n- 源自定义要求客户端和数据服务都支持 OData 协议版本2.0 和更高版本。 ", " \n \n 有关详细信息，请参阅 [数据服务版本控制](data-service-versioning-wcf-data-services.md)。 ", " \n \n## <a name=\"see-also\"></a>请参阅\n\n- [反射提供程序](reflection-provider-wcf-data-services.md)\n- [实体框架提供程序](entity-framework-provider-wcf-data-services.md)\n" ]

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[ "Susan M. Campbell\n\nSusan M. Campbell, Ph.D. (born July 16, 1941) is an American self-help author.", "\n\nBiography\nCampbell earned her Ph.D. in psychology from the University of Massachusetts in 1967, and remained as a member of that school’s Graduate Faculty until 1977, when joined Saybrook University in San Francisco where she holds an adjunct faculty appointment.", "\nShe was also on the faculty at International University of Professional Studies.", "\nSince 1967 she has also pursued a career as a professional speaker and a consultant and trainer. ", " She is also President of Getting Real Resources, a coaching and training company.", "\n\nHer work has been featured in magazines including New Woman, Psychology Today, Self, Harvard Business Review, Seventeen, Men's Health, New Age, Fast Company, and Yoga Journal, and she has been a guest on national TV talk shows such as Dr. Dean Edell, CNNs NewsNight, and Good Morning America, and has guest lectured at the Harvard, Stanford, and UCLA business schools.", "\n\nGetting Real\n\nHer most recent work, described in her best-selling book, Getting Real and her more recent Truth in Dating, and Saying Whats Real, centers on using honest communication for personal healing and expanded self-awareness. ", "The roots of this work are in Buddhist psychology, Gestalt Therapy, Sensory Awareness, Psychoanalysis, and Jungian psychology.", "\n\nPublished works\n\nBooks\n Expanding Your Teaching Potential: Education for Participation in a Changing World (Irvington, 1977)\n The Couple’s Journey: Intimacy as a Path to Wholeness (Impact, 1980)\n Beyond the Power Struggle: Dealing with Conflict in Love and Work (Impact, 1984)\n From Chaos to Confidence: Survival Strategies for the New Workplace (Simon & Schuster, 1995)\n Getting Real: 10 Truth Skills You Need to Live an Authentic Life (New World Library, 2001)\n The Everything Great Sex Book, Campbell, Susan, and Heumann, Suzie. (", "Adams Media, 2002)\n Truth in Dating: Finding Love by Getting Real (New World Library, 2002)\n Saying What’s Real: Seven Keys to Authentic Communication and Relationship Success (New World Library, 2003)\n\nArticles (In Juried professional journals)\n\n Anderson, Susan Campbell. “", "The Effects of Confrontation,” Journal of Counseling Psychology, 16(5) 1968.", "\n Anderson, Susan Campbell, and Jules Zimmer. “", "The Dimensions of Empathy and Positive Regard,” Journal of Counseling Psychology, 15 (5), 1968.", "\nCampbell, Susan. “", "Women and Success,” The Humanistic Psychology Institute Review, 1 (1) Summer 1978.", "\nCarkhuff, Robert, Susan Campbell Anderson and Mae Alixik, “Do We have a Theory of Vocational Choice?” ", "Journal of Personnel and *Guidance, 46 (4) 1968.", "\nCampbell, Susan. “", "Developing Ego-Strength in Drug-Dependent Persons Using Group Therapy,” Correctional Psychologist, 4, Fall 1971.", "\nCampbell, Susan. “", "Working through the Impasse in Self and Society: Gestalt Therapy Applications in Personal and Community Development,” The Gestalt Therapist, 11(1) Fall 1975.", "\nCampbell, Susan. “", "Working Through the Power-Vulnerability Polarity,” Journal of Contemporary Psychotherapy, 8 (2), 1977.", "\nCampbell, Susan. “", "The Co-Creative Teacher: A Key Dimension in Accelerated Learning,” Journal of Accelerated Learning, 10(3) Spring 1980.", "\n\nExternal links\n Official Website of Susan Campbell\n\nReferences\n\nCategory:Living people\nCategory:1941 births\nCategory:American self-help writers\nCategory:Relationship education" ]

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[ "Lady Gaga Rush Releases Second Single After \"Applause\" Flops\n\nIf you're in the mood for even more new music from Lady Gaga, your wish might be Universal Music Group's command.", "\n\nMusic websites are reporting that since \"Applause\" has apparently struggled to gain a standing O from fans on music charts around the world, Gaga's parent record label (UMG owns Interscope) is apparently ready to rush-release a second ARTPOP single ahead of schedule. ", "The new song \"Swine\" will likely see the light of day in early September, according to reports.", "\n\nIn Australia, ‘Applause’ has already fallen out of the Top 10 of the iTunes chart to number 15 after just one week on sale. ", "In the USA, ‘Applause’ is down to no. ", "7 and in the UK it has fallen to no. ", "10.", "\n\nThe lack of interest has become a major issue for Universal Music, Lady Gaga’s record label. ", "Universal will rush-release a second single ‘Swine’ within two weeks to hopefully reignite some interest in Gaga.", "\n\nIt gets worse. ", "Lady Gaga’s YouTube views for ‘Applause’ have been questioned after her fanbase was encouraged to hit refresh to inflate the figures. ", "Incentives were also given to fans who were encouraged to buy multiple copies of the song to win a prize in an effort to upstage ‘Roar’, the new song by Katy Perry.", "\n\nGone are the days when Gaga was named the final heir to the throne of Queen of Pop Today, the press and the critics take their statements with suspicion which exaggerates its music and its importance in the art world, while Twitter and Facebook begs his Little Monsters to buy multiple copies of their albums and singles.", "I have not fallen into that game, for me she is overrated.", "His talent is of course debatable.", "\n\nIf you're single hits top 10 on iTunes at all it's not a flop people, that's actually still really successful. ", "if you don't like the music, don't listen to it. ", "That simple. ", "Stop the hatred, start the music.", "\n\nI couldnt agree more. ", "She made so much hype about Applause before its release. ", "Interviews, Tweets, a countdown on Facebook... Well the song comes out and its mediocre. ", "Anyone who bought the single should have every right to feel duked. ", "It clearly wasn't released in the interest of a good listen but rather for promotional purposes. ", "In interviews she quotes \"this\", \"applause/ARTPOP\" is music for the fans. ", "Music that they will love. ", "The star who released Just Dance and Bad Romance knows what a good single sounds like. ", "Applause is simply not up to par and to promote it as such is not much less than fraudulence. ", "She's clearly a very talented person so when I say that I believe she can and should have released something better I don't think it's too critical.", "\n\nIt's slightly offensive to be honest. ", "She's sought with every demographic of the people in the world in a questionable ingenuine attempt to connect with them and create a larger fan base. ", "Shes a marketing genius. ", "That i'll give her. ", "It' a necessary skill for a pop star aiming at the top spot but when she turns to social media to invite her fans to help dummy the charts in promotion of her new single I think she crosses a line. ", "It should be no surprise to Gaga that Applause isn't doing as well as expected. ", "It's not that good of song to the fans standards or what many thought hers might have been.", "\n\nGaga is who she is and she has every right in the world but if leading turns to misleading it's not acceptable. ", "I urge anyone who relates this to consider buying the album.​ The seemingly incessant need to plug for fans, sales, and ratings is getting old. ", "The singel is an over-pormoted and insufficient pop tease to a now questionable album. ", "I've been a huge fan of much of Lady Gagas work but can't help note it all seems less and less sincere (the Interviews, the promotion, and ultimately the music!) ", "As a consumer in the spirit of good sincere music I won't be buying her new album (unless swayed by something signigicant) I'd urge the same form anyone who relates anyone who realates to any of this.", "\n\nHi now before I'm hung upside down. ", "I'd like to address the issue is not that GaGa isn't talented she clearly is.", "\n\nGAGA,\n\nplease stop with the \"victim\" act, please stop with the \"Im an artiste\" attitude you have going on these days. ", "Please stop with your twitter rants and asking us to buy multiple copies of the same song for your benefit. ", "I am a college student can barely afford tuition let alone buy multiple copies with receipts just to meet which by the if I had the money I'd totally love to meet you. ", "Please stop with the Madonna, David Bowie, Britney any referenced where people can say \" your copying\" because I'm sick of having to defend you then end up looking like an obsessed maniac. ", "Please stop making weird songs and get back to making them fun . ", "Please stop being so serious and just dance. ", "Nothing of your sounds scream deep so why not have fun! ", "I want to love you again :( I want to feel like I did when I'd hear Your older songs\n\nlady gaga does write her own songs. ", "I own all the cd's and the credits day she either wrote the songs and had co writers, producers, ect or she co wrote it with other artists. ", "thats how it works 99.9% of the time. ", "no one does EVERYTHING because its impossible its to much work for one person to do especially when you have her fame levil. ", "just because you guys don't like her music you assume she is a fraud. ", "She is truly an artist\n\nShe doesn't claim to be this amazing artist who writes her own music, create wings that light up as if they didnt exist prior and does all her music. ", "She self promotes herself and falls short every single time. ", "To be frank Beyonce will be around loooong after lady copy and paste\n\nthis is bull. ", "there was no pressure to buy multiple songs or to hit replay, the fans decided that themselves because they are dedicated. ", "Yes this song hasn't hit it off the way her past singles have but it is still doing amazing success and the rest of the album will be another one of gagas great works. ", "even if your not a gaga fan you have to admit she is smart, talented and really knows how to mold pop culture and fashion ( think of it she wore pointy nails before anyone else, thorns tooth and it came in style next season, mint and it came in style next season, studs and now grunge is in high fashion, she got bangs and EVERYONE got bangs, she changed what mainstream music was when she released pokerface before that it was more hip hop pop ) she knows that she is doing if you like it or not. ", "listen to her interviews the amount of thought and research that goes into her music and her videos is incredible. ", "I didn't like her that much untill i found out how much of an artist she is. ", "not many celebs write there music, art direct and direct there videos, write there videos, design there clothes and co coreograph there performances. ", "not only that but she stands for something. ", "she is everything\n\nGosh you sound really young ..studs has been in for quite sometime. ", "Madonna brought that in first. ", "But Rihanna in her various videos prior to Gaga had studs and spikes so she didnt bring that in. ", "This day in age it's not like the 80-90s where ever girl dressed and acted like Madonna. ", "Gaga is too out there to relate to. ", "I see people dress, hear and more like Britney if anything but I can be wrong. ", "Britney in my opinion is the Madonna of this age. ", "Miley from the looks of it will be the following Madonna/Britney\n\nthis is bull. ", "there was no pressure to buy multiple songs or to hit replay, the fans decided that themselves because they are dedicated. ", "Yes this song hasn't hit it off the way her past singles have but it is still doing amazing success and the rest of the album will be another one of gagas great works. ", "even if your not a gaga fan you have to admit she is smart, talented and really knows how to mold pop culture and fashion ( think of it she wore pointy nails before anyone else, thorns tooth and it came in style next season, mint and it came in style next season, studs and now grunge is in high fashion, she got bangs and EVERYONE got bangs, she changed what mainstream music was when she released pokerface before that it was more hip hop pop ) she knows that she is doing if you like it or not. ", "listen to her interviews the amount of thought and research that goes into her music and her videos is incredible. ", "I didn't like her that much untill i found out how much of an artist she is. ", "not many celebs write there music, art direct and direct there videos, write there videos, design there clothes and co coreograph there performances. ", "not only that but she stands for something. ", "she is everything\n\ngurl you stupid the pony tail thing Madonna did First Lady gagas version was a bootleg reductive version. ", "Pony tails in general Britney did in her first video nice try. ", "She asked her fans to play a playlist of her video to get views. ", "She is only doing ok because of those views not because people are buying her second class \"Girl Gone Wild\" song. ", "She is a carbon copy of all the true musical greats before her she hasn't molded anything that's a delusion she's made up in her head and her delusional fans 15 and under. ", "Bangs sweety your dumber than I thought Beyonce had bangs in her last videos. ", "Choreograph? ", "You mean holding eachother by the leg and hop on one foot. ", "Check out Beyonce, Rihanna, Britney and Janet for real choreography!! ", "Lady gaga is a one album wonder her videos are nothing to brag so I wouldn't go there. ", "Everything about her from her clothes to her fake accent is all MADONNA and Madonna does it better\n\nMadonna invented ponytail did she? ", "I am sure she also invented microwave and oxygen. ", "And all three of Gaga's albums, has sold more than 7million copies each. ", "How is that a 'one album wonder'? ", "Madonna's latest album MDNA hasn't even sold 2million copies after 1.5year. ", "Her song flopped so hard they pretended it wasn't a real single and started calling it a 'buzz' single. ", "You Madonna fans needs to stop being so delusional, Madonna is a copycat and had countless lawsuit against her for copyright infringement.", "\n\nGaga I think still might have it in her still make an album like Fame Monster. ", "Her popularity no doubt is at a decline not because \"the people aren't in tune with art\". ", "We live in an age where if your song even remotely sounds like another it will be heard\n\nGaga really just needs to stop focusing on being famous,fashion, her pretentious ways and get back to making a great pop album. ", "Does she have the staying power as her counter parts. ", "The future doesn't look bright for her. ", "She doesn't understand what an audience demands unlike Britney Spears she knows what her fans/audience love and she delivers same for Rihanna and Katy. ", "Gaga is trying to hard to push an envelope that's already been pushed by prior pop tarts.", "\n\nSo why not just make a great pop album without the speeches, without the bullshit. ", "That's when I think she'll gain a fan like myself and I think I pretty much speak about a lot of people.", "\n\nMost of this is petty and ridiculous. ", "People like what they like, and most people are smart enough to think for themselves and not be bullied into believing something else. ", "If you don't like Lady Gaga, fine. ", "Don't attack those that do. ", "If you do like her, fine. ", "Stop attacking those that don't. ", "I'm not sure why this is important enough to constitute name-calling and petty bickering, but she has released one song, and in today's world it seems that if your song is not immediately number one people automatically assume you are a failure and that your career is over. ", "Being passionate about your opinion is great, but being this pissed off about an artist that doesn't have anything to do with your life is silly. ", "Like your music, let other people like theirs and get on about your life! ", "Any of what is true about any of these comments will eventually come out, and if any of it is fraudulent or unseemly, then it will have its own consequences.", "\n\nThis latest album was not very well thought out. ", "Nothing has matched her first album and with such success often comes complacency. ", "Gaga is a great musician and singer who is in a downward spiral but, it is unfortunate there is so much negativity in the world. ", "Katy's song is your typical pop dribble and that seems to be what people prefer these days. ", "Both have their place in the world. ", "The overall record sales will be the defining mark since that's all the record industry cares about.", "\n\nI'm surprised Katy Perry was the one to take her out. ", "Britney's last album was great and performed better regards to being radio friendly and fun. ", "Madonna gave a blow with her reductive comment but it was Katy's simple fun song that knocked her from ever reaching that #1. ", "Her fans can say all they want but in the end, she is at a decline. ", "Numbers don't lie. ", "Well in her case she try's so hard to inflate\n\nLady gaga is no vocalist she is just like Pink, Rihanba and Katy Perry. ", "She is not now or ever will be a bonifide vocalist like Xtina and Mariah. ", "She is no icon like Michael Jackson Madonna Beyonce heck or even Britney these people are icons! ", "She is a fading fad much like the bump it and skinny jeans she will disappear into oblivion never to be heard from again.. Well be on a future Vh1 special of Remember when or dancing with the stars\n\nI respectfully disagree with you on one name. ", "P!nk is just as much of a powerhouse as Christina Aguilera, and sometimes even beats Christina on shear talent. ", "I think Lady Gaga is talented, but I really think she is trying TOO hard to be the best every time. ", "And we all know when you try too hard to be number one, you fall just short. ", "She can sing...very well (if you've ever been to one of her concerts). ", "But there's too much hype surrounding her.", "\n\nPink is awesome so is Rihanna these woman have the talent to stick around. ", "Lady gaga not so much. ", "She sold herself in being the next Madonna or Britney but fell flat. ", "I do wish lady gaga would stop being so serious and just dance\n\nPink is indeed amazing and very underrated. ", "However, Rihanna? ", "No. ", "Do you even know anything about her? ", "She doesn't even write her own songs, Her record label buys them from writers and just get her to record it. ", "How else do you think she can put out an album every year effortlessly? ", "Just last week, the person who wrote the hit song 'Diamond' for her said that she doesn't even know who he is when he walked passed her. ", "She's possibly the least talented artist out there right now.", "\n\nGagas little monstards are always picking on other people for liking anyone who is not gaga instead they should be picking this zits all over their faces because last time I checked that's the kind of fans she draws in. ", "Britney doesn't write her own material, frank Sinatra , Janet or Tina Turner and each one is an icon. ", "Do you need to write your own music nope it's how you sing I mean just Look at Britney and Janet they can't sing for shit but I'd pay top dollar to see them just like Rihanna! ", "Diamond, Shut and Drive, Ponde Replay, Umbrella, disturbia, Stay, only girl in the world, S&M,you da One, We Found Love, What's my name, Fly, Man down boo boo the list goes on and on and on with Rihanna.. Gaga you can't say the same. ", "The girl is a #flop\n\nLady Gaga is an imposter a human tumbler account. ", "All her music, costumes, and Madonna-esque persona come from brilliant artist before her. ", "She doesn't write her own songs ( look at her credits) she only wrote 2.. Yeup just 2 but takes credit for them all. ", "She is a flop con artist who shouldn't be paid for literally copying other people's work!!! ", "Lil monsters can cry all they want that she doesn't copy and writes all her albums the only people they fool are 10-19 year olds.", "\n\nShe has been credited as a writer on every song she has ever released, even producers who has worked with her has confirmed she writes everything herself. ", "Stop acting like you actually looked at the credits. ", "It's seriously sad how some people can hate a person so much that they need to make up lies and defame them like that. ", "She's just a musician, she makes music. ", "Just enjoy it, If you don't like her music then don't buy it or don't listen. ", "She's not forcing you to. ", "And honestly, who's original? ", "Ke$ha, Katy Perry, Jessie J, Rihanna, etc.. had been all accused of copying. ", "And back in the 80s, Madonna was worst than Gaga, everyone was also calling her a copycat.", "\n\nwow what a load of angry people i do agree with some of the comments regarding her fans i am sick of going onto other artists pages ( they are mainly on Madonnas on youtube) and looking at comments like die and calling her old which is totally out of order and posted by little monsters , im a fan of gaga and when she releases a new album im usually wowed by the first release but have to admit i havent taken to applause but her career is not in trouble far from it because you must remember how many times did Madonnas career take a nose dive then she returns bigger and better then ever them 2 lady,s are more alike then her monsters would like think i may get some monsters hating me now lol\n\nWow, so many panties getting into a twist here. ", "Lady Gaga is gonna be ok, she's a recording artist/saleswoman and only needs to earn back what was paid for by her record company. ", "In the end, the rich people get richer and we all go back to bitching about something else.", "\n\nLOL. ", "No Lady Gaga has been done for some time now. ", "Born This Way only delivered half the sales of \"The Fame Monster\". ", "She's not as big as her little monster fans claimed. ", "She will be okay, yes, but she will never be as big as she was. ", "It's OVER.", "\n\nI just threw up in my mouth a little the vile responses on here are incredibly disturbing. ", "The fact that this so called journalism comes from people like perez and a gaga hate site is even more ridiculous.", "\n\nGay men really tend to be horrible individuals... you would think they were talking about a murderer. ", "Gaga is one the most humble & nice human beings I've ever met. ", "Her success over the past 5 years won't go away. ", "People want to see her perform and that won't change with made up hateful stories about her.", "\n\nShe is a female of Kanye West. ", "She's addicted to cheap attention. ", "That's why.", "\n\nGaga a pop singer and self-proclaimed \"musician\" making mediocre pop song (now claiming she is an icon, yeah right!) ", "can only hit several notes. ", "I don't know what people are talking about when they go on about her talent. ", "In 5 years all she does if f***g moan on the media about Lupus, bullied at school, insomnia, cocaine addiction, hip surgery, weight issues and so on. ", "What's next? ", "Raped by a Taliban?", "\n\nWhy don't we as a community, support the people in the entertainment industry who DESERVE our support rather than throwing out $ to this overrated and \"manufactured musician\". ", "I gave her a fair chance in the beginning, but I can't stand liars, phonies and attention whore like Lady Gaga.", "\n\nThe single is #3 in US, and was #1 worldwide. ", "She garnered more music points in total than Katy Perry and beats her as the #1 streaming artist worldwide. ", "For a song with atypical lyrics to be at #1 in US and #1 in 35+ other countries, that's NOT flopping. ", "Please get your sources right.", "\n\nShe is also NOT rush releasing any second single, and Swine is definitely not the second single.", "\n\nI am in complete confusion how so many people are donning ArtPop a failure when they have only heard ONE song, Applause (or two if you've heard the leaked Burka, which isn't my taste at all). ", "Moreover, those who are denying she has talent or isn't a musician, I cannot understand this at all!", "\n\nFor people that actually play an instrument or sing and recognize \"musical talent\", whether you like Gaga's message, her tactics, marketing, style, or whatever, it is beyond me how anyone could not recognize her musical prowess. ", "Her ability to play and sing an enormous style and genre is credible alone. ", "If you take inventory and look, you'll find elements of classical, historic rock-n-roll riffs, unusual rhythms, complex chord progressions and melodic scales, and a clever and genius layering of vocal, rhythm and cadences. ", "I doubt the majority of people pick up on these techniques. ", "They are incredibly difficult to perform let alone create. ", "She writes and produces ALL of this! ", "There are very few artists that can claim this.", "\n\nI LOVE BLACK GOSPEL music. ", "I love the style, chords, rhythm, and soulful deep emotions behind it. ", "This is why I LOVED Madonna's Vogue and Like A Prayer, but Madonna did NOT write these songs. ", "I know I will offend here, but Madonna has a marginal voice. ", "She couldn't stand in the presence of the vocal gymnast Mariah Carey or Whitney Houston. ", "Madonna is a PERFORMER and NOT a musician. ", "Take away her \"risque\" outfits, sexual overtones, hip thrusting, and choreography, and you are left with BORING. ", "The lame accusations of Gaga \"stealing\" other people's work is preposterous! ", "There are countless songs with the SAME CHORD PROGRESSIONS. ", "You can trace the same pattern in rock-n-roll songs to works of Mozart, Beethoven and Bach. ", "The classic signature riff of the Doobie brothers (chord progression I-IV-I(7)) is laundered throughout all music genre). ", "Just because Gaga's song has the same chord progression as another artist (and I could technically argue that Express Yourself and Born This Way are more different than similar) really exposes the ignorance of those making the claim. ", "Madonna's appeal and talent largely rested with her \"shock\" value, persona, and her stage presence. ", "Cher is another. ", "Cher, which she admitted about herself, is not that great of a singer. ", "Cher and Madonna are very very similar in how they arrived at fame. ", "Yes, part of Gaga's draw is a reflection of how Madonna and Cher, but Gaga goes a step beyond: she is a TRUE MUSICIAN.", "\n\nIn contrast and if you truly do this with an unbiased approach, take a listen to Gaga sing Orange Skies, her special with Tony Bennett, her album arrangements then acoustical piano arrangements, her Edge of Glory on Howard Stern, and the list goes on..... If you are honest and have the ability to discern real talent, you'll find Gaga transcends ALL types of music genre. ", "She could easily sing Broadway, Jazz, Gospel, Rock, Pop, and even though I detest it, Rap too. ", "And she WRITES and COMPOSES all of these types of songs. ", "Take a listen to her compositions as \"Stephani Germanotta\" on YouTube, Whether you like the style or not, this is one TRUE musician.", "\n\nSo hate all you want. ", "Wish her failure. ", "Bash her fans. ", "But those who can dish out true and fair criticism, and not by their personal bias, can reach no other conclusion, she is undeniably a music genius.", "\n\nI agree with your assertion that many music artists benefit from qualities other than their vocal talent, so not really knowing Gaga music, I took your advice and listened to her version of Orange Colored Sky on Youtube. ", "I gave her a B minus. ", "Unfortunately for her, when singing standards you are up against the all time greats and legends. ", "But I also had to make it a minus because, for those lucky enough to live in California for instance, the weekday acts can often outsing Gaga. ", "So I have to agree with others who say that much of Gaga's success is from self promotion. ", "I have no problem with that. ", "I feel she would be doing better if her fanbase had not alienated so many other fanbases.", "\n\nwell at least you seem objective and i commend you taking the time to listen and comment. ", "where you give a B minus, someone else may give an A or an F; my point was not to claim she is the greatest vocalist, or specifically, the best vocalist for the \"standards\" but rather her repertoire is broad - showcases her talent's breadth. ", "for me, you cannot top michael buble for standards, at least for this generation, in my opinion. ", "and you may differ here as well.", "\n\nthe comments left for this article are ridiculous and nto backed up by substance. ", "it seems more entangled in juvenile \"tug-of-war\" btwn madonna or perry. ", "i concede that it takes all colors to make the rainbow. ", "we all have diff tastes and preferences. ", "so what? ", "what i take issue with is the baseless mud slinging. ", "dislike her for arrogance, false pretenses, values, etc... just something of substance, but to start claiming she has no talent, no musical ability, copies other artists, etc... i just have issues with that.", "\n\nif you want to get a feel for more of what i am referring to, just take a listen to gaga SOLO on a piano only. ", "listen to how many diff arrangements she does for the same song. ", "or, take a listen to her when she was stephanie germanotta, again playing solo on piano or with her small band. ", "you cannot \"synthesize\" that sound. ", "it is raw and the music styles are so varied. ", "so many diff sounds and styles, and all written by her. ", "yes, she has collaborators, but she writes the music. ", "most of her collaborators help write the synthesized part, NOT the melody, chord lines, or rhythm. ", "and take note, now with artpop released, she has picked up playing the guitar on stage, not just keyboard.", "\n\nlike her or not, madonna, perry, cyrus just dont share the same stage with gaga. ", "maybe in \"performance\" or choreography, but cannot touch her music prowess or composition. ", "but thank you again for at least being objective and not so hateful.", "\n\nI actually have no problem with Gaga & my girl, Miley Cyrus actually has admired her. ", "But her fans have been bugging me on some Miley posts. ", "Insulting Miley, putting down Miley's accomplishments, and trying to explain why Gaga is a goddess. ", "NOT that they simply love Gaga, but that Gaga is the total shit, and everyone else is shit. ", "It's gotten so bad that now I'm waiting for Gaga to go away so I don't have to deal with LM's on the internet anymore. ", "That's not fair to Gaga, but there it is.", "\n\nYou sound pressed sis.. She doesn't write her own music check the credits..she is no vocalist please listen to Mariah Beyonce and Christina. ", "BTW is a exact copy ofExpress Yourself. ", "She can say she is all about the gays but not too long ago there was a campaign for equality and all social media turn fantastically red with equal signs ever as people's profile pic.. We'd see support fromMadonna and Queen B herself.. Lady gaga was no where in sight ( probably because there wasn't an album to promote) the gays have awaken to this copy cat.. I see it.. We all see it\n\nLady Gaga will always be remembered as a Madonna Wannabe singer and she needs to be exposed. ", "Why?", "\n\nShe and her Haus of Deception (god knows those clowns running her promo) saw how Katy Perry's \"leaked\" song was roaring up the charts, within hours her song is mysteriously \"leaked\" too and now she is upset that people see through her latest marketing ploy? ", "She is so starved for attention and I feel sorry for her. ", "She is making completely fool of her self. ", "Whatever happened to pure talented artists without a \"shock\" factor?", "\n\nI wouldn’t pay a nickel to see her or buy her music.", "\n\nShe is manipulating gay community to sell albums. ", "You're so rich and so spoiled that you believe all the tripe your PR/ press agents spew. ", "You will discover America is a lot more than you think it is. ", "Times are about to change. ", "Okay, so why is the \"gay issue\" the one Gaga's picked when she's not gay? ", "Why not poverty or inequality in general? ", "Why not talk about racial equality? ", "Why the gay issue?", "\n\nBack in late December 2009, the L.A. Times did some digging around into the obscene amount of product placement featured in Lady GaGa’s music videos like “Bad Romance” and “Telephone”, and discovered that GaGa had either taken money from, or freely featured products from companies with anti-LGBT ties.", "\n\nMiracle Whip is owned by Kraft Foods, which donates almost exclusively to Republican candidates –including several who have gotten scores of 0 by Equality California, an organization whose mission it is “to ensure and promote dignity, safety and equality for all of lesbian, gay, bisexual and transgender (LGBT) Californians.”", "\n\nHewlett-Packard’s donation record is also mixed in this respect, contributing to some candidates with solid voting records in favor of LBGT issues, and some against.", "\n\nBut Chevrolet’s parent company contributed primarily to social conservatives, including House Whip Eric Cantor, who voted yes on a constitutional amendment to define marriage as between a man and a woman, and voted no on enforcing specific punishments for anti-gay hate crimes.", "\n\nDoes she just pick and choose where the money comes from based on whatever best fits her image​? ", "Lady Gaga needs to disappear for good. ", "I'm so over this pathetic woman !", "\n\nThis is the stupidest argument I've ever heard. ", "I am gay and I use Miracle Whip AND have an HP laptop. ", "Does this mean I'm \"exploiting the gay community?\" ", "Ridiculous.", "\n\nAdditionally, the leak and subsequent rush-release of her song actually hurt her single's sales. ", "Clearly Gaga and her team would not intentionally do this as a marketing move. ", "It's fine if you think Gaga is too similar to Madonna, but you're just making stuff up and jumping to conclusions.", "\n\nGaga is a marketing whore looking for a cheap publicity to sell garbage, just like her fashion and art.", "\n\nDidn't Gaga know about it? ", "Is she really THAT stupid? ", "For someone who is SO involved with the gay cause… I can conlude she surely is misinformed.", "\n\nI remember the Target scandal during Born This Way era where Gaga had dissolved her partnership with Target over disagreements about their policy on giving political donations. ", "Breaking the contract when her song still is #1 ? ", "Great timing, my friend and it was just a great way to keep her name on the headlines so she could claim herself as the \"savior of the gays\" as if she \"standing up for her gays\"\n\nIt just means that she should have chosen her sponsors more coherently with her supposed morals and the cause she was allegedly fighting for. ", "The fact that her sponsors were giving money to anti gay politicians, weakens and even nullifies her message and brings up serious questions about the honesty of her \"manifesto\". ", "You can use whatever brand you want, it is your call, you have to answer to your own conscience. ", "But if you were to become a public figure with so much influence you would have to think things more carefully, she clearly did not.", "\n\n........meaning she is just a record company's puppet who is being scripted how to behave, speak, sing and Tweet all in the name of ratings, sponsorship, endorsement and marketing obviously. ", "She knows nothing about GLBT because everything is pre-planned for her right from the beginning.", "\n\nGaga is a not an angel but more of a decaying precum just like her songs, fashion and art. ", "Last but not least, she bought her followers on Twitter. ", "71% are spammers. ", "Sad isn't it?", "\n\nLong post and I should have proof read. ", "The first paragraph should have said \"pit ONE against the other\" as opposed to \"on\". ", "The last paragraph should read \"20 years\" instead of 2 and \"how much the public see's\" (appostrophe \"s\", as in see is) in the event you indulged me and read the entire post. ", "Sorry.", "\n\nI typically refrain from getting into this banter, but had to jump in on this fiasco! ", "Gaga \"haters\" need a mic check. ", "The characterizations are ridiculous, but this is the same pattern, a blueprint, of the music industry and emerging artists. ", "I am old enough to remember the inception of Madonna, and anyone who can relate or those that want to really investigate, look back at the comparison of Madonna to Cher. ", "The majority tagged Madonna as a copy and fad, forecasting her to flop early on. ", "Now look. ", "Fans love to do this: pit on against the other. ", "And we (the fans) are bright enough to know this industry is dripping with jealousy, envy, and secret hope for their competition to fail.", "\n\nI am definitely on the outer fringe of the bell curve of Gaga's fan base. ", "In fact, I won't even claim to be a Little Monster, but I am a fan. ", "First, she is a creative genius. ", "She writes ALL her songs. ", "There are FEW musicians that can claim this feat. ", "Phil Collins, Elton John, Mariah Carey, Queen, Kiss, Dolly Parton, Buddy Holly are just a few. ", "But, to write your own music AND have them top of the charts, is an even greater dimension of true musical talent. ", "I play piano and can recognize how truly talented Gaga is. ", "The music, chord progression, vocal arrangements, etc... whether you like her or not, she is a musical genius and one of the best in this century.", "\n\nI don't really hold her responsible for her fan base's actions, but I do agree, I don' t think she has done enough to temper their fury. ", "I too find it reprehensible that her \"anti-bully\" and \"anti-gay\" campaign is the foundation of her empire, but her fan base launches some of the vilest examples of what she advertises and claims to be vehemently against. ", "She has no more control over people's actions (her fan base) but I do believe she should denounce what they are doing and take responsibility if she really wants to have credibility.", "\n\nI have seen her 3 times and I can attest, her fan base is NOT crazy, at least what I have witnessed at the concert. ", "Her messages are consistent. ", "I DO think she is sincere in what she preaches. ", "I know people can fool you and I like many, find a genuine thread in Gaga. ", "She always reminds the audience of where she came from, how thankful she is, what struggles she shares with so many, and has never been boastful or arrogant. ", "I worry if success will weed out these traits, probably the second most attractive thing about her (the first, her music prowess and true performer's talent).", "\n\nTo compare an artist like Madonna to Gaga is very premature. ", "Just wait another 2 years and then stack up Gaga's career against Madonna. ", "I may be very wrong, but I would make a sizable wager that Lady Gaga will dethrone Madonna. ", "Gaga is a true musician and this \"character\" is all part of her genius. ", "She has created a mystifying persona, one that we all can't wait to find out \"what is next\". ", "Don't get so caught up in the \"reality\" and take things so literal. ", "Her whole image and creation is all part of the genius. ", "I love \"Gaga\" and have no idea how much of this character the public sees representative of what she is truly like in her day to day affairs. ", "Every one of us understand this. ", "We ALL do this. ", "We are different at school, at work, at home with our family, friends, lovers, etc.... Gaga is no different and 'we\" the fans aren't either.", "\n\nLady gaga is spiraling downward from her music to the publics demand for it. ", "I bought Born this way thinking it was going to be a great album all it's doing now is collecting dust. ", "Tried to take it to Zia to sell it they won't take it because they already have like a zillion copies for 2.99! ", "To my disappointment I ended buying Britney's Blackout and as much of a train wreck she is the album is Nirvana to me anywho there is my two cents which is the amount I'd pay for another lady ga ga album\n\nLady Gaga never denounced or stepped in when it was brought to her attention that her little monster fans were out of control. ", "Her response was, \"They're just protective of me.\" ", "She needs to step down off her pedestal. ", "Her message has become null and void after the way her followers have behaved. ", "Granted the majority of them are 12 and have been given a computer, so what else do you expect.", "\n\nYes we're \"jalouz\" and yes \"cuz\" she has the best \"weave\". ", "You either must be brain dead, haven't graduated grade school or had no schooling. ", "Lady Gaga is done with washed up spit out. ", "Her music is mediocre and he schtick is old\n\nLMAOOOOOOOOOOOOOO LITTLE MONSTERS ARE NOT BULLIES. ", "PEREZ STALKED GAGA IN HER APARTMENT, LITTLE MONSTERS WERE ANGRY AND TWEETED THINGS TO HIM. ", "NOW PIGREZ ACTS LIKE HE IS THE VICTIM. ", "GTFO WITH YOUR LIES XOXOXOXO\n\nRight, but Gaga didn't act like a victim and post this for the world to read like a psycho on Twitter. ", "No class. ", "She's through and over, She's a joke. ", "A fan base of a bunch of little morons aka children with no lives. ,", "\n\nlike always she gets her fans to do the the hate to other artist. ", "The Monsters are nothing but hateful people that try to damage other artist careers... when GAGA got fat she went after Adele.... thats why I hate her fans.", "\n\nSome of you yourself are verging on billing. ", "I am a gaga fan and some of the things you're posting is obscured. ", "Not for you to take offence but do your research before making remarks like these. ", "In regards to the tweets between gaga and Perez. ", "That's for them so sort out, read the tweets. ", "As for some monsters they are like any other fans ie Britney Spears has Chris Crocker or stalker. ", "All celebrities have crazed fan don't rush to a conclusion that were all bad.", "\n\n\"For them to sort out.\" ", "Right which is why that psycho attention-whoring Madonna-wannabe should never have tweeted those crazy things about Perez in the first place. ", "She's turned me off of her with this desperado crazy behavior. ", "There is no humility with her like before.", "\n\nWait a minute. ", "Are you defending that talentless, fugly-faced, good-for-nothing vermin known as Perez Hilton? ", "The one who likes to OUT people before they are even ready. ", "The same Perez Hilton who likes to IMPOSE his standards on everyone else? ", "Seriously, if you need to pick sides, Perez Hilton is NOT the side you want to pick on. ", "No Integrity, No credibility and a nobody.", "\n\nVery true. ", "She does have the absolute worst fans in the world and what's sad about that is they have ironically contributed to her downfall. ", "Everyone just became turned off by them and by her for doing nothing about it. ", "As far as her music. ", "It's fun, dance, but the last album \"Born this way\" only had 3 great songs on it, the rest of it was noise. ", "This \"Applause\" is more of that noise.", "\n\nGaga fans are bullies??? ", "Only SOME of them are, as they are humans after all, and they get insulted when people are insulting Gaga. ", "Have you even read HALF the shit Madonna fans say and Britney fans say? ", "They're worse. ", "Gaga fans are the most open-minded fanbase out there right now.", "\n\nAnd did you know it's been exposed that haters have been POSING as Gaga fans on twitter, sending hate, just to make us look bad?", "\n\nDon't drag Britney into your rant please. ", "Britney has NEVER said anything bad about any artist. ", "Madonna can because her work was stolen and repackaged so she can say what she wants to lady gaga. ", "Lady gaga is vile I went to show once and she said quote \" I will never pay top dollar to see some blonde bitch lip sync\" only two artist that do is Britney and Madonna. ", "She is so insecure and pressed on being the next Britney or Madonna but judging by her last album and current single she isn't even close! ", "So Hun dont drag Britney she is truly humble and sweet.. But your a \" Lil monster\" what else can we expect.. Right\n\nAnti-bullying doesn't mean having to take crap from anyone lying down, child.", "\n\nIf Lady Gaga is really a hateful person, then why is it that so many celebrities want to work with her? ", "She will always remain strong simply because she is talented. ", "She has the goods and skills to back up her claim. ", "I do not think Lady Gaga has the worst fans. ", "That title belongs to Bieber's fans.", "\n\nWell you're one of the few :) Her fans are crazy. ", "LOL read the comments from her fan \"Germanotta\" on these postings. ", "He/she sounds borderline obsessive. ", "Sad, weird, little Morons. ", "Their mother moron is flopping and there is nothin they can do. :(", "\n\nI am sorry that was a typo i meant it to say, Why is there so much homophobia coming from GaGa fans? ", "And I am not just saying here. ", "The other day a GaGa fan told PerezHilton, \"Drink bleach and die fa*g*t\".", "What bothers me most about it is she has actually been encouraging this behavior, i thought she was anti-bully anti-homophobic\n\nI agree, Gaga's killing her own career by acting like this. ", "Why is Katy Perry doing so well? ", "Katy seems like a nice person, is grateful and polite to the TRUE queen of pop Madonna, and Katy genuinely comes off as grateful and humble as does Rihanna. ", "Gaga needs to learn a thing or two stat because her pop days are numbered. ", "She hasn't even had a lot of hits under her belt and allows herself to be called \"queen of pop\" lololol. ", "She's falling fast, and not just off the charts. ", "Karma I guess.", "\n\nBitch please you don't know shit abou her. ", "After SOME of her fans were threatening others, she POSTED IMMEDIATELY on her social media sites that she would like for them to STOP and that they're not true fans if they keep the negativity. ", "She has been fighting for a positive world from the start and has affected millions. ", "Me being one of them.", "\n\nGaga never ever said she was the queen of pop. ", "Don't make up shit. ", "She even commented once saying \"I don't want to be your queen, I want to be your friend. ", "I only want to make music to make people happy\". ", "So spiteful bitches like you sitting at home trashing her need to learn a thing or two. ", "Gaga is very humble. ", "She still lives in her APARTMENT in New York with her parents. ", "She don't own a million dollar mansion. ", "You really need to learn more before you post things like this. ", "It's upsetting. ", "I'm a close fan of hers and I'm a liable witness to her tale. ", "Trust me.", "\n\nI totally agree with you as well I think her \"fame\" has gotten to her head and like u said its hurting her. ", "She speaks about anti bulling and she just lets her brainwashed fans do it for her when she doesn't try to stop it. ", "Even When Perez Hilton was her friend... he is now telling the truth....pretty much that her and her label were paid to talk negatively about Bionic...thats why now he is promoting people to buy Xtina's Album on the same day as Gaga's album comes out......and she is crying Foul.", "\n\nUgh stupid bitch stfu. ", "Katy is FRIENDS WITH GAGA, We are LITTLE MONSTERS not you. ", "We know more about gaga than you. ", "So shut the fuck up and get your facts right. ", "Madonna is queen of pop, Gaga is the goddes of pop. ", "Byebye.", "\n\nI'm sorry but this is a rediculous comment. ", "Okay so there are some 'monsters' out there that are taking things to far but don't let that for a second reflect upon Gaga herself. ", "To say that she is endorsing homophobic and threatening behaviour is just absurd. ", "She is one of the greatest advocates for homosexual rights in the world. ", "And as for the comments towards Perez Hilton, Gaga has tweeted fairly often insisting that fans stop the negative comments, and to leave him along. ", "This goes along with the fact if you look at Perez Hilton's website and search Lady Gaga I don't think there has been one nice post about her. ", "I am not sure where you stand as far as a fan, but to judge someone based on other peoples behaviour is wrong. ", "How exactly is Gaga acting to kill her own career?" ]

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[ "Welcome to Northeast Service Inc!", "\n\nServing the Utility Industry in Texas since 1977\n\nOur company started in the utility industry servicing\nSBC (now AT&T) with a backhoe and a small trencher. ", "We have built our company\nfrom within with knowledge learned in the field. ", "Northeast Services was one of\nthe first in the metroplex to have directional capabilities. ", "Today our company\nnot only places HDPE and cable for local phone and cable companies but we also\nhave drills to do large casing and pipeline work. ", "Our drills are capable to do\ndrills up to 36’’ in diameter with lengths up to 2000’. ", "All NES machines have up\nto date locating equipment and our larger drills are equipped with wire line\ncapability. ", "With Northeast Services you not only get the bore done but have the\nconfidence that your product is placed inline and on grade using detailed\ninfield evaluation and providing our customers with complete bore logs and\ngraphs in both paper and electronic forms.", "\n\nBeing located in Dallas/Fort Worth we have a diverse\namount of soil types here. ", "We have worked in sandy, cobble, sand stone to lime\nstone and granite. ", "Our company is equipped to do all soil types having equipment\nto drill rock along with all support equipment such as mud motors, mud cleaners,\nhole openers, wire line equipment needed to do any job.", "\n\nContact us for a quote and we will be glad to give you everything you need to\nmake the best decision who to use for your project." ]

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[ "Love this show so much." ]

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[ "Long-term clinical outcome after transcervical thymectomy for myasthenia gravis.", "\nWe reviewed the long-term clinical outcome after transcervical thymectomy for generalized myasthenia gravis without thymoma in 52 patients who had this procedure at The Toronto Hospital between 1977 and 1986, and compared the results with those reported after more radical surgical approaches. ", "Preoperative and postoperative patient evaluations were based on a modified Osserman classification. ", "We defined complete remission as asymptomatic with normal strength and without medications for myasthenia gravis. ", "The complete remission rate was selected as the best measure for comparison between different surgical approaches. ", "The 52 patients were followed up for a mean of 8.4 years (+/-6.1 years [standard deviation]). ", "The preoperative mean Osserman grade was 2.7 compared with 0.4 at final follow-up. ", "Complete remission occurred in 44.2% of patients. ", "Similar results are reported after transsternal thymectomy. ", "Comparable results after transcervical and transsternal thymectomy favor the use of the less radical approach." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "2015 UCI Oceania Tour\n\nThe 2015 UCI Oceania Tour was the eleventh season of the UCI Oceania Tour. ", "The season began on 28 January 2015 with the New Zealand Cycle Classic and finished on 28 February 2015 with The REV Classic.", "\n\nThe points leader, based on the cumulative results of previous races, wears the UCI Oceania Tour cycling jersey. ", "Robert Power from Australia is the defending 2014 UCI Oceania Tour champion.", "\n\nThroughout the season, points are awarded to the top finishers of stages within stage races and the final general classification standings of each of the stages races and one-day events. ", "The quality and complexity of a race also determines how many points are awarded to the top finishers, the higher the UCI rating of a race, the more points are awarded.", "\nThe UCI ratings from highest to lowest are as follows:\n Multi-day events: 2.HC, 2.1 and 2.2\n One-day events: 1.HC, 1.1 and 1.2\n\nEvents\n\nFinal Ranking\n\nExternal links\n \n\nCategory:UCI Oceania Tour\nCategory:2015 in men's road cycling\nU" ]

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

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[ "Three types of liver cell dysplasia (LCD) in small cirrhotic nodules are distinguishable by karyometry and PCNA labelling, and their features resemble distinct grades of hepatocellular carcinoma.", "\nWe have studied the occurrence and specific features of liver cell dysplasia (LCD) in Chinese patients showing liver cirrhosis with or without hepatocellular carcinoma (HCC). ", "Three types of LCD (SLCD, LLCDo, LLCDe) were morphologically defined, and these types were further analyzed using karyometry, estimation of nucleic acid content and density, and PCNA immunostaining. ", "Features found for three types of LCD were compared with those of normal hepatocytes (NLC), simple regenerating hepatocytes (SRLC), and cells of HCCs covering different grades. ", "The results show that 1) karyometry and nucleic acid parameters allow an objective separation of LCD types both from NLC and SRLC; 2) karyometric features of LLCDe are most close to those of highly differentiated HCCs, whereas nuclear size and chromatin composition of SLCD closely reflect those of poorly differentiated HCCs; 3) the frequency of LCD clusters was higher in cirrhotic livers carrying HCC, being about double for all three LCD types; 4) the highest PCNA labelling occurred in the small cell group of LCD (SLCD), still, however, being smaller than that of simple regenerating hepatocytes. ", "Based on these findings it is suggested that, similar to atypical adenomatous hyperplasia, LCDs of distinct morphotypes may represent precursor lesions for HCC, and some cellular forms may mimick cell types known to occur in experimental carcinogenesis." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "\nThe Fantasy and the Cyberpunk Futurism of Singapore - lelf\nhttps://www.wired.com/story/opinion-the-fantasy-and-the-cyberpunk-futurism-of-singapore\n======\nMizza\nSingapore is a weird place. ", "During the flight, the stewardesses walked around\nand handed everybody something - I was expecting a wet towel, but in fact it\nwas a card in multiple languages which says \"If you are about to bring any\namount of drugs into the country, you are going to be executed.\" ", "Lovely first\nimpression to set the tone.", "\n\nOther than the omnipresent paranoia, the thing that struck me as the most\nbizarre is that almost nothing in the country is oriented around children. ", "The\nfertility rate is basically the lowest in the world, as the way of maintaining\nthe population seems to be simply skimming the top few percent of qualified\nworkers from India, China, and other southeast Asian countries, people who\nwill essentially live at the office until they have made enough money to\nreturn home, or simply retire and die alone in the country.", "\n\nAnother strange thing was the way the city is planned - everything is\nconcentrated to a district. ", "For instance, rather than having record shops\npeppered around the city, there is a the \"record shop area\", where there are a\ndozen record shops in a single place. ", "It's like this for lots of things -\nbooks, refrigerators, etc.", "\n\nThe food was great though. ", "I'm craving laksa just thinking about it..\n\n~~~\nrashkov\nI wonder, would there be an opportunity to flush any substances down the\ntoilet, at that point? ", "Sounds like a potentially terrifying situation,\nconsidering the number of stories I’ve heard from friends and family about\naccidentally flying with marijuana that they were unaware of was left over in\na backpack or whatnot.", "\n\n~~~\nMizza\nYou would have to use the airplane toilet. ", "Immediately after stepping off the\nplane, you are scanned by some kind of scanning IR(?) ", "camera, which I assumed\nwas looking for drugs. ", "I actually had some vitamins in a baggie which I was\nshitting bricks about, but the actually immigration point was very polite and\nchill, much moreso than, say, JFK.", "\n\n~~~\nschoen\nI think the IR camera was more likely to have been looking for _fever_ than\ndrugs. ", "I don't mean to say that Changi doesn't have drug-detection mechanisms,\nbut the commonest use of IR cameras at international airport gates is to try\nto find passengers who are showing signs of infectious disease.", "\n\n------\nJSavageOne\nThese comments seem to paid a really dystopian picture of Singapore. ", "Of course\nthere are problems with its government, but in my travels, Singapore was one\nof the most impressive countries I've ever visited. ", "By far the cleanest city\nI've ever seen, the most futuristic, most efficient, and my favorite food\ncity.", "\n\nSingaporeans visiting America for the first time are often shocked at how much\nworse the U.S. was compared to their expectations, almost third-world like. ", "If\nmore Americans visited countries like Singapore and saw how much further ahead\nthey are, maybe for once our people and politicians would have some modesty\nand fix things instead of just being complacent.", "\n\n------\nnoobermin\nI think it's funny how the author says the people sort of go along with the\ngovernment especially now just weeks after the recent election where\nopposition parties took a district, which sure in terms of actual governing\npower doesn't mean much, but means that the PAP is just starting to feel some\npressure from the outside, particularly among younger people and families who\nopted to vote in the WP in sengkang. ", "It doesn't really seem like sg will move\nbeyond a one-party state soon because of it but people are hoping the\ngovernment moves in a different direction especially after covid.", "\n\nWP taking sengkang was big big news in sg, people have to understand the PAP\nhas dominated singapore's government for decades. ", "In terms of actual power it\nmeans little but it was a blow to the PAP's soft power as it was a clear sign\nthat people want the government to reorient itself.", "\n\n------\nRyJones\nStrange place. ", "I was amazed how many homeless there are - which will be\ndenied, when mentioned.", "\n\nI guess the people sleeping on the walkway to Louis Vuitton island were not\nhomeless? ", "The sleeping people in the underpasses, sleeping under signs saying\nnot to sleep there also?", "\n\n~~~\nnoobermin\nMy impression actually is there are far fewer homeless, compared to say\nportland or LA.", "\n\n~~~\nTemasik\nthere are homeless in Singapore seriously?", "\n\n~~~\ntheCodeStig\nYes\n\n------\nPandaRider\n> Many hardworking Singaporeans today resoundingly choose a government that\n> promises economic stability even as censorship laws become more and more\n> stringent and inequality is rife.", "\n\nAs a Singaporean, this is the point that sticks out as proof that the author\nhas lost touch with local sentiment. ", "In the recent election, young Singaporean\ncitizens felt \" especially agitated by Raeesah Khan being hit with a\nsledgehammer.\" ", "and thus many voted against the PAP. [", "0]\n\nYet, on the author's point of paradox of cyberpunk... there is a kernel of\ntruth. ", "While most Singaporeans wouldn't scrape a temple for a new high tech\nmall like Jewel, (IMO) most Singaporeans would be okay if it was for a new\ntrain station so that we (ironically) can visit Jewel more conveniently.", "\n\n[0]: [https://mothership.sg/2020/07/inderjit-singh-pap-\nge2020-crit...](https://mothership.sg/2020/07/inderjit-singh-pap-\nge2020-criticism/)\n\n------\nordinaryradical\nAnd for those of you that want the greatest novelist of cyberpunk, William\nGibson, and his take on Singapore, \"Disney Land with the Death Penalty.", "\"[1]\n\n[1]\n[https://www.wired.com/1993/04/gibson-2/](https://www.wired.com/1993/04/gibson-2/)\n\n~~~\nbitwize\nI love how Gibson compared it to Stephenson's burbclaves, which to me is like\nthe literary equivalent of a famous musical artist singing the \"Weird Al\"\nYankovic version of their own song (which has also been known to happen).", "\n\n~~~\nmacando\nWhich artist did that?", "\n\n~~~\nbitwize\nI know of at least two. ", "The Barenaked Ladies have been known to interject\nlyrics from \"Jerry Springer\" into live performances of \"One Week\". ", "And The\nPresidents of the United States of America sometimes close out live versions\nof \"Lump\" with \"And that's all I have to say about that\" (the final line of\n\"Gump\").", "\n\n------\nCausality1\n\"Cyberpunk dystopia\" seems very inaccurate to me. ", "Nothing whatsoever about\nSingapore is \"punk\" in any sense of the word. \"", "Cyber-utopian\" is a better\ndescriptor, with the emphasis on the traditional connotations of the word\nutopian, that being an aim for perfection at significant cost to principals\nthat don't fit the vision.", "\n\n~~~\nApocryphon\nWell, the ruling corporate authority in a cyberpunk state isn't very punk,\neither. ", "It exists as an edifice to be opposed or exploited by such a\nrebellious subculture. ", "Maybe Singapore is a cybernetic dystopia in search of a\ncyberpunk movement.", "\n\nAlso, the street samurai/cowboy hacker trope isn't ubiquitous to every\ncyberpunk work. ", "Ghost in the Shell, a seminal work, is about law enforcement\nofficers who uphold the state, and occasionally chase down cyberpunk anarchist\nhackers. (", "Blade Runner is much the same.) ", "You can have the trappings of the\ngenre without all elements of it.", "\n\n------\npengaru\nAs someone who has lived in several tourist-ridden parts of California, the\nidea of turning the airport itself into a tourist trap is _very_ appealing.", "\n\n------\naaron695\nThe fact the \"Four Floors of Whores\" was government sanctioned always fit well\nwith the Disneyland feel to me.", "\n\n[https://en.wikipedia.org/wiki/Orchard_Towers](https://en.wikipedia.org/wiki/Orchard_Towers)\n\nI started seeing the beauty in rubbish after visiting Singapore a few times.", "\nThere's something quite unsettling when there is absolutely none.", "\n\n~~~\nValentineC\n> _I started seeing the beauty in rubbish after visiting Singapore a few\n> times. ", "There 's something quite unsettling when there is absolutely none._", "\n\nIf you were here during our lockdown, you might have seen plenty.", "\n\nSome parts of Singapore's population don't see the civic responsibility in\nthrowing trash into bins, unlike most of Japan and Taiwan.", "\n\nSingapore is a clean _ed_ city, not a clean city.", "\n\n------\nholografix\nAs draconian and harsh a lot of Singaporean laws seem to be it’s hard to argue\nwith the country’s success. ", "I’ve been to Singapore many times and a lot of\nsouth east Asia as well and as someone who grew up in a third world tropical\ncountry (Rio) I don’t have a romantic view of SEA as many Euros or Americans.", "\n\nSingapore is a paradise compared with Indonesia, Malaysia etc.", "\n\n~~~\nhatenberg\nGiven the pandemic its a paradise compared to most of the states too.", "\n\n------\nHHC-Hunter\nMy biggest disappointment about Singapore is the censorship.", "\n[https://en.wikipedia.org/wiki/Internet_censorship_in_Singapo...](https://en.wikipedia.org/wiki/Internet_censorship_in_Singapore)\n\nMy biggest boast about Singapore are the privacy laws and technology\ninfrastructure.", "\n\nSingapore could be great, if only a few things were to change.", "\n\n~~~\ndehrmann\nThe PAP is slowly losing popularity. ", "A second political party gaining power\ncould change things.", "\n\nMy take on the censorship and police state is that it's there so there aren't\nsignificant racial or religious tensions.", "\n\n------\nfrancobatta\nInteresting... regardless, I'd love to visit SG someday\n\n------\nsimonebrunozzi\nThe Wired website is a f*cking joke.", "\n\nI clicked to read the story, and I have pop-ups and banners all over the\nplace. ", "I try to click the \"X\" to close them, and I can't.", "\n\nGoodbye, Wired. ", "I'm not going to read the article and I'm not going to read\nyou in the future.", "\n\n" ]

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[ "The FBI's Digital Surveillance Might Be More Wide-Ranging Than the NSA's (Or, Delegating the Spying)\n\nAccording to a recent article in Foreign Affairs, the FBI conducts extensive digital surveillance on US soil on behalf of the National Security Agency—and, it turns out, probably spies even more intensively than the NSA:\n\nWhen the media and members of Congress say the NSA spies on Americans, what they really mean is that the FBI helps the NSA do it, providing a technical and legal infrastructure that permits the NSA, which by law collects foreign intelligence, to operate on U.S. soil. ", "It's the FBI, a domestic U.S. law enforcement agency, that collects digital information from at least nine American technology companies as part of the NSA's Prism system. ", "It was the FBI that petitioned the Foreign Intelligence Surveillance Court to order Verizon Business Network Services, one of the United States' biggest telecom carriers for corporations, to hand over the call records of millions of its customers to the NSA. ", "Sponsored Port Townsend Film Festival Stream 24/7 - Watch 75 curated films with filmmaker interviews & special events. ", "Support local arts! ", "But the FBI is no mere errand boy for the United States' biggest intelligence agency. ", "It carries out its own signals intelligence operations and is trying to collect huge amounts of email and Internet data from U.S. companies—an operation that the NSA once conducted, was reprimanded for, and says it abandoned.", "\n\nCooperation and information-sharing between agencies sounds good and efficient, but it also opens up big loopholes and opportunities for agencies to make end-runs around any restrictions placed on them by elected officials.", "\n\nCongress tells the NSA it can't do X? ", "Let the FBI take care of it. ", "Congress tells all federal agencies they can't spy on Y? ", "Fine. ", "Let the local police departments take care of it and share the information later.", "\n\nThat's one potential problem with the Department of Homeland Security handing out millions of dollars to cities, allowing local cops to quietly buy and maintain their own federal-grade surveillance equipment (or equipment with surveillance capabilities, depending on how you want to frame it). ", "That's especially problematic if the local cops aren't even telling their local mayors and councils what they're up to—as Seattle has recently experienced with DHS-funded police drones, cameras, and other surprises.", "\n\nLast month, the New York Times wrote about what happened when Homeland Security money hit Oakland. ", "The Stranger has written about the controversial wireless mesh network in downtown Seattle, which the Seattle Police Department quietly bought and installed with Homeland Security money. (", "Once the story ran, the SPD said it would turn off the network until there could be \"vigorous public debate\" about its use.)", "\n\nSince the feds pay for the equipment, the local police are almost guaranteed to share it—internal SPD documents even list where all the information from its mesh network was planned to be routed. ", "In the image below, towards the bottom of the list on the right, you'll see a \"fusion center\" as one of those recipients. (", "You'll also see input from \"existing airborn video,\" which must've been the drones the SPD was later forced to shelve.)", "\n\nBut the important thing is the fusion center—a free information-swapping node between local, state, and federal agencies with no real restrictions on what kind of information they can share. ", "Fusion centers are the Wild West of law-enforcement data sharing.", "\n\nEven if Congress takes strong action to curb the NSA and the FBI, it's nearly impossible to imagine all city councils across the country coordinating to pass identical restrictions on the intelligence-gathering activity of the local police departments.", "\n\nThe result could be a national proliferation of Homeland Security-funded equipment collecting data under a weak patchwork of local restrictions, most of which would become irrelevant if all the surveillance data is being routed through the free-for-all of local fusion centers.", "\n\nWhether that's part of a DHS strategy or just a happy accident, it's going to be a major challenge to any elected officials, small-time or big-time, who want to put a leash on the government agencies that specialize in spying on us.", "\n\nInformation sharing also provides p.r. ", "cover to dodgy intelligence-gathering activities. ", "Back to the Foreign Affairs story: \"... having the DITU [the FBI's Data Intercept Technology Unit] act as a conduit provides a useful public relations benefit: Technology companies can claim—correctly—that they do not provide any information about their customers directly to the NSA, because they give it to the DITU, which in turn passes it to the NSA.\"", "\n\nHere's more from the Foreign Affairs story about the FBI's Data Intercept Technology Unit (DITU):\n\nAfter Prism was disclosed in the Washington Post and the Guardian, some technology company executives claimed they knew nothing about a collection program run by the NSA. ", "And that may have been true. ", "The companies would likely have interacted only with officials from the DITU and others in the FBI and the Justice Department, said sources who have worked with the unit to implement surveillance orders.", "\n\nRecently, the DITU has helped construct data-filtering software that the FBI wants telecom carriers and Internet service providers to install on their networks so that the government can collect large volumes of data about emails and Internet traffic. ", "The software, known as a port reader, makes copies of emails as they flow through a network. ", "Then, in practically an instant, the port reader dissects them, removing only the metadata that has been approved by a court. ", "The FBI has built metadata collection systems before. ", "In the late 1990s, it deployed the Carnivore system, which the DITU helped manage, to pull header information out of emails. ", "But the FBI today is after much more than just traditional metadata — who sent a message and who received it. ", "The FBI wants as many as 13 individual fields of information, according to the industry representative.", "\n\nThe DITU devised the port reader after law enforcement officials complained that they weren't getting enough information from emails and Internet traffic. ", "The FBI has argued that under the Patriot Act, it has the authority to capture metadata and doesn't need a warrant to get them. ", "Some federal prosecutors have gone to court to compel port reader adoption, the industry representative said. ", "If a company failed to comply with a court order, it could be held in contempt. ", "The FBI's pursuit of Internet metadata bears striking similarities to the NSA's efforts to obtain the same information. ", "After the 9/11 terrorist attacks, the agency began collecting the information under a secret order signed by President George W. Bush. ", "Documents that were declassified Nov. 18 by Barack Obama's administration show that the agency ran afoul of the Foreign Intelligence Surveillance Court after it discovered that the NSA was collecting more metadata than the court had allowed. ", "The NSA abandoned the Internet metadata collection program in 2011, according to administration officials. ", "But the FBI has been moving ahead with its own efforts, collecting more metadata than it has in the past.", "\n\nThe DITU also runs a bespoke surveillance service, devising or building technology capable of intercepting information when the companies can't do it themselves. ", "In the early days of social media, when companies like LinkedIn and Facebook were starting out, the unit worked with companies on a technical solution for capturing information about a specific target without also capturing information related to other people to whom the target was connected, such as comments on posts, shared photographs, and personal data from other people's profiles, according to a technology expert who was involved in the negotiations. ", "Support The Stranger More than ever, we depend on your support to help fund our coverage. ", "Support local, independent media with a one-time or recurring donation. ", "Thank you!", "\n\nThe Operational Technology Division also specializes in so-called black-bag jobs to install surveillance equipment, as well as computer hacking, referred to on the website as \"covert entry/search capability,\" which is carried out under law enforcement and intelligence warrants. ", "The tech experts at Quantico are the FBI's silent cybersleuths. \"", "While [the division's] work doesn't typically make the news, the fruits of its labor are evident in the busted child pornography ring, the exposed computer hacker, the prevented bombing, the averted terrorist plot, and the prosecuted corrupt official,\" according to the website.", "\n\nThanks to Slog tipper Greg for the tip about the FA article." ]

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[ "Attached is the presentation I used for a very general update on \nderegulation; it includes some California material." ]

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[ "Q:\n\nCan I dinamically add new fields to my models/serializer/db ?", "\n\nI´m developing an application using Django Rest Framework, and I have a problem. ", "I´m trying to make the application as flexible as possible, so i wanted the possibility to dynamically add new fields to my models.", "\nFor example:\nI have the model robot with fields id and version.", "\nBut then the user wants to add a new field, the owner of the robot.", "\nWhat can i do so that with that I can can make the model and serializer reflect that new field. ", "I can see how can i easilly add a new field to the database, but then the model and the serializer will not reflect this change.", "\n\nA:\n\ni wanted the possibility to dynamically add new fields to my models.", "\n\nShort answer: you can't. ", "\nLong answer: you can use a related model where each record will represent a \"field\" for a given Robot instance, ie:\nclass RobotField(models.", "Model):\n robot = models.", "ForeignKey(Robot)\n fieldname = models.", "CharField(max_length=30)\n value = models.", "TextField()\n\n class Meta:\n unique_together = [(\"robot\", \"fieldname\")]\n\nBut then properly handling the value (and it's type), validations, etc etc, and most queries involving those \"fields\" will become a PITA.", "\nOr you could store \"user-defined\" fields as json in a kitchen-sink TextField, but then let's not even talk of SQL queries...\nThe point is that most often than not, adding a field to your schema means adding quite some business domain code using the field too - because usually the point of adding a field is to support some business rule. ", "\nFWIW peoples have tried to come with \"zero-code user extensible models\" apps for years and I yet have to see any app that actually succeeded in doing so. ", "The results have always ended up in bloated code bases filled with antipatterns (like storing user-written code and templates in the db) and exhibiting abysmal runtime performances - AND with a UI so complex that users pay developpers each time they need any of the evolutions they were supposed to be able to do by themselves, paying big bucks for this since the bloated code base and convuluted models means that something as simple as adding a simple fields in a models now takes five times more work.", "\nIOW : keep it simple stupid - code is quite often the simplest configuration tool.", "\n\n" ]

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[ "Q:\n\nUIMenuController didDismiss Method?", "\n\nI have a UITableView that has a didSelectRow method... it creates a UIMenuController and displays it.", "\nCurrently, it works correctly but when the UIMenuController dismisses I wanted to call a [tableView1 deselectRowAtIndexPath:path1 animated:YES];\nNSIndexPath *path1;\nUITableView *table1;\n#pragma maek - Table View\n- (void)tableView:(UITableView *)tableView didSelectRowAtIndexPath:(NSIndexPath *)indexPath\n{\n\n path1 = indexPath;\n\n tablview1 = tableview;\n\n CGRect location = [tableView rectForRowAtIndexPath:indexPath];\n\n location.origin.y = location.origin.y+30;\n\n [self becomeFirstResponder];\n\n UIMenuItem *menuItem = [[UIMenuItem alloc] initWithTitle:@\"View Item\" action:@selector(viewItem:)];\n UIMenuItem *menuItem1 = [[UIMenuItem alloc] initWithTitle:@\"Edit Item\" action:@selector(editItem:)];\n UIMenuItem *menuItem3 = [[UIMenuItem alloc] initWithTitle:@\"Cancel\" action:@selector(cancelSubMenu:)];\n\n UIMenuController *menuController = [UIMenuController sharedMenuController];\n [menuController setTargetRect:location inView:self.view];\n menuController.menuItems = [NSArray arrayWithObjects:menuItem, menuItem1,menuItem3, nil];\n\n menuController.arrowDirection = UIMenuControllerArrowUp;\n\n [menuController setMenuVisible:YES animated:YES];\n}\n\n-(IBAction)cancelSubMenu:(id)sender \n{\n [tableView1 deselectRowAtIndexPath:path1 animated:YES]; \n}\n\n-(BOOL)canBecomeFirstResponder \n{\n return YES; \n}\n\n-(BOOL)canPerformAction:(SEL)action withSender:(id)sender \n{\n if(action == @selector(viewItem:)){return YES;}\n if(action == @selector(editItem:)){return YES;}\n if(action == @selector(cancelSubMenu:)){return YES;}\n\n return NO; \n}\n\nWhen the user taps the cancel button on the UIMenuController the row is deselected properly. ", " But when the user taps anywhere else on the screen the UIMenuControlller dismisses but the row is still selected.", "\nIs there some kind of didDismiss UIMenuController method?", "\n\nA:\n\nThe UIMenuController will post a notification just after it hides called UIMenuControllerDidHideMenuNotification, you can subscribe to this notification to call a method that in turn calls deselectRowAtIndexPath on your table view. ", "for example:\n[[NSNotificationCenter defaultCenter] addObserver:self selector:@selector(yourMethodHere) name:UIMenuControllerDidHideMenuNotification object:nil];\n\n" ]

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[ "Q:\n\nTypeclasses: function with default implementation vs separate function\n\nWhen defining a typeclass, how do you decide between including/excluding a function in the typeclass' definition? ", "For example, what are the differences between these 2 cases:\nclass Graph g where\n ...\n\n insertNode :: g -> Node -> g\n insertNode graph node = ...\n\nvs \nclass Graph g where\n ...\n\ninsertNode :: (Graph g) => g -> Node -> g\ninsertNode graph node = ...\n\nA:\n\nI think there are a few elements in tension here. ", " There's the general idea that type class definitions ought to be minimal, and only contain independent functions. ", " As bhelkir's answer explains, if your class supports functions a, b and c, but c can be implemented in terms of a and b, that's an argument for defining c outside of the class.", "\nBut this general idea runs into a few other conflicting issues.", "\nFirst, there is often more than one minimal set of operations that can equivalently define the same class. ", " The classic definition of Monad in Haskell is this (cleaned up a bit):\nclass Monad m where\n return :: a -> m a\n (>>=) :: m a -> (a -> m b) -> m b\n\nBut it's well known that there are alternative definitions, like this one:\nclass Applicative m => Monad m where\n join :: m (m a) -> m a\n\nreturn and >>= are sufficient to implement join, but fmap, pure and join are also sufficient to implement >>=.", "\nA similar thing with Applicative. ", " This is the canonical Haskell definition:\nclass Functor f => Applicative f where\n pure :: a -> f a\n (<*>) :: f (a -> b) -> f a -> f b\n\nBut any of the following is equivalent:\nclass Functor f => Applicative f where\n unit :: f ()\n (<*>) :: f (a -> b) -> f a -> f b\n\nclass Functor f => Applicative f where\n pure :: a -> f a\n fpair :: f a -> f b -> f (a, b)\n\nclass Functor f => Applicative f where\n unit :: f ()\n fpair :: f a -> f b -> f (a, b)\n\nclass Functor f => Applicative f where\n unit :: f ()\n liftA2 :: (a -> b -> c) -> f a -> f b -> f c\n\nGiven any of these class definitions, you can write any of the methods in any of the others as a derived function outside the class. ", " Why was the first one picked? ", " I can't answer authoritatively, but I think it brings us to the third point: performance considerations. ", " The fpair operation in many of those combines the f a and f b values by creating tuples, but for most uses of the Applicative class we don't actually want those tuples, we just want to combine values drawn from f a and f b; the canonical definition allows us to choose what function to do this combination with.", "\nAnother performance consideration is that even if some methods in a class may be definable in terms of others, these generic definitions may not be optimal for all instances of the class. ", " If we take Foldable as an example, foldMap and foldr are interdefinable, but some types support one more efficiently than the other. ", " So often we have non-minimal class definitions to allow the instances to provide optimized implementations of methods.", "\n\nA:\n\nIncluding a function in the definition of a typeclass means that it can be overridden. ", " In this case, you would need for it to be inside the Graph typeclass since it returns a Graph g => g, and each specific instance of Graph would need to know how to construct that value. ", " Alternatively, you could specify a function in the typeclass for the purpose of constructing values of type Graph g => g and then insertNode could use that function in its result.", "\nKeeping a function outside of the typeclass means that it can't be modified, but also that it doesn't clutter up the class. ", " Consider as an example the mapM function. ", " There's no need for this to be in the Monad class, and you probably don't want people writing their own implementations of mapM, it should do the same thing in all contexts. ", " As another example, consider the function\n-- f(x) = 1 + 3x^2 - 5x^3 + 10x^4\naPoly :: Num a => a -> a\naPoly x = 1 + 3 * x * x - 5 * x * x * x + 10 * x * x * x * x\n\nObviously aPoly shouldn't be part of the Num typeclass, it's just a random function that happens to use Num methods. ", " It has nothing to do with what it means to be a Num.", "\nReally, it comes down to design. ", " Functions are usually specified within a typeclass if they are integral to what it means to be an instance of that typeclass. ", " Sometimes functions are included in a typeclass but with a default definition so that a specific type can overload it to make it more efficient, but for the most part it makes sense to keep class members at a minimum. ", " One way to look at it is by asking the question \"Can this function be implemented with only the constraint of the class?\" ", " If the answer is no, it should be in the class. ", " If the answer is yes, the vast majority of the time it means that the function should be moved outside of the class. ", " Only when there is value gained from being able to overload it should it be moved into the class. ", " If overloading that function can break other code that expects it to behave a particular way, then it shouldn't be overloaded.", "\nAnother case to consider is when you have functions in your typeclass that have sane defaults, but those defaults are mutually dependent. ", " Taking the Num class as an example, you have\nclass Num a where\n (+) :: a -> a -> a\n (*) :: a -> a -> a\n (-) :: a -> a -> a\n a - b = a + negate b\n negate :: a -> a\n negate a = 0 - a\n abs :: a -> a\n signum :: a -> a\n fromInteger :: Integer -> a\n\nNotice that (-) and negate are both implemented in terms of each other. ", " If you make your own numeric type then you would need to implement either or both of (-) and negate, since otherwise you'll have an infinite loop on your hands. ", " These are useful functions to overload, though, so they both stay inside the typeclass.", "\n\n" ]

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[ "Polymorphisms in the DNA repair gene XRCC1 and age-related disease.", "\nThe recent hypothesis that common variants (single nucleotide polymorphisms or SNPs) in the population may contribute significantly to genetic risk for common diseases permits a conceptually straightforward approach to identifying age-related disease-causing mutations. ", "Functional variants of DNA replication and repair genes might be expected to be highly significant to cancer and aging since replication must proceed with high fidelity in a cellular environment where an estimated 10000 nucleotides are damaged daily. ", "Single-strand breaks (SSB) are one of the results of DNA damage either by methylation, oxidation, reduction or fragmentation of bases by ionizing radiation, and arise in cells directly by disintegration of damaged sugars or indirectly as intermediates of base excision repair. ", "Studies have demonstrated a role for XRCC1 both in vitro and in vivo during the repair of SSB. ", "A number of SNPs have been identified for the XRCC1 gene, and several have been associated with age-related diseases, especially cancer. ", "This report provides resequencing data confirming the existence of commonly occurring SNPs, including Arg194Trp and Arg399Gln, and briefly summarizes epidemiological and functional relevance to cancer and other age-related diseases. ", "XRCC1 SNPs will be useful probes for investigating age-associated pathobiology in epidemiological and mechanistic studies." ]

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